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- Paciaroni, M., et al.
(författare)
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Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes
- 2020
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.
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- Giustozzi, M., et al.
(författare)
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Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation
- 2020
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Ingår i: Stroke. - 0039-2499. ; 51:8, s. 2347-2354
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 Georg Thieme Verlag. All rights reserved.
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- Cumplido-Mayoral, I., et al.
(författare)
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Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex
- 2023
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Ingår i: Elife. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Brain--age can be inferred from structural neuroimaging and compared to chronological age (brain--age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging--derived measures from the UK Biobank dataset (N=22,661) were used to predict brain--age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-ss, more advanced stages (AT) of AD pathology and APOE-e4 status. Brain--age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain--age delta as a non-invasive marker of biological brain aging in non--demented individuals with abnormal levels of biomarkers of AD and axonal injury.
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- Maslov, M., et al.
(författare)
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JET D-T scenario with optimized non-thermal fusion
- 2023
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Ingår i: Nuclear Fusion. - : Institute of Physics (IOP). - 0029-5515 .- 1741-4326. ; 63:11
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Tidskriftsartikel (refereegranskat)abstract
- In JET deuterium-tritium (D-T) plasmas, the fusion power is produced through thermonuclear reactions and reactions between thermal ions and fast particles generated by neutral beam injection (NBI) heating or accelerated by electromagnetic wave heating in the ion cyclotron range of frequencies (ICRFs). To complement the experiments with 50/50 D/T mixtures maximizing thermonuclear reactivity, a scenario with dominant non-thermal reactivity has been developed and successfully demonstrated during the second JET deuterium-tritium campaign DTE2, as it was predicted to generate the highest fusion power in JET with a Be/W wall. It was performed in a 15/85 D/T mixture with pure D-NBI heating combined with ICRF heating at the fundamental deuterium resonance. In steady plasma conditions, a record 59 MJ of fusion energy has been achieved in a single pulse, of which 50.5 MJ were produced in a 5 s time window (P fus = 10.1 MW) with average Q = 0.33, confirming predictive modelling in preparation of the experiment. The highest fusion power in these experiments, P fus = 12.5 MW with average Q = 0.38, was achieved over a shorter 2 s time window, with the period of sustainment limited by high-Z impurity accumulation. This scenario provides unique data for the validation of physics-based models used to predict D-T fusion power.
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| 9. |
- Collij, L. E., et al.
(författare)
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The amyloid imaging for the prevention of Alzheimer's disease consortium: A European collaboration with global impact
- 2023
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAmyloid-beta (A beta) accumulation is considered the earliest pathological change in Alzheimer's disease (AD). The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) consortium is a collaborative European framework across European Federation of Pharmaceutical Industries Associations (EFPIA), academic, and 'Small and Medium-sized enterprises' (SME) partners aiming to provide evidence on the clinical utility and cost-effectiveness of Positron Emission Tomography (PET) imaging in diagnostic work-up of AD and to support clinical trial design by developing optimal quantitative methodology in an early AD population. The AMYPAD studiesIn the Diagnostic and Patient Management Study (DPMS), 844 participants from eight centres across three clinical subgroups (245 subjective cognitive decline, 342 mild cognitive impairment, and 258 dementia) were included. The Prognostic and Natural History Study (PNHS) recruited pre-dementia subjects across 11 European parent cohorts (PCs). Approximately 1600 unique subjects with historical and prospective data were collected within this study. PET acquisition with [F-18]flutemetamol or [F-18]florbetaben radiotracers was performed and quantified using the Centiloid (CL) method. ResultsAMYPAD has significantly contributed to the AD field by furthering our understanding of amyloid deposition in the brain and the optimal methodology to measure this process. Main contributions so far include the validation of the dual-time window acquisition protocol to derive the fully quantitative non-displaceable binding potential (BPND), assess the value of this metric in the context of clinical trials, improve PET-sensitivity to emerging A beta burden and utilize its available regional information, establish the quantitative accuracy of the Centiloid method across tracers and support implementation of quantitative amyloid-PET measures in the clinical routine. Future stepsThe AMYPAD consortium has succeeded in recruiting and following a large number of prospective subjects and setting up a collaborative framework to integrate data across European PCs. Efforts are currently ongoing in collaboration with ARIDHIA and ADDI to harmonize, integrate, and curate all available clinical data from the PNHS PCs, which will become openly accessible to the wider scientific community.
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| 10. |
- Kim, Hyun-Tae, et al.
(författare)
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Validation of D-T fusion power prediction capability against 2021 JET D-T experiments
- 2023
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Ingår i: Nuclear Fusion. - 0029-5515 .- 1741-4326. ; 63:11
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Tidskriftsartikel (refereegranskat)abstract
- JET experiments using the fuel mixture envisaged for fusion power plants, deuterium and tritium (D-T), provide a unique opportunity to validate existing D-T fusion power prediction capabilities in support of future device design and operation preparation. The 2021 JET D-T experimental campaign has achieved D-T fusion powers sustained over 5 s in ITER-relevant conditions i.e. operation with the baseline or hybrid scenario in the full metallic wall. In preparation of the 2021 JET D-T experimental campaign, extensive D-T predictive modelling was carried out with several assumptions based on D discharges. To improve the validity of ITER D-T predictive modelling in the future, it is important to use the input data measured from 2021 JET D-T discharges in the present core predictive modelling, and to specify the accuracy of the D-T fusion power prediction in comparison with the experiments. This paper reports on the validation of the core integrated modelling with TRANSP, JINTRAC, and ETS coupled with a quasilinear turbulent transport model (Trapped Gyro Landau Fluid or QualLiKiz) against the measured data in 2021 JET D-T discharges. Detailed simulation settings and the heating and transport models used are described. The D-T fusion power calculated with the interpretive TRANSP runs for 38 D-T discharges (12 baseline and 26 hybrid discharges) reproduced the measured values within 20 % . This indicates the additional uncertainties, that could result from the measurement error bars in kinetic profiles, impurity contents and neutron rates, and also from the beam-thermal fusion reaction modelling, are less than 20 % in total. The good statistical agreement confirms that we have the capability to accurately calculate the D-T fusion power if correct kinetic profiles are predicted, and indicates that any larger deviation of the D-T fusion power prediction from the measured fusion power could be attributed to the deviation of the predicted kinetic profiles from the measured kinetic profiles in these plasma scenarios. Without any posterior adjustment of the simulation settings, the ratio of predicted D-T fusion power to the measured fusion power was found as 65%-96% for the D-T baseline and 81%-97% for D-T hybrid discharge. Possible reasons for the lower D-T prediction are discussed and future works to improve the fusion power prediction capability are suggested. The D-T predictive modelling results have also been compared to the predictive modelling of the counterpart D discharges, where the key engineering parameters are similar. Features in the predicted kinetic profiles of D-T discharges such as underprediction of ne are also found in the prediction results of the counterpart D discharges, and it leads to similar levels of the normalized neutron rate prediction between the modelling results of D-T and the counterpart D discharges. This implies that the credibility of D-T fusion power prediction could be a priori estimated by the prediction quality of the preparatory D discharges, which will be attempted before actual D-T experiments.
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