| 1. |
- Assenhöj, Maria, et al.
(författare)
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Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles–an interdisciplinary approach
- 2021
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Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:8, s. 1035-1038
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Tidskriftsartikel (refereegranskat)abstract
- Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle–protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both ‘danger signals’, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations. © 2021 The Author(s).
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| 2. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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| 3. |
- Abelsson, Tobias, et al.
(författare)
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Evidence-based practice in primary healthcare from the managerial point of view - a national survey
- 2021
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The vast availability of and demand for evidence in modern primary healthcare force clinical decisions to be made based on condensed evidence in the form of policies and guidelines. Primary healthcare managers play a key role in implementing these governing documents. Thus, the aim of this article is to investigate the use and availability of evidence-based practice resources from the perspective of first-line primary healthcare managers. Methods The study is based on a national survey of primary healthcare managers, consisting of 186 respondents, recruited nationally from Sweden. The data was analysed using empirically constructed concepts and validated using factor analysis. A chi-square test was utilized to determine the statistical significance of comparisons. Associations between variables were calculated using Spearman's correlation coefficients. All tests were two-sided, and the significance level was set to 0.05. Results A majority (97 %) of managers stated that guidelines and policy documents impacted primary healthcare; 84 % of managers observed a direct effect on daily practices. Most of the managers (70 %) stated that some adaptation was needed when new evidence was introduced. The managers emphasized the importance of keeping themselves updated and open to new information about work routines (96 %). Conclusions The study illustrates a nearly unanimous response about the influence of clinical evidence on daily practice. The emphasis on the importance of all staff members keeping their professional knowledge up to date is viewed as a direct result of this effect on daily practice. An information-dense organization such as a primary healthcare organization would have much to gain from increased cooperation with regional information resources such as clinical libraries.
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| 4. |
- Andersson, Camilla, et al.
(författare)
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Achievements and experiences from science–policy interaction in the field of air pollution : Synthesising 20 years of research and outreach,thinking about future needs
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- For 20 years, the Swedish Environmental Protection Agency together with the MISTRA research foundation have funded five air pollution research programmes with focus on producing knowledge that supports policy and emission control in national and international arenas. The research has been multidisciplinary and has included research on emissions, atmospheric transport and transformation processes, human health effects, ecosystem effects, and emission control strategies. Research has also been conducted on the interaction between air pollution and climate change.Over these years, the link between the research programmes and the development of emission control strategies and policies in Sweden, the EU, and the UNECE Air Convention has been of high importance. This report presents how the research programmes have created societal benefits through support for the development of air pollution policies and emission control measures. The report also identifies future research needs to ensure continued progress towards even better air quality for future generations.
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| 5. |
- Ara, Kazi Zubaida Gulshan, et al.
(författare)
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Engineering CGTase to improve synthesis of alkyl glycosides
- 2021
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 31:5, s. 603-612
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Tidskriftsartikel (refereegranskat)abstract
- Alkyl glycoside surfactants with elongated carbohydrate chains are useful in different applications due to their improved biocompatibility. Cyclodextrin glucanotransferases can catalyse the elongation process through the coupling reaction. However, due to the presence of a hydrophobic tail, the interaction between an alkyl glycoside acceptor and the active site residues is weaker than the interaction with maltooligosaccharides at the corresponding site. Here we report the mutations of F197, G263 and E266 near the acceptor subsites in the CGTase CspCGT13 from Carboxydocella sp. The results showed that substitutions of both F197 and G263 were important for the binding of acceptor substrate dodecyl maltoside during coupling reaction. The double mutant F197Y/G263A showed enhanced coupling activity and displayed a 2-fold increase of the primary coupling product using γ-cyclodextrin as donor when compared to wildtype CspCGT13. Disproportionation activity was also reduced, which was also the case for another double mutant (F197Y/E266A) that however not showed the corresponding increase in coupling. A triple mutant F197Y/G263A/E266A maintained the increase in primary coupling product (1.8-fold increase) using dodecyl maltoside as acceptor, but disproportionation was approximately at the same level as in the double mutants. In addition, hydrolysis of starch was slightly increased by the F197Y and G263A substitutions, indicating that interactions at both positions influenced the selectivity between glycosyl and alkyl moieties.
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| 6. |
- Casillas Trujillo, Luis, et al.
