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1.
  • Silventoinen, K., et al. (författare)
  • Educational attainment of same-sex and opposite-sex dizygotic twins : An individual-level pooled study of 19 twin cohorts
  • 2021
  • Ingår i: Hormones and Behavior. - : Elsevier. - 0018-506X .- 1095-6867. ; 136
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.
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  • Watts, Eleanor L., et al. (författare)
  • Observational and genetic associations between cardiorespiratory fitness and cancer : a UK Biobank and international consortia study
  • 2024
  • Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130, s. 114-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The association of fitness with cancer risk is not clear.Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.
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  • Brogaard, K., et al. (författare)
  • Age and helium content of the open cluster NGC 6791 from multiple eclipsing binary members : III. Constraints from a subgiant
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Models of stellar structure and evolution can be constrained using accurate measurements of the parameters of eclipsing binary members of open clusters. Multiple binary stars provide the means to tighten the constraints and, in turn, to improve the precision and accuracy of the age estimate of the host cluster. In the previous two papers of this series, we have demonstrated the use of measurements of multiple eclipsing binaries in the old open cluster NGC 6791 to set tighter constraints on the properties of stellar models than was previously possible, thereby improving both the accuracy and precision of the cluster age. Aims. We identify and measure the properties of a non-eclipsing cluster member, V56, in NGC 6791 and demonstrate how this provides additional model constraints that support and strengthen our previous findings. Methods. We analyse multi-epoch spectra of V56 from FLAMES in conjunction with the existing photometry and measurements of eclipsing binaries in NGC6971. Results. The parameters of the V56 components are found to be Mp = 1.103 ± 0.008 Mpdbl and Ms = 0.974 ± 0.007 Mpdbl, Rp = 1.764 ± 0.099 Rpdbl and Rs = 1.045 ± 0.057 Rpdbl, Teff,p = 5447 ± 125 K and Teff,s = 5552 ± 125 K, and surface [Fe/H] = +0.29 ± 0.06 assuming that they have the same abundance. Conclusions. The derived properties strengthen our previous best estimate of the cluster age of 8.3 ± 0.3 Gyr and the mass of stars on the lower red giant branch (RGB), which is MRGB = 1.15 ± 0.02 Mpdbl for NGC 6791. These numbers therefore continue to serve as verification points for other methods of age and mass measures, such as asteroseismology.
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  • Vogelezang, Suzanne, et al. (författare)
  • Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
  • 2020
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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  • Henthorn, Nicholas T., et al. (författare)
  • Mapping the Future of Particle Radiobiology in Europe : The INSPIRE Project
  • 2020
  • Ingår i: Frontiers in Physics. - : Frontiers Media SA. - 2296-424X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Particle therapy is a growing cancer treatment modality worldwide. However, there still remains a number of unanswered questions considering differences in the biological response between particles and photons. These questions, and probing of biological mechanisms in general, necessitate experimental investigation. The "Infrastructure in Proton International Research" (INSPIRE) project was created to provide an infrastructure for European research, unify research efforts on the topic of proton and ion therapy across Europe, and to facilitate the sharing of information and resources. This work highlights the radiobiological capabilities of the INSPIRE partners, providing details of physics (available particle types and energies), biology (sample preparation and post-irradiation analysis), and researcher access (the process of applying for beam time). The collection of information reported here is designed to provide researchers both in Europe and worldwide with the tools required to select the optimal center for their research needs. We also highlight areas of redundancy in capabilities and suggest areas for future investment.
