| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Becker, M, et al.
(författare)
-
Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis
- 2019
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:9, s. 1242-1248
-
Tidskriftsartikel (refereegranskat)abstract
- Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database.MethodsInclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression.ResultsOf 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model.ConclusionsThe use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials.
|
|
| 5. |
|
|
| 6. |
- Elhai, M, et al.
(författare)
-
Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
-
Tidskriftsartikel (refereegranskat)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
|
|
| 7. |
|
|
| 8. |
- Postmus, I., et al.
(författare)
-
Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- 2016
-
Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:12, s. 835-45
-
Tidskriftsartikel (refereegranskat)abstract
- Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1x10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Conclusions Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
|
|
| 9. |
- Acosta-Herrera, M, et al.
(författare)
-
Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases
- 2019
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:3, s. 311-319
-
Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.
|
|
| 10. |
- Diaz-Gallo, L. M., et al.
(författare)
-
Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis
- 2011
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:3, s. 454-462
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected) = 0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected) = 0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected) = 0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p = 0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.
|
|
| 11. |
- Distler, J. H. W., et al.
(författare)
-
Is there a role for TNF-alpha antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique
- 2011
-
Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 29:2, s. 40-45
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To obtain experiences and expert opinion on treatment of SSc patients with TNF-alpha antagonists. Methods: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-alpha antagonists. Assessment forms on the frequency of TNF-alpha inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-alpha inhibitors in SSc. Results: Seventy-nine centres returned information on use of TNF-alpha antagonists in SSc patients. A total of 65 patients were treated with TNF-alpha inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-alpha inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-alpha antagonists in SSc. Arthritis was suggested as an indication for TNF alpha antagonists by 75% of the experts. However; after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-alpha antagonists decreased and 59% recommended that TNF-alpha antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-alpha antagonists for arthritis associated with SSc. Conclusions: Most of the experts do not recommend the routine use of TNF-alpha antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-alpha antagonists are needed before general recommendations can be given.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Postmus, Iris, et al.
(författare)
-
Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
|
|
| 15. |
|
|
| 16. |
- Ranjan, V., et al.
(författare)
-
Spin-Echo Silencing Using a Current-Biased Frequency-Tunable Resonator
- 2022
-
Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 129:18
-
Tidskriftsartikel (refereegranskat)abstract
- The ability to control microwave emission from a spin ensemble is a requirement of several quantum memory protocols. Here, we demonstrate such ability by using a resonator whose frequency can be rapidly tuned with a bias current. We store excitations in an ensemble of rare-earth ions and suppress on demand the echo emission ("echo silencing") by two methods: (1) detuning the resonator during the spin rephasing, and (2) subjecting spins to magnetic field gradients generated by the bias current itself. We also show that spin coherence is preserved during silencing.
|
|
| 17. |
- Sacco, R. L., et al.
(författare)
-
Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
- 2008
-
Ingår i: New England Journal of Medicine. - Boston : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1238-51
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)
|
|
| 18. |
- Yusuf, S., et al.
(författare)
-
Telmisartan to prevent recurrent stroke and cardiovascular events
- 2008
-
Ingår i: New England Journal of Medicine. - : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1225-37
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. METHODS: In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. RESULTS: The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). CONCLUSIONS: Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)
|
|
| 19. |
- De Keyser, J., et al.
(författare)
-
In situ plasma and neutral gas observation time windows during a comet flyby : Application to the Comet Interceptor mission
- 2024
-
Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 244
-
Tidskriftsartikel (refereegranskat)abstract
- A comet flyby, like the one planned for ESA's Comet Interceptor mission, places stringent requirements on spacecraft resources. To plan the time line of in situ plasma and neutral gas observations during the flyby, the size of the comet magnetosphere and neutral coma must be estimated well. For given solar irradiance and solar wind conditions, comet composition, and neutral gas expansion speed, the size of gas coma and magnetosphere during the flyby can be estimated from the gas production rate and the flyby geometry. Combined with flyby velocity, the time spent in these regions can be inferred and a data acquisition plan can be elaborated for each instrument, compatible with the limited data storage capacity. The sizes of magnetosphere and gas coma are found from a statistical analysis based on the probability distributions of gas production rate, flyby velocity, and solar wind conditions. The size of the magnetosphere as measured by bow shock standoff distance is 105-106 km near 1 au in the unlikely case of a Halley-type target comet, down to a nonexistent bow shock for targets with low activity. This translates into durations up to 103-104 seconds. These estimates can be narrowed down when a target is identified far from the Sun, and even more so as its activity can be predicted more reliably closer to the Sun. Plasma and neutral gas instruments on the Comet Interceptor main spacecraft can monitor the entire flyby by using an adaptive data acquisition strategy in the context of a record-and-playback scenario. For probes released from the main spacecraft, the inter-satellite communication link limits the data return. For a slow flyby of an active comet, the probes may not yet be released during the inbound bow shock crossing.
