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- Grigull, Susanne, et al.
(author)
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Enkätstudie – Insamling och lagring av bergtekniska och hydrogeologiska data
- 2020
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Reports (other academic/artistic)abstract
- Insamling av bergtekniska och hydrogeologiska data sker kontinuerligt och i olika faser av bergbyggnadsprojekt. I nuläget är insamlingsprocesserna dock inte standardiserade och det finns inget centralt, nationellt system för att lagra insamlade data. Det är också svårt att värdera eller återanvända data från tidigare projekt och oftast måste all nödvändiga fältdata samlas in från noll inför nya infrastrukturprojekt, även i områden där det finns tidigare bergbyggnation. Arbete inför och under denna förstudie pekar på ett stort behov av dels en tydligare och delvis förbättrad metodik för insamling av data och dels önskemål om en nationell portal för åtkomst till arkiv och databaser, med information från tidigare bergbyggnadsprojekt i ett område.Med hjälp av två enkätstudier som skickades ut till olika aktörer i bergbyggbranschen har vi identifierat geologiska, bergtekniska och hydrogeologiska parametrar vars insamlingsmetodik och metodbeskrivningar är i behov av att förbättras och eventuellt standardiseras. Med hjälp av enkätsvaren har befintliga databaslösningar samt önskemål runt funktionaliteten av en framtida nationell databas också analyserats.Enkätstudien pekar också på att en standardisering av datainsamlingsprocessen är nödvändig för att säkerställa tillförlitligheten och spårbarheten av data, samt på att standardiserad metodik bör vara anpassad till projektkomplexitet och i möjligaste mån ansluta till nuvarande internationellt accepterad metodik. Studien visar dock även att bergbyggbranschens åsikter är mycket splittrade kring vissa frågor. Hur processen att driva utvecklingen och förvaltandet av metodik, metodbeskrivningar och dataportal/databas är inte heller självklart, eller hur detta ska finansieras och vilka förvaltande organ som ska ansvara.Det rekommenderas i denna förstudie att man vid en uppbyggnad av en nationell databas delar upp en sådan i ett sökbart dokumentarkiv och i en parameterdatabas. En eller flera statliga organisationer bör ha huvudansvaret för förvaltning.Föreliggande rapport är tänkt att tjäna som beslutsunderlag vid initiering och finansiering av projekt inom det aktuella området. Det rekommenderas starkt att den eller de organisationerna som ska bygga upp ett dokumentarkiv och en nationell parameterdatabas tar hänsyn till de funktionsönskemål som tas upp i rapporten.Notera att denna rapport även finns tillgänglig i PDF-format på Stiftelsen BergtekniskForskning – BeFos hemsida. Länkarna i rapporten kan enkelt öppnas direkt från PDF-filen och bilder kan förstoras.
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- Exarchou, Sofia, et al.
(author)
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Mortality in patients with psoriatic arthritis in Sweden: a nationwide, population-based cohort study
- 2024
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:4, s. 446-456
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Journal article (peer-reviewed)abstract
- ObjectivesTo compare all-cause mortality and causes of death between patients with psoriatic arthritis (PsA) and the general population in Sweden.MethodsAdults with at least one main PsA diagnosis (International Classification of Diseases-10: L40.5/M07.0-M07.3) from outpatient rheumatology/internal medicine departments 2001-2017 were identified from the National Patient Register. Each case was matched to five population comparator-subjects on sex/county/age at the case's first arthritis diagnosis. Follow-up ran from 1 January 2007, or from first PsA diagnosis thereafter, until death, emigration or 31 December 2018. Mortality was assessed overall, and stratified by sex and duration since diagnosis (diagnosis before/after 1 January 2007), using matched Cox proportional hazard regression (excluding/including adjustments for comorbidity) or Breslow test, as appropriate. Incidence rate ratios (IRR) of death, overall and stratified by sex/duration since diagnosis/age, as well as causes of death in PsA cases and comparator-subjects were also described.ResultsAll-cause mortality was elevated in PsA (HR: 1.11 (95% CI: 1.07 to 1.16); IRR: 1.18 (95% CI: 1.13 to 1.22)), mainly driven by increased risks in women (HR: 1.23 (95% CI: 1.16 to 1.30)) and cases with longer time since diagnosis (HR: 1.18 (95% CI: 1.12 to 1.25)). IRR of death were significantly increased for all ages except below 40 years, with the numerically highest point-estimates for ages 40-59 years. When adjusted for comorbidity, however, the elevated mortality risk in PsA disappeared. Causes of death were similar among PsA cases/comparator-subjects, with cardiovascular disease and malignancy as the leading causes.ConclusionsMortality risk in PsA in Sweden was about 10% higher than in the general population, driven by excess comorbidity and with increased risks mainly in women and patients with longer disease duration.