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  • Mathisen, J., et al. (författare)
  • Associations between psychosocial work environment factors and first-time and recurrent treatment for depression : a prospective cohort study of 24,226 employees
  • 2024
  • Ingår i: Epidemiology and Psychiatric Sciences. - 2045-7960 .- 2045-7979. ; 33
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. Adverse factors in the psychosocial work environment are associated with the onset of depression among those without a personal history of depression. However, the evidence is sparse regarding whether adverse work factors can also play a role in depression recurrence. This study aimed to prospectively examine whether factors in the psychosocial work environment are associated with first-time and recurrent treatment for depression.Methods. The study included 24,226 participants from the Danish Well-being in Hospital Employees study. We measured ten individual psychosocial work factors and three theoretical constructs (effort–reward imbalance, job strain and workplace social capital). We ascertained treatment for depression through registrations of hospital contacts for depression (International Statistical Classification of Diseases and Related Health Problems version 10 [ICD-10]: F32 and F33) and redeemed prescriptions of antidepressant medication (Anatomical Therapeutic Chemical [ATC]: N06A) in Danish national registries. We estimated the associations between work factors and treatment for depression for up to 2 years after baseline among those without (first-time treatment) and with (recurrent treatment) a personal history of treatment for depression before baseline. We excluded participants registered with treatment within 6 months before baseline. In supplementary analyses, we extended this washout period to up to 2 years. We applied logistic regression analyses with adjustment for confounding.Results. Among 21,156 (87%) participants without a history of treatment for depression, 350 (1.7%) had first-time treatment during follow-up. Among the 3070 (13%) participants with treatment history, 353 (11%) had recurrent treatment during follow-up. Those with a history of depression generally reported a more adverse work environment than those without such a history. Baseline exposure to bullying (odds ratio [OR] = 1.72, 95% confidence interval [95% CI]: 1.30–2.32), and to some extent also low influence on work schedule (OR = 1.27, 95% CI: 0.97–1.66) and job strain (OR = 1.24, 95% CI: 0.97–1.57), was associated with first-time treatment for depression during follow-up. Baseline exposure to bullying (OR = 1.40, 95% CI: 1.04–1.88), lack of collaboration (OR = 1.31, 95% CI: 1.03–1.67) and low job control (OR = 1.27, 95% CI: 1.00–1.62) were associated with recurrent treatment for depression during follow-up. However, most work factors were not associated with treatment for depression. Using a 2-year washout period resulted in similar or stronger associations.Conclusions. Depression constitutes a substantial morbidity burden in the working-age population. Specific adverse working conditions were associated with first-time and recurrent treatment for depression and improving these may contribute to reducing the onset and recurrence of depression.
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  • Misztal-Okońska, P., et al. (författare)
  • Importance of immediate electronic-based feedback to enhance feedback for first-time cpr trainees
  • 2021
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Sudden cardiac arrest is one of the leading causes of death globally. The recommended clinical management in out-of-hospital cardiac arrest cases is the immediate initiation of high-qual-ity cardiopulmonary resuscitation (CPR). Training mannequins should be combined with technology that provides students with detailed immediate feedback on the quality of CPR performance. This study aimed to verify the impacts of the type of feedback (basic or detailed) the responders receive from the device while learning CPR and how it influences the quality of their performance and the motivation to improve their skills. The study was conducted at the Medical University of Lublin among 694 multi-professional health students during first aid classes on basic life support (BLS). The students first practiced on an adult mannequin with a basic control panel; afterward, the same mannequin was connected to a laptop, ensuring a detailed record of the performed activities through a projector. Next, the participants expressed their subjective opinion on how the feedback provided during the classes, basic vs. detailed, motivated them to improve the quality of their CPR performance. Additionally, during the classes, the instructor conducted an extended observation of students’ work and behavior. In the students’ opinion, the CPR training with detailed feedback devices provided motivation for learning and improving CPR proficiency than that with a basic control panel. Furthermore, the comments given from devices seemed to be more acceptable to the students, who did not see any bias in the device’s evaluation compared to that of the instructor. Detailed device feedback motivates student health practitioners to learn and improve the overall quality of CPR. The use of mannequins that provide detailed feedback during BLS courses can improve survival in out-of-hospital cardiac arrest. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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  • Silventoinen, Karri, et al. (författare)
  • Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts
  • 2020
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
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  • Silventoinen, Karri, et al. (författare)
  • Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts
  • 2022
  • Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.
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  • Xu, Tianwei, et al. (författare)
  • Onset of Workplace Bullying and Risk of Weight Gain : A Multicohort Longitudinal Study
  • 2020
  • Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 28:11, s. 2216-2223
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: This study aimed to examine the onset of workplace bullying as a risk factor for BMI increase.Methods: Repeated biennial survey data from three Nordic cohort studies were used, totaling 46,148 participants (67,337 participant observations) aged between 18 and 65 who did not have obesity and who were not bullied at the baseline. Multinomial logistic regression was applied for the analysis under the framework of generalized estimating equations.Results: Five percent reported onset of workplace bullying within 2 years from the baseline. In confounder-adjusted models, onset of workplace bullying was associated with a higher risk of weight gain of >= 1 BMI unit (odds ratio = 1.09; 95% CI: 1.01-1.19) and of >= 2.5 BMI units (odds ratio = 1.24; 95% CI: 1.06-1.45). A dose-response pattern was observed, and those exposed to workplace bullying more frequently showed a higher risk (P-trend = 0.04). The association was robust to adjustments, restrictions, stratifications, and use of relative/absolute scales for BMI change.Conclusions: Participants with exposure to the onset of workplace bullying were more likely to gain weight, a possible pathway linking workplace bullying to increased long-term risk of type 2 diabetes.
