| 1. |
- Patel, Riyaz S., et al.
(författare)
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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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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)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. |
- Patel, Riyaz S., et al.
(författare)
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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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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Gusarova, Viktoria, et al.
(författare)
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Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
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| 4. |
- Fuzzi, Sandro, et al.
(författare)
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Overview of the Po valley fog experiment 1994 (CHEMDROP)
- 1998
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Ingår i: Contributions to Atmospheric Physics. - 0005-8173. ; 71:1, s. 3-19
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Forskningsöversikt (refereegranskat)abstract
- The paper presents an outline of the CHEMDROP field experiment, carried out in November 1994 at the field station of S. Pietro Capofiume in the Po Valley, Italy. The main objective of the project was to address the issue of the size-dependent chemical composition of fog droplets, by experimentally investigating the following processes, which are expected to affect (or be affected by) the chemical composition of fog droplets as a function of size: a) the connection of the size-dependent chemical composition of CCN to the size-dependent composition of fog droplets; b) the gas/liquid partitioning of the gaseous species NH3, SO2, HCHO, HNO3 in fog; c) the Fe(II)/Fe(III) redox cycle in fog water. Some general results and overall conclusions of the experiment are reported in this paper, while more specific scientific questions are discussed in other companion papers in this issue. CHEMDROP results show that several processes concur in determining the size-dependence of fog droplets chemical composition: nucleation scavenging of pre-existing CCN, fog dynamical evolution and gas/liquid exchange between interstitial air and fog droplets. Chemical transformations in the liquid phase can cause further changes in the chemical composition of the droplets. Only by taking into account the combination of all these processes, is it possible to explain the inhomogeneities in fog droplet chemical composition.
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| 5. |
- Berg, Olle H., et al.
(författare)
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Comparison of observed and modeled hygroscopic behavior of atmospheric particles
- 1998
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Ingår i: Contributions to Atmospheric Physics. - 0005-8173. ; 71:1, s. 47-64
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Forskningsöversikt (refereegranskat)abstract
- The hygroscopic behavior of sub-micrometer atmospheric aerosol particles was studied with a Tandem Differential Mobility Analyzer (TDMA) at a field site in the Po Valley, Italy. The measurements were done in a continental polluted aerosol during the CHEMDROP fog and haze field experiment at San Pietro di Capofiume in November 1994. In this study, hygroscopic diameter growth factors of individual particles were measured when taken from a dry state, to a relative humidity of 90 %. The aerosol consisted of two groups of particles with different hygroscopic properties, as also seen in an earlier field experiment at the same location in 1989 and at other continental sites. The present work is a closure study on the hygroscopic behavior of sub-micrometer aerosol particles and their mass. Ammonium sulfate was used to model the hygroscopic growth with a model based on thermodynamic data for non-ideal aqueous solutions at water vapor subsaturation. The study was made in two steps: The first step is a comparison between hygroscopic active aerosol volume fractions derived from TDMA measurements on individual particles integrated over the particle size distributions, and collected volume fractions of major ions sampled by size resolved cascade impactors. The model of hygroscopic growth was also used, in the second step, to calculate ambient sizes of individual aerosol particles. These sizes were then compared to the actual ambient sizes as measured by the Droplet Aerosol Analyzer. The result shows agreement, within the estimated errors, between the integrated hygroscopic active volume fractions and the collected volume fractions of inorganic salts, for five events out of six studied. A mass balance could also be obtained between the masses collected with the impactors and the integrated volume distributions, by attributing reasonable densities to the hygroscopically active and inactive fractions. The differences between the calculated and measured ambient sizes were within measurement errors, when Raoult's law was used to model the occasions with relative humidities larger than 95 %.
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| 6. |
- Fritzell, Peter, et al.
(författare)
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Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
- 2004
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Ingår i: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
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| 7. |
- Martinsson, Bengt G., et al.
(författare)
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Droplet nucleation and growth in orographic clouds in relation to the aerosol population
- 1999
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Ingår i: Atmospheric Research. - 0169-8095. ; 50:3-4, s. 289-315
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Tidskriftsartikel (refereegranskat)abstract
- The formation and development of orographic clouds was studied in a field experiment comprising several measurement sites at a mountain ridge. The influence of the aerosol population present on the cloud microstructure was studied in relation to the dynamics in the cloud formation. Droplet nucleation scavenging was investigated by the introduction of a non-dimensional particle diameter related to the process, and it was found that the scavenging rose rapidly in a relatively narrow particle size interval. The size dependency of the scavenging could partly be explained by external mixture of the aerosol. The large particles in the cloud interstitial aerosol was found to be of a chemical nature which allows for only a very weak uptake of water, implying that the chemical composition of these particles rather than entrainment of dry air prevented the droplet nucleation. The aerosol particle number concentration was found to strongly influence the cloud microstructure. Droplet number concentrations up to approximately 2000 cm-3 were observed together with a substantially reduced effective droplet diameter. The observed effect of elevated particle number concentrations in orographic clouds was generalised to the climatologically more important stratiform clouds by the use of a cloud model. It was found that the microstructure of stratiform clouds was strongly dependent on the aerosol population present as well on the dynamics in the cloud formation.
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| 8. |
- Martinsson, Bengt G., et al.