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- Rydberg Sterner, Therese, et al.
(author)
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The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
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In: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
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Journal article (peer-reviewed)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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9. |
- Stolt, Ragnar, et al.
(author)
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Second-Order Peak Detection for Multicomponent High-Resolution LC/MS Data
- 2006
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 78:4, s. 975-83
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Journal article (peer-reviewed)abstract
- The first step when analyzing multicomponent LC/MS data from complex samples such as biofluid metabolic profiles is to separate the data into information and noise via, for example, peak detection. Due to the complex nature of this type of data, with problems such as alternating backgrounds and differing peak shapes, this can be a very complex task. This paper presents and evaluates a two-dimensional peak detection algorithm based on raw vector-represented LC/MS data. The algorithm exploits the fact that in high-resolution centroid data chromatographic peaks emerge flanked with data voids in the corresponding mass axis. According to the proposed method, only 4‰ of the total amount of data from a urine sample is defined as chromatographic peaks; however, 94% of the raw data variance is captured within these peaks. Compared to bucketed data, results show that essentially the same features that an experienced analyst would define as peaks can automatically be extracted with a minimum of noise and background. The method is simple and requires a priori knowledge of only the minimum chromatographic peak widtha system-dependent parameter that is easily assessed. Additional meta parameters are estimated from the data themselves. The result is well-defined chromatographic peaks that are consistently arranged in a matrix at their corresponding m/z values. In the context of automated analysis, the method thus provides an alternative to the traditional approach of bucketing the data followed by denoising and/or one-dimensional peak detection. The software implementation of the proposed algorithm is available at http://www.anchem.su.se/peakd as compiled code for Matlab.
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- van der Valk, Ralf J P, et al.
(author)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Journal article (peer-reviewed)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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11. |
- Abele, Dace, et al.
(author)
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Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes
- 2024
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In: HUMAN IMMUNOLOGY. - 0198-8859 .- 1879-1166. ; 85:2
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Journal article (peer-reviewed)abstract
- Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and posttransplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior shortand long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.
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12. |
- Abrahamsson, Carl-Olof, et al.
(author)
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Xylosylated naphthoic acid-amino acid conjugates for investigation of glycosaminoglycan priming.
- 2008
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In: Carbohydrate Research. - : Elsevier BV. - 1873-426X .- 0008-6215. ; 343:9, s. 1473-1477
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Journal article (peer-reviewed)abstract
- Three different series of xylosylated naphthoic acid-amino acid conjugates containing one or two amino acid residues were synthesized for the investigation of glycosaminoglycan priming and potential use as anti-tumor drugs. All xylosylated naphthoic acid-conjugates inhibited the growth of normal lung fibroblasts to some extent, whereas the growth of tumor derived T24 carcinoma cells was not affected. There was no correlation between amino acid conjugation, retention time and the antiproliferative activity. Only one compound initiated the priming of glycosaminoglycans. Modification of the naphthalene ring with one or two amino acid residues did not have any effect on proteoglycan biosynthesis or glycosaminoglycan priming in T24 carcinoma cells.
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- Almén, Markus Sällman, et al.
(author)
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The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children
- 2010
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 11, s. 58-
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Journal article (peer-reviewed)abstract
- BACKGROUND: TMEM18 is a hypothalamic gene that has recently been linked to obesity and BMI in genome wide association studies. However, the functional properties of TMEM18 are obscure. METHODS: The evolutionary history of TMEM18 was inferred using phylogenetic and bioinformatic methods. The gene's expression profile was investigated with real-time PCR in a panel of rat and mouse tissues and with immunohistochemistry in the mouse brain. Also, gene expression changes were analyzed in three feeding-related mouse models: food deprivation, reward and diet-induced increase in body weight. Finally, we genotyped 502 severely obese and 527 healthy Swedish children for two SNPs near TMEM18 (rs6548238 and rs756131). RESULTS: TMEM18 was found to be remarkably conserved and present in species that diverged from the human lineage over 1500 million years ago. The TMEM18 gene was widely expressed and detected in the majority of cells in all major brain regions, but was more abundant in neurons than other cell types. We found no significant changes in the hypothalamic and brainstem expression in the feeding-related mouse models. There was a strong association for two SNPs (rs6548238 and rs756131) of the TMEM18 locus with an increased risk for obesity (p = 0.001 and p = 0.002). CONCLUSION: We conclude that TMEM18 is involved in both adult and childhood obesity. It is one of the most conserved human obesity genes and it is found in the majority of all brain sites, including the hypothalamus and the brain stem, but it is not regulated in these regions in classical energy homeostatic models.
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15. |
- Andersson, Håkan S., 1967-, et al.
