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  • Romeo, Alessandro, 1961-, et al. (författare)
  • A wavelet add-on code for new-generation N-body simulations and data de-noising (JOFILUREN)
  • 2004
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 354:4, s. 1208-1222
  • Tidskriftsartikel (refereegranskat)abstract
    • Wavelets are a new and powerful mathematical tool, whose most celebrated applications are data compression and de‐noising. In a previous paper, we have shown that wavelets can be used for removing noise efficiently from cosmological, galaxy and plasma N‐body simulations. The expected two‐orders‐of‐magnitude higher performance means, in terms of the well‐known Moore's law, an advance of more than one decade in the future. In this paper, we describe a wavelet add‐on code designed for such an application. Our code can be included in common grid‐based N‐body codes, is written in fortran, is portable and is available on request from the first author. The code can also be applied for removing noise from standard data, such as signals and images.
  • Bastholm Rahmner, Pia, et al. (författare)
  • Physicians' reported needs of drug information at point of care in Sweden
  • 2012
  • Ingår i: British Journal of Clinical Pharmacology. - 0306-5251 .- 1365-2125. ; 73:1, s. 115-125
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS Relevant and easily accessible drug information at point-of-care is essential for physicians' decision making when prescribing. However, the information available by using Clinical Decision Support Systems (CDSSs) often does not meet physicians' requirements. The Summary of Product Characteristics (SmPC) is statutory information about drugs. However, the current structure, content and format of SmPCs make it difficult to incorporate them into CDSSs and link them to relevant patient information from the Electronic Health Records. The aim of the study was to evaluate the perceived needs for drug information among physicians in Sweden. METHODS We recruited three focus group discussions with 18 physicians covering different specialities. The information from the groups was combined with a questionnaire administered at the beginning of the group discussions. RESULTS Physicians reported their needs for knowledge databases at the point of drug prescribing. This included more consistent information about existing and new drugs. They also wished to receive automatically generated alerts for severe drug-drug interactions and adverse effects, and to have functions for calculating glomerular filtration rate to enable appropriate dose adjustments to be made for elderly patients and those with impaired renal function. Additionally, features enhancing electronic communication with colleagues and making drug information more searchable were suggested. CONCLUSIONS The results from the current study showed the need for knowledge databases which provide consistent information about new and existing drugs. Most of the required information from physicians appeared to be possible to transfer from current SmPCs to CDSSs. However, inconsistencies in the SmPC information have to be reduced to enhance their utility.
  • Björnsson, Marcus A., et al. (författare)
  • Modelling of pain intensity and informative dropout in a dental pain model after naproxcinod, naproxen and placebo administration
  • 2011
  • Ingår i: British Journal of Clinical Pharmacology. - 0306-5251 .- 1365-2125. ; 71:6, s. 899-906
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS To describe pain intensity (PI) measured on a visual analogue scale (VAS) and dropout due to request for rescue medication after administration of naproxcinod, naproxen or placebo in 242 patients after wisdom tooth removal. METHODS Non-linear mixed effects modelling was used to describe the plasma concentrations of naproxen, either formed from naproxcinod or from naproxen itself, and their relationship to PI and dropout. Goodness of fit was assessed by simultaneous simulations of PI and dropout. RESULTS Baseline PI for the typical patient was 52.7 mm. The PI was influenced by placebo effects, using an exponential model, and by naproxen concentrations using a sigmoid E-max model. Typical maximal placebo effect was a decrease in PI by 20.2%, with an onset rate constant of 0.237 h-1. EC50 was 0.135 mu mol l-1. A Weibull time-to-event model was used for the dropout, where the hazard was dependent on the predicted PI and by the PI at baseline. Since the dropout was not at random, it was necessary to include the simulated dropout in visual predictive checks (VPC) of PI. CONCLUSIONS This model describes the relationship between drug effects, PI and the likelihood of dropout after naproxcinod, naproxen and placebo administration. The model provides an opportunity to describe the effects of other doses or formulations, after dental extraction. VPC created by simultaneous simulations of PI and dropout provides a good way of assessing the goodness of fit when there is informative dropout.
