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Sökning: WFRF:(Eriksson Oskar)

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  • Eriksson, Jens, et al. (författare)
  • Characterization of motility and piliation in pathogenic Neisseria
  • 2015
  • Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The type IV pili (Tfp) of pathogenic Neisseria (i. e., N. gonorrhoeae and N. meningitidis) are essential for twitching motility. Tfp retraction, which is dependent on the ATPase PilT, generates the forces that move bacteria over surfaces. Neisseria motility has mainly been studied in N. gonorrhoeae whereas the motility of N. meningitidis has not yet been characterized. Results: In this work, we analyzed bacterial motility and monitored Tfp retraction using live- cell imaging of freely moving bacteria. We observed that N. meningitidis moved over surfaces at an approximate speed of 1.6 mu m/s, whereas N. gonorrhoeae moved with a lower speed (1.0 mu/s). An alignment of the meningococcal and gonococcal pilT promoters revealed a conserved single base pair variation in the -10 promoter element that influence PilT expression. By tracking mutants with altered pilT expression or pilE sequence, we concluded that the difference in motility speed was independent of both. Live-cell imaging using total internal reflection fluorescence microscopy demonstrated that N. gonorrhoeae more often moved with fewer visible retracting filaments when compared to N. meningitidis. Correspondingly, meningococci also displayed a higher level of piliation in transmission electron microscopy. Nevertheless, motile gonococci that had the same number of filaments as N. meningitidis still moved with a lower speed. Conclusions: These data reveal differences in both speed and piliation between the pathogenic Neisseria species during twitching motility, suggesting a difference in Tfp-dynamics.
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  • Karlsson, Oskar, et al. (författare)
  • Pesticide-induced multigenerational effects on amphibian reproduction and metabolism
  • 2021
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 775
  • Tidskriftsartikel (refereegranskat)abstract
    • Underlying drivers of species extinctions need to be better understood for effective conservation of biodiversity. Nearly half of all amphibian species are at risk of extinction, and pollution may be a significant threat as seasonal high-level agrochemical use overlaps with critical windows of larval development. The potential of environmental chemicals to reduce the fitness of future generations may have profound ecological and evolutionary implications. This study characterized effects of male developmental exposure to environmentally relevant concentrations of the anti-androgenic pesticide linuron over two generations of offspring in Xenopus tropicalis frogs. The adult male offspring of pesticide-exposed fathers (F1) showed reduced body size, decreased fertility, and signs of endocrine system disruption. Impacts were further propagated to the grand-offspring (F2), providing evidence of transgenerational effects in amphibians. The adult F2 males demonstrated increased weight and fat body palmitoleic-to-palmitic acid ratio, and decreased plasma glucose levels. The study provides important cross-species evidence of paternal epigenetic inheritance and pollutant-induced transgenerational toxicity, supporting a causal and complex role of environmental contamination in the ongoing species extinctions, particularly of amphibians.
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  • Klaric, Lucija, et al. (författare)
  • Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
  • 2021
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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  • Lind, Lars, et al. (författare)
  • Obesity is associated with coronary artery stenosis independently of metabolic risk factors : the population-based SCAPIS study
  • 2022
  • Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 362, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. Methods: In the SCAPIS study (50–65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. Results: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34–1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87–1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. Conclusions: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.
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  • Rosmark, Oskar, et al. (författare)
  • Quantifying extracellular matrix turnover in human lung scaffold cultures
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Remodelling of the extracellular matrix is accomplished by altering the balance between matrix macromolecule production and degradation. However, it is not well understood how cells balance production of new matrix molecules and degradation of existing ones during tissue remodelling and regeneration. In this study, we used decellularized lung scaffolds repopulated with allogenic lung fibroblasts cultured with stable isotope labelled amino acids to quantify the balance between matrix production and degradation at a proteome-wide scale. Specific temporal dynamics of different matrisome proteins were found to correspond to the proliferative activity of the repopulating cells and the degree of extracellular deposition. The remodeling of the scaffold was characterized by an initial phase with cell proliferation and high production of cell adhesion proteins such as emilin-1 and fibronectin. Extended culture time resulted in increased levels of core matrisome proteins. In a comparison with monolayer cultures on plastic, culture in lung scaffolds lead to a pronounced accumulation of proteoglycans, such as versican and decorin, resulting in regeneration of an extracellular matrix with greater resemblance to native lung tissue compared to standard monolayer cultures. Collectively, the study presents a promising technique for increasing the understanding of cell- extracellular matrix interactions under healthy and diseased conditions.
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  • Östgren, Carl Johan, et al. (författare)
  • Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals-a Swedish population-based study.
  • 2023
  • Ingår i: Cardiovascular diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.The 30,154 study participants, 50-64years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.Study participants with prediabetes (n=4804, 16.0%) or diabetes (n=2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p<0.01). Among male participants with diabetes 35.3% had CACS≥100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.
