| 1. |
- Franke, Andre, et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Basu, Neil, et al.
(författare)
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EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 1468-2060 .- 0003-4967. ; 69:10, s. 1744-1750
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The systemic vasculitides are multiorgan diseases where early diagnosis and treatment can significantly improve outcomes. Robust nomenclature reduces diagnostic delay. However, key aspects of current nomenclature are widely perceived to be out of date, these include disease definitions, classification and diagnostic criteria. Therefore, the aim of the present work was to identify deficiencies and provide contemporary points to consider for the development of future definitions and criteria in systemic vasculitis. Methods The expert panel identified areas of concern within existing definitions/criteria. Consequently, a systematic literature review was undertaken looking to address these deficiencies and produce 'points to consider' in accordance with standardised European League Against Rheumatism (EULAR) operating procedures. In the absence of evidence, expert consensus was used. Results There was unanimous consensus for re-evaluating existing definitions and developing new criteria. A total of 17 points to consider were proposed, covering 6 main areas: biopsy, laboratory testing, diagnostic radiology, nosology, definitions and research agenda. Suggestions to improve and expand current definitions were described including the incorporation of anti-neutrophil cytoplasm antibody and aetiological factors, where known. The importance of biopsy in diagnosis and exclusion of mimics was highlighted, while equally emphasising its problems. Thus, the role of alternative diagnostic tools such as MRI, ultrasound and surrogate markers were also discussed. Finally, structures to develop future criteria were considered. Conclusions Limitations in current classification criteria and definitions for vasculitis have been identified and suggestions provided for improvement. Additionally it is proposed that, in combination with the updated evidence, these should form the basis of future attempts to develop and validate revised criteria and definitions of vasculitis.
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| 3. |
- Field, Christopher B., et al.
(författare)
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Summary for Policymakers
- 2014
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Ingår i: Climate Change 2014: Impacts, Adaptation, and Vulnerability. Part A: Global and SectoralAspects.. - 9781107415379 ; , s. 1-32
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Bokkapitel (refereegranskat)
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| 4. |
- Haynes, Roger, et al.
(författare)
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The 4MOST instrument concept overview
- 2014
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Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 0277-786X .- 1996-756X. ; 9147, s. 91476-91476
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Konferensbidrag (refereegranskat)abstract
- The 4MOST([1]) instrument is a concept for a wide-field, fibre-fed high multiplex spectroscopic instrument facility on the ESO VISTA telescope designed to perform a massive (initially >25x10(6) spectra in 5 years) combined all-sky public survey. The main science drivers are: Gaia follow up of chemo-dynamical structure of the Milky Way, stellar radial velocities, parameters and abundances, chemical tagging; eROSITA follow up of cosmology with x-ray clusters of galaxies, X-ray AGN/galaxy evolution to z similar to 5, Galactic X-ray sources and resolving the Galactic edge; Euclid/LSST/SKA and other survey follow up of Dark Energy, Galaxy evolution and transients. The surveys will be undertaken simultaneously requiring: highly advanced targeting and scheduling software, also comprehensive data reduction and analysis tools to produce high-level data products. The instrument will allow simultaneous observations of similar to 1600 targets at R similar to 5,000 from 390-900nm and similar to 800 targets at R>18,000 in three channels between similar to 395-675nm (channel bandwidth: 45nm blue, 57nm green and 69nm red) over a hexagonal field of view of similar to 4.1 degrees2. The initial 5-year 4MOST survey is currently expect to start in 2020. We provide and overview of the 4MOST systems: opto-mechanical, control, data management and operations concepts; and initial performance estimates.
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| 5. |
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| 6. |
- Lyons, Paul A, et al.
