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| 6. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 7. |
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| 9. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 22. |
- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 23. |
- Abreu, P., et al.
(författare)
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Measurement of the gluon fragmentation function and a comparison of the scaling violation in gluon and quark jets
- 2000
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 13:4, s. 573-589
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Tidskriftsartikel (refereegranskat)abstract
- The fragmentation functions of quarks and gluons are measured in various three-jet topologies in Z decays from the full data set collected with the DELPHI detector at the Z resonance between 1992 and 995. The results at different values of transverse momentum-like scales are compared. A parameterization of the quark and gluon fragmentation functions at a fixed reference scale is given. The quark and gluon fragmentation functions show the predicted pattern of scaling violations. The scaling violation for quark jets as a function of a transverse momentum-like scale is in a good agreement with that observed in lower energy e+e- annihilation experiments. For gluon jets it appears to be significantly stronger. The scale dependences of the gluon and quark fragmentation functions agree with the prediction of the DGLAP evolution equations from which the colour factor ratio CA/CF is measured to be: CA/CF = 2.26 ± 0.09stat. ± 0.06sys. ± 0.12clus.,scale..
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| 24. |
- Abreu, P., et al.
(författare)
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Study of dimuon production in photon-photon collisions and measurement of QED photon structure functions at LEP
- 2001
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 19:1, s. 15-28
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Tidskriftsartikel (refereegranskat)abstract
- Muon pair production in the process e+e- → e+e- μ+μ- is studied using the data taken at LEP1 (√s ≃ mz) with the DELPHI detector during the years 1992-1995. The corresponding integrated luminosity is 138.5 pb-1. The QED predictions have been tested over the whole Q2 range accessible at LEP1 (from several GeV2/c4 to several hundred GeV2/c4) by comparing experimental distributions with distributions resulting from Monte Carlo simulations using various generators. Selected events are used to extract the leptonic photon structure function Fγ 2. Azimuthal correlations are used to obtain information on additional structure functions, Fγ A and Fγ B, which originate from interference terms of the scattering amplitudes. The measured ratios Fγ A/Fγ 2 and FγB/Fγ 2 are significantly different from zero and consistent with QED predictions.
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| 25. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 26. |
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| 27. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 28. |
- Abdesselam, A., et al.
(författare)
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The ATLAS semiconductor tracker end-cap module
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 575:3, s. 353-389
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Tidskriftsartikel (refereegranskat)abstract
- The challenges for the tracking detector systems at the LHC are unprecedented in terms of the number of channels, the required read-out speed and the expected radiation levels. The ATLAS Semiconductor Tracker. (SCT) end-caps have a total of about 3 million electronics channels each reading out every 25 ns into its own on-chip 3.3 mu s buffer. The highest anticipated dose after 10 years operation is 1.4x10(14) cm(-2) in units of 1 MeV neutron equivalent (assuming the damage factors scale with the non-ionising energy loss). The forward tracker has 1976 double-sided modules, mostly of area similar to 70 cm(2), each having 2 x 768 strips read out by six ASICs per side. The requirement to achieve an average perpendicular radiation length of 1.5% X-0, while coping with up to 7 W dissipation per module (after irradiation), leads to stringent constraints on the thermal design. The additional requirement of 1500e(-) equivalent noise charge (ENC) rising to only 1800e(-) ENC after irradiation, provides stringent design constraints on both the high-density Cu/Polyimide flex read-out circuit and the ABCD3TA read-out ASICs. Finally, the accuracy of module assembly must not compromise the 16 mu m (r phi) resolution perpendicular to the strip directions or 580 mu m radial resolution coming from the 40 mrad front-back stereo angle. A total of 2210 modules were built to the tight tolerances and specifications required for the SCT. This was 234 more than the 1976 required and represents a yield of 93%. The component flow was at times tight, but the module production rate of 40-50 per week was maintained despite this. The distributed production was not found to be a major logistical problem and it allowed additional flexibility to take advantage of where the effort was available, including any spare capacity, for building the end-cap modules. The collaboration that produced the ATLAS SCT end-cap modules kept in close contact at all times so that the effects of shortages or stoppages at different sites could be rapidly resolved.
