| 1. |
- Chorell, Elin, et al.
(författare)
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A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 6:6, s. 2113-2120
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Tidskriftsartikel (refereegranskat)abstract
- A novel hypothesis-free multivariate screening methodology for the study of human exercise metabolism in blood serum is presented. Serum gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) data was processed using hierarchical multivariate curve resolution (H-MCR), and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to model the systematic variation related to the acute effect of strenuous exercise. Potential metabolic biomarkers were identified using data base comparisons. Extensive validation was carried out including predictive H-MCR, 7-fold full cross-validation, and predictions for the OPLS-DA model, variable permutation for highlighting interesting metabolites, and pairwise t tests for examining the significance of metabolites. The concentration changes of potential biomarkers were verified in the raw GC/TOFMS data. In total, 420 potential metabolites were resolved in the serum samples. On the basis of the relative concentrations of the 420 resolved metabolites, a valid multivariate model for the difference between pre- and post-exercise subjects was obtained. A total of 34 metabolites were highlighted as potential biomarkers, all statistically significant (p < 8.1E-05). As an example, two potential markers were identified as glycerol and asparagine. The concentration changes for these two metabolites were also verified in the raw GC/TOFMS data.The strategy was shown to facilitate interpretation and validation of metabolic interactions in human serum as well as revealing the identity of potential markers for known or novel mechanisms of human exercise physiology. The multivariate way of addressing metabolism studies can help to increase the understanding of the integrative biology behind, as well as unravel new mechanistic explanations in relation to, exercise physiology.
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| 2. |
- Chorell, Elin, et al.
(författare)
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Statistical multivariate metabolite profiling for aiding biomarker pattern detection and mechanistic interpretations in GC/MS based metabolomics
- 2006
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Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 2:4, s. 257-68
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Tidskriftsartikel (refereegranskat)abstract
- A strategy for robust and reliable mechanistic statistical modelling of metabolic responses in relation to drug induced toxicity is presented. The suggested approach addresses two cases commonly occurring within metabonomic toxicology studies, namely; 1) A pre-defined hypothesis about the biological mechanism exists and 2) No such hypothesis exists. GC/MS data from a liver toxicity study consisting of rat urine from control rats and rats exposed to a proprietary AstraZeneca compound were resolved by means of hierarchical multivariate curve resolution (H-MCR) generating 287 resolved chromatographic profiles with corresponding mass spectra. Filtering according to significance in relation to drug exposure rendered in 210 compound profiles, which were subjected to further statistical analysis following correction to account for the control variation over time. These dose related metabolite traces were then used as new observations in the subsequent analyses. For case 1, a multivariate approach, named Target Batch Analysis, based on OPLS regression was applied to correlate all metabolite traces to one or more key metabolites involved in the pre-defined hypothesis. For case 2, principal component analysis (PCA) was combined with hierarchical cluster analysis (HCA) to create a robust and interpretable framework for unbiased mechanistic screening. Both the Target Batch Analysis and the unbiased approach were cross-verified using the other method to ensure that the results did match in terms of detected metabolite traces. This was also the case, implying that this is a working concept for clustering of metabolites in relation to their toxicity induced dynamic profiles regardless if there is a pre-existing hypothesis or not. For each of the methods the detected metabolites were subjected to identification by means of data base comparison as well as verification in the raw data. The proposed strategy should be seen as a general approach for facilitating mechanistic modelling and interpretations in metabolomic studies.
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| 3. |
- Thysell, Elin, et al.
