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Sökning: WFRF:(Lindahl Katarina)

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1.
  • Björses, Katarina, et al. (författare)
  • In vitro and in vivo evaluation of chemically modified degradable starch microspheres for topical haemostasis
  • 2011
  • Ingår i: ACTA BIOMATERIALIA. - : Elsevier Science B.V. Amsterdam. - 1742-7061 .- 1878-7568. ; 7:6, s. 2558-2565
  • Tidskriftsartikel (refereegranskat)abstract
    • Degradable starch microspheres (DSMs) are starch chains cross-linked with epichlorhydrin, forming glycerol-ether links. DSMs have been used for many years for temporary vascular occlusion and drug delivery in treatment of malignancies. They are also approved and used for topical haemostasis by absorbing excess fluid from the blood and concentrating endogenous coagulation factors, thereby facilitating haemostasis. This mechanism of action is not sufficient for larger bleedings in current chemical formulations of DSMs, and modification of DSMs to trigger activation of platelets or coagulation would be required for use in such applications. Chemical modifications of DSMs with N-octenyl succinic anhydride, chloroacetic acid, acetic anhydride, diethylaminoethyl chloride and ellagic acid were performed and evaluated in vitro with thrombin generation and platelet adhesion tests, and in vivo using an experimental renal bleeding model in rat. DSMs modified to activate platelets in vitro were superior in haemostatic capacity in vivo. Further studies with non-toxic substances are warranted to confirm these results and develop the DSM as a more effective topical haemostatic agent.
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2.
  • Andersson, Kristofer, et al. (författare)
  • Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - A retrospective cohort study
  • 2017
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2). Dentinogenesis imperfecta (DGI) and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI. The clinical examination included radiographic evaluations. Teeth from 81 individuals were available for histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29% of the individuals (44/152) and through isolated histological findings in another 19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with a glycine substitution located C-terminal of p. Gly305 exhibited DGI in both dentitions while no individual (0/7) with a mutation N-terminal of this point exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2 mutation, 80% (8/10) of those with a glycine substitution located C terminal of p. Gly211 exhibited DGI in both dentitions while no individual (0/5) with a mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition. DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had missense mutations where glycine to serine was the most prevalent substitution (53%). Taurodontism occurred in 18% and retention of permanent second molars in 31% of the adolescents. Dental aberrations are strongly associated with qualitatively changed collagen I. The varying expressivity of DGI is related to the location of the collagen I mutation. Genotype information may be helpful in identifying individuals with OI who have an increased risk of dental aberrations.
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4.
  • Barbi, Florian, et al. (författare)
  • Fungal ecological strategies reflected in gene transcription - a case study of two litter decomposers
  • 2020
  • Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 22, s. 1089-1103
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbial communities interplay with their environment through their functional traits that can be a response or an effect on the environment. Here, we explore how a functional trait-the decomposition of organic matter, can be addressed based on genetic markers and how the expression of these markers reflect ecological strategies of two fungal litter decomposer Gymnopus androsaceus and Chalara longipes. We sequenced the genomes of these two fungi, as well as their transcriptomes at different steps of Pinus sylvestris needles decomposition in microcosms. Our results highlighted that if the gene content of the two species could indicate similar potential decomposition abilities, the expression levels of specific gene families belonging to the glycoside hydrolase category reflected contrasting ecological strategies. Actually, C. longipes, the weaker decomposer in this experiment, turned out to have a high content of genes involved in cell wall polysaccharides decomposition but low expression levels, reflecting a versatile ecology compare to the more competitive G. androsaceus with high expression levels of keystone functional genes. Thus, we established that sequential expression of genes coding for different components of the decomposer machinery indicated adaptation to chemical changes in the substrate as decomposition progressed.
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5.
  • Barreto Henriksson, Helena, et al. (författare)
  • Identification of Cell Proliferation Zones, Progenitor Cells and a Potential Stem Cell Niche in the Intervertebral Disc Region: A Study in Four Species.
  • 2009
  • Ingår i: SPINE. - 0362-2436. ; 34:21, s. 2278-2287
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY DESIGN.: Descriptive experimental study in 4 different mammals. OBJECTIVE.: To investigate cell proliferation/regeneration and localize stem cells/progenitor cells within the intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA.: Disc degeneration (DD) is believed to play a major role in patients with chronic lumbar pain. Lately, biologic treatment options for DD have gained increasing interest. Normal regeneration processes within the IVD and have previously been sparsely described and therefore it is of great interest to increase the knowledge about these processes. METHODS.: Detection of cell proliferations zones and label-retaining cells were done by in vivo 5-bromo-2-deoxyuridine (BrdU) labeling in 18 rabbits, killed after 4, 6, 10, 14, 28, or 56 days. Results were visualized with immunohistochemistry and fluorescence/confocal microscopy. Localization of progenitor cell were further investigated by immunohistochemistry using antibodies towards Notch1, Delta4, Jagged1, C-KIT, KI67, and Stro-1 in normal IVD from rabbits (n = 3), rats (n = 2), minipigs (n = 2), and in human degenerated IVD (n = 4). Further, flowcytometry analysis using progenitor markers were performed on additional human IVD cells (n = 3). RESULTS.: BrdU positive cells were found in comparable numbers at early and late time points in most regions of the anulus fibrosus (AF) and nucleus pulposus demonstrating slow ongoing cell proliferation. In the AF border to ligament zone (AFo) and the perichondriumregion (P) a stem cell niche-like pattern was determined (a high number of BrdU positive cells at early time points vs. only a few label retaining cells at later time points). In normal and DD tissue from the 4 investigated species progenitor cell markers were detected. CONCLUSION.: The IVD is a tissue with ongoing slow cell proliferation both in the AF and the nucleus pulposus. The stem cell niche pattern detected in AFo and P can be suggested to play a role for IVD morphology and function. These findings may be of importance for the development of biologic treatment strategies. PMID: 19755937 [PubMed - as supplied by publisher]
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7.
  • Bigdeli, Narmin, 1974, et al. (författare)
  • Adaptation of human embryonic stem cells to feeder-free and matrix-free culture conditions directly on plastic surfaces.
  • 2008
  • Ingår i: Journal of biotechnology. - : Elsevier BV. - 0168-1656. ; 133:1, s. 146-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have shown that cultivation of undifferentiated human embryonic stem (hES) cells requires human fibroblasts (hF) or mouse embryonic fibroblast (mEF) feeders or a coating matrix such as laminin, fibronectin or Matrigeltrade mark in combination with mEF or hF conditioned medium. We here demonstrate a successful feeder-free and matrix-free culture system in which undifferentiated hES cells can be cultured directly on plastic surfaces without any supportive coating, in a hF conditioned medium. The hES cells cultured directly on plastic surfaces grow as colonies with morphology very similar to cells cultured on Matrigel(TM). Two hES cell lines SA167 and AS034.1 were adapted to matrix-free growth (MFG) and have so far been cultured up to 43 passages and cryopreserved successfully. The lines maintained a normal karyotype and expressed the expected marker profile of undifferentiated hES cells for Oct-4, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81 and SSEA-1. The hES cells formed teratomas in SCID mice and differentiated in vitro into derivates of all three germ layers. Thus, the MFG-adapted hES cells appear to retain pluripotency and to remain undifferentiated. The present culture system has a clear potential to be scaleable up to a manufacturing level and become the preferred culture system for various applications such as cell therapy and toxicity testing.
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8.