  • Bogason, Alex, et al. (författare)
  • Inverse relationship between leukaemic cell burden and plasma concentrations of daunorubicin in patients with acute myeloidleukaemia
  • 2011
  • Ingår i: British Journal of Clinical Pharmacology. - 0306-5251 .- 1365-2125. ; 71:4, s. 514-521
  • Tidskriftsartikel (refereegranskat)abstract
    • center dot In vitro studies show that daunorubicin (DNR) cytotoxicity decreases with increasing cell density because of a high cellular uptake and depletion of drug in the medium.center dot It is not known whether such an effect also occurs in vivo.WHAT THIS STUDY ADDScenter dot We have shown that a large leukaemic cell burden lowers the plasma concentration of DNR in patients with acute myeloid leukaemia.center dot Our analysis supports that a large leukaemic cell burden increases the central volume of distribution for DNR.center dot Our study indicates that a dose adjustment of DNR may be of importance in acute myeloid leukaemia patients with high white blood cell counts.AIMSIt has been shown that the cellular uptake and cytotoxicity of anthracyclines decrease with increasing cell density in vitro, an event termed 'the inocculum effect'. It is not known whether such an effect occurs in vivo. In this study the relationships between white blood cell (WBC) count, plasma and cellular concentrations of daunorubicin (DNR) in patients with acute myeloid leukaemia were investigated.METHODSPlasma and mononuclear blood cells were isolated from peripheral blood from 40 patients with acute myeloid leukaemia at end of infusion (time 1 h), 5 and 24 h following the first DNR infusion. DNR concentrations were determined by high-pressure liquid chromatography and related to the WBC count at diagnosis. A population pharmacokinetic model was used to estimate the correlations between baseline WBC count, volume of distribution and clearance of DNR.RESULTSA clear but weak inverse relationship between the baseline WBC count and plasma concentrations of DNR (r2 = 0.11, P < 0.05) at time 1 was found. Furthermore, a clear relationship between baseline WBC count and DNR central volume of distribution using population pharmacokinetic modelling (dOFV 4.77, P < 0.05) was also noted. Analysis of plasma DNR and the metabolite daunorubicinol (DOL) concentrations in patients with a high WBC count support that the low DNR/DOL concentrations are due a distribution effect.CONCLUSIONThis study shows that the leukaemic cell burden influences the plasma concentrations of anthracyclines. Further studies are needed to explore if patients with high a WBC count may require higher doses of anthracyclines.
  • Bondesson, Eva, et al. (författare)
  • Site of deposition and absorption of an inhaled hydrophilic solute
  • 2007
  • Ingår i: British Journal of Clinical Pharmacology. - John Wiley and Sons Inc.. - 1365-2125. ; 63:6, s. 722-731
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. Methods Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid (Tc-99m-DTPA) in an open and crossover fashion. Pulmonary doses were administered as nebulized large and fine droplet-sized aerosols by Pari and UltraVent nebulizers at fairly rapid and slow inhalation flows, respectively. Plasma concentration-time profiles and 24 h urinary excretion of radioactivity were determined. One dose of Tc-99m-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for similar lung deposition as the Tc-99m-DTPA and followed by repeated chest gamma-imaging. Results Intrapulmonary deposition patterns of Tc-99m-DTPA differed significantly (the mean ratio of penetration index (Pari : UltraVent) was 76% with 95% CI 63%, 91%). However, no differences in rate or extent of Tc-99m-DTPA absorption were detected. Mean absorption time was 1.8 h (mean difference (Pari-UltraVent): -0.1 h with 95% CI -0.6 h, 0.3 h) and the bioavailability was 70% (mean ratio (Pari : UltraVent): 101% with 95% CI 90%, 115%). The pulmonary elimination half-life of Tc-99m-Nanocoll (8 h and 45 min) was significantly longer than that of Tc-99m-DTPA (less than 2 h). The oral bioavailability of Tc-99m-DTPA was estimated to be 3.1%. Conclusions The main elimination pathway of the inhaled hydrophilic solute Tc-99m-DTPA from the lungs is trans-epithelial absorption. Despite different intrapulmonary radioaerosol deposition patterns, as verified by gamma scintigraphy, no differences in Tc-99m-DTPA absorption kinetics or bioavailability were detected.
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