(författare)
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Reliable Profile Detection in Comparative Metabolomics
- 2007
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Ingår i: Omics. - : Mary Ann Liebert. - 1536-2310 .- 1557-8100. ; 11:2, s. 209-224
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Tidskriftsartikel (refereegranskat)abstract
- A strategy for processing of metabolomic GC/MS data is presented. By considering the relationship between quantity and quality of detected profiles, representative data suitable for multiple sample comparisons and metabolite identification was generated. Design of experiments (DOE) and multivariate analysis was used to relate the changes in settings of the hierarchical multivariate curve resolution (H-MCR) method to quantitative and qualitative characteristics of the output data. These characteristics included number of resolved profiles, chromatographic quality in terms of reproducibility between analytical replicates, and spectral quality defined by purity and number of spectra containing structural information. The strategy was exemplified in two datasets: one containing 119 common metabolites, 18 of which were varied according to a DOE protocol; and one consisting of rat urine samples from control rats and rats exposed to a liver toxin. It was shown that the performance of the data processing could be optimized to produce metabolite data of high quality that allowed reliable sample comparisons and metabolite identification. This is a general approach applicable to any type of data processing where the important processing parameters are known and relevant output data characteristics can be defined. The results imply that this type of data quality optimization should be carried out as an integral step of data processing to ensure high quality data for further modeling and biological evaluation. Within metabolomics, this degree of optimization will be of high importance to generate models and extract biomarkers or biomarker patterns of biological or clinical relevance.
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| 4. |
- Andersson, David C., 1978-, et al.
(författare)
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A multivariate approach to investigate docking parameters' effects on docking performance
- 2007
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Ingår i: Journal of chemical information and modeling. - : American Chemical Society Publications. - 1549-9596 .- 1549-960X. ; 47:4, s. 1673-1687
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Tidskriftsartikel (refereegranskat)abstract
- Increasingly powerful docking programs for analyzing and estimating the strength of protein-ligand interactions have been developed in recent decades, and they are now valuable tools in drug discovery. Software used to perform dockings relies on a number of parameters that affect various steps in the docking procedure. However, identifying the best choices of the settings for these parameters is often challenging. Therefore, the settings of the parameters are quite often left at their default values, even though scientists with long experience with a specific docking tool know that modifying certain parameters can improve the results. In the study presented here, we have used statistical experimental design and subsequent regression based on root-mean-square deviation values using partial least-square projections to latent structures (PLS) to scrutinize the effects of different parameters on the docking performance of two software packages: FRED and GOLD. Protein-ligand complexes with a high level of ligand diversity were selected from the PDBbind database for the study, using principal component analysis based on 1D and 2D descriptors, and space-filling design. The PLS models showed quantitative relationships between the docking parameters and the ability of the programs to reproduce the ligand crystallographic conformation. The PLS models also revealed which of the parameters and what parameter settings were important for the docking performance of the two programs. Furthermore, the variation in docking results obtained with specific parameter settings for different protein-ligand complexes in the diverse set examined indicates that there is great potential for optimizing the parameter settings for selected sets of proteins.
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| 5. |
- Berg, Thomas, et al.
(författare)
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The Effect of Study Design and Analysis Methods on Recovery Rates in Bell's Palsy
- 2009
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Ingår i: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 119:10, s. 2046-2050
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Tidskriftsartikel (refereegranskat)abstract
- Objectives/Hypothesis: We investigated how study design affects the rate of recovery in Bell's palsy. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Methods: Data were extracted from the Scandinavian Bell's palsy study, which included 829 patients. The study design was factorial; 416 patients given prednisolone, 413 not given prednisolone, 413 patients given valacyclovir, 416 not given valacyclovir. Data were analyzed with intention-to-treat principle and complete-case analysis methods and recovery was defined as Sunnybrook score 100, House-Brackmann grade I or <= grade II at 12 months. Results: With the intention-to-treat principle and last-observation-carried-forward method (n = 829) and recovery defined as Sunnybrook 100, 300 of the 416 patients (72%) receiving prednisolone had recovered compared with 237 of the 413 (57%) who did not receive prednisolone (P < .0001). With recovery defined as House-Brackmann grade 1, the corresponding recovery rates were 324 of 416 (78%) and 266 of 413 (64%) (P < .0001). With complete-case analysis and recovery defined House-Brackmann grade I (n = 782), 335 of 389 patients (86%) given prednisolone recovered compared with 277 of 393 (70%) in the group not given prednisolone (P < .0001). With recovery defined as House-Brackmann <= grade II (n = 797), the corresponding recovery rates were 380 of 396 (96%) and 353 of 401 (88%) (P < .0001). The analysis method affected the recovery rates in the valacyclovir and no-valacyclovir groups in a similar way as in the prednisolone and no-prednisolone groups. Conclusions: Recovery rates in a Bell's palsy study are substantially affected by the choice of analysis method and definition of recovery.