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  • Abel, Andreas, 1974, et al. (författare)
  • A Graded Modal Dependent Type Theory with a Universe and Erasure, Formalized
  • 2023
  • Ingår i: Proceedings of the ACM on Programming Languages. - 2475-1421. ; 7:ICFP, s. 920-954
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a graded modal type theory, a dependent type theory with grades that can be used to enforce various properties of the code. The theory has Pi-types, weak and strong Sigma-types, natural numbers, an empty type, and a universe, and we also extend the theory with a unit type and graded Sigma-types. The theory is parameterized by a modality, a kind of partially ordered semiring, whose elements (grades) are used to track the usage of variables in terms and types. Different modalities are possible. We focus mainly on quantitative properties, in particular erasure: with the erasure modality one can mark function arguments as erasable. The theory is fully formalized in Agda. The formalization, which uses a syntactic Kripke logical relation at its core and is based on earlier work, establishes major meta-theoretic properties such as subject reduction, consistency, normalization, and decidability of definitional equality. We also prove a substitution theorem for grade assignment, and preservation of grades under reduction. Furthermore we study an extraction function that translates terms to an untyped λ-calculus and removes erasable content, in particular function arguments with the "erasable"grade. For a certain class of modalities we prove that extraction is sound, in the sense that programs of natural number type have the same value before and after extraction. Soundness of extraction holds also for open programs, as long as all variables in the context are erasable, the context is consistent, and erased matches are not allowed for weak Sigma-types.
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  • Aberg, Mikael, et al. (författare)
  • Tissue Factor Noncoagulant Signaling : Mechanisms and Implications for Cell Migration and Apoptosis
  • 2015
  • Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 41:7, s. 691-699
  • Tidskriftsartikel (refereegranskat)abstract
    • Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also initiates noncoagulant signaling with broad biological implications. In this review, we discuss how TF interacts with other cell-surface proteins, which affect biological functions such as cell migration and cell survival. A vast number of publications have demonstrated the importance of TF-induced activation of protease-activated receptors, but recently published research has indicated a more complicated picture. As it has been discovered that TF interacts with integrins and receptor tyrosine kinases, novel signaling mechanisms for the TF/FVIIa complex have been presented. The knowledge of these new aspects of TF signaling may, for instance, facilitate the development of new treatment strategies for cancer and acute coronary syndromes, two examples of diseases characterized by aberrant TF expression and signaling.
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  • Andersson, Cecilia K, et al. (författare)
  • Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis
  • 2011
  • Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 12:139
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls. Methods: Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MCT and MCTC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-beta. Results: In the alveolar parenchyma in lungs from patients with CF, MCTC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTC and MCT cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-beta. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTC correlated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTC expression of TGF-beta, correlated negatively with patient lung function. Conclusions: The present study reveals that altered mast cell populations, with increased numbers of MCTC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.
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  • Andersson Sjöland, Annika, et al. (författare)
  • Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.
  • 2011
  • Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 30, s. 945-954
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS. METHODS: Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of the proteoglycans versican, perlecan, biglycan, and decorin, with and without transforming growth factor (TGF)-β(1). Fibroblast migration and proliferation were also studied. RESULTS: At 6 and 12 months after LTx, versican production was higher in fibroblasts from LTx patients (p < 0.01 p < 0.01) than from controls. Fibroblasts from patients who later developed BOS were more responsive to TGF-β(1)-induced synthesis of versican and biglycan than patients without signs of rejection (p < 0.05). Production of perlecan and decorin was negatively correlated with fibroblast proliferation in fibroblasts at 6 months after LTx. In a more detailed case study of 2 patients, one with and one without BOS, the altered proteoglycan profile was associated with impaired lung function. CONCLUSIONS: LTx changes the phenotype of fibroblasts to a non-proliferative but extracellular matrix-producing cell due to wound healing involving TGF-β(1). If not controlled, this may lead to development of BOS.
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  • Barrio, Alvaro Martinez, et al. (författare)
  • Targeted Resequencing and Analysis of the Diamond-Blackfan Anemia Disease Locus RPS19
  • 2009
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6172-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Ribosomal protein S19 gene locus (RPS19) has been linked to two kinds of red cell aplasia, Diamond-Blackfan Anemia (DBA) and Transient Erythroblastopenia in Childhood (TEC). Mutations in RPS19 coding sequences have been found in 25% of DBA patients, but not in TEC patients. It has been suggested that non-coding RPS19 sequence variants contribute to the considerable clinical variability in red cell aplasia. We therefore aimed at identifying non-coding variations associated with DBA or TEC phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: We targeted a region of 19'980 bp encompassing the RPS19 gene in a cohort of 89 DBA and TEC patients for resequencing. We provide here a catalog of the considerable, previously unrecognized degree of variation in this region. We identified 73 variations (65 SNPs, 8 indels) that all are located outside of the RPS19 open reading frame, and of which 67.1% are classified as novel. We hypothesize that specific alleles in non-coding regions of RPS19 could alter the binding of regulatory proteins or transcription factors. Therefore, we carried out an extensive analysis to identify transcription factor binding sites (TFBS). A series of putative interaction sites coincide with detected variants. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). CONCLUSIONS: Specific alleles at predicted TFBSs may alter the expression of RPS19, modify an important interaction between transcription factors with overlapping TFBS or remove an important stimulus for hematopoiesis. We suggest that the detected interactions are of importance for hematopoiesis and could provide new insights into individual response to treatment.
