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| 3. |
- Elhai, M, et al.
(författare)
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Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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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.
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| 4. |
- Becker, M, et al.
(författare)
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Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:9, s. 1242-1248
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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.
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| 5. |
- Amendola, L., et al.
(författare)
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Cosmology and fundamental physics with the Euclid satellite
- 2018
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Ingår i: Living Reviews in Relativity. - : Springer. - 1433-8351 .- 2367-3613. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015–2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid’s Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.
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| 6. |
- Boschini, M. J., et al.
(författare)
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A Hint of a Low-energy Excess in Cosmic-Ray Fluorine
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 925:2
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Tidskriftsartikel (refereegranskat)abstract
- Since its launch, the Alpha Magnetic Spectrometer–02 (AMS-02) has delivered outstanding quality measurements of the spectra of cosmic-ray (CR) species (, e±) and nuclei (H–O, Ne, Mg, Si, Fe), which resulted in a number of breakthroughs. The most recent AMS-02 result is the measurement of the spectrum of CR fluorine up to ∼2 TV. Given its very low solar system abundance, fluorine in CRs is thought to be mostly secondary, produced in fragmentations of heavier species, predominantly Ne, Mg, and Si. Similar to the best-measured secondary-to-primary boron to carbon nuclei ratio that is widely used to study the origin and propagation of CR species, the precise fluorine data would allow the origin of Si-group nuclei to be studied independently. Meanwhile, the secondary origin of CR fluorine has never been tested in a wide energy range due to the lack of accurate CR data. In this paper, we use the first ever precise measurements of the fluorine spectrum by AMS-02 together with ACE-CRIS and Voyager 1 data to actually test this paradigm. Our detailed modeling shows an excess below 10 GV in the fluorine spectrum that may hint at a primary fluorine component. We also provide an updated local interstellar spectrum (LIS) of fluorine in the rigidity range from a few MV to ∼2 TV. Our calculations employ the self-consistent GalProp–HelMod framework that has proved to be a reliable tool in deriving the LIS of CR and e−, and nuclei Z ≤ 28.
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| 7. |
- Boschini, M. J., et al.
(författare)
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Deciphering the Local Interstellar Spectra of Primary Cosmic-Ray Species with HELMOD
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 858:1
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Tidskriftsartikel (refereegranskat)abstract
- Local interstellar spectra (LIS) of primary cosmic ray (CR) nuclei, such as helium, oxygen, and mostly primary carbon are derived for the rigidity range from 10 MV to similar to 200 TV using the most recent experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and HELMOD, are combined into a single framework that is used to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. The developed iterative maximum-likelihood method uses GALPROP-predicted LIS as input to HELMOD, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The interstellar and heliospheric propagation parameters derived in this study are consistent with our prior analyses using the same methodology for propagation of CR protons, helium, antiprotons, and electrons. The resulting LIS accommodate a variety of measurements made in the local interstellar space (Voyager 1) and deep inside the heliosphere at low (ACE/CRIS, HEAO-3) and high energies (PAMELA, AMS-02).
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| 8. |
- Boschini, M. J., et al.
(författare)
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HelMod in the Works : From Direct Observations to the Local Interstellar Spectrum of Cosmic-Ray Electrons
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 854:2
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Tidskriftsartikel (refereegranskat)abstract
- The local interstellar spectrum (LIS) of cosmic-ray (CR) electrons for the energy range 1 MeV to 1 TeV is derived using the most recent experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and HELMOD, are combined to provide a single framework that is run to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. An iterative maximum-likelihood method is developed that uses GALPROP-predicted LIS as input to HELMOD, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The optimized HelMod parameters are then used to adjust GALPROP parameters to predict a refined LIS with the procedure repeated subject to a convergence criterion. The parameter optimization uses an extensive data set of proton spectra from 1997 to 2015. The proposed CR electron LIS accommodates both the low-energy interstellar spectra measured by Voyager 1 as well as the high-energy observations by PAMELA and AMS-02 that are made deep in the heliosphere; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The interstellar and heliospheric propagation parameters derived in this study agree well with our earlier results for CR protons, helium nuclei, and anti-protons propagation and LIS obtained in the same framework.
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| 9. |
- Boschini, M. J., et al.
(författare)
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Solution of Heliospheric Propagation : Unveiling the Local Interstellar Spectra of Cosmic-ray Species
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 840:2
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Tidskriftsartikel (refereegranskat)abstract
- Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with the data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range.
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| 10. |
- Boschini, M. J., et al.
(författare)
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Spectra of Cosmic-Ray Sodium and Aluminum and Unexpected Aluminum Excess
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 933:2
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Tidskriftsartikel (refereegranskat)abstract
- Since its launch, the Alpha Magnetic Spectrometer-02 (AMS-02) has delivered outstanding quality measurements of the spectra of cosmic-ray (CR) species, , e±, and nuclei (H–Si, Fe), which resulted in a number of breakthroughs. The most recent AMS-02 result is the measurement of the spectra of CR sodium and aluminum up to ∼2 TV. Given their low solar system abundances, a significant fraction of each element is produced in fragmentations of heavier species, predominantly Ne, Mg, and Si. In this paper, we use precise measurements of the sodium and aluminum spectra by AMS-02 together with ACE-CRIS and Voyager 1 data to test their origin. We show that the sodium spectrum agrees well with the predictions made with the GalProp-HelMod framework, while the aluminum spectrum shows a significant excess in the rigidity range from 2–7 GV. In this context, we discuss the origin of other low-energy excesses in Li, F, and Fe found earlier. The observed excesses in Li, F, and Al appear to be consistent with the local Wolf-Rayet stars hypothesis, invoked to reproduce anomalous 22Ne/20Ne, 12C/16O, and 58Fe/56Fe ratios in CRs, while excess in Fe is likely connected with a past supernova activity in the solar neighborhood. We also provide updated local interstellar spectra (LIS) of sodium and aluminum in the rigidity range from a few megavolts to ∼2 TV. Our calculations employ the self-consistent GalProp-HelMod framework, which has proved to be a reliable tool in deriving the LIS of CR , e−, and nuclei Z ≤ 28.
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