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  • Chen, Jie, et al. (författare)
  • Long-term exposure to ambient air pollution and bladder cancer incidence in a pooled European cohort : the ELAPSE project
  • 2022
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 126:10, s. 1499-1507
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The evidence linking ambient air pollution to bladder cancer is limited and mixed.Methods: We assessed the associations of bladder cancer incidence with residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight PM2.5 elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) in a pooled cohort (N = 302,493). Exposures were primarily assessed based on 2010 measurements and back-extrapolated to the baseline years. We applied Cox proportional hazard models adjusting for individual- and area-level potential confounders.Results: During an average of 18.2 years follow-up, 967 bladder cancer cases occurred. We observed a positive though statistically non-significant association between PM2.5 and bladder cancer incidence. Hazard Ratios (HR) were 1.09 (95% confidence interval (CI): 0.93–1.27) per 5 µg/m3 for 2010 exposure and 1.06 (95% CI: 0.99–1.14) for baseline exposure. Effect estimates for NO2, BC and O3 were close to unity. A positive association was observed with PM2.5 zinc (HR 1.08; 95% CI: 1.00–1.16 per 10 ng/m3).Conclusions: We found suggestive evidence of an association between long-term PM2.5 mass exposure and bladder cancer, strengthening the evidence from the few previous studies. The association with zinc in PM2.5 suggests the importance of industrial emissions.
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  • Dalaei, Farima, et al. (författare)
  • Body Contouring Surgery after Bariatric Surgery Improves Long-Term Health-Related Quality of Life and Satisfaction with Appearance : An International Longitudinal Cohort Study Using the BODY-Q
  • 2024
  • Ingår i: Annals of Surgery. - 0003-4932. ; 279:6, s. 1008-1017
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine health-related quality of life (HRQL) and satisfaction with appearance in patients who have undergone bariatric surgery (BS) with or without subsequent body contouring surgery (BCS) in relation to the general population normative for the BODY-Q. Background: The long-term impact of BS with or without BCS has not been established using rigorously developed and validated patient-reported outcome measures. The BODY-Q is a patient-reported outcome measure developed to measure changes in HRQL and satisfaction with appearance in patients with BS and BCS. Methods: Prospective BODY-Q data were collected from 6 European countries (Denmark, the Netherlands, Finland, Germany, Italy, and Poland) from June 2015 to February 2022 in a cohort of patients who underwent BS. Mixed-effects regression models were used to analyze changes in HRQL and appearance over time between patients who did and did not receive BCS and to examine the impact of patient-level covariates on outcomes. Results: This study included 24,604 assessments from 5620 patients. BS initially led to improved HRQL and appearance scores throughout the first postbariatric year, followed by a gradual decrease. Patients who underwent subsequent BCS after BS experienced a sustained improvement in HRQL and appearance or remained relatively stable for up to 10 years postoperatively. Conclusions: Patients who underwent BCS maintained an improvement in HRQL and satisfaction with appearance in contrast to patients who only underwent BS, who reported a decline in scores 1 to 2 years postoperatively. Our results emphasize the pivotal role that BCS plays in the completion of the weight loss trajectory.
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  • Kreibich, Heidi, et al. (författare)
  • Panta Rhei benchmark dataset : Socio-hydrological data of paired events of floods and droughts
  • 2023
  • Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 15:5, s. 2009-2023
  • Tidskriftsartikel (refereegranskat)abstract
    • As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions, and feedbacks in complex human-water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e. two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed and in the quantity of socio-hydrological data. The benchmark dataset comprises (1) detailed review-style reports about the events and key processes between the two events of a pair; (2) the key data table containing variables that assess the indicators which characterize management shortcomings, hazard, exposure, vulnerability, and impacts of all events; and (3) a table of the indicators of change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators of change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses, e.g. focused on causal links between risk management; changes in hazard, exposure and vulnerability; and flood or drought impacts. The data can also be used for the development, calibration, and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al., 2023, 10.5880/GFZ.4.4.2023.001).