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  • Bergström, Göran, 1964, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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  • Bergström, Göran, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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  • Borg, Tor, et al. (författare)
  • Mått på bostadsbristen : Förslag på hur återkommande bedömningar ska utföras
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Boverket fick i juni 2019 i uppdrag av regeringen att lämna förslag på hur återkommande bedömningar av bostadsbristen ska utföras samt att lämna förslag på enhetliga begrepp som ska användas vid kommunikation kring bostadsbristen. Avsikten är att de presenterade beräkningarna ska kunna användas i arbetet med bostadsförsörjningsfrågor och underlätta arbetet med att planera, utföra och följa upp insatser för att åtgärda bostadsbristen. Boverket har tagit fram en årlig beräkningsmodell där antalet hushåll som saknar en rimlig bostad beräknas på både nationell, regional och lokal nivå. Vad som är en rimlig bostad definieras enligt en uppsättning kriterier och normer. Kvantitativa mått visar hur många hushåll som har en boendesituation som inte uppfyller de olika kriterierna. Samråd har skett med Sveriges Kommuner och Regioner (SKR) samt med Socialstyrelsen under uppdragets gång. Båda anser att de givits utrymme att framföra sin mening och har förklarat sig nöjda med samrådet. Avstämningar har också gjorts med en rad andra aktörer. Denna rapport utgör Boverkets slutredovisning av uppdraget. Rapporten har tagits fram av en projektgrupp bestående av Tor Borg, Bengt J Eriksson, Oskar Gramstad, Ulla-Christel Götherström, Hans Jonsson, Bo Söderberg och Hang Zettervall, med den förstnämnda som projektledare.
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20.
  • Bäcklund, Nils, et al. (författare)
  • Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods
  • 2023
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:10, s. 1780-1791
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.
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21.
  • Börjesson, Stefan, 1979-, et al. (författare)
  • Detection of an IMI-2 carbapenemase-producing Enterobacter asburiae at a Swedish feed mill
  • 2022
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Occurrence of multidrug resistant Enterobacteriaceae in livestock is of concern as they can spread to humans. A potential introduction route for these bacteria to livestock could be animal feed. We therefore wanted to identify if Escherichia spp., Enterobacter spp., Klebsiella spp., or Raoutella spp. with transferable resistance to extended spectrum cephalosporins, carbapenems or colistin could be detected in the environment at feed mills in Sweden. A second aim was to compare detected isolates to previous described isolates from humans and animals in Sweden to establish relatedness which could indicate a potential transmission between sectors and feed mills as a source for antibiotic resistant bacteria. However, no isolates with transferable resistance to extended-cephalosporins or colistin could be identified, but one isolate belonging to the Enterobacter cloacae complex was shown to be carbapenem-resistant and showing carbapenemase-activity. Based on sequencing by both short-read Illumina and long-read Oxford Nanopore MinIon technologies it was shown that this isolate was an E. asburiae carrying a bla IMI-2 gene on a 216 Kbp plasmid, designated pSB89A/IMI-2, and contained the plasmid replicons IncFII, IncFIB, and a third replicon showing highest similarity to the IncFII(Yp). In addition, the plasmid contained genes for various functions such as plasmid segregation and stability, plasmid transfer and arsenical transport, but no additional antibiotic resistance genes. This isolate and the pSB89A/IMI-2 was compared to three human clinical isolates positive for bla IMI-2 available from the Swedish antibiotic monitoring program Swedres. It was shown that one of the human isolates carried a plasmid similar with regards to gene content to the pSB89A/IMI-2 except for the plasmid transfer system, but that the order of genes was different. The pSB89A/IMI-2 did however share the same transfer system as the bla IMI-2 carrying plasmids from the other two human isolates. The pSB89A/IMI-2 was also compared to previously published plasmids carrying bla IMI-2, but no identical plasmids could be identified. However, most shared part of the plasmid transfer system and DNA replication genes, and the bla IMI-2 gene was located next the transcription regulator imiR. The IS3-family insertion element downstream of imiR in the pSB89A was also related to the IS elements in other bla IMI-carrying plasmids.
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22.
  • Corsini, Christian, et al. (författare)
  • Patient-reported side effects 1 year after radical prostatectomy or radiotherapy for prostate cancer : a register-based nationwide study
  • 2024
  • Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 7:3, s. 605-613
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, population-based cohorts.OBJECTIVE: To assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot-assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient-reported outcome measures in the Swedish prostate cancer database.DESIGN, SETTING, AND PARTICIPANTS: This was a nationwide, population-based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics.RESULTS AND LIMITATIONS: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19-0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61).CONCLUSIONS: Short-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP.PATIENT SUMMARY: In our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects.
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23.
  • Corsini, Christian, et al. (författare)
  • Patient-reported Side Effects 1 Year After Radical Prostatectomy or Radiotherapy for Prostate Cancer : A Register-based Nationwide Study
  • 2024
  • Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 7:3, s. 605-613
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, populationbased cohorts. Objective: To assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot -assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient -reported outcome measures in the Swedish prostate cancer database. Design, setting, and participants: This was a nationwide, population -based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020. Outcome measurements and statistical analysis: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics. Results and limitations: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19- 0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61). Conclusions: Short-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP. Patient summary: In our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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24.
  • Criscuolo, Ivan, et al. (författare)
  • Model-Based Boost Pressure Control with System Voltage Disturbance Rejection
  • 2011
  • Ingår i: Proceedings of the 18th IFAC World Congress, 2011. - : International Federation of Automatic Control (IFAC). - 9783902661937 ; , s. 5058-5063
  • Konferensbidrag (refereegranskat)abstract
    • Actuation systems for automotive boost control incorporate a vacuum tank and PWM controlled vacuum valves to increase the boosting system flexibility. Physical models for the actuator system are constructed using measurement data from a dynamometer with an engine having a two stage turbo system. The actuator model is integrated in a complete Mean Value Engine Model and a boost pressure controller is constructed. The developed model is used as basis for a nonlinear compensator, that is capable of rejecting disturbances from system voltage. An IMC based boost pressure controller is developed for the vacuum actuator and engine by using the engine model and then tested on the test cell. The controller performance is quantified and system voltage disturbance rejection is demonstrated.
