| 1. |
- Pertsinidou, Eleftheria, et al.
(författare)
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In early rheumatoid arthritis, anticitrullinated peptide antibodies associate with low number of affected joints and rheumatoid factor associates with systemic inflammation
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:3, s. 277-287
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis.Methods: IgA, IgG, IgM rheumatoid factor (RF), antibodies against cyclic citrullinated peptide version 2 (anti-CCP2) and 16 individual antibodies against citrullinated protein (ACPA) reactivities were analysed centrally in baseline sera from 1600 patients with RA classified according to the 1987 American College of Rheumatology (ACR) criteria. These results were related to C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), number of swollen and tender joints (SJC and TJC), 28-joint disease activity scores (DAS28 and DAS28CRP), global disease activity evaluated by the patients and Health Assessment Questionnaire, all obtained at baseline.Results: Individually, all autoantibodies except immunoglobulin G (IgG) RF associated with low SJC and TJC and with high ESR. In IgM RF-negative patients, ACPA associated strictly with low number of swollen and tender joints. This association persisted in multiple regression and stratified analyses where IgM and IgA RF instead associated with inflammation expressed as ESR. Among subjects without any ACPA peptide reactivity, there was no association between RF isotypes and ESR. The effect of RF on ESR increased with the number of ACPA reactivities, especially for IgM RF. In patients fulfilling the 1987 ACR criteria without taking RF into account, associations between IgM RF and high ESR, as well as between ACPA and low joint counts, remained.Conclusion: Whereas ACPA associate with low counts of affected joints in early RA, RF associates with elevated measures of systemic inflammation in an ACPA-dependent manner. This latter finding corroborates in vitro models of ACPA and RF in immune complex-induced inflammation. These phenotypic associations are independent of classification criteria.
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| 2. |
- Westerlind, Helga, et al.
(författare)
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Anti-Citrullinated Protein Antibody Specificities, Rheumatoid Factor Isotypes, and Incident Cardiovascular Events in Patients With Rheumatoid Arthritis
- 2020
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 72:10, s. 1658-1667
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the relationship between anti–citrullinated protein antibodies (ACPAs), specific ACPA subspecificities, rheumatoid factor (RF) isotypes, and incident cardiovascular (CV) events in patients with rheumatoid arthritis (RA).Methods Serum samples from Swedish patients with new-onset RA (diagnosed within 1 year of symptom onset between 1996 and 2009) were centrally typed for anti–cyclic citrullinated peptide 2 (anti-CCP2) antibodies, 20 ACPA subspecificities, and RF isotypes. Patients were followed up longitudinally in nationwide registers to monitor the occurrence of acute coronary syndrome (ACS), stroke, CV-related death, and major adverse CV events (MACE). The association between each serologic marker and CV outcome, and the impact of adjustment for the Disease Activity Score in 28 joints (DAS28), smoking status, and income at baseline, were assessed using Cox proportional hazards models. In addition, associations of serologic markers with all-cause mortality were explored.Results In total, 2,814 patients with RA were included in the study. The median follow-up was 13 years, during which the CV end points of ACS, stroke, or CV-related death were reported to occur in 375 patients. Occurrence and/or levels of anti-CCP2 were associated with risk of incident ACS (hazard ratio [HR] 1.46, 95% confidence interval [95% CI] 1.03–2.06), stroke (HR 1.47, 95% CI 1.03–2.10), CV-related death (P = 0.024 for association with anti-CCP2 levels), and MACE (HR 1.34, 95% CI 1.06–1.70). Similarly, an association with the number of ACPA subspecificities was observed; however, this could not be attributed to any individual or group of ACPA subspecificities. Presence of IgM-RF was associated with all CV end points except ACS, and IgA-RF was exclusively associated with CV-related death. Adjustment for smoking status, income, and DAS28 scores decreased most of the HRs, whereas IgA-RF remained associated with CV-related death (HR 1.61, 95% CI 1.05–2.48). All of the assessed serologic makers were associated with all-cause mortality.Conclusion RF isotypes and ACPAs are associated with future CV events in patients with RA. ACPA levels and number of subspecificities seem more important than the occurrence of particular subspecificities, and these associations were not explained by a history of ever smoking.
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| 3. |
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| 4. |
- Reed, Evan, et al.
(författare)
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Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity
- 2020
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative.MethodsAnti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets.ResultsAutoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined “seronegative” RA, associated with worse clinical outcome.Conclusions“Seronegative” RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2−/IgM RF− patients with a high need for active treatment.
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| 5. |
- Terao, Chikashi, et al.
(författare)
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Distinct HLA Associations with Rheumatoid Arthritis Subsets Defined by Serological Subphenotype
- 2019
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 105:3, s. 616-624
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is the most common immune-mediated arthritis. Anti-citrullinated peptide antibodies (ACPA) are highly specific to RA and assayed with the commercial CCP2 assay. Genetic drivers of RA within the MHC are different for CCP2-positive and -negative subsets of RA, particularly at HLA-DRB1. However, aspartic acid at amino acid position 9 in HLA-B (Bpos-9) increases risk to both RA subsets. Here we explore how individual serologies associated with RA drive associations within the MHC. To define MHC differences for specific ACPA serologies, we quantified a total of 19 separate ACPAs in RA-affected case subjects from four cohorts (n = 6,805). We found a cluster of tightly co-occurring antibodies (canonical serologies, containing CCP2), along with several independently expressed antibodies (non-canonical serologies). After imputing HLA variants into 6,805 case subjects and 13,467 control subjects, we tested associations between the HLA region and RA subgroups based on the presence of canonical and/or non-canonical serologies. We examined CCP2(+) and CCP2(−) RA-affected case subjects separately. In CCP2(−) RA, we observed that the association between CCP2(−) RA and Bpos-9 was derived from individuals who were positive for non-canonical serologies (omnibus_p = 9.2 × 10−17). Similarly, we observed in CCP2(+) RA that associations between subsets of CCP2(+) RA and Bpos-9 were negatively correlated with the number of positive canonical serologies (p = 0.0096). These findings suggest unique genetic characteristics underlying fine-specific ACPAs, suggesting that RA may be further subdivided beyond simply seropositive and seronegative.
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| 6. |
- Thorén, Anna, et al.
