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2.
  • Poutanen, Markku, et al. (författare)
  • DynaQlim – Upper Mantle Dynamics and Quaternary Climate in Cratonic Areas
  • 2010
  • Ingår i: New Frontiers in Integrated Solid Earth Sciences. - Dordrecht : Springer. - 9789048127368 - 9789048127375 ; , s. 349-372
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • The isostatic adjustment of the solid Earth to the glacial loading (GIA, Glacial Isostatic Adjustment) with its temporal signature offers a great opportunity to retrieve information of Earth’s upper mantle to the changing mass of glaciers and ice sheets, which in turn is driven by variations in Quaternary climate. DynaQlim (Upper Mantle Dynamics and Quaternary Climate in Cratonic Areas) has its focus to study the relations between upper mantle dynamics, its composition and physical properties, temperature, rheology, and Quaternary climate. Its regional focus lies on the cratonic areas of northern Canada and Scandinavia.Geodetic methods like repeated precise levelling, tide gauges, high-resolution observations of recent movements, gravity change and monitoring of postglacial faults have given information on the GIA process for more than 100 years. They are accompanied by more recent techniques like GPS observations and the GRACE and GOCE satellite missions which provide additional global and regional constraints on the gravity field. Combining geodetic observations with seismological investigations, studies of the postglacial faults and continuum mechanical modelling of GIA, DynaQlim offers new insights into properties of the lithosphere. Another step toward a better understanding of GIA has been the joint inversion of different types of observational data – preferentially connected with geological relative sea-level evidence of the Earth’s rebound during the last 10,000 years.Due to the changes in the lithospheric stress state large faults ruptured violently at the end of the last glaciation in large earthquakes, up to the magnitudes MW = 7–8. Whether the rebound stress is still able to trigger a significant fraction of intraplate seismic events in these regions is not completely understood due to the complexity and spatial heterogeneity of the regional stress field. Understanding of this mechanism is of societal importance.Glacial ice sheet dynamics are constrained by the coupled process of the deformation of the viscoelastic solid Earth, the ocean and climate variability. Exactly how the climate and oceans reorganize to sustain growth of ice sheets that ground to continents and shallow continental shelves is poorly understood. Incorporation of nonlinear feedback in modelling both ocean heat transport systems and atmospheric CO2 is a major challenge. Climate-related loading cycles and episodes are expected to be important, hence also more short-term features of palaeoclimate should be explicitly treated.Within this Chapter View ChapterIntroductionObservational BasisCurrent Models and Problems to be SolvedClimateChallenges with DynaQlimReferencesReferencesOther actionsExport citationsAbout this BookReprints and Permissions
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  • Ekelund, Ulf, et al. (författare)
  • Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288,498 men and women.
  • 2011
  • Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 93, s. 826-835
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The protective effect of physical activity (PA) on abdominal adiposity is unclear. OBJECTIVE: We examined whether PA independently predicted gains in body weight and abdominal adiposity. DESIGN: In a prospective cohort study [the EPIC (European Prospective Investigation into Cancer and Nutrition)], we followed 84,511 men and 203,987 women for 5.1 y. PA was assessed by a validated questionnaire, and individuals were categorized into 4 groups (inactive, moderately inactive, moderately active, and active). Body weight and waist circumference were measured at baseline and self-reported at follow-up. We used multilevel mixed-effects linear regression models and stratified our analyses by sex with adjustments for age, smoking status, alcohol consumption, educational level, total energy intake, duration of follow-up, baseline body weight, change in body weight, and waist circumference (when applicable). RESULTS: PA significantly predicted a lower waist circumference (in cm) in men (β = -0.045; 95% CI: -0.057, -0.034) and in women (β = -0.035; 95% CI: -0.056, -0.015) independent of baseline body weight, baseline waist circumference, and other confounding factors. The magnitude of associations was materially unchanged after adjustment for change in body weight. PA was not significantly associated with annual weight gain (in kg) in men (β = -0.008; 95% CI: -0.02, 0.003) and women (β = -0.01; 95% CI: -0.02, 0.0006). The odds of becoming obese were reduced by 7% (P < 0.001) and 10% (P < 0.001) for a one-category difference in baseline PA in men and women, respectively. CONCLUSION: Our results suggest that a higher level of PA reduces abdominal adiposity independent of baseline and changes in body weight and is thus a useful strategy for preventing chronic diseases and premature deaths.
