| 1. |
- Chorell, Elin, et al.
(författare)
-
A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum
- 2007
-
Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 6:6, s. 2113-2120
-
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.
|
|
| 2. |
- Chorell, Elin, et al.
(författare)
-
Statistical multivariate metabolite profiling for aiding biomarker pattern detection and mechanistic interpretations in GC/MS based metabolomics
- 2006
-
Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 2:4, s. 257-68
-
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.
|
|
| 3. |
|
|
| 4. |
- Jonsson, Pär, et al.
(författare)
-
Constrained randomization and multivariate effect projections improve information extraction and biomarker pattern discovery in metabolomics studies involving dependent samples
- 2015
-
Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 11:6, s. 1667-1678
-
Tidskriftsartikel (refereegranskat)abstract
- Analytical drift is a major source of bias in mass spectrometry based metabolomics confounding interpretation and biomarker detection. So far, standard protocols for sample and data analysis have not been able to fully resolve this. We present a combined approach for minimizing the influence of analytical drift on multivariate comparisons of matched or dependent samples in mass spectrometry based metabolomics studies. The approach is building on a randomization procedure for sample run order, constrained to independent randomizations between and within dependent sample pairs (e.g. pre/post intervention). This is followed by a novel multivariate statistical analysis strategy allowing paired or dependent analyses of individual effects named OPLS-effect projections (OPLS-EP). We show, using simulated data that OPLS-EP gives improved interpretation over existing methods and that constrained randomization of sample run order in combination with an appropriate dependent statistical test increase the accuracy and sensitivity and decrease the false omission rate in biomarker detection. We verify these findings and prove the strength of the suggested approach in a clinical data set consisting of LC/MS data of blood plasma samples from patients before and after radical prostatectomy. Here OPLS-EP compared to traditional (independent) OPLS-discriminant analysis (OPLS-DA) on constrained randomized data gives a less complex model (3 versus 5 components) as well a higher predictive ability (Q2 = 0.80 versus Q2 = 0.55). We explain this by showing that paired statistical analysis detects 37 unique significant metabolites that were masked for the independent test due to bias, including analytical drift and inter-individual variation.
|
|
| 5. |
- Thysell, Elin, et al.
(författare)
-
Processing of mass spectrometry based metabolomics data for large scale screening studies and diagnostics
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In mass spectrometry based metabolomics predictive data processing and sample classification based on representative sample subsets makes it possible to screen large sample banks or data sets in an efficient fashion regarding both data quality and processing time. This is a requirement for making use of high sensitivity and complexity metabolite data and to turn the metabolomics field into a competitive omics platform for biological interpretation and diagnostics. Predictive metabolomics by means of hierarchical multivariate curve resolution (H-MCR) followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for the processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human blood serum samples collected in a study of strenuous physical exercise. The efficiency of the predictive processing as a high throughput tool for generating high quality data is clearly proven and stated as a main benefit of the method. Extensive model validation schemes by means of cross validation and external predictions verified the robustness of the extracted systematic patterns in the data. Comparisons regarding the extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power concerning longitudinal predictions provided proof for the diagnostic potential of the methodology. Finally, the predictive metabolite pattern was interpreted physiologically as well as verified in the literature, highlighting the biological relevance of the diagnostic pattern. The suggested approach makes it feasible to screen large data or sample sets with retained data quality and interpretation and to do this in a high throughput fashion. The method could be of value for sample bank mining, metabolome-wide association studies, verification of marker patterns and development of diagnostic systems.
|
|
| 6. |
- Thysell, Elin, et al.
(författare)
-
Reliable Profile Detection in Comparative Metabolomics
- 2007
-
Ingår i: Omics. - : Mary Ann Liebert. - 1536-2310 .- 1557-8100. ; 11:2, s. 209-224
-
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.
|
|
| 7. |
- Thysell, Elin, et al.
(författare)
-
Validated and predictive processing of gas chromatography-mass spectra screening studies, diagnostics and metabolite pattern verification
- 2012
-
Ingår i: Metabolites. - : M D P I AG. - 2218-1989 .- 2218-1989. ; 2:4, s. 796-817
-
Tidskriftsartikel (refereegranskat)abstract
- The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern.
|
|
| 8. |
- Thysell, Elin, et al.
(författare)
-
Validated and Predictive Processing of Gas Chromatography-Mass Spectrometry Based Metabolomics Data for Large Scale Screening Studies, Diagnostics and Metabolite Pattern Verification
- 2012
-
Ingår i: Metabolites. - Basel : MDPI. - 2218-1989. ; 2, s. 796-817
-
Tidskriftsartikel (refereegranskat)abstract
- The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern. The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern.
|
|
| 9. |
|
|
| 10. |
- Andersson, David C., 1978-, et al.
