| 1. |
- Akiba, K., et al.
(författare)
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The LHCb VELO Upgrade module construction
- 2024
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- The LHCb detector has undergone a major upgrade for LHC Run 3. This Upgrade I detector facilitates operation at higher luminosity and utilises full-detector information at the LHC collision rate, critically including the use of vertex information. A new vertex locator system, the VELO Upgrade, has been constructed. The core element of the new VELO are the double-sided pixelated hybrid silicon detector modules which operate in vacuum close to the LHC beam in a high radiation environment. The construction and quality assurance tests of these modules are described in this paper. The modules incorporate 200 mu m thick, n -on -p silicon sensors bump-bonded to 130 nm technology ASICs. These are attached with high precision to a silicon microchannel substrate that uses evaporative CO 2 cooling. The ASICs are controlled and read out with flexible printed circuits that are glued to the substrate and wire -bonded to the chips. The mechanical support of the module is given by a carbon fibre plate, two carbon fibre rods and an aluminium plate. The sensor attachment was achieved with an average precision of 21 mu m, more than 99.5% of all pixels are fully functional, and a thermal figure of merit of 3 Kcm 2 W - 1 was achieved. The production of the modules was successfully completed in 2021, with the final assembly and installation completed in time for data taking in 2022.
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| 2. |
- Diaz-Gallo, Lina-Marcela, et al.
(författare)
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Four Systemic Lupus Erythematosus Subgroups, Defined by Autoantibodies Status, Differ Regarding HLA-DRB1 Genotype Associations and Immunological and Clinical Manifestations
- 2022
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Ingår i: ACR Open Rheumatology. - : John Wiley & Sons. - 2578-5745. ; 4:1, s. 27-39
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The heterogeneity of systemic lupus erythematosus (SLE) constitutes clinical and therapeutical challenges. We therefore studied whether unrecognized disease subgroups can be identified by using autoantibody profiling together with HLA-DRB1 alleles and immunological and clinical data.Methods: An unsupervised cluster analysis was performed based on detection of 13 SLE-associated autoantibodies (double-stranded DNA, nucleosomes, ribosomal P, ribonucleoprotein [RNP] 68, RNPA, Smith [Sm], Sm/RNP, Sjögren's syndrome antigen A [SSA]/Ro52, SSA/Ro60, Sjögren's syndrome antigen B [SSB]/La, cardiolipin [CL]-Immunoglobulin G [IgG], CL-Immunoglobulin M [IgM], and β2 glycoprotein I [β2 GPI]-IgG) in 911 patients with SLE from two cohorts. We evaluated whether each SLE subgroup is associated with HLA-DRB1 alleles, clinical manifestations (n = 743), and cytokine levels in circulation (n = 446).Results: Our analysis identified four subgroups among the patients with SLE. Subgroup 1 (29.3%) was dominated by anti-SSA/Ro60/Ro52/SSB autoantibodies and was strongly associated with HLA-DRB1*03 (odds ratio [OR] = 4.73; 95% confidence interval [CI] = 4.52-4.94). Discoid lesions were more common for this disease subgroup (OR = 1.71, 95% CI = 1.18-2.47). Subgroup 2 (28.7%) was dominated by anti-nucleosome/SmRNP/DNA/RNPA autoantibodies and associated with HLA-DRB1*15 (OR = 1.62, 95% CI = 1.41-1.84). Nephritis was most common in this subgroup (OR = 1.61, 95% CI = 1.14-2.26). Subgroup 3 (23.8%) was characterized by anti-ß2 GPI-IgG/anti-CL-IgG/IgM autoantibodies and a higher frequency of HLA-DRB1*04 compared with the other patients with SLE. Vascular events were more common in Subgroup 3 (OR = 1.74, 95% CI = 1.2-2.5). Subgroup 4 (18.2%) was negative for the investigated autoantibodies, and this subgroup was not associated with HLA-DRB1. Additionally, the levels of eight cytokines significantly differed among the disease subgroups.Conclusion: Our findings suggest that four fairly distinct subgroups can be identified on the basis of the autoantibody profile in SLE. These four SLE subgroups differ regarding associations with HLA-DRB1 alleles and immunological and clinical features, suggesting dissimilar disease pathways.
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| 3. |
- Elvin, A, et al.