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  • Forsgren, Mikael, et al. (författare)
  • 31P MRS as a Potential Biomarker for Fibromyalgia
  • 2012
  • Ingår i: Proceedings of the 20th Annaal Meeting &amp; Exhibition, 5-11 May, Melbourne, Australia. ; , s. 1493-1493
  • Konferensbidrag (refereegranskat)abstract
    • Major clinical symptoms in fibromyalgia (FM) are muscle pain, stiffness and fatigue. Studies have shown reduced voluntary strength and exercise capacity, lower endurance and more muscular pain even at low workload. An impaired muscle energy metabolism has therefore been proposed as a result of the disease. An earlier study using magnetic resonance spectroscopy (MRS) showed that at maximal dynamic and static contractions the concentration of inorganic phosphate was lower in FM [1]. A decrease in ATP, ADP and PCr and an increase in AMP and creatine was found in FM biopsies [2]. The purpose of this study was to non-invasively analyze the quantitative content of  phosphagens in the resting muscle in FM in comparison to healthy controls using 31P MRS of the quadriceps muscle.
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  • Gerdle, Björn, et al. (författare)
  • Decreased muscle concentrations of ATP and PCR in the quadriceps muscle of fibromyalgia patients – A 31P-MRS study
  • 2013
  • Ingår i: European Journal of Pain. - : John Wiley & Sons. - 1090-3801 .- 1532-2149. ; 17:8, s. 1205-1215
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND METHODS:Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P magnetic resonance spectroscopy (31P-MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (Controls; n = 14) using (31) P-MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity.RESULTS:Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28-29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in Controls [FMS: 9.0 ± 0.5% vs. Controls: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities.CONCLUSIONS:Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.
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  • Gregersen, Søren, et al. (författare)
  • Seismicity and sources of stress in Fennoscandia
  • 2021
  • Ingår i: Glacially-Triggered Faulting. - Cambridge : Cambridge University Press. - 9781108779906 - 9781108490023 ; , s. 177-197
  • Bokkapitel (refereegranskat)abstract
    • This chapter investigates the Fennoscandian uplift area since the latest Ice Age and addresses the question if glacial isostatic adjustment may influence current seismicity. The region is in an intraplate area, with stresses caused by the lithospheric relative plate motions. Discussions on whether uplift and plate tectonics are the only causes of stress have been going on for many years in the scientific community.This review considers the improved sensitivity of the seismograph networks, and at the same time attempts to omit man-made explosions and mining events in the pattern, to present the best possible earthquake pattern. Stress orientations and their connection to the uplift pattern and known tectonics are evaluated. Besides plate motion and uplift, one finds that some regions are affected stress-wise by differences in geographical sediment loading as well as by topography variations. The stress release in the present-day earthquakes shows a pattern that deviates from that of the time right after the Ice Age. This chapter treats the stress pattern generalized for Fennoscandia and guides the interested reader to more details in the national chapters.
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9.