(författare)
-
A multivariate approach to investigate docking parameters' effects on docking performance
- 2007
-
Ingår i: Journal of chemical information and modeling. - : American Chemical Society Publications. - 1549-9596 .- 1549-960X. ; 47:4, s. 1673-1687
-
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.
|
|
| 11. |
|
|
| 12. |
- Basmarke-Wehelie, Rahma, et al.
(författare)
-
The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity
- 2011
-
Ingår i: Gastroenterology. - Baltimore : Elsevier BV. - 0016-5085 .- 1528-0012. ; 141:3, s. 918-928
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.
|
|
| 13. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 14. |
- Berg, Thomas, et al.
(författare)
-
The Effect of Prednisolone on Sequelae in Bell's Palsy
- 2012
-
Ingår i: Archives of Otolaryngology - Head & Neck Surgery. - 0886-4470 .- 1538-361X. ; 138:5, s. 443-447
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To study whether prednisolone reduces sequelae in Bell's palsy. Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial with 12 months of follow-up. Setting: Seventeen referral centers. Patients: In all, 829 patients aged 18 to 75 years. Interventions: Randomization within 72 hours in a factorial fashion to placebo plus placebo (n=206); prednisolone, 60 mg/d for 5 days, with the dosage then tapered for 5 days, plus placebo (n=210); valacyclovir hydrochloride, 1000 mg 3 times daily for 7 days, plus placebo (n=207); or prednisolone plus valacyclovir (n=206). Main Outcome Measures: Facial function at 12 months assessed with the Sunnybrook and House-Brackmann grading systems. Results: In 184 of the 829 patients, the Sunnybrook score was less than 90 at 12 months; 71 had been treated with prednisolone and 113 had not (P<.001). In 98 patients, the Sunnybrook score was less than 70; 33 had received prednisolone and 65 had not (P<.001). The difference between patients who received prednisolone and who did not in House-Brackmann gradings higher than I and higher than II was also significant (P<.001 and P=.01, respectively). No significant difference was found between patients who received prednisolone and those who did not in Sunnybrook scores less than 50 (P=.10) or House-Brackmann grades higher than III (P=.80). Synkinesis was assessed with the Sunnybrook score in 743 patients. Ninety-six patients had a synkinesis score more than 2, of whom 33 had received prednisolone and 63 had not (P=.001). Sixty patients had a synkinesis score more than 4, of whom 22 had received prednisolone and 38 had not (P=.005). Conclusion: Prednisolone significantly reduces mild and moderate sequelae in Bell's palsy.
|
|
| 15. |
- Berg, Thomas, et al.
(författare)
-
The Effect of Study Design and Analysis Methods on Recovery Rates in Bell's Palsy
- 2009
-
Ingår i: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 119:10, s. 2046-2050
-
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.
|
|
| 16. |
|
|
| 17. |
- Bjarnegard, Elin, et al.
(författare)
-
Sex instead of money: Conceptualizing sexual corruption
- 2024
-
Ingår i: Governance. An International Journal of Policy, Administration and Institutions. - : WILEY. - 0952-1895 .- 1468-0491.
-
Tidskriftsartikel (refereegranskat)abstract
- Research on the dynamics of corruption has rarely considered sex as a currency in corrupt transactions. This article puts forward the argument that the abuse of entrusted power in exchange for personal gain is relevant also when sex, rather than money, is the currency. It then contributes with a careful conceptualization of such transactions as sexual corruption. Anchoring our conceptualization in the abuse of entrusted power, the article defines sexual corruption, its elements, categories and delimitations, and proposes a conceptual framework that can be used to develop research on sexual corruption. We also address the implications of recognizing sex as a currency in corrupt transactions, providing insights as to why abuse of power is often overlooked when sex is the currency of the transaction. Our approach offers analytic precision and contributes to setting an agenda for the study of sexual corruption as an obstacle to good governance, at a time when efforts to collect data on sexual corruption are increasing.
|
|
| 18. |
- Boberg, Elin, 1980-, et al.
(författare)
-
Pollinator shifts and the evolution of spur length in the moth-pollinated orchid Platanthera bifolia
- 2014
-
Ingår i: Annals of Botany. - : Oxford University Press (OUP). - 0305-7364 .- 1095-8290. ; 113:2, s. 267-275
-
Tidskriftsartikel (refereegranskat)abstract
- Plantpollinator interactions are thought to have shaped much of floral evolution. Yet the relative importance of pollinator shifts and coevolutionary interactions for among-population variation in floral traits in animal-pollinated species is poorly known. This study examined the adaptive significance of spur length in the moth-pollinated orchid Platanthera bifolia. Geographical variation in the length of the floral spur of P. bifolia was documented in relation to variation in the pollinator fauna across Scandinavia, and a reciprocal translocation experiment was conducted in south-east Sweden between a long-spurred woodland population and a short-spurred grassland population. Spur length and pollinator fauna varied among regions and habitats, and spur length was positively correlated with the proboscis length of local pollinators. In the reciprocal translocation experiment, long-spurred woodland plants had higher pollination success than short-spurred grassland plants at the woodland site, while no significant difference was observed at the grassland site. The results are consistent with the hypothesis that optimal floral phenotype varies with the morphology of the local pollinators, and that the evolution of spur length in P. bifolia has been largely driven by pollinator shifts.
|
|
| 19. |
- Bommenel, Elin, et al.
