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2.
  • Enkirch, Theresa, et al. (författare)
  • Hepatitis A outbreak linked to imported frozen strawberries by sequencing, Sweden and Austria, June to September 2018
  • 2018
  • Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 23:41
  • Tidskriftsartikel (refereegranskat)abstract
    • Between June-September 2018, 20 hepatitis A cases were notified in six counties in Sweden. Combined epidemiological and microbiological investigations identified imported frozen strawberries produced in Poland as the source of the outbreak. Sequence analysis confirmed the outbreak strain IB in the strawberries with 100 % identity and the respective batch was withdrawn. Sharing the sequence information internationally led to the identification of 14 additional cases in Austria, linked to strawberries from the same producer.
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5.
  • Alakangas, Lena, et al. (författare)
  • Changes of groundwater quality in sulphide-bearing mine-tailings as a result of remediation at Kristineberg, northern Sweden
  • 2007
  • Ingår i: Mining and the Environment International Conference. - : Centre for Environmental Monitoring, Laurentian University. - 9780886670726
  • Konferensbidrag (refereegranskat)abstract
    • At the Kristineberg mine in northern Sweden, sulphide-rich tailings left open for 50 years were remediated in 1996 by applying double dry cover on one part of an impoundment, and raised groundwater level combined with simple till cover on the other part. Groundwater pipes installed in the impoundment were sampled from 1998 during a period of 6 years. The results showed that the groundwater quality varied considerably in the impoundment, even under the same type of cover. Secondarily retained Fe, S, Mg, Mn and Z were remobilised when the groundwater was raised. In the part with raised groundwater level, the average concentration of Fe ranged from 2700 to 9000mg/l in 1998, and the range for S was 2200 to 7000mg/l. During 2003 the average concentrations had decreased and ranged between 150 and 900 mg/l for Fe and between 130 and 900 mg/l for S. The improvement of the water quality was caused by inflow of less contaminated groundwater and decreasing sulphide oxidation rate. The redox potential generally decreased and pH increased. The concentrations of Cd, Cu and Pb in groundwater decreased rather rapidly all over the impoundment after remediation. In areas with relatively high pH and low redox potential, Al, Cd, Co, Cr, Cu, Fe, Ni, Pb and Zn were almost depleted.
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7.
  • Alakangas, Lena, et al. (författare)
  • Estimation of temporal changes in oxidation rates of sulphides in copper mine tailings at Laver, Northern Sweden
  • 2010
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 408:6, s. 1386-1302
  • Tidskriftsartikel (refereegranskat)abstract
    • Tailings containing pyrrhotite were deposited in an impoundment at a copper mine at Laver, Northern Sweden, which operated between 1936 and 1946. Since then the oxidation of sulphides has acidified recipient water courses and contaminated them with metals. Measurements from surface water sampled in 1993, 2001 and 2004-05 from a brook into which the tailing impoundment drains indicate that the amounts of sulphide-associated elements such as Cu, S and Zn released into the brook have decreased over time, while pH has increased. The mass transport of S in the brook during 1993 and 2001 corresponded well with the amount of S estimated to be released from the tailings by oxidation. Secondary precipitates such as covellite and gypsum, which can trap sulphur, were shown in earlier studies to be present in only low amounts. The annual release of elements from the tailings was estimated from the volume of tailings assumed to oxidise each year, which depends on movement of the oxidation front with time. The results indicate that the oxidation rate in the tailings has decreased over time, which may be due to the increased distance over which oxygen needs to diffuse to reach unoxidised sulphide grains, or their cores, in the tailings.
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8.
  • Alakangas, Lena, et al. (författare)
  • Pilot-scale studies of different covers on unoxidised sulphide-rich tailings, northern Sweden : oxygen diffusion
  • 2010
  • Ingår i: Mine Water and the Environment. - Ostrava : VSB - Technical University Ostrava, Faculty of Mining and Geology, Institute of Environmental Engineering. - 9788024817675 ; , s. 347-350
  • Konferensbidrag (refereegranskat)abstract
    • The efficiency of five cover systems to decrease oxygen intrusion into sulphide-rich tailings was studied in pilot-scale test cells (5x5x3 m(3)). The covers consisted of clayey till, sewage sludge, fine-grained apatite concentrate or Trisoplast (a mixture of a polymer, bentonite and tailings sand) as sealing layers and unspecified till as protective cover. In one reference cell, tailings were uncovered. Oxygen concentrations below the entire covers were highest below the Trisoplast and apatite layers, and lowest below the sewage sludge layer. Effective diffusion coefficients (D-eff) and oxygen fluxes were estimated in the covers with non-oxygen-consuming sealing layers (clayey till and apatite). For the protective covers the Deff ranged between E-09 and E-07 m(2)/s, and for the sealing layers between E-10 and E-09 m(2)/s, and for the entire covers between E-10 and E-08 m(2)/s. Seasonal variations in D-eff were larger within the covers than between the different cover systems. Oxygen fluxes through the entire covers with clayey till and apatite ranged between 0.2 and 4 mole m(2)/year, which was a reduction of more than 99% compared to uncovered dry tailings.
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10.
  • Alakangas, Lena, et al. (författare)
  • Simulation of pyrite oxidation in fresh mine tailings under near-neutral conditions
  • 2012
  • Ingår i: Journal of Environmental Monitoring. - 1464-0325 .- 1464-0333. ; 14:8, s. 2245-2253
  • Tidskriftsartikel (refereegranskat)abstract
    • Sulphidic residual products from ore processing may produce acid rock drainage, when exposed to oxygen and water. Predictions of the magnitude of ARD and sulphide oxidation rates are of great importance in mine planning because they can be used to minimize or eliminate ARD and the associated economic and environmental costs. To address the lack of field data of sulphide oxidation rate in fresh sulphide-rich tailings under near-neutral conditions, determination and simulation of the rate was performed in pilot-scale at Kristineberg, northern Sweden. The quality of the drainage water was monitored, along with oxygen and carbon dioxide concentrations. The chemical composition of the solid tailings was also determined. The field data were compared to predictions from simulations of pyrite oxidation using a 1-D numerical model. The simulations' estimates of the amount of Fe and S released over a seven year period (52 kg and 178 kg, respectively) were in reasonably good agreement with those obtained by analysing the tailings (34 kg and 155 kg, respectively). The discrepancy is probably due to the formation of secondary precipitates such as iron hydroxides and gypsum; which are not accounted for in the model. The observed mass transport of Fe and S (0.05 and 1.0 kg per year, respectively) was much lower than expected on the basis of the simulations and the core data. Neutralization reactions involving carbonates in the tailings result in a near-neutral pH at all depths except at the oxidation front (pH < 5), indicating that the dissolution of carbonates was too slow for the acid to be neutralized, which instead neutralized deeper down in the tailings. This was also indicated by the reduced abundance of solid Ca at greater depths and the high levels of carbon dioxide both of which are consistent with the dissolution of carbonates. It could be concluded that the near-neutral pH in the tailings has no decreasing effect on the rate of sulphide oxidation, but does reduce the concentrations of dissolved elements in the drainage water due to the formation of secondary minerals. This means that sulphide oxidation rates may be underestimated if determined from drainage alone.
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11.
  • Andersson, Lena, et al. (författare)
  • Methodological aspects on measurement of Clara cell protein in urine as a biomarker for airway toxicity, compared with serum levels.
