| 1. |
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| 2. |
- 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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| 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. |
- Saunois, M., et al.
(författare)
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The global methane budget 2000–2012
- 2016
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 8:2, s. 697-751
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Tidskriftsartikel (refereegranskat)abstract
- The global methane (CH4) budget is becoming an increasingly important component for managing realistic pathways to mitigate climate change. This relevance, due to a shorter atmospheric lifetime and a stronger warming potential than carbon dioxide, is challenged by the still unexplained changes of atmospheric CH4 over the past decade. Emissions and concentrations of CH4 are continuing to increase, making CH4 the second most important human-induced greenhouse gas after carbon dioxide. Two major difficulties in reducing uncertainties come from the large variety of diffusive CH4 sources that overlap geographically, and from the destruction of CH4 by the very short-lived hydroxyl radical (OH). To address these difficulties, we have established a consortium of multi-disciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate research on the methane cycle, and producing regular (∼ biennial) updates of the global methane budget. This consortium includes atmospheric physicists and chemists, biogeochemists of surface and marine emissions, and socio-economists who study anthropogenic emissions. Following Kirschke et al. (2013), we propose here the first version of a living review paper that integrates results of top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models, inventories and data-driven approaches (including process-based models for estimating land surface emissions and atmospheric chemistry, and inventories for anthropogenic emissions, data-driven extrapolations). For the 2003–2012 decade, global methane emissions are estimated by top-down inversions at 558 Tg CH4 yr−1, range 540–568. About 60 % of global emissions are anthropogenic (range 50–65 %). Since 2010, the bottom-up global emission inventories have been closer to methane emissions in the most carbon-intensive Representative Concentrations Pathway (RCP8.5) and higher than all other RCP scenarios. Bottom-up approaches suggest larger global emissions (736 Tg CH4 yr−1, range 596–884) mostly because of larger natural emissions from individual sources such as inland waters, natural wetlands and geological sources. Considering the atmospheric constraints on the top-down budget, it is likely that some of the individual emissions reported by the bottom-up approaches are overestimated, leading to too large global emissions. Latitudinal data from top-down emissions indicate a predominance of tropical emissions (∼ 64 % of the global budget, < 30° N) as compared to mid (∼ 32 %, 30–60° N) and high northern latitudes (∼ 4 %, 60–90° N). Top-down inversions consistently infer lower emissions in China (∼ 58 Tg CH4 yr−1, range 51–72, −14 %) and higher emissions in Africa (86 Tg CH4 yr−1, range 73–108, +19 %) than bottom-up values used as prior estimates. Overall, uncertainties for anthropogenic emissions appear smaller than those from natural sources, and the uncertainties on source categories appear larger for top-down inversions than for bottom-up inventories and models. The most important source of uncertainty on the methane budget is attributable to emissions from wetland and other inland waters. We show that the wetland extent could contribute 30–40 % on the estimated range for wetland emissions. Other priorities for improving the methane budget include the following: (i) the development of process-based models for inland-water emissions, (ii) the intensification of methane observations at local scale (flux measurements) to constrain bottom-up land surface models, and at regional scale (surface networks and satellites) to constrain top-down inversions, (iii) improvements in the estimation of atmospheric loss by OH, and (iv) improvements of the transport models integrated in top-down inversions. The data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (http://doi.org/10.3334/CDIAC/GLOBAL_METHANE_BUDGET_2016_V1.1) and the Global Carbon Project.
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| 5. |
- Saunois, M., et al.
