| 1. |
- Eriksson, Ulf G, et al.
(författare)
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Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopaedic surgery patients receiving subcutaneous melagatran and oral ximelagatran : a population model analysis
- 2003
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Ingår i: Clinical Pharmacokinetics. - 0312-5963 .- 1179-1926. ; 42:7, s. 687-701
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: Ximelagatran, an oral direct thrombin inhibitor, is rapidly bioconverted to melagatran, its active form. The objective of this population analysis was to characterise the pharmacokinetics of melagatran and its effect on activated partial thromboplastin time (APTT), an ex vivo measure of coagulation time, in orthopaedic surgery patients sequentially receiving subcutaneous melagatran and oral ximelagatran as prophylaxis for venous thromboembolism. To support the design of a pivotal dose-finding study, the impact of individualised dosage based on bodyweight and calculated creatinine clearance was examined. DESIGN AND METHODS: Pooled data obtained in three small dose-guiding studies were analysed. The patients received twice-daily administration, with either subcutaneous melagatran alone or a sequential regimen of subcutaneous melagatran followed by oral ximelagatran, for 8-11 days starting just before initiation of surgery. Nonlinear mixed-effects modelling was used to evaluate rich data of melagatran pharmacokinetics (3326 observations) and the pharmacodynamic effect on APTT (2319 observations) in samples from 216 patients collected in the three dose-guiding trials. The pharmacokinetic and pharmacodynamic models were validated using sparse data collected in a subgroup of 319 patients enrolled in the pivotal dose-finding trial. The impact of individualised dosage on pharmacokinetic and pharmacodynamic variability was evaluated by simulations of the pharmacokinetic-pharmacodynamic model. RESULTS: The pharmacokinetics of melagatran were well described by a one-compartment model with first-order absorption after both subcutaneous melagatran and oral ximelagatran. Melagatran clearance was correlated with renal function, assessed as calculated creatinine clearance. The median population clearance (creatinine clearance 70 mL/min) was 5.3 and 22.9 L/h for the subcutaneous and oral formulations, respectively. The bioavailability of melagatran after oral ximelagatran relative to subcutaneous melagatran was 23%. The volume of distribution was influenced by bodyweight. For a patient with a bodyweight of 75kg, the median population estimates were 15.5 and 159L for the subcutaneous and oral formulations, respectively. The relationship between APTT and melagatran plasma concentration was well described by a power function, with a steeper slope during and early after surgery but no influence by any covariates. Simulations demonstrated that individualised dosage based on creatinine clearance or bodyweight had no clinically relevant impact on the variability in melagatran pharmacokinetics or on the effect on APTT. CONCLUSIONS: The relatively low impact of individualised dosage on the pharmacokinetic and pharmacodynamic variability of melagatran supported the use of a fixed-dose regimen in the studied population of orthopaedic surgery patients, including those with mild to moderate renal impairment.
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| 2. |
- Köping Olsson, Bengt, 1963-
(författare)
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Beskrivningsspråk i och för kreativ praxis : Idéutveckling under gruppsession
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Generating and developing ideas constitute centerpieces for innovations processes, idea creation methods and techniques most urgent in their initial phases processes, though the need is no less in subsequent phases. Those early phases, however, allow for more deviant ideas, characterized by more of ambiguity and uncertainty. This is an innovation process theme that is recognized as among those least understood.Through comparative studies of seven groups from three different practices, their interactions in idea development and problem solving, a deeper understanding of descriptive languages and modus operandi has been acquired. The research was carried out in three settings: brainstorming in industrial design, musical improvisation and dialogue seminars with participants representing industrial design and music, respectively. The compilation of the three practices’ contributions results in a conceptual framework. It includes such concepts as, for example, ‘momentary formation’, ‘temporary epistemology’ and ‘the play with semantic key signature’. Those concepts give examples of the reconsidering of creative group processes, relative to previous frameworks, that is a result of these studies. From the perspective of group idea, individuals’ creative processes might be perceived as the searching for the different or the deviant while we suggest that group creativity is enhanced throughits members’ abilities to preserve their own perspectives and thought styles. Group creativity is based on a willingness to focus on the central group idea while simultaneously maintaining individual thought styles.A creative group’s way of forming and mediating ideas, its modus operandi, is referred to as its description language. The importance of descriptive languages driving mechanism for creative group processes should be seen in the perspective of fundamental social cognition processes.The problem area is mapped through the strategic use of different descriptive modus. Groups employ iteration as a strategy for stimulating collective reflection, that is, to think about the problem again but in other ways. We argue that critical thinking and the ability to make critical judgements is an important driving force in the creative groups’ iterative processes: criticism makes reconsideration meaningful. Different types of criticism are discussed, as is how they interact with groups’ idea development and creative processes.This research project has resulted in a deeper understanding of the relay race of initiatives that characterizes the interactions in groups solving problems and developing ideas. The project has developed an awareness of which descriptions that stimulate group creativity.