(författare)
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Rapid response team activation prior to in-hospital cardiac arrest: Areas for improvements based on a national cohort study
- 2023
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Ingår i: Resuscitation. - 0300-9572 .- 1873-1570. ; 193
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Rapid response teams (RRTs) are designed to improve the "chain of prevention" of in-hospital cardiac arrest (IHCA). We studied the 30-day survival of patients reviewed by RRTs within 24 hours prior to IHCA, as compared to patients not reviewed by RRTs.Methods: A nationwide cohort study based on the Swedish Registry of Cardiopulmonary Resuscitation, between January 1st, 2014, and December 31st, 2021. An explorative, hypothesis-generating additional in-depth data collection from medical records was performed in a small subgroup of general ward patients reviewed by RRTs.Results: In all, 12,915 IHCA patients were included. RRT-reviewed patients (n = 2,058) had a lower unadjusted 30-day survival (25% vs 33%, p < 0.001), a propensity score based Odds ratio for 30-day survival of 0.92 (95% Confidence interval 0.90-0.94, p < 0.001) and were more likely to have a respiratory cause of IHCA (22% vs 15%, p < 0.001). In the subgroup (n = 82), respiratory distress was the most common RRT trigger, and 24% of the RRT reviews were delayed. Patient transfer to a higher level of care was associated with a higher 30-day survival rate (20% vs 2%, p < 0.001).Conclusion: IHCA preceded by RRT review is associated with a lower 30-day survival rate and a greater likelihood of a respiratory cause of cardiac arrest. In the small explorative subgroup, respiratory distress was the most common RRT trigger and delayed RRT activation was frequent. Early detection of respiratory abnormalities and timely interventions may have a potential to improve outcomes in RRT-reviewed patients and prevent further progress into IHCA.
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| 7. |
- Too, Chun Lai, et al.
(författare)
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Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis : Implications for Disease Pathogenesis
- 2017
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 69:1, s. 58-69
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects. Methods. A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fiba563-583, Fib alpha 580-600, Fib beta 36-52, Fib beta 62-81a, Fib beta 62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%. Results. Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibb62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 ish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [P-corr] =1.06 x 10(-8)) and CitCII355-378 (17% versus 13%, P-corr = 0.02) were significantly higher, while the frequencies of antibodies to Vim2-17 (25% versus 32%, P-corr = 1.91 x 10(-4)), Fib beta 62-81b (15% versus 30%, P-corr = 2.47 x 10(-22)), and Eno5-21 (23% versus 50%, P-corr = 3.64 x 10(-57)) were significantly lower. Conclusion. Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.
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| 8. |
- Westerlind, Helga, et al.
(författare)
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The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:6, s. 2106-2112
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype. Methods A cohort of 2814 patients with newly diagnosed RA were followed for incident VTE through register linkages. Sera from RA diagnosis were centrally analysed for antibodies to second generation cyclic citrullinated peptides (anti-CCP2), 20 anti-citrullinated protein antibody (ACPA) fine-specificities, antibodies to additional protein modifications (carbamylation and acetylation) and RF by isotype. Association between baseline serology status and future VTE was analysed using Cox regression adjusted for age, sex and calendar period of RA diagnosis, overall and stratified by anti-CCP2 and RF positivity. Results During a median 16 years of follow-up, 213 first-ever VTE events were registered (5.0/1000 person-years). IgG anti-CCP2 (present in 65% of cohort) associated with VTE (hazard ratio [HR] = 1.33, 95% CI: 1.00, 1.78), in a dose-response manner. The risk of VTE increased with number of ACPA fine-specificities. IgM RF, but no other RF isotypes, associated with VTE (HR = 1.38, 95% CI: 1.04, 1.82). The associations were independent from smoking and HLA-DRB1 shared epitope alleles. None of the carbamylated or acetylated antibody reactivities associated with VTE. Conclusion Anti-CCP2, load of ACPA fine-specificities and IgM RF at RA diagnosis are associated with an increased risk of future VTE in RA. Antibodies to citrullinated fibrinogen did not differ substantially from other ACPA fine-specificities. Autoreactivity to other post-translational modifications was not associated with VTE risk.
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| 9. |
- Acevedo, Nathalie, et al.
(författare)
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DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:2
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p <= 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.
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| 10. |
- Ahlqvist, Sandra, et al.
(författare)
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Trocar site hernia after gastric sleeve
- 2022
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Ingår i: Surgical Endoscopy. - : Springer. - 0930-2794 .- 1432-2218. ; 36:6, s. 4386-4391
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Tidskriftsartikel (refereegranskat)abstract
- Background: Laparoscopy is common in abdominal surgery. Trocar site hernia (TSH) is a most likely underestimated complication. Among risk factors, obesity, the use of larger trocars and the umbilical trocar site has been described. In a previous study, CT scan in the prone position was found to be a reliable method for the detection of TSH following gastric bypass (LRYGB). In the present study, our aim was to examine the incidence of TSH after gastric sleeve, and further to investigate the proportion of symptomatic trocar site hernias.Methods: Seventy-nine patients subjected to laparoscopic gastric sleeve in 2011–2016 were examined using CT in the prone position upon a ring. Symptoms of TSH were assessed using a digital survey.Results: The incidence of trocar site hernia was 17 out of 79 (21.5%), all at the umbilical trocar site. The mean follow-up time was 37 months. There was no significant correlation between patient symptoms and a TSH.Conclusions: The incidence of TSH is high after laparoscopic gastric sleeve, a finding in line with several recent studies as well as with our first trial on trocar site hernia after LRYGB. Up to follow-up, none of the patients had been subjected to hernia repair. Although the consequence of a trocar site hernia can be serious, the proportion of symptomatic TSH needs to be more clarified.
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| 11. |
- Alm, Anna-Karin, et al.
(författare)
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Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2.
- 2000
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 275:1, s. 77-83
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Tidskriftsartikel (refereegranskat)abstract
- Proteinase-activated receptors (PARs) are activated by proteolytic removal of a short amino terminal peptide, thus exposing a new amino terminus that functions as a tethered ligand that activates the receptor. With the aim to identify and study potential activators of PAR-2 we have developed a new method to measure proteolytic cleavage of PARs. PAR-2 was tagged with the insulin C-peptide that upon receptor cleavage is released and quantified using an ELISA. The modified receptor, shown to be functional in mouse 3T3 cells, was expressed in an insect cell line and the ability of different proteinases to cleave PAR-2 was studied. Two different mast cell tryptases cleaved PAR-2 in a concentration dependent manner, but were much less potent than pancreatic trypsin and trypsin-2 isolated from a carcinoma cell line. Pancreatic trypsin and trypsin-2 were almost equally effective at cleaving PAR-2 suggesting that extrapancreatic trypsins are potential in vivo activators of PAR-2.
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| 12. |
- Alm, Erik, 1980-, et al.
(författare)
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A solution to the 1D NMR alignment problem using an extended generalized fuzzy Hough transform and mode support
- 2009
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 395:1, s. 213-223
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Tidskriftsartikel (refereegranskat)abstract
- This paper approaches the problem of intersample peak correspondence in the context of later applying statistical data analysis techniques to 1D 1H-nuclear magnetic resonance (NMR) data. Any data analysis methodology will fail to produce meaningful results if the analyzed data table is not synchronized, i.e., each analyzed variable frequency (Hz) does not originate from the same chemical source throughout the entire dataset. This is typically the case when dealing with NMR data from biological samples. In this paper, we present a new state of the art for solving this problem using the generalized fuzzy Hough transform (GFHT). This paper describes significant improvements since the method was introduced for NMR datasets of plasma in Csenki et al. (Anal Bioanal Chem 389:875-885, 15) and is now capable of synchronizing peaks from more complex datasets such as urine as well as plasma data. We present a novel way of globally modeling peak shifts using principal component analysis, a new algorithm for calculating the transform and an effective peak detection algorithm. The algorithm is applied to two real metabonomic 1H-NMR datasets and the properties of the method are compared to bucketing. We implicitly prove that GFHT establishes the objectively true correspondence. Desirable features of the GFHT are: (1) intersample peak correspondence even if peaks change order on the frequency axis and (2) the method is symmetric with respect to the samples.