(författare)
-
Att undervisa och delta i pedagogisk utveckling
- 2014
-
Ingår i: Efter festen. Om konsten att utvecklas från doktor till docent eller en överlevnadsguide för den postdoktorala tillvaron. - 9789144094809 ; , s. 73-89
-
Bokkapitel (refereegranskat)
|
|
| 20. |
- Bylund, Nina, et al.
(författare)
-
Quality of Life in Bell's Palsy : Correlation with Sunnybrook and House-Brackmann Over Time
- 2021
-
Ingår i: The Laryngoscope. - : John Wiley & Sons. - 0023-852X .- 1531-4995. ; 131:2, s. E612-E618
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo compare patient‐graded facial and social/well‐being function with physician‐graded facial function in Bell's palsy over time.Study DesignA prospective follow‐up study at two tertiary otorhinolaryngological centers.MethodsA total of 96 patients, 36 women and 60 men, aged 18–77 years, were included. Facial Clinimetric Evaluation (FaCE) scale and Facial Disability Index (FDI) scores were compared with Sunnybrook and House‐Brackmann scores.ResultsInclusion was on mean day 7 (96 patients) and follow‐up on days 53 (81 patients) and 137 (32 patients). Initially, correlations between FaCE total score, FaCE domains, FDI physical function, FDI social/well‐being function and Sunnybrook and House‐Brackmann scores were low to fair, except for FaCE facial movement (r = 0.55). Correlations between FaCE total score and Sunnybrook score were very good to excellent at visits 2 (r = 0.83) and 3 (r = 0.81). Women scored FaCE social and FDI social/well‐being function lower than men, despite similar Sunnybrook scores.ConclusionIn early stages of Bell's palsy, there were low to fair correlations between FaCE/FDI (except for facial movement) and Sunnybrook score. This implies that the design of the quality of life (QoL) instruments is less suited for the acute phase. The high correlations at follow‐ups suggest that the questionnaires can be used for evaluation of QoL over time. Our results indicate that women experience more facial palsy‐related psychosocial dysfunction.Level of Evidence4 Laryngoscope, 131:E612–E618, 2021
|
|
| 21. |
- Dahlén, Elin, et al.
(författare)
-
Sibship and dispensing patterns of asthma medication in young children : a population based study
- 2019
-
Ingår i: Pharmacoepidemiology & Drug Safety. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1053-8569 .- 1099-1557.
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Our aim was to study the association between sibship and dispensing patterns of asthma medication in young children, focusing on incidence and persistence, and taking sibship status, asthma diagnoses, and siblings’ medication into account. Methods: A register-based cohort study including all children (n=50,546) born in Stockholm, Sweden 2006–2007, followed up during 2006–2014. Exposure was sibling status; outcome was incidence of dispensed asthma medication and persistence over time. A Cox-model was used to study the association between sibship and asthma medication. Persistence was defined using two different time windows (4- and 18-months) in a refill sequence model including siblings’ and unrelated control children’s medication. Results: After one year of age, the adjusted hazard ratio of dispensed asthma medication was 0.85 (95%CI 0.80–0.90) among children with siblings compared to singletons. The estimated proportion of children with persistent controller medication was 7.2% (4-month model) and 64.5% (18-month model). When including the siblings’ controller medication, the estimated proportion was 8.8% (4-months) and 7.8% for control children (relative risk, RR 0.89, 95%CI 0.81-0.98). The persistence was lower for those with siblings compared to singletons (adj. RR 0.72, 95%CI 0.62-0.85 for 4-months) with similar estimates for older, younger, and full siblings and regardless of asthma diagnoses. Conclusions: Siblings have different dispensing patterns of asthma medications compared to singletons regardless of asthma diagnoses. After including the siblings’ asthma medication and compared with control children, the proportion of children with persistent medication increased which may indicate that siblings share asthma medications.
|
|
| 22. |
- Diesen, Veronica, et al.
