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| 11. |
- Arking, D. E., et al.
(author)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Journal article (peer-reviewed)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 12. |
- Shrine, N, et al.
(author)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Journal article (peer-reviewed)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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- Lytras, T., et al.
(author)
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Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts
- 2021
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In: Annals of the American Thoracic Society. - New York : American Thorax Society. - 1546-3222 .- 2329-6933 .- 2325-6621 .- 1943-5665. ; 18:2, s. 238-246
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Journal article (peer-reviewed)abstract
- Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up. Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking. Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts. Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
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| 23. |
- Lytras, T., et al.
(author)
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Occupational exposures and 20-year incidence of COPD: the European Community Respiratory Health Survey
- 2018
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In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 73:11
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Journal article (peer-reviewed)abstract
- Background Occupational exposures have been associated with an increased risk of COPD. However, few studies have related objectively assessed occupational exposures to prospectively assessed incidence of COPD, using postbronchodilator lung function tests. Our objective was to examine the effect of occupational exposures on COPD incidence in the European Community Respiratory Health Survey. Methods General population samples aged 20-44 were randomly selected in 1991-1993 and followed up 20 years later (2010-2012). Spirometry was performed at baseline and at follow-up, with incident COPD defined using a lower limit of normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD and without current asthma at baseline were included. Coded job histories during follow-up were linked to a Job-Exposure Matrix, generating occupational exposure estimates to 12 categories of agents. Their association with COPD incidence was examined in log-binomial models fitted in a Bayesian framework. Findings 3343 participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up (1.4 cases/1000 person-years). Participants exposed to biological dust had a higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6, 95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0 to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population attributable fraction for these exposures was 21.0%. Interpretation These results substantially strengthen the evidence base for occupational exposures as an important risk factor for COPD.
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| 24. |
- Lytras, T., et al.
(author)
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Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: The European Community Respiratory Health Survey
- 2019
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In: Occupational and environmental medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 76:4
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Journal article (peer-reviewed)abstract
- Objectives: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. Methods: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. Results: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. Conclusions: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation. © Author(s) (or their employer(s)) 2019.
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| 25. |
- Murray, Alison E., et al.
(author)
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Roadmap for naming uncultivated Archaea and Bacteria
- 2020
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In: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
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Journal article (peer-reviewed)abstract
- The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
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| 26. |
- Onthong, U., et al.
(author)
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X-ray and neutron diffraction studies and molecular dynamics simulations of liquid DMSO
- 2004
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 6, s. 2136-2144
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Journal article (peer-reviewed)abstract
- Liquid DMSO has been investigated by means of X-ray and neutron diffraction, quantum-chemical calculations and molecular dynamics (MD) simulations. A new analytical all-atom pair potential for DMSO-DMSO interactions was developed from quantum-chemical calculations and employed in the simulations. The MD-derived total structure function agrees favourably with those obtained from the X-ray and neutron diffraction experiments. An analysis of the local structure shows a rather unstructured liquid with a slight preference for antiparallel ordering of the S-O dipoles.
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- Artigas, MS, et al.
(author)
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Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation
- 2015
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8658-
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Journal article (peer-reviewed)abstract
- Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
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| 34. |
- Forster, T, et al.