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| 13. |
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| 14. |
- Alm, Erik, 1980-, et al.
(författare)
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Automated annotation and quantification of metabolites in (1)H NMR data of biological origin
- 2012
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 403:2, s. 443-455
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Tidskriftsartikel (refereegranskat)abstract
- In 1H NMR metabolomic datasets, there are often over a thousand peaks per spectrum, many of which change position drastically between samples. Automatic alignment, annotation, and quantification of all the metabolites of interest in such datasets have not been feasible. In this work we propose a fully automated annotation and quantification procedure which requires annotation of metabolites only in a single spectrum. The reference database built from that single spectrum can be used for any number of 1H NMR datasets with a similar matrix. The procedure is based on the generalized fuzzy Hough transform (GFHT) for alignment and on Principal-components analysis (PCA) for peak selection and quantification. We show that we can establish quantities of 21 metabolites in several 1H NMR datasets and that the procedure is extendable to include any number of metabolites that can be identified in a single spectrum. The procedure speeds up the quantification of previously known metabolites and also returns a table containing the intensities and locations of all the peaks that were found and aligned but not assigned to a known metabolite. This enables both biopattern analysis of known metabolites and data mining for new potential biomarkers among the unknowns.
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| 15. |
- Alm, Erik, 1980-, et al.
(författare)
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Time-resolved biomarker discovery inH-NMR data using generalized fuzzy Hough transform alignment and parallel factor analysis
- 2010
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 396:5, s. 1681-1689
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Tidskriftsartikel (refereegranskat)abstract
- This work addresses the subject of time-series analysis of comprehensive 1H-NMR data of biological origin. One of the problems with toxicological and efficacy studies is the confounding of correlation between the administered drug, its metabolites and the systemic changes in molecular dynamics, i.e., the flux of drug-related molecules correlates with the molecules of system regulation. This correlation poses a problem for biomarker mining since this confounding must be untangled in order to separate true biomarker molecules from dose-related molecules. One way of achieving this goal is to perform pharmacokinetic analysis. The difference in pharmacokinetic time profiles of different molecules can aid in the elucidation of the origin of the dynamics, this can even be achieved regardless of whether the identity of the molecule is known or not. This mode of analysis is the basis for metabonomic studies of toxicology and efficacy. One major problem concerning the analysis of 1H-NMR data generated from metabonomic studies is that of the peak positional variation and of peak overlap. These phenomena induce variance in the data, obscuring the true information content and are hence unwanted but hard to avoid. Here, we show that by using the generalized fuzzy Hough transform spectral alignment, variable selection, and parallel factor analysis, we can solve both the alignment and the confounding problem stated above. Using the outlined method, several different temporal concentration profiles can be resolved and the majority of the studied molecules and their respective fluxes can be attributed to these resolved kinetic profiles. The resolved time profiles hereby simplifies finding true biomarkers and bio-patterns for early detection of biological conditions as well as providing more detailed information about the studied biological system. The presented method represents a significant step forward in time-series analysis of biological 1H-NMR data as it provides almost full automation of the whole data analysis process and is able to analyze over 800 unique features per sample. The method is demonstrated using a 1H-NMR rat urine dataset from a toxicology study and is compared with a classical approach: COW alignment followed by bucketing.
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| 16. |
- Alm, Johan
(författare)
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A Universal A(infinity) Structure on BV Algebras with Multiple Zeta Value Coefficients
- 2016
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Ingår i: International mathematics research notices. - : Oxford University Press (OUP). - 1073-7928 .- 1687-0247. ; :24, s. 7414-7470
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Tidskriftsartikel (refereegranskat)abstract
- We construct an explicit and universal A-infinity deformation of Batalin-Vilkovisky algebras, with all coefficients expressed as rational sums of multiple zeta values. If the Batalin-Vilkovisky algebra that we start with is cyclic, then so is the A-infinity deformation. Moreover, the adjoint action of the odd Poisson bracket acts by derivations of the A-infinity structure. The construction conjecturally defines a new presentation of the Grothendieck-Teichmuller Lie algebra.
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| 17. |
- Alm, Johan
(författare)
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Atopy in children : association to life style
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of allergic diseases has risen; in some countries nearly half the children suffer from some type of hypersensitivity. The reason for this increase is obscure, but one explanation is suggested to be a changing panorama of microbial stimulation early in life. The overall objective of this work was to study the effect of certain life style factors on the development of atopy in children. In the first study the role of early BCG vaccination for development of atopy in children was investigated. A retrospective cohort study included 216 Swedish children with atopic heredity, hom between 1989 and 1992, who received BCG vaccination when they were younger than 6 months. Comparison was made with 358 age-matched un-vaccinated controls. In the BCG vaccinated group 29% were atopic, defined as positive serology and/or skin-prick test, compared to 24% in the control group. Risk factors for atopic disease were evenly distributed between the two groups. It may be concluded that early BCG vaccination in children with atopic heredity does not play an important role for development of atopic disease before school age. To assess gene-environment interactions the distribution of promoter alleles on the NRAMP1-gene and for a nearby micro satellite, D2S1471, was investigated in blood cells from the children in the first study. Atopy in relation to NRAMP1 was similarly distributed between the two groups. In the BCG vaccinated children, however, genotype associations were observed for D2S1471 and atopy (Odds Ratio (OR) 4.3 [95% Confidence Interval (CI) 1.7- 10.7]). Thus, stratification by BCG vaccination unmasked a genetic risk factor for atopy in the region of the NRAMP1 gene. The anthroposophic life style has several characteristics, which are of interest in relation to atopy, such as restrictive use of antibiotics and vaccinations, an a diet containing live lactobacilli. In a cross-sectional study, 295 children at anthroposophic (Steiner) schools were compared with 380 children of the same age at neighbouring schools. At the Steiner schools, around half as many children had been treated with antibiotics and antipyretics, and had few vaccinations as compared to the control schools. Vegetables fermented by lactobacilli, were eaten by 2/3 of the children at Steiner schools, but rarely by the controls. A lower prevalence of atopy, defined by objective tests, was shown in children from Steiner schools (OR 0.62 [95% Cl 0.43-0.91]) including an inverse relation between the number of characteristic features of the anthroposophic life style and atopy (p=0.01). Life style factors associated with anthroposophy appear to reduce the risk of atopy in childhood. A role of intestinal microflora in turning the immune system towards tolerance is proposed. An anthroposophical way of life, including giving birth at home, may affect the intestinal microflora in infancy. In a cross-sectional study the intestinal microflora in 69 infants with an anthroposophical life style was compared with 59 children of the same age with traditional life style. Breastfeeding and use of antibiotics correlated to faecal microflora, and to fatty acids produced by indigenous bacteria. The effect of antibiotics on the flora seemed to be long lasting. The diversity of lactobacilli and presence of caproic acid were higher in infants born at home, than in those born in hospital. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families. Thus, new aspects on the importance of genotype-environment interactions in determining susceptibility for atopic disease have been highlighted. In addition, our results show that life style influenced atopy prevalence in school children and the composition of the gut flora in infants.