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25.
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26.
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27.
  • Danielsson, Oskar, et al. (författare)
  • Study of a Longitudinal Flux Permanent Magnet Linear Generator for Wave Energy Converters
  • 2006
  • Ingår i: International Journal of Energy Research. - : Hindawi Limited. - 0363-907X .- 1099-114X. ; 30:14, s. 1130-1145
  • Tidskriftsartikel (refereegranskat)abstract
    • A directly coupled linear permanent magnet generator of longitudinal flux-type is investigated. The generator will be used for power take-off in a wave energy converter. A combined field- and circuit model, solved by a time stepping finite element technique, is used to model and analyse the electromagnetic behaviour of the machine. A large number of simulations form the basis of a design study where the influence of armature current level, number of cables per slot, and pole width is investigated with respect to efficiency, generator size, and the load angle. A case study is performed for a chosen generator design. The electromagnetic behaviour is examined both for nominal load and for overloads. The generator has a nominal output power of 10 kW for a constant piston speed of 0.7 m s(-1). The electromagnetic efficiency at nominal load is 86.0%, the load angle 6.6 degrees, and the power fluctuation 1.3%. At 300% overload the load angle barely exceeds 12 degrees and the cable temperature is below 25 degrees C provided that the stator back is thermally connected to the sea water. The numerical calculations have been verified for small speeds by experiments.
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28.
  • Eklund, Petter, 1989- (författare)
  • Design of Rare Earth Free Permanent Magnet Generators
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Low speed permanent magnet (PM) synchronous generators (SGs) are commonly used in renewable energy. Rare earth (RE) PMs such as neodymium-iron-boron are a popular choice due to their high performance. In 2011 supply and cost issues were added to the previously existing environmental concerns regarding REPM raw materials as the world's major producer China imposed export restrictions. This thesis aims to investigate and propose design solutions for PMSGs that do not use REPMs. Two approaches are used: to design generators using the cheaper and more abundant ferrite PM materials, and to investigate how properties of new PM materials influence SG design.A ferrite PM rotor is designed to replace a REPM rotor in an experimental 12 kW wind power generator. The new design employs a flux concentrating spoke type rotor to achieve performance similar to the old REPM rotor while using ferrite PMs. The ferrite PM rotor design is built. The air gap length, magnetic flux density in the air gap, PM remanence, and voltage at both load and no load are measured. The generator has lower no load voltage than expected, which is mainly explained by lower than specified remanence of the ferrite PMs in the prototype. With the measured remanence inserted into the calculations some discrepancy remains. It is found that the discrepancy can be explained by the magnetic leakage flux in the end regions of the spoke type rotor, which is not modeled in the two dimensional simulations used for the design calculations.To investigate the influence of PM material properties three different PM rotor topologies are optimized for torque production using PM materials described by their remanence, recoil permeability, and demagnetization resistance. Demagnetization is considered using currents determined by a novel, winding design independent short circuit model. It is found that the spoke type rotor gives the highest torque of the three rotor topologies for low remanence materials as long as the PMs have sufficient demagnetization resistance. For high remanence materials the surface mounted PM rotor can give higher torque if the demagnetization resistance is high, but otherwise a capped PM rotor gives higher torque.
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29.
  • Eliasson, Tove, 1985- (författare)
  • Empirical Essays on Wage Setting and Immigrant Labor Market Opportunities
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis consists of three self-contained essays.Essay 1: This essay estimates wage assimilation among non-western immigrants in Sweden, controlling for selection into employment by including individual fixed effects. Furthermore, using matched employer-employee panel data covering the complete Swedish labor market, this essay decomposes wage catch-up into relative wage growth within and between workplaces and occupations. The results show that failing to control for selection into employment is likely to underestimate relative wage growth of immigrants, as early entrants in the labor market differ from later entrants along unobservable dimensions. Even after 30 years in the country, the group of non-western immigrants still earns substantially lower wages than natives. Wages catch up mainly within workplaces and occupations, suggesting that improved signals of productivity, rather than improved knowledge of job options, are of importance for the wage growth of non-western immigrants.Essay 2: Earlier research has shown that immigrant- and minority entrepreneurs have difficulties accessing capital through the formal financial markets. This essay studies what role immigrant employees within the local bank sector have for the probability of immigrants to run their own businesses. I use linked employer-employee data covering the whole Swedish labor market for the years 1987 to 2003 and utilize a nationwide refugee dispersal policy to get exogenous variation in the exposure to co-ethnic bank employees. Results suggest that there is a positive relation between co-ethnic bank employees and the probability of being self-employed. This effect is most pronounced for immigrants who arrived with low education, for males and for those residing in metropolitan regions. The effects are substantial and robust to a wide set of controls for labor market characteristics of the ethnic group at the local level. These results provide evidence of an ethnic component in the formal credit markets.Essay 3 (with Oskar Nordström Skans): This essay investigates the impact of a collective agreement stipulating a one shot increase in establishment-specific wage levels in a public-sector setting where wages otherwise are set according to individualized wage bargaining. The agreement stipulated that wages should increase in proportion to the number of low-paid females within each establishment. We find that actual wages among incumbents responded to the share of females with a wage below the stipulated threshold, conditional on the separate effects of the share of low wage earners, and the share of females. We find clear evidence of path-dependence in wages, covered workers remained on higher wage levels 4 years after the agreement took effect. The increase in wages resulted in a reduced probability of exit among young workers with relatively good grades and a lower frequency of new hires at the establishment level. 
