| 1. |
- 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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| 2. |
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Chyz̊y, K.T., et al.
(författare)
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LOFAR MSSS: Flattening low-frequency radio continuum spectra of nearby galaxies
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 619
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The shape of low-frequency radio continuum spectra of normal galaxies is not well understood, the key question being the role of physical processes such as thermal absorption in shaping them. In this work we take advantage of the LOFAR Multifrequency Snapshot Sky Survey (MSSS) to investigate such spectra for a large sample of nearby star-forming galaxies. Methods. Using the measured 150 MHz flux densities from the LOFAR MSSS survey and literature flux densities at various frequencies we have obtained integrated radio spectra for 106 galaxies characterised by different morphology and star formation rate. The spectra are explained through the use of a three-dimensional model of galaxy radio emission, and radiation transfer dependent on the galaxy viewing angle and absorption processes. Results. Our galaxies' spectra are generally flatter at lower compared to higher frequencies: the median spectral index αlow measured between ≈ 50 MHz and 1.5 GHz is -0.57 ± 0.01 while the high-frequency one αhigh, calculated between 1.3 GHz and 5 GHz, is -0.77 ± 0.03. As there is no tendency for the highly inclined galaxies to have more flattened low-frequency spectra, we argue that the observed flattening is not due to thermal absorption, contradicting the suggestion of Israel & Mahoney (1990, ApJ, 352, 30). According to our modelled radio maps for M 51-like galaxies, the free-free absorption effects can be seen only below 30 MHz and in the global spectra just below 20 MHz, while in the spectra of starburst galaxies, like M 82, the flattening due to absorption is instead visible up to higher frequencies of about 150 MHz. Starbursts are however scarce in the local Universe, in accordance with the weak spectral curvature seen in the galaxies of our sample. Locally, within galactic disks, the absorption effects are distinctly visible in M 51-like galaxies as spectral flattening around 100-200 MHz in the face-on objects, and as turnovers in the edge-on ones, while in M 82-like galaxies there are strong turnovers at frequencies above 700 MHz, regardless of viewing angle. Conclusions. Our modelling of galaxy spectra suggests that the weak spectral flattening observed in the nearby galaxies studied here results principally from synchrotron spectral curvature due to cosmic ray energy losses and propagation effects. We predict much stronger effects of thermal absorption in more distant galaxies with high star formation rates. Some influence exerted by the Milky Way's foreground on the spectra of all external galaxies is also expected at very low frequencies.
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| 6. |
- Govoni, F., et al.
(författare)
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A radio ridge connecting two galaxy clusters in a filament of the cosmic web
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6444, s. 981-984
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Tidskriftsartikel (refereegranskat)abstract
- Galaxy clusters are the most massive gravitationally bound structures in the Universe. They grow by accreting smaller structures in a merging process that produces shocks and turbulence in the intracluster gas. We observed a ridge of radio emission connecting the merging galaxy clusters Abell 0399 and Abell 0401 with the Low-Frequency Array (LOFAR) telescope network at 140 megahertz. This emission requires a population of relativistic electrons and a magnetic field located in a filament between the two galaxy clusters. We performed simulations to show that a volume-filling distribution of weak shocks may reaccelerate a preexisting population of relativistic particles, producing emission at radio wavelengths that illuminates the magnetic ridge.
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| 7. |
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| 8. |
- Indriolo, Nick, et al.
(författare)
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SOFIA/EXES observations of water absorption in the protostar AFGL 2591 at high spectral resolution
- 2015
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Ingår i: Astrophysical Journal Letters. - 2041-8213. ; 802:2
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Tidskriftsartikel (refereegranskat)abstract
- We present high spectral resolution (similar to 3 km s(-1)) observations of the nu(2) ro-vibrational band of H2O in the 6.086-6.135 mu m range toward the massive protostar AFGL 2591 using the Echelon-Cross-Echelle Spectrograph (EXES) on the Stratospheric Observatory for Infrared Astronomy (SOFIA). Ten absorption features are detected in total, with seven caused by transitions in the nu(2) band of H2O, two by transitions in the first vibrationally excited nu(2) band of H2O, and one by a transition in the nu(2) band of (H2O)-O-18. Among the detected transitions is the nu(2) 1(1,1)-0(0,0) line that probes the lowest-lying rotational level of para-H2O. The stronger transitions appear to be optically thick, but reach maximum absorption at a depth of about 25%, suggesting that the background source is only partially covered by the absorbing gas or that the absorption arises within the 6 mu m emitting photosphere. Assuming a covering fraction of 25%, the H2O column density and rotational temperature that best fit the observed absorption lines are N(H2O) = (1.3 +/- 0.3) x 10(19) cm(-2) and T = 640 +/- 80 K.