(författare)
-
Silver enhanced TiO2 thin films : photocatalytic characterization using aqueous solutions of tris(hydroxymethyl)aminomethane
- 2014
-
Ingår i: Dalton Transactions. - 1477-9226 .- 1477-9234. ; 43:1, s. 344-351
-
Tidskriftsartikel (refereegranskat)abstract
- The photocatalytic activity in aqueous solutions of TiO2 and Ag enhanced TiO2 sol-gel produced films was characterized using tris(hydroxymethyl)aminomethane (Tris) under black light (365 nm) and the observed differences in efficiency were further investigated by O-2 adsorption studies using the same probe. Hydrogen abstracting species, such as hydroxyl radicals formed upon photocatalysis, are able to abstract hydrogen from Tris. This reaction leads to the formation of formaldehyde which was detected and quantified through a modified version of the Hantzsch reaction. It was found that the Ag enhanced TiO2 film increased the apparent quantum yield from 7% to 12%, partly as a result of a Schottky barrier formation at the metal-semiconductor interface and partly as the sensitizing effect of Ag nanoparticles extends the visible light absorption, which through electron transfer processes enable an efficient charge separation in the TiO2 by attracting acceptor species more efficiently than pure TiO2. The O-2 adsorption studies in this paper showed that the Ag enhanced TiO2 film has a stronger adsorption affinity than pure TiO2 towards O-2, which make the reduction of O-2 more efficient with a subsequent enhanced electron-hole lifetime. It was also found that the Ag enhanced TiO2 film had a poorer adsorption affinity for Tris than the pure TiO2 film, which is a consequence of fewer available surface adsorption sites due to the Ag coverage at 64% which agrees well with the obtained adsorption equilibrium constants (K-LH(TiO2) = 615 M-1 and KLH(Ag-TiO2) = 320 M-1).
|
|
| 23. |
- Dürango, Sofie, et al.
(författare)
-
Compliance with guidelines for postoperative pain management in infants and children
- 2017
-
Ingår i: International Journal of Healthcare Management. - : Informa UK Limited. - 2047-9700 .- 2047-9719. ; 10:4, s. 259-264
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative pain is still often being inadequately assessed and/or recorded in infants and young children despite evidence-based guidelines. Objectives: This prospective, observational study in a paediatric postoperative ward at a Swedish university hospital was designed to evaluate interventional effects on pain management by briefly reminding nursing staff of corresponding local guidelines. Methods: Individual structured postoperative information on the first day and night after mainly otorhinolaryngeal or plastic surgery was obtained in 100 pediatric patients from on-site bedside observation protocols, patient records, and telephone interviews over two 5-week periods before and after a study intervention with brief systematic information on local guideline contents. Results: The intervention was followed by significantly more assessments (P = 0.0012), hourly assessments (P < 0.0001), and use of validated tools for assessment (P < 0.0001) of pain intensity in out-hospital patients, but by no change in guardian satisfaction. There were non-significant corresponding changes in in-hospital patients. Conclusions: Bedside compliance with guidelines for postoperative pain management can be considerably improved in out-hospital (and possibly also in-hospital) paediatric patients by a structured brief reminder of existing guideline contents. Larger prospective studies are required to determine the importance of bedside compliance with clinical guidelines for postoperative comfort and safety in infants and children.
|
|
| 24. |
- Ekbladh, Elin, 1974-
(författare)
-
Return to Work : Assessment of Subjective Psychosocial and Environmental Factors
- 2008
-
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.
|
|
| 25. |
- Eldén, Åsa, et al.
(författare)
-
Sextortion : corruption and gender-based violence
- 2020
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sextortion är en form av korruption och könsbaserat våld. Det innebär att en person missbrukar sin maktposition för att få tillgång till en sexuell tjänst i utbyte mot en tjänst eller förmån som hen har möjlighet att bevilja eller undanhålla i kraft av sin position. Sextortion är en korrupt handling där valutan är sex, och en sexuell handling där utbytet, quid pro quo, medför en form av tvång. Ansvaret för sextortion ligger alltid hos den part som missbrukar sin position (förövaren), och utbytet bidrar till skam, rädsla och osynliggörande genom att offret framställs som ‘medskyldigt’. Sextortion är en kränkning av mänskliga rättigheter och ett missbruk av makt, och måste förstås i relation till de köns- och maktrelationer och -normer som utgör handlingens sammanhang.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Eriksson, Susanne, et al.
