| 1. |
- Patel, Riyaz S., et al.
(author)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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In: Circulation. - 2574-8300. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 2. |
- Abbasi, Rasha, et al.
(author)
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IceCube search for neutrinos from GRB 221009A
- 2023
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In: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
-
Conference paper (peer-reviewed)abstract
- GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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| 3. |
- Gaulton, Kyle J, et al.
(author)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Journal article (peer-reviewed)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 4. |
- Leander, Mai, et al.
(author)
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Impact of anxiety and depression on respiratory symptoms
- 2014
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 108:11, s. 1594-1600
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Journal article (peer-reviewed)abstract
- Psychological factors such as anxiety and depression are prevalent in patients with asthma. The purpose of this study was to investigate the relationship between respiratory symptoms and psychological status and to estimate the importance of psychological status in comparison with other factors that are known to be associated with respiratory symptoms. This study included 2270 subjects aged 20-44 (52% female) from Sweden, Iceland, and Norway. Each participant underwent a clinical interview including questions on respiratory symptoms. Spirometry and methacholine challenge were performed. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Eighty-two percent of the subjects reported no anxiety or depression whatsoever, 11% reported anxiety, 2.5% depression and 4% reported both anxiety and depression. All respiratory symptoms, such as wheezing, breathlessness and nightly symptoms, were more common, at a statistically significant level, in participants who had depression and anxiety, even after adjusting for confounders (ORs 1.33-1.94). The HADS score was the most important determinant for nightly symptoms and attacks of breathlessness when at rest whereas bronchial responsiveness was the most important determinant for wheezing, and breathlessness when wheezing. The probability of respiratory symptoms related to HADS score increased with increasing HADS score for all respiratory symptoms. In conclusion, there is a strong association between respiratory symptoms and psychological status. There is therefore a need for interventional studies designed to improve depression and anxiety in patients with respiratory symptoms. (C) 2014 Elsevier Ltd. All rights reserved.
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| 5. |
- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 6. |
- Patel, Riyaz S., et al.
(author)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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In: Circulation. - 2574-8300. ; 12:4
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 7. |
- Rask-Andersen, Anna, 1952-, et al.
(author)
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Health-related quality of life as associated with asthma control, psychological status and insomnia
- 2022
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In: Upsala Journal of Medical Sciences. - Uppsala : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 127
-
Journal article (peer-reviewed)abstract
- Background: Asthma is associated not only with lower health-related quality of life (HRQL) but also with psychological health and insomnia. The aim of this study was to investigate associations between HRQL, asthma symptoms, psychological status and insomnia in adults from three Nordic countries.Methods: This study comprised 2,270 subjects aged 29–55 from Sweden, Iceland and Norway. HRQL was measured with the 36-Item Short Form Health Survey (SF-36). The physical (PCS) and mental health (MCS) component scores were calculated with higher values, indicating better health status. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Insomnia was assessed with the Basic Nordic Sleep Questionnaire. An asthma score consisting of a sum of the positive answers to five respiratory symptoms was used in the analysis. Spirometry and allergy tests were also performed.Results: High HADS and sleep disturbance scores were both related to a low PCS and MCS, respectively, after adjusting for confounders. High age and high body mass index (BMI) were associated with low scores on the PCS, whilst the opposite was found for the MCS. A higher asthma score was related to a low PCS. An interaction between the HADS and the asthma symptom score was observed for the PCS (P = 0.0002), where associations between psychological status and the PCS were more pronounced for individuals with more symptoms than for individuals without symptoms.Conclusions: In this study, we found that HRQL of life was independently related to the HADS, insomnia and asthma symptoms. Further prospective studies to identify the most efficient target for intervention in order to improve asthma control are needed.
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| 8. |
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| 9. |
- Sarkadi, Anna, Professor, 1974-, et al.