(author)
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Alpha-nemertides - a novel family of nemertean peptide neurotoxins
- 2018
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Conference paper (other academic/artistic)abstract
- We recently discovered a novel family of neuroactive peptides in nemerteans, which we have named alpha-nemertides (1). One of these peptides, nemertide alpha-1, has been the subject of detailed studies with regard to structure and effects. The peptide exhibits exceptional potency against a number of arthropod species. Moreover, in vitro experiments suggest that alpha-1 acts primarily on voltage-gated sodium channels, and that this action is selective for arthropods by two orders of magnitude over vertebrate species. Using transcriptomic and proteomic approaches, we have identified 10 alpha-nemertides, but this number is likely to increase. These peptides alongside with a series of mutants are currently under evaluation by our group, with the goal to improve our understanding of structure-function relationships. In addition, we are considering potential practical uses of alpha-nemertides. In this talk, I will describe the current status of this research project.1. E. Jacobsson et al., Peptide ion channel toxins from the bootlace worm, the longest animal on Earth. Scientific reports 8, 4596 (2018).
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16. |
- Andersson, Håkan S., 1967-, et al.
(author)
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Discovery of novel ion-channel active peptide toxins in a North Sea Ribbon Worm
- 2016
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Conference paper (other academic/artistic)abstract
- Ribbon worms (nemerteans) are marine predators, which capture their prey using a proboscis containing a mixture of toxins which brings on rapid paralysis [1]. In addition, their epidermis contains thick mucus of similar toxic constitution. One very potent toxin reported in ribbon worm mucus is tetrodotoxin (TTX). However, despite significant efforts, Strand et al. [2] were unable to detect any TTX, neither in the mucus of the ribbon worm Lineus longissimus, nor from Vibrio alginolyticus cultures isolated from and cultivated in the mucus. These observations challenged the notion of general presence of TTX in ribbon worm mucus, and prompted us to look for other toxins [3]. Using LC-MS analysis of mucus extracts, we identified three peptides present in significant amounts. The peptides were sequenced using a combination of MS/MS analysis and transcriptomics, and whereas one of them strongly resembles the only peptide toxin previously characterized from ribbon worms, Neurotoxin B-IV [4], the other two were found to represent a previously unknown class of peptide toxins. The most abundant of these was synthesized, and its 3D structure determined. Preliminary toxicity tests on shore crab (C. maenas) indicated toxicity (through paralysis) on par with that of TTX. Further analyses have indicated that its toxic effects are due to binding to voltage sensitive sodium channels. With L. longissimus as our primary target, we are now mapping the presence of peptide toxins in ribbon worms, with the objectives to establish routes for synthesis, and to characterize the biological activities and structures of these peptides. The number of peptides of this novel class is increasing, and synthesis and characterization is well underway. The striking potencies of these peptides make them potentially amenable as novel insecticidal or anthelmintic leads, pharmacological tools or in biotechnology applications. References1. Strand M, Sundberg P. Nationalnyckeln till Sveriges flora och fauna [DO-DP]. Stjärnmaskar-Slemmaskar: Sipuncula-Nemertea: Artdatabanken, SLU; 2010.2. Strand M, Hedstrom M, Seth H, McEvoy EG, Jacobsson E, Goransson U, Andersson HS, Sundberg P. The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus-Just a False Positive? Marine Drugs. 2016;14(4).3. Strand M, Andersson HS. Slemmaskens hemlighet. Forskning & Framsteg. 2016;(2):26-33.4. Blumenthal KM, Kem WR. Structure and action of heteronemertine polypeptide toxins. Primary structure of Cerebratulus lacteus toxin B-IV. The Journal of Biological Chemistry. 1976;251(19):6025-9.
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- Andersson, Håkan S., 1967-, et al.
(author)
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The toxicity of ribbon worms: alpha-nemertides or tetrodotoxin, or both?
- 2016
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In: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 82:Supplement 1
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Journal article (other academic/artistic)abstract
- The marine ribbon worms (nemerteans) are predators which capture their prey by everting a proboscis carrying a mixture of toxins which brings on rapid paralysis [1]. Moreover, ribbon worms have a thick layer of epidermal mucus of similar constitution. Tetrodotoxin (TTX) has been identified as one of these toxins [2]. The extreme toxicity of TTX (lethal by ingestion of 0.5-2 mg) is due to its ability to block voltage-gated sodium channels. Although several bacterial species (among these Vibrio sp.) have been linked to its synthesis, the biogenic origin and biosynthesis is unclear. One hypothesis is that TTX production occurs in a symbiotic relationship with its host, in this case the ribbon worm [3]. We have made significant effort to identify TTX in a setup for production through the cultivation of Vibrio alginolyticus in nutrient broth infused with mucus from the ribbon worm Lineus longissimus. Toxicity was demonstrated by fraction injections into shore crabs, but no TTX was found, and it could be shown conclusively that toxicity was unrelated to TTX and the Vibrio culture itself, and rather a constituent of the ribbon worm mucus [4]. The following studies led us to the discovery of a new class of peptides, the alpha-nemertides, in the mucus of the ribbon worms, which could be directly linked to the toxic effects. A literature review of the available evidence for TTX in ribbon worms show that the evidence in most cases are indirect, although notable exceptions exist. This points to the necessity to further investigate the presence and roles of TTX and alpha-nemertides in ribbon worms.