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  • Kreibich, Heidi, et al. (författare)
  • The challenge of unprecedented floods and droughts in risk management
  • 2022
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 608:7921, s. 80-86
  • Tidskriftsartikel (refereegranskat)abstract
    • Risk management has reduced vulnerability to floods and droughts globally, yet their impacts are still increasing. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change.
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  • Roswall, Nina, et al. (författare)
  • Long-Term Exposure to Transportation Noise and Risk of Incident Stroke : A Pooled Study of Nine Scandinavian Cohorts
  • 2021
  • Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 129:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse.Objective: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population.Methods: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through linkage to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle confounders, and air pollution.Results: During follow-up (median=19.5y), 11,056 stroke cases were identified. Road traffic noise (Lden) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for individual- and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of ≤2.5μm (PM2.5) and NO2]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40–50 vs. ≤40 dB) (HR=1.12; 95% CI: 0.99, 1.27), but not with higher exposure (≥50 dB, HR=0.94HR; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke.Discussion: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise.
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  • Chen, Jie, et al. (författare)
  • Long-Term Exposure to Source-Specific Fine Particles and Mortality-A Pooled Analysis of 14 European Cohorts within the ELAPSE Project
  • 2022
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:13, s. 9277-9290
  • Tidskriftsartikel (refereegranskat)abstract
    • We assessed mortality risks associated with sourcespecific fine particles (PM2.5) in a pooled European cohort of 323,782 participants. Cox proportional hazard models were applied to estimate mortality hazard ratios (HRs) for source-specific PM2.5 identified through a source apportionment analysis. Exposure to 2010 annual average concentrations of source-specific PM2.5 components was assessed at baseline residential addresses. The source apportionment resulted in the identification of five sources: traffic, residual oil combustion, soil, biomass and agriculture, and industry. In single-source analysis, all identified sources were significantly positively associated with increased natural mortality risks. In multisource analysis, associations with all sources attenuated but remained statistically significant with traffic, oil, and biomass and agriculture. The highest association per interquartile increase was observed for the traffic component (HR: 1.06; 95% CI: 1.04 and 1.08 per 2.86 mu g/m(3) increase) across five identified sources. On a 1 mu g/m(3) basis, the residual oil-related PM2.5 had the strongest association (HR: 1.13; 95% CI: 1.05 and 1.22), which was substantially higher than that for generic PM2.5 mass, suggesting that past estimates using the generic PM2.5 exposure response function have underestimated the potential clean air health benefits of reducing fossil-fuel combustion. Source-specific associations with cause-specific mortality were in general consistent with findings of natural mortality.
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  • Deshmukh, Harshal A., et al. (författare)
  • Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity
  • 2021
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:1, s. 80-90
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. OBJECTIVE: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. DESIGN: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. RESULTS: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10-9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10-9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. CONCLUSION: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.
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  • Ervasti, Jenni, et al. (författare)
  • Long working hours and risk of 50 health conditions and mortality outcomes : a multicohort study in four European countries
  • 2021
  • Ingår i: The Lancet Regional Health. - : Elsevier BV. - 2666-7762. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies on the association between long working hours and health have captured only a narrow range of outcomes (mainly cardiometabolic diseases and depression) and no outcome-wide studies on this topic are available. To achieve wider scope of potential harm, we examined long working hours as a risk factor for a wide range of disease and mortality endpoints.Methods: The data of this multicohort study were from two population cohorts from Finland (primary analysis, n=59 599) and nine cohorts (replication analysis, n=44 262) from Sweden, Denmark, and the UK, all part of the Individual-participant Meta-analysis in Working Populations (IPD-Work) consortium. Baseline-assessed long working hours (≥55 hours per week) were compared to standard working hours (35-40 h). Outcome measures with follow-up until age 65 years were 46 diseases that required hospital treatment or continuous pharmacotherapy, all-cause, and three cause-specific mortality endpoints, ascertained via linkage to national health and mortality registers.Findings: 2747 (4·6%) participants in the primary cohorts and 3027 (6·8%) in the replication cohorts worked long hours. After adjustment for age, sex, and socioeconomic status, working long hours was associated with increased risk of cardiovascular death (hazard ratio 1·68; 95% confidence interval 1·08-2·61 in primary analysis and 1·52; 0·90-2·58 in replication analysis), infections (1·37; 1·13-1·67 and 1·45; 1·13-1·87), diabetes (1·18; 1·01-1·38 and 1·41; 0·98-2·02), injuries (1·22; 1·00-1·50 and 1·18; 0·98-1·18) and musculoskeletal disorders (1·15; 1·06-1·26 and 1·13; 1·00-1·27). Working long hours was not associated with all-cause mortality.Interpretation: Follow-up of 50 health outcomes in four European countries suggests that working long hours is associated with an elevated risk of early cardiovascular death and hospital-treated infections before age 65. Associations, albeit weak, were also observed with diabetes, musculoskeletal disorders and injuries. In these data working long hours was not related to elevated overall mortality.