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30.
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31.
  • Eriksson, Daniel, et al. (författare)
  • Health-related quality of life across all stages of autosomal dominant polycystic kidney disease
  • 2017
  • Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 32:12, s. 2106-2111
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess HRQoL in ADPKD across all stages of the disease, from patients with early chronic kidney disease (CKD) to patients with end-stage renal disease.METHODS: A study involving cross-sectional patient-reported outcomes and retrospective clinical data was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Patients were enrolled into four mutually exclusive stages of the disease: CKD stages 1-3; CKD stages 4-5; transplant recipients; and dialysis patients.RESULTS: Overall HRQoL was generally highest in patients with CKD stages 1-3, followed by transplant recipients, patients with CKD stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5.CONCLUSIONS: Later stages of ADPKD are associated with reduced physical health. The value of early treatment interventions that can delay progression of the disease should be considered.
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32.
  • Eriksson, Daniel, et al. (författare)
  • Real-world costs of autosomal dominant polycystic kidney disease in the Nordics
  • 2017
  • Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is limited real-world data on the economic burden of patients with autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to estimate the annual direct and indirect costs of patients with ADPKD by severity of the disease: chronic kidney disease (CKD) stages 1-3; CKD stages 4-5; transplant recipients; and maintenance dialysis patients. Methods: A retrospective study of ADPKD patients was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Data on medical resource utilisation were extracted from medical charts and patients were asked to complete a self-administered questionnaire. Results: A total of 266 patients were contacted, 243 (91%) of whom provided consent to participate in the study. Results showed that the economic burden of ADPKD was substantial at all levels of the disease. Lost wages due to reduced productivity were large in absolute terms across all disease strata. Mean total annual costs were highest in dialysis patients, driven by maintenance dialysis care, while the use of immunosuppressants was the main cost component for transplant care. Costs were twice as high in patients with CKD stages 4-5 compared to CKD stages 1-3. Conclusions: Costs associated with ADPKD are significant and the progression of the disease is associated with an increased frequency and intensity of medical resource utilisation. Interventions that can slow the progression of the disease have the potential to lead to substantial reductions in costs for the treatment of ADPKD.
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33.
  • Eriksson, Kristina M., 1976-, et al. (författare)
  • Manufacturing logistics courses aimed at competence development : Perspectives of coproduction between university and industry
  • 2021
  • Ingår i: Plans Forsknings- och tillämpningskonferens 2021. - : Plan - Logistikföreningen för effektiva flöden. ; , s. 349-363
  • Konferensbidrag (refereegranskat)abstract
    • New and elevated competences and knowledge needs arise as industry evolves and manufacturing is increasingly focusing digitalisation and sustainability. Facing those aspects of transformation one of the challenges is the continuous and growing need for competence development of professionals. In a work practice of constant implementation of new manufacturing processes, competence development becomes crucial for professionals within engineering fields such as production systems, product development and logistics. This paper reports a study of the design of courses within manufacturing logistics aimed at competence development for industrial professionals. We investigate how such courses can be designed to enable improved logistics practices in manufacturing industry. The course mode and its development are outlined, explaining the university and industry co-production of the incentive. The courses and their specified content are developed jointly with collaborating companies, and the courses are given free of charge as regular university courses advertised as free-standing courses. Data is collected between the period of spring semester 2019 – to spring semester 2021 from five completed courses of 2.5 ECTS on master level within manufacturing logistics. The data comprise quantitative data, such as throughput rate for course participants and qualitative data from focus groups. The focus groups emphasis the perspectives of the course participants and take place at the end of a completed course. Those focus groups serve as course evaluation coupled with highlighting themes of co-production and knowledge exchange between university and industry. The course concept of 2.5 ECTS credits on master level given during a period of five weeks has proven successful as regards meeting competence development need for professionals that are required to study in parallel with full time work. The results highlight participant’s perspectives, revealing that they value the potential of knowledge exchange enabled through the pedagogy of the course concept. Further, we emphasize that co-production between university and industry is beneficial to successfully design education aiming to meet real competence needs and challenges faced by manufacturing companies. To conclude, the results accentuate how the presented course concept can create and encourage conditions that lay the foundation for increased application of, at the companies, previously untried manufacturing logistic methods and new practices within logistics. 
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34.
  • Eriksson, Lars, et al. (författare)
  • Scalable Component-Based Modeling for Optimizing Engines with Supercharging, E-Boost and Turbocompound Concepts
  • 2012
  • Ingår i: SAE International Journal of Engines. - : SAE International. - 1946-3936 .- 1946-3944. ; 5:2, s. 579-595
  • Tidskriftsartikel (refereegranskat)abstract
    • Downsizing and turbocharging is a proven technology for fuel consumption reduction in vehicles. To further improve the performance, electrified components in the turbocharger arrangements have been proposed, and investigations have shown acceleration improvements, emission reductions, and further fuel conversion efficiency benefits. Simulation tools play an important role in the design process as the interplay between component selection, control strategy, system properties and constraints is very complex. Evaluations are performed with respect to BSFC map, fuel consumption in a drive cycle, acceleration performance, as well as many other aspects. A component-based engine and vehicle model is developed and evaluated to facilitate the process of assessing and optimizing the performance of e.g. engine, charging system, and electrical machine components. Considerations of the execution time and model fidelity have resulted in a choice of models in the mean value engine model family. The turbocharging and electrical system models have all been evaluated using experimental data from engine dynamometer tests and turbocharger gas stand measurements and other dedicated component measurements.