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20. |
- Andersson, Maria L.E., et al.
(author)
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Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
- 2023
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
-
Journal article (peer-reviewed)abstract
- Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.
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21. |
- Andersson, Peter, 1981-, et al.
(author)
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Design and initial 1D radiography tests of the FANTOM mobile fast-neutron radiography and tomography system
- 2014
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 756, s. 82-93
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Journal article (peer-reviewed)abstract
- The FANTOM system is a tabletop sized fast-neutron radiography and tomography system newly developed at the Applied Nuclear Physics Division of Uppsala University. The main purpose of the system is to provide time-averaged steam-and-water distribution measurement capability inside the metallic structures of two-phase test loops for Light Water Reactor thermal-hydraulic studies using a portable fusion neutron generator. The FANTOM system provides a set of 1D neutron transmission data, which may be inserted into tomographic reconstruction algorithms to achieve a 2D mapping of the steam-and-water distribution. In this paper, the selected design of FANTOM is described and motivated. The detector concept is based on plastic scintillator elements, separated for spatial resolution. Analysis of pulse heights on an event-to-event basis is used for energy discrimination. Although the concept allows for close stacking of a large number of detector elements, this demonstrator is equipped with only three elements in the detector and one additional element for monitoring the yield from the neutron generator. The first measured projections on test objects of known configurations are presented. These were collected using a Sodern Genie 16 neutron generator with an isotropic yield of about 1E8 neutrons per second, and allowed for characterization of the instrument’s capabilities. At an energy threshold of 10 MeV, the detector offered a count rate of about 500 cps per detector element. The performance in terms of spatial resolution was validated by fitting a Gaussian Line Spread Function to the experimental data, a procedure that revealed a spatial unsharpness in good agreement with the predicted FWHM of 0.5 mm.
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23. |
- Andreasson, Eskil, et al.
(author)
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Integrating Moldflow and Abaqus in the Package Simulation Workflow
- 2013
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Conference paper (peer-reviewed)abstract
- Tetra Pak has used numerical simulation tools for plastic injection molding (Moldflow) and structural analysis (Abaqus/Implicit and Abaqus/Explicit) for many years. Today these two simulation tools are used independently of each other without any coupling. How these two disciplines can be combined to better predict the mechanical response of a polymer component is presented in this work. The manufacturing process, in this case injection molding, creates the mechanical properties of the produced polymer part. Process settings, material selection and molding tool geometry affect the polymer flow, material orientation and rate of crystallinity. A method to build a layered finite element model in Abaqus using results from Moldflow simulations regarding crystallinity growth and molecular orientation is proposed. Relatively simple material models were utilized and assigned for each individual material layer through the thickness in the polymer part. These constitutive models were derived phenomenologically from experimental test results and could adequately capture both the microscopic and the macroscopic behavior in a more realistic way. The numerical results showed a good agreement with the experimental results, both regarding visual appearance and force/displacement response.
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- Annertz, Karin, et al.
(author)
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Alpha B-crystallin - a validated prognostic factor for poor prognosis in squamous cell carcinoma of the oral cavityl
- 2014
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In: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 134:5, s. 543-550
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Journal article (peer-reviewed)abstract
- Conclusion: Alpha B-crystallin was found to be an independent prognostic marker for poor prognosis in oral cavity tumours. For oropharyngeal cancer, alpha B-crystallin had no prognostic value. Objective: The aim of this study was to see if earlier findings of alpha B-crystallin as an independent prognostic marker, and SPARC/osteonectin, PAI-1 and uPA as a prognostic combination for poor outcome in squamous cell carcinoma (SCC) of the head and neck could be confirmed in a new set of tumours. Methods: In a consecutive series of patients, assessed and primarily treated at a tertiary referral centre, histological sections from 55 patients with oral and SCC (OOPHSSC) with complete clinical data and follow-up were obtained. Oral and oropharyngeal tumours were studied separately. Immunohistochemical detection of alpha B-crystallin, SPARC/osteonectin, PAI-1 and uPA expression was performed. Results: Thirty-five patients had an oral tumour and 20 patients an oropharyngeal tumour. Twenty-five oral tumours stained negatively and 10 positively for alpha B-crystallin. For oropharyngeal tumours the figures were 15 negatively and 5 positively. Median disease-specific survival (DSS) for both sites was 33.8 and 11.9 months, for negative and positive alpha B-crystallin staining, respectively (p=0.046). For the oral cavity, median DSS was 27.3 months for negative tumours and 7.5 months for positive tumours (p=0.012). Corresponding figures for oropharyngeal tumours were 33.8 and 34.1 months (p=0.95). Thus, significance in survival was only found in oral cavity tumours. In multivariate analyses there were no significant differences in DSS in the oropharyngeal group when adjusted for tumour size (T status) and presence of neck node metastasis (N status). In the oral cavity group, the significantly better DSS for negative tumours became even stronger when adjusted for T and N status. No statistical difference was found in DSS between positive and negative staining for SPARC/osteonectin, PAI-1 or uPA.