(författare)
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Variability and quasi-decadal changes in the methane budget over the period 2000–2012
- 2017
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 17:18, s. 11135-11161
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Tidskriftsartikel (refereegranskat)abstract
- Following the recent Global Carbon Project (GCP) synthesis of the decadal methane (CH4) budget over 2000–2012 (Saunois et al., 2016), we analyse here the same dataset with a focus on quasi-decadal and inter-annual variability in CH4 emissions. The GCP dataset integrates results from top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models (including process-based models for estimating land surface emissions and atmospheric chemistry), inventories of anthropogenic emissions, and data-driven approaches. The annual global methane emissions from top-down studies, which by construction match the observed methane growth rate within their uncertainties, all show an increase in total methane emissions over the period 2000–2012, but this increase is not linear over the 13 years. Despite differences between individual studies, the mean emission anomaly of the top-down ensemble shows no significant trend in total methane emissions over the period 2000–2006, during the plateau of atmospheric methane mole fractions, and also over the period 2008–2012, during the renewed atmospheric methane increase. However, the top-down ensemble mean produces an emission shift between 2006 and 2008, leading to 22 [16–32] Tg CH4 yr−1 higher methane emissions over the period 2008–2012 compared to 2002–2006. This emission increase mostly originated from the tropics, with a smaller contribution from mid-latitudes and no significant change from boreal regions. The regional contributions remain uncertain in top-down studies. Tropical South America and South and East Asia seem to contribute the most to the emission increase in the tropics. However, these two regions have only limited atmospheric measurements and remain therefore poorly constrained. The sectorial partitioning of this emission increase between the periods 2002–2006 and 2008–2012 differs from one atmospheric inversion study to another. However, all top-down studies suggest smaller changes in fossil fuel emissions (from oil, gas, and coal industries) compared to the mean of the bottom-up inventories included in this study. This difference is partly driven by a smaller emission change in China from the top-down studies compared to the estimate in the Emission Database for Global Atmospheric Research (EDGARv4.2) inventory, which should be revised to smaller values in a near future. We apply isotopic signatures to the emission changes estimated for individual studies based on five emission sectors and find that for six individual top-down studies (out of eight) the average isotopic signature of the emission changes is not consistent with the observed change in atmospheric 13CH4. However, the partitioning in emission change derived from the ensemble mean is consistent with this isotopic constraint. At the global scale, the top-down ensemble mean suggests that the dominant contribution to the resumed atmospheric CH4 growth after 2006 comes from microbial sources (more from agriculture and waste sectors than from natural wetlands), with an uncertain but smaller contribution from fossil CH4 emissions. In addition, a decrease in biomass burning emissions (in agreement with the biomass burning emission databases) makes the balance of sources consistent with atmospheric 13CH4 observations. In most of the top-down studies included here, OH concentrations are considered constant over the years (seasonal variations but without any inter-annual variability). As a result, the methane loss (in particular through OH oxidation) varies mainly through the change in methane concentrations and not its oxidants. For these reasons, changes in the methane loss could not be properly investigated in this study, although it may play a significant role in the recent atmospheric methane changes as briefly discussed at the end of the paper.
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| 6. |
- Adlard, B., et al.
(författare)
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Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme
- 2018
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Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.
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| 7. |
- Cantos, Irene Pardo, et al.
(författare)
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Determination and analysis of time series of CFC-11 (CCl3F) from FTIR solar spectra, in situ observations, and model data in the past 20 years above Jungfraujoch (46 degrees N), Lauder (45 degrees S), and Cape Grim (40 degrees S) stations
- 2022
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Ingår i: Environmental Science: Atmospheres. - : Royal Society of Chemistry (RSC). - 2634-3606. ; 2:6, s. 1487-1501
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Tidskriftsartikel (refereegranskat)abstract
- The atmospheric concentration of CFC-11 (CCl3F) has declined in response to the phase-out of its production by the Montreal Protocol. Nevertheless, this atmospheric concentration decline suffered a slow-down around 2012 due to emissions from non-reported production. Since CFC-11 is one of the most important ozone-depleting chlorofluorocarbons (CFCs), its continuous monitoring is essential. We present the CFC-11 total column time series (2000-2020) retrieved in a consistent way from ground-based high-resolution solar absorption Fourier transform infrared (FTIR) spectra. These observations were recorded at two remote stations of the Network for the Detection of Atmospheric Composition Change (NDACC): the Jungfraujoch station (Northern Hemisphere) and the Lauder station (Southern Hemisphere). These time series are new. They were produced using improved line parameters and merged considering the instrument changes and setup modifications. Afterwards, they were compared with Cape Grim station in situ surface observations conducted within the Advanced Global Atmospheric Gases Experiment (AGAGE) network and with total column datasets calculated by the TOMCAT/SLIMCAT 3-D chemical transport model. Trend analyses were performed, using an advanced statistical tool, in order to identify the timing and magnitude of the trend change in both hemispheres. The observations are consistent with the model results and confirm the slowdown in the CFC-11 atmospheric concentration decay, since approximate to 2011 in the Northern Hemisphere, and since approximate to 2014 in the Southern Hemisphere.