  • Jesper, Kristiansen, et al. (författare)
  • Effects of classroom acoustics and self-reported noise exposure on teacher’s well-being
  • 2013
  • Ingår i: Environment and Behavior. - : SAGE Publications. - 1552-390X .- 0013-9165. ; 45:2, s. 283-300
  • Tidskriftsartikel (refereegranskat)abstract
    • Beyond noise annoyance and voice problems, little is known about the effects that noise and poor classroom acoustics have on teachers’ health and well-being. The aim of this field study was therefore to investigate the effects of perceived noise exposure and classroom reverberation on measures of well-being. Data on self-reported noise exposure, job satisfaction, fatigue after work, and interest in leaving the job were obtained from 283 teachers at 10 schools in Copenhagen, Denmark. In addition, the schools’ acoustical working environment was classified as “low reverberation time (RT)” (3 schools, RT = 0.41-0.47 s), “medium RT” (3 schools, RT = 0.50-0.53 s), or “high RT” (4 schools, RT = 0.59-0.73 s). Significant associations were found between high RT and noise exposure, and, respectively, low job satisfaction, lack of energy after work, and interest in leaving the job. Noise exposure was also associated with lack of motivation and sleepiness. The results demonstrate the importance of good classroom acoustic conditions for teachers’ well-being.
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  • Kirchberger, Tanja, et al. (författare)
  • Cellular effects and metabolic stability of N1-cyclicinosinediphosphoribose and its derivatives
  • 2006
  • Ingår i: British Journal of Pharmacology. - : John Wiley & Sons. - 0007-1188 .- 1476-5381. ; 149:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose:Recently, a number of mimics of the second messenger cyclic ADP-ribose (cADPR) with replacement of adenosine by inosine were introduced. In addition, various alterations in the molecule ranging from substitutions at C8 of the base up to full replacement of the ribose moieties still retained biological activity. However, nothing is known about the metabolic stability and cellular effects of these novel analogues.Experimental approach:cADPR and the inosine-based analogues were incubated with CD38, ADP-ribosyl cyclase and NAD-glycohydrolase and metabolism was analysed by RP-HPLC. Furthermore, the effect of the analogues on cytokine expression and proliferation was investigated in primary T-lymphocytes and T-lymphoma cells.Key results:Incubation of cADPR with CD38 resulted in degradation to adenosine diphosphoribose. ADP-ribosyl cyclase weakly catabolised cADPR whereas NAD-glycohydrolase showed no such activity. In contrast, N1-cyclic inosine 5′-diphosphoribose (N1-cIDPR) was not hydrolyzed by CD38. Three additional N1-cIDPR analogues showed a similar stability. Proliferation of Jurkat T-lymphoma cells was inhibited by N1-cIDPR, N1-[(phosphoryl-O-ethoxy)-methyl]-N9-[(phosphoryl-O-ethoxy)-methyl]-hypoxanthine-cyclic pyrophosphate (N1-cIDP-DE) and N1-ethoxymethyl-cIDPR (N1-cIDPRE). In contrast, in primary T cells neither proliferation nor cytokine expression was affected by these compounds.Conclusions and Implications:The metabolic stability of N1-cIDPR and its analogues provides an advantage for the development of novel pharmaceutical compounds interfering with cADPR mediated Ca2+ signalling pathways. The differential effects of N1-cIDPR and N1-cIDPRE on proliferation and cytokine expression in primary T cells versus T-lymphoma cells may constitute a starting point for novel anti-tumor drugs.
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15.
  • Lund, Søren Søgaard, et al. (författare)
  • Insulin regimens in type 2 diabetes.
  • 2010
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 362:10, s. 959-960
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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16.