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| 3. |
- Littorin, Bengt, et al.
(författare)
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Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults : A nationwide study
- 2001
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 24:6, s. 1033-1037
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults. RESEARCH DESIGN AND METHODS - This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis. RESULTS - The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR] 2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients, however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends. CONCLUSIONS - Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.
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| 4. |
- Olsson, Emma, 1974-
(författare)
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Many-body Problems in the Theory of Stellar Collapse and Neutron Stars
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- When modelling the collapse of massive stars leading to supernova explosions and the cooling of neutron stars, understanding the microphysical processes, such as the interaction of neutrinos within a dense medium are of vital importance. The interaction of neutrinos with nucleons (neutrons and protons) is altered by the presence of the medium, compared to the same process with free nucleons. Neutrino scattering and production processes may be characterized in terms of the excitations that are created or destroyed in the nuclear medium. One way to analyse the effects of the medium is by using Landau's theory of normal Fermi liquids. This theory gives simple relationships between physical quantities such as the spin susceptibility or the response to a weak interaction probe in terms of Landau parameters, that are measures of the interaction between quasiparticles. One problem when using Landau Fermi liquid theory for nucleon matter is that the interaction has a tensor component. The tensor interaction does not conserve the total spin and, as a consequence, there are generally contributions to long-wavelength response functions from states that have more than one quasiparticle-quasihole pair in the intermediate state. Such contributions cannot be calculated in terms of Landau parameters alone, since in the usual formulation of Landau theory, only singlepair excitations are considered. In this thesis three problems are addressed. First, we obtain bounds on the contributions from more than one quasiparticle-quasihole pair by using sum-rule arguments. Second, we derive expressions for static response functions allowing for the tensor components of the interaction. We analyse which the most important effects are on the static response of nucleon matter, and find that the major contributions comes from renormalization of coupling constants and transitions to states with more than one quasiparticle-quasihole pair. Third, we show how contributions to the dynamical response coming from states containing two quasiparticle-quasihole pairs may be evaluated in terms of Landau theory if one allows for the effect of collisions in the Landau kinetic equation. We consider the case of asymmetric nuclear matter, and our work goes beyond earlier works in that they contain the effects of collisions in addition to those of the mean field.
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| 5. |
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| 6. |
- Simonsson, Bengt, et al.
(författare)
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Intensive treatment and stem cell transplantation in chronic myelogenous leukemia : long-term follow-up
- 2005
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Ingår i: Acta Haematologica. - : S. Karger AG. - 0001-5792 .- 1421-9662. ; 113:3, s. 155-162
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1–3 courses of intensive chemotherapy. Those who became Ph-negative after IFN + HU or after 1–3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN + HU reduced the percentage of Ph-positive metaphases in 56% of patients, and 1 patient became Ph-negative. After one or two intensive cytotherapies 86 and 88% had a Ph reduction, and 34 and 40% became Ph-negative, respectively. In patients receiving a third intensive chemotherapy 92% achieved a Ph reduction and 8% became Ph-negative. The median survival after auto-SCT (n = 46) was 7.5 years. The chance of remaining Ph-negative for up to 10 years after autologous SCT was around 20%. The overall survival for allo-SCT RD (n = 91) and URD (n = 28) was almost the same, i.e. ≈60% at 10 years. The median survival for all 251 patients registered was 8 years (historical controls 3.5 years). The role of the treatment schedule presented in the imatinib era is discussed.
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| 7. |
- Törn, Carina, et al.
(författare)
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Combinations of beta cell specific autoantibodies at diagnosis of diabetes in young adults reflects different courses of beta cell damage
- 2001
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Ingår i: Autoimmunity. - 0891-6934. ; 33:2, s. 115-120
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Tidskriftsartikel (refereegranskat)abstract
- To explore the natural course of beta cell function in recent onset diabetes, a subgroup (n = 157) of all incident cases (n = 879) 15-34 years old. 1992-1993 in Sweden. and with positivity for at least one autoantibody of islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (1A-2A) were followed prospectively thr the first four years with annual analysis of C-peptide. The aim was to relate the course of beta cell function, measured as C-peptide, in early diabetes with the presence of different islet autoantibodies at diagnosis. We found that patients positive for ICA alone (n = 11 ) had significantly higher C-peptide levels both at diagnosis and during the first three years compared with the other patients (n = 146; p = 0.022, p < 0.001, p = 0.004 and p = 0.0022). Patients positive for GADA alone or in combination with other antibodies (n = 125) had significantly lower C-peptide during the first three years after diagnosis compared with the other patients (n = 32. p < 0.001, p = 0.0011 and p = 0.0136). Patients with two or three autoantibodies had C-peptide levels similar to levels found in patients positive only for GADA. However. after four years, there were no significant differences between any of the groups of different autoantibody combinations. At diagnosis. 55% (86/157) of the patients had C-peptide: levels above the lower normal range of 0.25 nmol/l, but the frequency of patients with beta cell Function above this level decreased after two years to 41% (65/157; p = 0.035) and after four years to 22% (35/157; p = 0.0041).