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| 18. |
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| 19. |
- Alm, Johan, et al.
(författare)
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Brown's dihedral moduli space and freedom of the gravity operad
- 2017
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Ingår i: Annales Scientifiques de l'Ecole Normale Supérieure. - : Societe Mathematique de France. - 0012-9593 .- 1873-2151. ; 50:5, s. 1081-1122
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Tidskriftsartikel (refereegranskat)abstract
- Francis Brown introduced a partial compactification M-0,n(delta) of the moduli space M-0,M-n. We prove that the gravity cooperad, given by the degree-shifted cohomologies of the spaces M-0,M-n, is cofree as a nonsymmetric anticyclic cooperad; moreover, the cogenerators are given by the cohomology groups of M-0,n(delta). As part of the proof we construct an explicit diagrammatically defined basis of H.(M-0,M-n) which is compatible with cooperadic cocomposition, and such that a subset forms a basis of H.(M-0,n(delta)). We show that our results are equivalent to the claim that H-k (M-0,n(delta)) has a pure Hodge structure of weight 2k for all k, and we conclude our paper by giving an independent and completely different proof of this fact. The latter proof uses a new and explicit iterative construction of M-0,n(delta) from A(n-3) by blow-ups and removing divisors, analogous to Kapranov's and Keel's constructions of (M) over bar (0,n) from Pn-3 and (P-1)(n-3), respectively.
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| 20. |
- Alm, Johan, et al.
(författare)
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Grothendieck-Teichmuller group and Poisson cohomologies
- 2015
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Ingår i: Journal of Noncommutative Geometry. - 1661-6952 .- 1661-6960. ; 9:1, s. 185-214
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Tidskriftsartikel (refereegranskat)abstract
- We study actions of the Grothendieck-Teichmuller group GRT on Poisson cohomologies of Poisson manifolds, and prove some go and no-go theorems associated with these actions.
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| 21. |
- Alm, Johan, 1985-
(författare)
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Universal algebraic structures on polyvector fields
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The theory of operads is a conceptual framework that has become a kind of universal language, relating branches of topology and algebra. This thesis uses the operadic framework to study the derived algebraic properties of polyvector fields on manifolds.The thesis is divided into eight chapters. The first is an introduction to the thesis and the research field to which it belongs, while the second chapter surveys the basic mathematical results of the field.The third chapter is devoted to a novel construction of differential graded operads, generalizing an earlier construction due to Thomas Willwacher. The construction highlights and explains several categorical properties of differential graded algebras (of some kind) that come equipped with an action by a differential graded Lie algebra. In particular, the construction clarifies the deformation theory of such algebras and explains how such algebras can be twisted by Maurer-Cartan elements.The fourth chapter constructs an explicit strong homotopy deformation of polynomial polyvector fields on affine space, regarded as a two-colored noncommutative Gerstenhaber algebra. It also constructs an explicit strong homotopy quasi-isomorphism from this deformation to the canonical two-colored noncommmutative Gerstenhaber algebra of polydifferential operators on the affine space. This explicit construction generalizes Maxim Kontsevich's formality morphism.The main result of the fifth chapter is that the deformation of polyvector fields constructed in the fourth chapter is (generically) nontrivial and, in a sense, the unique such deformation. The proof is based on some cohomology computations involving Kontsevich's graph complex and related complexes. The chapter ends with an application of the results to properties of a derived version of the Duflo isomorphism.The sixth chapter develops a general mathematical framework for how and when an algebraic structure on the germs at the origin of a sheaf on Cartesian space can be "globalized" to a corresponding algebraic structure on the global sections over an arbitrary smooth manifold. The results are applied to the construction of the fourth chapter, and it is shown that the construction globalizes to polyvector fields and polydifferential operators on an arbitrary smooth manifold.The seventh chapter combines the relations to graph complexes, explained in chapter five, and the globalization theory of chapter six, to uncover a representation of the Grothendieck-Teichmüller group in terms of A-infinity morphisms between Poisson cohomology cochain complexes on a manifold.Chapter eight gives a simplified version of a construction of a family of Drinfel'd associators due to Carlo Rossi and Thomas Willwacher. Our simplified construction makes the connections to multiple zeta values more transparent--in particular, one obtains a fairly explicit family of evaluations on the algebra of formal multiple zeta values, and the chapter proves certain basic properties of this family of evaluations.
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| 22. |
- Alm, Kersti, et al.
(författare)
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Digital holography and cell studies
- 2011
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Ingår i: Holography, Research and Technologies. - : DKV - Deutscher Kälte- und Klimatechnischer Verein. - 9789533072272 ; , s. 237-252
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Digital holography microscopy (DHM) has developed into a broad field, and one of all the interesting applications is to study cells without staining, labeling or in any other way affecting them. Both fixed and living, dying or dead cells can be studied. The first DHM images showing living cells were published in 2004 and 2005 (Carl et al. 2004, Marquet et al. 2005), making this field of research rather new. Digital holography makes it possible to easily measure cell properties that previously have been very difficult to study, such as cell thickness and volume (Marquet et al. 2005, Mölder et al. 2008). Two of the major advantages of DHM is the 3-D imaging possibility and measurements over time. Digital holography has ben used to study several types of cells, such as nerve cells, red blood cells, stem cells and cancer cells (Emery et al. 2007, Kemper et al. 2006, Langehanenberg et al. 2009) . It has also been applied for studies of cell proliferation, cell movement, sub-cellular structures and cell morphology (Kemper et al. 2009, Yu et al. 2009). Both 2-D and 3-D cell movement can be determined ( Langehanenberg et al. 2009). Even cell viability status can be determined using DHM. Interestingly, it is possible to study both single cells and entire populations simultaneously, allowing for very nuanced studies. Older, well known techniques often require some degree of cell disturbance such as the fluorescent antibody labeling required for fluorescense or confocal microscopy studies. In this paper we will present some of the studies made possible by DHM. We will compare DHM with previously used techniques and discuss the benefits and drawbacks of digital holography cell measurements.