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| 6. |
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| 7. |
- Ekbladh, Elin, 1974-
(författare)
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Return to Work : Assessment of Subjective Psychosocial and Environmental Factors
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduktion: Sjukfrånvaron i Sverige är hög och kunskap om vad som påverkar återgång i arbete efter sjukskrivning behöver utvecklas. I processen kring återgång i arbete är bedömning av arbetsförmåga en viktig del. Bristen på valida, reliabla och teoretiskt förankrade bedömningsinstrument inom området är dock ett bekymmer eftersom tillförlitliga bedömningar av arbetsförmåga är en förutsättning för utformning och genomförande av interventioner för att stödja återgång i arbete. Denna typ av interventioner kräver multidisciplinär kompetens där arbetsterapeuter utgör en viktig funktion. Vid bedömning av arbetsförmåga bör personens subjektiva uppfattning om sin situation beaktas, då den har betydelse för utfallet av återgång i arbete. Worker Role Interview (WRI) och Work Environment Impact Scale (WEIS) är två arbetsrelaterade intervjuinstrument, som har utvecklats i syfte att bedöma subjektiva psykosociala och miljömässiga faktorers påverkan på arbetsförmåga. Den teoretiska grunden till WRI och WEIS är Model of Human Occupation, som är en modell med fokus på aktivitetsutförande i relation till psykosociala faktorer. Inledande prövningar av WRI och WEIS reliabilitet och validitet har genomförts. Bedömningsinstrumenten har bearbetats och översatts till svenska och används främst av arbetsterapeuter, som arbetar med personer med arbetsrelaterad problematik.Syfte: Det övergripande syftet med avhandlingen är att undersöka användbarheten av bedömningsinstrumenten Worker Role Interview och Work Environment Impact Scale för identifiering av psykosociala och miljömässiga rehabiliteringsbehov av betydelse för återgång i arbete.Metod: Avhandlingen består av fem empiriska studier. I samtliga studier har erhållen information bearbetats kvantitativt. I studie IV har även kvalitativ bearbetning genomförts. Studie I, II och IV är tvärsnittsstudier och studie II och V är två års longitudinella studier. I studie I samlades information in via enkät. I studie II, III och V bestod den huvudsakliga informationen av skattningar utifrån WRI variabler och i studie IV var bedömningar utifrån WEIS i form av skattningar och nedskrivna kommentarer till skattningarna den huvudsakliga informationen.Resultat: I studie I undersöktes vilka teoretiska utgångspunkter och professionsspecifika modeller arbetsterapeuter i Sverige ansåg påverka den psykiatriska vården och den psykiatriska arbetsterapin. Det psykosociala perspektivet var den teoretiska utgångspunkt som hade störst påverkan både på psykiatrisk vård och på psykiatrisk arbetsterapi. Den arbetsterapeutiska modell som flest identifierade var Model of Human Occupation. Detta resultat indikerar att Model of Human Occupation verkar vara användbar inom arbetsterapi och motiverade vidare användning av modellen i denna avhandling. Det som dock också framkom i studie I var att arbetsterapeuter inom psykiatrisk vård använde professionsspecifika modeller i en relativt liten utsträckning. Ett sätt att öka tillämpningen av teori i praktik är att använda teoretiskt grundade bedömningsinstrument. I studie II, III, IV och V har endera av de Model of Human Occupation- baserade bedömningsinstrumenten WRI och WEIS använts och värderats.I studie II och V prövades WRI:s förmåga att predicera återgång i arbete efter långvarig sjukskrivning. Det område i WRI som uppvisade bäst prediktivitet var området ”Självuppfattning” vars variabler beaktar personens motivation för återgång i arbete i form av personens upplevelse av kompetens och effektivitet för att utföra arbetsuppgifter och hantera utmaningar i arbetet. De två WRI variabler som bäst kunde predicera vilka som skulle återgå respektive inte återgå i arbete vid uppföljning efter två år var: ”Tro på sin arbetsförmåga”, och ”Dagliga vanor och rutiner”. Resultaten tyder på att kunskap om hur tro på den egna förmågan stärks och kunskap om dagliga vanor och rutiners påverkan på utförande av arbete är central vid genomförande av interventioner i syfte att stödja personer att återgå till arbete efter sjukskrivning.I studie III prövades WRI:s konstrukturella validitet i en internationell studie. Samtliga variabler i WRI, förutom de som tillhör