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| 29. |
- Abreu, P., et al.
(författare)
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Search for sleptons in e+e- collisions at √s = 183 to 189 GeV
- 2001
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 19:1, s. 29-42
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Tidskriftsartikel (refereegranskat)abstract
- Data taken by the DELPHI experiment at centre-of-mass energies of 183 GeV and 189 GeV with a total integrated luminosity of 212 pb-1 have been used to search for the supersymmetric partners of the electrons, muons, and taus in the context of the Minimal Supersymmetric Standard Model (MSSM). The decay topologies searched for were the direct decay (ℓ̃ → ℓx̃), producing acoplanar lepton pairs plus missing energy, and the cascade decay (ℓ → ℓx̃0 2 → ℓγx̃0 1), producing acoplanar lepton and photon pairs plus missing energy. The observed number of events is in agreement with Standard Model predictions. The 95% CL excluded mass limits for selectrons, smuons and staus are mẽ ≤ 87 GeV/c2, mμ̃ ≤ 80 GeV/c2 and mτ̃ 75 GeV/c2, respectively, for values of μ=-200 GeV/c2 and tanβ=1.5.
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| 30. |
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| 31. |
- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 32. |
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| 33. |
- Teumer, A, et al.
(författare)
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
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| 35. |
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| 36. |
- Akiba, K., et al.
(författare)
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The LHCb VELO Upgrade module construction
- 2024
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- The LHCb detector has undergone a major upgrade for LHC Run 3. This Upgrade I detector facilitates operation at higher luminosity and utilises full-detector information at the LHC collision rate, critically including the use of vertex information. A new vertex locator system, the VELO Upgrade, has been constructed. The core element of the new VELO are the double-sided pixelated hybrid silicon detector modules which operate in vacuum close to the LHC beam in a high radiation environment. The construction and quality assurance tests of these modules are described in this paper. The modules incorporate 200 mu m thick, n -on -p silicon sensors bump-bonded to 130 nm technology ASICs. These are attached with high precision to a silicon microchannel substrate that uses evaporative CO 2 cooling. The ASICs are controlled and read out with flexible printed circuits that are glued to the substrate and wire -bonded to the chips. The mechanical support of the module is given by a carbon fibre plate, two carbon fibre rods and an aluminium plate. The sensor attachment was achieved with an average precision of 21 mu m, more than 99.5% of all pixels are fully functional, and a thermal figure of merit of 3 Kcm 2 W - 1 was achieved. The production of the modules was successfully completed in 2021, with the final assembly and installation completed in time for data taking in 2022.
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| 37. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 38. |
- Harcourt, R., et al.
(författare)
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Animal-borne telemetry: An integral component of the ocean observing toolkit
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUN
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Tidskriftsartikel (refereegranskat)abstract
- Animal telemetry is a powerful tool for observing marine animals and the physical environments that they inhabit, from coastal and continental shelf ecosystems to polar seas and open oceans. Satellite-linked biologgers and networks of acoustic receivers allow animals to be reliably monitored over scales of tens of meters to thousands of kilometers, giving insight into their habitat use, home range size, the phenology of migratory patterns and the biotic and abiotic factors that drive their distributions. Furthermore, physical environmental variables can be collected using animals as autonomous sampling platforms, increasing spatial and temporal coverage of global oceanographic observation systems. The use of animal telemetry, therefore, has the capacity to provide measures from a suite of essential ocean variables (EOVs) for improved monitoring of Earth's oceans. Here we outline the design features of animal telemetry systems, describe current applications and their benefits and challenges, and discuss future directions. We describe new analytical techniques that improve our ability to not only quantify animal movements but to also provide a powerful framework for comparative studies across taxa. We discuss the application of animal telemetry and its capacity to collect biotic and abiotic data, how the data collected can be incorporated into ocean observing systems, and the role these data can play in improved ocean management. © 2019 Harcourt, Sequeira, Zhang, Roquet, Komatsu, Heupel, McMahon, Whoriskey, Meekan, Carroll, Brodie, Simpfendorfer, Hindell, Jonsen, Costa, Block, Muelbert, Woodward, Weise, Aarestrup, Biuw, Boehme, Bograd, Cazau, Charrassin, Cooke, Cowley, de Bruyn, Jeanniard du Dot, Duarte, Eguíluz, Ferreira, Fernández-Gracia, Goetz, Goto, Guinet, Hammill, Hays, Hazen, Hückstädt, Huveneers, Iverson, Jaaman, Kittiwattanawong, Kovacs, Lydersen, Moltmann, Naruoka, Phillips, Picard, Queiroz, Reverdin, Sato, Sims, Thorstad, Thums, Treasure, Trites, Williams, Yonehara and Fedak.