(author)
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An Integrated Care Strategy for Pre-schoolers with Suspected Developmental Disorders : The Optimus Co-design Project that has Made it to Regular Care
- 2021
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In: International Journal of Integrated Care. - : Ubiquity Press. - 1568-4156. ; 21:2
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Journal article (peer-reviewed)abstract
- Introduction: Multiple neurodevelopmental problems affect 7-8% of children and require evaluation by more than one profession, posing a challenge to care systems.Description: The local problem comprised distressed parents, diagnostic processes averaging 36 months and 28 visits with 42% of children >4 years at referral to adequate services, and no routines for patient involvement. The co-design project was developed through a series of workshops using standard quality improvement methodology, where representatives of all services, as well as parents participated. The resulting integrated care model comprises a team of professionals who evaluate the child during an average of 5.4 appointments (N = 95), taking 4.8 weeks. Parents were satisfied with the holistic service model and 70% of children were under 4 at referral (p < 0.05). While 75% of children were referred, 25% required further follow-up by the team.Discussion: The Optimus model has elements of vertical, clinical and service integration. Reasons for success included leadership support, buy-in from the different organisations, careful process management, a team co-ordinator, and insistent user involvement.Conclusion: Evaluating multiple neurodevelopmental problems in children requires an integrated care approach. The Optimus care model is a relevant showcase for how people-initiated integrated care reforms can make it into usual care.
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| 10. |
- Sederholm Lawesson, Sofia, 1973-, et al.
(author)
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Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.
- 2023
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In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 329:5, s. 393-404
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Journal article (peer-reviewed)abstract
- Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown.To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.Cross-sectional study of a population-based cohort of women in Sweden (n=10528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected.Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures.Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100.A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.
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| 11. |
- Aalberts, Tanja, et al.
(author)
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Rituals of World Politics: On (Visual) Practices Disordering Things
- 2020
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In: Critical Studies on Security. - : Informa UK Limited. - 2162-4909 .- 2162-4887. ; 8:3, s. 240-264
-
Journal article (peer-reviewed)abstract
- Rituals are customarily muted into predictable routines aimed to stabilise social orders and limit conflict. As a result, their magic lure recedes into the background, and the unexpected and disruptive elements are downplayed. Our collaborative contribution counters this move by foregrounding rituals of world politics as social practices with notable disordering effects. We engage a series of ‘world pictures’ to show the worlding and disruptive work enacted in rituals designed to sustain the sovereign exercise of violence and war, here colonial treatymaking, state commemoration, military/service dog training, cyber-security podcasts, algorithmically generated maps, the visit of Prince Harry to a joint NATO exercise and border ceremonies in India, respectively. We do so highlighting rituals’ immanent potential for disruption of existing orders, the fissures, failures and unforeseen repercussions. Reappraising the disordering role of ritual practices sheds light on the place of rituals in rearticulating the boundaries of the political. Rituals can generate dissensus and re-divisions of the sensible rather than only impose a consensus by policing the boundaries of the political, as Rancière might phrase it. Our images are essential to the account. They help disinterring the fundamentals and ambiguities of the current worldings of security, capturing the affective atmosphere of rituals.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- de Vries, Paul S., et al.
(author)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Journal article (peer-reviewed)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 16. |
- Fuks, Kateryna B., et al.
(author)
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Arterial blood pressure and long-term exposure to traffic-related air pollution : an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2014
-
In: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 122:9, s. 896-905
-
Research review (peer-reviewed)abstract
- BACKGROUND: Long-term exposure to air pollution is hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country-specific. OBJECTIVES: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. METHODS: Fifteen population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE), were analysed. Residential exposure to particulate matter and nitrogen oxides was modelled with land use regression using a uniform protocol. Traffic exposure was assessed with traffic indicator variables. We analysed systolic and diastolic BP in participants medicated and non-medicated with BP lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. RESULTS: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in non-medicated participants (0.35 mmHg [95% CI: 0.02-0.68] and 0.22 mmHg [95% CI: 0.04-0.40] per 4,000,000 vehicles × m/day, respectively). The estimated odds ratio for prevalent hypertension was 1.05 [95% CI: 0.99-1.11] per 4,000,000 vehicles × m/day. Modelled air pollutants and BP were not clearly associated. CONCLUSIONS: In this first comprehensive meta-analysis of European population-based cohorts we observed a weak positive association of high residential traffic exposure with BP in non-medicated participants, and an elevated OR for prevalent hypertension. The relationship of modelled air pollutants with BP was inconsistent.
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| 17. |
- Funk, Eva, 1953-, et al.