|
|
| 20. |
- Fayolle, E. C., et al.
(författare)
-
Protostellar and cometary detections of organohalogens
- 2017
-
Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 1:10, s. 703-708
-
Tidskriftsartikel (refereegranskat)abstract
- Organohalogens, a class of molecules that contain at least one halogen atom bonded to carbon, are abundant on the Earth where they are mainly produced through industrial and biological processes(1). Consequently, they have been proposed as biomarkers in the search for life on exoplanets(2). Simple halogen hydrides have been detected in interstellar sources and in comets, but the presence and possible incorporation of more complex halogen-containing molecules such as organohalogens into planet-forming regions is uncertain(3,4). Here we report the interstellar detection of two isotopologues of the organohalogen CH3Cl and put some constraints on CH3F in the gas surrounding the low-mass protostar IRAS 16293-2422, using the Atacama Large Millimeter/submillimeter Array (ALMA). We also find CH3Cl in the coma of comet 67P/Churyumov-Gerasimenko (67P/C-G) by using the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) instrument. The detections reveal an efficient pre-planetary formation pathway of organohalogens. Cometary impacts may deliver these species to young planets and should thus be included as a potential abiotical production source when interpreting future organohalogen detections in atmospheres of rocky planets.
|
|
| 21. |
- Heritier, K. L., et al.
(författare)
-
Ion composition at comet 67P near perihelion : Rosetta observations and model-based interpretation
- 2017
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 469, s. S427-S442
-
Tidskriftsartikel (refereegranskat)abstract
- We present the ion composition in the coma of comet 67P with newly detected ion species over the 28-37 u mass range, probed by Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA)/Double Focusing Mass Spectrometer (DFMS). In summer 2015, the nucleus reached its highest outgassing rate and ion-neutral reactions started to take place at low cometocentric distances. Minor neutrals can efficiently capture protons from the ion population, making the protonated version of these neutrals a major ion species. So far, only NH4+ has been reported at comet 67P. However, there are additional neutral species with proton affinities higher than that of water (besides NH3) that have been detected in the coma of comet 67P: CH3OH, HCN, H2CO and H2S. Their protonated versions have all been detected. Statistics showing the number of detections with respect to the number of scans are presented. The effect of the negative spacecraft potential probed by the Rosetta Plasma Consortium/LAngmuir Probe on ion detection is assessed. An ionospheric model has been developed to assess the different ion density profiles and compare them to the ROSINA/DFMS measurements. It is also used to interpret the ROSINA/DFMS observations when different ion species have similar masses, and their respective densities are not high enough to disentangle them using the ROSINA/DFMS high-resolution mode. The different ion species that have been reported in the coma of 67P are summarized and compared with the ions detected at comet 1P/Halley during the Giotto mission.
|
|
| 22. |
- Keyser, Ailsa K.V., et al.
(författare)
-
Pulsed electron spin resonance of an organic microcrystal by dispersive readout
- 2020
-
Ingår i: Journal of Magnetic Resonance. - : Elsevier BV. - 1090-7807 .- 1096-0856. ; 321
-
Tidskriftsartikel (refereegranskat)abstract
- We establish a testbed system for the development of high-sensitivity Electron Spin Resonance (ESR) techniques for small samples at cryogenic temperatures. Our system consists of a NbN thin-film planar superconducting microresonator designed to have a concentrated mode volume to couple to a small amount of paramagnetic material, and to be resilient to magnetic fields of up to 400mT. At 65mK we measure high-cooperativity coupling (C≈19) to an organic radical microcrystal containing 1012 spins in a pico-litre volume. We detect the spin–lattice decoherence rate via the dispersive frequency shift of the resonator. Techniques such as these could be suitable for applications in quantum information as well as for pulsed ESR interrogation of very few spins to provide insights into the surface chemistry of, for example, the material defects in superconducting quantum processors.
|
|
| 23. |
- Maggiolo, R., et al.