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35.
  • Eriksson, Leif, et al. (författare)
  • Skattehandboken
  • 2016
  • Ingår i: Skattehandboken. - Stockholm : Wolters Kluwer Sverige AB.
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • Skattehandboken är en komplett handbok för företagsbeskattning, personbeskattning och moms som fyra gånger om året uppdateras med aktuella bestämmelser. Skattehandboken vänder sig till alla som arbetar med skattefrågor. Det är ett självklart hjälpmedel för varje skattekonsult, ekonomiavdelning, revisor eller redovisningskonsult. De två handbokspärmarna behandlar företagets inkomstbeskattning, d.v.s frågor som rör beräkningen av ett företags skattepliktiga inkomst. Innehållet har disponerats så att det knyter an till företagets resultaträkning, men här behandlas också frågor som dels rör den personliga beskattningen, dels företagets hantering av sociala avgifter, skatteuppbörd m.m. Momsområdet ägnas stort utrymme, liksom internationella skattefrågor.
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36.
  • Eriksson, Mikael, et al. (författare)
  • Benefit of pazopanib in advanced gastrointestinal stromal tumours: results from a phase II trial (SSG XXI, PAGIST)
  • 2021
  • Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were ≥18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission + partial remission + stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. RESULTS: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. CONCLUSION: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.
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37.
  • Eriksson, Mattias, 1980-, et al. (författare)
  • Optimal vs. Heuristic Integrated Code Generation for Clustered VLIW Architectures.
  • 2008
  • Ingår i: 11th ACM SIGBED Int. Workshop on Software and Compilers for Embedded Systems SCOPES 2008,2008. - New York, USA : Association for Computing Machinery (ACM). ; , s. 11-20
  • Konferensbidrag (refereegranskat)abstract
    • In this paper we present two algorithms for integrated code generation for clustered VLIW architectures. One algorithm is a heuristic based on genetic algorithms, the other algorithm is based on integer linear programming. The performance of the algorithms are compared on a portion of the Mediabench benchmark suite. We found the results of the genetic algorithm to be within one or two clock cycles from optimal for the cases where the optimum is known. In addition the heuristic algorithm produces results in predictable time also when the optimal integer linear program fails.
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38.
  • Eriksson, Oskar, et al. (författare)
  • A stromal cell population in the large intestine identified by tissue factor expression that is lost during colorectal cancer progression
  • 2016
  • Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 116:6, s. 1050-1059
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is a major cause of morbidity and mortality, and the composition of the tumour stroma is a strong predictor of survival in this cancer type. Tissue factor (TF) functions as the trigger of haemostasis together with its ligand coagulation factor VII/ VIIa, and TF expression has been found in tumour cells of colorectal tumours. However, TF expression in the CRC tumour stroma or its relationship to patient outcome has not yet been studied. To address this question we developed and validated a specific anti-TF antibody using standardised methods within the Human Protein Atlas project. We used this antibody to investigate TF expression in normal colorectal tissue and CRC using immunofluorescence and immunohistochemistry in two patient cohorts. TF was strongly expressed in a cell population immediately adjacent to the colorectal epithelium. These TF-positive cells were ACTA2-negative but weakly vimentin-positive, defining a specific population of pericryptal sheath cells. In colorectal tumours, TF-positive sheath cells were progressively lost after the adenoma-to-carcinoma transition, demonstrating downregulation of this source of TF in CRC. Furthermore, loss of sheath cell TF was significantly associated with poor overall and disease-specific survival in rectal but not colon cancers. In conclusion, we demonstrate that TF is a marker of a specific cell population in the large intestine, which is lost during CRC progression. Our results highlight the role of the tumour stroma in this cancer type and suggest TF to be a potential prognostic biomarker in rectal cancers through the identification of pericryptal sheath cells.
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39.
  • Eriksson, Oskar, et al. (författare)
  • Cross-talk between the Tissue Factor/coagulation factor VIIa complex and the tyrosine kinase receptor EphA2 in cancer
  • 2016
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Tissue Factor (TF) forms a proteolytically active complex together with coagulation factor VIIa (FVIIa) and functions as the trigger of blood coagulation or alternatively activates cell signaling. We recently described that EphA2 of the Eph tyrosine kinase receptor family is cleaved directly by the TF/FVIIa complex. The aim of the present study was to further characterize the cross-talk between TF/FVIIa and EphA2 using in vitro model systems and human cancer specimens. Methods: Cleavage and phosphorylation of EphA2 was studied by Western blot. Subcellular localization of TF and EphA2 was investigated by a proximity ligation assay and confocal microscopy. Phalloidin staining of the actin cytoskeleton was used to study cell rounding and retraction fiber formation. Expression of TF and EphA2 in human colorectal cancer specimens was examined by immunohistochemistry. Results: TF and EphA2 co-localized constitutively in MDA-MB-231 cells, and addition of FVIIa resulted in cleavage of EphA2 by a PAR2-independent mechanism. Overexpression of TF in U251 glioblastoma cells lead to co-localization with EphA2 at the leading edge and FVIIa-dependent cleavage of EphA2. FVIIa potentiated ephrin-A1-induced cell rounding and retraction fiber formation in MDA-MB-231 cells through a RhoA/ROCK-dependent pathway that did not require PAR2-activation. TF and EphA2 were expressed in colorectal cancer specimens, and were significantly correlated. Conclusions: These results suggest that TF/FVIIa-EphA2 cross-talk might potentiate ligand-dependent EphA2 signaling in human cancers, and provide initial evidence that it is possible for this interaction to occur in vivo.