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| 9. |
- Kowal-Bielecka, Otylia, et al.
(författare)
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Update of EULAR recommendations for the treatment of systemic sclerosis
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
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| 10. |
- Vacca, V., et al.
(författare)
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Statistical methods for the analysis of rotation measure grids in large scale structures in the SKA era
- 2015
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Ingår i: Proceedings of Science. - 1824-8039. ; 9-13-June-2014
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Konferensbidrag (refereegranskat)abstract
- Determining magnetic field properties in different environments of the cosmic large-scale structure as well as their evolution over redshift is a fundamental step toward uncovering the origin of cosmic magnetic fields. Radio observations permit the study of extragalactic magnetic fields via measurements of the Faraday depth of extragalactic radio sources. Our aim is to investigate how much different extragalactic environments contribute to the Faraday depth variance of these sources. We develop a Bayesian algorithm to distinguish statistically Faraday depth variance contributions intrinsic to the source from those due to the medium between the source and the observer. In our algorithm the Galactic foreground and the measurement noise are taken into account as the uncertainty correlations of the galactic model. Additionally, our algorithm allows for the investigation of possible redshift evolution of the extragalactic contribution. This work presents the derivation of the algorithm and tests performed on mock observations. With cosmic magnetism being one of the key science projects of the new generation of radio interferometers we have made predictions for the algorithm's performance on data from the next generation of radio interferometers. Applications to real data are left for future work.
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| 11. |
- Vacca, V., et al.
(författare)
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Using rotation measure grids to detect cosmological magnetic fields: A Bayesian approach
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 591, s. Art. no. A13-
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Tidskriftsartikel (refereegranskat)abstract
- Determining magnetic field properties in different environments of the cosmic large-scale structure as well as their evolution over redshift is a fundamental step toward uncovering the origin of cosmic magnetic fields. Radio observations permit the study of extragalactic magnetic fields via measurements of the Faraday depth of extragalactic radio sources. Our aim is to investigate how much different extragalactic environments contribute to the Faraday depth variance of these sources. We develop a Bayesian algorithm to distinguish statistically Faraday depth variance contributions intrinsic to the source from those due to the medium between the source and the observer. In our algorithm the Galactic foreground and measurement noise are taken into account as the uncertainty correlations of the Galactic model. Additionally, our algorithm allows for the investigation of possible redshift evolution of the extragalactic contribution. This work presents the derivation of the algorithm and tests performed on mock observations. Because cosmic magnetism is one of the key science projects of the new generation of radio interferometers, we have predicted the performance of our algorithm on mock data collected with these instruments. According to our tests, high-quality catalogs of a few thousands of sources should already enable us to investigate magnetic fields in the cosmic structure.
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| 12. |
- O'Sullivan, Shane P., et al.