(author)
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Patient-initiated breath-holds in MRI : an alternative for reducing respiratory artifacts and improving image quality
- 2015
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In: Clinical imaging. - : Elsevier. - 0899-7071 .- 1873-4499. ; 39:4, s. 619-622
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Journal article (peer-reviewed)abstract
- Purpose: To investigate MRI image quality using two different breath-hold techniques.Materials and methods: Thirty patients remitted for MRI, 2D-dual gradient echo acquisition of the liver conducted two separate breath-hold acquisitions in randomized order, operator-instructed and patient-initiated. The images were reviewed by two radiologists.Results: There were no significant differences in image quality between the two breath-hold techniques either in overall image quality or respiratory motion artifacts. This assessment was equal and concordant for both radiologists.Conclusion: In terms of image quality, the patient self-initiated breath-hold was shown to be an equal alternative to conventional breath-hold imaging.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Guzzini, Stefano, 1963-, et al.
(author)
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Preface and acknowledgements
- 2006
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In: Constructivism and International Relations. - London, New York : Routledge. - 0415411203 ; , s. xvii-xxii
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Book chapter (other academic/artistic)
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| 22. |
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| 23. |
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| 24. |
- Jonsson, Ulf, 1974-, et al.
(author)
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Internet-delivered psychological treatment as an add-on to treatment as usual for common mental disorders : A systematic review with meta-analysis of randomized trials
- 2023
-
In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 322, s. 221-234
-
Research review (peer-reviewed)abstract
- BACKGROUND: Psychological treatments for common mental disorders are increasingly being delivered remotely via the internet. Evidence suggests that internet-delivered cognitive behavioural therapy (iCBT) is superior to waitlist. However, the benefits are unclear of using this treatment modality as an add-on to treatment as usual (TAU) in regular healthcare.METHODS: The literature was systematically searched up to August 2021 for randomized trials of internet-delivered psychological treatments using TAU as the comparator. Eligible participants were diagnosed with depressive, anxiety, obsessive-compulsive, or trauma- and stress-related disorders. Outcomes of interest were symptoms, functioning, quality of life, healthcare utilization, and negative effects. Results were synthesized using random-effects meta-analyses. Quality of evidence was assessed using GRADE.RESULTS: The included studies evaluated iCBT for adults with depression (k = 9), depressive or anxiety disorders (k = 4), and post-traumatic stress disorder (k = 2) and were conducted in primary care or similar settings. For depression, low-certainty evidence suggested beneficial short-term effects on symptoms (g = -0.23; 95 % CI: = -0.37, -0.09), response rate (OR = 2.46; 1.31, 4.64), and remission (OR = 1.70; 1.19, 2.42;). The certainty of evidence was very low for long-term effects, other outcomes, and other disorders.LIMITATIONS: TAU varied across studies and was often insufficiently described.CONCLUSIONS: iCBT as a complement to usual care for adult with depression may result in a small incremental effect, which potentially could be clinically important. Studies are lacking for several common disorders and for children, adolescents, and the elderly. More robust studies of long-term effects are also needed, to better inform clinical decision-making.
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| 25. |
- Justice, A. E., et al.
(author)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 26. |
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| 27. |
- Leander, Jacob, 1987, et al.
(author)
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NLMEModeling: A Wolfram Mathematica Package for Nonlinear Mixed Effects Modeling of Dynamical Systems
- 2020
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Journal article (other academic/artistic)abstract
- Nonlinear mixed effects modeling is a powerful tool when analyzing data from several entities in an experiment. In this paper, we present NLMEModeling, a package for mixed effects modeling in Wolfram Mathematica. NLMEModeling supports mixed effects modeling of dynamical systems where the underlying dynamics are described by either ordinary or stochastic differential equations combined with a flexible observation error model. Moreover, NLMEModeling is a user-friendly package with functionality for model validation, visual predictive checks and simulation capabilities. The package is freely available and provides a flexible add-on to Wolfram Mathematica.
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| 28. |
- Leander, Jacob, 1987, et al.
(author)
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Nonlinear Mixed Effects Modeling of Deterministic and Stochastic Dynamical Systems in Wolfram Mathematica
- 2021
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In: IFAC-PapersOnLine. - : Elsevier BV. - 2405-8963 .- 2405-8963. ; 54:7, s. 409-414
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Conference paper (peer-reviewed)abstract
- Nonlinear mixed effects (NLME) modeling is a powerful tool to analyze timeseries data from several individual entities in an experiment. In this paper, we give a brief overview of a package for NLME modeling in Wolfram Mathematica entitled NLMEModeling, implementing the first-order conditional estimation method with sensitivity equation-based gradients for parameter estimation. NLMEModeling supports mixed effects modeling of dynamical systems where the underlying dynamics are described by either ordinary or stochastic differential equations combined with observation equations with flexible observation error models. Moreover, NLMEModeling is a user-friendly package with functionality for parameter estimation, model diagnostics (such as goodness-of-fit analysis and visual predictive checks), and model simulation. The package is freely available and provides an extensible add-on to Wolfram Mathematica.