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40.
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41.
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42.
  • Eriksson, Oskar, 1984-, et al. (författare)
  • Mannose-Binding Lectin is Associated with Thrombosis and Coagulopathy in Critically Ill COVID-19 Patients
  • 2020
  • Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:12, s. 1720-1724
  • Tidskriftsartikel (refereegranskat)abstract
    • The ongoing COVID-19 pandemic has caused significant morbidity and mortality worldwide, as well as profound effects on society. COVID-19 patients have an increased risk of thromboembolic (TE) complications, which develop despite pharmacological thromboprophylaxis. The mechanism behind COVID-19-associated coagulopathy remains unclear. Mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, has been suggested as a potential amplifier of blood coagulation during thromboinflammation. Here we describe data from a cohort of critically ill COVID-19 patients ( n =65) treated at a tertiary hospital center intensive care unit (ICU). A subset of patients had strongly elevated MBL plasma levels, and activity upon ICU admission, and patients who developed symptomatic TE (14%) had significantly higher MBL levels than patients without TE. MBL was strongly correlated to plasma D-dimer levels, a marker of COVID-19 coagulopathy, but showed no relationship to degree of inflammation or other organ dysfunction. In conclusion, we have identified complement activation through the MBL pathway as a novel amplification mechanism that contributes to pathological thrombosis in critically ill COVID-19 patients. Pharmacological targeting of the MBL pathway could be a novel treatment option for thrombosis in COVID-19. Laboratory testing of MBL levels could be of value for identifying COVID-19 patients at risk for TE events.
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43.
  • Eriksson, Oskar, et al. (författare)
  • Neutrophil CD64 expression - comparison of two different flow cytometry protocols on EPICs MCL and the Leuko64 (TM) assay on a Celldyn Sapphire haematology analyser
  • 2015
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 75:5, s. 428-433
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To evaluate the Trillium Diagnostics Leuko64 (TM) assay on Abbott Celldyn Sapphire haematology analyser compared to two flow cytometry protocols on Beckman Coulter EPICS MCL flow cytometer. Materials and methods. CD64 expression on neutrophils was determined by two flow cytometry protocols and by a commercial assay on an automatic haematology analyser. The inclusion of study subjects was based on elevated procalcitonin (PCT) values, identifying patients where a systemic infection was suspected. Healthy blood donors were used as a reference group. Results. Statistically significant correlations between the Trillium Diagnostics Leuko64 (TM) assay and the flow cytometry methods were found when measuring neutrophil CD64 expression. Conclusions. The good correlation between a reference method and an automated haematology analyser method for CD64 expression on neutrophils supports introduction of the latter assay for routine use as an independent biomarker of bacterial infection and inflammation.
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44.
  • Eriksson, Oskar, et al. (författare)
  • On Hybrid ARQ Adaptive Forward Error Correction in Wireless Sensor Networks
  • 2011
  • Ingår i: IECON 2011. - : IEEE conference proceedings. - 9781612849720 ; , s. 3004-3010
  • Konferensbidrag (refereegranskat)abstract
    • The use of wireless technology in the process industry is becoming increasingly important to obtain fast deployment at low cost. However, poor channel quality often leads to retransmissions, which are governed by Automatic Repeat Request (ARQ) schemes. While ARQ is a simple and useful tool to alleviate packet errors, it has considerable disadvantages: retransmissions lead to an increase in energy expenditure and latency. The use of Forward Error Correction (FEC) however offers several advantages. We consider a Hybrid-ARQ-Adaptive-FEC scheme (HAF) based on BCH codes and Channel State Information. This scheme is evaluated on AWGN and fading channels. It is shown that HAF offers significantly improved performance both in terms of energy efficiency and latency, as compared to ARQ.
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45.
  • Eriksson, Oskar, et al. (författare)
  • Predicting scenario doses for robust automated radiation therapy treatment planning
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Methods: The scenario dose prediction pipeline is divided into the prediction of nominal dose from input image and the prediction of scenario dose from nominal dose, each using a deep learning model with U-net architecture. By using a specially developed dose-volume histogram-based loss function, the predicted scenario doses are ensured sufficient target coverage despite the possibility of the training data being non-robust. Deliverable plans may then be created by solving a robust dose mimicking problem with the predictions as scenario-specific reference doses.Results: Numerical experiments are performed using a dataset of 52 intensity-modulated proton therapy plans for prostate patients. We show that the predicted scenario doses resemble their respective ground truth well, in particular while having target coverage comparable to that of the nominal scenario. The deliverable plans produced by the subsequent robust dose mimicking were showed to be robust against the same scenario set considered for prediction.Conclusions: We demonstrate the feasibility and merits of the proposed methodology for incorporating robustness into automated treatment planning algorithms.
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46.
