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Sökning: WFRF:(Karlsson Torgny)

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1.
  • Clark, DW, et al. (författare)
  • Associations of autozygosity with a broad range of human phenotypes
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
  • Tidskriftsartikel (refereegranskat)abstract
    • In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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3.
  • Åberg-Bengtsson, Lisbeth, et al. (författare)
  • När Agnes fick va solen så fattade man ju precis : Om illustrationer i undervisning av yngre elever
  • 2014
  • Ingår i: Resultatdialog. - Stockholm : Vetenskapsrådet. - 9789173072472 ; , s. 246-254
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Att göra adekvata tolkningar av bilder och modeller kan vara verkliga stötestenar för många barn. Särskilt besvärligt förefaller det vara att tolka bilder av processer och förlopp i tryckta läromedel. Även enk-lare bilder och vanliga symboler kan dock leda till icke avsedda tolkningar. Barnen i studien föreföll i många fall betrakta illustrationerna som enbart dekoration och förbigick dem ofta om de inte direkt uppmärksammades på dem. Å andra sidan kunde illustrationer också, särskilt sådana som visade på extremer av något slag, väcka förundran och intresse.
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4.
  • Åsberg, Dennis, 1988-, et al. (författare)
  • A quality control method enhancement concept : Continual improvement of regulatory approved QC methods
  • 2016
  • Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 129, s. 273-281
  • Tidskriftsartikel (refereegranskat)abstract
    • Quality Control methods (QC-methods) play an important role in the overall control strategy for drug manufacturing. However, efficient life-cycle management and continual improvement are hindered due to a variety of post-approval variation legislations across territories and a lack of harmonization of the requirements. As a result, many QC-methods fall behind the technical development. Developing the QC-method in accordance with the Quality by Design guidelines gives the possibility to do continual improvements inside the original Method Operable Design Region (MODR). However, often it is necessary to do changes outside the MODR, e.g. to incorporate new technology that was not available at the time the original method was development. Here, we present a method enhancement concept which allows minor adjustments, within the same measuring principle, outside the original MODR without interaction with regulatory agencies. The feasibility of the concept is illustrated by a case study of a QC-method based on HPLC, assumed to be developed before the introduction of UHPLC, where the switch from HPLC to UHPLC is necessary as a continual improvement strategy. The concept relies on the assumption that the System Suitability Test (SST) and failure modes are relevant for other conditions outside the MODR as well when the same measuring principle is used. It follows that it should be possible to move outside the MODR as long as the SST has passed. All minor modifications of the original, approved QC-method must be re-validated according to a template given in the original submission and a statistical equivalence should be shown between the original and modified QC-methods. To summarize, revalidation is handled within the pharmaceutical quality control system according to internal change control procedures, but without interaction with regulating agencies.
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5.
  • Abrahamsson, Agneta, et al. (författare)
  • Making sense of the challenge of smoking cessation during pregnancy : a phenomenographic approach.
  • 2005
  • Ingår i: Health Education Research. - : Oxford University Press. - 0268-1153 .- 1465-3648. ; 20:3, s. 367-378
  • Tidskriftsartikel (refereegranskat)abstract
    • In general, most women are familiar with the need to stop smoking when they are pregnant. In spite of this, many women find it difficult to stop. Using a phenomenographic approach, this study explored Swedish pregnant and post-pregnant women's ways of making sense of smoking during pregnancy. A total of 17 women who either smoked throughout pregnancy or stopped smoking during pregnancy were interviewed. Five different story types of how they are making sense of smoking during pregnancy were identified: smoking can be justified; will stop later; my smoking might hurt the baby; smoking is just given up; smoking must be taken charge of. Based on the study it is argued that the approach used in health education in relation to smoking cessation in antenatal care needs to move from information transfer and advice-giving to the creation of a dialogue. The starting point should be the woman's knowledge, concerns, rationalizations and prejudices. A model is suggested in which a woman may move in a space on three axes depending on life encounters, dialogue and reflections on meaning. The goal in health education would be to encourage movement along three axes: 'increase of self-efficacy towards control', 'increase awareness by reflection on meaning of the smoking issue' and 'avoidance of defense of the smoking behavior'.
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6.
  • Abrahamsson, Agneta, et al. (författare)
  • Some lessons from Swedish midwives' experiences of approaching women smokers in antenatal care.