(författare)
-
Different beef breed sires used for crossbreeding with Swedish dairy cows - effects on calving performance and carcass traits
- 2020
-
Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 232
-
Tidskriftsartikel (refereegranskat)abstract
- Improved potential for weight gain and carcass classification traits in calves aimed at slaughter from dairy herds would increase the calves' economic value, and enable an increased beef production. At present, relatively low economic weights are placed on beef traits in the comprehensive Nordic dairy cattle breeding goal. An effective way to improve beef production from dairy herds is therefore to inseminate a larger proportion of dairy heifers and cows with beef bull semen. In the choice of beef bull breed, both effects on calving traits, carcass weight gain and carcass traits need to be considered. The aim of this study was therefore to compare different beef x dairy crosses regarding calving performance and carcass traits. Field data comprising in total close to 1.6 million calving records from Swedish herds, and more than 1.1 million carcass records from commercial slaughter houses, were analyzed using linear models. Differences in least-square means between different breed combinations were estimated for percentage of calving difficulty, stillbirth, daily carcass gain, carcass weight, EUROP conformation and fat classification. The dams were purebred Swedish Red (SR) or Swedish Holstein (SH), and the sires were either of purebred dairy (SR or SH) or of the beef breeds Angus, Hereford, Limousin, Simmental or Charolais. The results showed that crossbreeding dairy cows with beef bulls, especially of late maturing breeds, has potential to considerably improve beef production from dairy herds. Improvement of carcass characteristics and carcass gain were most noticeable in young crossbred bulls, where the highest increase for single breed combinations was 67% for conformation and 17% for carcass gain. Offspring of different beef x dairy combinations displayed varying average carcass gain and characteristics in terms of fatness and conformation in heifers, steers and young bulls, and would fit different types of production systems. Whereas crossbreeding had small or favorable effects on stillbirth, the use of late maturing beef breed sires negatively influenced the calving performance, especially in primiparous dairy cows. By choosing individual beef bulls with high estimated breeding values for calving ease, the percentage of calving difficulty could be reduced, even when using late maturing beef breed sires for crossbreeding.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Granbom, Marianne, et al.
(författare)
-
'Normality in all the abnormality' : Older adults' experiences of holidays and celebrations from the COVID-19 pandemic
- 2024
-
Ingår i: Australian Occupational Therapy Journal. - : John Wiley & Sons. - 1440-1630 .- 0045-0766.
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The importance of holidays, traditions, and family celebrations to human culture and occupational engagement has been neglected. The aim of this study was to explore how older adults experienced holidays and celebrations with social and physical distancing during the COVID-19 pandemic.METHODS: A secondary analysis was made on data from the At-Risk Study. Seventeen community-living adults (11 women and 6 men) aged 71-87 years, from Sweden participated. They were interviewed remotely four times during the first year of the pandemic. Data were analysed with qualitative content analysis. No consumer/community involvement occurred.FINDINGS: Three categories on how the participants hoped for, planned, decided, adapted, avoided, and experienced holidays and celebrations with social and physical distancing included expectations and preparations in unpredictable times; the constant need for re-evaluation; and almost everything turned out differently.CONCLUSIONS: The desire to celebrate despite pandemic restrictions shows the importance and meaning holidays hold for older adults. Celebrations can be disrupted for many reasons, not only as extreme as the ongoing pandemic. For wellbeing in later life health care, social care, and society need to understand the inherent components and acknowledge ways of supporting participation in occasional events such as holidays, traditions, and family celebrations.
|
|
| 32. |
- Grönwall, Caroline, et al.
(författare)
-
Selection and characterization of Affibody ligands binding to Alzheimer amyloid beta peptides
- 2007
-
Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 128:1, s. 162-183
-
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.
|
|
| 33. |
- Hansson, Martin, et al.
(författare)
-
Tunga ting med text : Sivert Grubbe och eftermälet
- 2019
-
Ingår i: Tidens landskap : En vänbok till Anders Andrén - En vänbok till Anders Andrén. - 0349-4128. - 9789188909121 ; :77, s. 48-50
-
Bokkapitel (refereegranskat)abstract
- Den här artikeln diskuterar den danske adelsmannen Sivert Grubbe och de tavlor med långa inskrifter på latin som han satte upp på sina herrgårdar Torup och Hovdala på 1630-talet. Tavlorna sattes upp mot slutet av hans liv och kan ses som ett försök att skapa ett minnesmärke över sig själv, att styra det egna eftermälet.
|
|
| 34. |
- Hassan, Saadia Bashir, et al.
(författare)
-
A hollow fiber model for in vitro studies of cytotoxic compounds : Activity of the cyanoguanidine CHS 828
- 2001
-
Ingår i: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 12:1, s. 33-42
-
Tidskriftsartikel (refereegranskat)abstract
- The hollow fiber assay is currently used as an in vivo model for anticancer drug screening in nude mice, but it can also be used as an in vitro model. In the current study, an in vitro hollow fiber model was used to study the effect and mode of induced cell death of a new cyanoguanidine, CHS 828. Human leukemia, adenocarcinoma and lymphoma cell lines as well as primary cultures of human tumor cells from patients with chronic lymphocytic leukemia (CLL) and ovarian cancer (OC) and normal human lymphocytes were cultured in semipermeable hollow fibers. The fibers were incubated for 3 or 14 days prior to CHS 828 exposure for 72 h, followed by determination of living cell density by MTT staining. For cell morphology, using harvested cultures on cytospin slides had technical advantages compared to using paraffin sections of the formalin-fixed fibers. CHS 828 showed higher antitumor activity on CLL and normal human lymphocyte cultures compared to OC cultures, and cell lines cultured 3 days were more sensitive than those cultured 14 days. Morphological examination of CHS 828-treated cultures revealed a mixture of apoptosis and necrosis.
|
|
| 35. |
|
|
| 36. |
- Hassan, Saadia Bashir, et al.