(författare)
-
The Effect of Cosmic Rays on Cometary Nuclei. II. Impact on Ice Composition and Structure
- 2020
-
Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 901:2
-
Tidskriftsartikel (refereegranskat)abstract
- Since their formation in the protosolar nebula some similar to 4.5 billion years ago, comets are in storage in cold distant regions of the solar system, the Kuiper Belt/scattered disk or Oort Cloud. Therefore, they have been considered as mostly unaltered samples of the protosolar nebula. However, a significant dose of energy is deposited by galactic cosmic rays (GCRs) into the outermost tens of meters of cometary nuclei during their stay in the Oort Cloud or Kuiper Belt. We investigate the impact of energy deposition by GCRs on cometary nuclei. We use experimental results from laboratory experiments and the energy deposition by GCRs estimated by Gronoff et al. (2020), to discuss the depth down to which the cometary nucleus is altered by GCRs. We show that GCRs do not significantly change the isotopic composition of cometary material but modify the chemical composition and the ice structure in the outer layers of the nucleus, which cannot be considered as pristine solar nebula material. We discuss the effect of the collisional history of comets on the distribution of processed material inside the nucleus and its implication on the observation of comets.
|
|
| 24. |
- Ntaios, G, et al.
(författare)
-
The European Stroke Organisation Guidelines: a standard operating procedure
- 2015
-
Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 1010 Suppl A100, s. 128-135
-
Tidskriftsartikel (refereegranskat)abstract
- In 2008, the recently founded European Stroke Organisation published its guidelines for the management of ischemic stroke and transient ischemic attack. This highly cited document was translated in several languages and was updated in 2009. Since then, the European Stroke Organisation has published guidelines for the management of intracranial aneurysms and subarachnoidal hemorrhage, for the establishment of stroke units and stroke centers, and recently for the management of intracerebral hemorrhage. In recent years, the methodology for the development of guidelines has evolved significantly. To keep pace with this progress and driven by the strong determination of the European Stroke Organisation to further promote stroke management, education, and research, the European Stroke Organisation decided to delineate a detailed standard operating procedure for its guidelines. There are two important cornerstones in this standard operating procedure: The first is the implementation of the Grading of Recommendations Assessment, Development, and Evaluation methodology for the development of its Guideline Documents. The second one is the decision of the European Stroke Organisation to move from the classical model of a single Guideline Document about a major topic (e.g. management of ischemic stroke) to focused modules (i.e. subdivisions of a major topic). This will enable the European Stroke Organisation to react faster when new developments in a specific stroke field occur and update its recommendations on the related module rather swiftly; with the previous approach of a single large Guideline Document, its entire revision had to be completed before an updated publication, delaying the production of up-to-date guidelines. After discussion within the European Stroke Organisation Guidelines Committee and significant input from European Stroke Organisation members as well as methodologists and analysts, this document presents the official standard operating procedure for the development of the Guideline Documents of the European Stroke Organisation.
|
|
| 25. |
- Retinò, A., et al.
(författare)
-
Particle energization in space plasmas : towards a multi-point, multi-scale plasma observatory
- 2021
-
Ingår i: Experimental astronomy. - : Springer Nature. - 0922-6435 .- 1572-9508.
-
Tidskriftsartikel (refereegranskat)abstract
- This White Paper outlines the importance of addressing the fundamental science theme “How are charged particles energized in space plasmas” through a future ESA mission. The White Paper presents five compelling science questions related to particle energization by shocks, reconnection, waves and turbulence, jets and their combinations. Answering these questions requires resolving scale coupling, nonlinearity, and nonstationarity, which cannot be done with existing multi-point observations. In situ measurements from a multi-point, multi-scale L-class Plasma Observatory consisting of at least seven spacecraft covering fluid, ion, and electron scales are needed. The Plasma Observatory will enable a paradigm shift in our comprehension of particle energization and space plasma physics in general, with a very important impact on solar and astrophysical plasmas. It will be the next logical step following Cluster, THEMIS, and MMS for the very large and active European space plasmas community. Being one of the cornerstone missions of the future ESA Voyage 2050 science programme, it would further strengthen the European scientific and technical leadership in this important field.
|
|
