| 1. |
- Elhai, M, et al.
(author)
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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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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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Journal article (peer-reviewed)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. |
- Andersson, L. Robin, et al.
(author)
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Characterization of Flow Structures Induced by Highly Rough Surface Using Particle Image Velocimetry, Proper Orthogonal Decomposition and Velocity Correlations
- 2018
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In: Engineering. - : Scientific Research Publishing. - 1947-3931 .- 1947-394X. ; 10, s. 399-416
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Journal article (peer-reviewed)abstract
- High Reynolds number flow inside a channel of rectangular cross section is examined using Particle Image Velocimetry. One wall of the channel has been replaced with a surface of a roughness representative to that of real hydropower tunnels, i.e. a random terrain with roughness dimensions typically in the range of ≈10% - 20% of the channels hydraulic radius. The rest of the channel walls can be considered smooth. The rough surface was captured from an existing blasted rock tunnel using high resolution laser scanning and scaled to 1:10. For quantification of the size of the largest flow structures, integral length scales are derived from the auto-correlation functions of the temporally averaged velocity. Additionally, Proper Orthogonal Decomposition (POD) and higher-order statistics are applied to the instantaneous snapshots of the velocity fluctuations. The results show a high spatial heterogeneity of the velocity and other flow characteristics in vicinity of the rough surface, putting outer similarity treatment into jeopardy. Roughness effects are not confined to the vicinity of the rough surface but can be seen in the outer flow throughout the channel, indicating a different behavior than postulated by Townsend’s similarity hypothesis. The effects on the flow structures vary depending on the shape and size of the roughness elements leading to a high spatial dependence of the flow above the rough surface. Hence, any spatial averaging, e.g. assuming a characteristic sand grain roughness factor, for determining local flow parameters becomes less applicable in this case.
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| 4. |
- Andersson, Robin, et al.
(author)
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Inlet Blockage Effects in a Free Surface Channel With Artificially Generated Rough Walls
- 2018
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In: Proceedings of the 7th IAHR International Symposium on Hydraulic Structures. - 9780692132777 ; , s. 723-732
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Conference paper (peer-reviewed)abstract
- When considering free surface flow in channels, it is essential to have in-depth knowledge about the inlet flow conditions and the effect of surface roughness on the overall flow field. Hence, we hereby investigate flow inside an 18m long channel by using Particle Tracking Velocimetry (PTV) and Acoustic Doppler Velocimetry (ADV). The roughness of the channel walls is generated using a diamond-square fractal algorithm and is designed to resemble the actual geometry of hydropower tunnels. Four different water levels ranging from 20 to 50cm are investigated. For each depth, the inlet is blocked by 25 and 50% at three positions each, at the centre, to the right and to the left in the flow-direction. The flow is altered for each depth to keep the flow velocity even throughout the measurements. PTV is applied to measure the velocity of the free water surface; four cameras are placed above the setup to capture the entirety of the channel. The results show a clear correlation between roughness-height and velocity distribution at depths 20-30 cm. The surface roughness proved effective in dispersing the subsequent perturbations following the inlet blockage. At 50cm, perturbations from the 50% blockage could be observed throughout the channel. However, at 20cm, most perturbations had subsided by a third of the channel length. The ADV was used to capture the velocity in a total of 375 points throughout the channel, at a depth of 50 cm with no inlet perturbations.
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| 5. |
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| 6. |
- Andersson, Robin, 1987-, et al.
(author)
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Numerical investigation of a hydropower tunnel : Estimating localised head-loss using the manning equation
- 2019
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In: Water. - : MDPI. - 2073-4441. ; 11:8
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Journal article (peer-reviewed)abstract
- The fluid dynamics within a water tunnel is investigated numerically using a RANS approach with the k-ε turbulence model. The computational model is based on a laser scan of a hydropower tunnel located in Gävunda, Sweden. The tunnel has a typical height of 6.9 m and a width of 7.2 m. While the average cross-sectional shape of the tunnel is smooth the local deviations are significant, where some roughness elements may be in the size of 5 m implying a large variation of the hydraulic radius. The results indicate that the Manning equation can successfully be used to study the localised pressure variations by taking into account the varying hydraulic radius and cross-sectional area of the tunnel. This indicates a dominant effect of the tunnel roughness in connection with the flow, which has the potential to be used in the future evaluation of tunnel durability. ANSYS-CFX was used for the simulations along with ICEM-CFD for building the mesh.
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| 7. |
- Andreasson, K. I., et al.