  • 2007
  • Ingår i: Journal of applied toxicology : JAT. - : Wiley. - 0260-437X .- 1099-1263. ; 27:1, s. 60-6
  • Tidskriftsartikel (refereegranskat)abstract
    • The Clara cell protein CC16, secreted from Clara cells in the lung, is discussed as a potential biomarker for toxic effects on the airways. An increased concentration of CC16 in serum may be caused by increased permeability of the lungs, caused by high levels of air pollution. Since CC16 is eliminated by renal excretion, it may be possible to use urine instead of serum samples. Few studies have been conducted on urinary CC16 (U-CC16), however.The aim was to investigate the optimal way of sampling and quantifying CC16 in urine samples and compare CC16 in human serum and urinary samples. Repeated sampling was performed in two groups of healthy subjects. First morning urine, 24 h urine, and matched blood and urine samples were collected.The excretion of U-CC16 increased over the day, e.g. from 0.08 microg h(-1) in the morning to 0.28 microg h(-1) in daytime and 0.16 microg h(-1) in the evening (medians in males). Morning samples (microg h(-1)) from males properly reflected the 24 h excretion (r = 0.91). The best correlation with 24 h excretion was obtained with creatinine-corrected first morning urine samples (r > 0.9). Generally, females had lower excretion of CC16 than males (medians 2.5 microg 24 h(-1) in females and 16 microg 24 h(-1) in males). There was significant intraindividual variation, but the interindividual variation was larger in both groups. There was an association between serum CC16 (S-CC16) and U-CC16 in morning samples. With optimal methods for sampling U-CC16, urine samples may be used in experimental studies of air pollution.
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12.
  • Aranzana-Climent, Vincent, et al. (författare)
  • Translational in vitro and in vivo PKPD modelling for apramycin against Gram-negative lung pathogens to facilitate prediction of human efficacious dose in pneumonia
  • 2022
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier B.V.. - 1198-743X .- 1469-0691. ; 28:10, s. 1367-1374
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: New drugs and methods to efficiently fight carbapenem-resistant gram-negative pathogens are sorely needed. In this study, we characterized the preclinical pharmacokinetics (PK) and pharmacodynamics of the clinical stage drug candidate apramycin in time kill and mouse lung infection models. Based on in vitro and in vivo data, we developed a mathematical model to predict human efficacy. Methods: Three pneumonia-inducing gram-negative species Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were studied. Bactericidal kinetics were evaluated with time-kill curves; in vivo PK were studied in healthy and infected mice, with sampling in plasma and epithelial lining fluid after subcutaneous administration; in vivo efficacy was measured in a neutropenic mouse pneumonia model. A pharmacokinetic-pharmacodynamic model, integrating all the data, was developed and simulations were performed. Results: Good lung penetration of apramycin in epithelial lining fluid (ELF) was shown (area under the curve (AUC)ELF/AUCplasma = 88%). Plasma clearance was 48% lower in lung infected mice compared to healthy mice. For two out of five strains studied, a delay in growth (∼5 h) was observed in vivo but not in vitro. The mathematical model enabled integration of lung PK to drive mouse PK and pharmacodynamics. Simulations predicted that 30 mg/kg of apramycin once daily would result in bacteriostasis in patients. Discussion: Apramycin is a candidate for treatment of carbapenem-resistant gram-negative pneumonia as demonstrated in an integrated modeling framework for three bacterial species. We show that mathematical modelling is a useful tool for simultaneous inclusion of multiple data sources, notably plasma and lung in vivo PK and simulation of expected scenarios in a clinical setting, notably lung infections. © 2022 The Author(s)
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13.
  • Arrazuria, Rakel, et al. (författare)
  • Expert workshop summary : Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
  • 2022
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • The rise in antimicrobial resistance (AMR), and increase in treatment-refractory AMR infections, generates an urgent need to accelerate the discovery and development of novel anti-infectives. Preclinical animal models play a crucial role in assessing the efficacy of novel drugs, informing human dosing regimens and progressing drug candidates into the clinic. The Innovative Medicines Initiative-funded "Collaboration for prevention and treatment of MDR bacterial infections" (COMBINE) consortium is establishing a validated and globally harmonized preclinical model to increase reproducibility and more reliably translate results from animals to humans. Toward this goal, in April 2021, COMBINE organized the expert workshop "Advancing toward a standardized murine model to evaluate treatments for AMR lung infections". This workshop explored the conduct and interpretation of mouse infection models, with presentations on PK/PD and efficacy studies of small molecule antibiotics, combination treatments (beta -lactam/beta -lactamase inhibitor), bacteriophage therapy, monoclonal antibodies and iron sequestering molecules, with a focus on the major Gram-negative AMR respiratory pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Here we summarize the factors of variability that we identified in murine lung infection models used for antimicrobial efficacy testing, as well as the workshop presentations, panel discussions and the survey results for the harmonization of key experimental parameters. The resulting recommendations for standard design parameters are presented in this document and will provide the basis for the development of a harmonized and bench-marked efficacy studies in preclinical murine pneumonia model.
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14.
  • Arrazuria, Rakel, et al. (författare)
  • Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents
  • 2022
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
  • Forskningsöversikt (refereegranskat)abstract
    • Antimicrobial resistance has become one of the greatest threats to human health, and new antibacterial treatments are urgently needed. As a tool to develop novel therapies, animal models are essential to bridge the gap between preclinical and clinical research. However, despite common usage of in vivo models that mimic clinical infection, translational challenges remain high. Standardization of in vivo models is deemed necessary to improve the robustness and reproducibility of preclinical studies and thus translational research. The European Innovative Medicines Initiative (IMI)-funded "Collaboration for prevention and treatment of MDR bacterial infections" (COMBINE) consortium, aims to develop a standardized, quality-controlled murine pneumonia model for preclinical efficacy testing of novel anti-infective candidates and to improve tools for the translation of preclinical data to the clinic. In this review of murine pneumonia model data published in the last 10 years, we present our findings of considerable variability in the protocols employed for testing the efficacy of antimicrobial compounds using this in vivo model. Based on specific inclusion criteria, fifty-three studies focusing on antimicrobial assessment against Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii were reviewed in detail. The data revealed marked differences in the experimental design of the murine pneumonia models employed in the literature. Notably, several differences were observed in variables that are expected to impact the obtained results, such as the immune status of the animals, the age, infection route and sample processing, highlighting the necessity of a standardized model.
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15.
  • Becker, K., et al. (författare)
  • Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis
  • 2021
  • Ingår i: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 73
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The clinical-stage drug candidate EBL-1003 (apramycin) represents a distinct new subclass of aminoglycoside antibiotics for the treatment of drug-resistant infections. It has demonstrated best-in-class coverage of resistant isolates, and preclinical efficacy in lung infection models. However, preclinical evidence for its utility in other disease indications has yet to be provided. Here we studied the therapeutic potential of EBL-1003 in the treatment of complicated urinary tract infection and acute pyelonephritis (cUTI/AP). Methods: A combination of data-base mining, antimicrobial susceptibility testing, time-kill experiments, and four murine infection models was used in a comprehensive assessment of the microbiological coverage and efficacy of EBL-1003 against Gram-negative uropathogens. The pharmacokinetics and renal toxicology of EBL-1003 in rats was studied to assess the therapeutic window of EBL-1003 in the treatment of cUTI/AP. Findings: EBL-1003 demonstrated broad-spectrum activity and rapid multi-log CFU reduction against a phenotypic variety of bacterial uropathogens including aminoglycoside-resistant clinical isolates. The basicity of amines in the apramycin molecule suggested a higher increase in positive charge at urinary pH when compared to gentamicin or amikacin, resulting in sustained drug uptake and bactericidal activity, and consequently in potent efficacy in mouse infection models. Renal pharmacokinetics, biomarkers for toxicity, and kidney histopathology in adult rats all indicated a significantly lower nephrotoxicity of EBL-1003 than of gentamicin. Interpretation: This study provides preclinical proof-of-concept for the efficacy of EBL-1003 in cUTI/AP. Similar efficacy but lower nephrotoxicity of EBL-1003 in comparison to gentamicin may thus translate into a higher safety margin and a wider therapeutic window in the treatment of cUTI/API. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. © 2021 The Author(s)
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16.
