| 1. |
- Martinsson, Ulla, et al.
(författare)
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Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019
- 2023
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Ingår i: ACTA ONCOLOGICA. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:10, s. 1348-1356
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019.Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position.Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each).Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.
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| 2. |
- Kristensen, Ingrid, et al.
(författare)
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A dose based approach for evaluation of inter-observer variations in target delineation
- 2017
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Ingår i: Technical Innovations and Patient Support in Radiation Oncology. - : Elsevier. - 2405-6324. ; 3-4, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Substantial inter-observer variations in target delineation have been presented previously. Target delineation for paediatric cases is difficult due to the small number of children, the variation in paediatric targets, the number of study protocols, and the individual patient's specific needs and demands. Uncertainties in target delineation might lead to under-dosage or over-dosage. The aim of this work is to apply the concept of a consensus volume and good quality treatment plans to visualise and quantify inter-observer target delineation variations in dosimetric terms in addition to conventional geometrically based volume concordance indices.Material and methods: Two paediatric cases were used to demonstrate the potential of adding dose metrics when evaluating target delineation diversity; Hodgkin's disease (case 1) and rhabdomyosarcoma of the parotid gland (case 2). The variability in target delineation (PTV delineations) between six centres was quantified using the generalised conformity index, CIgen, generated for volume overlap. The STAPLE algorithm, as implemented in CERR, was used for both cases to derive a consensus volumes. STAPLE is a probabilistic estimate of the true volume generated from all observers. Dose distributions created by each centre for the original target volumes were then applied to this consensus volume.Results: A considerable variation in target segmentation was seen in both cases. For case 1 the variation was 374-960 cm3 (average 669 cm3) and for case 2; 65-126 cm3 (average 109 cm3). CIgen were 0.53 and 0.70, respectively. The DVHs in absolute volume displayed for the delineated target volume as well as for the consensus volume adds information on both ''compliant" target volumes as well as outliers which are hidden with just the use of concordance indices.Conclusions: The DVHs in absolute volume add valuable and easily understood information to various indices for evaluating uniformity in target delineation.
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| 3. |
- Svärd, Anna, et al.
(författare)
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Associations to smoking and shared epitope differ between IgA and IgG class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis
- 2015
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Ingår i: Arthritis & Rheumatology. - : Wiley-Blackwell. - 2326-5191 .- 2326-5205. ; 67:8, s. 2032-2037
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Tidskriftsartikel (refereegranskat)abstract
- Background Smoking and HLA-DRB1/shared epitope (SE) are well-known interacting risk factors for developing rheumatoid arthritis (RA) with IgG anticitrullinated protein/peptide antibodies (ACPA). It remains unknown to what extent SE-genes and smoking associate with mucosal immune responses.Objectives This study was done to explore relations between cigarette smoking habits and SE versus circulating IgA and IgG anti-cyclic citrullinated peptide antibodies (anti-CCP) among early RA patients.Methods Patients from two early-RA cohorts were analysed, EIRA-1 (n=1663) and TIRA-2 (n=199). The patients were grouped into four subsets based on anti-CCP: IgG-/IgA-, IgG-/IgA+, IgG+/IgA- and IgG+/IgA+. Interaction between smoking and SE was calculated by the attributable proportion due to deviation from additivity. Analyzed controls (n=1100) were randomly selected from the EIRA-1 study base.Results Anti-CCP occurrence was similar in the two cohorts. Only in EIRA was IgA anti-CCP detected alone in a minority of cases (3%). Smoking was significantly overrepresented among IgA anti-CCP+ patients with or without IgG-class anti-CCP, but not with IgG anti-CCP alone. Presence of SE genes was overrepresented among IgG anti-CCP+ patients with or without IgA-class anti-CCP, but not with IgA anti-CCP alone. Smoking and SE interacted regarding the risk of IgG+/IgA+ RA (AP=0.5, 95 % CI=0.4-0.6), whereas no significant interaction was observed regarding IgG-/IgA+ or IgG+/IgA- RA.Conclusions Association between cigarette smoking and anti-CCP is limited to cases with IgA-class antibodies in addition to IgG anti-CCP. This suggests a causal relation between chronic mucosal irritation/inflammation, induction of a systemic IgA anti-CCP response and subsequent development of RA.
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| 4. |
- Westberg, Lars, 1973, et al.
(författare)
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Variation in the Oxytocin Receptor Gene Is Associated with Face Recognition and its Neural Correlates
- 2016
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The ability to recognize faces is crucial for daily social interactions. Recent studies suggest that intranasal oxytocin administration improves social recognition in humans. Oxytocin signaling in the amygdala plays an essential role for social recognition in mice, and oxytocin administration has been shown to influence amygdala activity in humans. It is therefore possible that the effects of oxytocin on human social recognition depend on mechanisms that take place in the amygdala a central region for memory processing also in humans. Variation in the gene encoding the oxytocin receptor (OXTR) has been associated with several aspects of social behavior. The present study examined the potential associations between nine OXTR polymorphisms, distributed across the gene, and the ability to recognize faces, as well as face-elicited amygdala activity measured by functional magnetic resonance imaging (fMRI) during incidental encoding of faces. The OXTR 3' polymorphism rs7632287, previously related to social bonding behavior and autism risk, was associated with participants ability to recognize faces. Carriers of the GA genotype, associated with enhanced memory, displayed higher amygdala activity during face encoding compared to carriers of the GG genotype. In line with work in rodents, these findings suggest that, in humans, naturally occurring endogenous modulation of OXTR function affects social recognition through an amygdala-dependent mechanism. These findings contribute to the understanding of how oxytocin regulates human social behaviors.
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| 5. |
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| 6. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 7. |
- Davour, Anna, et al.
(författare)
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Applying image analysis techniques to tomographic images of irradiated nuclear fuel assemblies
- 2016
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 96, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we present a set of image analysis techniques used for extraction of information from cross-sectional images of nuclear fuel assemblies, achieved from gamma emission tomography measurements. These techniques are based on template matching, an established method for identifying objects with known properties in images.We demonstrate a rod template matching algorithm for identification and counting of the fuel rods present in the image. This technique may be applicable in nuclear safeguards inspections, because of the potential of verifying the presence of all fuel rods, or potentially discovering any that are missing.We also demonstrate the accurate determination of the position of a fuel assembly, or parts of the assembly, within the imaged area. Accurate knowledge of the assembly position enables detailed modelling of the gamma transport through the fuel, which in turn is needed to make tomographic reconstructions quantifying the activity in each fuel rod with high precision.Using the full gamma energy spectrum, details about the location of different gamma-emitting isotopes within the fuel assembly can be extracted. We also demonstrate the capability to determine the position of supporting parts of the nuclear fuel assembly through their attenuating effect on the gamma rays emitted from the fuel. Altogether this enhances the capabilities of non-destructive nuclear fuel characterization.
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| 8. |
- Davour, Anna, 1975-, et al.
(författare)
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Image analysis methods for partial defect detection using tomographic images on nuclear fuel assemblies
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A promising non-destructive assay method for verification of irradiated nuclear fuel is gammatomography, i.e. the use of measurements of the gamma radiation field around a nuclear fuel assembly to reconstruct detailed information about the internal source distribution.Typically, tomographic reconstructions result in two-dimensional images of cross sections of the fuel. We demonstrate how such images can be searched for fuel rods using a template matching technique, which is a method commonly used in the field of image analysis. In this case, a template or mask corresponding to the size and shape of a fuel rod is translated across the image in order to find the region with the highest reconstructed activity, which is assumed to correspond to the location of a fuel rod in the image. This is done iteratively, allowing no overlap of the rods. By defining the threshold between background and fuel rod objects in the image, we can identify and count the fuel rods using no other assumptions than the rod radius.Thus the rod identification procedure provides a possible means to verify whether all fuel rods arepresent, and it may also be implemented to identify the fuel type of the measured assembly. Theprocedure is robust in cases of irregularities, such as assembly bow or torsion, or the dislocation ofindividual fuel rods in the measured cross section.Here we demonstrate fuel rod identification procedure, using authentic images collected with a tomographic measurement device on commercial fuel assemblies. The results show that image analysis can support tomographic partial defect verification of irradiated nuclear fuel assemblies, even on the single fuel rod level.