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| 29. |
- Leander, Jacob, 1987, et al.
(author)
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Parameter Estimation for Nonlinear Mixed Effects Models Implemented in Mathematica
- 2019
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Conference paper (other academic/artistic)abstract
- In many applications within biology and medicine, measurements are gathered from several entities in the same experiment. This could for example be patients exposed to a treatment or cells measured after stimuli. To characterize the variability in response between entities, the nonlinear mixed effects (NLME) model is a suitable statistical model. An NLME model enables quantification of both within- and between subject variability. The parameter estimation in NLME models is not straightforward, due to the intractable expression of the likelihood function. In this work we present a Mathematica package for parameter estimation in NLME models where the longitudinal model is defined by differential equations. The parameter estimation problem is solved by the first-order conditional estimation (FOCE) method with exact gradients. The package is demonstrated using data from a simulated drug concentration model.
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| 30. |
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| 31. |
- Leander, Mai, et al.
(author)
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Associations Between Mortality, Asthma, and Health-Related Qualityof Life in an Elderly Cohort of Swedes
- 2010
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In: Journal of Asthma. - : Informa UK Limited. - 0277-0903 .- 1532-4303.
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Journal article (peer-reviewed)abstract
- Background. Asthma is a common chronic health condition among the elderly and an important cause of morbidity and mortality. Some studiesshow that subjective assessments of health-related quality of life (HRQL) are important predictors of mortality and survival. The primary aim ofthis study was to investigate whether low HRQL was a predictor of mortality in elderly subjects and whether such an association differed betweensubjects with and without asthma. Methods. In 1990, a cohort in middle Sweden was investigated using a respiratory questionnaire. To assess HRQL,the generic instrument Gothenburg Quality of Life (GQL) was used. The participants were also investigated by spirometry and allergy testing. Thepresent study was limited to the subjects in the oldest age group, aged 60–69 years in 1990, and included 222 subjects with clinically verified asthma,148 subjects with respiratory symptoms but no asthma or other lung diseases, and 102 subjects with no respiratory symptoms. Mortality in thecohort was followed during 1990–2008. Results. Altogether, 166 of the 472 subjects in the original cohort had died during the follow-up period of1990–2008. Mortality was significantly higher in men, in older subjects, in smokers, and subjects with a low forced expiratory volume in one second(FEV1). There was, however, no difference in mortality between the asthmatic and the nonasthmatic groups. A higher symptoms score for GQLwas significantly related to increased mortality. No association between HRQL and mortality was found when limiting the analysis to the asthmaticgroup, although the asthmatics had a lower symptom score for GQL compared to the other groups. Conclusion. A higher symptom score in the GQLinstrument was significantly related to increased mortality, but this association was not found when analyzing the asthmatic group alone. The negativeprognostic implications of a low HRQL in the whole group and the fact that the asthmatic group had a lower HRQL than the other group supports theuse of HRQL instruments in clinical health assessments.
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| 32. |
- Leander, Mai, 1953-, et al.
(author)
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Determinants for a low health-related quality of life in asthmatics
- 2012
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 117:1, s. 57-66
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Journal article (peer-reviewed)abstract
- People with asthma suffer from impaired health-related quality of life (HRQL) but the determinants of HRQL among asthmatics are not completely understood. The aim of this study was to study determinants of low HRQL in asthmatics and to study whether the determinants of HRQL differ between sexes and age groups. A cohort of three age groups in Sweden was investigated in 1990 using a respiratory questionnaire. To study quality of life, the generic instrument Gothenburg Quality of Life was used. The participants were also investigated with interviews, spirometry and allergy testing. Asthma was diagnosed in 616 subjects. Fifty-eight percent (n=359) of the subjects were women. Twenty-four percent were smokers, 22% ex-smokers and 54% were non-smokers. Women were more likely than men to report poor health-related quality of life. Respiratory symptoms severity was another independent determinant of a lower quality of life as well as airway responsiveness to irritants. Current and former smokers also reported lower quality of life. Finally, absenteeism from school and work was associated with lower quality of life. Factors such as sex, smoking habits, airway responsiveness to irritants, respiratory symptom severity, allergy, and absenteeism from school and work were associated with low HRQL in asthmatics.