  • Berg, Anders, et al. (författare)
  • Benefiting from an open-ended experiment? A comparison of attitudes to, and outcomes of, an expository versus an open-inquiry version of the same experiment
  • 2003
  • Ingår i: International Journal of Science Education. - : Informa UK Limited. - 0950-0693 .- 1464-5289. ; 25:3, s. 351-372
  • Tidskriftsartikel (refereegranskat)abstract
    • In this article we compare outcomes of an open-inquiry and an expository version of a chemistry laboratory experiment at university level for 190 students. The aim of the study was to investigate if these two versions would result in different outcomes depending on the students' attitudes towards learning. We used a questionnaire to find out their attitude position prior to the laboratory experiment. The outcome in the different version of the experiment was evaluated by interviews, questions asked during the experiment and students self-evaluations. The main findings were that the open-inquiry version shows the most positive outcomes regarding learning outcome, preparation time, time spent in the laboratory and student perception of the experiment. The students with low attitude position needed more support to meet the challenge of an open-inquiry experiment, the support being a clearer explanation of the aims, and feedback from the instructor during the experiment.
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17.
  • Bergström, Ida, et al. (författare)
  • Annexin A1 expression in blood mononuclear cells : a potential marker of glucocorticoid activity in patients with coronary artery disease
  • 2014
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • An imbalance between pro- and anti-inflammatory actions is believed to drive progression of atherosclerosis. Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of anti-inflammatory effects of glucocorticoids. Here, we investigated whether expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) was altered in patients with coronary artery disease (CAD) and also related findings to glucocorticoid sensitivity ex vivo.We included 57 patients 6-12 months after acute coronary syndrome (ACS), 10 patients with ACS, and healthy controls. AnxA1 mRNA was measured in PBMCs and AnxA1 protein was assessed in monocytes and lymphocyte subsets by flow cytometry. In post-ACS patients and controls, glucocorticoid sensitivity was determined by measuring inhibitory effects of dexamethasone on LPS46 induced cytokine secretion.AnxA1 mRNA levels in PBMCs were higher in patients compared with controls, although most pronounced in ACS patients. AnxA1 protein was most abundant in the monocyte fraction. ACS patients exhibited the highest levels of cell surface-associated AnxA1 protein while levels in post-ACS patients and controls were similar. Ex vivo assays showed that PBMCs from post-ACS patients were more prone to release IL-6. Glucocorticoid sensitivity correlated with cell surface-associated AnxA1 protein in peripheral monocytes. Dexamethasone also induced upregulation of AnxA1 mRNA.AnxA1 expression in PBMCs is closely associated with glucocorticoid actions and cell surface associated AnxA1 appears to be a marker of glucocorticoid sensitivity. Although still speculative, a “normal” expression of cell surface-associated AnxA1 in post-ACS patients may suggest that glucocorticoid actions in vivo are insufficient to provide adequate anti-inflammatory effects in these patients.
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18.
  • Bergström, Ida, et al. (författare)
  • Annexin A1 in blood mononuclear cells from patients with coronary artery disease : Its association with inflammatory status and glucocorticoid sensitivity
  • 2017
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.
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19.
  • Bergström, Ida, et al. (författare)
  • Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells : Potential implications for coronary artery disease
  • 2014
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Increased proportions of circulating proinflammatory CD56+ T cells have been reported in patients with coronary artery disease (CAD). Yet, little is known about regulation of these cells. In the present study, we investigated the expression and potential role of the glucocorticoid-mediated protein annexin A1 (AnxA1) in CD56+ and CD56-T cell subsets, with focus on CAD.Methods and Results: We included totally 52 healthy individuals, 28 patients with acute coronary syndrome (ACS) and 57 patients with a history of ACS. AnxA1 mRNA expression was assessed in peripheral blood mononuclear cells. AnxA1 protein expression (total and cell surface-associated) was measured by whole blood flow cytometry in circulating CD56+ and CD56- T cell subsets. Furthermore, inhibitory effects of dexamethasone and/or recombinant AnxA1 on cytokine secretion by CD56+ and CD56- T cells were explored in vitro. We found that CD56+ T cells (the majority CD8+), expressed higher levels of AnxA1 mRNA and protein than did CD56- T cells. When comparing CAD patients with healthy controls, significantly higher levels of cell surface-associated AnxA1 expression were seen in patients, most pronounced in ACS patients. In vitro, dexamethasone reduced cytokine secretion by CD56+ T cells, whereas AnxA1 alone had no effect, and AnxA1 combined with dexamethasone abolished the dexamethasone-induced suppressive effects.Conclusion: AnxA1 was expressed more abundantly in proinflammatory CD56+ T cells. Patients with ACS exhibited increased levels of cell surface-associated AnxA1, thus indicating increased activation of the AnxA1 pathway. Our data further suggested that AnxA1 might counteract glucocorticoid mediated anti-inflammatory effects in T cells.
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20.
  • Bergström, Ida, et al. (författare)
  • Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease
  • 2012
  • Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 224:2, s. 515-520
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There is emerging evidence for CD8(+) T cell alterations in blood from patients with coronary artery disease (CAD). We examined whether the distribution and phenotype of CD8(+)CD56(+) T cells differed according to the clinical manifestation of CAD. less thanbrgreater than less thanbrgreater thanMethods: Patients with acute coronary syndrome (ACS, n = 30), stable angina (SA, n = 34) and controls (n = 36) were included. Blood was collected before and up to 12 months after referral for coronary investigation. CD8(+)CD56(+) T cells were assessed by flow cytometry for expression of surface markers, apoptosis, and intracellular expression of cytokines. less thanbrgreater than less thanbrgreater thanResults: The proportions of CD8(+)CD56(+) T cells were significantly higher in both ACS and SA patients compared with controls, and remained so after 3 and 12 months. This was independent of age, sex, systemic inflammation and cytomegalovirus seropositivity. CD8(+)CD56(+) T cells differed from CD8(+)CD56(-) T cells in terms of lower CD28 expression and fewer apoptotic cells. Both CD8(+) T cell subsets were positive for interferon (IFN)-gamma and tumor necrosis factor, although IFN-gamma was significantly more confined to the CD8(+)CD56(+) T cells. less thanbrgreater than less thanbrgreater thanConclusion: The persistent accumulation of CD8(+)CD56(+) T cells in ACS and SA patients share several features with immunological aging. It also contributes to a larger IFN-gamma(+) pool in blood, and may thereby hypothetically drive the atherosclerotic process in a less favorable direction.
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23.
  • Björck, Lena, 1959, et al. (författare)
  • Body mass index in women aged 18 to 45 and subsequent risk of heart failure.
