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- Sherratt, K., et al.
(författare)
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Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations
- 2023
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1–4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance.Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models’ forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models’ forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models’ forecasts of deaths (N=763 predictions from 20 models). Across a 1–4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models.Conclusions: Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks.
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- Edlmann, E, et al.
(författare)
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Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 5885-
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Tidskriftsartikel (refereegranskat)abstract
- The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.
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- Moreau, V., et al.
(författare)
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Pool CFD modelling : lessons from the SESAME project
- 2019
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Ingår i: Nuclear Engineering and Design. - : ELSEVIER SCIENCE SA. - 0029-5493 .- 1872-759X. ; 355
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Tidskriftsartikel (refereegranskat)abstract
- The current paper describes the Computational Fluid-Dynamics (CFD) modelling of Heavy Liquid Metal (HLM) flows in a pool configuration and in particular how this is approached within the Horizon 2020 SESAME project. SESAME's work package structure, based on a systematic approach of redundancy and diversification, is explained along with its motivation. The main achievements obtained and the main lessons learned during the project are illustrated. The paper focuses on the strong coupling between the experimental activities and CFD simulations performed within the SESAME project. Two different HLM fluids are investigated: pure lead and Lead-Bismuth Eutectic. The objective is to make CFD a valid instrument used during the design of safe and innovative Gen-IV nuclear plants. Some effort has also been devoted to Proper Orthogonal Decomposition with Galerkin projection modelling (POD-Galerkin), a reduced order model suited for Uncertainty Quantification that operates by post-processing CFD results. Assessment of Uncertainty highly improves the reliability of CFD simulations. Dedicated experimental campaigns on heavily instrumented facilities have been conceived with the specific objective to build a series of datasets suited for the calibration and validation of the CFD modelling. In pool configuration, the attention is focused on the balance between conductive and convective heat transfer phenomena, on transient test-cases representative of incidental scenarios and on the possible occurrence of solidification phenomena. Four test sections have been selected to generate the datasets: (i) the CIRCE facility from ENEA, (ii) the TALL-3D pool test section from KTH, (iii) the TALL-3D Solidification Test Section (STS) from KTH and (iv) the SESAME Stand facility from CVR. While CIRCE and TALL-3D were existing facilities, the STS and SESAME Stand facility have been conceived, built and operated within the project, heavily relying on the use of CFD support. Care has been taken to ensure that almost all tasks were performed by at least two partners. Specific examples are given on how this strategy has allowed to uncover flaws and overcome pitfalls. Furthermore, an overview of the performed work and the achieved results is presented, as well as remaining or new uncovered issues. Finally, the paper is concluded with a description of one of the main goals of the SESAME project: the construction of the Gen-IV ALFRED CFD model and an investigation of its general circulation.
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- Antonioli, P, et al.
(författare)
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The AQUA-RICH atmospheric neutrino experiment
- 1999
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Ingår i: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 433:1-2, s. 104-120
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We describe a 125 m diameter spherical detector containing 1 Mt of water, capable of high rate observation of atmospheric neutrino events (30000/y). The ring imaging Cherenkov (RICH) technique is used to measure velocity, momentum and direction of particl
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- Levy, Rebecca C., et al.
(författare)
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Outflows from Super Star Clusters in the Central Starburst of NGC 253
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 912:1
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Tidskriftsartikel (refereegranskat)abstract
- Young massive clusters play an important role in the evolution of their host galaxies, and feedback from the high-mass stars in these clusters can have profound effects on the surrounding interstellar medium. The nuclear starburst in the nearby galaxy NGC 253 at a distance of 3.5 Mpc is a key laboratory in which to study star formation in an extreme environment. Previous high-resolution (1.9 pc) dust continuum observations from the Atacama Large Millimeter/submillimeter Array (ALMA) discovered 14 compact, massive super star clusters (SSCs) still in formation. We present here ALMA data at 350 GHz with 28 mas (0.5 pc) resolution. We detect blueshifted absorption and redshifted emission (P-Cygni profiles) toward three of these SSCs in multiple lines, including CS 7-6 and (HCN)-C-13 4-3, which represent direct evidence for previously unobserved outflows. The mass contained in these outflows is a significant fraction of the cluster gas masses, which suggests we are witnessing a short but important phase. Further evidence of this is the finding of a molecular shell around the only SSC visible at near-IR wavelengths. We model the P-Cygni line profiles to constrain the outflow geometry, finding that the outflows must be nearly spherical. Through a comparison of the outflow properties with predictions from simulations, we find that none of the available mechanisms completely explains the observations, although dust-reprocessed radiation pressure and O star stellar winds are the most likely candidates. The observed outflows will have a very substantial effect on the clusters' evolution and star formation efficiency.
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- Rotili, Dante, et al.
(författare)
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Exploring the role of 2-chloro-6-fluoro substitution in 2-alkylthio-6-benzyl-5-alkylpyrimidin-4(3H)-ones : effects in HIV-1-infected cells and in HIV-1 reverse transcriptase enzymes.
- 2014
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 57:12, s. 5212-25
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Tidskriftsartikel (refereegranskat)abstract
- A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomolar activity against wt HIV-1. Against clinically relevant HIV-1 mutants and in enzyme assays, the simultaneous C5(methyl)/C6(methyl/ethyl) substitution in the 2-Cl-6-F- and 2,6-F2-benzyl series furnished compounds with the highest, wide-spectrum inhibitory activity against HIV-1. Three representative 2-Cl-6-F-S-DABOs carrying two (9c, 10c) or one (10a) stereogenic centers were resolved into their individual stereoisomers and showed a significant diastereo- and enantioselectivity in HIV-1 inhibition, the highest antiviral activity well correlating with the R absolute configuration to the stereogenic center of the C6-benzylic position in both cellular and enzymatic tests. Application of previously reported COMBINEr protocol on 9c and 10c confirmed the influence of the stereogenic centers on their binding modes in the HIV-1 RT.
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