  • Boberg, Johanna, et al. (författare)
  • Decomposing capacity of fungi commonly detected in Pinus sylvestris needle litter
  • 2011
  • Ingår i: Fungal Ecology. - : Elsevier BV. - 1754-5048 .- 1878-0083. ; 4, s. 110-114
  • Tidskriftsartikel (refereegranskat)abstract
    • A major part of the fungal community in coniferous litter consists of fungi whose taxonomic position and ecology are unknown. Here, nine isolates from within commonly occurring phylogenetic groups were tested for their ability to decompose Pinus sylvestris needles. In a 1-yr long incubation study, needle mass loss as well as changes in cellulose and lignin content were determined and compared to those caused by two litter basidiomycetes (Marasmius androsaceus and Mycena epipterygia) with recognized ability to decompose needles. A basidiomycetous Clavulina/Sistotrema strain appeared to be cellulolytic but not ligninolytic. Chalara longipes and three other strains within Helotiales also decomposed cellulose but not lignin, whereas Mollisia cinerea (also Helotiales) and two Dothideomycetes - Sydowia polyspora and a Mytilinidion sp., seemed unable to cause significant mass loss of cellulose. Lophodermium pinastri (Rhytismatales) readily decomposed cellulose, and also caused considerable loss of lignin. (C) 2010 Elsevier Ltd and The British Mycological Society. All rights reserved.
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10.
  • Castaño Soler, Carles, et al. (författare)
  • Optimized metabarcoding with Pacific biosciences enables semi-quantitative analysis of fungal communities
  • 2020
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 228, s. 1149-1158
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have questioned the use of high-throughput sequencing of the nuclear ribosomal internal transcribed spacer (ITS) region to derive a semi-quantitative representation of fungal community composition. However, comprehensive studies that quantify biases occurring during PCR and sequencing of ITS amplicons are still lacking. We used artificially assembled communities consisting of 10 ITS-like fragments of varying lengths and guanine-cytosine (GC) contents to evaluate and quantify biases during PCR and sequencing with Illumina MiSeq, PacBio RS II and PacBio Sequel I technologies. Fragment length variation was the main source of bias in observed community composition relative to the template, with longer fragments generally being under-represented for all sequencing platforms. This bias was three times higher for Illumina MiSeq than for PacBio RS II and Sequel I. All 10 fragments in the artificial community were recovered when sequenced with PacBio technologies, whereas the three longest fragments (> 447 bases) were lost when sequenced with Illumina MiSeq. Fragment length bias also increased linearly with increasing number of PCR cycles but could be mitigated by optimization of the PCR setup. No significant biases related to GC content were observed. Despite lower sequencing output, PacBio sequencing was better able to reflect the community composition of the template than Illumina MiSeq sequencing.
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11.
  • Chaireti, Roza, et al. (författare)
  • Inflammatory and endothelial markers during the menstrual cycle
  • 2016
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : TAYLOR & FRANCIS LTD. - 0036-5513 .- 1502-7686. ; 76:3, s. 190-194
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The menstrual cycle exhibits a pattern of repeated inflammatory activity. The present study aims to evaluate inflammatory and endothelial markers during the two phases of a menstrual cycle. Methods The study cohort consisted of 102 women with regular menstrual cycles. Inflammatory and endothelial markers (interleukin-6 [IL-6], pentraxin-3 [PTX-3], hs-C reactive protein [hs-CRP], sE-selectin, sP-selectin, intracellular and vascular cell adhesion molecules [ICAM-1 and VCAM-1] and cathepsins L, B and S) were measured during the early follicular and the late luteal phase of a normal menstrual cycle. Results Pentraxin-3 (PTX-3) and hs-CRP were significantly higher during the follicular phase compared to the luteal phase (p < 0.001 respectively p = 0.025). The other inflammatory and endothelial markers, with the exception of cathepsin B, were higher, albeit not significantly, during the follicular phase. Conclusions Inflammatory activity, expressed mainly by members of the pentraxin family, is higher during the early follicular compared to the luteal phase. This could be associated to menstruation but the exact mechanisms behind this pattern are unclear and might involve the ovarian hormones or an effect on hepatocytes.
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12.
  • Clemmensen, Karina, et al. (författare)
  • Sample preparation for fungal community analysis by high-throughput sequencing of barcode amplicons
  • 2023
  • Ingår i: Microbial Environmental Genomics (MEG) ; second edition. - New York, NY : Springer US. - 9781071628706 ; :2605, s. 37-64
  • Bokkapitel (refereegranskat)abstract
    • Fungal species participate in vast numbers of processes in the landscape around us. However, their cryptic mycelial growth, inside various substrates and in highly diverse species assemblages, has been a major obstacle to thorough analysis of fungal communities, hampering exhaustive description of the fungal kingdom. Technological developments allowing rapid, high-throughput sequencing of mixed communities from many samples at once are currently having a tremendous impact in fungal community ecology. Universal DNA extraction followed by amplification and sequencing of fungal species-level barcodes such as the nuclear internal transcribed spacer (ITS) region now enables identification and relative quantification of fungal community members across well-replicated experimental settings. Here, we present the sample preparation procedure presently used in our laboratory for fungal community analysis by high-throughput sequencing of amplified ITS2 markers. We focus on the procedure optimized for studies of total fungal communities in humus-rich soils, wood, and litter. However, this procedure can be applied to other sample types and markers. We focus on the laboratory-based part of sample preparation, i.e., the procedure from the point where samples enter the laboratory until amplicons are submitted for sequencing. Our procedure comprises four main parts: (1) universal DNA extraction, (2) optimization of PCR conditions, (3) production of tagged ITS amplicons, and (4) preparation of the multiplexed amplicon pool to be sequenced. The presented procedure is independent of the specific highthroughput sequencing technology used, which makes it highly versatile.
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13.
  • Engelbrecht Clemmensen, Karina, et al. (författare)
  • Sample Preparation for Fungal Community Analysis by High-Throughput Sequencing of Barcode Amplicons
  • 2016
  • Ingår i: Microbial Environmental Genomics. - New York, NY : Springer New York. - 9781493933679 ; 1399, s. 61-88
  • Bokkapitel (refereegranskat)abstract
    • Fungal species participate in vast numbers of processes in the landscape around us. However, their often cryptic growth, inside various substrates and in highly diverse species assemblages, has been a major obstacle to thorough analysis of fungal communities, hampering exhaustive description of the fungal kingdom. Recent technological developments allowing rapid, high-throughput sequencing of mixed communities from many samples at once are currently having a tremendous impact in fungal community ecology. Universal DNA extraction followed by amplification and sequencing of fungal species-level barcodes such as the nuclear internal transcribed spacer (ITS) region now enable identification and relative quantification of fungal community members across well-replicated experimental settings.Here, we present the sample preparation procedure presently used in our laboratory for fungal community analysis by high-throughput sequencing of amplified ITS2 markers. We focus on the procedure optimized for studies of total fungal communities in humus-rich soils, wood, and litter. However, this procedure can be applied to other sample types and markers. We focus on the laboratory-based part of sample preparation, that is, the procedure from the point where samples enter the laboratory until amplicons are submitted for sequencing. Our procedure comprises four main parts: (1) universal DNA extraction, (2) optimization of PCR conditions, (3) production of tagged ITS amplicons, and (4) preparation of the multiplexed amplicon mix to be sequenced. The presented procedure is independent of the specific high-throughput sequencing technology used, which makes it highly versatile.