  • 2020
  • Ingår i: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 27:11, s. 1165-1174
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence of heart failure (HF) is decreasing in older ages, but increasing rates have been observed among younger persons in Sweden. Therefore, we investigated the relationship between risk of hospitalization for HF and body mass index (BMI).This was a prospective registry-based cohort study. We included 1,374,031 women aged 18-45 years (mean age 27.9 years) who gave birth during 1982-2014, and were registered in the Medical Birth Register. Information on hospitalization because of HF was collected through linkage to the National Inpatient Register.Compared to women with a BMI of 20-<22.5kg/m2, women with a BMI of 22.5-<25.0 had a hazard ratio (HR) of 1.24 (95% confidence interval (CI), 1.10-1.39) for HF after adjustment for age, year, parity, baseline disorders, smoking, and education. The HR (95% CI) increased to 1.56 (1.36-1.78), 2.39 (2.05-2.78), 2.82 (2.43-3.28), and 4.51 (3.63-5.61) in women with a BMI of 25-<27.5, 27.5-<30, 30-<35, and ≥35kg/m2, respectively. The multiple-adjusted HRs (95% CI) associated with risk of HF per one-unit increase in BMI in women with a BMI≥22.5kg/m2 ranged from 1.01 (0.97-1.06) for HF related to valvular disease to 1.14 (1.12-1.15) for coronary heart disease, diabetes, or hypertension.Increasing body weight was strongly associated with the risk of early HF in women. Compared with lean women, the risk for HF started to increase at high-normal BMI levels, and was nearly five-fold in women with a BMI≥35kg/m2.
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24.
  • Björck, Lena, 1959, et al. (författare)
  • Trends in survival of Swedish men and women with heart failure from 1987 to 2014: a population-based case-control study
  • 2022
  • Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 9:1, s. 486-495
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To compare trends in short-term and long-term survival of patients with heart failure (HF) compared with controls from the general population. Methods and results We used data from the Swedish National Inpatient Registry to identify all patients aged >= 18 years with a first recorded diagnosis of HF between 1 January 1987 and 31 December 2014 and compared them with controls matched on age and sex from the Total Population Register. We included 702 485 patients with HF and 1 306 183 controls. In patients with HF aged 18-64 years, short-term (29 days to 6 months) and long-term mortality (>11 years) decreased from 166 and 76.6 per 1000 person-years in 1987 to 2000 to 99.6 and 49.4 per 1000 person-years, respectively, in 2001 to 2014. During the same period, mortality improved marginally, in those aged >= 65 years: short-time mortality from 368.8 to 326.2 per 1000 person-years and long-term mortality from 219.6 to 193.9 per 1000 person-years. In 1987-2000, patients aged <65 years had more than three times higher risk of dying at 29 days to 6 months, with an hazard ratio (HR) of 3.66 [95% confidence interval (CI) 3.46-3.87], compared with controls (P < 0.0001) but substantially higher in 2001-2014 with an HR of 11.3 (95% CI 9.99-12.7, P < 0.0001). HRs for long-term mortality (6-10 and >11 years) increased moderately from 2.49 (95% CI 2.41-2.57) and 3.16 (95% CI 3.07-3.24) in 1987-2000 to 4.35 (95% CI 4.09-4.63) and 4.11 (95% CI 3.49-4.85) in 2001-2014, largely because survival among controls improved more than that among patients with HF (P < 0.0001). Conclusions Absolute survival improved in HF patients aged <65 years, but only marginally so in those aged >= 65 years. Compared with controls, both short-term and long-term relative risk of dying increased, especially in younger patients with HF.
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25.
  • Björkman Lundberg, Kerstin, et al. (författare)
  • Compliance to National Guidelines for Pharmaceutical Treatment of Sleeping Disorders among Elderly Incident Patients in Sweden in PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, vol 20, issue , pp S203-S203
  • 2011
  • Ingår i: PHARMACOEPIDEMIOLOGY AND DRUG SAFETY. - : John Wiley and Sons. ; , s. S203-S203
  • Konferensbidrag (refereegranskat)abstract
    • Background:National guidelines for pharmaceutical treatmentof sleeping disorders among elderly state that zopicloneshould be the first choice and that other hypnotics,such as long acting benzodiazepines and propiomazine,should be avoided. According to aggregated data describingprevalent users compliance to guidelines is fairly high. Objectives:The objective of this study was to investigatechoice and volume (DDD) of substance among incidentusers 75 years and older (75+) of hypnotics (N05C) in Swedenand compare between different county councils andwith incident users below 75 years of age. Methods:Data from the Swedish Prescribed Drug registercovering all dispensed prescriptions in Sweden was analyzedfor incident users of hypnotics (15–44, 45–64, 65–74 and 75+ years of age). Incident users were defined aspeople who filled a prescription (index date) of a hypnotic(N05C) during the period December 2009 - November2010 and had not filled any prescription for a hypnotic duringa wash-out period of 24 months before the index date. Results:Among incident patients 75+ (n= 38,620) zopiclone(52.9%), zolpidem (25.4%), and propiomazine(10.4%) were the most frequently used hypnotics. Therewere however differences between different county councilsin Sweden, with zopiclone ranging from 30 % to 68 %. Theincidence for recommended and appropriate hypnoticsincreased with increasing age, whereas the incidence ofinappropriate hypnotics did not. The prescribed volume ofinappropriate hypnotics was generally larger than the prescribedvolume of recommended hypnotics. Conclusions:The compliance to current guidelines onchoice of hypnotics for the elderly is fairly good, althoughthere is considerable variation between county councils.There are tendencies towards larger mean volumes of inappropriatehypnotics, although further studies are needed toconfirm these findings. Another aspect of quality in treatmentwith sleeping agents is to which extent incident userscontinue their treatment and for how long. This is an issuefor further research.
  •  
26.
  • Boman, Inga-Lill, et al. (författare)
  • First steps in designing a videophone for people with dementia : Identification of users' potentials and the requirements of communication technology
  • 2012
  • Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 1748-3107 .- 1748-3115. ; sept:5, s. 356-363
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To identify, based on the literature, people with dementia´s potentials to manage an easy-to-use videophone, and to develop a videophone requirement specification for people with dementia.Method:The study is based on the Inclusive Design method, utilising the first two of four phases. Content analyses of literature reviews were used to identify users´potentials for managing a videophone and to gather recommendations regarding communication technology design for the target group. Existing videophones in Sweden were examined regarding potentia fit to users with dementia.Findings: This led to detailed identification of cognitive, physical and psychosocial challenges that people with dementia will probably have when using an ordinary telephone or videophone. A requirement specification for videophone design to fit users with dementia was formulated, with the seven principles of Universal Design as a framework.Conclusions: The requirement specification presented here is aimed at designing a videophone but might also facilitate design of other products for people with dementia, particularly in the field of communication technology. Based on this, further work will focus on developing a design concept and a prototype to be empirically tested by people with dementia and their significant others, i.e. the final two design process phases.
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27.
  • Borell, Lena, et al. (författare)
  • Kognitiva köket - framtidens kök
  • 2010
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Äldre personer som har en demenssjukdom eller andra medicinska diagnoser som kan leda till kognitiva problem och som bor i egna hem är en växande grupp. Samtidigt så förväntas alla oavsett funktionsnedsättning kunna hantera matlagning och andra köksrelaterade aktiviteter på egen hand. Personer med kognitiva problem, och personer som arbetar med denna grupp definierar problem relaterade till matlagning och att hålla ordning i köket som några av de viktigaste att lösa (Wherton and Monk 2008). Att kunna utföra köksrelaterade aktiviteter betraktas som något som höjer livskvaliteten. Trots det växande behovet av att kunna skapa köksmiljöer och köksprodukter, både generellt och med individuella anpassningar, finns det i dag ingen samlad kunskap om hur sådana miljöer och produkter bäst kan utformas. I det här projektet ses köket som en plats där flera dimensioner av livet pågår. Förutom matlagning och förvaring av mat så är köket även en plats för socialt umgänge, och utgör vardagens nav. Kökets roll i hemmet är alltså central. Projektet utgår från att det är möjligt att skapa inkluderande köksmiljöer som tar hänsyn till personer med nedsatt kognition, men som samtidigt förenklar för alla. Modern design av kök handlar idag mycket om eleganta ytor och dolda, och därmed svårdefinierade, funktioner vilket skapar problem för personer med kognitiva funktionsnedsättningar. Dessa problem måste lyftas fram och diskuteras för att kunna utforma framtida inkluderande köksmiljöer. Syftet med projektet är att, i dialog med intressenter och experter inom området, sammanställa och generera kunskap om hur kök och köksprodukter kan designas för att underlätta för äldre människor med kognitiva nedsättningar att kunna använda sina kök utan problem.
