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- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 2. |
- Holmes, Robin B., et al.
(författare)
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Creation of an anthropomorphic CT head phantom for verification of image segmentation
- 2020
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Ingår i: Medical physics (Lancaster). - : Wiley-Blackwell. - 0094-2405 .- 2473-4209. ; 47:6, s. 2380-2391
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Many methods are available to segment structural magnetic resonance (MR) images of the brain into different tissue types. These have generally been developed for research purposes but there is some clinical use in the diagnosis of neurodegenerative diseases such as dementia. The potential exists for computed tomography (CT) segmentation to be used in place of MRI segmentation, but this will require a method to verify the accuracy of CT processing, particularly if algorithms developed for MR are used, as MR has notably greater tissue contrast.Methods: To investigate these issues we have created a three-dimensional (3D) printed brain with realistic Hounsfield unit (HU) values based on tissue maps segmented directly from an individual T1 MRI scan of a normal subject. Several T1 MRI scans of normal subjects from the ADNI database were segmented using SPM12 and used to create stereolithography files of different tissues for 3D printing. The attenuation properties of several material blends were investigated, and three suitable formulations were used to print an object expected to have realistic geometry and attenuation properties. A skull was simulated by coating the object with plaster of Paris impregnated bandages. Using two CT scanners, the realism of the phantom was assessed by the measurement of HU values, SPM12 segmentation and comparison with the source data used to create the phantom.Results: Realistic relative HU values were measured although a subtraction of 60 was required to obtain equivalence with the expected values (gray matter 32.9-35.8 phantom, 29.9-34.2 literature). Segmentation of images acquired at different kVps/mAs showed excellent agreement with the source data (Dice Similarity Coefficient 0.79 for gray matter). The performance of two scanners with two segmentation methods was compared, with the scanners found to have similar performance and with one segmentation method clearly superior to the other.Conclusion: The ability to use 3D printing to create a realistic (in terms of geometry and attenuation properties) head phantom has been demonstrated and used in an initial assessment of CT segmentation accuracy using freely available software developed for MRI.
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| 3. |
- Takacs, J., et al.
(författare)
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Community engagement in public health emergency preparedness
- 2019
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 29:Suppl 4, s. 574-574
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCommunities that could be affected by infectious disease outbreaks are increasingly recognised as resources that may be effectively utilized by the authorities during public health emergencies.MethodsThis case study project, aiming to identify synergies between communities and authorities, was based on qualitative sources of evidence, including document and media review, stakeholder mapping, interviews and FGDs (N = 137). Four countries were selected for inclusion: Spain and the Netherlands on the basis of emerging tick-born disease incidents; Iceland and Ireland on the basis of acute gastroenteritis outbreaks.ResultsIn the Netherlands and Spain strong synergies were identified in tick surveillance activities, and the value of pre-existing networks of interest groups for preparedness and response activities was recognised. The Icelandic norovirus event was unexpected and fast-moving, while VTEC in Ireland is a familiar and slower-burning challenge. As a relatively common disease in Ireland, VTEC-protocols are closely followed, while a generic all-hazards approach was taken in Iceland. There was considerable community support in the responses in both countries., and in Iceland community representatives also actively participated in producing institutional post-event evaluations.ConclusionsAn over-riding principle emerging from this study is that an informed, at-risk community understands the challenges to adopting effective preventive practices for themselves better than anyone. Additional good practices included the utilisation of pre-existing stakeholder networks for information dissemination; and of monitoring community perceptions of any public health incident, including through social media, in order to identify and manage misperceptions. Efforts to build on the community engagement activities that are already in place in the four countries could contribute to better preparedness planning and more efficient and timely responses in future outbreaks.Key messagesRecognise the community as a real partner in outbreak preparedness, response, and recovery.Optimise communications with communities who may be affected by outbreaks.
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