| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Abarenkov, Kessy, et al.
(författare)
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Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
- 2016
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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| 3. |
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| 4. |
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| 5. |
- Barredo, José I., et al.
(författare)
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Mapping and assessment of forest ecosystems and their services : Applications and guidance for decision making in the framework of MAES
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this report is to illustrate by means of a series of case studies the implementation of mapping and assessment of forest ecosystem services in different contexts and geographical levels. Methodological aspects, data issues, approaches, limitations, gaps and further steps for improvement are analysed for providing good practices and decision making guidance. The EU initiative on Mappingand Assessment of Ecosystems and their Services (MAES), with the support of all Member States, contributes to improve the knowledge on ecosystem services. MAES is one of the building-block initiatives supporting the EU Biodiversity Strategy to 2020.
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| 6. |
- Bengtsson, Anders A., et al.
(författare)
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Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren’s Syndrome and Systemic Sclerosis
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diag- nose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.
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| 7. |
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| 8. |
- Bengtsson, Lars, 1958-, et al.
(författare)
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Innovativa konkurrenter från tillväxtekonomier : vad gör svenska företag?
- 2018
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Ingår i: MGMT of Innovation and Technology. - 2001-208X. ; 1, s. 10-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Konkurrensen från tillväxtekonomier handlar inte längre om lågkostnadsproduktion. I Kina, Turkiet och Brasilien har många företag utvecklat förmågor till både innovativ och snabb produktframtagning. Vad karaktäriserar dessa företag? Och vad kan svenska företag göra för att hantera de nya utmaningarna och möjligheterna?
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| 9. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Metaxa2 Database Builder: enabling taxonomic identification from metagenomic or metabarcoding data using any genetic marker
- 2018
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Ingår i: Bioinformatics (Oxford, England). - : Oxford University Press (OUP). - 1367-4811 .- 1367-4803. ; 34:23, s. 4027-4033
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Tidskriftsartikel (refereegranskat)abstract
- Correct taxonomic identification of DNA sequences is central to studies of biodiversity using both shotgun metagenomic and metabarcoding approaches. However, no genetic marker gives sufficient performance across all the biological kingdoms, hampering studies of taxonomic diversity in many groups of organisms. This has led to the adoption of a range of genetic markers for DNA metabarcoding. While many taxonomic classification software tools can be re-trained on these genetic markers, they are often designed with assumptions that impair their utility on genes other than the SSU and LSU rRNA. Here, we present an update to Metaxa2 that enables the use of any genetic marker for taxonomic classification of metagenome and amplicon sequence data.We evaluated the Metaxa2 Database Builder on eleven commonly used barcoding regions and found that while there are wide differences in performance between different genetic markers, our software performs satisfactorily provided that the input taxonomy and sequence data are of high quality.Freely available on the web as part of the Metaxa2 package at http://microbiology.se/software/metaxa2/.Supplementary data are available at Bioinformatics online.
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| 10. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Metaxa2 Diversity Tools: Easing microbial community analysis with Metaxa2
- 2016
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Ingår i: Ecological Informatics. - : Elsevier BV. - 1574-9541. ; 33, s. 45-50
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Tidskriftsartikel (refereegranskat)abstract
- DNA sequencing has become an integrated part of microbial ecology, and taxonomic marker genes such as the SSU and LSU rRNA are frequently used to assess community structure. One solution for taxonomic community analysis based on shotgun metagenomic data is the Metaxa2 software, which can extract and classify sequence fragments belonging to the rRNA genes. This paper describes the Metaxa2 Diversity Tools, a set of new open-source software programs that extends the capabilities of the Metaxa2 software. These tools allow for better handling of data from multiple samples, improved species classifications, rarefaction analysis accounting for unclassified entries, and determination of significant differences in community composition of different samples. We demonstrate the performance of the software tools on rRNA data extracted from different shotgun metagenomes, and find the tools to streamline and improve the assessments of community diversity, particularly for samples from environments for which few reference genomes are available. Finally, we establish that our resampling algorithm for determining community dissimilarity is robust to differences in coverage depth, suggesting that it forms a complement to multidimensional visualization approaches for finding differences between communities. The Metaxa2 Diversity Tools are included in recent versions (2.1 and later) of Metaxa2 (http://microbiology.se/software/metaxa2/) and facilitate implementation of Metaxa2 within software pipelines for taxonomic analysis of environmental communities.