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| 9. |
- Ekman, Diana, et al.
(författare)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 10. |
- Embring, A., et al.
(författare)
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Re-irradiation in Paediatric Tumours of the Central Nervous System: National Guidelines from the Swedish Workgroup of Paediatric Radiotherapy
- 2023
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Ingår i: Clinical Oncology. - : Elsevier. - 0936-6555 .- 1433-2981. ; 35:9, s. 571-575
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Tidskriftsartikel (refereegranskat)abstract
- There is a lack of clinical protocols for re-irradiation in paediatric central nervous system (CNS) tumours. To fill this void, the Swedish Workgroup of Paediatric Radiotherapy (SBRTG) compiled national guidelines on re-irradiation in paediatric CNS tumours (diffuse intrinsic pontine glioma, ependymoma, germinoma and medulloblastoma). These have been in clinical practice since 2019 in all paediatric radiotherapy centres in Sweden. Since the implementation, the guidelines have been complemented with a yearly review on clinical outcome and toxicities in all paediatric patients treated according to the guidelines. This article presents the Swedish national guidelines on re-irradiation in paediatric CNS tumours. & COPY; 2023 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.
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| 11. |
- Engvall, Gunn, et al.
(författare)
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It Is Tough and Tiring but It Works - Children's Experiences of Undergoing Radiotherapy
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children's experiences of preparing for and undergoing radiotherapy, and furthermore to describe children's suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children's suggestions for improvement during radiotherapy. An overarching theme emerged: "It is tough and tiring but it works". Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs.
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| 12. |
- Ericson, Jenny, et al.
(författare)
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Total Nitrite and Nitrate Concentration in Human Milk and Saliva during the First 60 Days Postpartum : A Pilot Study
- 2024
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 12:6, s. 1195-1195
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Nitric oxide (NO) in human milk may have important functions in lactation and infant health. This longitudinal pilot cohort study investigated the total nitrite and nitrate (NOx) concentration in human milk and maternal saliva during the first 60 days postpartum. Additionally, we explored the association between selected breastfeeding variables and milk and saliva NOx concentration. Human milk and maternal saliva samples were collected on days 2, 5, 14, 30, and 60 postpartum and analyzed for NOx concentration. Breastfeeding data were collected through self-assessed questions. Data analyses were performed using mixed models. The concentration of NOx in milk was significantly higher during the first 30 days compared to day 60, and there was a positive association between milk and saliva NOx concentrations throughout the entire study period. In absolute numbers, partially breastfeeding mothers had a lower concentration of NOx in milk on day 2 compared to exclusively breastfeeding mothers (8 vs. 15.1 μM, respectively). Partially breastfeeding mothers reported a later start of secretory activation and fewer mothers in this group started breastfeeding within the first hour after birth. Due to the small numbers, these differences could not be statistically evaluated. Further research is warranted to elucidate the role of NO in lactation success and breastfeeding outcomes.
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| 13. |
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| 14. |
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| 15. |
- Finnveden, Göran, et al.
(författare)
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Evaluation of integration of sustainable development in higher education in Sweden
- 2020
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Ingår i: International Journal of Sustainability in Higher Education. - : Emerald Group Publishing Limited. - 1467-6370 .- 1758-6739. ; 21:4, s. 685-698
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Since 2006, higher education institutions (HEIs) in Sweden, should according to the Higher Education Act, promote sustainable development (SD). In 2016, the Swedish Government asked the Swedish higher education authority to evaluate how this study is proceeding. The authority chose to focus on education. This paper aims to produce a report on this evaluation. Design/methodology/approach All 47 HEIs in Sweden were asked to write a self-evaluation report based on certain evaluation criteria. A panel was appointed consisting of academics and representatives for students and working life. The panel wrote an evaluation of each HEI, a report on general findings and recommendations, and gave an overall judgement of each HEI in two classes as follows: the HEI has well-developed processes for integration of SD in education or the HEI needs to develop their processes. Findings Overall, a mixed picture developed. Most HEIs could give examples of programmes or courses where SD was integrated. However, less than half of the HEIs had overarching goals for integration of SD in education or had a systematic follow-up of these goals. Even fewer worked specifically with pedagogy and didactics, teaching and learning methods and environments, sustainability competences or other characters of education for SD. Overall, only 12 out of 47 got a higher judgement. Originality/value This is a unique study in which all HEIs in a country are evaluated. This provides unique possibilities for identifying success factors and barriers. The importance of the leadership of the HEIs became clear.
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| 16. |
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| 17. |
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| 18. |
- Grönwall, Caroline, et al.
(författare)
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A Comprehensive Evaluation of the Relationship Between Different IgG and IgA Anti-Modified Protein Autoantibodies in Rheumatoid Arthritis
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), and malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. In this comprehensive study, we analyze 30 different IgG and IgA AMPA reactivities to Cit, Carb, KAc, and MAA antigens detected by ELISA and autoantigen arrays in N=1985 newly diagnosed RA patients. Association with patient characteristics such as smoking and disease activity were explored. Carb and KAc reactivities by different assays were primarily seen in patients also positive for anti-citrulline reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG reactivity to acetylation was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking status. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles. Our serology results were complemented by screening of monoclonal antibodies derived from single B cells from RA patients for the same antigens as the RA cohort. Certain CCP2+ clones had Carb or Carb+KAc+ multireactivity, while such reactivities were not found in CCP2- clones. We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Carb and KAc could be considered reactivities within the "Cit-umbrella" similar to ACPA fine-specificities, while MAA reactivity is distinctly different.
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| 19. |
- Hallqvist, Andreas, 1973, et al.
(författare)
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Dose escalation to 84 Gy with concurrent chemotherapy in stage III NSCLC appears excessively toxic: Results from a prematurely terminated randomized phase II trial
- 2018
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 122, s. 180-186
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. Materials and Methods: NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. Results: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).
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| 20. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Association between polymorphisms in NOS3 and KCNH2 and social memory
- 2015
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Social memory, including the ability to recognize faces and voices, is essential for social relationships. It has a large heritable component, but the knowledge about the contributing genes is sparse. The genetic variation underlying inter-individual differences in social memory was investigated in an exploratory sample (n = 55), genotyped with a chip comprising approximately 200,000 single nucleotide polymorphisms (SNPs), and in a validation sample (n = 582), where 30 SNPs were targeted. In the exploratory study face identity recognition was measured. The validation study also measured vocal sound recognition, as well as recognition of faces and vocal sounds combined (multimodal condition). In the exploratory study, the 30 SNPs that were associated with face recognition at puncorrected < 0.001 and located in genes, were chosen for further study. In the validation study two of these SNPs showed significant associations with recognition of faces, vocal sounds, and multimodal stimuli: rs1800779 in the gene encoding nitric oxide synthase 3 (NOS3) and rs3807370 in the gene encoding the voltage-gated channel, subfamily H, member 2 (KCNH2), in strong linkage disequilibrium with each other. The uncommon alleles were associated with superior performance, and the effects were present for men only (p < 0.0002). The exploratory study also showed a weaker but significant association with (non-emotional) word recognition, an effect that was independent of the effect on face recognition. This study demonstrates evidence for an association between NOS3 and KCNH2SNPs and social memory.
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| 21. |
- Herstad-Svärd, S., et al.