  • Lund, Sören, et al. (författare)
  • The dynamics of the LPS triggered inflammatory response of murine microglia under different culture and in vivo conditions
  • 2006
  • Ingår i: J Neuroimmunol. ; 180:1-2, s. 71-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Overall, the inflammatory potential of lipopolysaccharide (LPS) in vitro and in vivo was investigated using different omics technologies. We investigated the hippocampal response to intracerebroventricular (i.c.v) LPS in vivo, at both the transcriptional and protein level. Here, a time course analysis of interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) showed a sharp peak at 4 h and a return to baseline at 16 h. The expression of inflammatory mediators was not temporally correlated with expression of the microglia marker F4/80, which did not peak until 2 days after LPS injection. Of 480 inflammation-related genes present on a microarray, 29 transcripts were robustly up-regulated and 90% of them were also detected in LPS stimulated primary microglia (PM) cultures. Further in vitro to in vivo comparison showed that the counter regulation response observed in vivo was less evident in vitro, as transcript levels in PM decreased relatively little over 16 h. This apparent deficiency of homeostatic control of the innate immune response in cultures may also explain why a group of genes comprising tnf receptor associated factor-1, endothelin-1 and schlafen-1 were regulated strongly in vitro, but not in vivo. When the overall LPS-induced transcriptional response of PM was examined on a large Affymetrix chip, chemokines and cytokines constituted the most strongly regulated and largest groups. Interesting new microglia markers included interferon-induced protein with tetratricopeptide repeat (ifit), immune responsive gene-1 (irg-1) and thymidylate kinase family LPS-inducible member (tyki). The regulation of the former two was confirmed on the protein level in a proteomics study. Furthermore, conspicuous regulation of several gene clusters was identified, for instance that of genes pertaining to the extra-cellular matrix and enzymatic regulation thereof. Although most inflammatory genes induced in vitro were transferable to our in vivo model, the observed discrepancy for some genes potentially represents regulatory factors present in the central nervous system (CNS) but not in vitro.
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17.
  • Lund Stetler, Katarina, 1982- (författare)
  • Innovation under pressure : Reclaiming the micro-level exploration space
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Research & Development (R&D) departments are becoming increasingly structured and routine-based, with tight schedules and daily follow-ups. This way of working stems from increased demands for delivering products to customers quickly and with high quality at a low price. At the same time, these organisations are faced with the challenge of coming up with new ideas that can become the foundations of tomorrow’s innovations. This means that R&D departments must achieve both exploration, in terms of coming up with new ideas, and exploitation in terms of turning existing ideas into products available on the market. If these dual perspectives are to be met within a single work unit, the employees in that unit must achieve what we call contextual ambidexterity. Previous research has shown this to be difficult to achieve and has offered little guidance for organisations about how to organise and manage their operations in order to increase their chances of achieving contextual ambidexterity.The aim of this thesis is to explore challenges related to innovation that are encountered at the micro-level in contextually ambidextrous organisations and to shed light on factors that explain those challenges.This study has combined survey data with interview data from several organisations to analyse the relationship between aspects of efficiency and aspects of creativity. It was found that employees in a contextually ambidextrous organisation struggle to ensure enough micro-level exploration space, in other words, they have trouble finding time to explore ideas and making room for novel ideas.This research shows that a contextually ambidextrous approach in R&D will likely exert two main challenges related to innovation. The first challenge is a crowding out of exploratory activities in favour of exploitatory activities. One reason for this is the combination of using productivity goals for exploitation and not using any similar targets for exploration activities. Large discrepancies in how these two types of activities are treated runs the risk that the one that is less monitored – most often exploration – is likely to be crowded out in favour of the one that is more intensely monitored.A second possible challenge is the demand on predictability in project progress that is often built into organisations as a means to enhance exploitation. This aim for predictability might create a reluctance to introduce new projects with high levels of novelty because the introduction of novel ideas contains uncertainties that jeopardise the adherence to the project plan. The combination of this view of novelty in the later phases of product development and the crowding out of exploratory activities could possibly lead to insufficient room for novel ideas to gain ground in the organisation, and this could lead to less innovative output.
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18.