(författare)
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Experimental and theoretical evidence of charge transfer in multi-component alloys : how chemical interactions reduce atomic size mismatch
- 2021
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Ingår i: Materials Chemistry Frontiers. - : Royal Society of Chemistry. - 2052-1537. ; 5:15, s. 5746-5759
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Tidskriftsartikel (refereegranskat)abstract
- Ab initio simulations of a multi-component alloy using density functional theory (DFT) were combined with experiments on thin films of the same material using X-ray photoelectron spectroscopy (XPS) to study the connection between the electronic and atomic structures of multi-component alloys. The DFT simulations were performed on an equimolar HfNbTiVZr multi-component alloy. Structure and charge transfer were evaluated using relaxed, non-relaxed, as well as elemental reference structures. The use of a fixed sphere size model allowed quantification of charge transfer, and separation into different contributions. The charge transfer was generally found to follow electronegativity trends and results in a reduced size mismatch between the elements, and thus causes a considerable reduction of the lattice distortions compared to a traditional assumption based on tabulated atomic radii. A calculation of the average deviation from the average radius (i.e. the so-called δ-parameter) based on the atomic Voronoi volumes gave a reduction of δ from ca. 6% (using the volumes in elemental reference phases) to ca. 2% (using the volumes in the relaxed multi-component alloy phase). The reliability of the theoretical results was confirmed by XPS measurements of a Hf22Nb19Ti18V19Zr21 thin film deposited by sputter deposition. The experimentally observed core level binding energy shifts (CLS), as well as peak broadening due to a range of chemical surroundings, for each element showed good agreement with the calculated DFT values. The single solid solution phase of the sample was confirmed by X-ray diffraction (XRD) and transmission electron microscopy (TEM) including energy dispersive spectroscopy (EDS) with nm-resolution. These observations show that the HfNbTiVZr solid solution phase is non-ideal, and that chemical bonding plays an important part in the structure formation, and presumably also in the properties. Our conclusions should be transferable to other multi-component alloy systems, as well as some other multi-component material systems, and open up interesting possibilities for the design of material properties via the electronic structure and controlled charge transfer between selected metallic elements in the materials.
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| 7. |
- Dahl, Maria, et al.
(författare)
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Bone marrow transplantation without myeloablative conditioning in a mouse model for Diamond-Blackfan anemia corrects the disease phenotype
- 2021
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Ingår i: Experimental Hematology. - : Elsevier BV. - 0301-472X. ; 99, s. 2-53
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Tidskriftsartikel (refereegranskat)abstract
- Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes coding for ribosomal proteins. Among these genes, the ribosomal protein S19 (RPS19) gene is the most frequently mutated. Previously, a mouse model deficient in RPS19 was developed by our laboratory, which recapitulates the hematopoietic disease phenotype by manifesting pathologic features and clinical symptoms of DBA. Characterization of this model revealed that chronic RPS19 deficiency leads to exhaustion of hematopoietic stem cells and subsequent bone marrow (BM) failure. In this study, we evaluated a nonmyeloablative conditioning protocol for BM transplants in RPS19-deficient mice by transplanting wild-type BM cells to RPS19-deficient recipients given no conditioning or sublethal doses of irradiation before transplant. We describe full correction of the hematopoietic phenotype in mice given sublethal doses of irradiation, as well as in animals completely devoid of any preceding irradiation. In comparison, wild-type animals receiving the same preconditioning regimen and number of transplanted cells exhibited significantly lower engraftment levels. Thus, robust engraftment and repopulation of transplanted cells can be achieved in reduced-intensity conditioned RPS19-deficient recipients. As gene therapy studies with autologous gene-corrected hematopoietic stem cells are emerging, we propose the results described here can guide determination of the level of conditioning for such a protocol in RPS19-deficient DBA. On the basis of our findings, a relatively mild conditioning strategy would plausibly be sufficient to achieve sufficient levels of engraftment and clinical success.
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| 8. |
- Dahl, Maria, et al.
(författare)
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Correction of pathology in mice displaying Gaucher disease type 1 by a clinically-applicable lentiviral vector
- 2021
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Ingår i: Molecular Therapy - Methods and Clinical Development. - : Elsevier BV. - 2329-0501. ; 20, s. 312-323
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluates a clinically applicable lentiviral vector for treatment of Gaucher disease type 1. Hematopoietic stem cells transduced with the vector and transplanted into a mouse model successfully halted or reversed pathology. These data were used as proof-of-concept for regulatory filing enabling the commencement of an international phase 1/2 clinical trial.