(författare)
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Ramprogram – Åtgärder för samtidig minimering av alkalirelaterade driftproblem, Etapp 2
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Combustion of an increasing amount of biofuel and waste woods has resulted in certainenvironmental advantages, including decreased emissions of fossil CO2, SO2 andmetals. On the other hand, a number of chloride and alkali related operational problemshave occurred which are related to combustion of these fuels.Alkali related operational problems have been studied in a project consisting of twoparts. The overall scope has been to characterise the operational problems and to studymeasures to minimise them. The first part was reported in Värmeforsk report 997 wherethe results were summarised in a table of different measures. In part two, additionalmeasures have been included in the test plan and initial corrosion has been studiedlinked to the different measures. The tests have also in part two been carried out at the12 MW CFB boiler at Chalmers. The effect of the selected measures has beeninvestigated concerning both deposit formation and bed agglomeration, and at the sametime emissions and other operational conditions were characterised.The second part of the project has among other things focused on:• To investigate measures which decrease the content of alkali and chloride in thedeposits, and consequently decrease the risk for corrosion (by investigating theinitial corrosion). Focus was also on trying to explain favourable effects.• To investigate if it is possible to combine a rather low dosage of kaolin and injectionof ammonium sulphate. This was done in order to reduce both bed agglomerationand problems from deposits during combustion of fuels rich in chlorine.• To investigate if co-combustion with sewage sludge, de-inking sludge or peat withhigh ash content, could give similar advantages as conventional additives.• Investigate if ash from PFBC is possible to use as an alternative bed material.By comparing the different measures in part two, it could be concluded that cocombustionof sewage sludge gave the best overall effect. The judgement was based onthe effects concerning bed agglomeration, level of alkali chloride in the flue gas,deposits and initial corrosion. Simultaneous addition of kaolin and ammonia sulphatealso had a favourable impact both in the bed and on the alkali chlorides in the gas phase.Dosage of kaolin did not reduce the effect of injected ammonium sulphate. Cocombustionof peat could also be a very attractive alternative, but it is critical to select asuitable peat type. It is of special concern to avoid peat with a high content of calcium,since it can increase the level of alkali chlorides by reacting with available sulphur.Change of bed material to ash from PFBC can decrease problems with bedagglomeration, but there is a risk of increased deposit formation and corrosion. A boileroperated with high steam data should consequently combine the change of bed materialwith injection of ammonium sulphate or another source of sulphur.Co-combustion of de-inking sludge from pulp and paper production can reduceproblems with bed agglomeration. There is, however, an increased chance of corrosiondue to the high content of calcium. Injection of sulphates may improve the situationconcerning corrosion. The results also showed that low potassium chlorine content in the flue gas decreasesthe risk of corrosion. Increased amount of potassium chlorine content in the flue gaswill not necessary give a high amount of chlorine content in the deposits if there is sulphur in the system.Key words: agglomeration, deposits, corrosion, alkali, kaolin, ammonium sulphate,sludge
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| 22. |
- Jacobsson Svärd, Staffan, 1972-, et al.
(författare)
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Gamma-ray Emission Tomography: Modelling and evaluation of partial-defect testing capabilities
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Assessment of gamma emission tomography (GET) for spent nuclear fuel verification is the task in IAEA MSP project JNT1955. In line with IAEA Safeguards R&D plan 2012-2023, the aim of this effort is to “develop more sensitive and less intrusive alternatives to existing NDA instruments to perform partial defect tests on spent fuel assemblies prior to transfer to difficult to access storage". The current viability study constitutes the first phase of three, with evaluation and decision points between each phase. Two verification objectives have been identified; (1) counting of fuel pins in tomographic images without any a priori knowledge of the fuel assembly under study, and (2) quantitative measurements of pin-by-pin properties, e.g. burnup, for the detection of anomalies and/or verification of operator-declared data.Previous measurements performed in Sweden and Finland have proven GET highly promising for detecting removed or substituted fuel pins (i.e. partial defects) in BWR and VVER-440 fuel assemblies even down to the individual fuel pin level. The current project adds to previous experiences by pursuing a quantitative assessment of the capabilities of GET for partial defect detection, across a broad range of potential IAEA applications, fuel types, and fuel parameters. A modelling and performance-evaluation framework has been developed to provide quantitative GET performance predictions, incorporating burn-up and cooling-time calculations, Monte Carlo radiation-transport and detector-response modelling, GET instrument definitions (existing and notional) and tomographic reconstruction algorithms, which use recorded gamma-ray intensities to produce cross-sectional images of the source distribution in the fuel assembly or conclusive pin-by-pin data. The framework also comprises image-processing algorithms and performance metrics that recognize the inherent trade-off between the probability of detecting missing pins and the false-alarm rate. Here, the modelling and analysis framework is described and preliminary results are presented.
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| 23. |
- Jacobsson Svärd, Staffan, 1970-, et al.
(författare)
-
Tomographic determination of spent fuel assembly pin-wise burnup and cooling time for detection of anomalies
- 2015
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The IAEA has initiated Member States’ Support Program project JNT A 1955 to assess the partial defect detection capabilities of gamma emission tomography (GET) for spent nuclear fuel assembly verification. The GET technique is based on measurements of the gamma-ray flux distribution around a spent fuel assembly using dedicated, tomographic equipment and subsequent reconstruction of the internal source distribution using tomographic algorithms applied on the recorded data. One of the verification objectives identified for the project is the quantitative measurement of pin-by-pin properties, e.g. burnup and/or cooling time, for the detection of anomalies and/or verification of operator-declared data. For this objective, reconstruction algorithms that return quantitative, isotopic pin-by-pin data are applied.Previously, GET measurements performed on commercial nuclear fuel assemblies in Sweden have proven capable of determining the relative pin-by-pin power distribution with high precision in BWR fuel with short cooling time, based on the measured distribution of the gamma-ray emitting fission product 140Ba/La in the fuel. In the current project, the capabilities of GET to determine additional pin-wise fuel parameters in additional fuel types are being assessed. The evaluations are based on Monte Carlo simulations of the emission of gamma-rays from the fuel and their detection in a tomographic measurement device.This paper describes the algorithms used for reconstructing quantitative pin-wise data and the results that are anticipated with this technique. It is argued that detailed modelling of the gamma-ray attenuation through the highly inhomogeneous mix of strongly-attenuating fuel rods and less-attenuating surrounding water (wet storage) or air (dry storage) is required to yield high precision in the reconstructed data. The burnup distribution assessment would be based on the recording of 662-keV gamma radiation from 137Cs, whereas the assessment of both burnup and cooling time simultaneously requires the GET measurement and pin-wise reconstruction of at least two isotopes, which puts constraints on the measurement equipment used.
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| 24. |
- Jansson, Peter, 1971-, et al.
(författare)
-
Gamma Transport Calculations for Gamma Emission Tomography on Nuclear Fuel within the UGET Project
- 2014
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The unattended gamma emission tomography (UGET) for spent nuclear fuel verification is an on-going project in the IAEA member states’ support program. In line with the long term R&D plan of the IAEA Department of Safeguards, it is anticipated that this effort will help develop “more sensitive and less intrusive alternatives to existing NDA instruments to perform partial defect test on spent fuel assembly prior to transfer to difficult to access storage”.In the first phase of the project, gamma transport calculations and modelling of exist- ing and proposed new designs of tomographic instruments is performed. In this paper, a set of Monte Carlo calculations regarding modelling of various tomographic devices are presented, including two existing tomographic instruments previously used for spent fuel measurements; one instrument based on scintillator detectors, developed by Uppsala University, and another based on CdTe detector arrays, developed by the JNT 1510 col- laborative effort (Hungary, Finland). Detailed models of the tomographic instruments, including structural materials, and the measured fuel assemblies are used in the simula- tions. The calculated results are compared to the experimentally measured data to provide a benchmark for the simulation procedure.The developed modelling capabilities are also used for evaluation of the partial-defect detection capabilities of the tomographic technique based on a proposed GET instrument design.
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| 25. |
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| 26. |
- Khalaf, Hazem, et al.