(författare)
-
Model for time dependency of the cytotoxic effect of CHS 828 in vitro suggests two different mechanisms of action
- 2001
-
Ingår i: Journal of Pharmacology and Experimental Therapeutics. - 0022-3565 .- 1521-0103. ; 299:3, s. 1140-1147
-
Tidskriftsartikel (refereegranskat)abstract
- CHS 828 is a novel drug belonging to the cyanoguanidines. It has shown promising anticancer activity in many preclinical systems and is currently in early clinical trials. Our aim in this study was to assess the growth inhibitory effect of CHS 828 in comparison with paclitaxel, etoposide, and topotecan as a function of concentration and time. U937 GTB, RPMI 8226/S, MDA 231, primary cells from chronic lymphocytic leukemia, and normal mononuclear cells were exposed to CHS 828 and U937 GTB cells were exposed to paclitaxel, etoposide, and topotecan in 18 concentrations for times ranging from 1 to 72 h. Cell survival was measured after 72-h incubation by using the fluorometric microculture cytotoxicity assay. Nonlinear mixed effect modeling was used to model the concentration-effect curves with a modified Hill equation. Patterns of change of drug potency (IC(50)), slope of the concentration-effect curves, and plateau with time were studied. The log IC(50) for CHS 828 decreased with log time in a sigmoid manner for all cell types tested. Although very steep at short and long incubation, the concentration-effect curves became shallow at intermediate times. The log IC(50) for etoposide and topotecan was decreased with log time in a sigmoid manner. The log IC(50) for paclitaxel decreased linearly with log time. The information obtained from modeling the cytotoxic effect of CHS 828 and changes of IC(50) and slope parameters with exposure time suggests a heterogeneous cell response to CHS 828. This could indicate two distinct mechanisms of induction of cell death.
|
|
| 37. |
|
|
| 38. |
- Hedén, Martin, 1976, et al.
(författare)
-
Thermal radiation from CN+ and La@CN
- 2005
-
Ingår i: J. Chem. Phys.. - : AIP Publishing. - 0021-9606. ; 123
-
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.
|
|
| 39. |
- Hedlund, Martin, et al.
(författare)
-
BlocklyVR : Exploring Block-based Programming in Virtual Reality
- 2023
-
Ingår i: MUM'23: Proceedings of the 22nd International Conference on Mobile and Ubiquitous Multimedia. - : Association for Computing Machinery. - 9798400709210 ; , s. 251-263
-
Konferensbidrag (refereegranskat)abstract
- As programming is typically a static activity in front of a screen, we perform an initial exploration around the capabilities of block-based programming in the immersive space using Virtual Reality (VR) to make an early charting on how programming could involve moving the programmer's body. We created a block-based programming interface in a VR space called BlocklyVR based on the existing Blockly programming environment. To investigate programmer performance and experience in BlocklyVR, we conducted a controlled lab experiment (N = 20) with eight programming tasks that covered mathematical operations, if-statements, and function creation. Our initial exploration contributes by classifying movement types made by BlocklyVR programmers and reflecting on how these movements are related to the programming tasks. Additionally, our data suggests that participant performance in BlocklyVR was not affected compared to the 2D Blockly, even if participants were physically moving in VR space. We also found that the virtual reality sickness was marginal. Lastly, we identified four types of interaction that can potentially be employed by VR designers and developers aiming to convert a static task, like programming at a desk, into a "mobile"immersive experience. © 2023 Owner/Author.
|
|
| 40. |
- Henningsson, Susanne, 1977, et al.
(författare)
-
Possible association between the androgen receptor gene and autism spectrum disorder.
- 2009
-
Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 34:5, s. 752-761
-
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.
|
|
| 41. |
|
|
| 42. |
- Hovstadius, Peter, et al.