(författare)
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Genetically Distinct Subsets within ANCA-Associated Vasculitis
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 367:3, s. 214-223
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND less thanbrgreater than less thanbrgreater thanAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegeners granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. less thanbrgreater than less thanbrgreater thanMETHODS less thanbrgreater than less thanbrgreater thanA genomewide association study was performed in a discovery cohort of 1233 U. K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. less thanbrgreater than less thanbrgreater thanRESULTS less thanbrgreater than less thanbrgreater thanWe found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2x10(-89), P = 5.6x10(-12), and P = 2.6x10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1x10(-8)). less thanbrgreater than less thanbrgreater thanCONCLUSIONS less thanbrgreater than less thanbrgreater thanThis study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.)
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| 7. |
- Aartsen, M. G., et al.
(författare)
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Evidence for High-Energy Extraterrestrial Neutrinos at the IceCube Detector
- 2013
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 342:6161, s. 947-
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Tidskriftsartikel (refereegranskat)abstract
- We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4 sigma level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.
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| 8. |
- Aartsen, M. G., et al.
(författare)
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First Observation of PeV-Energy Neutrinos with IceCube
- 2013
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 111:2, s. 021103-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04 +/- 0.16 and 1.14 +/- 0.17 PeV, respectively, the highest neutrino energies observed so far. These events are consistent with fully contained particle showers induced by neutral-current nu(e,mu,tau) ((nu) over bar (e,mu,tau)) or charged-current nu(e) ((nu) over bar (e)) interactions within the IceCube detector. The events were discovered in a search for ultrahigh energy neutrinos using data corresponding to 615.9 days effective live time. The expected number of atmospheric background is 0.082 +/- 0.004(stat)(-0.057)(+0.041)(syst). The probability of observing two or more candidate events under the atmospheric background-only hypothesis is 2.9 x 10(-3) (2.8 sigma) taking into account the uncertainty on the expected number of background events. These two events could be a first indication of an astrophysical neutrino flux; the moderate significance, however, does not permit a definitive conclusion at this time.
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| 9. |
- Aartsen, M. G., et al.
(författare)
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IceCube search for dark matter annihilation in nearby galaxies and galaxy clusters
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:12
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a first search for self-annihilating dark matter in nearby galaxies and galaxy clusters using a sample of high-energy neutrinos acquired in 339.8 days of live time during 2009/10 with the IceCube neutrino observatory in its 59-string configuration. The targets of interest include the Virgo and Coma galaxy clusters, the Andromeda galaxy, and several dwarf galaxies. We obtain upper limits on the cross section as a function of the weakly interacting massive particle mass between 300 GeV and 100 TeV for the annihilation into b (b) over bar, W+(W) over bar (-), tau(+)tau(-), mu(+)mu(-) , and nu(nu) over bar. A limit derived for the Virgo cluster, when assuming a large effect from subhalos, challenges the weakly interacting massive particle interpretation of a recently observed GeV positron excess in cosmic rays.
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| 10. |
- Aartsen, M. G., et al.
(författare)
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Improvement in fast particle track reconstruction with robust statistics
- 2014
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 736, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube project has transformed 1 km(3) of deep natural Antarctic ice into a Cherenkov detector Muon neutrinos are detected and their direction is inferred by mapping the light produced by the secondary muon track inside the volume instrumented with photomultipliers. Reconstructing the muon track from the observed light is challenging due to noise, light scattering in the ice medium, and the possibility of simultaneously having multiple muons inside the detector, resulting from the large flux of cosmic ray muons. This paper describes work on two problems: (1) the truck reconstruction problem, in which, given a set of observations, the goal is to recover the track of a muon; and (2) the coincident event problem, which is to determine how many muons are active in the detector during a time window. Rather than solving these problems by developing more complex physical models that are applied at later stages of the analysis, our approach is to augment the detector's early reconstruction with data filters and robust statistical techniques. These can be implemented at the level of on-line reconstruction and, therefore, improve all subsequent reconstructions. Using the metric of median angular resolution, a standard metric for track reconstruction, we improve the accuracy in the initial reconstruction direction by 13%. We also present improvements in measuring the number of muons in coincident events: we can accurately determine the number of muons 98% of the time.
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