  •  
28.
  • Borgquist, Lars, et al. (författare)
  • The Relationship between Health-state Utilities and the SF-12 in a General Population
  • 1999
  • Ingår i: Medical decision making. - : SAGE. - 1552-681X .- 0272-989X. ; 19:2, s. 128-140
  • Tidskriftsartikel (refereegranskat)abstract
    • It would be a major advance if quality-of-life instruments could be translated into health- state utilities. The aim with this study was to investigate the relationship between the SF-12 and health-state utilities, based on responses to a postal questionnaire sent to a random sample of 8,000 inhabitants, aged 20-84 years, in the general population. The questionnaire included the SF-12, a rating-scale (RS) question, and a time-tradeoff (TTO) question; the response rate was 68%. Age, gender, and the 12 items of the SF- 12 were used as explanatory variables in a linear regression analysis of the health- state utilities. The regression models explained about 50% of the variance in the RS answers and about 25% of the variance in the TTO answers. Most of the SF-12 items were related to the health-state utilities in the expected ways, with especially strong results for the RS method. The results suggest that the SF-12 can be converted to health-state utilities, but that further work is needed to reliably estimate the conversion function. Key words: health status; SF-12; rating scale; time-tradeoff; health-related quality of life; health-state utilities; population study. (Med Decis Making 1999;19:128- 140)
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29.
  • Chung, Rosanna W S, et al. (författare)
  • Lutein exerts anti-inflammatory effects in patients with coronary artery disease.
  • 2017
  • Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 262, s. 87-93
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients.METHODS: Lutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene, α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media.RESULTS: Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = -0.366, p < 0.001) and follow-up (r = -0.546, p < 0.001). Ex vivo, lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1β (p < 0.01) and TNF (p < 0.05), and also reduced IL-6, IL-1β and TNF mRNA expression (p < 0.05).CONCLUSIONS: Clinical findings highlighted the inverse association between lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients.
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30.
  • Claesson, Lena, et al. (författare)
  • Expert Competence in Remote Diagnostics : Industrial Interests, Educational Goals, Flipped Classroom & Laboratory Settings
  • 2018
  • Ingår i: Online Engineering &amp; Internet of Things. - Cham : Springer. - 9783319643526 - 9783319643519 ; , s. 438-451
  • Konferensbidrag (refereegranskat)abstract
    • The manufacturing industry are dependent of engineering expertise. Currently the ability to supply the industry with engineering graduates and staff that have an up-to- date and relevant competences might be considered as a challenge for the society. In this paper an education approach is presented where academia - industry - research institutes cooperate around the development and implementation of master level courses. The methods applied to reach the educational goals, concerning expert competence within remote diagnostics, have been on site and remote lectures given by engineering, medical and metrology experts. The pedagogical approach utilized has been flipped classroom. The main results show that academic courses developed in cooperation with industry requires flexibility, time and effort from the involved partners. The evaluation interviews indicate that student are satisfied with the courses and pedagogical approach but suggests more reconciliation meetings for course development. Labs early in the course was considered good, and division of labs at the system and the component level. However further long- term studies of evaluation of impact is necessary.
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31.
  • Dikaiou, Pigi, et al. (författare)
  • Obesity, overweight and risk for cardiovascular disease and mortality in young women
  • 2021
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 28:12, s. 1351-1359
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The aim of this study was to investigate the relation between body mass index (BMI) in young women, using weight early in pregnancy as a proxy for pre-pregnancy weight, and risk for early cardiovascular disease (CVD) and mortality. Methods and results In this prospective, registry-based study, we used weight data in early pregnancy from women, registered in the Swedish Medical Birth Registry, and who gave birth between 1982 and 2014 (n = 1,495,499; median age 28.3 years). Of the women, 118,212 (7.9%) were obese (BMI >= 30 kg/m(2)) and 29,630 (2.0%) severely obese (BMI >= 35 kg/m(2)). After a follow-up of median 16.3 years, we identified 3295 and 4375 cases of acute myocardial infarction (AMI) and ischemic stroke (IS) corresponding to 13.4 and 17.8 per 100,000 observation years, respectively, occurring at mean ages of 49.8 and 47.3 years. Compared to women with a BMI 20-<22.5 kg/m(2), the hazard ratio (HR) of AMI increased with higher BMI from 1.40 (95% confidence interval (CI) 1.27-1.54) among women with BMI 22.5-<25.0 kg/m(2) to 4.71 (95% CI 3.88-5.72) among women with severe obesity, with similar findings for IS and CVD death, after adjustment for age, pregnancy year, parity and comorbidities at baseline. Women with BMI 30-<35.0 and >= 35 kg/m(2) had increased all-cause mortality with adjusted HR 1.53 (95% CI 1.43-1.63) and 1.83 (95% CI 1.63-2.05), respectively. Conclusion A significant increase in the risk for early AMI, IS and CVD death was noticeable in overweight young women, with a marked increase in obese women.
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32.
  • Edgren, M., et al. (författare)
  • High dose-rate brachytherapy of prostate cancer utilising Iridium-192 after-loading technique: technical and methodological aspects
  • 2006
  • Ingår i: Int J Oncol. - 1019-6439. ; 29:6, s. 1517-24
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to focus on certain characteristic problems associated with Iridium-192 high dose-rate brachytherapy (Ir-192 HDR-BT) in combination with external beam radiation therapy (EBRT) in the treatment of patients with localised prostate cancer. Over a period of 16 years, >2,000 patients with prostate cancer have been treated in Sweden with a combination of two fractions of 10 Gy Ir-192 HDR-BT and 50 Gy of fractionated EBRT. Although this treatment is usually well tolerated, there are biological and technical factors to be considered before and during the treatment of the patient to avoid side effects or under-treatment of the target volume. Some of the problems facing the doctors are transducer stability, needle deviation, target definition, target motion, pubic arch interference, concomitant diseases and tolerance doses for different organs at risk. These problems are discussed and possible solutions are presented in this study.
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33.
  • Edqvist, Jon, 1988, et al. (författare)
  • Severe COVID-19 Infection in Type 1 and Type 2 Diabetes During the First Three Waves in Sweden.
  • 2023
  • Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:3, s. 570-578
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 2 diabetes is an established risk factor for hospitalization and death in COVID-19 infection, while findings with respect to type 1 diabetes have been diverging.Using nationwide health registries, we identified all patients aged ≥18 years with type 1 and type 2 diabetes in Sweden. Odds ratios (ORs) describe the general and age-specific risk of being hospitalized, need for intensive care, or dying, adjusted for age, socioeconomic factors, and coexisting conditions, compared with individuals without diabetes. Machine learning models were used to find predictors of outcomes among individuals with diabetes positive for COVID-19.Until 30 June 2021, we identified 365 (0.71%) and 11,684 (2.31%) hospitalizations in 51,402 and 504,337 patients with type 1 and 2 diabetes, respectively, with 67 (0.13%) and 2,848 (0.56%) requiring intensive care unit (ICU) care and 68 (0.13%) and 4,020 (0.80%) dying (vs 7,824,181 individuals without diabetes [41,810 hospitalizations (0.53%), 8,753 (0.11%) needing ICU care, and 10,160 (0.13%) deaths). Although those with type 1 diabetes had moderately raised odds of being hospitalized (multiple-adjusted OR 1.38 [95% CI 1.24-1.53]), there was no independent effect on ICU care or death (OR of 1.21 [95% CI 0.94-1.52] and 1.13 [95% CI 0.88-1.48], respectively). Age and socioeconomic factors were the dominating features for predicting hospitalization and death in both types of diabetes.Type 2 diabetes was associated with increased odds for all outcomes, whereas patients with type 1 diabetes had moderately increased odds of hospitalization but not ICU care and death.
