| 1. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 2. |
- Engström, Linda, et al.
(author)
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Lipopolysaccharide-Induced Fever Depends on Prostaglandin E2 Production Specifically in Brain Endothelial Cells
- 2012
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In: Endocrinology. - : Endocrine Society. - 0013-7227 .- 1945-7170. ; 153:10, s. 4849-4861
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Journal article (peer-reviewed)abstract
- Immune-induced prostaglandin E2 (PGE2) synthesis is critical for fever and other centrally elicited disease symptoms. The production of PGE2 depends on cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1), but the identity of the cells involved has been a matter of controversy. We generated mice expressing mPGES-1 either in cells of hematopoietic or nonhematopoietic origin. Mice lacking mPGES-1 in hematopoietic cells displayed an intact febrile response to lipopolysaccharide, associated with elevated levels of PGE2 in the cerebrospinal fluid. In contrast, mice that expressed mPGES-1 only in hematopoietic cells, although displaying elevated PGE2 levels in plasma but not in the cerebrospinal fluid, showed no febrile response to lipopolysaccharide, thus pointing to the critical role of brain-derived PGE2 for fever. Immunohistochemical stainings showed that induced cyclooxygenase-2 expression in the brain exclusively occurred in endothelial cells, and quantitative PCR analysis on brain cells isolated by flow cytometry demonstrated that mPGES-1 is induced in endothelial cells and not in vascular wall macrophages. Similar analysis on liver cells showed induced expression in macrophages and not in endothelial cells, pointing at the distinct role for brain endothelial cells in PGE2 synthesis. These results identify the brain endothelial cells as the PGE2-producing cells critical for immune-induced fever.
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| 3. |
- Falk, Anna, et al.
(author)
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Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging : a histogram analysis approach
- 2014
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In: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 56:12, s. 1031-1038
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Journal article (peer-reviewed)abstract
- IntroductionPerfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas.MethodsMRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n = 7) gliomas. Statistical analysis of differences between grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated.ResultsIn DCE, the skewness of transfer constant (k trans) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80).ConclusionsHistogram parameters from k trans (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas.
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| 4. |
- Gottvall, Maria, et al.
(author)
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Trust versus concerns : how parents reason when they accept HPV vaccination for their young daughter
- 2013
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:4, s. 263-270
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Journal article (peer-reviewed)abstract
- Background. From spring of 2012, human papillomavirus (HPV) vaccine against cervical cancer is offered free of charge to all girls aged 10-12 years through a school-based vaccination programme in Sweden. The aim of this study was to explore how parents reason when they accept HPV vaccination for their young daughter and also their views on HPV-related information. Methods. Individual interviews with parents (n = 27) of 11-12-year-old girls. The interviews were recorded, transcribed verbatim, and analysed using thematic content analysis. Results. Three themes emerged through the analysis: Trust versus concern, Responsibility to protect against severe disease, and Information about HPV and HPV vaccination is important. The parents expressed trust in recommendations from authorities and thought it was convenient with school-based vaccination. They believed that cervical cancer was a severe disease and felt a responsibility to protect their daughter from it. Some had certain concerns regarding side effects and vaccine safety, and wished for a dialogue with the school nurse to bridge the information gaps. Conclusions. Trust in the recommendations from authorities and a wish to protect their daughter from a severe disease outweighed concerns about side effects. A school-based vaccination programme is convenient for parents, and the school nurse has an important role in bridging information gaps. The findings from this qualitative study cannot be generalized; however, it can provide a better understanding of how parents might reason when they accept the HPV vaccination for their daughter.
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| 5. |
- Mamhidir, Anna-Greta, et al.
(author)
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Deficient knowledge of multidrug-resistant bacteria and preventive hygiene measures among primary healthcare personnel
- 2011
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In: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 67:4, s. 756-762
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Journal article (peer-reviewed)abstract
- AIM:This paper is a report of a study conducted to describe primary healthcare personnel's knowledge of multidrug-resistant and preventive hygiene measures.BACKGROUND:The group of patients at risk for multi-drug resistant bacteria is largely cared for in primary care. Knowledge of multidrug-resistant and hygiene preventive measures among primary healthcare personnel is therefore essential.METHOD:A descriptive and comparative questionnaire survey among primary healthcare personnel was performed in 2008. In total, five urban and rural primary healthcare centres situated in one county in central Sweden were included. Convenient sampling was used and 10 physicians, 38 district nurses and 10 nursing assistants participated. Knowledge/medical facts concerning multidrug-resistant and hygiene preventive measures were investigated and data were analysed using a quantitative approach.RESULTS:Knowledge/medical facts concerning several aspects of multidrug-resistant bacteria, particularly Extended-Spectrum-Beta-Lactamase producing bacteria, were deficient as was knowledge of different aspects of hygiene preventive measures. Physicians showed significantly better results than district nurses and nursing assistants did. Awareness of proper hand-washing as an effective preventive method and use of aprons in nursing care was high among all participants. Staff who knew they had cared for these patients had significantly better results than the others did.CONCLUSION:Our findings suggest that evidence-based education of multidrug-resistant and hygiene preventive measures, in primary health with subsequent follow-ups should become a prioritized clinician and management concern. Research is needed that focus implementation of evidence-based educations, staff attitudes and responsibilities related to the work with patients at risk of multidrug-resistant bacteria.
