| 1. |
- Tabassum, R, et al.
(författare)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 2. |
- Coustenis, A., et al.
(författare)
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TandEM : Titan and Enceladus mission
- 2009
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 893-946
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Tidskriftsartikel (refereegranskat)abstract
- TandEM was proposed as an L-class (large) mission in response to ESA's Cosmic Vision 2015-2025 Call, and accepted for further studies, with the goal of exploring Titan and Enceladus. The mission concept is to perform in situ investigations of two worlds tied together by location and properties, whose remarkable natures have been partly revealed by the ongoing Cassini-Huygens mission. These bodies still hold mysteries requiring a complete exploration using a variety of vehicles and instruments. TandEM is an ambitious mission because its targets are two of the most exciting and challenging bodies in the Solar System. It is designed to build on but exceed the scientific and technological accomplishments of the Cassini-Huygens mission, exploring Titan and Enceladus in ways that are not currently possible (full close-up and in situ coverage over long periods of time). In the current mission architecture, TandEM proposes to deliver two medium-sized spacecraft to the Saturnian system. One spacecraft would be an orbiter with a large host of instruments which would perform several Enceladus flybys and deliver penetrators to its surface before going into a dedicated orbit around Titan alone, while the other spacecraft would carry the Titan in situ investigation components, i.e. a hot-air balloon (MontgolfiSre) and possibly several landing probes to be delivered through the atmosphere.
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| 3. |
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| 4. |
- Kurki, MI, et al.
(författare)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Tidskriftsartikel (refereegranskat)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 5. |
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| 6. |
- Nilsson, Hans, et al.
(författare)
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Evolution of the ion environment of comet 67P/Churyumov-Gerasimenko
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 583
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Rosetta spacecraft is escorting comet 67P/Churyumov-Gerasimenko from a heliocentric distance of >3.6 AU, where the comet activity was low, until perihelion at 1.24 AU. Initially, the solar wind permeates the thin comet atmosphere formed from sublimation. Aims. Using the Rosetta Plasma Consortium Ion Composition Analyzer (RPC-ICA), we study the gradual evolution of the comet ion environment, from the first detectable traces of water ions to the stage where cometary water ions accelerated to about 1 keV energy are abundant. We compare ion fluxes of solar wind and cometary origin. Methods. RPC-ICA is an ion mass spectrometer measuring ions of solar wind and cometary origins in the 10 eV-40 keV energy range. Results. We show how the flux of accelerated water ions with energies above 120 eV increases between 3.6 and 2.0 AU. The 24 h average increases by 4 orders of magnitude, mainly because high-flux periods become more common. The water ion energy spectra also become broader with time. This may indicate a larger and more uniform source region. At 2.0 AU the accelerated water ion flux is frequently of the same order as the solar wind proton flux. Water ions of 120 eV-few keV energy may thus constitute a significant part of the ions sputtering the nucleus surface. The ion density and mass in the comet vicinity is dominated by ions of cometary origin. The solar wind is deflected and the energy spectra broadened compared to an undisturbed solar wind. Conclusions. The flux of accelerated water ions moving from the upstream direction back toward the nucleus is a strongly nonlinear function of the heliocentric distance.
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| 7. |
- Osterlund, P., et al.
(författare)
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Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study
- 2022
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Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce.Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity.Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/ infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11).Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
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| 8. |
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| 9. |
- Pollinger, F., et al.
(författare)
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The European GeoMetre project : developing enhanced large-scale dimensional metrology for geodesy
- 2023
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Ingår i: Applied Geomatics. - : Springer Science and Business Media Deutschland GmbH. - 1866-9298 .- 1866-928X. ; 15:2, s. 371-381
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Tidskriftsartikel (refereegranskat)abstract
- We provide a survey on the joint European research project “GeoMetre”, which explores novel technologies and their inclusion to existing surveying strategies to improve the traceability of geodetic reference frames to the SI definition of the metre. This work includes the development of novel distance meters with a range of up to 5 km, the realisation of optical multilateration systems for large structure monitoring at an operation distance of 50 m and beyond, and a novel strategy for GNSS-based distance determination. Different methods for refractivity compensation, based on classical sensors, on dispersion, on spectroscopic thermometry, and on the speed of sound to reduce the meteorological uncertainties in precise distance measurements, are developed further and characterised. These systems are validated at and applied to the novel European standard baseline EURO5000 at the Pieniny Kippen Belt, Poland, which was completely refurbished and intensely studied in this project. We use our novel instruments for a reduced uncertainty of the scale in the surveillance networks solutions for local tie measurements at space-geodetic co-location stations. We also investigate novel approaches like close-range photogrammetry to reference point determination of space-geodetic telescopes. Finally, we also investigate the inclusion of the local gravity field to consider the deviations of the vertical in the data analysis and to reduce the uncertainty of coordinate transformations in this complex problem.
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| 10. |
- Carlsson, Ella, et al.
(författare)
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Mass composition of the escaping plasma at Mars
- 2006
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 182:2, s. 320-328
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Tidskriftsartikel (refereegranskat)abstract
- Data from the Ion Mass Analyzer (IMA) sensor of the ASPERA-3 instrument suite on Mars Express have been analyzed to determine the mass composition of the escaping ion species at Mars. We have examined 77 different ion-beam events and we present the results in terms of flux ratios between the following ion species: CO2+/O+ and O-2(+)/O+. The following ratios averaged over all events and energies were identified: CO2+/O+ = 0.2 and O-2(+)/O+ = 0.9. The values measured are significantly higher, by a factor of 10 for O-2(+)/O+, than a contemporary modeled ratio for the maximum fluxes which the martian ionosphere can supply. The most abundant ion species was found to be O+, followed by O-2(+) and CO2+. We estimate the loss of CO2+ to be 4.0 x 10(24) s(-1) (0.29 kg s(-1)) by using the previous measurements of Phobos-2 in our calculations. The dependence of the ion ratios in relation to their energy ranges we studied, 0.3-3.0 keV, indicated that no clear correlation was found.
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