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26. |
- Annertz, Karin, et al.
(author)
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High-risk HPV and survival in patients with oral and oropharyngeal squamous cell carcinoma : 5-year follow up of a population-based study
- 2014
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In: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 8:134, s. 843-851
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Journal article (peer-reviewed)abstract
- CONCLUSION: No statistically significant 5-year survival difference was seen in patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between high-risk HPV-positive and -negative groups in this population-based study. OBJECTIVES: To see if the formerly observed higher risk for recurrence or second primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds to worse survival. METHODS: A total of 128 consecutive, previously untreated patients with OOPSCC, who were part of a population-based case-control study in southern Sweden during 2000-2004, were included. A mouthwash sample was collected and exfoliated cells were collected with cotton-tipped swabs from the tonsillar fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between HPV-negative and HPV-positive patients were calculated. The relationship between age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal tumours were assessed separately. RESULTS: Mean DSS in months was 80.7/68.6 (high-risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and 67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage all showed significant differences in DSS. For oropharyngeal tumours, no significant difference regarding DSS was found.
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27. |
- Artursson, Tom, et al.
(author)
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Study of Preprocessing Methods for the Determination of Crystalline Phases in Binary Mixtures of Drug Substances by X-ray Powder Diffraction and Multivariate Calibration
- 2000
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In: Applied Spectroscopy. - : SAGE Publications. - 0003-7028 .- 1943-3530. ; 54:8, s. 272A-301A
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Journal article (peer-reviewed)abstract
- In this paper, various preprocessing methods were tested on data generated by X-ray powder diffraction (XRPD) in order to enhance the partial least-squares (PLS) regression modeling performance. The preprocessing methods examined were 22 different discrete wavelet transforms, Fourier transform, Savitzky-Golay, orthogonal signal correction (OSC), and combinations of wavelet transform and OSC, and Fourier transform and OSC. Root mean square error of prediction (RMSEP) of an independent test set was used to measure the performance of the various preprocessing methods. The best PLS model was obtained with a wavelet transform (Symmlet 8), which at the same time compressed the data set by a factor of 9.5. With the use of wavelet and X-ray powder diffraction, concentrations of less than 10% of one crystal from could be detected in a binary mixture. The linear range was found to be in the range 10-70% of the crystalline form of phenacetin, although semiquantitative work could be carried out down to a level of approximately 2%. Furthermore, the wavelet-pretreated models were able to handle admixtures and deliberately added noise.
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28. |
- Askling, Johan, et al.
(author)
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Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
- 2008
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
-
Journal article (peer-reviewed)abstract
- Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365 026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998–2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
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29. |
- Askling, Johan, et al.
(author)
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Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas : relative risks and time trends in the Swedish Biologics Register
- 2009
-
In: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
-
Journal article (peer-reviewed)abstract
- BACKGROUND:Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.METHODS:Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67,743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471,024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.RESULTS:Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26,981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365,026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3,355,849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.CONCLUSION:Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
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30. |
- Askling, Johan, et al.
(author)
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Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies : does the risk change with the time since start of treatment?
- 2009
-
In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:11, s. 3180-3189
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.METHODS:By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.RESULTS:During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.CONCLUSION:During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.
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31. |
- Askling, Johan, et al.
(author)
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Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden
- 2005
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:7, s. 1986-1992
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA.METHODS:Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.RESULTS:During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.CONCLUSION:Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
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32. |
- Askling, Johan, et al.
(author)
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Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
- 2007
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344
-
Journal article (peer-reviewed)abstract
- OBJECTIVES:The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.METHODS:First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.RESULTS:Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.CONCLUSION:Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
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33. |
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34. |
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35. |
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36. |
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37. |
- Bengtsson, Karin, 1980, et al.
(author)
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Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study
- 2017
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
-
Journal article (peer-reviewed)abstract
- Background: To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP). Methods: This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001-2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively. Results: Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31-1.82)), PsA (1.76 (1.59-1.95)) and uSpA (1.36 (1.05-1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37-0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06-1.48)) and PsA (1.34 (1.22-1.48)), and nonsignificantly increased in uSpA (1.16 (0.91-1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP. Conclusions: Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.
