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  • A.O., Tillmar, et al. (författare)
  • Using X-chromosomal markers in relationship testing: : How to calculate likelihood ratios taking linkage and linkage disequilibrium into account
  • 2011
  • Ingår i: Forensic Science International : Genetics. - Elsevier. - 1872-4973. ; 5:5, s. 506-511
  • Tidskriftsartikel (refereegranskat)abstract
    • X-chromosomal markers in forensic genetics have become more widely used during the recent years, particularly for relationship testing. Linkage and linkage disequilibrium (LD) must typically be accounted for when using close X-chromosomal markers. Thus, when producing the weight-of-evidence, given by a DNA-analysis with markers that are linked, the normally used product rule is invalid. Here we present an efficient model for calculating likelihood ratio (LR) with markers on the X-chromosome which are linked and in LD. Furthermore, the model was applied on several cases based on data from the eight X-chromosomal loci included in the Mentype® Argus X-8 (Biotype). Using a simulation approach we showed that the use of X-chromosome data can offer valuable information for choosing between the alternatives in each of the cases we studied, and that the LR can be high in several cases. We demonstrated that when linkage and LD were disregarded, as opposed to taken into account, the difference in calculated LR could be considerable. When these differences were large, the estimated haplotype frequencies often had a strong impact and we present a method to estimate haplotype frequencies. Our conclusion is that linkage and LD should be accounted for when using the tested set of markers, and the presented model is an efficient way of doing so.
  • Aars, M, et al. (författare)
  • A conceptual framework for curriculum design in physiotherapy education - An international perspective
  • 2003
  • Ingår i: Advances in Physiotherapy. - 1403-8196. ; 5:4, s. 161-168
  • Tidskriftsartikel (refereegranskat)abstract
    • Globalization is having a significant impact on healthcare and physiotherapy education, among other sectors, can benefit from this trend. The main aim of this work was to develop and describe a conceptual framework for physiotherapy curriculum design and, in doing so, to stimulate international debate on physiotherapy education. The framework was developed through an international collaboration and was tried out in the participating schools in order to refine it further. The current framework consists of three elements to be taken into account in physiotherapy curriculum design: (1) The content aspect or the knowledge base of physiotherapy, (2) the learning aspect or the student's learning process, and (3) the socio-cultural context aspect, which concerns the way in which physiotherapy is experienced and practised. The content aspect includes a description of core concepts of physiotherapy: body, movement and interaction, and acknowledges that physiotherapy should be science-based. The learning aspect and the socio-cultural context aspect form separate parts of the framework. Nonetheless, all aspects are intertwined and reflect theory-practice integration. This framework is offered for critical reflection and as the basis for a debate on the development and evaluation of physiotherapy programmes. Further work is needed in testing the relevance of this framework for curriculum design in different countries and setting.
  • Aasa, M, et al. (författare)
  • Cost and health outcome of primary percutaneous coronary intervention versus thrombolysis in acute ST-segment elevation myocardial infarction-Results of the Swedish Early Decision reperfusion Study (SWEDES) trial.
  • 2010
  • Ingår i: American heart journal. - 1097-6744. ; 160:2, s. 322-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In ST-elevation myocardial infarction, primary percutaneous coronary intervention (PCI) has a superior clinical outcome, but it may increase costs in comparison to thrombolysis. The aim of the study was to compare costs, clinical outcome, and quality-adjusted survival between primary PCI and thrombolysis. Methods Patients with ST-elevation myocardial infarction were randomized to primary PCI with adjunctive enoxaparin and abciximab (n = 101), or to enoxaparin followed by reteplase (n = 104). Data on the use of health care resources, work loss, and health-related quality of life were collected during a 1-year period. Cost-effectiveness was determined by comparing costs and quality-adjusted survival. The joint distribution of incremental costs and quality-adjusted survival was analyzed using a nonparametric bootstrap approach. Results Clinical outcome did not differ significantly between the groups. Compared with the group treated with thrombolysis, the cost of interventions was higher in the PCI-treated group ($4,602 vs $3,807; P = .047), as well as the cost of drugs ($1,309 vs $1,202; P = .001), whereas the cost of hospitalization was lower ($7,344 vs $9,278; P = .025). The cost of investigations, outpatient care, and loss of production did not differ significantly between the 2 treatment arms. Total cost and quality-adjusted survival were $25,315 and 0.759 vs $27,819 and 0.728 (both not significant) for the primary PCI and thrombolysis groups, respectively. Based on the 1-year follow-up, bootstrap analysis revealed that in 80%, 88%, and 89% of the replications, the cost per health outcome gained for PCI will be andlt;$0, $50,000, and $100,000 respectively. Conclusion In a 1-year perspective, there was a tendency toward lower costs and better health outcome after primary PCI, resulting in costs for PCI in comparison to thrombolysis that will be below the conventional threshold for cost-effectiveness in 88% of bootstrap replications.
  • Abtahi, Jahan, et al. (författare)
  • A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants
  • 2012
  • Ingår i: Bone. - Elsevier. - 8756-3282. ; 50:5, s. 1148-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.
  • Abtahi, Jahan, et al. (författare)
  • Bisphosphonate coating might improve fixation of dental implants in the maxilla: : A pilot study
  • 2010
  • Ingår i: International Journal of Oral and Maxillofacial Surgery. - Elsevier Science B.V., Amsterdam. - 0901-5027. ; 39:7, s. 673-677
  • Tidskriftsartikel (refereegranskat)abstract
    • This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Branemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized blinded study.
  • Adner, Mikael, et al. (författare)
  • TLR3 in human eosinophils: functional effects and decreased expression during allergic rhinitis.