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| 8. |
- 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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| 9. |
- Saunois, Marielle, et al.
(författare)
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The Global Methane Budget 2000–2017
- 2020
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3516 .- 1866-3508. ; 12:3, s. 1561-1623
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorter atmospheric lifetime, stronger warming potential, and variations in atmospheric growth rate over the past decade, the causes of which are still debated. Two major challenges in reducing uncertainties in the atmospheric growth rate arise from the variety of geographically overlapping CH4 sources and from the destruction of CH4 by short-lived hydroxyl radicals (OH). To address these challenges, we have established a consortium of multidisciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate new research aimed at improving and regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations).For the 2008–2017 decade, global methane emissions are estimated by atmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximum estimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or ∼ 60 % is attributed to anthropogenic sources, that is emissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is 29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009), and 24 Tg CH4 yr−1 larger than the one reported in the previous budget for 2003–2012 (Saunois et al., 2016). Since 2012, global CH4 emissions have been tracking the warmest scenarios assessed by the Intergovernmental Panel on Climate Change. Bottom-up methods suggest almost 30 % larger global emissions (737 Tg CH4 yr−1, range 594–881) than top-down inversion methods. Indeed, bottom-up estimates for natural sources such as natural wetlands, other inland water systems, and geological sources are higher than top-down estimates. The atmospheric constraints on the top-down budget suggest that at least some of these bottom-up emissions are overestimated. The latitudinal distribution of atmospheric observation-based emissions indicates a predominance of tropical emissions (∼ 65 % of the global budget, < 30∘ N) compared to mid-latitudes (∼ 30 %, 30–60∘ N) and high northern latitudes (∼ 4 %, 60–90∘ N). The most important source of uncertainty in the methane budget is attributable to natural emissions, especially those from wetlands and other inland waters.Some of our global source estimates are smaller than those in previously published budgets (Saunois et al., 2016; Kirschke et al., 2013). In particular wetland emissions are about 35 Tg CH4 yr−1 lower due to improved partition wetlands and other inland waters. Emissions from geological sources and wild animals are also found to be smaller by 7 Tg CH4 yr−1 by 8 Tg CH4 yr−1, respectively. However, the overall discrepancy between bottom-up and top-down estimates has been reduced by only 5 % compared to Saunois et al. (2016), due to a higher estimate of emissions from inland waters, highlighting the need for more detailed research on emissions factors. Priorities for improving the methane budget include (i) a global, high-resolution map of water-saturated soils and inundated areas emitting methane based on a robust classification of different types of emitting habitats; (ii) further development of process-based models for inland-water emissions; (iii) intensification of methane observations at local scales (e.g., FLUXNET-CH4 measurements) and urban-scale monitoring to constrain bottom-up land surface models, and at regional scales (surface networks and satellites) to constrain atmospheric inversions; (iv) improvements of transport models and the representation of photochemical sinks in top-down inversions; and (v) development of a 3D variational inversion system using isotopic and/or co-emitted species such as ethane to improve source partitioning.The data presented here can be downloaded from https://doi.org/10.18160/GCP-CH4-2019 (Saunois et al., 2020) and from the Global Carbon Project.
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