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| 39. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 40. |
- Aktas, Özge, et al.
(författare)
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Single-particle structures in 85,87Ge
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X.
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray transitions have been identified for the first time in the extremely neutron-rich (N =Z + 25) nucleus 87 Ge following nucleon knockout reactions studied at the RIBF, RIKEN, Japan.New γ-ray transitions from excited states in 85 Ge were also observed and placed in a tentative levelscheme. The exclusive parallel momentum distribution was measured for the 1/2 + state for theneutron knockout reaction leading to 85 Ge which is compared with calculated distorted wave impulseapproximation (DWIA) distributions. The 85,87 Ge results are compared with large-scale shell-modelcalculations and potential energy surface calculations based on the total Routhian surface formalism.
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| 41. |
- Pfaller, M.A., et al.
(författare)
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Twelve years of fluconazole in clinical practice : Global-trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida
- 2004
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 10:SUPPL. 1, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI) isolates of Candida spp. collected from 250 medical centres in 32 nations over a 10-year period from 1992 through 2001. The species included 3401 C. albicans, 984 C. glabrata, 796 C. parapsilosis, 585 C. tropicalis, 153 C. krusei, 67 C. lusitaniae, 48 C. guilliermondii, 10 C. famata, 10 C. kefyr, six C. pelliculosa, five C. rugosa, four C. lipolytica, three C. dubliniensis, three C. inconspicua, two C. sake and one isolate each of C. lambica, C. norvegensis and C. zeylanoides. Minimum inhibitory concentration determinations were made using the National Committee for Clinical Laboratory Standards reference broth microdilution method. Variation in the rank order and frequency of the different species of Candida was observed over time and by geographic area. The proportion of BSI due to C. albicans and C. glabrata increased and C. parapsilosis decreased over time in Canada, the USA and Europe. C. glabrata was an infrequent cause of BSI in Latin America and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observed among isolates of C. albicans, C. tropicalis and C. parapsilosis. These species accounted for 78% of all BSI and remained highly susceptible (91-100% susceptible) to fluconazole from 1992 to 2001 irrespective of geographic origin. The prevalence of fluconazole resistance among C. glabrata isolates was variable both over time and among the various countries and regions. Resistance to fluconazole among C. glabrata isolates was greatest in the USA and varied by US census region (range 0-23%). These observations are generally encouraging relative to the sustained usefulness of fluconazole as a systemically active antifungal agent for the treatment of candida BSI. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.
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| 42. |
- Pirozhkov, A. S., et al.
(författare)
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Diagnostic of laser contrast using target reflectivity
- 2009
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 94:24
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Tidskriftsartikel (refereegranskat)abstract
- Using three different laser systems, we demonstrate a convenient and simple plasma based diagnostic of the contrast of high-power short-pulse lasers. The technique is based on measuring the specular reflectivity from a solid target. The reflectivity remains high even at relativistic intensities above 10(19) W/cm(2) in the case of a high-contrast prepulse-free laser. On the contrary, the specular reflectivity drops with increasing intensities in the case of systems with insufficient contrast due to beam breakup and increased absorption caused by preplasma.
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| 43. |
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| 44. |
- Nijkamp, P., et al.