  • Eriksson, Oskar, 1984- (författare)
  • Studies on Tissue Factor with Focus on Cell Signaling and Cancer
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis have explored the functions of the protein Tissue Factor (TF), which together with its ligand coagulation factor VII/VIIa (FVII/FVIIa) forms a proteolytic complex that functions in initiation of blood coagulation and activation of cell signaling.In paper I, the mechanisms behind the observation that TF/FVIIa signaling protects cells from apoptosis were further investigated. Using cell culture models, we found that antiapoptotic signaling by TF/FVIIa requires signaling by the Insulin-like growth factor I receptor (IGF-1R), as synthetic IGF-1R inhibitors and IGF1-R siRNA knock-down abolished the antiapoptotic effect of FVIIa. Furthermore, the IGF-1R translocated to the cell nucleus after FVIIa stimulation, implying a role in regulation of gene expression.Papers II and III describe the discovery that the Eph tyrosine kinase receptors EphB2 and EphA2 are proteolytically cleaved directly by TF/FVIIa. By using mass spectrometry and N-terminal Edman sequencing, the exact cleavage site was identified after a conserved arginine residue in the EphA2/EphB2 ligand binding domains, in agreement with the cleavage preferences of FVIIa. TF and EphA2/EphB2 co-localized in cancer cell lines and FVIIa potentiated ligand-dependent Eph signaling by increasing cytoskeletal remodeling and cell repulsion, demonstrating a novel proteolytical event that modulates Eph receptor signaling.In paper IV, expression of TF was investigated in colorectal cancer in both the stromal and tumor cell compartments by immunohistochemistry using an anti-TF-antibody developed and validated by the Human Protein Atlas project. In normal large intestine, TF was strongly expressed in the innermost pericryptal sheath cell layer lining the epithelium, in a cell population distinct from intestinal pericryptal myofibroblasts. We evaluated TF expression in two colorectal cancer materials, and found that TF was variably present in both the stromal and tumor cell compartments. TF expressed by pericryptal sheath cells was progressively lost after the adenoma-to-carcinoma transition and was a strong predictor of survival in rectal but not colon cancer patients independently of disease stage, histological tumor grade and age.In summary, this thesis demonstrates novel signaling mechanisms for the TF/FVIIa complex, and provides evidence of a hitherto unknown role of TF expressed by a specific population of stromal cells in colorectal cancer.
  •  
47.
  • Eriksson, Oskar, et al. (författare)
  • The Eph Tyrosine Kinase Receptors EphB2 and EphA2 Are Novel Proteolytic Substrates of Tissue Factor/Coagulation Factor VIIa
  • 2014
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:47
  • Tidskriftsartikel (refereegranskat)abstract
    • Tissue factor (TF) binds the serine protease factor VIIa (FVIIa) to form a proteolytically active complex that can trigger coagulation or activate cell signaling. Here we addressed the involvement of tyrosine kinase receptors (RTKs) in TF/FVIIa signaling by antibody array analysis and subsequently found that EphB2 and EphA2 of the Eph RTK family were cleaved in their ectodomains by TF/FVIIa. We used N-terminal Edman sequencing and LC-MS/MS analysis to characterize the cleaved Eph isoforms and identified a key arginine residue at the cleavage site, in agreement with the tryptic serine protease activity of FVIIa. Protease-activated receptor 2 (PAR2) signaling and downstream coagulation activity was non-essential in this context, in further support of a direct cleavage by TF/FVIIa. EphB2 was cleaved by FVIIa concentrations in the subnanomolar range in a number of TF expressing cell types, indicating that the active cellular pool of TF was involved. FVIIa caused potentiation of cell repulsion by the EphB2 ligand ephrin-B1, demonstrating a novel proteolytical event to control Eph-mediated cell segregation. These results define Eph RTKs as novel proteolytical targets of TF/FVIIa and provide new insights into how TF/FVIIa regulates cellular functions independently of PAR2.
  •  
48.
  • Eriksson, Oskar, 1984-, et al. (författare)
  • The Human Platelet as an Innate Immune Cell : Interactions Between Activated Platelets and the Complement System
  • 2019
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10, s. 1-16
  • Forskningsöversikt (refereegranskat)abstract
    • Platelets play an essential role in maintaining homeostasis in the circulatory system after an injury by forming a platelet thrombus, but they also occupy a central node in the intravascular innate immune system. This concept is supported by their extensive interactions with immune cells and the cascade systems of the blood. In this review we discuss the close relationship between platelets and the complement system and the role of these interactions during thromboinflammation. Platelets are protected from complement-mediated damage by soluble and membrane-expressed complement regulators, but they bind several complement components on their surfaces and trigger complement activation in the fluid phase. Furthermore, localized complement activation may enhance the procoagulant responses of platelets through the generation of procoagulant microparticles by insertion of sublytic amounts of C5b9 into the platelet membrane. We also highlight the role of post-translational protein modifications in regulating the complement system and the critical role of platelets in driving these reactions. In particular, modification of disulfide bonds by thiol isomerases and protein phosphorylation by extracellular kinases have emerged as important mechanisms to fine-tune complement activity in the platelet microenvironment. Lastly, we describe disorders with perturbed complement activation where part of the clinical presentation includes uncontrolled platelet activation that results in thrombocytopenia, and illustrate how complement-targeting drugs are alleviating the prothrombotic phenotype in these patients. Based on these clinical observations, we discuss the role of limited complement activation in enhancing platelet activation and consider how these drugs may provide opportunities for further dissecting the complex interactions between complement and platelets.
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49.
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