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| 11. |
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| 12. |
- Bhadani, Kanishk, 1991, et al.
(författare)
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Student Perspectives on Video-Based Learning in CDIO-Based Project Courses
- 2017
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Ingår i: The 13th International CDIO Conference Proceedings, Calgary, Canada. - 1796-9964. - 9780889533998 ; , s. 689-704
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Konferensbidrag (refereegranskat)abstract
- This paper aims at demonstrating the applicability of video learning in CDIO based project courses and at evaluating to what extent it benefits students. The courses are Machine Elements (PPU210), Product Planning - Needs and Opportunities (PPU085) and Engineering Design and Optimization (PPU190) in the Mechanical Engineering programme at Chalmers University of Technology. The research was carried out by first creating a set of videos for selected topics in three courses. In total, 22 videos were created including topics such as “Benchmarking”, “SWOT”, and “Prototype lab equipment instructions”. The learning outcomes of the video lectures were mapped to the CDIO syllabus. A blended learning environment was developed, i.e. the videos were utilised as additional support alongside existing learning activities. The videos were then used in the courses and the students’ feedbacks collected through a dedicated questionnaire, the regular course evaluation survey, and in student-teacher group meetings during and after the courses. The collected data was analysed to produce inferences about the applicability and utility of the video lectures. The resulting analysis shows the students’ preferences regarding the evaluated video lectures and instructions. The students find videos more appealing compared to traditional lectures. One of the main benefits highlighted is the possibility of watching the videos in parallel to the design-build-test project execution rather having the classroom lecture only. This helps in reinforcing concepts, and results in less dependency on supervisors during the project execution. Videos proved to be suitable for creating a blended learning environment and improved the perceived learning experience for the students. In order to maximize student satisfaction and interaction with the videos, the videos should be short and closely aligned to the other learning activities. The paper also suggests future improvements to be carried out for video-based learning in the courses, and proposes an easy adaptable way for teachers to develop video material.
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| 13. |
- Brackmann, Christian, et al.
(författare)
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Experimental studies of nitromethane flames and evaluation of kinetic mechanisms
- 2018
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Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180. ; 190, s. 327-336
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Tidskriftsartikel (refereegranskat)abstract
- The present work reports new experimental data for premixed flames of nitromethane, CH3NO2, at atmospheric pressure, and an evaluation of two contemporary kinetic mechanisms based on these new flame studies as well as previously published experimental data on laminar burning velocity and ignition. Flames of nitromethane + air at lean (ϕ = 0.8) and rich (ϕ = 1.2) conditions were stabilized on a flat-flame burner, where profiles of CH2O, CO and NO were obtained using laser-induced fluorescence and temperature profiles using coherent anti-Stokes Raman spectroscopy. Laminar burning velocities for nitromethane + O2 + CO2 were measured using the heat flux method for ϕ = 0.8–1.3 at 348 K and ϕ = 0.8–1.6 at 358 K, and an oxidizer composition of 35% O2 and 65% CO2. In addition, the effect of the oxidizer composition was examined for a stoichiometric flame at 358 K by varying oxygen fraction from 30% to 40%. The mechanism by Mathieu et al. (Fuel 2016, 182, 597), previously not validated for flames, was able to reproduce experimental laminar burning velocities for nitromethane + air, but under predicted new results for CH3NO2 + O2 + CO2 mixtures. The mechanism by Brequigny et al. (Proc. Combust. Inst. 2014, 35, 703) under predicted experimental laminar burning velocities significantly at all investigated conditions. Previous studies have shown that none of the mechanisms can accurately predict ignition delay time over a wide range of conditions with respect to pressure, temperature, diluent and dilution ratio. The evaluation of the mechanisms reveals that the understanding of nitromethane combustion is at the present time not sufficient to produce a widely applicable mechanism.
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| 14. |
- Brackmann, Christian, et al.