(författare)
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Duplex Doppler ultrasound in carcinoid metastases
- 1991
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Ingår i: European Radiology. - 0938-7994 .- 1432-1084. ; 1:2, s. 108-112
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Tidskriftsartikel (refereegranskat)abstract
- In a prospective study, the role of duplex Doppler ultrasound in monitoring interferon treatment-related changes in carcinoid metastases was evaluated. The Doppler findings from the tumours were correlated to the clinical and laboratory status of the patients to test the hypothesis that successful treatment results in increased vascular resistance. The patients were divided into 4 groups: untreated (n = 10), progressive disease (n = 17), stable disease (n = 20) and objective response (n = 18). In 7 cases Doppler evaluation was made before and after treatment. No significant difference in Doppler values were found between the groups, and at present duplex Doppler ultrasound does not seem to play a role in the evaluation of tumour therapy in carcinoid patients.
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| 4. |
- Elvin, A, et al.
(författare)
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Optic neuritis. Doppler ultrasonography compared with MR and correlated with visual evoked potential assessments
- 1998
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 39:3, s. 243-248
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To establish the role of Doppler ultrasonography (US) in the examination of patients with acute unilateral optic neuritis Material and Methods: Twenty-five patients with a clinical diagnosis of optic neuritis were prospectively evaluated and 18 of them were included in the study. The inclusion criteria were MR findings of unilateral disease and age below 50 years. All patients were examined with MR in order to objectively detect, localize and measure the optic nerve lesions and in order to exclude patients with unidentifiable optic nerve involvement. Evaluation with US was performed to determine nerve morphology, nerve swelling, and resistance to flow in the central retinal artery. The patients' contralateral optic nerve served as an internal control. The US findings were correlated to the degree of visual impairment, both initially and at follow-up Visual evoked potential (VEP) assessments were also performed in 16 patients Results: A statistically significant difference was found in the optic nerve diameter and in the resistance to flow in the central retinal artery between the affected and unaffected eyes. Patients with a prolonged impairment of visual acuity initially had a more swollen nerve and an increased resistance to flow in the affected optic nerve. Prognostic information was also gathered solely by evaluating the unaffected nerve diameter: patients who normally had thinner optic nerves had a more severe form of optic neuritis. VEP assessments were positive in all patients investigated Conclusion: Doppler US can be used together with a VEP assessment as an indicator of the disease process in acute optic neuritis. These methods offer a potential for monitoring patients over time
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| 5. |
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| 6. |
- Grönwall, Caroline, et al.
(författare)
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Depressed serum IgM levels in SLE are restricted to defined subgroups
- 2017
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 183, s. 304-315
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Tidskriftsartikel (refereegranskat)abstract
- Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM targeting phosphoiylcholine (PC) antigens and malondialdehyde (MDA) modified-protein, as well as total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/beta(2)glycoprotein-I. We also observed an association of reduced IgM levels with the HEA-DRB1*03 allelic variant among SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM. Our results suggest that low IgM levels in SLE patients reflect immunological and genetic differences between SLE subgroups.
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| 7. |
- Gustafsson, Johanna T, et al.
(författare)
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Cigarette smoking, antiphospholipid antibodies and vascular events in Systemic Lupus Erythematosus
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:8, s. 1537-1543
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Smoking can induce autoantibodies in persons who are genetically predisposed to rheumatoid arthritis. We investigated the association between smoking and antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE), a question not previously addressed. Further, we explored the relationship between smoking, aPL and vascular events (arterial and venous, VE).METHODS: In this cross-sectional study, clinical evaluation and questionnaire data were collected from 367 prevalent SLE patients. At the same time, we measured aPL (anticardiolipin (aCL), anti-β2 glycoprotein-1 (aβ2GP1) antibodies IgG/IgM/IgA, and lupus anticoagulant (LA)), and a large set of other SLE-associated autoantibodies for comparison. Association analyses using logistic regression models with smoking, (ever, former and current with never as reference) and antibody status as outcome variable were performed. As a secondary outcome, we investigated the associations between aPL, smoking and VE.RESULTS: In multivariable-adjusted models ever, and in particular former, cigarette smoking was associated with the most pathogenic aPL; LA, aCL IgG and aβ2GP1 IgG. Other SLE-associated autoantibodies were not associated with smoking. The combination of smoking and aPL was strongly associated with VE. We noted a positive interaction between smoking-LA and smoking-'triple aPL' positivity for previous VE.CONCLUSIONS: We investigated a large set of commonly occurring autoantibodies in SLE, but only aPL were positively associated with a history of smoking. This association was especially apparent in former smokers. Among ever regular smokers who were aPL positive, we observed a strikingly high frequency of former VE. The underlying mechanisms and temporality between smoking, aPL and VE need further investigations.