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14.
  • Fahlgren, Anna, 1972-, et al. (författare)
  • Design and Outcome of a CDIO Syllabus Survey for a Biomedicine Program
  • 2019
  • Ingår i: The 15th International CDIO Conference: Proceedings – Full Papers. - Aarhus : Aarhus University. - 9788775074594 ; , s. 191-200
  • Konferensbidrag (refereegranskat)abstract
    • The CDIO Syllabus survey has successfully been applied to the Bachelor’s and Master’s programs in Experimental and Medical Biosciences, within the Faculty of Medicine and Health Sciences at Linköping University, Sweden. The programs are and have been, subject to considerable redesign with strong influence from the CDIO framework. One of the main drivers for the redesign is a shift concerning the main job market after graduation, from an academic career to industry and healthcare. One of the steps in the development process has been to carry out a Syllabus survey based on an adapted version of the CDIO Syllabus. The survey was sent out to students and to various categories of professionals, and in total 87 responses were received. The adapted version of the Syllabus and the design, execution, and outcome of the survey is presented.
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15.
  • Gummesson, Christina, et al. (författare)
  • Entrustable professional activities (EPAs) for undergraduate medical education : development and exploration of social validity
  • 2023
  • Ingår i: BMC Medical Education. - : BioMed Central (BMC). - 1472-6920. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders.Aim: The aim of our work was to define Core EPAs for undergraduate medical education and further explore the social validity of the constructs.Method and material: In a nationwide collaboration, EPAs were developed using a modified Delphi procedure and validated according to EQual by a group consisting of teachers nominated from each of the seven Swedish medical schools, two student representatives, and an educational developer (n = 16). In the next step, social validity was explored in a nationwide survey. The survey introduced the suggested EPAs. For each EPA, the importance of the EPA was rated, as was the rater’s perception of the present graduates’ required level of supervision when performing the activity. Free-text comments were also included and analyzed.Results: Ten Core EPAs were defined and validated. The validation scores for EQual ranged from 4.1 to 4.9. The nationwide survey had 473 responders. All activities were rated as “important” by most responders, ranging from 54 to 96%. When asked how independent current graduates were in performing the ten activities, 6 to 35% reported “independent”. The three themes of the free text comments were: ‘relevant target areas and content’; ‘definition of the activities’; and ‘clinical practice and learning’.Conclusion: Ten Core EPAs were defined and assessed as relevant for Swedish undergraduate medical education. There was a consistent gap between the perceived importance and the certainty that the students could perform these professional activities independently at the time of graduation. These results indicate that the ten EPAs may have a role in undergraduate education by creating clarity for all stakeholders.
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16.
  • Heins, Nico, et al. (författare)
  • Clonal derivation and characterization of human embryonic stem cell lines.
  • 2006
  • Ingår i: Journal of biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 122:4, s. 511-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Human embryonic stem cells (hESC) are isolated as clusters of cells from the inner cell mass of blastocysts and thus should formally be considered as heterogeneous cell populations. Homogenous hESC cultures can be obtained through subcloning. Here, we report the clonal derivation and characterization of two new hESC lines from the parental cell line SA002 and the previously clonally derived cell line AS034.1, respectively. The hESC line SA002 was recently reported to have an abnormal karyotype (trisomy 13), but within this population of cells we observed rare individual cells with an apparent normal karyotype. At a cloning efficiency of 5%, we established 33 subclones from SA002, out of which one had a diploid karyotype and this subline was designated SA002.5. From AS034.1 we established one reclone designated AS034.1.1 at a cloning efficiency of 0.1%. These two novel sublines express cell surface markers indicative of undifferentiated hESC (SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81), Oct-4, alkaline phosphatase, and they display high telomerase activity. In addition, the cells are pluripotent and form derivatives of all three embryonic germ layers in vitro as well as in vivo. These results, together with the clonal character of SA002.5 and AS034.1.1 make these homogenous cell populations very useful for hESC based applications in drug development and toxicity testing. In addition, the combination of the parental trisomic hESC line SA002 and the diploid subclone SA002.5 provides a unique experimental system to study the molecular mechanisms underlying the pathologies associated with trisomy 13.
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18.
  • Karlsson, Camilla, 1977, et al. (författare)
  • Human embryonic stem cell-derived mesenchymal progenitors-Potential in regenerative medicine.
  • 2009
  • Ingår i: Stem cell research. - : Elsevier BV. - 1876-7753 .- 1873-5061. ; 3:1, s. 39-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Tissue engineering and cell therapy require large-scale production of homogeneous populations of lineage-restricted progenitor cells that easily can be induced to differentiate into a specific tissue. We have developed straightforward protocols for the establishment of human embryonic stem (hES) cell-derived mesenchymal progenitor (hES-MP) cell lines. The reproducibility was proven by derivation of multiple hES-MP cell lines from 10 different hES cell lines. To illustrate clinical applicability, a xeno-free hES-MP cell line was also derived. None of the markers characteristic for undifferentiated hES cells were detected in the hES-MP cells. Instead, these cells were highly similar to mesenchymal stem cells with regard to morphology and expression of markers. The safety of hES-MP cells following transplantation was studied in severely combined immunodeficient (SCID) mice. The implanted hES-MP cells gave rise to homogeneous, well-differentiated tissues exclusively of mesenchymal origin and no teratoma formation was observed. These cells further have the potential to differentiate toward the osteogenic, adipogenic, and chondrogenic lineages in vitro. The possibility of easily and reproducibly generating highly expandable hES-MP cell lines from well-characterized hES cell lines with differentiation potential into several mesodermal tissues entails an enormous potential for the field of regenerative medicine.
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19.
  • Karlstads moské : Förhandlingar om islam i Värmland
  • 2018
  • Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
    • Antologin Karlstads moské är den första sammanhängandestudien som belyser muslimer och islam i Värmland.Antologin utgörs av ett studentbaserat forskningsprojektsom ägde rum hösten 2017.
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20.
  • Lindahl, Johan, 1984, et al. (författare)
  • Economic analysis of the early market of centralized photovoltaic parks in Sweden
  • 2022
  • Ingår i: Renewable Energy. - : Elsevier BV. - 0960-1481 .- 1879-0682. ; 185, s. 1192-1208
  • Tidskriftsartikel (refereegranskat)abstract
    • Sweden is one of the countries that experience growing installation volumes of Solar photovoltaic. Traditionally, in Sweden, most of the solar photovoltaic investments and policy incentives have focused on distributed photovoltaic systems. Yet, despite limited policy incentives and pessimistic forecasts, an increasing number of centralized photovoltaic parks have been commissioned and plans for substantial new capacities are communicated. Hence, the current paper investigates why. Detailed information about the underlying costs of six PV parks commissioned in2019 and 2020 in Sweden were obtained by in-depth interviews with stakeholders and were analysed through levelized cost of electricity calculations. We conclude that the unsubsidised levelized cost of electricity ranged from 27.37 to 49.39 €/MWh, with an average of 40.79 €/MWh. This is lower than what are assessed for photovoltaic parks in some recent Swedish electricity system scenario studies. The main reason for the discrepancy is identified to be the assumed interest rates in the system scenario studies and the actual cost of capital experienced in the market. Comparing the levelized cost of electricity values with the market value of solar photovoltaic electricity on the spot market show that four of the six studied parks would be profitable under a merchant business model with the last years spot prices. If the downward price trend continues, Sweden may face an unexpected expansion of photovoltaic parks.