(författare)
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Structure of premixed ammonia plus air flames at atmospheric pressure: Laser diagnostics and kinetic modeling
- 2016
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Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180. ; 163, s. 370-381
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Tidskriftsartikel (refereegranskat)abstract
- The structure of premixed ammonia air flames, burning at atmospheric pressure under strain-stabilized conditions on a porous-plug burner, has been investigated using laser-diagnostic methods. Profiles of OH, NH, and NO were acquired by laser-induced fluorescence (LIF) and quantitative concentrations of OH and NO were retrieved using a concept for calibration versus absorption utilizing the LIF-signal itself, whereas NH concentrations were evaluated employing a saturated fluorescence signal. In addition, temperatures and relative oxygen concentrations were measured by rotational Coherent Anti-stokes Raman Spectroscopy (CARS). The new experimental data for flames with equivalence ratios of 0.9, 1.0, and 1.2 were used to validate and rank the performance of four contemporary detailed kinetic models. Simulations were carried out using experimental temperature profiles as well as by solving the energy equation. Two models of the same origin, developed by Mendiara and Glarborg (2009) and by Klippenstein et al. (2011), in most cases showed good agreement in terms of radical concentrations, however, the model of Mendiara and Glarborg had better prediction of temperatures and flame front positions. The model by Shmakov et al. (2010) had comparable performance concerning radical species, but significant discrepancies appeared in the prediction of flame front positions. The model of Duynslaegher et al. (2012), in addition to the flame front positions, deviated from experiments or other models in terms of NH and NO concentrations. A sensitivity analysis for the Mendiara-Glarborg mechanism indicated that remaining uncertainties of the rate constants implemented in the recent H/N/O models are difficult to scrutinize unambiguously due to experimental uncertainties. (C) 2015 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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| 15. |
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| 16. |
- Dellborg, Mikael, 1954, et al.
(författare)
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Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.
- 2019
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Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6845 .- 2055-6837. ; 5:4, s. 200-206
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Tidskriftsartikel (refereegranskat)abstract
- In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60mg b.i.d. initiated up to 2years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.Of the 21162 patients enrolled in PEGASUS-TIMI 54, 10779 patients were included in the primary analysis for this study, randomized to ticagrelor 60mg (n=5388) or matching placebo (n=5391). The cumulative proportions of patients with events at 36months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P=0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P=0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P<0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P=0.58).In PEGASUS-TIMI 54, treatment with ticagrelor 60mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60mg in this population.http://www.clinicaltrials.gov NCT01225562.
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| 17. |
- Dengler, Juergen, et al.
(författare)
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GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands
- 2018
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Ingår i: Phytocoenologia. - : Schweizerbart. - 0340-269X. ; 48:3, s. 331-347
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Tidskriftsartikel (refereegranskat)abstract
- GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
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| 18. |
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| 19. |
- Enquist, Henrik, et al.
(författare)
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FemtoMAX - An X-ray beamline for structural dynamics at the short-pulse facility of MAX IV
- 2018
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 25:2, s. 570-579
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Tidskriftsartikel (refereegranskat)abstract
- The FemtoMAX beamline facilitates studies of the structural dynamics of materials. Such studies are of fundamental importance for key scientific problems related to programming materials using light, enabling new storage media and new manufacturing techniques, obtaining sustainable energy by mimicking photosynthesis, and gleaning insights into chemical and biological functional dynamics. The FemtoMAX beamline utilizes the MAX IV linear accelerator as an electron source. The photon bursts have a pulse length of 100fs, which is on the timescale of molecular vibrations, and have wavelengths matching interatomic distances (Å). The uniqueness of the beamline has called for special beamline components. This paper presents the beamline design including ultrasensitive X-ray beam-position monitors based on thin Ce:YAG screens, efficient harmonic separators and novel timing tools.The FemtoMAX beamline facilitates studies of the structural dynamics of materials on the femtosecond timescale. The first commissioning results are presented.
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| 20. |
- Eslami, Mohammad H.