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| 6. |
- Nilsson, R. Henrik, 1976, et al.
(author)
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Improving ITS sequence data for identification of plant pathogenic fungi
- 2014
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In: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 67:1, s. 11-19
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Journal article (peer-reviewed)abstract
- Plant pathogenic fungi are a large and diverse assemblage of eukaryotes with substantial impacts on natural ecosystems and human endeavours. These taxa often have complex and poorly understood life cycles, lack observable, discriminatory morphological characters, and may not be amenable to in vitro culturing. As a result, species identification is frequently difficult. Molecular (DNA sequence) data have emerged as crucial information for the taxonomic identification of plant pathogenic fungi, with the nuclear ribosomal internal transcribed spacer (ITS) region being the most popular marker. However, international nucleotide sequence databases are accumulating numerous sequences of compromised or low-resolution taxonomic annotations and substandard technical quality, making their use in the molecular identification of plant pathogenic fungi problematic. Here we report on a concerted effort to identify high-quality reference sequences for various plant pathogenic fungi and to re-annotate incorrectly or insufficiently annotated public ITS sequences from these fungal lineages. A third objective was to enrich the sequences with geographical and ecological metadata. The results – a total of 31,954 changes – are incorporated in and made available through the UNITE database for molecular identification of fungi (http://unite.ut.ee), including standalone FASTA files of sequence data for local BLAST searches, use in the next-generation sequencing analysis platforms QIIME and mothur, and related applications. The present initiative is just a beginning to cover the wide spectrum of plant pathogenic fungi, and we invite all researchers with pertinent expertise to join the annotation effort.
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| 7. |
- Alrutz, Marie, et al.
(author)
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Projektledning
- 2013
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Book (pop. science, debate, etc.)abstract
- Projektledning är ett yrke med egen certifiering. Det pågår en spännande utveckling inom området och det blir allt viktigare att hålla sig ajour med utvecklingen.Det övergripande målet med den här handboken är att vara en ständigt aktuell heltäckande bok om projektarbete. Innehållsmässigt täcker den både frågor som har med struktur och styrning att göra och frågor om ledning av människor och mänskliga processer i grupp. Kompetens inom projekt byggs av både kunskap och erfarenhet. Vi följer kontinuerligt aktuell forskning inom dessa områden och bjuder in intressanta forskare att medverka som författare. Vi skildrar verkliga projekt och låter erfarenheterna få plats, både de bästa erfarenheterna och de utmaningar som man tagit sig igenom.Handboken är levande och det innebär att artiklar tas bort för att ge plats för nya, i takt med att den uppdateras fortlöpande.
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| 8. |
- Beecham, Ashley H, et al.
(author)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Journal article (peer-reviewed)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 9. |
- Berntsson, Shala Ghaderi, et al.
(author)
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Perfusion and diffusion MRI combined with (11)C-methionine PET in the preoperative evaluation of suspected adult low-grade gliomas
- 2013
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In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 114:2, s. 241-249
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Journal article (peer-reviewed)abstract
- Perfusion and diffusion magnetic resonance imaging (pMRI, dMRI) are valuable diagnostic tools for assessing brain tumors in the clinical setting. The aim of this study was to determine the correlation of pMRI and dMRI with (11)C-methionine positron emission tomography (MET PET) in suspected low-grade gliomas (LGG) prior to surgery. Twenty-four adults with suspected LGG were enrolled in an observational study and examined by MET PET, pMRI and dMRI. Histological tumor diagnosis was confirmed in 23/24 patients (18 gliomas grade II, 5 gliomas grade III). The maximum relative cerebral blood volume (rCBVmax) and the minimum mean diffusivity (MDmin) were measured in tumor areas with highest MET uptake (hotspot) on PET by using automated co-registration of MRI and PET scans. A clearly defined hotspot on PET was present in all 23 tumors. Regions with rCBVmax corresponded with hotspot regions in all tumors, regions with MDmin corresponded with hotspot regions in 20/23 tumors. The correlation between rCBVmax (r = 0.19, P = 0.38) and MDmin (r = -0.41, P = 0.053) with MET uptake in the hotspot was not statistically significant. Taken into account the difficulties of measuring perfusion abnormalities in non-enhancing gliomas, this study demonstrates that co-registered MET PET and pMRI facilitates the identification of regions with rCBVmax. Furthermore, the lack of a clear positive correlation between tumor metabolism in terms of MET uptake and tumor vascularity measured as rCBVmax suggests that combined pMRI/PET provides complementary baseline imaging data in these tumors.
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| 10. |
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