| 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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| 3. |
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| 4. |
- Heap, Graham A., et al.
(författare)
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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| 5. |
- Heap, Michael J., et al.
(författare)
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Hydrothermal alteration of andesitic lava domes can lead to explosive volcanic behaviour
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Dome-forming volcanoes are among the most hazardous volcanoes on Earth. Magmatic outgassing can be hindered if the permeability of a lava dome is reduced, promoting pore pressure augmentation and explosive behaviour. Laboratory data show that acid-sulphate alteration, common to volcanoes worldwide, can reduce the permeability on the sample lengthscale by up to four orders of magnitude and is the result of pore- and microfracture-filling mineral precipitation. Calculations using these data demonstrate that intense alteration can reduce the equivalent permeability of a dome by two orders of magnitude, which we show using numerical modelling to be sufficient to increase pore pressure. The fragmentation criterion shows that the predicted pore pressure increase is capable of fragmenting the majority of dome-forming materials, thus promoting explosive volcanism. It is crucial that hydrothermal alteration, which develops over months to years, is monitored at dome-forming volcanoes and is incorporated into real-time hazard assessments.
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| 6. |
- Darmawan, Herlan, et al.
(författare)
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Hidden mechanical weaknesses within lava domes provided by buried high-porosity hydrothermal alteration zones
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Catastrophic lava dome collapse is considered an unpredictable volcanic hazard because the physical properties, stress conditions, and internal structure of lava domes are not well understood and can change rapidly through time. To explain the locations of dome instabilities at Merapi volcano, Indonesia, we combined geochemical and mineralogical analyses, rock physical property measurements, drone-based photogrammetry, and geoinformatics. We show that a horseshoe-shaped alteration zone that formed in 2014 was subsequently buried by renewed lava extrusion in 2018. Drone data, as well as geomechanical, mineralogical, and oxygen isotope data suggest that this zone is characterized by high-porosity hydrothermally altered materials that are mechanically weak. We additionally show that the new lava dome is currently collapsing along this now-hidden weak alteration zone, highlighting that a detailed understanding of dome architecture, made possible using the monitoring techniques employed here, is essential for assessing hazards associated with dome and edifice failure at volcanoes worldwide.
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| 7. |
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| 8. |
- Harnett, Claire E., et al.
(författare)
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Large-scale lava dome fracturing as a result of concealed weakened zones
- 2022
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Ingår i: Geology. - : Geological Society of America. - 0091-7613 .- 1943-2682. ; 50:12, s. 1346-1350
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Tidskriftsartikel (refereegranskat)abstract
- Mechanically weakened alteration zones in lava domes are thought to jeopardize their stability. Such zones can be hazardous when concealed within the dome, either because they formed by subsurface hydrothermal circulation or because they formed on the surface but were subsequently buried by renewed lava extrusion. We present a new suite of computa-tional models showing how the size and position of a weakened brittle zone within a dome can affect large-scale fracture formation, displacement, and the collapse mechanism. By combining recent laboratory data for the mechanical behavior of dome rocks with discrete element method models, we show (1) the presence of a weak zone increases instability, which is exacerbated when the size of the zone increases or the zone is positioned off-center; (2) the position of the weak zone changes the deformation mechanism from slumping-type slope de-formation when the zone is positioned centrally, compared with deep-seated rotational slope failure when the zone is positioned toward the dome flank; and finally, (3) dome-cutting tensile fractures form in the presence of a small weak zone (60 m diameter, -14% of dome width), whereas large weak zones (120 m diameter, -27% of dome width) promote the formation of longer and deeper fractures that jeopardize larger dome volumes. Our results corroborate previous field observations at lava domes and indicate that large fracture formation, which greatly influences dome stability and outgassing, can be explained by the presence of con-cealed alteration zones. This improved understanding of the mechanisms responsible for dome instability enables better hazard assessment at volcanoes worldwide.
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| 10. |
- Heap, Michael J., et al.
(författare)
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The thermal properties of porous andesite
- 2020
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Ingår i: Journal of Volcanology and Geothermal Research. - : ELSEVIER. - 0377-0273 .- 1872-6097. ; 398
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Tidskriftsartikel (refereegranskat)abstract
- The thermal properties of volcanic rocks are crucial to accurately model heat transfer in volcanoes and in geothermal systems located within volcanic deposits. Here we provide laboratory measurements of thermal conductivity and thermal diffusivity for variably porous andesites from Mt. Ruapehu (New Zealand) and variably altered basaltic-andesites from Merapi volcano (Indonesia) measured at ambient laboratory pressure and temperature using the transient hot-strip method. The specific heat capacity of each sample was then calculated using these measured values and the bulk sample density. Thermal conductivity and thermal diffusivity decrease as a function of increasing porosity, but specific heat capacity does not vary systematically with porosity. For a given porosity, saturation with water increases thermal conductivity and specific heat capacity, but decreases thermal diffusivity. Measurements on samples from Merapi volcano show that, compared to the unaltered samples from Mt. Ruapehu, hydrothermal alteration deceases thermal conductivity and thermal diffusivity, and increases specific heat capacity. We use an effective medium approach to parameterise these data, showing that when the porosity and pore-fluid properties are scaled for, the measured values agree well with theoretical predictions. We find that despite the microstructural complexity of the studied andesites, porosity is the principal parameter dictating their thermal properties. To understand whether the measured changes in thermal properties are sufficient to influence natural processes, we model heat transfer from magma to the surrounding host-rock by solving Fick's second law cast in 1D Cartesian (dyke geometry) and cylindrical (conduit geometry) coordinates. We provide models for different host-rock porosities (0-0.6), different initial magmatic temperatures (800-1200 degrees C), and different levels of host-rock alteration. Our modelling shows how the cooling of a dyke and conduit is slowed by a higher host-rock porosity and by increased hydrothermal alteration. The thermal properties provided herein can help improve modelling designed to inform on volcanic and geothermal processes. (C) 2020 Elsevier B.V. All rights reserved.
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