(författare)
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Validation of very high cloud droplet number concentrations in air masses transported thousands of kilometres over the ocean
- 2000
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Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - 0280-6509. ; 52:2, s. 801-814
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Tidskriftsartikel (refereegranskat)abstract
- The microstructure of orographic clouds related to the aerosol present was studied during the second Aerosol Characterisation Experiment (ACE-2). Very high cloud droplet number concentrations (almost 3000 cm -3 ) were observed. These high concentrations occurred when clouds formed on a hill slope at Tenerife in polluted air masses originating in Europe that had transported the order of 1000 km over the Atlantic Ocean. The validity of the measured droplet number concentrations was investigated by comparing with measurements of the aerosol upstream of the cloud and cloud interstitial aerosol. Guided by distributions of the ratios between the measurements, three criteria of typically 30% in maximum deviation were applied to the measurements to test their validity. Agreement was found for 88% of the cases. The validated data set spans droplet number concentrations of 150-3000 cm -3 . The updraught velocity during the cloud formation was estimated to 2.2 m s -1 by model calculations, which is typical of cumuliform clouds. The results of the present study are discussed in relation to cloud droplet number concentrations previously reported in the literature. The importance of promoting the mechanistic understanding of the aerosol/cloud interaction and the use of validation procedures of cloud microphysical parameters is stressed in relation to the assessment of the indirect climatic effect of aerosols.
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| 9. |
- Swietlicki, Erik, et al.
(författare)
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A closure study of sub-micrometer aerosol particle hygroscopic behaviour
- 1999
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Ingår i: Atmospheric Research. - 0169-8095. ; 50:3-4, s. 205-240
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Tidskriftsartikel (refereegranskat)abstract
- The hygroscopic properties of sub-micrometer aerosol particles were studied in connection with a ground-based cloud experiment at Great Dun Fell, in northern England in 1995. Hygroscopic diameter growth factors were measured with a Tandem Differential Mobility Analyser (TDMA) for dry particle diameters between 35 and 265 nm at one of the sites upwind of the orographic cloud. An external mixture consisting of three groups of particles, each with different hygroscopic properties, was observed. These particle groups were denoted less-hygroscopic, more-hygroscopic and sea spray particles and had average diameter growth factors of 1.11-1.15, 1.38-1.69 and 2.08-2.21 respectively when taken from a dry state to a relative humidity of 90%. Average growth factors increased with dry particle size. A bimodal hygroscopic behaviour was observed for 74-87% of the cases depending on particle size. Parallel measurements of dry sub-micrometer particle number size distributions were performed with a Differential Mobility Particle Sizer (DMPS). The inorganic ion aerosol composition was determined by means of ion chromatography analysis of samples collected with Berner-type low pressure cascade impactors at ambient conditions. The number of ions collected on each impactor stage was predicted from the size distribution and hygroscopic growth data by means of a model of hygroscopic behaviour assuming that only the inorganic substances interacted with the ambient water vapour. The predicted ion number concentration was compared with the actual number of all positive and negative ions collected on the various impactor stages. For the impactor stage which collected particles with aerodynamic diameters between 0.17-0.53 μm at ambient relative humidity, and for which all pertinent data was available for the hygroscopic closure study, the predicted ion concentrations agreed with the measured values within the combined measurement and model uncertainties for all cases but one. For this impactor sampling occasion, the predicted ion concentration was significantly higher than the measured. The air mass in which this sample was taken had undergone extensive photochemical activity which had probably produced hygroscopically active material other than inorganic ions, such as organic oxygenated substances.
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| 10. |
- Swietlicki, Erik, et al.
(författare)
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Hygroscopic properties of aerosol particles in the northeastern Atlantic during ACE-2
- 2000
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Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 52:2, s. 201-227
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of the hygroscopic properties of sub-micrometer atmospheric aerosol particles were performed with hygroscopic tandem differential mobility analysers (H-TDMA) at 5 sites in the subtropical north-eastern Atlantic during the second Aerosol Characterization Experiment (ACE-2) from 16 June to 25 July 1997. Four of the sites were in the marine boundary layer and one was, at least occasionally, in the lower free troposphere. The hygroscopic diameter growth factors of individual aerosol particles in the dry particle diameter range 10-440 nm were generally measured for changes in relative humidity (RH) from <10% to 90%. In the marine boundary layer, growth factors at 90% RH were dependent on location, air mass type and particle size. The data was dominated by a unimodal growth distribution of more-hygroscopic particles, although a bimodal growth distribution including less-hygroscopic particles was observed at times, most often in the more polluted air masses. In clean marine air masses the more-hygroscopic growth factors ranged from about 1.6 to 1.8 with a consistent increase in growth factor with increasing particle size. There was also a tendency toward higher growth factors as sodium to sulphate molar ratio increased with increasing sea-salt contribution at higher wind speeds. During outbreaks of European pollution in the ACE-2 region, the growth factors of the largest particles were reduced, but only slightly. Growth factors at all sizes in both clean and polluted air masses were markedly lower at the Sagres, Portugal site due to more proximate continental influences. The frequency of occurrence of less-hygroscopic particles with a growth factor of ca. 1.15 was greatest during polluted conditions at Sagres. The free tropospheric 50 nm particles were predominately less-hygroscopic, with an intermediate growth factor of 1.4, but more-hygroscopic particles with growth factors of about 1.6 were also frequent. While these particles probably originate from within the marine boundary layer, the less-hygroscopic particles are probably more characteristic of lower free tropospheric air masses. For those occasions when measurements were made at 90% and an intermediate 60% or 70% RH, the growth factor G(RH) of the more-hygroscopic particles could be modelled empirically by a power law expression. For the ubiquitous more-hygroscopic particles, the expressions G(RH) = (1 - RH/100)-0.210 for 50 nm Aitken mode particles and G(RH) = (1 - RH/100)-0.233 for 166 nm accumulation mode particles are recommended for clean marine air masses in the north-eastern Atlantic within the range 0 < RH < 95%, and for wind speeds for which the local sea-salt production is small (< ca. 8 m s-1).
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