(författare)
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The intergalactic magnetic field probed by a giant radio galaxy
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 622
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Forskningsöversikt (refereegranskat)abstract
- Cosmological simulations predict that an intergalactic magnetic field (IGMF) pervades the large scale structure (LSS) of the Universe. Measuring the IGMF is important to determine its origin (i.e. primordial or otherwise). Using data from the LOFAR Two Metre Sky Survey (LoTSS), we present the Faraday rotation measure (RM) and depolarisation properties of the giant radio galaxy J1235+5317, at a redshift of z = 0.34 and 3.38 Mpc in size. We find a mean RM difference between the lobes of 2.5 ±0.1 rad m -2 , in addition to small scale RM variations of ∼0.1 rad m -2 . From a catalogue of LSS filaments based on optical spectroscopic observations in the local universe, we find an excess of filaments intersecting the line of sight to only one of the lobes. Associating the entire RM difference to these LSS filaments leads to a gas density-weighted IGMF strength of ∼0.3 μG. However, direct comparison with cosmological simulations of the RM contribution from LSS filaments gives a low probability (∼5%) for an RM contribution as large as 2.5 rad m -2 , for the case of IGMF strengths of 10-50 nG. It is likely that variations in the RM from the Milky Way (on 11′ scales) contribute significantly to the mean RM difference, and a denser RM grid is required to better constrain this contribution. In general, this work demonstrates the potential of the LOFAR telescope to probe the weak signature of the IGMF. Future studies, with thousands of sources with high accuracy RMs from LoTSS, will enable more stringent constraints on the nature of the IGMF.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- 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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| 17. |
- 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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| 18. |
- 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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| 19. |
- Diluvio, G, et al.
(författare)
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NOTCH3 inactivation increases triple negative breast cancer sensitivity to gefitinib by promoting EGFR tyrosine dephosphorylation and its intracellular arrest
- 2018
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 7:5, s. 42-
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Tidskriftsartikel (refereegranskat)abstract
- Notch dysregulation has been implicated in numerous tumors, including triple-negative breast cancer (TNBC), which is the breast cancer subtype with the worst clinical outcome. However, the importance of individual receptors in TNBC and their specific mechanism of action remain to be elucidated, even if recent findings suggested a specific role of activated-Notch3 in a subset of TNBCs. Epidermal growth factor receptor (EGFR) is overexpressed in TNBCs but the use of anti-EGFR agents (including tyrosine kinase inhibitors, TKIs) has not been approved for the treatment of these patients, as clinical trials have shown disappointing results. Resistance to EGFR blockers is commonly reported. Here we show that Notch3-specific inhibition increases TNBC sensitivity to the TKI-gefitinib in TNBC-resistant cells. Mechanistically, we demonstrate that Notch3 is able to regulate the activated EGFR membrane localization into lipid rafts microdomains, as Notch3 inhibition, such as rafts depletion, induces the EGFR internalization and its intracellular arrest, without involving receptor degradation. Interestingly, these events are associated with the EGFR tyrosine dephosphorylation at Y1173 residue (but not at Y1068) by the protein tyrosine phosphatase H1 (PTPH1), thus suggesting its possible involvement in the observed Notch3-dependent TNBC sensitivity response to gefitinib. Consistent with this notion, a nuclear localization defect of phospho-EGFR is observed after combined blockade of EGFR and Notch3, which results in a decreased TNBC cell survival. Notably, we observed a significant correlation between EGFR and NOTCH3 expression levels by in silico gene expression and immunohistochemical analysis of human TNBC primary samples. Our findings strongly suggest that combined therapies of TKI-gefitinib with Notch3-specific suppression may be exploited as a drug combination advantage in TNBC treatment.
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| 20. |
- Dimopoulos, Meletios A., et al.
(författare)
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Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010) : A phase 3b study in refractory multiple myeloma
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:4, s. 497-503
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Tidskriftsartikel (refereegranskat)abstract
- Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day cycles with low-dose dexamethasone 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22 until progressive disease or unacceptable toxicity. Safety was the primary end point; secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Among 682 patients enrolled, median age was 66 years, and median time since diagnosis was 5.3 years. Median number of prior regimens was 5. Most patients were refractory to both lenalidomide and bortezomib (80.2%). Median follow-up was 16.8 months; median duration of treatment was 4.9 months. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia [49.7%], anemia [33.0%], and thrombocytopenia [24.1%]). Most common grade 3/4 nonhematologic toxicities were pneumonia (10.9%) and fatigue (5.9%). Grade 3/4 venous thromboembolism and peripheral neuropathy were rare (1.6% each). The ORR was 32.6%, and the median DOR was 7.4 months. Median PFS and OS were 4.6 months and 11.9 months, respectively. We present the largest trial to date evaluating pomalidomide plus low-dose dexamethasone in patients with RRMM, further confirming that this regimen offers clinically meaningful benefit and is generally well tolerated. www.Clinicaltrials.gov identifier NCT01712789.
