| 1. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 2. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 3. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 4. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 5. |
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| 6. |
- Alam, Naveed, et al.
(författare)
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Large scale travelling fire tests with open ventilation conditions and their effect on the surrounding steel structure– The second fire test
- 2022
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Ingår i: Journal of constructional steel research. - : Elsevier Ltd. - 0143-974X .- 1873-5983. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- In the frame of the European RFCS (Research Fund for Coal and Steel) TRAFIR (Characterization of TRAvelling FIRes in large compartments) project, three natural fire tests in a large compartment were conducted at Ulster University. The aim of this investigation was to understand the conditions in which the travelling fires develop and to study the impact of such fires on the surrounding steel structure. This paper provides details of the second fire test where the size of the openings was reduced to induce different ventilation conditions in comparison to the first fire test. During the test, behaviour of the travelling fire was observed and the gas temperatures at different levels and locations were recorded. The influence of travelling fires on the surrounding structure is studied in terms of the temperatures recorded in the selected steel columns and beams. The influence of change in the ventilation conditions is presented and highlighted through the comparison of results of the second fire test with those recorded earlier during the first fire test. It was found that the travelling fires produce non-uniform temperatures in the compartment irrespective of the ventilation conditions although the magnitude of this non-uniformity is related with the opening sizes. This non-uniformity exists along the length as well as along the height of the test compartment. It was found that for reduced opening sizes, more heat is retained within the compartment which induces higher temperatures in the surrounding steel structure. The transient heating of the surrounding structure caused by travelling fires should be considered while performing the structural fire design of large compartments. The results obtained during the test are state-of-the-art and will help in understating the behaviour of travelling fires and their influence on the surrounding structure which will help to devise fire design methods for future use.
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| 7. |
- Anderson, Johan, et al.
(författare)
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FDS SIMULATIONS AND MODELLING EFFORTS OF TRAVELLING FIRES IN A LARGE ELONGATED COMPARTMENT
- 2019
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Ingår i: Interflam 2019, proceedings. - : Interscience Communications. ; , s. 2085-
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Konferensbidrag (refereegranskat)abstract
- The present paper investigates a travelling fire scenario in an elongated structure (Length 18 m x width 6 m x height 3 m) with a controlled fire source of six pans filled with diesel (width 4 m x length 0.5 m). The fire spread is controlled manually by initiating fires subsequently in the pools. Fire Dynamics Simulator (FDS) is used to a-priori investigate variations in geometry, material data and fire load whereas simulations using the final design were performed after the test. The input to the model beside fire source and geometry are thermal material data. The FDS simulation were used to determine the appropriate size of the downstands (2 m from the ceiling in the final design) on the side to create a sufficiently one-dimensional fire spread. The post test simulations indicate that although there are a lot of variations not included in the model similar results were obtained as in the test.
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| 8. |
- Anderson, Johan, et al.
(författare)
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FDS simulations and modelling efforts of travelling fires in a large elongated compartment
- 2021
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Ingår i: Fire and Materials. - : John Wiley and Sons Ltd. - 0308-0501 .- 1099-1018. ; 45:6, s. 699-
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Tidskriftsartikel (refereegranskat)abstract
- The present paper investigates a travelling fire scenario in an elongated structure (Length 18 m × width 6 m × height 3 m) with a controlled fire source of six trays filled with diesel (width 4 m × length 0.5 m). The fire spread is controlled manually by initiating fires consecutively in the pools. Fire dynamics simulator (FDS) is used to a-priori investigate variations in geometry, material data and fire load, whereas simulations using the final design and measured heat release rates (HRR) were performed after the test. The input to the model beside fire source and geometry are thermal material data. The FDS simulations were used to determine the appropriate size of the downstands (2 m from the ceiling in the final design) on the side to create a sufficiently one-dimensional fire spread. The post-test simulations indicate that although there are a lot of variations not included in the model similar results were obtained as in the test.
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| 9. |
- Bazarian, Jeffrey J., et al.
(författare)
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Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI) : a multicentre observational study
- 2018
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Ingår i: Lancet Neurology. - : Lancet Publishing Group. - 1474-4422 .- 1474-4465. ; 17:9, s. 782-789
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Tidskriftsartikel (refereegranskat)abstract
- Background: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI.Methods: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT.Findings: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative.Interpretation: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted.Funding: Banyan Biomarkers and US Army Medical Research and Materiel Command.
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| 10. |
- Charlier, Marion, et al.
(författare)
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TRAFIR: Characterization of TRAvelling FIRes in large compartments
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Inspection of recent fire events in large compartments reveals them to have a great deal of non-uniformity, they generally burn locally and move across floor plates over a period of time. This phenomenon which generates transient heating of the structure is idealized as “travelling fire”.A first series of tests was launched to define a fire load representative of an office building according to Eurocodes. Additional tests where the fire dynamics were controlled were launched to develop an understanding of the fire exposure to steel structures.Then, a second series of large scale tests were performed in real building dimensions. These tests had no artificial control over the dynamics, which allowed a realistic characterization of the fire. The fire load was identical for all tests, only the openings were modified.CFD numerical models were developed to reproduce the experimental campaign and to launch parametrical analyses. This allowed to provide information concerning the conditions which may lead (or not) to a travelling fire scenario.An analytical model for the characterization of a travelling fire was developed and implemented in a simple calculation tool. It allows to evaluate the fire location, the gas temperatures in the flames, the heat fluxes in the different parts of the compartment and the temperature in a steel member. In addition, the methodology is introduced in the FEM software SAFIR and OpenSees.Ultimately, a design guide was prepared including worked examples which are detailed step-by-step and for which the influence of the inputs on the results is analysed.
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