miljöområdet, uppvisade en god konstrukturell validitet dvs mätte psykosociala faktorers påverkan på arbetsförmågan. WRI:s skattningsskala verkar stabil och valid mellan olika länder och för personer med olika diagnoser. I analysen framkom att WRI kunde särskilja mellan personers psykosociala arbetsförmåga på tre olika nivåer.I studie IV undersöktes hur personer med erfarenhet av långtidssjukskrivning uppfattar att faktorer i arbetsmiljön stödjer respektive hindrar personens utförande av arbete och välbefinnande genom bedömningar utifrån WEIS. De faktorer som uppfattades som meststödjande var olika former av sociala interaktioner på arbetet samt uppfattningen om arbetets värde och mening. De faktorer som uppfattades som mest hindrande var olika krav i relation till arbetsgenomförandet samt den belöning som erhålls för arbetet.Konklusion: Sammanfattningsvis så kan WRI användas för bedömning av psykosociala faktorers påverkan på arbetsförmågan. I WRI ingår variabler som kan predicera återgång till arbete upp till två år efter genomförd bedömning. WEIS verkar användbart för att identifiera arbetsmiljöfaktorer som stödjer respektive hindrar personers välbefinnande och utförande av arbete. Att komplettera olika datainsamlingsmetoder är en förutsättning för att uppnå en så god bedömning av arbetsförmåga som möjligt. Den information som WRI- och WEISintervjuer genererar är värdefull, då den kan utgöra en viktig grund för planering av individspecifika rehabiliteringsinsatser. Bedömningsinstrumenten WRI och WEIS med sin teoretiska förankring i Model of Human Occupation kan anses vara användbara för att identifiera psykosociala och miljömässiga rehabiliteringsbehov i syfte att stödja personer i processen åter till arbete efter sjukskrivning.
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| 8. |
- Grönwall, Caroline, et al.
(författare)
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Selection and characterization of Affibody ligands binding to Alzheimer amyloid beta peptides
- 2007
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 128:1, s. 162-183
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Tidskriftsartikel (refereegranskat)abstract
- Affibody (Affibody) ligands specific for human amyloid beta (Abeta) peptides (40 or 42 amino acid residues in size), involved in the progress of Alzheimer's disease, were selected by phage display technology from a combinatorial protein library based on the 58-amino acid residue staphylococcal protein A-derived Z domain. Post-selection screening of 384 randomly picked clones, out of which 192 clones were subjected to DNA sequencing and clustering, resulted in the identification of 16 Affibody variants that were produced and affinity purified for ranking of their binding properties. The two most promising Affibody variants were shown to selectively and efficiently bind to Abeta peptides, but not to the control proteins. These two Affibody ligands were in dimeric form (to gain avidity effects) coupled to affinity resins for evaluation as affinity devices for capture of Abeta peptides from human plasma and serum. It was found that both ligands could efficiently capture Abeta that were spiked (100 microgml(-1)) to plasma and serum samples. A ligand multimerization problem that would yield suboptimal affinity resins, caused by a cysteine residue present at the binding surface of the Affibody ligands, could be circumvented by the generation of second-generation Affibody ligands (having cysteine to serine substitutions). In an epitope mapping effort, the preferred binding site of selected Affibody ligands was mapped to amino acids 30-36 of Abeta, which fortunately would indicate that the Affibody molecules should not bind the amyloid precursor protein (APP). In addition, a significant effort was made to analyze which form of Abeta (monomer, dimer or higher aggregates) that was most efficiently captured by the selected Affibody ligand. By using Western blotting and a dot blot assay in combination with size exclusion chromatography, it could be concluded that selected Affibody ligands predominantly bound a non-aggregated form of analyzed Abeta peptide, which we speculate to be dimeric Abeta. In conclusion, we have successfully selected Affibody ligands that efficiently capture Abeta peptides from human plasma and serum. The potential therapeutic use of these optimized ligands for extracorporeal capture of Abeta peptides in order to slow down or reduce amyloid plaque formation, is discussed.