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31.
  • Lindgren Belal, Sarah, et al. (författare)
  • Automated quantification of PET/CT skeletal tumor burden in prostate cancer using artificial intelligence: The PET index
  • 2023
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 50:5, s. 1510-1520
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Consistent assessment of bone metastases is crucial for patient management and clinical trials in prostate cancer (PCa). We aimed to develop a fully automated convolutional neural network (CNN)-based model for calculating PET/CT skeletal tumor burden in patients with PCa. Methods A total of 168 patients from three centers were divided into training, validation, and test groups. Manual annotations of skeletal lesions in -[F-18]fluoride PET/CT scans were used to train a CNN. The AI model was evaluated in 26 patients and compared to segmentations by physicians and to a SUV 15 threshold. PET index representing the percentage of skeletal volume taken up by lesions was estimated. Results There was no case in which all readers agreed on prevalence of lesions that the AI model failed to detect. PET index by the AI model correlated moderately strong to physician PET index (mean r = 0.69). Threshold PET index correlated fairly with physician PET index (mean r = 0.49). The sensitivity for lesion detection was 65-76% for AI, 68-91% for physicians, and 44-51% for threshold depending on which physician was considered reference. Conclusion It was possible to develop an AI-based model for automated assessment of PET/CT skeletal tumor burden. The model's performance was superior to using a threshold and provides fully automated calculation of whole-body skeletal tumor burden. It could be further developed to apply to different radiotracers. Objective scan evaluation is a first step toward developing a PET/CT imaging biomarker for PCa skeletal metastases.
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32.
  • Lopes, Renato D., et al. (författare)
  • Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer : The Primary Results of the PRONOUNCE Randomized Trial
  • 2021
  • Ingår i: Circulation. - 1524-4539. ; 144:16, s. 1295-1307
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial. METHODS: In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months. RESULTS: Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53). CONCLUSIONS: PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.
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33.
  • Merid, Simon Kebede, et al. (författare)
  • Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
  • 2020
  • Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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34.
  • Nyberg, Solja T., et al. (författare)
  • Association of alcohol use with years lived without major chronic diseases : A multicohort study from the IPD-Work consortium and UK Biobank
  • 2022
  • Ingår i: The Lancet Regional Health - Europe. - : Elsevier. - 2666-7762. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Heavy alcohol consumption increases the risk of several chronic diseases. In this multicohort study, we estimated the number of life-years without major chronic diseases according to different characteristics of alcohol use.Methods In primary analysis, we pooled individual-level data from up to 129,942 adults across 12 cohort studies with baseline data collection on alcohol consumption, drinking patterns, and history between 1986 and 2005 (the IPD-Work Consortium). Self-reported alcohol consumption was categorised according to UK guidelines - non-drinking (never or former drinkers); moderate consumption (1-14 units); heavy consumption (>14 units per week). We further subdivided moderate and heavy drinkers by binge drinking pattern (alcohol-induced loss of consciousness). In addition, we assessed problem drinking using linked data on hospitalisations due to alcohol abuse or poisoning. Follow-up for chronic diseases for all participants included incident type 2 diabetes, coronary heart disease, stroke, cancer, and respiratory disease (asthma and chronic obstructive pulmonary disease) as ascertained via linkage to national morbidity and mortality registries, repeated medical examinations, and/or self-report. We estimated years lived without any of these diseases between 40 and 75 years of age according to sex and characteristics of alcohol use. We repeated the main analyses using data from 427,621 participants in the UK Biobank cohort study.Findings During 1.73 million person-years at risk, 22,676 participants in IPD-Work cohorts developed at least one chronic condition. From age 40 to 75 years, never-drinkers [men: 29.3 (95%CI 27.9-30.8) years, women 29.8 (29.2 - 30.4) years)] and moderate drinkers with no binge drinking habit [men 28.7 (28.4-29.0) years, women 29.6 (29.4-29.7) years] had the longest disease-free life span. A much shorter disease-free life span was apparent in participants who experienced alcohol poisoning [men 23.4 (20.9-26.0) years, women 24.0 (21.4-26.5) years] and those with self-reported heavy overall consumption and binge drinking [men: 26.0 (25.3-26.8), women 27.5 (26.4 - 28.5) years]. The pattern of results for alcohol poisoning and self-reported alcohol consumption was similar in UK Biobank. In IPD-Work and UK Biobank, differences in disease-free years between self-reported moderate drinkers and heavy drinkers were 1.5 years or less.Interpretation Individuals with alcohol poisonings or heavy self-reported overall consumption combined with a binge drinking habit have a marked 3- to 6-year loss in healthy longevity. Differences in disease-free life between categories of self-reported weekly alcohol consumption were smaller.