(författare)
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Knowledge integration with customers in collaborative product development project
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Driven by rapid technological developments, greater customer expectations, and increased product complexity,product development processes increasingly rely on the integration of dispersed specialist knowledge.Consequently, many industrial firms are changing the way they approach product development. Productdevelopment increasingly relies on knowledge integration across firm boundaries. Customers are one of the mostindispensable sources of knowledge, and their knowledge needs to be integrated during product development.However, little is known about the processes and mechanisms used to integrate customer knowledge in productdevelopment.Therefore, firms must devise processes and mechanisms that support knowledge integration withcustomers. This thesis aims to investigate knowledge integration with customers in collaborative productdevelopment.The work described in this thesis combines a case study with a survey approach. More specifically, five casestudies were conducted at three industrial manufacturing firms. Data were collected in 46 interviews, along withinformal discussions, workshops, and secondary material. The case studies revealed the role of knowledgeintegration, knowledge integration mechanisms, and the importance of contextual factors related to the customer’stechnical capability, and the locus of initiative for the product development project. A cross-sectional survey wasperformed in order to ascertain the role of knowledge integration and its effect on innovation performance and theeffect of firms and customers’ technical capability and locus of initiative on knowledge integration withcustomers. The survey study generated 216 responses from firms operating in the Swedish manufacturingindustry.This thesis consists of a compiled summary and five appended papers. The results in these provide the basis formodelling knowledge integration with customers. The findings confirm that integrating knowledge withcustomers in product development is associated with better innovation performance. Further, the results point tothe dynamic characteristics of knowledge integration in product development processes. More specifically, firmstend to apply different combinations of mechanisms in different phases, depending on the intended content of theknowledge contribution of the customer and the requirements of each phase in the development process. Inaddition, the degree of technical capability, internal integration capability, and locus of initiative are importantfactors influencing knowledge integration processes. This thesis sheds new light on collaborative productdevelopment with customers by demonstrating that knowledge, and particularly the integration of knowledgeacross firm boundaries, is a central property of product development. The study focuses on industrial andmanufacturing firms, complementing current perspectives on the role of customers in other sectors. In thisparticular sector, complexity and system-wide implications need to be resolved together with customers throughknowledge integration activities. An important implication of the thesis is that firms need to devise mechanismsfor knowledge integration with customers, and be prepared to redevise these as the firm progresses through theproduct development phases.
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| 21. |
- González-Bengtsson, Amanda, 1986-
(författare)
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ELOVL2 and PUFA biosynthesis : Impact on sex-specific processes in mammals
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Endogenously synthesized PUFAs (Polyunsaturated Fatty Acids) vary in production depending on medical conditions, gender, developmental phase, age, fertility status, pregnancy and lactation. PUFA biosynthesis is further regulated via amount of dietary intake as well as genetically. A key player in the PUFA biosynthesis enzyme machinery is the fatty acid elongase Elongation of very long-chain fatty acids 2 (ELOVL2) that is essential for the production of the omega-3 PUFA docosahexaenoic acid (DHA, 22:6 n-3) that has many beneficial health effects. In the omega-6 PUFA series, ELOVL2 produces docosapentaenoic acid (DPA n-6, 22:5 n-6). Specifically, ELOVL2 enables the elongation of PUFA with 22 carbons to generate precursors of 24 carbons for the generation of the previously mentioned end products as well as very long-chain (VLC) PUFA up to C34.This thesis elucidates that estrogen has the power to modulate ELOVL2 expression in breast cancer cells and that this probably is due to ligand dependent binding of the estrogen receptor alpha (ERα) to the Elovl2 enhancer. In addition, estrogen via ERα modulates hepatic levels of Elovl2 in mice in a gender specific manner. Ablation of Elovl2 leads to whole body deficiency of DHA. The thesis unravels that systemic DHA levels in neonatal mice is determined both by the ELOVL2 status of the mother and the offspring. Ablation of Elovl2 also leads to impaired spermatogenesis and infertility in male mice. However, heterozygous Elovl2-ablated mice, differ in fertility potency depending on strain. Here we show that this discrepancy is linked to an altered ratio between saturated and mono-unsaturated fatty acids and VLC-PUFA moieties of glucosylceramides in testis.
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| 22. |
- Hosseinnia, Ali, et al.