(författare)
-
Antibacterial effects of Lactobacillus and bacteriocin PLNC8 alpha beta on the periodontal pathogen Porphyromonas gingivalis
- 2016
-
Ingår i: BMC Microbiology. - : BIOMED CENTRAL LTD. - 1471-2180. ; 16:188
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The complications in healthcare systems associated with antibiotic-resistant microorganisms have resulted in an intense search for new effective antimicrobials. Attractive substances from which novel antibiotics may be developed are the bacteriocins. These naturally occurring peptides are generally considered to be safe and efficient at eliminating pathogenic bacteria. Among specific keystone pathogens in periodontitis, Porphyromonas gingivalis is considered to be the most important pathogen in the development and progression of chronic inflammatory disease. The aim of the present study was to investigate the antimicrobial effects of different Lactobacillus species and the two-peptide bacteriocin PLNC8 alpha beta on P. gingivalis. Results: Growth inhibition of P. gingivalis was obtained by viable Lactobacillus and culture media from L. plantarum NC8 and 44048, but not L. brevis 30670. The two-peptide bacteriocin from L. plantarum NC8 (PLNC8 alpha beta) was found to be efficient against P. gingivalis through binding followed by permeabilization of the membranes, using Surface plasmon resonance analysis and DNA staining with Sytox Green. Liposomal systems were acquired to verify membrane permeabilization by PLNC8 alpha beta. The antimicrobial activity of PLNC8 alpha beta was found to be rapid (1 min) and visualized by TEM to cause cellular distortion through detachment of the outer membrane and bacterial lysis. Conclusion: Soluble or immobilized PLNC8 alpha beta bacteriocins may be used to prevent P. gingivalis colonization and subsequent pathogenicity, and thus supplement the host immune system against invading pathogens associated with periodontitis.
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| 27. |
- Khalaf, Hazem, 1981-, et al.
(författare)
-
Antibacterial effects of Lactobacillus and bacteriocin PLNC8 αβ on the periodontal pathogen Porphyromonas gingivalis
- 2016
-
Ingår i: BMC Microbiology. - London, United Kingdom : BioMed Central (BMC). - 1471-2180. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The complications in healthcare systems associated with antibiotic-resistant microorganisms have resulted in an intense search for new effective antimicrobials. Attractive substances from which novel antibiotics may be developed are the bacteriocins. These naturally occurring peptides are generally considered to be safe and efficient at eliminating pathogenic bacteria. Among specific keystone pathogens in periodontitis, Porphyromonas gingivalis is considered to be the most important pathogen in the development and progression of chronic inflammatory disease. The aim of the present study was to investigate the antimicrobial effects of different Lactobacillus species and the two-peptide bacteriocin PLNC8 αβ on P. gingivalis.Results: Growth inhibition of P. gingivalis was obtained by viable Lactobacillus and culture media from L. plantarum NC8 and 44048, but not L. brevis 30670. The two-peptide bacteriocin from L. plantarum NC8 (PLNC8 αβ) was found to be efficient against P. gingivalis through binding followed by permeabilization of the membranes, using Surface plasmon resonance analysis and DNA staining with Sytox Green. Liposomal systems were acquired to verify membrane permeabilization by PLNC8 αβ. The antimicrobial activity of PLNC8 αβ was found to be rapid (1 min) and visualized by TEM to cause cellular distortion through detachment of the outer membrane and bacterial lysis.Conclusion: Soluble or immobilized PLNC8 αβ bacteriocins may be used to prevent P. gingivalis colonization and subsequent pathogenicity, and thus supplement the host immune system against invading pathogens associated with periodontitis.
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| 28. |
- Krakovka, Sascha, et al.
(författare)
-
Giardia intestinalis thymidine kinase is a high-affinity enzyme crucial for DNA synthesis and an exploitable target for drug discovery
- 2022
-
Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 298:6
-
Tidskriftsartikel (refereegranskat)abstract
- Giardiasis is a diarrheal disease caused by the unicellular parasite Giardia intestinalis, for which metronidazole is the main treatment option. The parasite is dependent on exogenous deoxyribonucleosides for DNA replication and thus is also potentially vulnerable to deoxyribonucleoside analogs. Here, we characterized the G. intestinalis thymidine kinase, a divergent member of the thymidine kinase 1 family that consists of two weakly homologous parts within one polypeptide. We found that the recombinantly expressed enzyme is monomeric, with 100-fold higher catalytic efficiency for thymidine compared to its second-best substrate, deoxyuridine, and is furthermore subject to feedback inhibition by dTTP. This efficient substrate discrimination is in line with the lack of thymidylate synthase and dUTPase in the parasite, which makes deoxy-UMP a dead-end product that is potentially harmful if converted to deoxy-UTP. We also found that the antiretroviral drug azidothymidine (AZT) was an equally good substrate as thymidine and was active against WT as well as metronidazole-resistant G. intestinalis trophozoites. This drug inhibited DNA synthesis in the parasite and efficiently decreased cyst production in vitro, which suggests that it could reduce infectivity. AZT also showed a good effect in G. intestinalis–infected gerbils, reducing both the number of trophozoites in the small intestine and the number of viable cysts in the stool. Taken together, these results suggest that the absolute dependency of the parasite on thymidine kinase for its DNA synthesis can be exploited by AZT, which has promise as a future medication effective against metronidazole-refractory giardiasis.
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| 29. |
- Martinsson, Klara, et al.
(författare)
-
Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis
- 2023
-
Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA.Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls.Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65).Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.
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| 30. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten : 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
- 2022
-
Ingår i: Aftonbladet. - : Aftonbladet. ; :2022-12-07
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Vi, 1 620 forskare samt lärare vid universitet och högskolor, är eniga med de unga bakom Auroramålet: De drabbas och riskerar att drabbas allvarligt av klimatkrisen under sin livstid. De klimatåtgärder vi vidtar i närtid avgör deras framtid. Sverige måste ta ansvar och göra sin rättvisa andel av det globala klimatarbetet. I strid med Parisavtalet ökar utsläppen av växthusgaser i en takt som gör att 1,5-gradersmålet kan överskridas om några år. De globala effekterna blir allt mer synliga med ständiga temperaturrekord, smältande isar, havshöjning och extremväder som torka, förödande bränder och skyfall med enorma översvämningar, som i Pakistan nyligen. Försörjningen av befolkningen utsätts för allvarliga hot i många länder.Minskningen av den biologiska mångfalden är extrem. Klimatkrisen är enligt WHO det största hotet mot människors hälsa i hela världen och barn utgör en särskilt sårbar grupp. Med Sveriges nordliga läge sker uppvärmningen här dubbelt så fort som det globala genomsnittet. Det förskjuter utbredningsområden för växtlighet och sjukdomsbärande insekter och ökar förekomsten av extremväder såsom värmeböljor, skogsbränder och översvämningar samt av många olika sorters infektioner och allergier. När extremväder ökar, ökar även stressen och risken för mental ohälsa. Värmeböljor ökar risken för sjukdom och död hos sårbara grupper som äldre, små barn och personer med kroniska sjukdomar. De negativa effekterna på hälsan kommer att öka i takt med klimatkrisen och barn riskerar att drabbas av ackumulerade negativa hälsoeffekter under hela sina liv. Redan i dag är mer än hälften av unga mellan 12 och 18 år i Sverige ganska eller mycket oroliga för klimat och miljö. Detta är förståeligt när våra beslutsfattare inte gör vad som krävs.Den juridiska och moraliska grunden för arbetet mot klimatförändringarna är att varje land måste göra sin rättvisa andel av det globala klimatarbetet. Centralt i det internationella klimatramverket är att rika länder med höga historiska utsläpp, däribland Sverige, måste gå före resten av världen. Dessa länder måste också bidra till att finansiera klimatomställningen i länderna i det Globala Syd, som är minst ansvariga för klimatkrisen men drabbas hårdast. Denna rättviseprincip är tydlig i Parisavtalet och var en het diskussionsfråga under COP27 i Sharm el-Sheikh, men lyser med sin frånvaro i det svenska klimatarbetet. Sverige har satt mål för att minska sina utsläpp. Men de är helt otillräckliga: minskningstakten är för låg och målen tillåter samtidigt att åtgärder skjuts på framtiden. Dessutom exkluderas merparten av Sveriges utsläpp från de svenska nationella utsläppsmålen; bland annat utelämnas utsläpp som svensk konsumtion orsakar utanför Sveriges gränser, utsläpp från utrikes transporter och utsläpp från markanvändning och skogsbruk, exempelvis utsläpp från förbränning av biobränslen eller utsläpp från dikade våtmarker (Prop. 2016/17:146 s.25-28).Sverige saknar dessutom ett eget mål för att öka upptaget av växthusgaser genom utökat skydd och restaurering av ekosystem, något som krävs för att begränsa de värsta konsekvenserna av klimatkrisen (IPCC s.32). Trots dessa låga ambitioner misslyckas Sverige med att nå sina utsläppsmål, konstaterar både Klimatpolitiska rådet och Naturvårdsverket. En klimatpolitik i linje med Parisavtalet kräver både att alla typer av växthusgasutsläpp minskar samtidigt som – inte i stället för – upptaget av växthusgaser maximeras: i dag misslyckas Sverige på bägge fronter.Slutsatsen är tydlig. Sverige vidtar inte de åtgärder som krävs för att skydda barns och ungdomars rättigheter enligt Europakonventionen till skydd för de mänskliga rättigheterna. Detta medför allvarliga risker för liv och hälsa för unga generationer, människor i andra länder och särskilt utsatta grupper. Detta kan inte fortsätta. Därför ställer vi oss bakom Auroras krav att Sverige börjar göra sin rättvisa andel och omedelbart sätter igång ett omfattande och långtgående klimatarbete som vilar på vetenskaplig grund och sätter rättvisa i centrum.