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21.
  • Lindahl, Katarina, et al. (författare)
  • Allele dependent silencing of COL1A2 using small interfering RNAs
  • 2008
  • Ingår i: International Journal of Medical Sciences. - 1449-1907. ; 5:6, s. 361-365
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteogenesis imperfecta (OI) is generally caused by a dominant mutation in Collagen I, encoded by the genes COL1A1 and COL1A2. To date there is no satisfactory therapy for OI, but inactivation of the mutant allele through small interfering RNAs (siRNA) is a promising approach, as siRNAs targeting each allele of a polymorphism could be used for allele-specific silencing irrespective of the location of the actual mutations. In this study we examined the allele dependent effects of several tiled siRNAs targeting a region surrounding an exonic COL1A2 T/C polymorphism (rs1800222) in heterozygous primary human bone cells. Relative abundances of COL1A2 alleles were determined by cDNA sequencing and overall COL1A2 abundance was analyzed by quantitative PCR. One of the siRNAs decreased overall COL1A2 abundance by 71% of which 75% was due to silencing of the targeted T-allele. In conclusion, allele-preferential silencing of Collagen type I genes may be a future therapeutic approach for OI.
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22.
  • Lindahl, Katarina, et al. (författare)
  • Allele Dependent Silencing of Collagen Type I Using Small Interfering RNAs Targeting 3'UTR Indels : a Novel Therapeutic Approach in Osteogenesis Imperfecta
  • 2013
  • Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 10:10, s. 1333-1343
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteogenesis imperfecta, also known as "brittle bone disease", is a heterogeneous disorder of connective tissue generally caused by dominant mutations in the genes COL1A1 and COL1A2, encoding the α1 and α2 chains of type I (pro)collagen. Symptomatic patients are usually prescribed bisphosphonates, but this treatment is neither curative nor sufficient. A promising field is gene silencing through RNA interference. In this study small interfering RNAs (siRNAs) were designed to target each allele of 3'UTR insertion/deletion polymorphisms (indels) in COL1A1 (rs3840870) and COL1A2 (rs3917). For both indels, the frequency of heterozygous individuals was determined to be approximately 50% in Swedish cohorts of healthy controls as well as in patients with osteogenesis imperfecta. Cultures of primary human bone derived cells were transfected with siRNAs through magnet-assisted transfection. cDNA from transfected cells was sequenced in order to measure targeted allele/non-targeted allele ratios and the overall degree of silencing was assessed by quantitative PCR. Successful allele dependent silencing was observed, with promising results for siRNAs complementary to both the insertion and non-insertion harboring alleles. In COL1A1 cDNA the indel allele ratios were shifted from 1 to 0.09 and 0.19 for the insertion and non-insertion allele respectively while the equivalent resulting ratios for COL1A2 were 0.05 and 0.01. Reductions in mRNA abundance were also demonstrated; in cells treated with siRNAs targeting the COL1A1 alleles the average COL1A1 mRNA levels were reduced 65% and 78% compared to negative control levels and in cells treated with COL1A2 siRNAs the average COL1A2 mRNA levels were decreased 26% and 49% of those observed in the corresponding negative controls. In conclusion, allele dependent silencing of collagen type I utilizing 3'UTR indels common in the general population constitutes a promising mutation independent therapeutic approach for osteogenesis imperfecta.
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23.
  • Lindahl, Katarina, et al. (författare)
  • COL1 C-Propeptide Cleavage Site Mutations Cause High Bone Mass Osteogenesis Imperfecta
  • 2011
  • Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 32:6, s. 598-609
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteogenesis imperfecta (OI) is most often caused by mutations in the type I procollagen genes (COL1A1/COL1A2). We identified two children with substitutions in the type I procollagen C-propeptide cleavage site, which disrupt a unique processing step in collagen maturation and define a novel phenotype within OI. The patients have mild OI caused by mutations in COL1A1 (Patient 1: p.Asp1219Asn) or COL1A2 (Patient 2: p.Ala1119Thr), respectively. Patient 1 L1-L4 DXA Z-score was +3.9 and pQCT vBMD was +3.1; Patient 2 had L1-L4 DXA Z-score of 0.0 and pQCT vBMD of -1.8. Patient BMD contrasts with radiographic osteopenia and histomorphometry without osteosclerosis. Mutant procollagen processing is impaired in pericellular and in vitro assays. Patient dermal collagen fibrils have irregular borders. Incorporation of pC-collagen into matrix leads to increased bone mineralization. FTIR imaging confirms elevated mineral/matrix ratios in both patients, along with increased collagen maturation in trabecular bone, compared to normal or OI controls. Bone mineralization density distribution revealed a marked shift toward increased mineralization density for both patients. Patient 1 has areas of higher and lower bone mineralization than controls; Patient 2's bone matrix has a mineral content exceeding even classical OI bone. These patients define a new phenotype of high BMD OI and demonstrate that procollagen C-propeptide cleavage is crucial to normal bone mineralization.
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24.
  • Lindahl, Katarina, Fil. lic. i ämnesdidaktik (författare)
  • Collaborative writing in group work
  • 2021
  • Ingår i: Designing Courses with Digital Technologies. - New York : Routledge. - 9780367700003 - 9781003144175 ; , s. 52-56
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • This chapter focuses on how shared documents are used for practical and collaborative writing assignments such as giving peer feedback in a course on English teaching for upper secondary school teacher students. The students use shared documents for their group work during seminars, and the discussions when working collaboratively contribute to students’ positive experiences of the course. In addition, the course is taught in a way in which students become learning resources for each other, and in turn, they develop both their teaching skills as well as their own language proficiency. The students learn how to give formative feedback, they improve their own writing and they learn how to use digital tools in language teaching.
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25.
  • Lindahl, Katarina, 1987 (författare)
  • Connecting Teacher Education to Research and Practice
  • 2023
  • Ingår i: ISSOTL 2023, Amsterdam, Nederländerna.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Teacher education, like many other professional education programmes, exists in a field of tension between theory and practice. Students often express that they struggle to see the relevance of the research they study in teacher education courses in relation to the classroom practice they encounter in the schools. In addition, studies show that professional teachers in secondary school have difficulties connecting research with teaching and view research as irrelevant to their profession (Angerwall m.fl., 2020; Marsden & Kasprowicz, 2017; Medgyes, 2017; Sato & Loewen, 2018; Säljö & Söderling, 2006; Åman & Kroksmark, 2018). Teacher professionalism consists of both scientific knowledge and a pedagogical professionalism, and teacher educators need to train teacher students in both the academic and scientific fields while also developing their professional judgement. Within teacher education, we need to find a way to relate to the everyday life of professional teachers and their tacit knowledge while at the same time linking to relevant and current research in the various subject areas that are part of a teacher education. Dodillet et al. (2019) divide teacher professionalism into two categories: science-based and pedagogical professionalism. Science-based professionalism aims to develop theories that can be used as "recipes" for effective practice, while pedagogical professionalism focuses more on students' education, maturity, independence, and autonomy. Teacher education must contribute to developing both aspects of teacher professionalism and consider both the educational and professional context. How do we base education at all levels on a scientific basis while considering the practical experience of working teachers? In this presentation, a possible solution of how the task of teaching for the future profession while at the same time giving students the academic and scientific knowledge they need as academics is discussed.
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26.