(author)
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Targeting innate immunity for neurodegenerative disorders of the central nervous system
- 2016
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; , s. 653-693
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Journal article (peer-reviewed)abstract
- Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7–9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. (Figure presented.) Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7–9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. © 2016 International Society for Neurochemistry
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| 8. |
- Andreasson, Ulf, 1968, et al.
(author)
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Commutability of the certified reference materials for the standardization of beta-amyloid 1-42 assay in human cerebrospinal fluid: lessons for tau and beta-amyloid 1-40 measurements
- 2018
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In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 56:12, s. 2058-2066
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Journal article (peer-reviewed)abstract
- Background: The core Alzheimer's disease cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), beta-amyloid 1-42 (A beta 42) and beta-amyloid 1-40 (A beta 40) are increasing in importance and are now part of the research criteria for the diagnosis of the disease. The main aim of this study is to evaluate whether a set of certified reference materials (CRMs) are commutable for A beta 42 and to serve as a feasibility study for the other markers. This property is a prerequisite for the establishment of CRMs which will then be used by manufacturers to calibrate their assays against. Once the preanalytical factors have been standardized and proper selection criteria are available for subject cohorts this harmonization between methods will allow for universal cut-offs to be determined. Methods: Thirty-four individual CSF samples and three different CRMs where analyzed for T-tau, P-tau, A beta 42 and A beta 40, using up to seven different commercially available methods. For A beta 40 and A beta 42 a mass spectrometry-based procedure was also employed. Results: There were strong pairwise correlations between the different methods (Spearman's p>0.92) for all investigated analytes and the CRMs were not distinguishable from the individual samples. Conclusions: This study shows that the CRMs are commutable for the different assays for A beta 42. For the other analytes the results show that it would be feasible to also produce CRMs for these. However, additional studies are needed as the concentration interval for the CRMs were selected based on A beta 42 concentrations only and did in general not cover satisfactory large concentration intervals for the other analytes.
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| 9. |
- Babicheva, T., et al.
(author)
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The matching problem of empty vehicle redistribution in autonomous taxi systems
- 2018
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In: The 9th International Conference on Ambient Systems, Networks and Technologies (ANT 2018) / The 8th International Conference on Sustainable Energy Information Technology (SEIT-2018) / Affiliated Workshops. - : Elsevier. ; , s. 119-125
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Conference paper (peer-reviewed)abstract
- This article discusses empty vehicle redistribution algorithms for PRT and autonomous taxi services from a passenger service perspective. In modern literature reactive methods such as nearest neighbours are commonly used. In this article we first formulate the general matching problem on a bipartite graph of available vehicles and stations. In addition, we propose a new index-based proactive redistribution (IBR) algorithm based on predicted near-future demand at stations. Test results of six variations of combined proactive and reactive strategies on a test case in Saclay, France with 20 stations and 100 vehicles are given. The combined Nearest Neighbour / IBR provides a promising solution for both peak and off-peak demand, significantly outperforming all other methods considered, in terms of passenger waiting time (both average and maximum) as well as in terms of station queue lengths.
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| 10. |
- Bedoni, Nicola, et al.
(author)
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Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility
- 2016
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In: Human Molecular Genetics. - 0964-6906. ; 25:20, s. 4546-4555
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Journal article (peer-reviewed)abstract
- Hereditary retinal degenerations encompass a group of genetic diseases characterized by extreme clinical variability. Following next-generation sequencing and autozygome-based screening of patients presenting with a peculiar, recessive form of cone-dominated retinopathy, we identified five homozygous variants [p.(Asp594fs), p.(Gln117*), p.(Met712fs), p.(Ile756Phe), and p.(Glu543Lys)] in the polyglutamylase-encoding gene TTLL5, in eight patients from six families. The two male patients carrying truncating TTLL5 variants also displayed a substantial reduction in sperm motility and infertility, whereas those carrying missense changes were fertile. Defects in this polyglutamylase in humans have recently been associated with cone photoreceptor dystrophy, while mouse models carrying truncating mutations in the same gene also display reduced fertility in male animals. We examined the expression levels of TTLL5 in various human tissues and determined that this gene has multiple viable isoforms, being highly expressed in testis and retina. In addition, antibodies against TTLL5 stained the basal body of photoreceptor cells in rat and the centrosome of the spermatozoon flagellum in humans, suggesting a common mechanism of action in these two cell types. Taken together, our data indicate that mutations in TTLL5 delineate a novel, allele-specific syndrome causing defects in two as yet pathogenically unrelated functions, reproduction and vision.
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