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| 23. |
- Alm, Maria
(författare)
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Nationell kraft och lokal motkraft : En diskursanalys av konflikten kring SwePol Link
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Facility siting conflicts are increasing in our society. This is a study of a HVDC-link between Blekinge, Sweden and Slupsk, Poland called The SwePol Link. This link has transferred electricity between the two electricity systems since the year 2000 and the decision making process can be described as a struggle between conflicting interests. The aim of this study is to investigate where in the decision making process conflicting interests become visible, and how the actors involved have acted and argued in order to try to influence the process to benefit their respective causes. This aim is further developed through a discourse analysis of the variety of arguments, ideas and conceptions that in different situations of the process construct patterns and statements. The purpose of the discourse analysis is to identify and categorize patterns and statements that are expressed in three chosen practices; the concession practice, the court practice and the practice concerning the debate articles and editorials published in Blekinge Läns Tidning during the period 1996-2000. This practice is referred to as the mass media practice in the study. It is clear that the conflict deepens and that the system-builders and critical actors (including Blekinge Läns Tidning) started to distrust each other and their respective ways of acting during the process. Both supporters and critics used scientific and juridical enrolments in order to try to strengthen their positions in the conflict. Both scientifically and juridically formulated arguments were central patterns in the discourse. This was also the case with technically formulated arguments. These patterns of arguments were mainly expressed through academics, or experts, for or against the system and might thereby be looked upon as rather exclusive ways of arguing in the practices. One exception from this was, for example, when fishers argued against different scientific results on the basis of their experiences. This was, however, not a very successful way of criticizing scientific results. The study shows that there, for example, were conflicts around the meaning of a sustainable energy system, where a central system-builder pattern meets a peripheral systemcritical pattern and both sides held themselves as arguing for a sustainable energy system. Another result of the study is that the discourse varied depending on which practice it was expressed in. It became clear that holistic perspectives regarding a sustainable energy system or the landscape as such became peripheral in all of the “formal” practices, where the decisions regarding the system took place. These types of holistic patterns were mainly articulated in other practices like the mass media.
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| 24. |
- Alm, Stina, et al.
(författare)
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Erythrocyte transfusions increased the risk of elevated serum ferritin in very low birth weight infants and were associated with altered longitudinal growth
- 2020
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 109:7, s. 1354-1360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: There has been a lack of population‐based longitudinal data on serum ferritin in very low birth weight (VLBW) infants during hospitalisation. Our aim was to fill this gap in the knowledge and investigate risk factors for elevated serum ferritin and associations between erythrocyte transfusions and longitudinal growth.Methods: We retrospectively reviewed longitudinal data on 126 VLBW infants treated at Umeå University Hospital, Sweden, between 2010‐2013.Results: The infants’ mean gestational age and birth weight were 26.9 weeks and 899 grams. Most (91%) received erythrocyte transfusions and the majority had multiple erythrocyte transfusions. There was a significant correlation between serum ferritin and the volume of transfusions. Almost two‐thirds had at least one serum ferritin measurement of more than 350 µg/L, indicating iron overload. In those with complete anthropometric data (n=78) there was no significant effect of serum ferritin concentrations in relation to longitudinal growth, but there was a positive association between the erythrocyte transfusion dose and longitudinal growth in VLBW infants born before 25 weeks.Conclusion: This is the first population‐based study to investigate longitudinal data on serum ferritin in VLBW infants during hospitalisation. The unexpected positive finding in the subgroup born at less than 25 weeks needs further research with a larger cohort.
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| 25. |
- Alm, Tove, et al.
(författare)
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A small bispecific protein selected for orthogonal affinity purification
- 2010
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Ingår i: BIOTECHNOL J. - : Wiley. - 1860-6768. ; 5:6, s. 605-617
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Tidskriftsartikel (refereegranskat)abstract
- A novel protein domain with dual affinity has been created by randomization and selection. The small alkali-stabilized albumin-binding domain (ABD(star)), used as scaffold to construct the library, has affinity to human serum albumin (HSA) and is constituted of 46 amino acids of which 11 were randomized. To achieve a dual binder, the binding site of the inherent HSA affinity was untouched and the randomization was made on the opposite side of the molecule. Despite its small size and randomization of almost a quarter of its amino acids, a bifunctional molecule, ABDz1, with ability to bind to both HSA and the Z(2) domain/protein A was successfully selected using phage display. Moreover, the newly selected variant showed improved affinity for HSA compared to the parental molecule. This novel protein domain has been characterized regarding secondary structure and affinity to the two different ligands. The possibility for affinity purification on two different matrices has been investigated using the two ligands, the HSA matrix and the protein A-based, MabSelect SuRe matrix, and the new protein domain was purified to homogeneity. Furthermore, gene fusions between the new domain and three different target proteins with different characteristics were made. To take advantage of both affinities, a purification strategy referred to as orthogonal affinity purification using two different matrices was created. Successful purification of all three versions was efficiently carried out using this strategy.
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| 26. |
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| 27. |
- Andersson, Karin, et al.
(författare)
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Miljöprestanda och samhällsekonomi för saneringsmetoder
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Förord Ett av riksdagens miljömål är Giftfri miljö, och i detta mål ingår att efterbehandla och sanera förorenade områden. Brist på kunskap om risker med förorenade områden och hur de bör hanteras har identifierats som hinder för ett effektivt saneringsarbete. Naturvårdsverket har därför initierat kunskapsprogrammet Hållbar Sanering.Föreliggande rapport redovisar projektet ”Miljöprestanda och samhällsekonomi för saneringsmetoder” som genomförts inom Hållbar sanering. Följande personer har ingått i den projektgrupp som genomfört projektet och skrivit rapporten: Karin Andersson, SIK AB, Institutet för Livsmedel och Bioteknik/Akzo Nobel, Technology & Engineering, Sustainable Development, Johan Alm, WSP Environmental, Thomas Angervall, SIK AB, Institutet för Livsmedel och Bioteknik, Joakim Johansson, WSP Analys & Strategi, John Sternbeck, WSP Environmental samt Friederike Ziegler, SIK AB, Institutet för Livsmedel och Bioteknik.Följande personer har ingått i projektets referensgrupp: Jonny Bergman, Soilrem - Envirotech AB, Marcus Carlsson Reich, Naturvårdsverket, HenrikEkman, EkoTec AB, Tomas Ekvall, IVL Svenska Miljöinstitutet AB, Per Johansson, WSP Environmental samt Sverker Molander, Chalmers. Författarna riktar ett stort tack till referensgruppen! Stort tack också till SPIMFAB för tillgång till haltdata i förorenad jord! Kontaktperson för Hållbar Sanering har varit Knut Per Hasund, Sveriges Lantbruksuniversitet. Naturvårdsverket har inte tagit ställning till innehållet i rapporten. Författarna svarar ensamma för innehåll, slutsatser och eventuella rekommendationer. Naturvårdsverket februari 2008
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| 28. |
- Bengtsson, Johan, 1985, et al.