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| 9. |
- Hedén, Martin, 1976, et al.
(författare)
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Thermal radiation from CN+ and La@CN
- 2005
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Ingår i: J. Chem. Phys.. - : AIP Publishing. - 0021-9606. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- The radiative cooling of positively charged fullerene and endohedral fullerene fragments of C60, C70, C84, and La@C82 has been measured in a time-of-flight mass spectrometer. The radiative cooling is measured via its influence on the metastable decay. The emissivity extracted from the data is between 4×10–4 and 13×10–4. These values agree fairly well with the emissivity calculated from considering the low-energy tail of the surface plasmon. No major difference is found in the emission behavior of empty and endohedral fullerenes.
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| 10. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Possible association between the androgen receptor gene and autism spectrum disorder.
- 2009
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 34:5, s. 752-761
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Tidskriftsartikel (refereegranskat)abstract
- Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other observations, has led to the suggestion that prenatal brain exposure to androgens may be of importance for the development of this condition. Prompted by this hypothesis, we investigated the potential influence of variation in the androgen receptor (AR) gene on the susceptibility for autism. To this end, 267 subjects with autism spectrum disorder and 617 controls were genotyped for three polymorphisms in exon 1 of the AR gene: the CAG repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected siblings were genotyped for 118 and 32 of the cases, respectively. Case-control comparisons revealed higher prevalence of short CAG alleles as well as of the A allele of the rs6152 SNP in female cases than in controls, but revealed no significant differences with respect to the GGN repeat. Analysis of the 118 families using transmission disequilibrium test, on the other hand, suggested an association with the GGN polymorphism, the rare 20-repeat allele being undertransmitted to male cases and the 23-repeat allele being overtransmitted to female cases. Sequencing of the AR gene in 46 patients revealed no mutations or rare variants. The results lend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition.
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| 11. |
- Jonsson, Pär, et al.
(författare)
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Predictive metabolite profiling applying hierarchical multivariate curve resolution to GC-MS data : a potential tool for multi-parametric diagnosis
- 2006
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Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 5:6, s. 1407-1414
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Tidskriftsartikel (refereegranskat)abstract
- A method for predictive metabolite profiling based on resolution of GC-MS data followed by multivariate data analysis is presented and applied to three different biofluid data sets (rat urine, aspen leaf extracts, and human blood plasma). Hierarchical multivariate curve resolution (H-MCR) was used to simultaneously resolve the GC-MS data into pure profiles, describing the relative metabolite concentrations between samples, for multivariate analysis. Here, we present an extension of the H-MCR method allowing treatment of independent samples according to processing parameters estimated from a set of training samples. Predictions or inclusion of the new samples, based on their metabolite profiles, into an existing model could then be carried out, which is a requirement for a working application within, e.g., clinical diagnosis. Apart from allowing treatment and prediction of independent samples the proposed method also reduces the time for the curve resolution process since only a subset of representative samples have to be processed while the remaining samples can be treated according to the obtained processing parameters. The time required for resolving the 30 training samples in the rat urine example was approximately 13 h, while the treatment of the 30 test samples according to the training parameters required only approximately 30 s per sample (approximately 15 min in total). In addition, the presented results show that the suggested approach works for describing metabolic changes in different biofluids, indicating that this is a general approach for high-throughput predictive metabolite profiling, which could have important applications in areas such as plant functional genomics, drug toxicity, treatment efficacy and early disease diagnosis.