  • Lindahl, Katarina, et al. (författare)
  • Decreased fracture rate, pharmacogenetics and BMD response in 79 Swedish children with osteogenesis imperfecta types I, III and IV treated with Pamidronate
  • 2016
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 87, s. 11-18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Osteogenesis imperfecta (OI) is an inherited heterogeneous bone fragility disorder, usually caused by collagen I mutations. It is well established that bisphosphonate treatment increases lumbar spine (LS) bone mineral density (BMD), as well as improves vertebral geometry in severe 01; however, fracture reduction has been difficult to prove, pharmacogenetic studies are scarce, and it is not known at which age, or severity of disease, treatment should be initiated.Materials and methods: COL1A1 and COL1A2 were analyzed in 79 children with OI (type I n = 33, type III n = 25 and type IV n = 21) treated with Pamidronate. Data on LS BMD, height, and radiologically confirmed non vertebral and vertebral fractures were collected prior to, and at several time points during treatment.Results: An increase in LS BMD Z-score was observed for all types of OI, and a negative correlation to A LS BMD was observed for both age and LS BMD Z-score at treatment initiation. Supine height Z-scores were not affected by Pamidronate treatment, The fracture rate was reduced for all OI types at all time points during treatment (overall p < 0.0003, < 0.0001 and 0.0003 for all 01 types 1, III and IV respectively). The reduced fracture rate was maintained for types I and IV, while an additional decrease was observed over time for type III. The fracture rate was reduced also in individuals with continued low BMD after >4 yrs Pamidronate. Twice as many boys as girls with 01 type I were treated with Pamidronate, and the fracture rate the year prior treatment was 2.2 times higher for boys (p = 0.0236). Greater Delta LS BMD, but smaller Delta fracture numbers were observed on Pamidronate for helical glycine mutations in COL1A1 vs. COL1A2. Vertebral compression fractures did not progress in any individual during treatment; however, they did not improve in 9%, and these individuals were all >11 years of age at treatment initiation. (p < 0.0001).Conclusion: Pamidronate treatment in children with all types of 01 increased LS BMD, decreased fracture rate, and improved vertebral compression fractures. Fracture reduction was prompt and maintained during treatment, irrespective of age at treatment initiation and collagen I mutation type.
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27.
  • Lindahl, Katarina (författare)
  • Engelskdidaktik i ett omvänt klassrum
  • 2018. - 1
  • Ingår i: Digitalisering av högre utbildning. - Lund : Studentlitteratur AB. - 9789144119724 ; , s. 163-167
  • Bokkapitel (populärvet., debatt m.m.)
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28.
  • Lindahl, Katarina, et al. (författare)
  • Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta
  • 2015
  • Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23:8, s. 1042-1050
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on 4100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the alpha 1-and alpha 2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the alpha 1-chain were associated with blue sclera (P = 0.0110). Comparing glycine with serine substitutions, alpha 1-alterations were associated with more severe phenotype (P = 0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P < 0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in > 95% of an entire OI population.
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29.
  • Lindahl, Katarina, et al. (författare)
  • Genotype-phenotype correlations and pharmacogenetic studies in 140 Swedish families with osteogenesis imperfecta
  • 2012
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 50, s. S109-S109
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: Osteogenesis imperfecta (OI) is a rare heterogeneous disease of connective tissue leading to varying degrees of bone fragility. The worst form (type II) is peri-natally lethal whereas the mildest form (type I) is compatible with a normal life span. Over 1000 mutations causing OI have been described in the genes encoding collagen type I. As COL1A1 and COL1A2 are large genes, there are still many codon positions where no mutations have been reported and only a fraction of theoretically possible glycine substitutions have been described. In this study the spectrum of mutations causing OI in Sweden will be investigated and genotype–phenotype correlations as well as pharmacogenetics will be studied. Method: All patients with OI cared for at the Uppsala Osteoporosis Unit (Uppsala University Hospital) or Astrid Lindgren's Paediatric Hospital (Karolinska Institutet, Stockholm) were offered to enter the study. Patients from 140 unrelated families with OI accepted participation; 77 type I, 34 type IV, 20 type III, 5 without previous diagnosis and 4 with unclear OI type. Extensive clinical data is currently being collected on enrolled patients. Exons and flanking intron sequences of COL1A1 and COL1A2 are being sequenced in these families. Results: So far 133/140 families have been completely analyzed and in 27 no mutation was found. A total of 120 mutations have been detected, of which 104 are of a typical OI-type. In COL1A1 73 mutations were found and in COL1A2 31 mutations were noted. In 7 families 2 mutations were present, but only one of these was a typical OI-causing mutation. To date 16 amino acid changing mutations that were not of a typical OI-causing type have been noted and the majority of these have an unclear significance. Calculations of delta BMD Z-score response to bisphosphonate treatment did not show a difference in treatment response between groups with different types of OI or between patients with OI type I due to a qualitative vs. a quantitative collagen type I defect. Conclusion: The spectrum of mutations causing OI described in this Swedish cohort is of the expected type, with the exception of the amino acid changing mutations. It is notable that in seven families two separate mutations were identified. Calculations do not support a mutation dependent response to bisphosphonate treatment.
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30.
  • Lindahl, Katarina, et al. (författare)
  • Genotype-Phenotype Correlations, Response to Bisphosphonate Treatment and Pharmaco-genetics in 150 Swedish Families with Osteogenesis Imperfecta (Type I, IV and III)
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Osteogenesis imperfecta (OI) is a rare heterogeneous disorder leading to bone fragility, spanning from mild to lethal in severity. Over 1500 mutations have been described in collagen type I, encoded by COL1A1 and COL1A2. Bisphosphonate treatment is standard of care and published studies clearly show beneficial effects on Bone Mineral Density (BMD) and vertebral geometry. However, information on BMD increase in relation to age and BMD at onset is limited and there are few studies on influence of mutation type on treatment response. In this study Swedish patients with OI types I, IV and III were investigated with respect to genotype-phenotype correlations, BMD response on bisphosphonate treatment, and pharmaco-genetics.Materials and Methods: 150 families (202 individuals) with OI participated: 137 type I, 40 type IV and 25 type III. Data on phenotype and bisphosphonate treatment were collected and sequencing of COL1A1 and COL1A2 performed.Results: In 119 families a mutation was detected; in COL1A1 52 quantitative and 35 qualitative mutations were found and in COL1A2 32 qualitative mutations were found. Several unrelated individuals were found to harbor mutations with the same positions and substitutions and only 15 qualitative mutations were novel, supporting the idea of mutational hotspots. Genotype-phenotype analysis confirmed that mutations situated in the a1-chain are associated with a more severe phenotype, blue sclerae are strongly associated with COL1A1 null alleles, qualitative mutations are associated with DI, and for qualitative mutations position relative to N- and C-terminal is correlated to phenotype. A few novel mutations with unconventional locations were found.Bisphosphonate treatment response was inversely correlated with age (p=<0.0001) and lumbar spine BMD at onset (p=0.006). Mutations associated with a more severe phenotype had an improved response to treatment when analyzing 2-year delta lumbar spine Z-score values; mutations in COL1A1 vs. COL1A2 (p=0.03), qualitative mutations in COL1A1 vs. COL1A2 (p=0.006), serine substitutions in COL1A1 vs. COL1A2 (p=0.007) and qualitative vs. qualitative mutations in COL1A1 (p=0.02) all exhibited this pattern. Bisphosphonate response was not correlated to either OI type or gender.Conclusions: The genotype-phenotype correlations described here confirm previous reports of influence of chain affected, intrachain location, and mutation type on phenotype. BMD response to bisphosphonate treatment is inversely related to age and BMD at onset. Pharmaco-genetic analyses show an increased response to bisphosphonate treatment for more severe mutations types. This effect is attenuated over time.
