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- 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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- Herrick, A. L., et al.
(författare)
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Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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- Midtvedt, Daniel, 1988, et al.
(författare)
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Direct measurement of nitric oxide (NO) in the gastrointestinal tract of cod (Gadus morhua)
- 2009
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Ingår i: Microbial Ecology in Health and Disease. - : Informa UK Limited. - 0891-060X .- 1651-2235. ; 21:3-4, s. 175-177
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In mammals, the biological messenger nitric oxide (NO) is generated throughout the gastrointestinal (GI) tract from the reduction of dietary nitrate and nitrite. The aim of the present study was to investigate the amount of GI NO in Atlantic cod (Gadus morhua) in relation to intake of food. Methods: A total of 28 cod were divided into 3 groups, fed at different times before the experiment (1 week, 1 day, and 3 h, respectively). Results: In the stomach, the measured NO concentrations were consistently higher in the group fed 3 h before the measurement, implying that the NO3-NO2-NO pathway is present in the stomach of cod. We also measured the NO concentration in the large intestine. Again, the values were higher in cod fed 3 h before the experiment. Conclusion: We conclude that NO is formed in the GI tract of cod, likely via the reduction of dietary nitrate and nitrite. The physiological importance of this NO production remains to be determined.
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- Lindahl, Niklas, 1981, et al.
(författare)
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Determination of the Bending Rigidity of Graphene via Electrostatic Actuation of Buckled Membranes
- 2012
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 12:7, s. 3526-3531
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Tidskriftsartikel (refereegranskat)abstract
- Classical continuum mechanics is used extensively to predict the properties of nanoscale materials such as graphene. The bending rigidity, kappa, is an important parameter that is used, for example, to predict the performance of graphene nanoelectromechanical devices and also ripple formation. Despite its importance, there is a large spread in the theoretical predictions of kappa for few-layer graphene. We have used the snap-through behavior of convex buckled graphene membranes under the application of electrostatic pressure to determine experimentally values of kappa for double-layer graphene membranes. We demonstrate how to prepare convex-buckled suspended graphene ribbons and fully clamped suspended membranes and show how the determination of the curvature of the membranes and the critical snap-through voltage, using AFM, allows us to extract kappa. The bending rigidity of bilayer graphene membranes under ambient conditions was determined to be 35.5(-15.0)(+20.0) eV. Monolayers are shown to have significantly lower kappa than bilayers.
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- Svensson, Johannes, et al.
(författare)
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Carbon Nanotube Field Effect Transistors with Suspended Graphene Gates
- 2011
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 11:9, s. 3569-3575
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Tidskriftsartikel (refereegranskat)abstract
- Novel field effect transistors with suspended graphene gates are demonstrated. By incorporating mechanical motion of the gate electrode, it is possible to improve the switching characteristics compared to a static gate, as shown by a combination of experimental measurements and numerical simulations. The mechanical motion of the graphene gate is confirmed by using atomic force microscopy to directly measure the electrostatic deflection. The device geometry investigated here can also provide a sensitive measurement technique for detecting high-frequency motion of suspended membranes as required, e.g., for mass sensing.
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