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| 33. |
- Leander, Mai
(author)
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Health-Related Quality of Life in Asthma
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- Health-related quality of life (HRQL) has become an important outcome in asthma, since traditional outcomes, such as respiratory symptoms and pulmonary function, might not entirely express the patient’s perception of the limitations caused by the disease. The aim of this thesis was to study HRQL in asthma and to analyse if HRQL was related to asthma onset and prognosis. Other aims were to identify determinants of low HRQL in clinically-verified asthmatics, and to study whether low HRQL was a predictor of mortality. In 1990, a self-administered questionnaire was completed by 12,560 individuals from three age groups (16, 30-39, and 60-69 years) in two counties of Sweden. In a second phase, all subjects who reported a history of obstructive respiratory symptoms (n = 1,851) and 600 randomly-selected controls were invited to a clinical investigation including spirometry, allergy testing, and assessment of HRQL with the Gothenburg Quality of Life instrument. In 2003, the eligible subjects in the cohort (n=11,282) were sent a new questionnaire. Mortality data in the cohort was followed up during 1990–2008 using data from the National Board of Health and Welfare Mortality Database. The 616 subjects with clinically-verified asthma 1990 had significantly lower HRQL than subjects without asthma. In the 2003 follow-up, the 305 subjects with persistent asthma had a lower HRQL than the 155 subjects who showed improvement in asthma during the follow-up. Subjects who had developed asthma by the follow-up had a significantly lower HRQL at baseline than those who did not develop asthma. Significant determinants of quality of life in asthma were female sex, smoking habits, higher airway responsiveness to irritants, respiratory symptom severity, positive skin prick test, and absenteeism from work or school. Low HRQL was related to increased mortality, but this association was not found when analyzing the asthmatic group alone. In conclusion, measurements of HRQL are of value for evaluating both the impact and progression of asthma.
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| 34. |
- Leander, Mai, et al.
(author)
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Health-related quality of life predicts onset of asthma in a longitudinal population study
- 2009
-
In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 103:2, s. 194-200
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Health-related quality of life (HRQL) has been increasingly used as an outcome measure in asthma, but less is known about the prognostic implication of low health-related quality of life. The purpose of this study was to investigate if a set of quality of life measures could predict onset of asthma. METHODS: In the baseline study 391 subjects without asthma answered a respiratory questionnaire and the Gothenburg Quality of Life (GQL) instrument in 1990. The GQL questionnaire included two parts: (1) the prevalence of HRQL-related symptoms and (2) well-being scores for physical, mental and social dimensions. The participants were also investigated with spirometry and allergy testing. In 2003, the same respiratory questionnaire that had been used in 1990 was sent. There were 290 responders, of whom 22 subjects had developed asthma. RESULTS: Participants who had developed asthma by the follow-up had a higher prevalence of sleep disturbances (30% vs. 10%), problems with chest pain (16% vs. 2%), depression (40% vs. 20%) difficulty relaxing (40% vs. 13%) and constipation (25% vs. 2%) at baseline than participants who did not develop asthma (p<0.05). Subjects who developed asthma also scored significantly lower on well-being variables as sleep, energy, mood, patience, memory, appetite, fitness and sense of appreciation outside home. These differences remained after adjusting for age, sex, smoking habits, asthma heredity, socioeconomic groups and building dampness. CONCLUSION: Participants with low health-related quality of life at baseline were more likely to report having developed asthma 12 years later.
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| 35. |
- Leander, Mai, et al.