(author)
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Cetuximab in Pancreatic Cancer Therapy: A Systematic Review and Meta-Analysis
- 2020
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In: Oncology. - : S. Karger AG. - 1423-0232 .- 0030-2414. ; 98:1, s. 53-60
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Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> The present study evaluated the potential benefit of adding cetuximab to neoadjuvant, adjuvant, or palliative standard therapy for pancreatic cancer. <b><i>Methods:</i></b> A systematic literature search was performed in MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). Only randomised controlled trials (RCTs) investigating the effect of adding cetuximab to standard chemotherapy in pancreatic cancer were included. Evaluated outcomes were overall survival, progression-free survival, objective response, and toxicity. For overall survival and progression-free survival, hazard ratios (HR) with 95% confidence intervals (CI) were chosen as effect measure. For objective response, odds ratios (OR) with 95% CI were used. Analysis was based on a random effects model. <b><i>Results:</i></b> After screening 568 publications, a total of 4 RCTs with 924 patients were included. In all trials, patients were adequately randomised with balanced intervention and control groups. There was no significant difference in overall survival (HR 1.04; 95% CI: 0.90–1.19; <i>p</i> = 0.60), progression-free survival (HR 1.06; 95% CI: 0.93–1.22; <i>p</i> = 0.36), or objective response (OR 0.99; 95% CI: 0.66 –1.49; <i>p</i> = 0.96) when adding cetuximab to a standard therapy. Toxicity was the same or higher in each of the included trials. According to GRADE, the certainty of the evidence is high. Therefore, adding cetuximab to pancreatic cancer therapy has no clinically relevant benefit. <b><i>Conclusion:</i></b> In the presence of no survival benefit, increased toxicity, and higher costs, a decreased cost-benefit ratio compared to the standard care must be suggested. Conducting further RCTs in unselected pancreatic cancer populations is unlikely to change this conclusion.
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| 36. |
- Jackson, Victoria E, et al.
(author)
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Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
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In: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Journal article (peer-reviewed)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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| 37. |
- Lahrouchi, Najim, et al.
(author)
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Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
- 2020
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In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338
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Journal article (peer-reviewed)abstract
- Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
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| 39. |
- Marcon, A., et al.
(author)
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The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories
- 2021
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:5
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Journal article (peer-reviewed)abstract
- Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden. Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477). Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated. Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life. The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.
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| 40. |
- Markevych, I., et al.
(author)
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Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study
- 2023
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In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
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Journal article (peer-reviewed)abstract
- Background: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected.Objective: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey.Methods: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990-1994), 44 (1999-2003), and 55 (2010-2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures.Results: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (-1.25 mL/year [95% confidence interval:-2.18 to-0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent asso-ciations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. Conclusions: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detri-mental association requires verification in future studies.
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| 41. |
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| 42. |
- Mauracher, Andreas, et al.
(author)
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Metastable anions of dinitrobenzene : Resonances for electron attachment and kinetic energy release
- 2010
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 133:24, s. 244302-
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Journal article (peer-reviewed)abstract
- Attachment of free, low-energy electrons to dinitrobenzene (DNB) in the gas phase leads to DNB− as well as several fragment anions. DNB−, (DNB-H)−, (DNB-NO)−, (DNB-2NO)−, and (DNB-NO2)− are found to undergo metastable (unimolecular) dissociation. A rich pattern of resonances in the yield of these metastable reactions versus electron energy is observed; some resonances are highly isomer-specific. Most metastable reactions are accompanied by large average kinetic energy releases (KER) that range from 0.5 to 1.32 eV, typical of complex rearrangement reactions, but (1,3-DNB-H)− features a resonance with a KER of only 0.06 eV for loss of NO. (1,3-DNB-NO)− offers a rare example of a sequential metastable reaction, namely, loss of NO followed by loss of CO to yield C5H4O− with a large KER of 1.32 eV. The G4(MP2) method is applied to compute adiabatic electron affinities and reaction energies for several of the observed metastable channels
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| 44. |
- Olivieri, M., et al.
(author)
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Effects of smoking bans on passive smoking exposure at work and at home. The European Community respiratory health survey
- 2019
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In: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 29:4, s. 670-679
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Journal article (peer-reviewed)abstract
- This longitudinal study investigated whether smoking bans influence passive smoking at work and/or at home in the same subjects. Passive smoking at work and/or at home was investigated in random population samples (European Community Respiratory Health Survey) in 1990-1995, with follow-up interviews in 1998-2003 and 2010-2014. National smoking bans were classified as partial (restricted to public workplaces) or global (extended to private workplaces). Multivariable analysis was accomplished by three-level logistic regression models, where level-1, level-2, and level-3 units were, respectively, questionnaire responses, subjects, and centers. Passive smoking at work was reported by 31.9% in 1990-1995, 17.5% in 1998-2003, and 2.5% in 2010-2014. Concurrently, passive smoking at home decreased from 28.9% to 18.2% and 8.8%. When controlling for sex, age, education, smoking status, and ECHRS wave, the odds of passive smoking at work was markedly reduced after global smoking bans (OR = 0.45, 95% CI 0.25-0.81), particularly among non-smokers, while the protective effect of global smoking bans on passive smoking at home was only detected in non-smokers. Smoking bans both in public and private workplaces were effective in reducing passive smoking at work in Europe. However, given the inefficacy of smoking bans in current smokers' dwellings, better strategies are needed to avoid smoking indoors.