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| 8. |
- Törn, Carina, et al.
(författare)
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Glutamic acid decarboxylase antibodies (GADA) is the most important factor for prediction of insulin therapy within 3 years in young adult diabetic patients not classified as Type 1 diabetes on clinical grounds
- 2000
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Ingår i: Diabetes/Metabolism Research and Reviews. - 1520-7552 .- 1520-7560. ; 16:6, s. 442-447
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Tidskriftsartikel (refereegranskat)abstract
- Background Differentiation between Type 1 and Type 2 diabetes in adults is difficult at diagnosis. In this study we tested the hypothesis that autoantibodies at diagnosis are predictive for insulin treatment within 3 years in patients initially not classified as Type 1 diabetes. Methods In a nationwide population-based study, blood samples were obtained from 764 patients, all diagnosed with diabetes during a 2-year period. At diagnosis, 583 (76%) were classified as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classified. Results Among patients not classified as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassified patients were positive for islet cell antibodies CICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A). These patients (n=94) had lower body mass index (BMI) (p<0.001) and lower C-peptide (p<0.001) compared to the autoantibody negative patients (n=87). Compared to clinically classified Type 1 diabetes patients positive for autoantibodies (n=477), they have higher BMI (p<0.001), higher C-peptide (p<0.001) and the same levels of ICA, GADA and IA-2A. After 3 years, 93% of autoantibody positive patients initially not classified as Type 1 were on insulin. When ICA, GADA, IA-2A, BMI and C-peptide were tested in a multiple logistic regression, only GADA was signiificant for insulin treatment within 3 years (OR = 18.8; 95% CI 1.8-191) in patients treated with diet or oral drugs at diagnosis. Conclusions A correct classification is difficult in adult diabetic patients. The presence of pancreatic autoantibodies, especially GADA, at diagnosis of diabetes are highly predictive for insulin therapy within 3 years from diagnosis.
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| 9. |
- Andersson, Agneta, et al.
(författare)
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Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men
- 2000
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - 0193-1849 .- 1522-1555. ; 279:4, s. E744-E751
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Tidskriftsartikel (refereegranskat)abstract
- Endurance trained (n = 14) and untrained young men (n = 15) were compared regarding the fatty acid profile of the vastus lateralis muscle after 8 wk on diets with a similar fatty acid composition. The skeletal muscle phospholipids in the trained group contained lower proportions of palmitic acid (16:0) (-12.4%, P < 0.001) and di-homo-gamma-linolenic acid [20:3(n-6)] (-15.3%, P = 0.018), a lower n-6-to-n-3 ratio (-42.0%, P = 0.015), higher proportions of stearic acid (18:0) (+9.8%, P = 0.004) and sum of n-3 polyunsaturated fatty acids (+33.8%, P = 0.009), and a higher ratio between 20:4(n-6) to 20:3(n-6) (+18.4%, P = 0.006) compared with those in the untrained group. The group differences in 16:0, 20:3(n-6), 18:0/16:0, and 20:4(n-6)/20:3(n-6) were independent of fiber-type distribution. The trained group also showed a lower proportion of 16:0 (-7.9%, P < 0.001) in skeletal muscle triglycerides irrespective of fiber type. In conclusion, the fatty acid profile of the skeletal muscle differed between trained and untrained individuals, although the dietary fatty acid composition was similar. This difference was not explained by different fiber-type distribution alone but appears to be a direct consequence of changes in fatty acid metabolism due to the higher level of physical activity.
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| 10. |
- Andersson, Mats, et al.
(författare)
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Road Friction Estimation
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This project is part of the Swedish IVSS program. The aim of IVSS is to stimulate research and development for the road safety of the future. Road conditions with low friction have been identified as a frequent cause of traffic accidents. Therefore, technology to automaticallydetect changes in road conditions and alert the driver or take proper actions with active driver support systems would be a key contribution to increased road safety.The aim of this project was to investigate the possibilities to estimate the tire to road friction.Three different approaches have been developed and evaluated, from concept to early prototypes in test vehicles. In the first method, the estimation of the coefficient of friction is based on the forces and torques that are produced at the front tires at cornering maneuvers.The second method is based on a physical model of the tire behavior and estimates road friction from information on the forces that are produced at straight driving. The third method is based on an optical sensor that classifies the road surface ahead of the vehicle.The three methods have been successfully evaluated in proving ground and public road tests in summer and winter conditions with different tires, and have been compared with reference measurements. The conclusion is that all three methods can be used for tire to road frictionestimation and are recommended for further development and industrialization.
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