(author)
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Non-respiratory symptoms and well-being in asthmatics from a general population sample
- 2009
-
In: Journal of Asthma. - : Informa UK Limited. - 0277-0903 .- 1532-4303. ; 46:6, s. 552-559
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Different instruments have been developed to assess health-related quality of life (HRQL) in asthma patients. However, relatively few studies have assessed HRQL in asthma patients from a general population, and it is still unclear which instrument is most suitable. The purpose of this study was to compare HRQL in clinically verified asthmatics with subjects with respiratory symptoms without asthma and with subjects with no respiratory symptoms from a general population. The generic instrument Gothenburg Quality of Life (GQL) was used. A secondary aim was to study if GQL had any prognostic value in asthma. METHODS: A cohort of three age groups in Sweden was investigated in 1990 using a respiratory questionnaire and GQL. The cohort consisted of 616 subjects with asthma, 488 subjects with respiratory symptoms but no asthma, and 347 subjects without respiratory symptoms. The participants were also investigated by spirometry and allergy testing. In a follow-up study, subjects were identified who had persistent and improved asthma. RESULTS: The prevalence of 28 of the 30 common symptoms in GQL was significantly increased (p < 0.001) in subjects with asthma as compared to non-asthmatics. All symptoms in the domains heart and lung, head, musculoskeletal, tension, and depression were significantly increased among the asthmatics. The asthmatics also rated their physical well-being lower (p < 0.001) than subjects with no respiratory symptoms. Subjects with persistent asthma had a significantly higher prevalence of 7 of the 30 symptoms and lower social well-being than subjects showing improvement in asthma during the follow-up. All differences remained significant after adjusting for age, sex, and smoking habits. CONCLUSION: Subjects with asthma had different symptom-profiles compared to those of non-asthmatics, with a higher prevalence of both respiratory and non-respiratory symptoms. Asthma is also a disease that is related to low well-being. The use of quality-of-life questionnaires such as the GQL may provide useful information for evaluating the non-respiratory aspects of asthma as well as for assessing the impact of disease on health status and well-being.
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| 36. |
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| 37. |
- Mohlin, Marcus, 1965-
(author)
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The Strategic Use of Military Contractors : American Commercial Military Service Providers in Bosnia and Liberia: 1995-2009
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- Drawing from strategic theory, this study investigates the strategic roles of commercial companies providing military services, frequently referred to as private military companies. Theoretically, the thesis analyzes how states organize its military capabilities in order to be able to wield power within the international system while empirically, it examines the character and role of commercial companies that provide military training services to the United States Government and partner nations. The reason for this rather instrumental and functional, rather than critical, approach is that this work is written within the discipline known as War Studies.Strategic theory is used first to logically organize the empirical findings in two case studies and then to develop an analytical framework with which the strategic roles of companies providing military services can be investigated.The analysis has been conducted using both new and hitherto unknown sources in the shape of interviews as well as previously classified telegrams, but also draws on previous research and other secondary sources.The main findings are that commercial companies have five typical strategic roles: first, they cloak the state by substituting traditional uniformed troops; second, they act as trailblazers by securing US influence in new regions and by breaking new ground by contributing to the build-up of new partners; third, they act as scene setters by preparing the ground for military exit out of a theater of operations or by facilitating inter-operability between foreign militaries and the US military; fourth, they can be used to infiltrate the security structures of foreign countries; fifth and finally, they can be used to provide offensive capabilities by providing either kinetic or cyber warfare effects. Another finding is that military service contracting is an important part of the US strategic culture.
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| 38. |
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| 39. |
- Nilsson, Sigrid, 1997-
(author)
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Vasomotor Symptoms, Cardiovascular Risk and the Role of Physical Activity in Midlife Women