  • Pasquier, Coralie, et al. (författare)
  • Anisotropic protein-protein interactions in dilute and concentrated solutions
  • 2023
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797. ; 629, s. 794-804
  • Tidskriftsartikel (refereegranskat)abstract
    • Interactions between biomolecules are ubiquitous in nature and crucial to many applications including vaccine development; environmentally friendly textile detergents; and food formulation. Using small angle X-ray scattering and structure-based molecular simulations, we explore protein–protein interactions in dilute to semi-concentrated protein solutions. We address the pertinent question, whether interaction models developed at infinite dilution can be extrapolated to concentrated regimes? Our analysis is based on measured and simulated osmotic second virial coefficients and solution structure factors at varying protein concentration and for different variants of the protein Thermomyces Lanuginosus Lipase (TLL). We show that in order to span the dilute and semi-concentrated regime, any model must carefully capture the balance between spatial and orientational correlations as the protein concentration is elevated. This requires consideration of the protein surface morphology, including possible patch interactions. Experimental data for TLL is most accurately described when assuming a patchy interaction, leading to dimer formation. Our analysis supports that the dimeric proteins predominantly exist in their open conformation where the active site is exposed, thereby maximising hydrophobic attractions that promote inter-protein alignment.
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  • Persson, Roger, et al. (författare)
  • Classroom acoustics and hearing ability as determinants for perceived social climate and intentions to stay at work.
  • 2013
  • Ingår i: Noise & Health. - : Medknow. - 1463-1741. ; 15:67, s. 446-453
  • Tidskriftsartikel (refereegranskat)abstract
    • Background noise and room acoustics may impede social interactions by interfering with oral communication and other cognitive processes. Accordingly, recent research in school environments has showed that social relationships with peers and teachers are described more negatively in rooms with long reverberation times (RT). The purpose of this study was to investigate how RT and hearing ability (i.e., hearing thresholds [HT] and distortion product oto-acoustic emissions) were associated with schoolteachers' perceptions of the social climate at work and their intentions to stay on the job. Schoolteachers (n = 107) from 10 schools that worked in classrooms classified by acoustical experts as "short RT" (3 schools, mean RT 0.41-0.47 s), "medium RT" (3 schools, mean RT 0.50-0.53 s), and "long RT" (4 schools, mean RT 0.59-0.73 s) were examined. Teachers who worked in classrooms with long RT perceived their social climate to be more competitive, conflict laden, and less relaxed and comfortable. They were more doubtful about staying on the job. Even if the teachers were generally satisfied with their work the results suggest that the comfort at work may have been further improved by acoustical interventions that focus on reducing sound reflections in the classrooms. Yet, due the study design and the novelty of the findings the potential practical significance of our observations remains to be evaluated.
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  • Roelsgaard, Ida Kristiane, et al. (författare)
  • The effect of an intensive smoking cessation intervention on disease activity in patients with rheumatoid arthritis : Study protocol for a randomised controlled trial
  • 2017
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Rheumatoid arthritis (RA) is a chronic, inflammatory rheumatic disease with the potential to induce significant disability. Patients with RA are at increased risk of cardiovascular diseases (CVD). Smokers with RA tend to experience more pain and fatigue, higher disease activity, more erosive joint destruction and a lower health-related quality of life (HR-QoL) than non-smokers. It remains to be determined whether these effects can be reduced by smoking cessation. This randomised controlled trial (RCT) in patients with RA aims to examine the effect of intensive smoking cessation intervention (motivational counselling combined with tailored nicotine replacement therapy) versus standard care on smoking cessation, and consequently on disease activity. Secondary objectives are to explore the effect on flare, risk factors for CVD, lung function, physical function, HR-QoL, pain and fatigue in patients with RA. Methods: This will be a multicentre, open label, two arm, parallel group, RCT, including 150 daily smokers with RA, being in remission or having low-moderate disease activity (DAS28 ≤ 5.1). The intervention group (n = 75) will receive five counselling sessions with a trained smoking cessation counsellor based on the principles of motivational counselling. Furthermore, intervention patients will be offered nicotine replacement therapy tailored to individual needs. Participants randomised to the control group will receive standard care. The co-primary outcome is a hierarchical endpoint, which will be evaluated at 3 months follow-up and will include (1) self-reported smoking cessation biochemically validated by exhaled carbon monoxide and (2) achievement of EULAR clinical response (an improvement in DAS28 of > 0.6). Follow-up visits will be performed at 3, 6 and 12 months post-intervention. Discussion: This trial will reveal whether intensive smoking cessation counselling helps smokers with RA to achieve continuous smoking cessation and whether, as a concomitant benefit, it will reduce their RA disease activity. The trial aims to generate high quality evidence for the feasibility of a health promotion intervention for smokers with RA. Trial registration: ClinicalTrials.gov, identifier: NCT02901886. Registered on 10 September 2016. Recruitment status updated on 10th October 2016.