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35.
  • Pyko, Andrei, et al. (författare)
  • Long-Term Exposure to Transportation Noise and Ischemic Heart Disease: A Pooled Analysis of Nine Scandinavian Cohorts.
  • 2023
  • Ingår i: Environmental health perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 131:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Transportation noise may induce cardiovascular disease, but the public health implications are unclear.The study aimed to assess exposure-response relationships for different transportation noise sources and ischemic heart disease (IHD), including subtypes.Pooled analyses were performed of nine cohorts from Denmark and Sweden, together including 132,801 subjects. Time-weighted long-term exposure to road, railway, and aircraft noise, as well as air pollution, was estimated based on residential histories. Hazard ratios (HRs) were calculated using Cox proportional hazards models following adjustment for lifestyle and socioeconomic risk factors.A total of 22,459 incident cases of IHD were identified during follow-up from national patient and mortality registers, including 7,682 cases of myocardial infarction. The adjusted HR for IHD was 1.03 [95% confidence interval (CI) 1.00, 1.05] per 10 dB Lden for both road and railway noise exposure during 5 y prior to the event. Higher risks were indicated for IHD excluding angina pectoris cases, with HRs of 1.06 (95% CI: 1.03, 1.08) and 1.05 (95% CI: 1.01, 1.08) per 10 dB Lden for road and railway noise, respectively. Corresponding HRs for myocardial infarction were 1.02 (95% CI: 0.99, 1.05) and 1.04 (95% CI: 0.99, 1.08). Increased risks were observed for aircraft noise but without clear exposure-response relations. A threshold at around 55 dB Lden was suggested in the exposure-response relation for road traffic noise and IHD.Exposure to road, railway, and aircraft noise in the prior 5 y was associated with an increased risk of IHD, particularly after exclusion of angina pectoris cases, which are less well identified in the registries. https://doi.org/10.1289/EHP10745.
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36.
  • Roswall, Nina, et al. (författare)
  • Long-term exposure to traffic noise and risk of incident colon cancer : A pooled study of eleven Nordic cohorts
  • 2023
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 224
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundColon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this.ObjectivesThe objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons.MethodsWe identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data.ResultsDuring follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99–1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98–1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO2-exposure.DiscussionA prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin.
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37.
  • Thacher, Jesse D., et al. (författare)
  • Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts
  • 2023
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 <60 dB as a cutoff, we found HRs of 1.08 (0.99–1.18) for road traffic and 1.19 (0.95–1.49) for railway noise.Conclusions: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before conclusions regarding noise as a risk factor for breast cancer can be made.
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38.
  • Walhovd, Kristine B., et al. (författare)
  • Education and Income Show Heterogeneous Relationships to Lifespan Brain and Cognitive Differences Across European and US Cohorts
  • 2022
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 32:4, s. 839-854
  • Tidskriftsartikel (refereegranskat)abstract
    • Higher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4-97 years, N = 500 000; 54 000 w/brain imaging). There was substantial heterogeneity across cohorts for all associations. Education was positively related to intracranial (ICV) and total gray matter (GM) volume. Income was related to ICV, but not GM. We did not observe reliable differences in associations as a function of age. SES was more strongly related to brain and cognition in US than European cohorts. Sample representativity varies, and this study cannot identify mechanisms underlying differences in associations across cohorts. Differences in neuroanatomical volumes partially explained SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. The relatively stronger SES-ICV associations rather are compatible with SES-brain volume relationships being established early in life, as ICV stabilizes in childhood. The findings underscore that SES has no uniform association with, or impact on, brain and cognition.
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