(författare)
-
A Phase I Study of CHS 828 in Patients with Solid Tumor Malignancy
- 2002
-
Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 8:9, s. 2843-2850
-
Tidskriftsartikel (refereegranskat)abstract
- CHS 828 is a cyanoguanidine, which has demonstrated potent antitumor activity in preclinical tumor models. The activity of CHS 828 in vitro showed only low to moderate correlation to other antineoplastic agents suggesting a unique mechanism of action. Ten females and 6 males (median age 58 years) with solid tumors refractory to standard therapy were included in this Phase I study. The study drug was administered to fasting patients as a single oral dose on days 1–5 of each treatment cycle. Patients received one to six cycles of treatment. The doses ranged from 30 mg to 200 mg (total dose within a cycle). Hematological toxicity was generally mild and dominated by transient thrombocytopenia and lymphocytopenia. Nonhematological toxicity most frequently consisted of nausea, vomiting, diarrhea, fatigue, and localized genital mucositis. The dose-limiting toxicities were thrombocytopenia, thrombosis, esophagitis, diarrhea, and constipation. The recommended Phase II dose of CHS 828 was 20 mg once daily for 5 days in cycles of 28 days duration. The extent of systemic exposure of CHS 828 across patients was approximately dose proportional. The time at which the highest drug concentration occurs was 2.2 ± 1.3 h and half-life was 2.1 ± 0.52 h (mean ± SD). Large intra- and interindividual variation in dose level-adjusted maximum plasma concentration and the area under the curve from time 0 h to infinity were observed. There was an apparent inverse relationship between systemic exposure of CHS 828, and thrombocyte and lymphocyte nadir levels. No objective tumor responses were observed, and 7 patients showed stable disease after two courses of therapy.
|
|
| 43. |
- Högberg, Anders, 1968-, et al.
(författare)
-
Uppdragsarkeologiska möjligheter : Nya sätt att tänka om en samtidsverksamhet i en framtidsbransch
- 2021
-
Ingår i: In Situ Archaeologica. - Göteborg : University of Gothenburg. - 2000-4044 .- 2002-7656. ; 15, s. 5-30
-
Tidskriftsartikel (refereegranskat)abstract
- In this text we discuss how Swedish contract archaeology can develop its social engagement by creating new areas of relevance to society, beyond the general activities of disseminating results. We do so by giving concrete examples of how this can be done, using archaeological excavations as a starting point. The examples include engaging the local community in future planning for a social sustainable living environment, collaboration with the tourism sector, development of teaching materials for secondary schools, memory training for people with acquired brain damage, and school programs focusing on a socially sustainable and inclusive society. The purpose of the text is to inspire change, by showing development opportunities for future contract archaeology that will benefit both performers and recipients, and contribute to society’s multifaceted needs.
|
|
| 44. |
- Hörbeck, Elin, 1984, et al.
(författare)
-
Dissecting the impact of complement component 4A in bipolar disorder.
- 2023
-
Ingår i: Brain, behavior, and immunity. - 1090-2139. ; 116, s. 150-159
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic overlap between schizophrenia (SZ) and bipolar disorder (BD) is substantial. Polygenic risk scores have been shown to dissect different symptom dimensions within and across these two disorders. Here, we focused on the most strongly associated SZ risk locus located in the extended MHC region, which is largely explained by copy numbers of the gene coding for complement component 4A (C4A). First, we utilized existing brain tissue collections (N=1,202 samples) and observed no altered C4A expression in BD samples. The generated C4A seeded co-expression networks displayed no genetic enrichment for BD. To study if genetically predicted C4A expression discriminates between subphenotypes of BD, we applied C4A expression scores to symptom dimensions in a total of 4,739 BD cases with deep phenotypic data. We identified a significant association between C4A expression and psychotic mood episodes in BD type 1 (BDI). No significant association was observed between C4A expression and the occurrence of non-affective psychotic episodes in BDI, the psychosis dimensions in the total BD sample, or any other subphenotype of BD. Overall, these results points to a distinct role of C4A in BD that is restricted to vulnerability for developing psychotic symptoms during mood episodes in BDI.
|
|
| 45. |
- Johannesson, Kerstin, 1955, et al.
(författare)
-
Oceanographic barriers to gene flow promote genetic subdivision of the tunicate Ciona intestinalis in a North Sea archipelago
- 2018
-
Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 165:8
-
Tidskriftsartikel (refereegranskat)abstract
- Pelagic larval development has the potential to connect populations over large geographic distances and prevent genetic structuring. The solitary tunicate Ciona intestinalis has pelagic eggs and a swimming larval stage lasting for maximum a few days, with the potential for a homogenizing gene flow over relatively large areas. In the eastern North Sea, it is found in a geomorphologically complex archipelago with a mix of fjords and open costal habitats. Here, the coastal waters are also stratified with a marked pycnocline driven by salinity and temperature differences between shallow and deep waters. We investigated the genetic structure of C. intestinalis in this area and compared it with oceanographic barriers to dispersal that would potentially reduce connectivity among local populations. Genetic data from 240 individuals, sampled in 2 shallow, and 4 deep-water sites, showed varying degrees of differentiation among samples (F (ST) = 0.0-0.11). We found no evidence for genetic isolation by distance, but two distant deep-water sites from the open coast were genetically very similar indicating a potential for long-distance gene flow. However, samples from different depths from the same areas were clearly differentiated, and fjord samples were different from open-coast sites. A biophysical model estimating multi-generation, stepping-stone larval connectivity, and empirical data on fjord water mass retention time showed the presence of oceanographic barriers that explained the genetic structure observed. We conclude that the local pattern of oceanographic connectivity will impact on the genetic structure of C. intestinalis in this region.