(författare)
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Metaxa: Automated detection and discrimination among ribosomal small subunit (12S/16S/18S) sequences of archaea, bacteria, eukaryotes, mitochondria, and chloroplasts
- 2011
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Ingår i: SocBiN Bioinformatics Conference, Helsinki, Finland, 2011.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The ribosomal small subunit (SSU) rRNA gene has emerged as an important genetic marker for taxonomic identification in environmental sequencing datasets. However, the gene is not only present in the nuclear genome of eukaryotes and the core genome of prokaryotes, but also in the mitochondria and chloroplasts of eukaryotes. The SSU genes in the core genome, mitochondria and chloroplast are conceptually paralogous and should in most situations not be aligned and analyzed jointly, e.g. when estimating species diversity. Identifying the origin of SSU sequences in complex sequence datasets is a time-consuming and largely manual undertaking. To ease this situation, we have created Metaxa, an automated software tool to extract full-length and partial SSU sequences from larger sequence datasets and assign them to an archaeal, bacte- rial, nuclear eukaryote, mitochondrial, or chloroplast origin. Metaxa very efficiently detects SSU sequences from fragments as short as 200 base pairs, and correctly classifies 97% of the identified genes at read lengths typically obtained from pyrosequencing. In addition, Metaxa shows a false positive rate of 0.00012% when run on random DNA fragments, showing the robustness of the method. We believe that this tool will be useful in microbial and evolutionary ecology as well as in metagenomics.
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| 29. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Metagenomics reveals that detoxification systems are underrepresented in marine bacterial communities
- 2014
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15:749
-
Tidskriftsartikel (refereegranskat)abstract
- Background Environmental shotgun sequencing (metagenomics) provides a new way to study communities in microbial ecology. We here use sequence data from the Global Ocean Sampling (GOS) expedition to investigate toxicant selection pressures revealed by the presence of detoxification genes in marine bacteria. To capture a broad range of potential toxicants we selected detoxification protein families representing systems protecting microorganisms from a variety of stressors, such as metals, organic compounds, antibiotics and oxygen radicals. Results Using a bioinformatics procedure based on comparative analysis to finished bacterial genomes we found that the amount of detoxification genes present in marine microorganisms seems surprisingly small. The underrepresentation is particularly evident for toxicant transporters and proteins involved in detoxifying metals. Exceptions are enzymes involved in oxidative stress defense where peroxidase enzymes are more abundant in marine bacteria compared to bacteria in general. In contrast, catalases are almost completely absent from the open ocean environment, suggesting that peroxidases and peroxiredoxins constitute a core line of defense against reactive oxygen species (ROS) in the marine milieu. Conclusions We found no indication that detoxification systems would be generally more abundant close to the coast compared to the open ocean. On the contrary, for several of the protein families that displayed a significant geographical distribution, like peroxidase, penicillin binding transpeptidase and divalent ion transport protein, the open ocean samples showed the highest abundance. Along the same lines, the abundance of most detoxification proteins did not increase with estimated pollution. The low level of detoxification systems in marine bacteria indicate that the majority of marine bacteria have a low capacity to adapt to increased pollution. Our study exemplifies the use of metagenomics data in ecotoxicology, and in particular how anthropogenic consequences on life in the sea can be examined.
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| 30. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Metaxa: a software tool for automated detection and discrimination among ribosomal small subunit (12S/16S/18S) sequences of archaea, bacteria, eukaryotes, mitochondria, and chloroplasts in metagenomes and environmental sequencing datasets
- 2011
-
Ingår i: Antonie van Leeuwenhoek: international journal of general and molecular microbiology. - : Springer Science and Business Media LLC. - 0003-6072 .- 1572-9699. ; 100:3, s. 471-475
-
Tidskriftsartikel (refereegranskat)abstract
- The ribosomal small subunit (SSU) rRNA gene has emerged as an important genetic marker for taxonomic identification in environmental sequencing datasets. In addition to being present in the nucleus of eukaryotes and the core genome of prokaryotes, the gene is also found in the mitochondria of eukaryotes and in the chloroplasts of photosynthetic eukaryotes. These three sets of genes are conceptually paralogous and should in most situations not be aligned and analyzed jointly. To identify the origin of SSU sequences in complex sequence datasets has hitherto been a time-consuming and largely manual undertaking. However, the present study introduces Metaxa (http://microbiology.se/software/metaxa/), an automated software tool to extract full-length and partial SSU sequences from larger sequence datasets and assign them to an archaeal, bacterial, nuclear eukaryote, mitochondrial, or chloroplast origin. Using data from reference databases and from full-length organelle and organism genomes, we show that Metaxa detects and scores SSU sequences for origin with very low proportions of false positives and negatives. We believe that this tool will be useful in microbial and evolutionary ecology as well as in metagenomics.
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| 31. |
- Boman, Antonia, et al.
(författare)
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Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis : a prospective longitudinal inception cohort study
- 2019
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Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Anticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inception cohort.Methods: The ACPA reactivities were assessed in 1022 patients with early RA (symptoms <12 months) using the custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden) in a prospective longitudinal study of observational assessments of Disease Activity Score (DAS28 and its components) and radiology during the first 24 months, accounting for the treatment.Results: Frequency of ACPA reactivities varied between 13.3% and 63.1%. Of the anticyclic citrullinated peptide-2 (anti-CCP2) antibody-negative patients, ACPA reactivities were positive in 32.6%. Smoking, human leucocyte antigen-shared epitope (HLA-SE), anti-CCP2/rheumatoid factor, protein tyrosine phosphatase non-receptor type 22 (1858C/T) and DAS28 were significantly associated with number of ACPA reactivities. The ACPA reactivities modified differently the development of DAS28 over 24 months (identified using trajectories). Anti-Filaggrin307-324, anti-hnRNP (Peptide)-Z1 and anti-F4-CIT-R antibodies anticipated lower DAS28 values (p<0.01–0.05), while positivity for anti-Fibrinogen(Fib)β62-78(74), and anti-Fibα563-583 predicted higher DAS28 (p<0.01 both). Interaction between anti-Fibß36-52, anti-Pept-5 and anti-Bla-26 antibodies, respectively, and DAS28 during 24 months decreased significantly the DAS28 values (p<0.01–0.05). Corticosteroids and biologicals were related to DAS28-area under the curve and Larsen score 24 months. Anti-vimentin2-17 antibodies remained significantly associated with Larsen score at baseline and 24 months, respectively, and radiological progression, besides biologicals at 24 months adjusted for sex and age.Conclusions: Several ACPA reactivities modified significantly the DAS28 development during the first 24 months and were significantly associated with Larsen score at baseline, 24 months and radiological progression.
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| 32. |
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| 33. |
- Brink, Mikael, et al.
(författare)
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Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis
- 2016
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious. Methods: Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays. Results: The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects (p < 0.0001). In samples collected >= 15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [a-enolase (CEP-1/Eno(5-21))], fibrinogen (Fib)beta(36-52), Fiba(580-600), filaggrin (CCP-1/Fil(307-324)) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms (p < 0.001-0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development. Conclusions: RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies.
