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Sökning: WFRF:(Hasler P) > (2015-2019)

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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Elhai, M, et al. (författare)
  • Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
  • 2019
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
  • Tidskriftsartikel (refereegranskat)abstract
    • To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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  • Wang, J., et al. (författare)
  • Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:11, s. 1396-1406
  • Tidskriftsartikel (refereegranskat)abstract
    • Human gut microbiota is an important determinant for health and disease, and recent studies emphasize the numerous factors shaping its diversity. Here we performed a genome-wide association study (GWAS) of the gut microbiota using two cohorts from northern Germany totaling 1,812 individuals. Comprehensively controlling for diet and non-genetic parameters, we identify genome-wide significant associations for overall microbial variation and individual taxa at multiple genetic loci, including the VDR gene (encoding vitamin D receptor). We observe significant shifts in the microbiota of Vdr(-/-) mice relative to control mice and correlations between the microbiota and serum measurements of selected bile and fatty acids in humans, including known ligands and downstream metabolites of VDR. Genome-wide significant (P < 5 x 10(-8)) associations at multiple additional loci identify other important points of host-microbe intersection, notably several disease susceptibility genes and sterol metabolism pathway components. Non-genetic and genetic factors each account for approximately 10% of the variation in gut microbiota, whereby individual effects are relatively small.
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  • Kowal-Bielecka, Otylia, et al. (författare)
  • Update of EULAR recommendations for the treatment of systemic sclerosis
  • 2017
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
  • 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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  • Siwowska, K., et al. (författare)
  • Therapeutic Potential of Sc-47 in Comparison to Lu-177 and Y-90: Preclinical Investigations
  • 2019
  • Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Targeted radionuclide therapy with Lu-177- and Y-90-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. Sc-47 is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy beta(-)particles. In this study, Sc-47 was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of Lu-17-folate and Y-90-folate, respectively. In vitro, Sc-47-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to Lu-177-folate, but Y-90-folate was more potent at equal activities due to the higher energy of emitted beta(-)particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (similar to 21 Gy) when treated with Sc-47-folate (12.5 MBq), Lu-177-folate (10 MBq), and Y-90-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, Sc-47 is likely to be comparable to Lu-177 when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with Sc-44 or Sc-43 as a diagnostic match, enabling the realization of radiotheragnostics in future.
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  • Reusch, T. B. H., et al. (författare)
  • The Baltic Sea as a time machine for the future coastal ocean
  • 2018
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Coastal global oceans are expected to undergo drastic changes driven by climate change and increasing anthropogenic pressures in coming decades. Predicting specific future conditions and assessing the best management strategies to maintain ecosystem integrity and sustainable resource use are difficult, because of multiple interacting pressures, uncertain projections, and a lack of test cases for management. We argue that the Baltic Sea can serve as a time machine to study consequences and mitigation of future coastal perturbations, due to its unique combination of an early history of multistressor disturbance and ecosystem deterioration and early implementation of cross-border environmental management to address these problems. The Baltic Sea also stands out in providing a strong scientific foundation and accessibility to long-term data series that provide a unique opportunity to assess the efficacy of management actions to address the breakdown of ecosystem functions. Trend reversals such as the return of top predators, recovering fish stocks, and reduced input of nutrient and harmful substances could be achieved only by implementing an international, cooperative governance structure transcending its complex multistate policy setting, with integrated management of watershed and sea. The Baltic Sea also demonstrates how rapidly progressing global pressures, particularly warming of Baltic waters and the surrounding catchment area, can offset the efficacy of current management approaches. This situation calls for management that is (i) conservative to provide a buffer against regionally unmanageable global perturbations, (ii) adaptive to react to new management challenges, and, ultimately, (iii) multisectorial and integrative to address conflicts associated with economic trade-offs.
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12.
  • Thormar, Jonas, et al. (författare)
  • Eelgrass (Zostera marina) food web structure in different environmental settings.
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • This study compares the structure of eelgrass (Zostera marina L.) meadows and associated food webs in two eelgrass habitats in Denmark, differing in exposure, connection to the open sea, nutrient enrichment and water transparency. Meadow structure strongly reflected the environmental conditions in each habitat. The eutrophicated, protected site had higher biomass of filamentous algae, lower eelgrass biomass and shoot density, longer and narrower leaves, and higher above to below ground biomass ratio compared to the less nutrient-enriched and more exposed site. The faunal community composition and food web structure also differed markedly between sites with the eutrophicated, enclosed site having higher biomass of consumers and less complex food web. These relationships resulted in a column shaped biomass distribution of the consumers at the eutrophicated site whereas the less nutrient-rich site showed a pyramidal biomass distribution of consumers coupled with a more diverse consumer community. The differences in meadow and food web structure of the two seagrass habitats, suggest how physical setting may shape ecosystem response and resilience to anthropogenic pressure. We encourage larger, replicated studies to further disentangle the effects of different environmental variables on seagrass food web structure.
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  • Wang, Y. T., et al. (författare)
  • Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule : influence of age, gender, study country and testing protocol
  • 2015
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 42:6, s. 761-772
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner. AimTo investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. MethodsRegional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. ResultsFor GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52min, P=0.0063) and colonic transit time (CTT; longer with protocol 2: median 140min, P=0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17min, P=0.0307), and also longer CTT by (104min, P=0.0285) and whole gut transit time by (263min, P=0.0077). Increasing age was associated with shorter small bowel transit time (P=0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. ConclusionsRegional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research.
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  • Zhang, H., et al. (författare)
  • Frequency response improvement with synchronous condenser and power electronics converters
  • 2017
  • Ingår i: 2017 IEEE 3rd International Future Energy Electronics Conference and ECCE Asia, IFEEC - ECCE Asia 2017. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781509051571 ; , s. 1002-1007
  • Konferensbidrag (refereegranskat)abstract
    • This paper gives an overall review of the working principle of the inertial response from the synchronous condenser for frequency support in the grid. In addition to this, four proposed frequency control strategies for improvement of network frequency response by static energy storage devices, such as the Static Synchronous Compensator (STATCOM) with suitable energy storage elements or the battery energy storage system (BESS), are presented. The proposed frequency control strategies are evaluated and benchmarked with the synchronous condenser in the same network. It is shown that a power electronic converter based system with energy storage can be designed with lower rating, still providing the same or better frequency support than the synchronous condenser.
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  • Zhang, H., et al. (författare)
  • SISO Transfer Functions for Stability Analysis of Grid-Connected Voltage-Source Converters
  • 2019
  • Ingår i: IEEE transactions on industry applications. - : Institute of Electrical and Electronics Engineers Inc.. - 0093-9994 .- 1939-9367. ; 55:3, s. 2931-2941
  • Tidskriftsartikel (refereegranskat)abstract
    • Converter-grid interaction is of great interest in a weak-grid condition. This paper presents a single-input-single-output (SISO) open-loop transfer function for the stability analysis of grid-connected voltage-source converters. Differing from the conventional input impedance method and the eigenvalue analysis, an alternative multi-input-multi-output closed-loop system is developed in the paper and it eventually yields an SISO open-loop transfer function. This enables the application of a single Nyquist curve for analyzing the overall system stability. The model is validated against time-domain simulations as well as experimental results showing excellent accuracy for predicting the system stability.
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