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21.
  • Rosenbak, Søren, 1987-, et al. (författare)
  • OSLO magazine vol. 1+2+3
  • 2016
  • Annan publikation (populärvet., debatt m.m.)
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22.
  • Sakhnini, Laila I, et al. (författare)
  • Improving the Developability of an Antigen Binding Fragment by Aspartate Substitutions
  • 2019
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 58:24, s. 2750-2759
  • Tidskriftsartikel (refereegranskat)abstract
    • Aggregation can be a major challenge in the development of antibody-based pharmaceuticals as it can compromise the quality of the product during bioprocessing, formulation, and drug administration. To avoid aggregation, developability assessment is often run in parallel with functional optimization in the early screening phases to flag and deselect problematic molecules. As developability assessment can be demanding with regard to time and resources, there is a high focus on the development of molecule design strategies for engineering molecules with a high developability potential. Previously, Dudgeon et al. [(2012) Proc. Natl. Acad. Sci. U. S. A. 109, 10879-10884] demonstrated how Asp substitutions at specific positions in human variable domains and single-chain variable fragments could decrease the aggregation propensity. Here, we have investigated whether these Asp substitutions would improve the developability potential of a murine antigen binding fragment (Fab). A full combinatorial library consisting of 393 Fab variants with single, double, and triple Asp substitutions was first screened in silico with Rosetta; thereafter, 26 variants with the highest predicted thermodynamic stability were selected for production. All variants were subjected to a set of developability studies. Interestingly, most variants had thermodynamic stability on par with or improved relative to that of the wild type. Twenty-five of the variants exhibited improved nonspecificity. Half of the variants exhibited improved aggregation resistance. Strikingly, while we observed remarkable improvement in the developability potential, the Asp substitutions had no substantial effect on the antigenic binding affinity. Altogether, by combining the insertion of negative charges and the in silico screen based on computational models, we were able to improve the developability of the Fab rapidly.
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23.
  • Sliwinska-Kowalska, Mariola, et al. (författare)
  • Ototoxicity of organic solvents - from scientific evidence to health policy.
  • 2007
  • Ingår i: International journal of occupational medicine and environmental health. - Lodz : Nofer Institute of Occupational Medicine. - 1232-1087 .- 1896-494X. ; 20:2, s. 215-22
  • Tidskriftsartikel (refereegranskat)abstract
    • The scientific workshop, organized under the 6th European Framework Programme, the Marie Curie Host Fellowship for the Transfer of Knowledge "NoiseHear" Project, by the Nofer Institute of Occupational Medicine (Åódź, Poland, 15-16 November 2006), gathered world specialists in noise, chemicals, and ototoxicity, including hearing researchers, toxicologists, otolaryngologists, audiologists and occupational health physicians.The workshop examined the evidence and the links between isolated exposure to organic solvents, combined exposure to noise and solvents, and effects on the auditory system. Its main purpose was to review the key scientific evidence to gather the necessary knowledge for developing adequate occupational health policies. This paper summarizes the workshop sessions and subsequent discussions.
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25.
  • Stenström, Johan, et al. (författare)
  • Carl Snoilsky och Bellman
  • 2010
  • Ingår i: Bellman i billed og digt. Rapport fra Bellmanfestivalen i København september-oktober 2006. - 9788779172692 ; , s. 223-241
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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26.