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- Background: The menopausal transition is, for most women, accompanied by hot flushes and night sweats (i.e., vasomotor symptoms, VMS). VMS has been associated with a worsened cardiovascular risk profile, but whether VMS constitutes an independent risk marker for developing subclinical atherosclerotic cardiovascular disease (ASCVD) is still uncertain. Visceral adipose tissue (VAT) contributes more to systemic low-grade inflammation than abdominal subcutaneous adipose tissue (ASAT), enhancing atherosclerosis development. Physical activity is an effective behavioral strategy to maintain and improve cardiovascular health. Whether a resistance training intervention (RTI) could reduce low-grade inflammation and VAT volume in postmenopausal women with VMS remains unclear, and whether the RTI-associated effects could be maintained over time requires further investigation.Material and Methods: This thesis is based on three studies. Study 1 was conducted on a subset of participants from the cross-sectional population-based Swedish CArdioPulmonary BioImage Study (SCAPIS), including women 50-64 years of age. The women underwent comprehensive cardiovascular assessments and completed an extensive female-specific questionnaire. VMS was assessed on a 4-point scale. Subclinical ASCVD was detected via coronary computed tomography angiography (CCTA), computed tomography (CT), and carotid ultrasound. Study 2 is a sub-study of 65 postmenopausal women with VMS and low physical activity, randomized to either three days/week of an RTI or unchanged physical activity for 15 weeks. Women underwent anthropometric measurements, magnetic resonance imaging (MRI), and blood sampling at baseline and after 15 weeks. During the last followup contact in Study 2 after two years, 35 women agreed to attend an additional clinic visit to reevaluate cardiovascular risk markers, marking the inception of Study 3.Results: Of 2995 women included in Study 1, 14.2% reported severe VMS (n = 425), 18.1% moderate VMS (n = 543), and 67.7% no or mild VMS (n = 2027). Current or previous severe VMS, but not moderate VMS, was significantly associated with CCTA-detected coronary atherosclerosis, with odds ratio (OR) before and after multivariable adjustment 1.36, 95% confidence interval (CI) 1.08 – 1.72 and 1.33, 95% CI 1.02 – 1.72, respectively. This association was only present for >5 years durations of severe VMS or when the onset of severe VMS occurred before menopause. Adjustment for menopausal hormone therapy strengthened the association for women with severe VMS >5 years (OR 1.67, 95% CI 1.16 – 2.40). Women compliant with an RTI had compared to a control group (CG), decreased adiponectin (p < 0.01), ASAT (p < 0.01), VAT (p < 0.01), total abdominal adipose tissue (TAAT) (p < 0.01) and fat ratio (p <0.001). Furthermore, an RTI reduced moderate to severe VMS frequency to six months post-intervention compared to a CG, but did neither contribute to preserved cardiovascular health markers nor improved health-related quality of life (HRQoL) after two years compared to a CG.Conclusions: There is a need for extra vigilance regarding cardiovascular risk factors in the group of women suffering from severe VMS. Implementing a 15-week RTI in these women could counteract the VAT redistribution and alter the frequency of moderate to severe VMS with maintained effects up to six months.
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| 40. |
- Olsson, Tina M., et al.
(author)
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Systematic review and meta-analysis of noninstitutional psychosocial interventions to prevent juvenile criminal recidivism
- 2021
-
In: Journal of Consulting and Clinical Psychology. - : American Psychological Association (APA). - 0022-006X .- 1939-2117. ; 89:6, s. 514-527
-
Journal article (peer-reviewed)abstract
- Objective: To assess the effectiveness of noninstitutional psychosocial interventions in preventing recidivism among criminal adolescents. Method: We performed a systematic review and meta-analysis of randomized and nonrandomized controlled trials assessing the impact on recidivism among juveniles aged 12–17. The included studies had a low to medium risk of bias and were published between 2000 and 2019. Standardized mean differences or risk differences were calculated. Results: We included 35 (20 randomized, 15 nonrandomized) studies evaluating 17 unique, noninstitutional psychosocial interventions. A meta-analysis found no significant reductions in recidivism for studied interventions compared to control conditions. Although single studies suggested some positive effects, the evidence provided by these studies was found to have very low certainty. Post hoc analyses indicated that studies including a low-intensity control condition might have stronger relative intervention effects compared to studies with medium or high-intensity control conditions. Conclusion: This systematic review did not find any one noninstitutional psychosocial intervention to be more effective than control treatments in reducing future criminality among juvenile offenders aged 12–17. We discuss the implications of the present findings for social work and child and adolescent psychiatry practices.
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| 41. |
- Peden, John F., et al.
(author)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 42. |
- Persson, Asa, et al.