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38. |
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39. |
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40. |
- Bengtsson, Karin, 1980, et al.
(author)
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Incidence of extra-articular manifestations in ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis : Results from a national register-based cohort study
- 2021
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In: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:6, s. 2725-2734
-
Journal article (peer-reviewed)abstract
- Objectives: To estimate the incidence and strength of association of extra-articular manifestations [EAMs, here: anterior uveitis (AU), IBD and psoriasis] in patients with AS, undifferentiated SpA (uSpA) and PsA, compared with controls. Methods: Three mutually exclusive cohorts of patients aged 18-69 years with AS (n = 8517), uSpA (n = 10 245) and PsA (n = 22 667) were identified in the Swedish National Patient Register 2001-2015. Age-, sex- and geography-matched controls were identified from the Swedish Population Register. Follow-up began 1 January 2006, or six months after the first SpA diagnosis, whichever occurred later, and ended at the first date of the EAM under study, death, emigration, 70 years of age, and 31 December 2016. Incidence rates (IRs) and incidence rate ratios were calculated for each EAM, and stratified by sex and age. Results: Incidence rate ratios for incident AU, IBD and psoriasis were significantly increased in AS (20.2, 6.2, 2.5), uSpA (13.6, 5.7, 3.8) and PsA (2.5, 2.3, n.a) vs controls. Men with AS and uSpA had significantly higher IRs per 1000 person-years at risk for incident AU than women with AS (IR 15.8 vs 11.2) and uSpA (IR 10.1 vs 6.0), whereas no such sex difference was demonstrated in PsA or for the other EAMs. Conclusions: AU, followed by IBD and psoriasis, is the EAM most strongly associated with AS and uSpA. Among the SpA subtypes, AS and uSpA display a largely similar pattern of EAMs, whereas PsA has a considerably weaker association with AU and IBD.
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41. |
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42. |
- Bengtsson, Karin, 1980, et al.
(author)
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Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population : A register-based study from Sweden
- 2018
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 541-548
-
Journal article (peer-reviewed)abstract
- Objectives To describe the incidence of atrioventricular (AV) block II-III, atrial fibrillation (AF), pacemaker implantation (PM) and aortic regurgitation in patients with ankylosing spondylitis (AS), undifferentiated spondyloarthritis (uSpA) and psoriatic arthritis (PsA) compared with the general population (GP) and with each other. Methods A prospective nationwide study with cohorts of patients with AS (n=6448), PsA (n=16 063) and uSpA (n=5190) and a GP (n=2 66 435) cohort, identified in 2001-2009 in the Swedish National Patient and Population registers. Follow-up began on 1 January 2006 and ended at event, death, emigration or 31 December 2012. Age-standardised and sex-standardised incidence rates and hazard ratios (HRs) were calculated. Results The highest incidence rates were noted for AF (5.5-7.4 events per 1000 person-years), followed by PM (1.0-2.0 events per 1000 person-years). HRs for AV block, AF, PM and aortic regurgitation were significantly increased in AS (HRs 2.3, 1.3, 2.1 and 1.9), uSpA (HRs 2.9, 1.3, 1.9 and 2.0) and PsA (HRs 1.5, 1.5, 1.6 and 1.8) compared with the GP cohort. The highest HRs were seen for AV block in male uSpA (HR 4.2) and AS (HR 2.5) compared with GP. Compared with PsA, significantly increased HRs were noted for PM (HR 1.5) in AS and for AV block (HR 1.8) in uSpA. Conclusions Patients with SpA are at increased risk of aortic regurgitation, cardiac rhythm disturbances and, as a probable consequence, also PM. Particularly for AF, the most common arrhythmia, increased caution is warranted, whereas AV block should be looked for especially in men with AS or uSpA.
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43. |
- Boysen, Marianne E., et al.
(author)
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Molecular identification of species from the Penicillium roqueforti group associated with spoiled animal feed
- 2000
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In: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 66:4, s. 1523-1526
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Journal article (peer-reviewed)abstract
- The Penicillium roqueforti group has recently been split into three species, P, roqueforti, Penicillium carneum, and Penicillium paneum, on the basis of differences in ribosomal DNA sequences and secondary metabolite profiles. We reevaluated the taxonomic identity of 52 livestock feed isolates from Sweden, previously identified by morphology as P. roqueforti, by comparing the sequences of the ribosomal internal transcribed spacer region. Identities were confirmed with random amplified polymorphic DNA analysis and secondary metabolite profiles. Of these isolates, 48 were P. roqueforti, 2 were P. paneum, and 2 were Penicillium expansum. No P. carneum isolates were found, The three species produce different mycotoxins, but no obvious relationship between mold and animal disease was detected, based on medical records, P. roqueforti appears to dominate in silage, but the ecological and toxicological importance of P. carneum and P. paneum as feed spoilage fungi is not clear. This is the first report of P. expansum in silage.