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| 34. |
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| 35. |
- Båve, Ullvi, et al.
(författare)
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Activation of the type I interferon system in primary Sjögren's syndrome : a possible etiopathogenic mechanism
- 2005
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:4, s. 1185-1195
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Tidskriftsartikel (refereegranskat)abstract
- Objective The etiopathogenesis of primary Sjögren's syndrome (SS) is largely unknown. In other autoimmune diseases, type I interferon (IFN) may play a pivotal role by triggering and sustaining the disease process. We therefore aimed to determine whether patients with primary SS had an activated type I IFN system. Methods Salivary gland biopsy specimens and sera from patients with primary SS were investigated for the occurrence of IFNα-producing cells and measurable IFNα levels, respectively. The ability of primary SS sera together with apoptotic or necrotic cells to induce IFNα production in normal peripheral blood mononuclear cells was examined. The IFNα inducer was characterized, and IFNα-producing cells were identified. Clinical data were correlated with the IFNα-inducing capacity of primary SS sera. Results Numerous IFNα-producing cells were detected in salivary gland biopsy specimens, despite low serum IFNα levels. Autoantibodies to RNA-binding proteins, combined with material released by necrotic or late apoptotic cells, were potent inducers of IFNα production in plasmacytoid dendritic cells (PDCs). This appeared to be attributable to RNA-containing immune complexes triggering PDCs by means of RNA and interaction with Fcγ receptor IIa. The IFNα-inducing capacity of sera was associated with positive results of a labial salivary gland biopsy (focus score ≥1) and with dermatologic, hematologic, and pulmonary manifestations. Conclusion Patients with primary SS have an activated type I IFN system. Although virus may initiate the production of IFN, the continued IFNα synthesis is caused by RNA-containing immune complexes that activate PDCs to prolong IFNα production at the tissue level. This IFNα promotes the autoimmune process by a vicious circle–like mechanism, with increased autoantibody production and formation of more endogenous IFNα inducers.
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| 36. |
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| 37. |
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| 38. |
- Csenki, Leonard, et al.
(författare)
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Hyphenated chromatography and chemometrics : breaking new grounds in the analysis of complex samples
- 2007
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Ingår i: G.I.T. Laboratory Journal Europe. - 1611-6038. ; 11:1-2, s. 39-40
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Tidskriftsartikel (refereegranskat)abstract
- The task of analyzing complex samples has always been the challenge for the analytical sciences. Today more effort is put into characterizing a greater number of sample constituents, at lower levels and with higher speed and accuracy, all in one analytical run. Present challenges consist of, for example, the analysis of samples with biological/environmental origin measuring as many constituents in the sample as possible. By hyphenating chromatography (GC or (UP)LC) with mass spectrometry (MS) several hundreds of different molecules can be screened in one analysis - now we are faced with the problem of analyzing the large amounts of generated data, trying to extract the relevant information. This is where the fields of chemometrics and data processing, and hyphenated chromatography are successfully married. Here we outline some of the data requirements and new algorithms making exploratory analytical chemistry possible.
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| 39. |
- Csenki, Leonard, et al.
(författare)
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Proof of principle of a generalized fuzzy Hough transform approach to peak alignment of one-dimensional 1H NMR data
- 2007
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 389:3, s. 875-885
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Tidskriftsartikel (refereegranskat)abstract
- In metabolic profiling, multivariate data analysis techniques are used to interpret one-dimensional (1D) 1H NMR data. Multivariate data analysis techniques require that peaks are characterised by the same variables in every spectrum. This location constraint is essential for correct comparison of the intensities of several NMR spectra. However, variations in physicochemical factors can cause the locations of the peaks to shift. The location prerequisite may thus not be met, and so, to solve this problem, alignment methods have been developed. However, current state-of-the-art algorithms for data alignment cannot resolve the inherent problems encountered when analysing NMR data of biological origin, because they are unable to align peaks when the spatial order of the peaks changes—a commonly occurring phenomenon. In this paper a new algorithm is proposed, based on the Hough transform operating on an image representation of the NMR dataset that is capable of correctly aligning peaks when existing methods fail. The proposed algorithm was compared with current state-of-the-art algorithms operating on a selected plasma dataset to demonstrate its potential. A urine dataset was also processed using the algorithm as a further demonstration. The method is capable of successfully aligning the plasma data but further development is needed to address more challenging applications, for example urine data.
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| 40. |
- Ekerman, Petrus, 1697-1783
(författare)
-
Dissertatio gradualis, de principiis oratoriæ psychologicis, quam, consentiente ampliss. facult. philosoph. in regia academia Vpsaliensi, præside ... Petro Ekerman ... ad publicum examen modeste defert, stipendiarius Stieglerianus, Johannes P. Alm, Stockholmiensis. In audit. Gustav. maj. ad diem 5 Maji, anni MDCCXL. Horis, ante meridiem, solitis.
- 1740
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 41. |
- Eloranta, Maija-Leena, et al.
(författare)
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Regulation of the interferon-alpha production induced by RNA-containing immune complexes in plasmacytoid dendritic cells
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:8, s. 2418-2427
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Interferon-alpha (IFNalpha) is produced in several autoimmune diseases, including systemic lupus erythematosus (SLE), and may be important in their pathogenesis. We undertook this study to investigate how IFNalpha production induced by RNA-containing immune complexes (ICs) in plasmacytoid dendritic cells (PDCs) is regulated. METHODS: Normal PDCs purified from peripheral blood mononuclear cells (PBMCs) were cocultivated with other cell populations isolated from healthy individuals or SLE patients. IFNalpha production was induced by RNA-containing ICs, which consisted of anti-RNP autoantibodies and U1 small nuclear RNP particles, and the effects of prostaglandin E2 (PGE2), reactive oxygen species (ROS), or the cytokines IFNalpha2b, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), or tumor necrosis factor alpha (TNFalpha) were explored. RESULTS: Monocytes inhibited IFNalpha production by PDCs in PBMC cultures, while natural killer (NK) cells were stimulatory. The monocytes had little effect on IFNalpha production by pure PDCs but inhibited its stimulation by NK cells. Monocytes from SLE patients were less inhibitory. Exposure of PBMCs or PDCs to IFNalpha2b/GM-CSF increased their IFNalpha production. RNA-containing ICs caused production of ROS, PGE2, and TNFalpha, especially in monocytes. These mediators and IL-10 suppressed IFNalpha production in PBMC cultures, with ROS and PGE2 also inhibiting IFNalpha production by purified PDCs. Inhibition by all of these agents, except for ROS, was abolished by IFNalpha2b/GM-CSF. The inhibitory effect of monocytes was significantly counteracted by the ROS scavengers serotonin and catalase. CONCLUSION: IFNalpha production induced by RNA-containing ICs in PDCs is regulated by a network of interactions between monocytes, NK cells, and PDCs, involving several pro- and antiinflammatory molecules. This should be considered when designing and applying new therapies.
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| 42. |
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| 43. |
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| 44. |
- Fagerlönn, Johan, et al.