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| 12. |
- Marsell, Richard, et al.
(författare)
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Fibroblast growth factor-23 is associated with parathyroid hormone and renal function in a population-based cohort of elderly men.
- 2008
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 158:1, s. 125-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Fibroblast growth factor-23 (FGF23) is a circulating factor involved in phosphate (Pi) and vitamin D metabolism. Serum FGF23 is increased at later stages of chronic kidney disease due to chronic hyperphosphatemia and decreased renal clearance. Recent studies also indicate that FGF23 may directly regulate the expression of parathyroid hormone (PTH) in vitro. Therefore, the objective of the current study was to determine the relationship between FGF23, PTH, and other biochemistries in vivo in subjects with no history of renal disease. DESIGN: Serum biochemistries were measured in a subsample of the population-based Swedish part of the MrOS study. In total, 1000 Caucasian men aged 70-80 years were randomly selected from the population. METHODS: Intact FGF23, Pi, calcium, albumin, estimated glomerular filtration rate (eGFR, calculated from cystatin C), PTH, and 25(OH)D3 were measured. Association studies were performed using linear univariate and multivariate regression analyses. RESULTS: The median FGF23 level was 36.6 pg/ml, ranging from 0.63 to 957 pg/ml. There was a significant correlation between log FGF23 and eGFR (r=-0.21; P<0.00001) and log PTH (r=0.13; P<0.001). These variables remained as independent predictors of FGF23 in multivariate analysis. In addition, log PTH (beta=0.082; P<0.05) and eGFR (beta=-0.090; P<0.05) were associated with log FGF23 in subjects with eGFR>60 ml/min. Only eGFR (beta=-0.35; P<0.0001) remained as a predictor of log FGF23 in subjects with eGFR<60 ml/min. CONCLUSIONS: Serum FGF23 and PTH are associated in vivo, supporting recent findings that FGF23 directly regulates PTH expression in vitro. Additionally, eGFR is associated with FGF23 in subjects with normal or mildly impaired renal function, indicating that GFR may modulate FGF23 levels independent of serum Pi.
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| 13. |
- Quartino, Angelica, et al.
(författare)
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Modeling of in vitro drug activity and prediction of clinical outcome in acute myeloid leukemia
- 2007
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Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:8, s. 1014-1021
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of this study were to develop a population pharmacodynamic model describing the in vitro drug sensitivity of tumor cells and to relate in vitro parameters to clinical outcome. Cell samples from 179 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and daunorubicin, and cytotoxicity was analyzed using the fluorometric microculture cytotoxicity assay. A sigmoid E(max)-model for daunorubicin and an E(max)-model for cytosine arabinoside described the data. The model predicted drug potency (EC(50)) adequately from 1 concentration measurement. A logistic regression on individual in vitro parameters of 46 patients treated with the daunorubicin plus cytosine arabinoside regimen showed that the probability of complete response was significantly (P < .05) related to the product of the E(max)/EC(50) ratio of the two drugs. The findings demonstrate the value of population pharmacodynamic modeling of in vitro drug sensitivity data and a significant relationship between the in vitro parameters and clinical outcome.
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| 14. |
- Rigné, Eva Marie, et al.
(författare)
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Kunskapandets och den lokala politikens utmaningar : En idéskrift till ett forskningsprogram
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten presenterar en plattform för kommunrelaterad forskning och utveckling (FoU) utifrån ett kunskapssociologiskt perspektiv på en ny roll för kommuner som "kunskapande aktörer", vid sidan av den traditionella rollen som förvaltare/implementerare av FoU-arbete bedrivet nationellt. Den diskuterar olika styrningsperspektiv och föreställningar om kunskapsproduktion och -användning, och föreslår tre grundläggande inriktningar för kommande kommunforskning vid CKS.
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| 15. |
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