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44. |
- Broberg, Anders, et al.
(author)
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Metabolite profiles of lactic acid bacteria in grass silage
- 2007
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In: Applied and Environmental Microbiology. - Washington, USA : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 73:17, s. 5547-5552
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Journal article (peer-reviewed)abstract
- The metabolite production of lactic acid bacteria JAB) on silage was investigated. The aim was to compare the production of antifungal metabolites in silage with the production in liquid cultures previously studied in our laboratory. The following metabolites were found to be present at elevated concentrations in silos inoculated with LAB strains: 3-hydroxydecanoic acid, 2-hydroxy-4-methylpentanoic acid, benzoic acid, catechol, hydrocinnamic acid, salicylic acid, 3-phenyllactic acid, 4-hydroxybenzoic acid, (trans, trans)-3,4-dihydroxycyclohexane-1-carboxylic acid, p-hydrocoumaric acid, vanillic acid, azelaic acid, hydroferulic acid, p-coumaric acid, hydrocaffeic acid, ferulic acid, and caffeic acid. Among these metabolites, the antifungal compounds 3-phenyllactic acid and 3-hydroxydecanoic acid were previously isolated in our laboratory from liquid cultures of the same LAB strains by bioassay-guided fractionation. It was concluded that other metabolites, e.g., p-hydrocoumaric acid, hydroferulic acid, and p-coumaric acid, were released from the grass by the added LAB strains. The antifungal activities of the identified metabolites in 100 mM lactic acid were investigated. The MICs against Pichia anomala, Penicillium roqueforti, and Aspergillus fumigatus were determined, and 3-hydroxydecanoic acid showed the lowest MIC (0.1 mg ml(-1) for two of the three test organisms).
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45. |
- Casar-Borota, Olivera, et al.
(author)
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A novel dynamin-2 gene mutation associated with a late-onset centronuclear myopathy with necklace fibres
- 2015
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In: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966 .- 1873-2364. ; 25:4, s. 345-348
-
Journal article (peer-reviewed)abstract
- Nuclear centralisation and internalisation, sarcoplasmic radiating strands and type 1 muscle fibre predominance and hypotrophy characterise dynamin-2 (DNM2) associated centronuclear myopathy, whereas necklace fibres are typically seen in late onset myotubularin-1 (MTM1)-related myopathy. We report a woman with unilateral symptoms probably related to brachial plexus neuritis. Electromyography revealed localised neuropathic and generalised myopathic abnormalities. The typical features of DNM2 centronuclear myopathy with additional necklace fibres were found in the muscle biopsy. Sequencing of the DNM2 and MTM1 genes revealed a novel heterozygous missense mutation in exon 18 of the DNM2, leading to replacement of highly conserved proline at position 647 by arginine. The muscle symptoms have not progressed during the 3-year follow-up. However, the patient has developed bilateral subtle lens opacities. Our findings support the concept that necklace fibres may occasionally be found in DNM2-related myopathy, possibly indicating a common pathogenic mechanism in DNM2 and MTM1 associated centronuclear myopathy. (C) 2015 Elsevier B.V. All rights reserved.
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46. |
- Casar-Borota, Olivera, et al.
(author)
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A novel dynamin-2 gene mutation associated with a late-onset centronuclear myopathy with unusual clinical presentation and necklace fibres
- 2012
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In: Neuromuscular Disorders. - Oxford : Elsevier BV. - 0960-8966 .- 1873-2364. ; 22:9-10, s. 843-843
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Journal article (other academic/artistic)abstract
- Nuclear centralisation and internalisation, sarcoplasmic radiating strands and type 1 muscle fibre predominance and hypotrophy are morphologic features of centronuclear myopathy (CNM) related to dynamin-2 (DNM2) gene defects, whereas necklace fibres characterise late-onset myopathy associated with myotubularin-1 (MTM1) gene defects. We report a 40-year-old woman with 1-year history of pain and paresthesia in the left shoulder and arm that was clinically interpreted as brachial plexus neuritis. Electromyography revealed both myopathic and neuropathic abnormalities, and because of the myopathic changes a muscle biopsy was performed. The typical morphologic features of dynamin-2 CNM with additional numerous necklace fibres were found in the muscle biopsy. Sequencing of the DNM2 and MTM1 genes revealed a not previously described heterozygous missense mutation in exon 18 of DNM2 leading to replacement of highly conserved Proline in position 647 by Arginine. The muscle symptoms have not progressed during the two-year follow-up, but the patient has developed bilateral subtle lens opacities. Necklace fibres were originally described as fibres that had usually a small diameter and internalized nuclei aligned in a basophilic ring at a few micrometers beneath the sarcolemma. They were described in association with myopathies caused by MTM1 mutations, and similar but not identical fibres have also been reported in a case of DNM2 associated CNM. Our findings support the concept that necklace fibres are not specific but indicate common pathogenic mechanisms in DNM2 and MTM1 associated CNM. This case report expands the clinical, morphological and molecular genetic variability of DNM2 associated CNM.