(författare)
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Towards a regional science academy : A manifesto
- 2016
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Ingår i: Region. - : European Regional Science Association. - 2409-5370. ; 3:1, s. R1-R16
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Tidskriftsartikel (refereegranskat)abstract
- This Manifesto provides a joint proposal to create a Regional Science Academy as a think-tank support platform for a strategic development of the spatial sciences. The Regional Science Academy is a strategic spatial knowledge catalyst: it acts as a global intellectual powerhouse for new knowledge network initiatives and scholarly views on regions and cities as vital centrepieces of interconnected spatial systems. This contribution highlights its role and presents various activity plans.
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| 45. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 46. |
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| 47. |
- Wang, T, et al.
(författare)
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Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4932-
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Tidskriftsartikel (refereegranskat)abstract
- Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E−06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E−07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype–genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.
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| 48. |
- Aktas, Özge, 1987-, et al.
(författare)
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First observation of γ-ray transitions in 111Mo
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X.
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the extremely neutron-rich nuclei 109Mo and 111Mo have been studied following nucleon knock-out reactions. Seven $\gamma$-ray transitions, some of them in prompt mutual coincidence, have been identified for the first time in 11Mo using the DALI2 and MINOS detector systems at the BigRIPS and ZeroDegree electromagnetic fragments separator at the RIBF, RIKEN, Japan. Total Routhian surface (TRS) and Particle- Plus Rotor calculations have been performed to investigate the predicted shape coexistence and its effect on the structure of nuclei in this region of the nuclear chart. Following the results of the calculations, theoretical level schemes are proposed for positive and negative parity states and compared with the experimental findings.
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| 49. |
- Blom, A. W., et al.
(författare)
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Infection after total joint replacement of the hip and knee: research programme including the INFORM RCT
- 2022
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Ingår i: Programme Grants for Applied Research. - 2050-4322. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: People with severe osteoarthritis, other joint conditions or injury may have joint replacement to reduce pain and disability. In the UK in 2019, over 200,000 hip and knee replacements were performed. About 1 in 100 replacements becomes infected, and most people with infected replacements require further surgery. Objectives: To investigate why some patients are predisposed to joint infections and how this affects patients and the NHS, and to evaluate treatments. Design: Systematic reviews, joint registry analyses, qualitative interviews, a randomised controlled trial, health economic analyses and a discrete choice questionnaire. Setting: Our studies are relevant to the NHS, to the Swedish health system and internationally. Participants: People with prosthetic joint infection after hip or knee replacement and surgeons. Interventions: Revision of hip prosthetic joint infection with a single-or two-stage procedure. Main outcome measures: Long-term patient-reported outcomes and reinfection. Cost-effectiveness of revision strategies over 18 months from two perspectives: health-care provider and Personal Social Services, and societal. Data sources: National Joint Registry; literature databases; published cohort studies; interviews with 67 patients and 35 surgeons; a patient discrete choice questionnaire; and the INFORM (INFection ORthopaedic Management) randomised trial. Review methods: Systematic reviews of studies reporting risk factors, diagnosis, treatment outcomes and cost comparisons. Individual patient data meta-analysis. Results: In registry analyses, about 0.62% and 0.75% of patients with hip and knee replacement, respectively, had joint infection requiring surgery. Rates were four times greater after aseptic revision. The costs of inpatient and day-case admissions in people with hip prosthetic joint infection were about five times higher than those in people with no infection, an additional cost of > £30,000. People described devastating effects of hip and knee prosthetic joint infection and treatment. In the treatment of hip prosthetic joint infection, a two-stage procedure with or without a cement spacer had a greater negative impact on patient well-being than a single-or two-stage procedure with a custom-made articulating spacer. Surgeons described the significant emotional impact of hip and knee prosthetic joint infection and the importance of a supportive