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| 9. |
- Desai, Pia, et al.
(författare)
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Recreational Runners With a History of Injury Are Twice as Likely to Sustain a Running-Related Injury as Runners With No History of Injury: A 1-Year Prospective Cohort Study
- 2021
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Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - 0190-6011. ; 51:3, s. 144-150
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Tidskriftsartikel (refereegranskat)abstract
- To investigate (1) the cumulative incidence proportion and the most common anatomical locations of running-related injuries in recreational runners, and (2) the associations between running-related injuries and previous injury, running experience, weekly running distance, age, gender and body mass index (BMI).A one-year prospective cohort study.224 recreational runners (average of 15km weekly running distance for the past 12 months) were included (89 women, 135 men). Pain information was reported weekly for one year and all running-related injuries with time-loss or requiring medical consultation were recorded. We accounted for censoring when calculating cumulative incidence proportion, and used crude Cox proportional hazards regression to evaluate if the variables of interest were associated with running-related injuries.The one-year cumulative incidence proportion of running-related injuries was 46% (95% CI: 38.4-54.1). The most common anatomical locations were the knee (20 of 75, 27%) and Achilles tendon/calf (19 of 75, 25%). Previous injury was associated with a higher injury rate (hazard ratio: 1.9, 95% CI: 1.2-3.2), while the other variables had no statistically significant association with injury.There were 75 running-related injuries during the one-year surveillance period for a cumulative incidence proportion of 46%. The most common injuries were to the knee and Achilles tendon/calf. Recreational runners with a previous injury were twice as likely to sustain a running-related injury than runners with no previous injury.
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| 10. |
- Grip, Lena, 1978-, et al.
(författare)
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Räddningsutbildades karriärval : En genus- och mångfaldsanalys av yrkesverksamhet bland alumner från SMO och RUB-utbildningar.
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sedan utbildningen Skydd mot olyckor, SMO startades 2003 har andelen examinerade kvinnor varit runt 16 procent. Det har funnits en förväntan att andelen kvinnorsom jobbar inom operativ räddningstjänst ska öka i takt med att antalet SMO-utbildade kvinnor ökar, men dessa förväntningar har inte infriats i den grad som motsetts. Det har rest frågor om varför det ser ut på detta sätt, och vad det är för faktorer som ligger till grund för kvinnornas karriärval. I föreliggande undersökning har vi närmat oss dessa frågor genom att undersöka karriärval bland hela gruppen examinerade från SMO under åren 2007-2016 i en enkätundersökning samt några kompletterande intervjuer. Detta ger en bred bild av olika karriärval och omfattar såväl dem som valt att aldrig söka sig till räddningstjänsten till dem som jobbat där en kortare tid och sedan sökt sig till annat arbete, samt dem som arbetat inom räddningstjänsten sedan sin utbildning, i en eller flera räddningstjänstorganisationer. I undersökningen ingår också de personer som examinerats från Påbyggnads-utbildning i räddningstjänst för brandingenjörer (RUB) under motsvarande år. Brandingenjörer inom kommunal räddningstjänst är en grupp som det i dagsläget finns ganska lite kunskap om, inte minst i fråga om jämställdhet och mångfald, och genom undersökningen ges ett bidrag till en inledande förståelse för denna grupps karriärval och syn på räddningstjänsten som arbetsplats.Rapporten bygger på ett utrednings- och forskningsuppdrag från MSB att ta fram en forskningsinriktad studie, som kan utgöra ett underlag för beslut om inriktning och handlingsplan för stöd till kommunal räddningstjänst i arbetet för ökad jämställdhet och mångfald.Studien landar i fyra förbättringsområden för räddningstjänsten som organisation, men där även MSB har en viktig roll att spela: Kompetensutvecklings- och karriärmöjligheter, Jämställdhet och mångfald, Organisation och ledning, samt Koppling mellan utbildning och arbete. Alla dessa fyra områden innehåller viktiga förklaringsfaktorer till varför såväl kvinnor som män väljer att inte jobba inom räddningstjänsten trots att de lagt kraft och energi i utbildning för ett arbete inom organisationen. Det är också viktiga områden att jobba vidare med för att fler inte ska välja att sluta.
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