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34.
  • Ekdahl, Anna-Lena, et al. (författare)
  • Matematik i förskoleklassen VA-MER : Ett samverkansprojekt mellan Vaggeryds kommun och Mathematics Education Research
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • De senaste åren har en rad förändringar gällande förskoleklassen genomförts. Den 1 juli 2016 fick förskoleklassen en egen del i läroplanen och från och med läsåret 2018/19 blev förskoleklassen obligatorisk och omfattas nu av skolplikten. Det förändrade uppdraget i förskoleklassen samt det obligatoriska kartläggningsmaterialet, har ökat lärares behov av att möta uppdraget. Kartläggningsmaterialet i matematiskt tänkande ska hjälpa lärare att tidigt identifiera elever som visar en indikation på att inte nå de kunskapskrav som sen ska uppnås i årskurs 3 i grundskolan. Däremot saknas direkta implikationer för undervisning som stimulerar alla elevers möjlighet att utveckla sina förmågor i matematik.I ett nystartat samverkansprojekt mellan Vaggeryds kommun och Högskolan för Lärande och Kommunikation kommer kommunens alla lärare i förskoleklass att arbeta tillsammans med forskare tillhörande forskargruppen i matematik (MER-gruppen), i syfte att stärka likvärdighet i utbildningen inom Vaggeryd kommun.Syftet med projektet är att se hur en pedagogisk verksamhet i samverkan med forskare kan bidra till att lärarna:utvecklar förmågan att diskutera ämnesinnehåll i matematikundervisningen,utvecklar förmågan att utifrån kartläggningsmaterialet diskutera didaktiska implikationerna för undervisning,gemensamt bygger ett fundament i matematikundervisningen, med stöd av aktuell forskning, i syfte att utveckla alla elevers förmågor i matematik.Erfarenheter från ett nyligen avslutat forskningsprojekt där lärare och forskare i tätt samarbete genomförde och reflekterade över undervisningsaktiviteter, visar att detta verkade vara en framgångsrik modell för att utveckla undervisning. Därför väljs ett liknande upplägg i detta samverkansprojekt.I den inledande fasen av projektet träffas lärargruppen och forskarna en gång per månad. Träffarna förläggs på kommunens skolor. De påbörjade samtalen mellan deltagarna i samverkansprojektet visar att det finns ett stort behov av att diskutera matematikundervisning och att utveckla ett målinriktat arbete som främjar alla elevers möjligheter att lära matematik.
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35.
  • Erhardt, Sophie, et al. (författare)
  • Connecting Inflammation with Glutamate Agonism in Suicidality
  • 2013
  • Ingår i: Neuropsychopharmacology. - : Nature Publishing Group: Open Access Hybrid Model Option A. - 0893-133X .- 1740-634X. ; 38:5, s. 743-752
  • Tidskriftsartikel (refereegranskat)abstract
    • The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the Montgomery Asberg Depression Rating Scale (MADRS). We found that QUIN, but not KYNA, was significantly elevated in the CSF of suicide attempters (Pandlt;0.001). As predicted, the increase in QUIN was associated with higher levels of CSF interleukin-6. Moreover, QUIN levels correlated with the total scores on Suicide Intent Scale. There was a significant decrease of QUIN in patients who came for follow-up lumbar punctures within 6 months after the suicide attempt. In summary, we here present clinical evidence of increased QUIN in the CSF of suicide attempters. An increased QUIN/KYNA quotient speaks in favor of an overall NMDA-receptor stimulation. The correlation between QUIN and the Suicide Intent Scale indicates that changes in glutamatergic neurotransmission could be specifically linked to suicidality. Our findings have important implications for the detection and specific treatment of suicidal patients, and might explain the observed remedial effects of ketamine. Neuropsychopharmacology (2013) 38, 743-752; doi:10.1038/npp.2012.248; published online 9 January 2013
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36.
  • Erlandsson, Lena, et al. (författare)
  • Joining chain-expressing and -nonexpressing B cell populations in the mouse
  • 2001
  • Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 194:5, s. 557-570
  • Tidskriftsartikel (refereegranskat)abstract
    • The diphtheria toxin A chain (DTA) was gene targeted into the Joining chain (J chain) locus to create a mouse strain selecting against J chain-expressing cells, JDTA mice. Serum immunoglobulin (Ig)M and serum IgG were reduced six to eightfold, while serum IgA was elevated 14-fold in these mice. JDTA mice were immune competent although the serum Ig response compared with wild-type mice was reduced sixfold at day 14 but only fourfold at day 45 after immunization. Exchanging the DTA gene with a cDNA for c-myc resulted in mice with a distinct phenotype with increased Ig production and enhanced humoral immune responses. Analysis of single B cells stimulated by lipopolysaccharide in vitro using reverse transcription-polymerase chain reaction showed that J chain-nonexpressing B cells could be detected that had a secretory phenotype as determined by an abundance of transcript for secretory IgM. Finally, limiting dilution analysis of peripheral B cells showed that J chain expression was a clonal property already established in naive, peripheral B lymphocytes.
  •  
37.
  • Esgard, Veronica Frey, et al. (författare)
  • Diagnostic methods and written advice for acute otitis media in primary health care
  • 2024
  • Ingår i: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Otomicroscopy and pneumatic methods are superior to otoscopy alone in diagnosing acute otitis media (AOM). There is a lack of knowledge regarding the use of different diagnostic methods for AOM in primary health care in Sweden and Norway. Methods: This cross-sectional study included a questionnaire completed by general practitioners (GPs) and specialist trainees (STs/residents/registrars) working in primary care in Sweden and Norway. Multivariable binary logistic regressions were performed to evaluate the use of diagnostic methods and written advice adjusted for educational level, sex and country. Results: Otoscopy was the most frequently used method. Sweden had greater access to the more accurate diagnostic methods. In Norway, the following methods were used to a lesser extent: pneumatic otoscopy, adjusted OR 0.15 (95% CI 0.10-0.23; p < .001), otomicroscopy, adjusted OR 0.013 (95% CI 0.070-0.027; p < .001), pneumatic otomicroscopy, adjusted OR 0.028 (95% CI 0.010-0.078; p < .001) and tympanometry, adjusted OR 0.31 (95% CI 0.21-0.45; p < .001). Written advice was used to a greater extent in Norway, adjusted OR 4.5 (95% CI 3.1-6.7; p < .001). The STs used pneumatic otoscopy and pneumatic otomicroscopy to a lesser extent, adjusted OR 0.65 (95% CI 0.45-0.93; p = .019) and 0.63 (95% CI 0.43-0.92; p = .016). Conclusions: Swedish physicians both used and had greater access to the significantly better diagnostic methods compared with Norwegian physicians while the opposite applied to the use of written information. The GPs used pneumatic otoscopy and pneumatic otomicroscopy to a greater extent than STs. Compared with 2012, the Swedish physicians now more frequently used pneumatic otoscopy.
  •  
38.