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| 31. |
- Nissen, Anna, 1981-
(författare)
-
High Order Finite Difference Methods with Artificial Boundary Treatment in Quantum Dynamics
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The investigation of the dynamics of chemical reactions, both from the theoretical and experimental side, has drawn an increasing interest since Ahmed H. Zewail was awarded the 1999 Nobel Prize in Chemistry for his work on femtochemistry. On the experimental side, new techniques such as femtosecond lasers and attosecond lasers enable laser control of chemical reactions. Numerical simulations serve as a valuable complement to experimental techniques, not only for validation of experimental results, but also for simulation of processes that cannot be investigated through experiments. With increasing computer capacity, more and more physical phenomena fall within the range of what is possible to simulate. Also, the development of new, efficient numerical methods further increases the possibilities. The focus of this thesis is twofold; numerical methods for chemical reactions including dissociative states and methods that can deal with coexistence of spatial regions with very different physical properties. Dissociative chemical reactions are reactions where molecules break up into smaller components. The dissociation can occur spontaneously, e.g. by radioactive decay, or be induced by adding energy to the system, e.g. in terms of a laser field. Quantities of interest can for instance be the reaction probabilities of possible chemical reactions. This thesis discusses a boundary treatment model based on the perfectly matched layer (PML) approach to accurately describe dynamics of chemical reactions including dissociative states. The limitations of the method are investigated and errors introduced by the PML are quantified. The ability of a numerical method to adapt to different scales is important in the study of more complex chemical systems. One application of interest is long-range molecules, where the atoms are affected by chemical attractive forces that lead to fast movement in the region where they are close to each other and exhibits a relative motion of the atoms that is very slow in the long-range region. A numerical method that allows for spatial adaptivity is presented, based on the summation-by-parts-simultaneous approximation term (SBP-SAT) methodology. The accuracy and the robustness of the numerical method are investigated.
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| 32. |
- Nyman, J., et al.
(författare)
-
Dose Escalated Chemo-RT to 84 Gy in Stage III NSCLC Appears Excessively Toxic : Results from a Randomized Phase II Trial
- 2018
-
Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 13:10, s. S373-S373
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease, however, with a rather high probability of locoregional and metastatic recurrence further treatment optimization is warranted. Based on previous one-armed trials with dose escalated radiotherapy, showing feasibility, the Swedish Lung Cancer Study Group aimed to investigate whether dose escalation based on individual normal tissue constraints could improve outcome in this randomized phase II trial.Method: NSCLC patients with stage III disease, good performance status (0-1), adequate lung function (FEV1 > 1.0 L and CO diff. > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. The radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to a total dose of 68 Gy (standard arm A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week while keeping the total treatment time constant at seven weeks with the same dose to involved nodes and primary tumor.Result: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in the dose escalated group compared to 28 and 45 months in the standard group. The 1-, 3- and 5-year survival rates were 56%, 33% and 17% in the escalated arm and 72%, 61% and 34% in the standard arm. There were four toxicity-related deaths due to esophageal perforations (one in arm A and three in arm B) and three deaths due to pneumonitis (one in arm A and two in arm B).Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 5-year survival of 34%. A possible step forward will be to improve systemic therapy, but future approaches with escalated radiotherapy may include boost techniques to remaining PET positive areas or different escalation schedules to the primary tumor and mediastinal nodes.
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| 33. |
- Palomar, Quentin, 1991-, et al.
(författare)
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Detection of gingipain activity using solid state nanopore sensors
- 2022
-
Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 368
-
Tidskriftsartikel (refereegranskat)abstract
- Accurate, robust, and rapid diagnostics is the basis for all well-functioning healthcare. There is a large need in point-of-care biosensors to facilitate diagnosis and reduce the need for cumbersome laboratory equipment. Proteases are key virulence factors in periodontitis. Periodontal disease is very common and characterized by inflammation and infection in the tooth-supporting structures and is linked to many systemic diseases such as cardiovascular disease, diabetes, and Alzheimer's disease. Proteases present in periodontal disease, gingipains, are highly responsible for the disease onset and progression and are therefore a promising biomarker. Here we show a novel nanopore-based biosensor strategy for protease activity monitoring. Solid-state nanopores were modified with a proteolytic substrate, restricting the ionic current through the apertures of the nanopores. Protease can digest the proteolytic substrate thus enlarge the aperture and the ionic current. Trypsin was used as an initial model protease to investigate the performance of the sensor. We show that the solid-state nanoporebiosensor can detect trypsin with a limit of detection (LOD) of 0.005 ng/mL (0.2 pM). The detection system developed for the model enzyme was then applied to the detection of gingipains. The LOD for detection of gingipains was 1 ng/mL (0.02 nM), with a 27% recovery of the signal at 0.1 mu g/mL, indicating that the sensitivity and dynamic range are relevant for the clinical diagnosis of periodontitis. The generic detection of protease activity and high sensitivity make this a promising sensor technology for both diagnosis of periodontal disease and monitoring of other disease-related proteases.
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| 34. |
- Roos, Karin, et al.
(författare)
-
Circulating anti-citrullinated protein antibodies containing secretory component are prognostic for arthritis onset in at-risk patients
- 2021
-
Ingår i: Clinical and Experimental Immunology. - : Wiley. - 0009-9104 .- 1365-2249. ; 204:3, s. 344-351
-
Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.
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| 35. |
- Roos, Karin, et al.
(författare)
-
Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking
- 2016
-
Ingår i: Arthritis Research & Therapy. - : BIOMED CENTRAL LTD. - 1478-6362. ; 18:119
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A possible association between mucosal immunization and inflammation, as well as the initiation and propagation of rheumatoid arthritis (RA), is attracting renewed interest. The aim of this study was to evaluate the possible occurrence and clinical correlations of circulating secretory immunoglobulin A (SIgA) antibodies against the second-generation cyclic citrullinated peptides (CCP) among patients with recent-onset RA followed prospectively over 3 years. Methods: Baseline serum samples from 636 patients with recent-onset RA were analyzed for SIgA anti-CCP antibodies by using an enzyme-linked immunosorbent assay with a secondary antibody directed against secretory component. SIgA anti-CCP status at baseline was analyzed in relation to smoking, HLA-DRB1/shared epitope (SE), and the disease course over 3 years. Significant findings were evaluated in regression analysis that included age, sex, smoking, and SE. Results: Seventeen percent of the patients tested positive for circulating SIgA anti-CCP, and the occurrence was confirmed by detection of secretory component in an affinity-purified IgA anti-CCP fraction. SIgA anti-CCP positivity at baseline was associated with slightly higher baseline erythrocyte sedimentation rate (ESR) (mean 38 vs. 31 mm/first hour, p = 0.004) and C-reactive protein (CRP) (mean 30 vs. 23 mg/L, p = 0.047). During follow-up, SIgA anti-CCP-positive patients had a higher mean AUC regarding ESR (adjusted p = 0.003), although there were no significant differences regarding CRP, tender and swollen joint counts, or radiological joint damage (median Larsen progression 1.0 vs. 1.0, p = 0.22). SIgA anti-CCP was associated significantly with smoking (79 % ever smokers among SIgA anti-CCP-positive patients vs. 59 % in SIgA anti-CCP-negative patients, adjusted OR 2.19, 95 % CI 1.01-4.37, p = 0.027) but not with carriage of the SE (80 % vs. 73 %, p = 0.62). Conclusions: Circulating SIgA anti-CCP, which is present in a subgroup of patients with early RA, is not related to SE, but it is environmentally linked to cigarette smoking. This finding strengthens the hypothesis that immunization against citrullinated peptides and/or proteins may occur at mucosal surfaces of the airways. Analysis of SIgA antibodies in serum may be a convenient and more versatile means to investigate the "mucosal connection" in RA compared with analyses in mucosal fluid samples.