(författare)
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Auditory signs to support traffic awareness
- 2009
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Ingår i: 16th World Congress and Exhibition on Intelligent Transport Systems 2009. - Red Hook : Curran Associates, Inc.. - 9781617385896
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Konferensbidrag (refereegranskat)abstract
- Informative systems might contribute to sensory and cognitive driver distraction, which in turn can lead to a more dangerous driving behavior. In this study we evaluated auditory signs to support drivers traffic awareness during simulated driving. 18 truck drivers identified traffic situations based on information conveyed by brief sounds. Aspects of learning, interpretation and pleasantness of sounds were monitored and rated by the drivers. Sounds which were arbitrary mapped to traffic situations required longer learning times, resulted in degraded choice reaction performance, and were rated as less pleasant compared to sounds with a high level in context specific meaning.
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| 45. |
- Fagerlönn, Johan, et al.
(författare)
-
Auditory signs to support traffic awareness
- 2010
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Ingår i: IET Intelligent Transport Systems. - : Institution of Engineering and Technology (IET). - 1751-956X .- 1751-9578. ; 4:4, s. 262-269
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Tidskriftsartikel (refereegranskat)abstract
- In-vehicle information systems (IVIS) may contribute to increased levels of cognitive workload, which in turn can lead to a more dangerous driving behaviour. An experiment was conducted to examine the use of auditory signs to support drivers' traffic situation awareness. Eighteen experienced truck drivers identified traffic situations based on information conveyed by brief sounds. Aspects of learning, cognitive demand and pleasantness were monitored and rated by the drivers. Differences in cognitive effort was estimated using a dual-task set-up, in which drivers responded to auditory signs while simultaneously performing a simulated driving task. As expected, arbitrary sounds required significantly longer learning times compared to sounds that have a natural meaning in the driving context. The arbitrary sounds also resulted in a significant degradation in response performance, even after the drivers got a chance to learn the sounds. Finally, the results indicate that the use of arbitrary sounds can negatively impact driver satisfaction. These results have implications for a broad range of developing intelligent transport systems designed to assist drivers in absence of fundamental visual information or in visually demanding traffic situations.
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| 46. |
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| 47. |
- Fahlman, Åsa, et al.
(författare)
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Measurement of catestatin and vasostatin in wild boar Sus scrofa captured in a corral trap
- 2021
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Ingår i: BMC Research Notes. - : BioMed Central (BMC). - 1756-0500. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Our aim was to analyse the chromogranin A-derived peptides vasostatin and catestatin in serum from wild boar (Sus scrofa) captured in a corral trap. Acute capture-related stress quickly leads to a release of adrenalin and noradrenalin, but these hormones have a short half-life in blood and are difficult to measure. Chromogranin A (CgA), a glycoprotein which is co-released with noradrenalin and adrenalin, is relatively stable in circulation and the CgA-derived peptides catestatin and vasostatin have been measured in domestic species, but not yet in wildlife. Results Vasostatin and catestatin could be measured and the median (range) serum concentrations were 0.91 (0.54-2.86) and 0.65 (0.35-2.62) nmol/L, respectively. We conclude that the CgA-derived peptides vasostatin and catestatin can be measured in wild boar serum and may thus be useful as biomarkers of psychophysical stress.
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| 48. |
- Fahlman, Åsa, et al.
(författare)
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Wild boar behaviour during live-trap capture in a corral-style trap : implications for animal welfare
- 2020
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 62:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWildlife traps are used in many countries without evaluation of their effect on animal welfare. Trap-capture of wild animals should minimise negative effects on animal welfare, irrespective of whether the animals are trapped for hunting, research, or management purposes. Live-trap capture of wild boar (Sus scrofa) followed by killing inside the trap by gunshot is a recently introduced but disputed hunting method in Sweden. Approval of trap constructions is based on gross necropsy findings of 20 trapped and shot wild boars. For improved animal welfare evaluation, our aim was to study wild boar behaviour during live-trapping in a 16 m2 square corral-style trap. Behavioural assessments were conducted after filming 12 capture events of in total 38 wild boars (five adults, 20 subadults, 13 piglets). Selected behavioural traits were compared with pathological changes (trap-related lesions) found at necropsy of the 20 subadults, to determine if these variables were useful proxies of capture-induced stress in wild boar.ResultsThe wild boars spent less time resting in the evening than in the night and morning. Using Friedman’s ANOVA, there was an overall difference in the time spent foraging. However, we only found a difference between the evening and morning in the Wilcoxon matched pairs test after the Sequential Bonferroni correction, where the wild boars spent more time foraging in the evening than in the morning. Single captured individuals showed more escape behaviours and reacted more strongly to external stimuli than individuals captured in a group. It was more common for animals to charge against the mesh walls of the trap upon human approach compared to upon initial capture when the trap door closed. Trap-related pathological findings due to trauma were documented in 13 of the 20 subadults that were necropsied. Behavioural alterations indicative of capture-induced stress (e.g. charging into the trap walls) were documented in trapped wild boars with no or minor physical injuries (e.g. skin abrasions, subcutaneous haemorrhage).ConclusionsBehavioural assessment provided valuable information for determination of capture-induced stress in wild boar when evaluating live-trapping in a corral-style trap, whereas pathological evaluation through necropsy did not fully reflect the animal welfare aspects of live-trapping. We emphasize the inclusion of species-specific behavioural data assessment for evaluation of capture-related stress during live-trapping and for testing of new trap constructions before approval.
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| 49. |
- Grann, Martin, et al.
(författare)
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Methodological development : structured outcome assessment and community risk monitoring (SORM)
- 2005
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Ingår i: International Journal of Law and Psychiatry. - : Elsevier BV. - 0160-2527 .- 1873-6386. ; 28:4, s. 442-456
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes an effort to develop a clinical tool for the continuous monitoring of risk for violence in forensic mental health clients who have left their institutions and who are dwelling in the community on a conditional release basis. The model is called Structured Outcome Assessment and Community Risk Monitoring (SORM). The SORM consists of 30 dynamic factors and each factor in SORM is assessed in two ways: The current absence, presence or partial och intermittent presence of the factors, which is an actuarial (systematized and 'objective') assessment. Secondly, the risk effect, i.e. whether the presence/absence of factors currently increases, decreases or is perceived as unrelated to violence risk, is a clinical (or impressionistic) assessment. Thus, the factors considered via the SORM can be coded as risk factors or protective factors (or as factors unimportant to risk of violence) depending on circumstances that apply in the individual case. Further, the SORM has a built-in module for gathering idiographical information about risk-affecting contextual factors. The use of the SORM and its potential as a risk monitoring instrument is illustrated via preliminary data and case vignettes from an ongoing multicenter project. In this research project, patients leaving any of the 9 participating forensic hospitals in Sweden is assessed at release on a variety of static background factors, and the SORM is then administered every 30 days for 2 years.
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| 50. |
- 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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