multidisciplinary team. In systematic reviews and registry analyses, the risk factors for hip and knee prosthetic joint infection included male sex, diagnoses other than osteoarthritis, high body mass index, poor physical status, diabetes, dementia and liver disease. Evidence linking health-care setting and surgeon experience with prosthetic joint infection was inconsistent. Uncemented fixation, posterior approach and ceramic bearings were associated with lower infection risk after hip replacement. In our systematic review, synovial fluid alpha-defensin and leucocyte esterase showed high diagnostic accuracy for prosthetic joint infection. Systematic reviews and individual patient data meta-analysis showed similar reinfection outcomes in patients with hip or knee prosthetic joint infection treated with single-and two-stage revision. In registry analysis, there was a higher rate of early rerevision after single-stage revision for hip prosthetic joint infection, but, overall, 40% fewer operations are required as part of a single-stage procedure than as part of a two-stage procedure. The treatment of hip or knee prosthetic joint infection with early debridement and implant retention may be effective in > 60% of cases. In the INFORM randomised controlled trial, 140 patients with hip prosthetic joint infection were randomised to single-or two-stage revision. Eighteen months after randomisation, pain, function and stiffness were similar between the randomised groups (p = 0.98), and there were no differences in reinfection rates. Patient outcomes improved earlier in the single-stage than in the two-stage group. Participants randomised to a single-stag procedure had lower costs (mean difference –£10,055, 95% confidence interval –£19,568 to –£542) and higher quality-adjusted life-years (mean difference 0.06, 95% confidence interval –0.07 to 0.18) than those randomised to a two-stage procedure. Single-stage was the more cost-effective option, with an incremental net monetary benefit at a threshold of £20,000 per quality-adjusted life-year of £11,167 (95% confidence interval £638 to £21,696). In a discrete choice questionnaire completed by 57 patients 18 months after surgery to treat hip prosthetic joint infection, the most valued characteristics in decisions about revision were the ability to engage in valued activities and a quick return to normal activity. Limitations: Some research was specific to people with hip prosthetic joint infection. Study populations in meta-analyses and registry analyses may have been selected for joint replacement and specific treatments. The INFORM trial was not powered to study reinfection and was limited to 18 months’ follow-up. The qualitative study subgroups were small. Conclusions: We identified risk factors, diagnostic biomarkers, effective treatments and patient preferences for the treatment of hip and knee prosthetic joint infection. The risk factors include male sex, diagnoses other than osteoarthritis, specific comorbidities and surgical factors. Synovial fluid alpha-defensin and leucocyte esterase showed high diagnostic accuracy. Infection is devastating for patients and surgeons, both of whom describe the need for support during treatment. Debridement and implant retention is effective, particularly if performed early. For infected hip replacements, single-and two-stage revision appear equally efficacious, but single-stage has better early results, is cost-effective at 18-month follow-up and is increasingly used. Patients prefer treatments that allow full functional return within 3–9 months.
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- Gonzalez-Sevilla, S., et al.
(författare)
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A double-sided silicon micro-strip Super-Module for the ATLAS Inner Detector upgrade in the High-Luminosity LHC
- 2014
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 9, s. P02003-
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS experiment is a general purpose detector aiming to fully exploit the discovery potential of the Large Hadron Collider (LHC) at CERN. It is foreseen that after several years of successful data-taking, the LHC physics programme will be extended in the so-called High-Luminosity LHC, where the instantaneous luminosity will be increased up to 5 x 10(34) cm(-2) s(-1). For ATLAS, an upgrade scenario will imply the complete replacement of its internal tracker, as the existing detector will not provide the required performance due to the cumulated radiation damage and the increase in the detector occupancy. The current baseline layout for the new ATLAS tracker is an all-silicon-based detector, with pixel sensors in the inner layers and silicon micro-strip detectors at intermediate and outer radii. The super-module is an integration concept proposed for the strip region of the future ATLAS tracker, where double-sided stereo silicon micro-strip modules are assembled into a low-mass local support structure. An electrical super-module prototype for eight double-sided strip modules has been constructed. The aim is to exercise the multi-module readout chain and to investigate the noise performance of such a system. In this paper, the main components of the current super-module prototype are described and its electrical performance is presented in detail.
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