|
|
| 46. |
- Jonsson, Elin
(författare)
-
Application of new methodology for preclinical development of anticancer drugs : With special focus on camptothecin derivatives and the cyanoguanidine CHS 828
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This work describes the development and evaluation of new methods for preclinical anticancer drug development. The methods were specifically applied to study camptothecin analogues and the new compound CHS 828 (N-(4-chlorophenoxyhexyl)-N'-cyano-N"-4-pyridylguanidine) currently in early clinical trials.The tumour type-specific patterns of cytotoxicity of several anticancer drugs were evaluated ex vivo in fresh human tumour cells from patients using a non-clonogenic cytotoxicity assay (FMCA). The activity pattern ex vivo correlated well with known clinical activity.The camptothecin analogues topotecan, irinotecan and its active metabolite SN-38 were studied and differential activity patterns were observed in fresh human tumour cells but not in a panel of ten human tumour cell lines. Topotecan showed synergistic interactions with cisplatin in a high fraction of fresh human tumour samples, while CHS 828 seemed to interact positively with melphalan.CHS 828 showed a high activity in vivo on MCF-7 breast cancer and NYH small-cell lung cancer xenografts in nude mice, at doses with low host animal toxicity.A recently described in vivo hollow-fiber model, where tumour cells were cultured in semipermeable fibers, was developed further. The model allowed simultaneous monitoring of antitumour effect, host animal toxicity and pharmacokinetics in immunocompetent rats. In one study, the hollow fibers were filled with cells from breast-cancer cell lines, and the effectand pharmacokinetics of some standard cytotoxic agents and CHS 828 was measured. CHS 828 showed the highest activity of the drugs studied, and the effect was more pronounced when the drug was administered five days instead of one. Tumour cells from patients with chronic lymphocytic leukaemia and ovarian cancer were also cultured in the hollow fibers, and promising antitumour effect of CHS 828 was demonstrated in vivo.The results indicate a feasibility of using primary human tumour cells from patients in anticancer drug development and they also describe a new in vivo hollow-fiber model that can be used to study drug pharmacokinetics, toxicity and antitumour effect. The preclinical data on the cyanoguanidine CHS 828 appears promising.
|
|
| 47. |
|
|
| 48. |
- Jonsson, Elin, et al.
(författare)
-
Determination of drug effect on tumour cells, host animal toxicity and drug pharmacokinetics in a hollow-fibre model in rats
- 2000
-
Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 46:6, s. 493-500
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Based on the previously published hollow-fibre assay mainly used for early in vivo anticancer drug screening, we wanted to develop an extended hollow-fibre model in which antitumour activity, haematological toxicity and pharmacokinetics could be studied in the same animal. METHOD The breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in semipermeable hollow fibres. The fibres were implanted subcutaneously into immunocompetent male Sprague Dawley rats, and the rats were treated with 5-fluorouracil (5-FU, 125 mg/kg), epirubicin (EPI, 10 mg/kg) or cyclophosphamide (CP, 120 mg/kg) intraperitoneally, the new cyanoguanidine CHS 828 (375 mg/kg or 75 mg/kg x 5) orally, or vehicle only. After 6 days the fibres were retrieved and the cell density was evaluated. Haematological parameters were monitored and two to four samples per animal were drawn to determine the pharmacokinetic parameters in NONMEM. RESULTS Drug treatment had generally low effects on the tumour cells. Of the standard drugs (5-FU, EPI and CP), only CP exerted a statistically significant antiproliferative effect. CHS 828 had only a minor effect as a single dose, but divided into five daily doses had a pronounced effect on both cell lines. 5-FU, EPI and CP all caused a marked decrease in leucocytes, platelets and haemoglobin, while CHS 828 did not seem to affect these parameters. The pharmacokinetics of 5-FU and EPI were in accordance with previously established pharmacokinetic models. The pharmacokinetics of CP and CHS 828 were both described by one-compartment models. CONCLUSIONS This study illustrates the possibility of measuring antitumour effect, haematological toxicity and pharmacokinetics in the same animal using the hollow-fibre model.
|
|
| 49. |
|
|
| 50. |
|
|