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| 21. |
- Elhai, Muriel, et al.
(författare)
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Mapping and predicting mortality from systemic sclerosis
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:11, s. 1897-1905
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.
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| 22. |
- Farnes, J.S., et al.
(författare)
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Source finding in linear polarization for LOFAR, and SKA predecessor surveys, using Faraday moments
- 2018
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 474:3, s. 3280-3296
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Tidskriftsartikel (refereegranskat)abstract
- The optimal source-finding strategy for linear polarization data is an unsolved problem, with many inhibitive factors imposed by the technically challenging nature of polarization observations. Such an algorithm is essential for Square Kilometre Array (SKA) pathfinder surveys, such as the Multifrequency Snapshot Sky Survey with the LOw Frequency ARray (LOFAR), as data volumes are significant enough to prohibit manual inspection. We present a new strategy of 'Faraday Moments' for source-finding in linear polarization with LOFAR, using the moments of the frequency-dependent full-Stokes data (i.e. the mean, standard deviation, skewness, and excess kurtosis). Through simulations of the sky, we find that moments can identify polarized sources with a high completeness: 98.5 per cent at a signal to noise of 5. While the method has low reliability, rotation measure (RM) synthesis can be applied per candidate source to filter out instrumental and spurious detections. This combined strategy will result in a complete and reliable catalogue of polarized sources that includes the full sensitivity of the observational bandwidth. We find that the technique can reduce the number of pixels on which RM Synthesis needs to be performed by a factor of ≈1 × 10 5 for source distributions anticipated with modern radio telescopes. Through tests on LOFAR data, we find that the technique works effectively in the presence of diffuse emission. Extensions of this method are directly applicable to other upcoming radio surveys such as the POlarization Sky Survey of the Universe's Magnetism with the Australia Square Kilometre Array Pathfinder, and the SKA itself.
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| 23. |
- Ingegnoli, Francesca, et al.
(författare)
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A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study
- 2015
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 102, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% Cl 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% Cl 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% Cl 0.34-3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of sderoderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. (C) 2015 Elsevier Inc. All rights reserved.
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| 24. |
- Oppermann, N., et al.
(författare)
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Estimating extragalactic Faraday rotation
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 575
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Tidskriftsartikel (refereegranskat)abstract
- Observations of Faraday rotation for extragalactic sources probe magnetic fields both inside and outside the Milky Way. Building on our earlier estimate of the Galactic contribution, we set out to estimate the extragalactic contributions. We discuss the problems involved; in particular, we point out that taking the difference between the observed values and the Galactic foreground reconstruction is not a good estimate for the extragalactic contributions. We point out a degeneracy between the contributions to the observed values due to extragalactic magnetic fields and observational noise and comment on the dangers of over-interpreting an estimate without taking into account its uncertainty information. To overcome these difficulties, we develop an extended reconstruction algorithm based on the assumption that the observational uncertainties are accurately described for a subset of the data, which can overcome the degeneracy with the extragalactic contributions. We present a probabilistic derivation of the algorithm and demonstrate its performance using a simulation, yielding a high quality reconstruction of the Galactic Faraday rotation foreground, a precise estimate of the typical extragalactic contribution, and a well-defined probabilistic description of the extragalactic contribution for each data point. We then apply this reconstruction technique to a catalog of Faraday rotation observations for extragalactic sources. The analysis is done for several different scenarios, for which we consider the error bars of different subsets of the data to accurately describe the observational uncertainties. By comparing the results, we argue that a split that singles out only data near the Galactic poles is the most robust approach. We find that the dispersion of extragalactic contributions to observed Faraday depths is most likely lower than 7 rad/m(2), in agreement with earlier results, and that the extragalactic contribution to an individual data point is poorly constrained by the data in most cases.
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| 25. |
- Ryde, N., et al.