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47. |
- Davidsson, Paul, et al.
(author)
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Agreement Technologies for Supporting the Planning and Execution of Transports
- 2013
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In: Agreement Technologies, Law, Governance and Technology Series. - Dordrecht : Springer Netherlands. - 9789400755833 ; , s. 533-547
-
Book chapter (peer-reviewed)abstract
- The use of agreement technologies in the planning and execution of goods transports is analyzed. We have previously suggested an approach called Plug and Play Transport Chain Management (PnP TCM) that provides agent-based support for key tasks, such as, finding the best sequence of transport services for a particular goods transport, monitoring the execution of the transport, and managing the interaction between the involved actors. In this paper we analyze five agreement technologies in the context of PnP TCM, i.e., semantics, norms, organizations, argumentation and negotiation, and trust. We conclude that all five technologies play a critical role in the realization of PnP TCM.
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48. |
- Davidsson, Paul, et al.
(author)
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Agreement technologies for supporting the planning and execution of transports
- 2013
-
In: Agreement Technologies. - Dordrecht : Springer. - 9789400755826 - 9789400755833 ; , s. 533-547
-
Book chapter (other academic/artistic)abstract
- The use of agreement technologies in the planning and execution of goods transports is analyzed. We have previously suggested an approach called Plug and Play Transport Chain Management (PnP TCM) that provides agent-based support for key tasks, such as, finding the best sequence of transport services for a particular goods transport, monitoring the execution of the transport, and managing the interaction between the involved actors. In this paper we analyze five agreement technologies in the context of PnP TCM, i.e., semantics, norms, organizations, argumentation and negotiation, and trust. We conclude that all five technologies play a critical role in the realization of PnP TCM.
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49. |
- Davidsson, Paul, et al.
(author)
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Plug and Play Transport Chain Management : Agent-Based Support to the Planning and Execution of Transports
- 2011
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In: e-Business and Telecommunications. - Berlin, Heidelberg : Springer. ; , s. 139-155, s. 139-155
-
Conference paper (peer-reviewed)abstract
- A novel approach to efficiently plan and execute effective transport solutions is presented. It provides agent-based support for key tasks, such as, finding the best sequence of transport services for a particular goods transport, monitoring the execution of the transport, as well as the interaction between the involved actors. The approach is based on the FREIGHTWISE framework in which a minimal set of information packages is defined. The purpose is to capture all the information that needs to be communicated between the actors involved in a transport, such as, transport users, transport providers, and infrastructure managers, during the complete process from planning to termination. The approach is inspired by the concepts of virtual enterprises and breeding environments. We analyse the requirements of such an approach and describe a multi-agent system architecture meeting these requirements.
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50. |
- de Vries, Mirjam K, et al.
(author)
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Tuberculosis risk in ankylosing spondylitis, other spondyloarthritis and psoriatic arthritis in Sweden: a population-based cohort study.
- 2018
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In: Arthritis care & research. - : Wiley. - 2151-4658 .- 2151-464X. ; 70:10, s. 1563-1567
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) is a risk factor for tuberculosis (TB), particularly following treatment with biologicals. Since these therapies are increasingly used in ankylosing spondylitis (AS), other types of spondyloarthritis (SpA) and psoriatic arthritis (PsA), we investigated the corresponding TB risks in these patients.We identified individuals with AS/SpA/PsA, and non-AS/SpA/PsA comparators by linking Swedish national Patient, Population, TB and Rheumatology registers, and followed them for TB occurrence. Incidence rates were estimated for biological-naïve and biological-exposed patients, and the comparators. We calculated hazard ratios (HR) adjusted for age, sex and country of birth.38,702 patients with AS/SpA/PsA, and 200,417 general population persons were included. Among patients, 11 active TB cases were identified, with an incidence rate (per 105 ) of 22 (95%CI 8.3 to 59.2) for biological-exposed patients, 2.7 (95%CI 1.3 to 5.6) for biological-naïve patients and 2.4 (95%CI 1.8 to 3.3) for non-AS/SpA/PsA comparators. The adjusted HR comparing biological-naïve patients to the general population was 1.2 (95%CI 0.5 to 2.7), and 7.5 (95%CI 1.9 to 29) comparing biological-exposed to biological-naïve patients.Biological-naïve AS/PsA /SpA are not at an increased TB risk in Sweden. Following treatment with biologicals, risks increased but the absolute TB risk was low. This article is protected by copyright. All rights reserved.
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