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31.
  • Lindahl, Katarina, et al. (författare)
  • Heterozygosity for a coding SNP in COL1A2 confers a lower BMD and an increased stroke risk.
  • 2009
  • Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 384:4, s. 501-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variation plays an important role in osteoporosis and a prime candidate gene is Collagen alpha2(I) (COL1A2). A coding polymorphism (rs42524) in COL1A2 has previously been associated with intracranial aneurysms. Here the effects of this polymorphism have been studied in relation to bone mineral density (BMD) and prevalences of stroke and myocardial infarction (MI). rs42524 was genotyped in elderly men (n = 2004) from the Swedish MrOS cohort. Genotypes were analysed for association to BMD and certain health parameters. Significant associations (overall P < 0.05), were observed between rs42524 genotype and BMD at several skeletal sites. Surprisingly, the heterozygote genotype class exhibited lower BMD than either homozygote group. When subjects were classified as heterozygotes or homozygotes, the heterozygous genotype was found to confer a lower BMD at total hip, femoral neck and trochanter Furthermore, the heterozygote genotype had an increased risk of stroke and MI, with population Attributable Risks being 0.12 and 0.08, respectively.
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32.
  • Lindahl, Katarina, et al. (författare)
  • Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy
  • 2018
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 114, s. 268-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.
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33.
  • Lindahl, Katarina, Fil. lic. i ämnesdidaktik (författare)
  • Kollaborativa arbetsformer i nätbaserad undervisning
  • 2020
  • Konferensbidrag (refereegranskat)abstract
    • Syftet med presentationen är att dela erfarenheter och reflektioner kring nya arbetsformer och metoder som använts i en nätbaserad kurs. På Högskolan Dalarna läser 64 % av studenterna nätbaserade kurser. Vi arbetar framförallt med synkron undervisning där studenterna förväntas delta vid seminarier och föreläsningar i realtid online. En särskild utmaning med just nätbaserad undervisning har varit att främja samarbete mellan studenter. I en nyutvecklad kurs, Språkdidaktik III för blivande ämneslärare i engelska, har jag därför särskilt arbetat med kollaborativa arbetsformer och försökt tänka innovativt kring kursstruktur, uppgifter och övningar. I arbetet med att planera den nya kursen var målet förbättra och fördjupa studenters möjligheter att lära av och med varandra samt att bättre utnyttja lärarresurserna i kursen.Kursen genomfördes första gången hösten 2019 och läses varje termin av ca 10–12 studenter. Kursen genererar cirka 50 timmar som fördelas på lärarledd undervisning, bedömning, återkoppling och administration. Genom att utforma undervisningen på ett sätt där studenterna används som resurser för varandra ges de bättre förutsättningar att utvecklas som kritiskt tänkande och socialt ansvarstagande blivande lärare. Kursen är utvecklad för att svara mot de kursutvärderingar och programutvärderingar tidigare studenter lämnat in om ämneslärarprogrammet. Seminarierna bygger på en växling mellan föreläsning, grupparbete och seminarium. Under grupparbetet får studenterna exempelvis träna på att bedöma elevuppgifter i Engelska eller gemensamt arbeta med återkoppling på egna texter i ett delat dokument. Wicks m.fl. (2015) har visat att användningen av ”high collaboration technologies”, som delade dokument, inte verkar påverka studenternas slutbetyg i kurser. Däremot värdesatte studenter som arbetade i grupp varandra högre och de menar att  ”designing courses that promote high collaboration could facilitate increased value in openness, meaning-making, and co-construction of knowledge” (Wicks m.fl., 2015, s. 19). Därför lämpar sig kollaborativa arbetsformer särskilt bra för att utveckla studenternas kritiska tänkande och meningsskapande. Samtidigt är det viktigt att inte glömma bort lärarens roll i seminarierna. Noddings (2012) betonar vikten av att läraren uppmärksamt lyssnar på studenterna. Genom att låta studenter tänka högt, och genom att visa att deras tänkande respekteras, vågar de i högre utsträckning delta i samtalet (Noddings, 2012, s. 774). Genom att låta studenterna arbeta självständigt i grupparbetet visar vi också hur viktigt det är att de inte ständigt blir bedömda och utvärderade. Studenterna visar i kursutvärderingen att de upplevt seminarierna som välorganiserade och givande. Målgruppen för presentationen är universitetslärare som arbetar eller vill arbeta med onlineundervisning och som vill utveckla studenternas onlinesamarbete.ReferenserNoddings, N. (2012). The caring relation in teaching. Oxford Review of Education, 38(6), 771-781. https://doi.org/10.1080/03054985.2012.745047Wicks, D., Craft, B., Lee, D., Lumpe, A., Henrikson, R., Baliram, N., Bian, X., Mehlberg, S., & Wicks, K. (2015). An Evaluation of Low Versus High Collaboration in Online Learning. Online Learning Journal, 19. https://doi.org/10.24059/olj.v19i4.552
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34.
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35.
  • Lindahl, Katarina (författare)
  • Online teaching through information and communications technology
  • 2020
  • Konferensbidrag (refereegranskat)abstract
    • Information and communications technology (ICT) has opened an entire world of opportunities for both teachers and students. When all upper secondary schools and universities in Sweden had to switch to online teaching within a few days due to the COVID-19 pandemic, it became evident how useful and valuable ICT-tools are for teaching. Online teaching is common at Dalarna University, and 64% of our students study net-based distance courses. The aim of this presentation is to give examples of successful integration of ICT-tools in addition to discussing the challenges and drawbacks of relying heavily on technological solutions. Furthermore, the development of a new online course for teacher students will be discussed with a focus on how different ICT-tools are used to further collaboration and communication between students. The course is called “English Language Learning and Teaching III” and is aimed at future English teachers in upper secondary school. In the course, students are expected to both develop their knowledge about teaching methods as well as improve their language proficiency skills.The main difference between teaching online and teaching on campus is that we must find new ways for students to communicate and collaborate. The students gain access to course materials through our learning management system Blackboard Learn. They also meet for online teacher-led seminars every week in the online meeting tool Zoom. Through these synchronous meetings we ensure the quality of our online teaching and the seminar discussion becomes an important part of the course. In the seminars, students frequently use shared documents to collaborate in real time. By doing so, we encourage cooperation between students and at the same time teach them how they can use these online tools with their own future pupils. Between seminars, students are also expected to use digital tools for assignments, which makes it possible for the university teachers to see more of the students’ work process than what was previously possible. 
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36.