(författare)
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Evolved Stars with Complex Atmospheres - the High Spectral Resolution, mid-IR View
- 2015
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Ingår i: Why galaxies care about AGB stars III. - : ASTRONOMICAL SOC PACIFIC. - 9781583818794 - 9781583818787 ; , s. 67-71
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Konferensbidrag (refereegranskat)abstract
- The physical structures of the outer atmospheres of red giants are not known. They are certainly complex, and a range of recent observations are showing that we need to embrace non-classical model atmospheres to interpret these regions. This region's properties are of importance, not the least for an understanding of the mass-loss mechanism for these stars. Here we present observational constraints on the outer regions of red giants, based on mid-IR, high spectral resolution spectra. We also discuss possible non-LTE effects and highlight a new non-LTE code that will be used to analyse the spectra of these atmospheric layers. We conclude by mentioning our new SOFIA/EXES observations of red giants at 67 mu m, where the vibration-rotation lines of water vapour can be detected and spectrally resolved for the first time.
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| 26. |
- Vacca, A, et al.
(författare)
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Conserved temporal ordering of promoter activation implicates common mechanisms governing the immediate early response across cell types and stimuli
- 2018
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Ingår i: Open biology. - : The Royal Society. - 2046-2441. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- The promoters of immediate early genes (IEGs) are rapidly activated in response to an external stimulus. These genes, also known as primary response genes, have been identified in a range of cell types, under diverse extracellular signals and using varying experimental protocols. Whereas genomic dissection on a case-by-case basis has not resulted in a comprehensive catalogue of IEGs, a rigorous meta-analysis of eight genome-wide FANTOM5 CAGE (cap analysis of gene expression) time course datasets reveals successive waves of promoter activation in IEGs, recapitulating known relationships between cell types and stimuli: we obtain a set of 57 (42 protein-coding) candidate IEGs possessing promoters that consistently drive a rapid but transient increase in expression over time. These genes show significant enrichment for known IEGs reported previously, pathways associated with the immediate early response, and include a number of non-coding RNAs with roles in proliferation and differentiation. Surprisingly, we also find strong conservation of the ordering of activation for these genes, such that 77 pairwise promoter activation orderings are conserved. Using the leverage of comprehensive CAGE time series data across cell types, we also document the extensive alternative promoter usage by such genes, which is likely to have been a barrier to their discovery until now. The common activation ordering of the core set of early-responding genes we identify may indicate conserved underlying regulatory mechanisms. By contrast, the considerably larger number of transiently activated genes that are specific to each cell type and stimulus illustrates the breadth of the primary response.
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| 27. |
- Van Eck, C.L., et al.
(författare)
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Polarized point sources in the LOFAR Two-meter Sky Survey: A preliminary catalog
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 613
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Forskningsöversikt (refereegranskat)abstract
- The polarization properties of radio sources at very low frequencies (<200 MHz) have not been widely measured, but the new generation of low-frequency radio telescopes, including the Low Frequency Array (LOFAR: a Square Kilometre Array Low pathfinder), now gives us the opportunity to investigate these properties. In this paper, we report on the preliminary development of a data reduction pipeline to carry out polarization processing and Faraday tomography for data from the LOFAR Two-meter Sky Survey (LOTSS) and present the results of this pipeline from the LOTSS preliminary data release region (10h45m–15h30m right ascension, 45°–57° declination, 570 square degrees). We have produced a catalog of 92 polarized radio sources at 150 MHz at 4.′3 resolution and 1 mJy rms sensitivity, which is the largest catalog of polarized sources at such low frequencies. We estimate a lower limit to the polarized source surface density at 150 MHz, with our resolution and sensitivity, of 1 source per 6.2 square degrees. We find that our Faraday depth measurements are in agreement with previous measurements and have significantly smaller errors. Most of our sources show significant depolarization compared to 1.4 GHz, but there is a small population of sources with low depolarization indicating that their polarized emission is highly localized in Faraday depth. We predict that an extension of this work to the full LOTSS data would detect at least 3400 polarized sources using the same methods, and probably considerably more with improved data processing.
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