  • Stenström, Johan, et al. (författare)
  • Några nedslag i 1800-talets Fredmanikonografi
  • 2010
  • Ingår i: Bellman i billed og digt. Rapport fra Bellmanfestivalen i København september-oktober 2006. - 9788779172692 ; , s. 50-74
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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27.
  • Storgaard, Ida Klitzing, et al. (författare)
  • Population pharmacokinetic–pharmacodynamic model of subcutaneous bupivacaine in a novel extended-release microparticle formulation
  • Ingår i: Basic and Clinical Pharmacology and Toxicology. - 1742-7835.
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to develop a population pharmacokinetic–pharmacodynamic model of subcutaneously administered bupivacaine in a novel extended-release microparticle formulation for postoperative pain management. Bupivacaine was administered subcutaneously in the lower leg to 28 healthy male subjects in doses from 150 to 600 mg in a phase 1 randomized, placebo-controlled, double-blind, dose-ascending study with two different microparticle formulations, LIQ865A and LIQ865B. Warmth detection threshold was used as a surrogate pharmacodynamic endpoint. Population pharmacokinetic–pharmacodynamic models were fitted to plasma concentration-effect-time data using non-linear mixed-effects modelling. The pharmacokinetics were best described by a two-compartment model with biphasic absorption as two parallel absorption processes: a fast, zero-order process and a slower, first-order process with two transit compartments. The slow absorption process was found to be dose-dependent and rate-limiting for elimination at higher doses. Apparent bupivacaine clearance and the transit rate constant describing the slow absorption process both appeared to decrease with increasing doses following a power function with a shared covariate effect. The pharmacokinetic–pharmacodynamic relationship between plasma concentrations and effect was best described by a linear function. This model gives new insight into the pharmacokinetics and pharmacodynamics of microparticle formulations of bupivacaine and the biphasic absorption seen for several local anaesthetics.
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28.
  • Vaag, Allan, et al. (författare)
  • Non-obese patients with type 2 diabetes and prediabetic subjects: distinct phenotypes requiring special diabetes treatment and (or) prevention?
  • 2007
  • Ingår i: Applied Physiology, Nutrition and Metabolism. - 1715-5320. ; 32:5, s. 912-920
  • Tidskriftsartikel (refereegranskat)abstract
    • A major reason for the increased incidence of type 2 diabetes mellitus (T2DM) across the world is the so-called obesity epidemic, which occurs both in developed and developing countries. However, a large proportion of patients with T2DM in European and, in particular, Asian countries are non-obese. The non-obese T2DM phenotype is characterized by disproportionally reduced insulin secretion and less insulin resistance, as compared with obese patients with T2DM. Importantly, non-obese patients with T2DM have a similar increased risk of cardiovascular disease as obese T2DM patients. The risk of T2DM in non-obese patients is influenced by genetics as well as factors operating in utero indicated by low birth weight. Furthermore, this phenotype is slightly more prevalent among patients with latent autoimmune diabetes in adults, characterized by positive anti-GAD antibodies. The recently identified TCF7L2 gene polymorphism resulting in low insulin secretion influences the risk of T2DM in both obese and non-obese subjects, but is relatively more prevalent among non-obese patients with T2DM. Furthermore, the Prol2Ala polymorphism of the PPAR-gamma gene influencing insulin action increases the risk of T2DM in non-obese subjects. Despite a "normal" body mass index, non-obese patients with T2DM are generally characterized by a higher degree of both abdominal and total fat masses (adiposity). Prevention of T2DM with lifestyle intervention is at least as effective in non-obese as in obese prediabetic subjects, and recent data suggest that metformin treatment targeting insulin resistance and non-glycemic cardiovascular disease risk factors is as beneficial in non-obese as in obese patients with T2DM. Nevertheless, non-obese patients with T2DM may progress to insulin treatment more rapidly as compared with obese patients with T2DM.
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