  • Lindahl, Katarina (författare)
  • Osteogenesis Imperfecta : Genetic and Therapeutic Studies
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Osteogenesis imperfecta (OI) is a heterogeneous disease of connective tissue, the cardinal symptom being fractures and severity ranging from mild to lethal. Dominant mutations in collagen I, encoded by COL1A1 and COL1A2, cause >90% of cases.To delineate genotype-phenotype correlations and pharmaco-genetic response, collagen I was sequenced in 150 unrelated Swedish families and clinical data were collected in Paper I. Mutation type, gene affected, and N- to C-terminal location correlated with phenotype and severity. Bisphosphonate response assessed by calculated yearly change in lumbar spine bone mineral density (BMD) was inversely related to age and BMD at treatment initiation. Mutations associated with a more severe phenotype exhibited an increased response after 2 years; however, all types of OI responded well.To investigate the effect of naturally occurring variations in collagen I, the only common coding single nucleotide polymorphism (rs42524 in COL1A2) was genotyped in 2004 healthy men in Paper II. Heterozygous genotype was associated with decreased BMD and an increased risk of stroke.An adolescent with repeated fractures despite a markedly high BMD harbored a unique C-terminal procollagen cleavage-site mutation in COL1A1, which motivated extensive investigations in concert with a similar COL1A2 case in Paper III. The probands were found to have impaired procollagen processing, incorporation of collagen with retained C-propeptide in matrix and increased mineral to matrix ratio, which demonstrates that C-propeptide cleavage is crucial to normal bone mineralization and structure.Bisphosphonate therapy has insufficient effect in OI, and as classical OI is a dominant disorder severe cases would benefit from silencing of the mutated allele. In Paper IV and V small interfering RNAs (siRNAs) were used to allele-specifically target primary human bone cells heterozygous for I) a coding polymorphism in COL1A2 and II) insertion/deletions in the 3’UTR of COL1A1 and COL1A2. Results were promising with altered allele ratios and decreased mRNA levels in the predicted fashion.To summarize, this thesis found that collagen I is crucial to bone and connective tissue and that collagen I mutations create markedly diverse phenotypes. Age, BMD and pharmaco-genetic effects influence the response to bisphosphonate therapy in individuals with OI; however, novel approaches are needed. Utilizing allele-specific siRNAs may be a way forward in the treatment of severe OI. 
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37.
  • Lindahl, Katarina (författare)
  • Teaching Teacher Students through Innovative Teaching Approaches in Online Learning
  • 2019
  • Ingår i: 12th International Conference Innovation in Language Learning. - Florence. - 9788885813809 ; , s. 386-389
  • Konferensbidrag (refereegranskat)abstract
    • Innovative teaching and new teaching and learning approaches are needed in order to prepare the language teachers of tomorrow. As an alternative to asynchronous online instruction, teacher students have teacher-led online seminars every week. In addition to these seminars, several different ICT-tools and language teaching and learning approaches are used in order to prepare the teacher students for a digital future. The purpose of this paper is to discuss how digital resources and online teaching are used both for teaching university students, but also as examples of pedagogical approaches that these teacher students can use in school. The net-based courses on English language learning and teaching for future primary, secondary or upper secondary school teachers are structured in a similar way around online seminars. An online learning platform with course information and assignments is used for communication with students outside of the seminars. What makes these courses different from other net-based courses are that the additional tools that are used are tools that can be used in language teaching with younger pupils as well. For example, multi-modal resources such as video and audio recordings are used both for giving feedback and as an alternative to written assignments. In addition, free, readily available online tools for flipped classroom are used both for teaching the course, but also as examples of what our teacher students can use them for with their own pupils. Through collaborative writing projects where shared documents are used, university teachers gain a better insight in how students work together. In the online seminars, the teacher students discuss how these pedagogical approaches can be used in primary, secondary or upper secondary school. The aim is to let the teacher students experience an innovative approach to language learning in addition to reading about it.
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38.
  • Lindahl, Katarina, et al. (författare)
  • Therapy of Endocrine Disease : Treatment of osteogenesis imperfecta in adults
  • 2014
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 171:2, s. R79-R90
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Osteogenesis imperfecta (OI) is a heterogeneous rare connective tissue disorder commonly caused by mutations in the collagen type I genes. Pharmacological treatment has been most extensively studied in children, and there are only few studies comprising adult OI patients. Objectives: i) To review the literature on the current medical management of OI in children and adults, and thereby identify unmet medical needs and ii) to present an overview of possible future treatment options. Results: Individualization and optimization of OI treatment in adults remain a challenge, because available treatments do not target the underlying collagen defect, and available literature gives weak support for treatment decisions for adult patients. Conclusions: Bisphosphonates are still the most widely used pharmacological treatment for adult OI, but the current evidence supporting this is sparse and investigations on indications for choice and duration of treatment are needed.
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39.
  • Lindahl, Katarina (författare)
  • Vocational English : The gap between policy and practice
  • 2017
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • A new structure for upper secondary school was introduced in Sweden 2011. In light of this new educational policy reform, which has differentiated vocational programmes and academic programmes from each other, the relationship between policy and practice is relevant to explore. It could be argued that this differentiation is a part of an international trend towards marketization and internationalization. Subjects, such as English, are adapted to different programmes in order to contribute to the increased employability of students. The purpose of this paper is to explore the gap between policy and practice for teachers when working with vocational English, and how this can affect vocational education in the future. The study consists of a textual policy analysis of the three latest upper secondary reforms in Sweden and semi-structured interviews with six teachers in the Building and Construction Programme. The perspective policy enactment is used rather than policy implementation, since policy text is constantly struggled over through a complex and creative recontextualisation process (Ball et al., 2012; Ozga, 2000). Bernstein’s concepts of classification and horizontal and vertical discourse are also used. Classification, which can be strong or weak, refers to boundaries between categories based on power relations (Bernstein, 1999; 2000). Horizontal and vertical discourse explain how knowledge is divided in two forms: the everyday knowledge  and the more abstract, official knowledge (Bernstein, 1999). This becomes relevant for the analysis since the school systematically selects the knowledge it provides to students. The results show that the teachers in this study perceived their vocational students as unmotivated to study “theoretical subjects”, they described them as “theoretical or practical”, and some teachers placed lower demands on vocational students than on students in other programmes. This is not in line with current policies, which shows that there is a distinct gap between policy and practice.
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40.
  • Lindahl, Katarina, 1987- (författare)
  • Vocational English in policy and practice
  • 2015
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this licentiate thesis is to examine how, and in what ways, vocational English is a part of English language teaching in the Building and Construc­tion Programme in Sweden, and what the influences are for such pedagogy. The main research question is how policy documents relate to the views of teachers and their educational practice regarding vocational English. The study consists of two parts: a textual policy analysis of the three latest upper secondary school reforms in Sweden (Lgy 70, Lpf 94, and Gy 2011), and semi-structured interviews with practicing English teachers in the Building and Construction Programme. The interviews are categorised by using Spradley’s (1979) semantic relationships and taxonomies. Balls’ (Ball, 1993) and Ozga’s (1990; 2000) concept of policy enactment is used in the analysis as well as Bernstein’s (1990; 2000) theoretical framework of classification, framing, and horizontal and vertical discourse.The results show that five of the six teachers in the interviews work with vocational English in some way. The study also shows that there is a distinct gap between policy and practice. Several of the teachers have the notion that they are supposed to work with vocational English and that it must be written down in policy somewhere. The greatest influence on the teaching for these teachers are their students, either indirectly or directly. Further, the study shows that different frame factors such as time poverty hinders the teachers from reading policy texts and cooperating with the vocational teachers in the Building and Construction Programme.
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41.
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42.