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| 45. |
- Onthong, U., et al.
(author)
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Molecular dynamics simulation of lithium iodide in liquid dimethylsulfoxide
- 2005
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In: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 401:03-jan, s. 217-222
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Journal article (peer-reviewed)abstract
- We report results of a molecular dynamics simulation on a system consisting of 343 DMSO molecules, one Li+ cation and one I- anion in the NVE ensemble at 310 K, employing our recently developed all-atom potential functions for the intermolecular interactions derived from quantum chemical calculations. The structure of the solvation shell around the cation and the anion are investigated in terms of radial and angular distribution functions. The first solvation shell around lithium ion consists of 4 DMSO molecules; 8 DMSO molecules coordinate to iodide ion. DMSO coordinates to both ions in a well-defined way. The results are in good agreement with other molecular dynamics simulations of alkali halides in DMSO.
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| 47. |
- Pesce, G., et al.
(author)
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Low serum DHEA-S is associated with impaired lung function in women
- 2020
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In: EClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 23
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Journal article (peer-reviewed)abstract
- Background: Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS). Methods: Lung function and serum DHEA-S concentrations were measured in n = 2,045 and n = 1,725 women in 1999–2002 and in 2010–2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999–2002 with incidence of restrictive pattern and airflow limitation in 2010–2013 were also assessed. Findings: Women with low DHEA-S (z-score<-1) had lower FEV1 (% of predicted, adjusted difference: -2.2; 95%CI: -3.5 to -0.9) and FVC (-1.7; 95%CI: -2.9 to -0.5) and were at a greater risk of having airflow limitation and restrictive pattern on spirometry than women with higher DHEA-S levels. In longitudinal analyses, low DHEA-S at baseline was associated with a greater incidence of airflow limitation after an 11-years follow-up (incidence rate ratio, 3.43; 95%CI: 1.91 to 6.14). Interpretation: Low DHEA-S levels in women were associated with impaired lung function and a greater risk of developing airflow limitation later in adult life. Our findings provide new evidence supporting a role of DHEA-S in respiratory health. Funding: EU H2020, grant agreement no.633212 © 2020 The Authors
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| 48. |
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| 49. |
- Probst, M., et al.
(author)
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Ionization energy studies for ozone and OClO monomers and dimers
- 2002
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 116:3, s. 984-992
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Journal article (peer-reviewed)abstract
- Electron impact ionization cross sections measured close to threshold are reported for both the monomers and dimers of ozone and OClO using a new high resolution electron impact apparatus. The present appearance energies AE(O-3(+)/O-3)=12.70 +/-0.02 eV, AE (OClO+/OClO)=10.55 +/-0.02 and AE(ClO+/OClO=13.37 +/-0.03 eV derived from the measured ionization cross sections are in excellent agreement with the vertical threshold values determined for these ions by high resolution PES and PIMS photoionization studies. The corresponding appearance energies determined for the dimer ions, 10.10 +/-0.3 eV for (O-3)(2)(+) and 9.87 +/-0.2 eV for (OClO)(2)(+), are both red shifted with respect to the monomer case. The bond energy (0.70-0.3+0.5) eV of (OClO)(2)(+) estimated from these data is similar to that of other dimer ions, whereas the bond energy of (O-3-O-3(+)) with (2.55-0.4+0.6) eV is rather large suggesting an unusual structure for the cationic ozone dimer ion. Based on quantum chemical calculations on various levels we are led to the conclusion that the ion produced by ionization of the ozone dimer is no longer a conventional dimer ion where the two monomer units are still present (as is the case for the OClO system), but rather an ion of form O-2.O-4(+) or a twisted ring structure of (O-6)(+).
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| 50. |
- Sakornsakolpat, Phuwanat, et al.
(author)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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