  • Eskilsson, Lena, et al. (författare)
  • Film Tourism collaborations: a critical analysis of INTERREG destination development projects
  • 2018
  • Ingår i: The Routledge Handbook on Popular Culture and Tourism. - 9781138678354 - 9781315559018
  • Bokkapitel (refereegranskat)abstract
    • This chapter discusses the different stakeholders that take part in film tourism development projects, how do they collaborate, and what is actually possible to achieve? It is a critical analysis especially when it comes to the selection of stakeholders, the project process and potential outcomes in EU-funded INTERREG projects. The analysis contributes to enhance the knowledge about the different stakeholders involved. It is evident that a new stakeholder has emerged in film tourism development projects; film commissions. Moreover, the analysis shows that it is important that a diverse range of partners collaborate. However, organizations sometimes weak knowledge of the phenomenon in play as well as of each other’s work creates problems especially in the beginning. The idea of measurability is another complicating factor since there are conflicting understandings of what is possible to measure within collaborating organizations. There is also a search for best cases that can be used as role models that totally neglects local characteristics, which raises questions of transferability. What can be concluded is that projects such as these can make a difference to single destinations with for example new policies being developed, local and international networks created and possibilities for new tourism development.
  •  
39.
  •  
40.
  • Frey Esgård, Veronica, et al. (författare)
  • Diagnostic methods and written advice for acute otitis media in primary health care
  • 2024
  • Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis. - 0281-3432 .- 1502-7724.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Otomicroscopy and pneumatic methods are superior to otoscopy alone in diagnosing acute otitis media (AOM). There is a lack of knowledge regarding the use of different diagnostic methods for AOM in primary health care in Sweden and Norway.Methods: This cross-sectional study included a questionnaire completed by general practitioners (GPs) and specialist trainees (STs/residents/registrars) working in primary care in Sweden and Norway. Multivariable binary logistic regressions were performed to evaluate the use of diagnostic methods and written advice adjusted for educational level, sex and country.Results: Otoscopy was the most frequently used method. Sweden had greater access to the more accurate diagnostic methods. In Norway, the following methods were used to a lesser extent: pneumatic otoscopy, adjusted OR 0.15 (95% CI 0.10–0.23; p < .001), otomicroscopy, adjusted OR 0.013 (95% CI 0.070–0.027; p < .001), pneumatic otomicroscopy, adjusted OR 0.028 (95% CI 0.010–0.078; p < .001) and tympanometry, adjusted OR 0.31 (95% CI 0.21–0.45; p < .001). Written advice was used to a greater extent in Norway, adjusted OR 4.5 (95% CI 3.1–6.7; p < .001). The STs used pneumatic otoscopy and pneumatic otomicroscopy to a lesser extent, adjusted OR 0.65 (95% CI 0.45–0.93; p = .019) and 0.63 (95% CI 0.43–0.92; p = .016).Conclusions: Swedish physicians both used and had greater access to the significantly better diagnostic methods compared with Norwegian physicians while the opposite applied to the use of written information. The GPs used pneumatic otoscopy and pneumatic otomicroscopy to a greater extent than STs. Compared with 2012, the Swedish physicians now more frequently used pneumatic otoscopy.
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41.
  •  
42.
  • Grönwall, Caroline, et al. (författare)
  • A Comprehensive Evaluation of the Relationship Between Different IgG and IgA Anti-Modified Protein Autoantibodies in Rheumatoid Arthritis
  • 2021
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), and malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. In this comprehensive study, we analyze 30 different IgG and IgA AMPA reactivities to Cit, Carb, KAc, and MAA antigens detected by ELISA and autoantigen arrays in N=1985 newly diagnosed RA patients. Association with patient characteristics such as smoking and disease activity were explored. Carb and KAc reactivities by different assays were primarily seen in patients also positive for anti-citrulline reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG reactivity to acetylation was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking status. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles. Our serology results were complemented by screening of monoclonal antibodies derived from single B cells from RA patients for the same antigens as the RA cohort. Certain CCP2+ clones had Carb or Carb+KAc+ multireactivity, while such reactivities were not found in CCP2- clones. We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Carb and KAc could be considered reactivities within the "Cit-umbrella" similar to ACPA fine-specificities, while MAA reactivity is distinctly different.
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43.
  • Gudjonsson, Sigurdur, et al. (författare)
  • Can tissue microarray-based analysis of protein expression predict recurrence of stage Ta bladder cancer?
  • 2011
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 1651-2065 .- 0036-5599. ; 45, s. 270-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Objective. Being able to predict the recurrence or progression of non-muscle-invasive bladder cancer would facilitate effective planning of treatments and follow-up. Biomarkers are needed that can supply prognostic information beyond that provided by clinical and pathological parameters. Tissue microarray (TMA)-based analysis of Ta bladder tumours was used to investigate the prognostic value of expression of several proteins involved in bladder carcinogenesis. Material and methods. Tumour tissue from 52 patients with Ta bladder cancer was investigated. At least three 0.6 mm punch cores from each tumour were placed in a paraffin array block. Tumour expression of tumour protein 53 (TP53), CDH1 (E-cadherin), proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX2), fibroblast growth factor receptor-3 (FGFR3) and epidermal growth factor receptor (EGFR) was quantified by immunohistochemistry (IHC) and correlated with time to recurrence. Median follow-up time was 3.1 years. Whole-section IHC analysis was performed to validate significant findings. Results. Of all patients, 69% (36/52) experienced recurrence. In univariate analysis, recurrence was associated with multifocality, number of earlier recurrences and a low quantity score for EGFR. In a multivariate model, a low EGFR quantity score was correlated with early recurrence (hazard ratio = 5.5, p = 0.003). However, whole-section IHC results for EGFR differed markedly from the TMA findings (κ = 0.07) and no association with time to recurrence was found (p = 0.65). Conclusions. Expression of EGFR measured by TMA-IHC, but not by whole-section IHC, was associated with early recurrence. The results suggest that the proteins assessed have no predictive value for recurrences. Concerns are raised regarding the methodology and generalization of results obtained with TMA-IHC.
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44.
  • Gudjonsson, Sigurdur, et al. (författare)
  • The Value of the UroVysion((R)) Assay for Surveillance of Non-Muscle-Invasive Bladder Cancer.
  • 2008
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 54:2, s. 402-408
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally followed by repeat cystoscopy and urine cytology. A fluorescence in situ hybridisation technique called UroVysion((R)) (UV) is now available for clinical diagnosis of urothelial cancer cells. The aim of the present study was to compare UV analysis with routine follow-up methods. METHODS: We studied an unselected cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in 2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay. The UV assay was evaluated with regards to sensitivity, specificity, and positive predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed. UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70% sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The specificity of UV was 95%. UV detected all six CIS cases in the study and was predictive in two additional patients who developed CIS within 1 yr of inclusion. Cytology was positive in four of those eight CIS cases and atypical in the other four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of patients with non-muscle-invasive bladder cancer, but it may be valuable as a supplement to traditional measures for detecting CIS. Before any conclusions can be drawn regarding the efficacy of novel markers of bladder cancer, they must be studied in bladder cancer patients undergoing endoscopic surveillance.
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45.
  • Hammaréus, Filip, 1998-, et al. (författare)
  • Plasma type I collagen α1 chain in relation to coronary artery disease : findings from a prospective population-based cohort and an acute myocardial infarction prospective cohort in Sweden.