  • Ljunggren, Östen, et al. (författare)
  • Allele-Specific Gene Silencing in Osteogenesis Imperfecta
  • 2011
  • Ingår i: Cartilage and Bone Development and Its Disorders. - : S. Karger AG. - 9783805597920 ; 21, s. 85-90
  • Konferensbidrag (refereegranskat)abstract
    • OI is caused by mutations in the genes encoding for collagen type I COL1A1 and COL1A2, respectively. The patients suffer from bone fragility, and the severity can range from mild, with fractures in the youth, to lethal forms. Today, there is no effective treatment for the disorder. OI is caused by dominant negative mutations. A tempting approach to treat the disease would be to silence the allele carrying the mutation. This could in theory be done with siRNAs. Today, more than 800 various mutations are reported, and to create siRNA against a specific mutation is difficult. Instead, by developing siRNA against common polymorphic variations, it would be possible to silence the mutation by a standardized method regardless where the mutation is located on the allele. If the concept of allele-specific gene silencing by inhibitory RNA directed towards dominant negative mutations could be proven, this might be a novel approach to gene therapy in OI.
  •  
43.
  • Malmgren, B., et al. (författare)
  • Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen type I genes
  • 2017
  • Ingår i: Oral Diseases. - : Wiley. - 1354-523X .- 1601-0825. ; 23:1, s. 42-49
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundOsteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2). Tooth agenesis is a common feature of OI. We investigated the association between tooth agenesis and collagen type I mutations in individuals with OI. Subjects and methodsIn this cohort study, 128 unrelated individuals with OI were included. Panoramic radiographs were analyzed regarding dentinogenesis imperfecta (DGI) and congenitally missing teeth. The collagen I genes were sequenced in all individuals, and in 25, multiplex ligation-dependent probe amplification was performed. ResultsMutations in the COL1A1 and COL1A2 genes were found in 104 of 128 individuals. Tooth agenesis was diagnosed in 17% (hypodontia 11%, oligodontia 6%) and was more frequent in those with DGI (P=0.016), and in those with OI type III, 47%, compared to those with OI types I, 12% (P=0.003), and IV, 13% (P=0.017). Seventy-five percent of the individuals with oligodontia (6 missing teeth) had qualitative mutations, but there was no association with OI type, gender, or presence of DGI. ConclusionThe prevalence of tooth agenesis is high (17%) in individuals with OI, and OI caused by a qualitative collagen I mutation is associated with oligodontia.
  •  
44.
  • Nilsson, Ingegerd, et al. (författare)
  • Professional supervision in nursing
  • 2004
  • Ingår i: Workgroup of European nurse researchers. Biennial conference (12 : Lisboa : 2004). - Lisbon : WENR. ; , s. 95-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
  •  
45.
  • Rosling, Anna, et al. (författare)
  • Archaeorhizomycetes: Unearthing an Ancient Class of Ubiquitous Soil Fungi
  • 2011
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 333, s. 876-879
  • Tidskriftsartikel (refereegranskat)abstract
    • Estimates suggest that only one-tenth of the true fungal diversity has been described. Among numerous fungal lineages known only from environmental DNA sequences, Soil Clone Group 1 is the most ubiquitous. These globally distributed fungi may dominate below-ground fungal communities, but their placement in the fungal tree of life has been uncertain. Here, we report cultures of this group and describe the class, Archaeorhizomycetes, phylogenetically placed within subphylum Taphrinomycotina in the Ascomycota. Archaeorhizomycetes comprises hundreds of cryptically reproducing filamentous species that do not form recognizable mycorrhizal structures and have saprotrophic potential, yet are omnipresent in roots and rhizosphere soil and show ecosystem and host root habitat specificity.
  •  
46.
  • Stenlund, Therese, 1970-, et al. (författare)
  • Cognitively Oriented Behavioral Rehabilitation in Combination with Qigong for Patients on Long-Term Sick Leave Because of Burnout : REST-A Randomized Clinical Trial
  • 2009
  • Ingår i: International Journal of Behavioral Medicine. - : Springer Science and Business Media LLC. - 1070-5503 .- 1532-7558. ; 16:3, s. 294-303
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite an increase in the occurrence of burnout, there is no agreement on what kind of rehabilitation these patients should be offered. Primary aim of this study was to evaluate effects on psychological variables and sick leave rates by two different group rehabilitation programs for patients on long-term sick leave because of burnout. Rehabilitation program A (Cognitively oriented Behavioral Rehabilitation (CBR) and Qigong) was compared with rehabilitation program B (Qigong only). In a randomized clinical trial, 96 women and 40 men with a mean age of 41.6 +/- 7.4 years were allocated to one of the two rehabilitation programs. A per-protocol analysis showed no significant difference in treatment efficacy between the groups. Both groups improved significantly over time with reduced levels of burnout, self-rated stress behavior, fatigue, depression, anxiety, obsessive-compulsive symptoms, and sick leave rates. In an intention-to-treat analysis, patients in program A had fewer obsessive-compulsive symptoms and larger effect sizes in self-rated stress behavior and obsessive-compulsive symptoms compared to patients in program B. This study showed no differences in effect between CBR and Qigong compared with Qigong only in a per-protocol analysis. Both rehabilitation programs showed positive effect for patients with burnout.
  •  
47.
  • Strid, Ylva, et al. (författare)
  • Bark beetles have a decisive impact on fungal communities in Norway spruce stem sections
  • 2014
  • Ingår i: Fungal Ecology. - : Elsevier BV. - 1754-5048 .- 1878-0083. ; 7, s. 47-58
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the importance of insects in the establishment of fungi, stem sections of Norway spruce were placed in mature managed conifer forests in Southeast Sweden. After one or two flying seasons, fungal communities in wood, bark and bark beetle samples were analysed by molecular methods. Excluding insects from stem sections with cages had a significant effect on the fungal community. Small wounds made in the bark to mimic insect activity did not significantly alter the fungal community, indicating that physical holes as such only played a minor role for the insect interaction with the fungal community development. Several white rot species were significantly more abundant in stem sections with insect access and were also detected from bark beetle samples. This suggests that insects do contribute to the development of early fungal succession on dead wood, but that creating small disturbances in the bark only have a minor contributing effect. (C) 2013 Elsevier Ltd and The British Mycological Society. All rights reserved.
  •  
48.
  • Yndigegn, Troels, et al. (författare)
  • Design and rationale of randomized evaluation of decreased usage of beta-blockers after acute myocardial infarction (REDUCE-AMI)
  • 2022
  • Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837 .- 2055-6845. ; 9:2, s. 192-197
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Most trials showing benefit of beta-blocker treatment after myocardial infarction (MI) included patients with large MIs and are from an era before modern biomarker-based MI diagnosis and reperfusion treatment. The aim of the Randomized Evaluation of Decreased Usage of betabloCkErs after Acute Myocardial Infarction (REDUCE-AMI) trial is to determine whether long-term oral beta-blockade in patients with an acute MI and preserved left ventricular ejection fraction (EF) reduces the composite endpoint of death of any cause or recurrent MI.METHODS: It is a registry-based, randomized, parallel, open-label, multicenter trial performed at 38 centers in Sweden, one center in Estonia and six centers in New Zealand. About 5000 patients with an acute MI who have undergone coronary angiography and with EF ≥ 50% will be randomized to long-term treatment with beta-blockade or not. The primary endpoint is the composite endpoint of death of any cause or new non-fatal MI. There are several secondary endpoints, including all-cause death, cardiovascular death, new MI, readmission because of heart failure and atrial fibrillation, symptoms, functional status, health related quality of life after 6-10 weeks and after 1 year of treatment. Safety endpoints are bradycardia, AV-block II-III, hypotension, syncope or need for pacemaker, asthma or chronic obstructive pulmonary disease and stroke.CONCLUSION: The results from REDUCE-AMI will add important evidence regarding the effect of beta-blockers in patients with MI and preserved EF and may change guidelines and clinical practice.
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