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| 36. |
- Roos Ljungberg, Karin, et al.
(författare)
-
Presence of salivary IgA anti-citrullinated protein antibodies associate with higher disease activity in patients with rheumatoid arthritis
- 2020
-
Ingår i: Arthritis Research & Therapy. - : BMC. - 1478-6362. ; 22
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating IgA anti-citrullinated protein antibodies (ACPA) associate with more active disease, but a previous study implied that salivary IgA ACPA is related to a less severe disease. Therefore, we aimed to characterize the IgA ACPA response in the saliva and serum in relation to clinical picture and risk factors among patients with rheumatoid arthritis (RA).Methods: RA patients (n=196) and healthy blood donors (n=101), included in the cross-sectional study "Secretory ACPA in Rheumatoid Arthritis" (SARA), were analyzed for ACPA of IgA isotype, and for subclasses IgA1 and IgA2 ACPA in paired saliva and serum samples using modified enzyme-linked immunosorbent assays (ELISA) targeting reactivity to a cyclic citrullinated peptide (anti-CCP). Cutoff levels for positive tests were set at the 99th percentile for blood donors. Antibody levels were related to clinical characteristics, radiographic damage, smoking habits, and carriage of HLA-DRB1/shared epitope (SE).Results: IgA ACPA in the saliva was found in 12% of RA patients, IgA1 occurred in 10%, and IgA2 in 9%. In serum, IgA ACPA was found in 45% of the patients, IgA1 in 44%, and IgA2 in 39%. Levels of IgA ACPA in the saliva correlated significantly with serum levels of IgA (r=0.455). The presence of salivary IgA ACPA was associated with a higher erythrocyte sedimentation rate (ESR), 28-joint disease activity score, tender joint count, and patient global assessment at the time of sampling. None of the antibodies was associated with smoking, SE, or radiographic damage.Conclusion: Salivary IgA ACPAs were detected in a subset of RA patients in association with higher disease activity. This suggests that mucosal ACPA responses in the oral cavity may contribute to disease-promoting processes in RA.
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| 37. |
- Roos Ljungberg, Karin, et al.
(författare)
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Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis
- 2020
-
Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 59:4, s. 852-859
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Tidskriftsartikel (refereegranskat)abstract
- Objective. A 'mucosal connection' in RA presently attracts increasing attention. We recently described the occurrence of secretory antibodies to citrullinated protein (SC-ACPA) in sera from patients with recent-onset RA. The current study was performed to evaluate possible associations between serum levels of secretory ACPA and signs of lung involvement in patients with early, untreated RA. Methods. One hundred and forty-two RA patients were included as part of the 'LUng Investigation in newly diagnosed RA' study. One hundred and six patients were examined with high-resolution CT (HRCT) and 20 patients underwent bronchoscopy, where bronchial biopsies and bronchoalveolar lavage fluid (BALF) samples were obtained. SC-ACPA in serum and BALF were detected by an enzyme-linked immunoassay. Antibody levels were related to smoking history, pulmonary function, HRCT, BALF cell counts and findings in bronchial biopsies. Results. SC-ACPA occurred in 16% of the serum samples and in 35% of the BALF samples. SC-ACPA levels in serum correlated with SC-ACPA levels in BALF (sigma = 0.50, P = 0.027) and were higher among patients with HRCT parenchymal lung abnormalities (P = 0.022) or bronchiectasis (P = 0.042). Also, ever smoking was more frequent among serum SC-ACPA-positive patients (91% vs 67%, P = 0.023), and the SC-ACPA levels correlated with the number of pack-years (sigma=0.20, P = 0.020). Conclusion. In early, untreated RA, serum levels of SC-ACPA reflect lung involvement in terms of local ACPA levels, smoking and lung abnormalities on HRCT. These findings strengthen the link between mucosal ACPA responses and the lungs in RA.
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| 38. |
- Roos Ljungberg, Karin, 1988-
(författare)
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Secretory Autoantibodies in Rheumatoid Arthritis
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease in which autoantibodies, such as anti-citrullinated protein antibodies (ACPA), can be detected in the serum of patients. Autoantibodies may appear in the circulation years before clinical signs of joint inflammation occur, indicating that early immunological pathogenetic steps take place outside of the joints. Although many of these mechanisms are currently unknown, the initial events leading up to ACPA production are thought to occur at mucosal surfaces. In this thesis, mucosa-associated secretory ACPA are investigated in the circulation and in local mucosal secretions to: (i) improve the understanding of the mucosal connection in RA; and (ii) investigate whether these antibodies can improve diagnostics and prognostics in early RA. We identified circulating secretory component containing (SC) ACPA in a subpopulation of patients (both early and established RA) and at-risk patients, with a prevalence of 16%-21%. In addition, SC ACPA was detected in bronchoalveolar lavage fluid (BALF) and IgA ACPA in saliva, indicating local production in the lungs and in the oral cavity. In at-risk patients who were positive for IgG ACPA, we found that the levels of circulating SC ACPA at inclusion predicted arthritis development. Circulating SC ACPA was associated with higher disease activity, including increased levels of inflammatory markers, in patients with early RA. Levels of circulating SC ACPA were associated with high-resolution computed tomography (HRCT) findings (parenchymal lung abnormalities and bronchiectasis) and smoking, but not with risk genes (shared epitope). We confirmed the presence of salivary ACPA and identified a novel association with increased disease activity and functional disability. In summary, SC ACPA is present in the sera of patients with RA who manifest different phases of the disease, and we found associations with arthritis onset, smoking, systemic inflammation, and lung abnormalities. SC ACPA is also detectable in mucosal secretions from the lungs and the oral cavity. These findings suggest that mucosal ACPA production may be an important factor in RA development and progression, and that serum SC ACPA should be further evaluated as a prognostic marker for disease onset among at-risk individuals.
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| 39. |
- Rouhbakhsh, Zeinab, et al.
(författare)
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Self-Assembly of a Structurally Defined Chiro-Optical Peptide-Oligothiophene Hybrid Material
- 2018
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 3:11, s. 15066-15075
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Tidskriftsartikel (refereegranskat)abstract
- Conducting polymers are routinely used in optoelectronic biomaterials, but large polymer polydispersity and poor aqueous compatibility complicate integration with biomolecular templates and development of discrete and defined supramolecular complexes. Herein, we report on a chiro-optical hybrid material generated by the self-assembly of an anionic peptide and a chemically defined cationic pentameric thiophene in aqueous environment. The peptide acts as a stereochemical template for the thiophene and adopts an α-helical conformation upon association, inducing optical activity in the thiophene π-π* transition region. Theoretical calculations confirm the experimentally observed induced structural changes and indicate the importance of electrostatic interactions in the complex. The association process is also probed at the substrate-solvent interface using peptide-functionalized gold nanoparticles, indicating that the peptide can also act as a scaffold when immobilized, resulting in structurally well-defined supramolecular complexes. The hybrid complex could rapidly be assembled, and the kinetics of the formation could be monitored by utilizing the local surface plasmon resonance originating from the gold nanoparticles. We foresee that these findings will aid in designing novel hybrid materials and provide a possible route for the development of functional optoelectronic interfaces for both biomaterials and energy harvesting applications.