  • 2023
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:9
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the association between type I collagen α1 chain (COL1α1) levels and coronary artery disease (CAD) by using absolute quantification in plasma. Also, to investigate the correlates of COL1α1 to clinical characteristics and circulating markers of collagen metabolism.DESIGN: Life conditions, Stress and Health (LSH) study: prospective cohort study, here with a nested case-control design.Assessing Platelet Activity in Coronary Heart Disease (APACHE) study: prospective cohort study.SETTING: LSH: primary care setting, southeast Sweden.APACHE: cardiology department, university hospital, southeast Sweden.PARTICIPANTS: LSH: 1007 randomly recruited individuals aged 45-69 (50% women). Exclusion criteria was serious disease. After 13 years of follow-up, 86 cases with primary endpoint were identified and sex-matched/age-matched to 184 controls.APACHE: 125 patients with myocardial infarction (MI), 73 with ST-elevation MI and 52 with non-ST-elevation MI.EXCLUSION CRITERIA: Intervention study participation, warfarin treatment and short life expectancy.PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the association between baseline COL1α1 and first-time major event of CAD, defined as fatal/non-fatal MI or coronary revascularisation after 13 years. Secondary outcomes were the association between the collagen biomarkers PRO-C1 (N-terminal pro-peptide of type I collagen)/C1M (matrix metalloproteinase-mediated degradation of type I collagen) and CAD; temporal change of COL1α1 after acute MI up to 6 months and lastly, correlates between COL1α1 and patient characteristics along with circulating markers of collagen metabolism.RESULTS: COL1α1 levels were associated with CAD, both unadjusted (HR=0.69, 95% CI=0.56 to 0.87) and adjusted (HR=0.55, 95% CI=0.41 to 0.75). PRO-C1 was associated with CAD, unadjusted (HR=0.62, 95% CI=0.47 to 0.82) and adjusted (HR=0.61, 95% CI=0.43 to 0.86), while C1M was not. In patients with MI, COL1α1 remained unchanged up to 6 months. COL1α1 was correlated to PRO-C1, but not to C1M.CONCLUSIONS: Plasma COL1α1 was independently and inversely associated with CAD. Furthermore, COL1α1 appeared to reflect collagen synthesis but not degradation. Future studies are needed to confirm whether COL1α1 is a clinically useful biomarker of CAD.
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46.
  • Hammaréus, Filip, et al. (författare)
  • Wall shear stress measured with 4D flow CMR correlates with biomarkers of inflammation and collagen synthesis in mild-to-moderate ascending aortic dilation and tricuspid aortic valves
  • 2024
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : OXFORD UNIV PRESS. - 2047-2404 .- 2047-2412.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic haemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR), and circulating biomarkers in aortic dilation. Methods and results Forty-seven cases with aortic dilation (diameter >= 40 mm) and 50 sex-and age-matched controls (diameter < 40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D flow CMR, and biomarkers including interleukin-6, collagen type I alpha 1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared with controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between haemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, P < 0.001), and maximum oscillatory shear index and collagen type I alpha 1 chain (r = -0.575, P < 0.001 in cases). Conclusion Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between haemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves.
  •  
47.
  • Hansson, Monika, et al. (författare)
  • Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides
  • 2012
  • Ingår i: ARTHRITIS RESEARCH & THERAPY. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 14:5, s. R201-
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Autoantibodies directed against citrullinated proteins/peptides (ACPAs) are highly specific and predictive for the development of rheumatoid arthritis (RA). Different subgroups of RA patients, which have different prognoses and may require different treatments, are characterized by different autoantibody profiles. The objective of this study was to develop a microarray for the detection of multiple RA-associated autoantibodies, initially focusing on responses against citrullinated epitopes on candidate autoantigens in RA. Methods: The microarray is based on Phadia's ImmunoCAP ISAC system, with which reactivity to more than 100 antigens can be analyzed simultaneously, by using minute serum volumes (<10 mu l). Twelve citrullinated peptides, and the corresponding native arginine-containing control peptides, were immobilized in an arrayed fashion onto a chemically modified glass slide, allowing a three-dimensional layer with high binding capacity. The assay was optimized concerning serum dilution and glass surface, whereas each individual antigen was optimized concerning coupling chemistry, antigen concentration, and selection of spotting buffer. The performance of each peptide in the ImmunoCAP ISAC system was compared with the performance in enzyme-linked immunosorbent assays (ELISAs). Serum from 927 RA patients and 461 healthy controls from a matched case-control study were applied onto reaction sites on glass slides, followed by fluorescent-labeled anti-human immunoglobulin G (IgG) antibody. Fluorescence intensities were detected with a laser scanner, and the results analyzed by using image-analysis software. Results: Strong correlations between the ImmunoCAP ISAC system and ELISA results were found for individual citrullinated peptides (Spearman rho typically between 0.75 and 0.90). Reactivity of RA sera with the peptides was seen mainly in the anticyclic citrullinated peptide 2 (CCP2)-positive subset, but some additional reactivity with single citrullinated peptides was seen in the anti-CCP2-negative subset. Adjusting for reactivity against arginine-containing control peptides did not uniformly change the diagnostic performance for antibodies against the individual citrullinated peptides. Conclusions: The multiplexed array, for detection of autoantibodies against multiple citrullinated epitopes on candidate RA autoantigens, will be of benefit in studies of RA pathogenesis, diagnosis, and potentially as a guide to individualized treatment.
  •  
48.
  • Hasib, Lekbira, et al. (författare)
  • Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease
  • 2016
  • Ingår i: Journal of Internal Medicine. - : WILEY-BLACKWELL. - 0954-6820 .- 1365-2796. ; 279:1, s. 63-77
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveRegulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non-ST elevation (NSTE)-ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naive (n) and memory (m)Tregs in patients with NSTE-ACS and in patients 6-12months post-ACS. MethodsBased on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA-4, Tregsubsets were defined by flow cytometry in whole blood or isolated CD4(+) T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)-induced cytokine secretion and ultrasound-defined carotid atherosclerosis. ResultsBoth NSTE-ACS and post-ACS patients exhibited reduced levels of nTregs (P<0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T-cell proliferation and secretion of interferon-gamma and IL-10. The Treg defect was also associated with LPS-induced cytokine secretion and increased burden of carotid atherosclerosis. ConclusionOur results demonstrate a functional and homeostatic Treg defect in patients with NSTE-ACS and also in stabilized patients 6-12months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune-restoring strategies in CAD.
  •  
49.
  • Hedén, Lena, 1971- (författare)
  • Distressing Symptoms in Children with Cancer in General; During Needle Procedures in Particular
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The main aims of this thesis were to investigate the effect of distraction, midazolam and morphine on fear, distress, and pain during needle procedures, and to longitudinally describe parents’ perceptions of their children’s symptom burden during and after cancer treatment.The design in Study I-III was that of a randomized controlled trial (RCT) conducted in a medical setting; Studies II-III were placebo controlled. Study IV has a longitudinal design, and data were collected at three times during treatment and three times after the end of successful treatment. Participants in Study I were children aged 1 to 7 (n=28), in Study II children aged 1 to 19 (n=50), in Study III children aged 1 to 19 (n=50), and in Study IV parents (n=160) of children aged 1 to 19.Blowing soap bubbles or having a heated pillow reduces children’s fear and distress in connection with needle procedures. Low-dose oral midazolam 0.3mg/kg body weight is effective in reducing fear and distress, especially in younger children. Interestingly, oral morphine at a dose of 0.25mg/kg body weight does not reduce fear, distress or pain.These studies have evaluated interventions that may be of help for the most frightened children during needle procedures. We suggest that the first-line intervention against procedural fear, distress, and/or pain should be standard care (i.e. EMLA) in addition to distraction interventions when needed, and only when this is insufficient to add pharmacological interventions.According to parents, feeling drowsy, pain, and lack of energy are initially the most prevalent symptoms in their children, whereas less hair than usual is the most prevalent symptom during treatment. Pain, feeling sad, and nausea are initially the most distressing symptoms. Pain is both prevalent and distressing throughout treatment. The child’s symptom burden, as reported by parents, decreases over time. Information about distressing symptoms and when they can be expected may increase acceptance and adaptation in children and parents during and after cancer treatment.
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50.
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