  • 2010
  • Ingår i: International archives of allergy and immunology. - 1423-0097. ; 151:2, s. 118-28
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/AIM: Viral respiratory infections are increasingly implicated in allergic exacerbations. Virus-induced activation of eosinophils through Toll-like receptors (TLRs) could be involved. The present study was designed to examine TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB) during symptomatic allergic rhinitis, and to evaluate the functional responsiveness of TLR3 in purified eosinophils.METHODS: BM and PB samples were obtained from healthy volunteers and patients with seasonal allergic rhinitis outside and during the pollen season. Eosinophils were analyzed for TLR3 expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an agonist for TLR3, was used to assess its functional role in purified eosinophils and the intracellular signaling pathways involved.RESULTS: TLR3 expression was demonstrated in BM and PB eosinophils. It was higher in BM-derived than in circulating cells and it was downregulated in both compartments during symptomatic allergic rhinitis. TLR3 expression was also downregulated in the presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects mediated via the p38 mitogen-activated protein kinases and nuclear factor-kappaB signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)-induced IL-8 release.CONCLUSIONS: Eosinophils activated via TLR3 might be more able to home and recruit leukocytes to sites of inflammation. The decreased TLR3 expression during symptomatic allergic rhinitis and in the presence of Th2 cytokines indicates a role in allergic airway inflammation. Thus, eosinophils might function as a link between viral infections and exacerbations of allergic disease.
  • Adolfsson, Jan, et al. (författare)
  • A single-nucleotide polymorphism in the XPG gene, and tumour stage, grade, and clinical course in patients with nonmuscle-invasive neoplasms of the urinary bladder
  • 2006
  • Ingår i: BJU Int. - 1464-4096. ; 97:4, s. 847
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate whether the single nucleotide polymorphism (SNP), Asp1104His (G3507C), in the XPG gene affects malignant phenotypes of nonmuscle-invasive urinary bladder neoplasms (NIBN), by investigating associations between the SNP and clinicopathological variables in patients with NIBN.<h1>PATIENTS AND METHODS</h1>The 233 patients constituted newly diagnosed cases of primary NIBN in the Stockholm area. The Asp1104His polymorphism in the XPG gene was genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique.<h1>RESULTS</h1>The GC + CC genotypes were more frequent in stage pT1 tumours at initial diagnosis than pTa (odds ratio 1.9, 95% confidence interval 1.0–3.5, P = 0.048). The difference was larger in the young group (4.6, 1.9–11.8, P = 0.001). In the young group, the GC + CC genotypes were significantly more frequent in high-grade than in low-grade tumours (3.1, 1.5–6.8, P = 0.004) whereas in the older group the genotypes were less frequent in high-grade tumours (0.3, 0.1–0.7, P = 0.007). The XPG genotypes were not associated with tumour recurrence, stage progression or survival.<h1>CONCLUSION</h1>These results suggest that the SNP in the XPG gene might be related to tumour invasiveness in NIBN.
  • Adolfsson, J, et al. (författare)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
  • 2007
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599. ; 41:6, s. 456-477
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising &gt;97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of &gt;100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of &lt;20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged &lt;75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer
  • Agholme, F, et al. (författare)
  • Local bisphosphonate release versus hydroxyapatite coating for stainless steel screw fixation in rat tibiae
  • 2012
  • Ingår i: Journal of materials science. Materials in medicine. - Springer Verlag (Germany). - 0957-4530. ; 23:3, s. 743-752
  • Tidskriftsartikel (refereegranskat)abstract
    • Implant fixation in bone can be improved by a coating that delivers bisphosphonates locally, or by a hydroxyapatite (HA) coating. In this study, we compared these different types of coatings. For mechanical testing, 30 rats were assigned into three groups, and similar screws were implanted bilaterally in the proximal tibiae. The rats received screws that were either uncoated, coated with nano-crystalline hydroxyapatite or coated with a bisphosphonate releasing protein matrix. After 4 weeks, one screw was subjected to pull-out testing, and the contra-lateral one to torsion testing. For morphology, 30 rats were assigned to similar treatment groups, but received only one screw each. Bisphosphonates enhanced the pull-out force by 41% (P = 0.02) compared to controls, HA increased the pull-out force although not significantly. Conversely, HA increased the maximal torque by 64% (P = 0.02). Morphometry showed higher bone volume around bisphosphonate screws in comparison to HA-coated screws (P andlt; 0.001) and controls (P andlt; 0.001). The results suggest that bisphosphonates improve fixation by increasing the amount of surrounding bone, whereas HA mainly improves bone to implant attachment.
  • Ahlen, Gustaf, et al. (författare)
  • Limited effect on NS3-NS4A protein cleavage after alanine substitutions within the immunodominant HLA-A2-restricted epitope of the hepatitis C virus genotype 3a non-structural 3/4A protease.
  • 2012
  • Ingår i: The Journal of general virology. - 1465-2099. ; 93:Pt 8, s. 1680-1686
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been well established that immunological escape mutations within the hepatitis C virus genotype (gt) la non-structural (NS) 3/4A protease are partly prevented by a reduction in viral protease fitness. Surprisingly little is known about whether similar mutations affect proteases from other genotypes. In the present study, we assessed both the HLA-A2-restricted CTL response and gt3a NS3/4A protease fitness. Similar to gt1, the 1073-1081 epitope was immunodominant within the gt3a-specific HLA-A2-restricted CTL response, despite sequence similarity of only 56% between the gt1a and gt3a genes. However, unlike the gt1a NS3/4A protease, all residues within the gt3a 1073-1081 epitope could be replaced sequentially by alanine while retaining protease activity, at least in part.
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