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| 40. |
- Sandholt, Arnar K. S., et al.
(författare)
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Dual RNA-seq transcriptome analysis of caecal tissue during primary Eimeria tenella infection in chickens
- 2021
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Ingår i: BMC Genomics. - : BioMed Central (BMC). - 1471-2164. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coccidiosis is an infectious disease with large negative impact on the poultry industry worldwide. It is an enteric infection caused by unicellular Apicomplexan parasites of the genus Eimeria. The present study aimed to gain more knowledge about interactions between parasites and the host immune system during the early asexual replication phase of E. tenella in chicken caeca. For this purpose, chickens were experimentally infected with E. tenella oocysts, sacrificed on days 1-4 and 10 after infection and mRNA from caecal tissues was extracted and sequenced.Results: Dual RNA-seq analysis revealed time-dependent changes in both host and parasite gene expression during the course of the infection. Chicken immune activation was detected from day 3 and onwards with the highest number of differentially expressed immune genes recorded on day 10. Among early (days 3-4) responses up-regulation of genes for matrix metalloproteinases, several chemokines, interferon (IFN)-gamma along with IFN-stimulated genes GBP, IRF1 and RSAD2 were noted. Increased expression of genes with immune suppressive/regulatory effects, e.g. IL10, SOCS1, SOCS3, was also observed among early responses. For E. tenella a general up-regulation of genes involved in protein expression and energy metabolism as well as a general down-regulation genes for DNA and RNA processing were observed during the infection. Specific E. tenella genes with altered expression during the experiment include those for proteins in rhoptry and microneme organelles.Conclusions: The present study provides novel information on both the transcriptional activity of E. tenella during schizogony in ceacal tissue and of the local host responses to parasite invasion during this phase of infection. Results indicate a role for IFN-gamma and IFN-stimulated genes in the innate defence against Eimeria replication.
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| 41. |
- Sandholt, Arnar K. S., et al.
(författare)
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Dual RNA-Seq transcriptome analysis of chicken macrophage-like cells (HD11) infected in vitro with Eimeria tenella
- 2021
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Ingår i: Parasitology. - : Cambridge University Press. - 0031-1820 .- 1469-8161. ; 148:6, s. 712-725
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to monitor parasite and host gene expression during the early stages of Eimeria tenella infection of chicken cells using dual RNA-Seq analysis. For this, we used chicken macrophage-like cell line HD11 cultures infected in vitro with purified E. tenella sporozoites. Cultures were harvested between 2 and 72 h post-infection and mRNA was extracted and sequenced. Dual RNA-Seq analysis showed clear patterns of altered expression for both parasite and host genes during infection. For example, genes in the chicken immune system showed upregulation early (2-4 h), a strong downregulation of genes across the immune system at 24 h and a repetition of early patterns at 72 h, indicating that invasion by a second generation of parasites was occurring. The observed downregulation may be due to immune self-regulation or to immune evasive mechanisms exerted by E. tenella. Results also suggested pathogen recognition receptors involved in E. tenella innate recognition, MRC2, TLR15 and NLRC5 and showed distinct chemokine and cytokine induction patterns. Moreover, the expression of several functional categories of Eimeria genes, such as rhoptry kinase genes and microneme genes, were also examined, showing distinctive differences which were expressed in sporozoites and merozoites.
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| 42. |
- Schindele, Anna ChuChu, et al.
(författare)
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Associations between and intersectional implications on openness about HIV status and suicide thoughts in a diverse national sample of young people living with HIV in Sweden
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe focus in HIV care so far have been to reach good physical conditions and through the UNAIDS 90-90-90 target. However, health also includes mental and social well-being as well as the absence of stigma and discrimination. The overall aim of this study is to explore the association between living as open with HIV as one wants and suicide thoughts among 16-29-year old young people living with HIV in Sweden. A secondary aim is to see how this can be understood in the intersections of gender and sexual identity.MethodsThis study is based on a national survey of young people living with HIV conducted at HIV-clinics in 2018. The survey had 173 respondents, giving a response rate of 36 percent. Logistic regression models were used to calculate odds ratios (OR) using suicide thoughts as the outcome variable and open with HIV status, gender and sexual identity as exposure variables. Gender and sexual identity was combined to investigate intersections.Results: The results show that suicidal thoughts are more common among young people who report that they were not as open as they wanted to be with their HIV status (OR 1.71 95% CI : 0.90 – 3.25). The analysis also indicate that the associations of suicide thoughts intersects with gender, sexual identity and openness with one’s HIV. In general, men had higher odds ratios of suicide thoughts if they reported not being as open as they wanted to with their HIV status, or belonging to a sexual minority, compared to heterosexual men being as open as they wanted. In women, the groups were smaller and the same pattern was not observed.ConclusionsThe findings add to previous knowledge and guide policy and practise as it point not only to the possibilities if being as open as one wants with HIV status but also to how this has different implications depending on the intersection of sex and sexual identity. The results pinpoint the need of larger studies to investigate intersections further.
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| 43. |
- Sedelius, Helene, et al.
(författare)
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Professionals' perspectives on existing practice and conditions for nurse-led gout care based on treatment recommendations: a qualitative study in primary healthcare
- 2022
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Ingår i: Bmc Primary Care. - : Springer Science and Business Media LLC. - 2731-4553. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Gout affects nearly 2 % of the population and is associated with repeated painful flares of arthritis. Preventive urate-lowering therapy is widely available, but only one third of patients receive adequate treatment. Lack of knowledge among healthcare professionals and patients within primary healthcare are implicated as partial explanations for this undertreatment. Nurse-led care has proved to be an effective model when treating patients with gout, but there is a need for more knowledge about factors that can be expected to influence the future implementation of such care. The aim of this study was to describe factors influencing existing gout care in primary healthcare and the conditions for a future implementation of nurse-led gout care based on national treatment recommendations. Methods In this qualitative study, focus group discussions with 56 nurses and physicians and individual interviews with eight managers were conducted at nine primary healthcare units in central Sweden. A deductive qualitative content analysis based on the main constructs of the framework Integrated Promoting Action on Research Implementation in Health Services was followed by an inductive analysis within the frames of the main constructs: innovation, recipients and context. Results Gout-related contacts with primary healthcare was described as being patient initiated, diagnostics was in some respects complex and nurse-led care was experienced as a favourable primary healthcare model in general (innovation). Gout was seen as a low-priority condition with acute flares and there was inadequate knowledge of gout, including preventive treatment (recipients). Primary healthcare was perceived as having a holistic but fragmented responsibility for gout care, recommendations against keeping waiting lists complicated follow-up appointments and a need for motivation and support when introducing new practices was emphasised (context). Conclusion In this study, investigating the perspective of professionals, several factors were found to influence existing gout care. It will be crucial to target these factors in the development of a future implementation strategy.
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| 44. |
- Sigurdardottir, Valgerdur, et al.
(författare)
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Gout - a common and well known disease : Gikt – en känd och vanlig sjukdom.
- 2020
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Ingår i: Läkartidningen. - 1652-7518. ; 117:35-36
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Forskningsöversikt (refereegranskat)abstract
- Hyperuricemia is defined by a blood urate level > 405 µmol/L, the cut-off value at which urate forms crystals in vivo. In 15-20% these individuals develop gout, clinically characterized by attacks of acute arthritis, initially and most commonly affecting MTP 1 or other joints, tendons and soft tissues of the foot. These attacks usually subside within 1 to 2 weeks. Over time attacks occur more frequently and can transform into chronic arthritis characterized by tophi. The gold standard for diagnosis relies on identification of urate crystals by polarization microscopy in aspirated joint fluid. This procedure is rarely performed in primary care where the majority of patients are seen, and gout is usually diagnosed by clinical criteria. New imaging technologies (ultrasound, dual-energy CT) can be helpful when aspiration is not available and when the diagnosis is unclear. Gout has a prevalence of 1.7% and incidence rate of approximately 200 per 100000 person-years in Sweden, figures that increase over time.