(författare)
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Pure rotational coherent anti-Stokes Raman spectroscopy of ethylene, experiments and modelling
- 2019
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Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier BV. - 0022-4073. ; 234, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- Rotational coherent anti-Stokes Raman spectroscopy (CARS) is an established diagnostic technique for temperature and concentration measurements in combustion-related experiments. CARS has mainly been applied on di- and tri-atomics with linear molecular symmetry, for which good agreement is achieved between experimental and theoretical spectra. Hydrocarbons have so far been less attractive for rotational CARS studies, partly because of their complex molecular symmetries making it challenging to obtain molecular parameters necessary for a successful modeling. Nevertheless, in this work we have studied the asymmetric top molecule ethylene (C2H4) using rotational CARS through experiments and theoretical modelling. Experimental spectra have been recorded at temperatures between 293 K and 804 K, and theoretical spectra have been calculated with a novel method for which the crucial temperature-dependent linewidth parameters were determined by comparison of experimental and theoretically calculated spectra. Line-mixing effects and temperature dependence of the isolated linewidths were studied using a semi-classical approach considering an exponential gap law and a scaling law. Subsequently, theoretically calculated spectra were used to evaluate the temperatures of the experimental spectra for validation of the method. The evaluated temperatures were in good agreement with thermocouple temperatures with differences up to ±7 K. Hence, this work not only investigates the potential of using rotational CARS on ethylene for diagnostic purposes, but also expands the applicability of the technique to a whole new class of molecules with asymmetric-top molecular symmetry.
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| 23. |
- Jordan, Stanley C, et al.
(författare)
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IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.
- 2017
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:5, s. 442-453
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function was performed, as were renal biopsies. Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound.RESULTS: Recipients in the U.S. study had a significantly longer cold ischemia time (the time elapsed between procurement of the organ and transplantation), a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study. A total of 38 serious adverse events occurred in 15 patients (5 events were adjudicated as being possibly related to IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total of 24 of 25 patients had perfusion of allografts after transplantation. Antibody-mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in the Swedish study) at 2 weeks to 5 months after transplantation; all these patients had a response to treatment. One graft loss, mediated by non-HLA IgM and IgA antibodies, occurred.CONCLUSIONS: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).
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| 24. |
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| 25. |
- Kozarcanin, Huda, et al.
(författare)
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The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation
- 2016
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 14:3, s. 531-545
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Tidskriftsartikel (refereegranskat)abstract
- The lectin pathway's MASP-1/2 activates coagulation factors but the trigger of the activation is unknown. MASP-1/2 activation was assessed by quantifying complexes between MASPs and antithrombin/C1-inhibitor. Activated platelets and fibrin were demonstrated to activate MASP-1 and MASP-2 both invitro and invivo. These findings may represent a crossroad between the complement and the coagulation systems. Summary Background The activated forms of the complement lectin pathway (LP) proteases MASP-1 and MASP-2 are able to cleave the coagulation factors prothrombin, fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor invitro. In vivo studies also show that MASP-1 is involved in thrombogenesis. Objectives To clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions. Methods Novel sandwich-ELISAs for detection of complexes between MASP-1 or MASP-2 and the serpins C1 inhibitor (C1-INH) or antithrombin (AT), were used to specifically detect and quantify the activated forms of MASP-1 and MASP-2. Results Activated platelets were shown by flow cytometry to bind Ficolin-1, -2 and -3 but not MBL, which was associated with activation of MASP-1 and MASP-2. We also demonstrated that fibrin and the plasmin-generated fibrin fragment DD in plasma, bind and activate MASP-1 and MASP-2. As demonstrated by the ELISA and SDS-PAGE/Western blotting, the fibrin-associated activation was reflected in a specific inactivation by AT during clotting without the assistance of heparin. In all other cases the MASPs were, as previously reported, inactivated by C1-INH. In systemic lupus erythematosus patients with thrombotic disease and in polytrauma patients, the levels of activated MASP-1 and MASP-2 in complex with both AT and C1-INH were associated with markers of thrombotic disease and contact/coagulation system activation. Conclusions MASP-1 and MASP-2 are activated during blood clotting. This activation is triggered by activated platelets and by the generation of fibrin during thrombotic reactions invitro and invivo, and may represent a novel activation/amplification mechanism in thromboinflammation.
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