(author)
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Long-term exposure to transportation noise and obesity: A pooled analysis of eleven Nordic cohorts
- 2024
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In: ENVIRONMENTAL EPIDEMIOLOGY. - 2474-7882. ; 8:4
-
Journal article (peer-reviewed)abstract
- Background:Available evidence suggests a link between exposure to transportation noise and an increased risk of obesity. We aimed to assess exposure-response functions for long-term residential exposure to road traffic, railway and aircraft noise, and markers of obesity. Methods:Our cross-sectional study is based on pooled data from 11 Nordic cohorts, including up to 162,639 individuals with either measured (69.2%) or self-reported obesity data. Residential exposure to transportation noise was estimated as a time-weighted average L-den 5 years before recruitment. Adjusted linear and logistic regression models were fitted to assess beta coefficients and odds ratios (OR) with 95% confidence intervals (CI) for body mass index, overweight, and obesity, as well as for waist circumference and central obesity. Furthermore, natural splines were fitted to assess the shape of the exposure-response functions. Results:For road traffic noise, the OR for obesity was 1.06 (95% CI = 1.03, 1.08) and for central obesity 1.03 (95% CI = 1.01, 1.05) per 10 dB L-den. Thresholds were observed at around 50-55 and 55-60 dB L-den, respectively, above which there was an approximate 10% risk increase per 10 dB L-den increment for both outcomes. However, linear associations only occurred in participants with measured obesity markers and were strongly influenced by the largest cohort. Similar risk estimates as for road traffic noise were found for railway noise, with no clear thresholds. For aircraft noise, results were uncertain due to the low number of exposed participants. Conclusion:Our results support an association between road traffic and railway noise and obesity.
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| 43. |
- Pyko, Andrei, et al.
(author)
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Long-Term Exposure to Transportation Noise and Ischemic Heart Disease: A Pooled Analysis of Nine Scandinavian Cohorts.
- 2023
-
In: Environmental health perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 131:1
-
Journal article (peer-reviewed)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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| 44. |
- Roswall, Nina, et al.
(author)
-
Long-term exposure to traffic noise and risk of incident colon cancer : A pooled study of eleven Nordic cohorts
- 2023
-
In: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 224
-
Journal article (peer-reviewed)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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| 45. |
- Roswall, Nina, et al.
(author)
-
Long-Term Exposure to Transportation Noise and Risk of Incident Stroke : A Pooled Study of Nine Scandinavian Cohorts
- 2021
-
In: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 129:10
-
Journal article (peer-reviewed)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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| 46. |
- Schillemans, Tessa, et al.
(author)
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Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis
- 2022
-
In: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 13
-
Journal article (peer-reviewed)abstract
- Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged >= 65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.
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| 47. |
- Sikkema, Lisa, et al.
(author)
-
An integrated cell atlas of the lung in health and disease
- 2023
-
In: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
-
Journal article (peer-reviewed)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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| 48. |
- Silveira, Angela, et al.
(author)
-
Plasma IL-5 concentration and subclinical carotid atherosclerosis
- 2015
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 239:1, s. 125-130
-
Journal article (peer-reviewed)abstract
- Objective: Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT).Methods: We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline.Results: IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women.Conclusions: Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease.
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| 49. |
- Thacher, Jesse D., et al.
(author)
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Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts
- 2023
-
In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
-
Journal article (peer-reviewed)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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| 50. |
- Uddenfeldt, Monica, et al.
(author)
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High BMI is related to higher incidence of asthma, while a fish and fruit diet is related to a lower : - Results from a long-term follow-up study of three age groups in Sweden
- 2010
-
In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 104:7, s. 972-980
-
Journal article (peer-reviewed)abstract
- The causes of the worldwide increase in asthma seen during the last decades remain largely unexplained, but lifestyle and diet are suggested to play important roles. In this follow up of a large-scale population sample in Sweden, we wanted to identify modifiable risk factors for the cumulative incidence over a 13-year follow-up period.In 1990, a self-administered questionnaire was completed by 12,560 individuals from three age groups (16, 30–39 and 60–69 years of age) in two counties of Sweden. In 2003, the eligible subjects (n = 11,282) were sent a new postal questionnaire.In total 8150 (response rate 73%) answered the questionnaire. The prevalence of asthma in 2003 had increased in all ages. In the young adults, the asthma prevalence rose from 11.3% in 1990 to 25.0% in 2003. Adult asthma onset was identified in 791 of the participants. Smoking [RR (95% CI) = 1.37 (1.12–1.68)], BMI [1.49 (1.25–1.77 per inter quartile range)], and nocturnal gastro-oesophageal reflux (GOR) [2.16 (1.72–2.72)] were significant independent risk factors for the cumulative incidence of asthma. The impact of risk factors differed between the age groups where BMI and GOR had a significantly higher impact in the middle aged and the elderly (p < 0.05). High consumption of fruit and fish was protective especially in the elderly [0.52 (0.35–0.77)]. No significant difference was found in the impact of risk factors between men and women.Weight loss, smoking cessation and a diet rich in fruit and fish may be of importance in preventing onset of adult asthma.
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