| 1. |
- Cleynen, Isabelle, et al.
(author)
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Inherited determinants of Crohn's disease and ulcerative colitis phenotypes : a genetic association study
- 2016
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In: The Lancet. - New York, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 387:10014, s. 156-167
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Journal article (peer-reviewed)abstract
- Background: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile.Findings: After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10(-78)), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10(-18)). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10(-4)).Interpretation: Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time.Funding: International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).
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| 2. |
- Daly, Tim, et al.
(author)
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Experimental investigation of the effects of the presence and operation of tidal turbine arrays in a split tidal channel
- 2011
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In: Proceedings of the World Renewable Energy Congress. - : Linköping University.
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Book chapter (peer-reviewed)abstract
- The installation of arrays and farms is the next major step in the development of tidal energy converters. Many tidal farms are currently in the process of development. A number of studies have also identified potentially lucrative sites for future farm and array development elsewhere. In some of these sites, the flow velocities can at least in part be attributed to the presence of constraining landmasses and the resultant splitting of channels into two or more sub channels. Given the cubic relationship between flow velocity and kinetic energy flux, even modest acceleration in these areas can cause a considerable increase the potential power available. The analysis in this paper investigates flow acceleration effects in a split tidal channel due to the presence of tidal turbine arrays. As well as their presence, the effect of changing lateral and longitudinal position of the array and number of turbines in the array was also examined. Results show that flow acceleration of up to 14% can occur in an empty channel due to the presence of tidal arrays. This could potentially have major implications for tidal farm design in areas where channels branch into multiple sub channels
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| 3. |
- Franke, Andre, et al.
(author)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Journal article (peer-reviewed)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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| 4. |
- Goyette, Philippe, et al.
(author)
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High-density mapping of the MHC identifies a shared role for HLA-DRB1*01 : 03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis
- 2015
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In: Nature Genetics. - New York, USA : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:2, s. 172-179
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Journal article (peer-reviewed)abstract
- Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
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| 5. |
- Martell, Josefin, et al.
(author)
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The scale of a martian hydrothermal system explored using combined neutron and x-ray tomography
- 2022
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:19
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Journal article (peer-reviewed)abstract
- Nakhlite meteorites are igneous rocks from Mars that were aqueously altered ~630 million years ago. Hydrothermal systems on Earth are known to provide microhabitats; knowledge of the extent and duration of these systems is crucial to establish whether they could sustain life elsewhere in the Solar System. Here, we explore the three-dimensional distribution of hydrous phases within the Miller Range 03346 nakhlite meteorite using nondestructive neutron and x-ray tomography to determine whether alteration is interconnected and pervasive. The results reveal discrete clusters of hydrous phases within and surrounding olivine grains, with limited interconnectivity between clusters. This implies that the fluid was localized and originated from the melting of local subsurface ice following an impact event. Consequently, the duration of the hydrous alteration was likely short, meaning that the martian crust sampled by the nakhlites could not have provided habitable environments that could harbor any life on Mars during the Amazonian.
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| 6. |
- Zachén, Gabriel, et al.
(author)
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A Survey of Metal Microstructures in the Vaca Muerta Mesosiderite
- 2019
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Conference paper (other academic/artistic)abstract
- Summary: Microstructures from the millimeter- tonanometer scale have been studied and described in ametal nodule from the Vaca Muerta mesosiderite. Ourobservations are interpreted in the context of formationmechanisms.
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| 7. |
- Glasbey, JC, et al.
(author)
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- 2021
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| 8. |
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| 9. |
- Bravo, L, et al.
(author)
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- 2021
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| 10. |
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| 11. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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