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| 45. |
- Sigurdardottir, Valgerdur, et al.
(författare)
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Gout in Dalarna, Sweden - a population-based study of gout occurrence and compliance to treatment guidelines
- 2022
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732.
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to describe the incidence and prevalence of gout, describe the use of allopurinol among prevalent gout cases, and determine persistence with allopurinol and degree of compliance with treat-to-target recommendations before and after the publication of Swedish national guidelines in 2016. Method Prospectively registered data on gout diagnoses and allopurinol prescriptions were used to calculate incidence and prevalence, and the proportion of prevalent patients on allopurinol. Gout patients starting allopurinol during 2013-2015 versus 2016-2018 were compared regarding persistence and compliance with treat-to-target principles. Results The incidence of gout was 221-247 per 100 000 person-years during 2014-2019, prevalence in 2018 was 2.45%. Among prevalent cases, the proportion on allopurinol ranged from 21% to 25%. Allopurinol persistence was better for individuals starting therapy during 2016-2018 compared with 2013-2015 (45% vs 39%, p = 0.031), as were several outcomes related to treat-to-target principles, e.g. measuring baseline serum urate (SU) (84% vs 77%, p < 0.001), follow-up SU (50% vs 36%, p < 0.001), and the proportion of patients reaching an SU level < 360 mu mol/L (45% vs 30%, p < 0.001). Conclusion Incidence and prevalence were slightly higher than in previous Swedish reports. Allopurinol use among prevalent gout patients did not increase during 2014-2019. Only a minor improvement in persistence was seen, and a moderate increase in compliance with guidelines, suggesting a need for improved management and extended patient involvement to increase and optimize the use of urate lowering therapy.
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| 46. |
- Sigurdardottir, Valgerdur, et al.
(författare)
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Occupational exposure to inorganic dust and risk of gout: A population-based study
- 2020
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Risk factors operating independently of hyperuricemia could be of importance in determining why only a minority of people with hyperuricemia develop gout. Exposure to inorganic dust has been linked to other inflammatory diseases and could influence the development of gout. Objectives To evaluate if occupational exposure to inorganic dust increases the risk of gout. Methods Individuals aged 30-65 years with a first gout diagnosis in 2006-2012 in the population-based healthcare database of the Western Swedish Healthcare Region (VEGA) and population controls matched by age and sex were included. Data on occupation was collected from the Swedish occupational register. Exposure status was assigned by means of a job exposure matrix. Data on gout-related comorbidities was collected from VEGA. Alcohol use disorder and obesity were related both to gout and exposure to inorganic dust and were adjusted for in multivariate analyses. ORs were calculated using conditional logistic regression. Results 5042 gout cases and 20 682 controls were included. Exposure to inorganic dust was associated with gout in both unadjusted (OR 1.12, 95% CI 1.04 to 1.20) and multivariate (OR 1.08, 95% CI 1.00 to 1.16) analyses of the whole population. In sex-stratified multivariate analyses, dust exposure was significantly associated with gout in women (adjusted OR 1.26, 95% CI 1.05 to 1.51), but not in men (adjusted OR 1.05, 95% CI 0.97 to 1.13). Conclusions We describe for the first time an association between exposure to inorganic dust and gout. After adjusting for confounders, the findings were statistically significant for women but not for men. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 47. |
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| 48. |
- Sigurdardottir, Valgerdur, et al.
(författare)
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Work disability in gout: a population-based case-control study
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:3, s. 399-404
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Tidskriftsartikel (refereegranskat)abstract
- To examine the extent and cost of work disability among patients with gout compared with matched population controls and to analyse predictors of work disability.A regional cohort study using data from Swedish national and regional registries from January 2000 through December 2012, including 4571 patients with gout of working age, with a first recorded diagnosis of gout in the years 2003-2009 and 22482 population controls, matched by age, sex and place of residence. Differences in baseline characteristics (educational level, income, previous employment and comorbidities) and the number of work-loss days (absenteeism) due to sick leave and disability pension for 3 years after identification were calculated. Predictors for new-onset work absenteeism (>90days/year) in a subset were determined by conditional logistic regression.Patients with gout (median age 53years) had significantly more comorbidities, lower income and lower level of education than matched controls. The average work absentee rate during the 3-year follow-up period was higher among patients with gout than controls, 22% and 14%, respectively (P<0.0001). New-onset absenteeism was in multivariate analyses significantly predicted by gout (OR 1.47; 95%CI 1.23 to 1.75). Other variables independently related to new-onset absenteeism were education ≤12years, previous unemployment and history of sick leave, in addition to several comorbidities (renal disease, cardiovascular disease, alcohol abuse and obesity). Gout is associated with substantially higher work absenteeism and costs for society due to productivity loss, after adjusting for associated comorbidities and socioeconomic differences. Whether more intensive treatment of gout is cost-effective needs to be addressed in future studies.
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| 49. |
- Stairs, Courtney W., et al.
(författare)
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Oxygen induces the expression of invasion and stress response genes in the anaerobic salmon parasite Spironucleus salmonicida
- 2019
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Ingår i: BMC Biology. - : BioMed Central (BMC). - 1741-7007. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Spironucleus salmonicida is an anaerobic parasite that can cause systemic infections in Atlantic salmon. Unlike other diplomonad parasites, such as the human pathogen Giardia intestinalis, Spironucleus species can infiltrate the blood stream of their hosts eventually colonizing organs, skin and gills. How this presumed anaerobe can persist and invade oxygenated tissues, despite having a strictly anaerobic metabolism, remains elusive.Results: To investigate how S. salmonicida response to oxygen stress, we performed RNAseq transcriptomic analyses of cells grown in the presence of oxygen or antioxidant-free medium. We found that over 20% of the transcriptome is differentially regulated in oxygen (1705 genes) and antioxidant-depleted (2280 genes) conditions. These differentially regulated transcripts encode proteins related to anaerobic metabolism, cysteine and Fe-S cluster biosynthesis, as well as a large number of proteins of unknown function. S. salmonicida does not encode genes involved in the classical elements of oxygen metabolism (e.g., catalases, superoxide dismutase, glutathione biosynthesis, oxidative phosphorylation). Instead, we found that genes encoding bacterial-like oxidoreductases were upregulated in response to oxygen stress. Phylogenetic analysis revealed some of these oxygen-responsive genes (e.g., nadh oxidase, rubrerythrin, superoxide reductase) are rare in eukaryotes and likely derived from lateral gene transfer (LGT) events into diplomonads from prokaryotes. Unexpectedly, we observed that many host evasion- and invasion-related genes were also upregulated under oxidative stress suggesting that oxygen might be an important signal for pathogenesis.Conclusion: While oxygen is toxic for related organisms, such as G. intestinalis, we find that oxygen is likely a gene induction signal for host invasion- and evasion-related pathways in S. salmonicida. These data provide the first molecular evidence for how S. salmonicida could tolerate oxic host environments and demonstrate how LGT can have a profound impact on the biology of anaerobic parasites.
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| 50. |
- Svärd, Anna, et al.
(författare)
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A Comparison Between IgG- and IgA-class Antibodies to Cyclic Citrullinated Peptides and to Modified Citrullinated Vimentin in Early Rheumatoid Arthritis and Very Early Arthritis
- 2011
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Ingår i: Journal of Rheumatology. - : Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 38:7, s. 1265-1272
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis. less thanbrgreater than less thanbrgreater thanMethods. Two Swedish arthritis populations were examined: 215 patients with early RA (andlt;= 12 months duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (andlt;= 3 months duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. less thanbrgreater than less thanbrgreater thanResults were related to disease course, smoking habits, and shared epitope status. Results. In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive. less thanbrgreater than less thanbrgreater thanConclusion. The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.
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