  • 2005
  • Ingår i: Midwifery. - : Elsevier BV. - 1532-3099 .- 0266-6138. ; 21:Jul 14, s. 335-345
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: to describe the qualitatively different ways in which midwives make sense of how to approach women smokers. Design, setting and participants: a more person-centred national project 'Smoke-free pregnancy' has been in progress in Sweden since 1992. Using a phenomenographic approach, 24 midwives who have been regularly working in antenatal care were interviewed about addressing smoking during pregnancy. Findings: four different story types of how the midwives made sense of their experiences in addressing smoking in pregnancy were identified: 'avoiding', 'informing', 'friend-making', 'co-operating'. Key conclusion: the midwives' story types about how they approached women who smoke illustrated the difficulties of changing from being an expert who gives information and advice to being an expert on how to enable a woman in finding out why she smoked and how to stop smoking. Implications for practice: health education about smoking that is built on cooperation and dialogue was seen by the midwives as a productive way of working. The starting point should be the lay perspective of a woman, which means that her thoughts about smoking cessation are given the space to grow while she talks.
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7.
  • Ahsan, Muhammad, et al. (författare)
  • The relative contribution of DNA methylation and genetic variants on protein biomarkers for human diseases.
  • 2017
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 13:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs. We performed epigenome-wide association study (EWAS) and genome-wide association study (GWAS) analyses, and integrated biomarker, DNA methylation and SNP data using between 698 and 1033 samples depending on data availability for the different analyses. We identified 124 and 45 loci (Bonferroni adjusted P < 0.05) with effect sizes up to 0.22 standard units' change per 1% change in DNA methylation levels and up to four standard units' change per copy of the effective allele in the EWAS and GWAS respectively. Most GWAS loci were cis-regulatory whereas most EWAS loci were located in trans. Eleven EWAS loci were associated with multiple biomarkers, including one in NLRC5 associated with CXCL11, CXCL9, IL-12, and IL-18 levels. All EWAS signals that overlapped with a GWAS locus were driven by underlying genetic variants and three EWAS signals were confounded by smoking. While some cis-regulatory SNPs for biomarkers appeared to have an effect also on DNA methylation levels, cis-regulatory SNPs for DNA methylation were not observed to affect biomarker levels. We present associations between protein biomarker and DNA methylation levels at numerous loci in the genome. The associations are likely to reflect the underlying pattern of genetic variants, specific environmental exposures, or represent secondary effects to the pathogenesis of disease.
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8.
  • Andersson, Patiyan, 1978-, et al. (författare)
  • Genome-wide analysis of penile cancer using high-density single nucleotide polymorphism arrays
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The availability of genome-wide high-density single nucleotide polymorphism (SNP) arrays makes it possible to in a structured manner study chromosome aberrations in penile cancer where little is known of disruptive genetic events. In this study 19 penile squamous cell carcinomas were analyzed using the 250k NspI SNP array from Affymetrix. We find major regions of frequent copy number gain in chromosome arms 3q, 5p and 8q, and slightly less frequent in 1p, 16q and 20q. The chromosomal regions of most frequent copy number losses were 3p, 4q, 11p and 13q. We identified four candidate genes residing in the major chromosomal regions of aberration. Eight tumours showed copy number gain of the PIK3CA gene located to 3q26.3. Five of the remaining tumours carried an activating mutation of the PIK3CA gene and these tumours showed very few chromosomal aberrations. Collectively, disruption of the PIK3CA gene was found in 13/19 samples, and presence of active phosphorylated AKT was confirmed immunohistochemically in these tumours indicating an active signalling pathway. We found copy number gain of the hTERT gene (5p15.33) in 7 samples and of the Myc gene (8q24.21) in 7 samples. Copy number loss of the tumoursuppressor gene FHIT (3p14.2) was observed in 8 samples, the same 8 samples that showed copy number gain of the PIK3CA gene. In total the PI3K/AKT and RAS/MAPK pathways were found to be activated through mutation or amplification in 64% of the cases, indicating the significance of these pathways in the aetiology of penile cancer.
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9.
  • Andersson, Patiyan, 1978-, et al. (författare)
  • PIK3CA, HRAS and KRAS gene mutations in human penile cancer
  • 2008
  • Ingår i: Journal of Urology. - New York, USA : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 179:5, s. 2030-2034
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways. Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors. Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma. Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.
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10.
  • Arvidsson, Åke, et al. (författare)
  • Reduction of Routing Complexity in Telecommunication Networks by a Novel Decomposition Method
  • 1996
  • Konferensbidrag (refereegranskat)abstract
    • Routing problems are often encountered when designing and managing telecommuni- cation networks. Today, routing problems are affected by the growing sizes of networks, which increase the complexity, and by introduction of new services and technologies, which rise the demands. Rather than resorting to entirely heuristic algorithms and/or large data bases with off-line precomputed routing information for various situations, we propose a a new decomposition method whereby any routing algorithm is speeded up considerably, thus permitting the deployment of well founded routing algorithms even for real time purposes. In our paper, we present this new method in formal terms, and apply it to a real routing problem. Finally, investigating the performance of our fast implementation by comparing it to the optimal, non-accelerated solution, we find that considerable time savings can be made at a limited cost in terms of non-optimality of the final solution. It is also emphasised that in real-time applications with non-constant traffics, this nominal degradation might be more than compensated for by the prompt delivery.
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