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| 8. |
- Gustafsson, Johanna T, et al.
(författare)
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Excess atherosclerosis in systemic lupus erythematosus A matter of renal involvement : Case control study of 281 SLE patients and 281 individually matched population controls
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups.METHODS: 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls.RESULTS: Median age was 49 (IQR 36-59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035).CONCLUSIONS: In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.
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| 9. |
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| 10. |
- Lundström, Emeli, et al.
(författare)
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HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 72:6, s. 1018-1025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES:Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients.METHODS:665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR.RESULTS: HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL—cardiolipin IgG and IgM, β2-glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04—while HLA-DRB1*13 was associated with IgG antibodies (β2-glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD.CONCLUSIONS:The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability.
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| 11. |
- Popiolek, Katarzyna, 1981-, et al.
(författare)
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Rehospitalization and suicide following electroconvulsive therapy for bipolar depression–A population-based register study
- 2018
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 226, s. 146-154
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Tidskriftsartikel (refereegranskat)abstract
- Background Electroconvulsive therapy (ECT) is effective in bipolar depression, but relapse is common. The aim of the study was (i) to identify prognostic factors (ii) and to determine the impact of pharmacological approaches on the risk for rehospitalization or suicide. Methods This register study analyzed data from individuals treated with inpatient ECT for bipolar depression. Subjects were identified using the Swedish National Patient Register between 2011 and 2014 and the Swedish National Quality Register for ECT. Other national registers provided data on psychopharmacotherapy, socio-demographic factors, and causes of death. The endpoint was the composite of rehospitalization for any psychiatric disorder, suicide attempt or completed suicide (RoS). Cox regression was used to calculate hazard ratios in univariate and multivariate models. Results Data from 1255 patients were analyzed. The mean period of follow-up was 346 days. A total of 29%, 41%, and 52% of patients reached RoS at 3, 6, and 12 months post-discharge. A history of multiple psychiatric admissions, lower age, and post-discharge treatment with antipsychotics or benzodiazepines was associated with RoS. Limitations Indication bias may have affected the results. Conclusions A history of multiple hospital admissions and lower age are key predictors of the composite of rehospitalization or suicide in patients treated with ECT for bipolar depression. Lithium might be effective. By contrast, antipsychotics and benzodiazepines were associated with increased risk, but possibly this finding was influenced by indication bias. © 2017 The Authors
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| 12. |
- Svenugnsson, Elisabet, et al.
(författare)
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Decreased levels of autoantibodies against apolipoprotein B-100 antigens are associated with cardiovascular disease in systemic lupus erythematosus.
- 2015
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 181:3, s. 417-426
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Tidskriftsartikel (refereegranskat)abstract
- Increased production of autoantibodies is a characteristic feature of systemic lupus erythematosus (SLE) and there is evidence that several of these autoantibodies may contribute to the increased cardiovascular disease (CVD) in SLE. Autoantibodies against the apolipoprotein (apo) B-100 peptides p45 and p210 have been associated with a lower CVD risk in non-SLE cohorts. The aim of the present study was to investigate how SLE affects the occurrence of these potentially protective autoantibodies. The study cohort consisted of 434 SLE patients and 322 age and sex-matched population controls. Antibodies against native and malondialdehyde (MDA)-modified p45 and p210 were measured by ELISA. SLE patients had significantly lower levels of p210 IgG and p45 IgM (both the native and MDA-modified forms). SLE patients with manifest CVD (myocardial infarction, ischemic cerebrovascular disease or peripheral vascular disease) had lower levels p210 IgG and p45 IgM than SLE patients without CVD. Decreased levels of these autoantibodies were also observed in SLE patients with permanent organ damage as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI). The present findings show that patients with SLE, a condition generally characterized by abundance of autoantibodies of multiple specificities, have reduced levels of antibodies against the apo B-100 antigens p45 and p210 and that the levels of these antibodies are further reduced in SLE patients with CVD. These observations suggest the possibility that an impaired antibody-mediated removal of damaged LDL particles may contribute to the development of vascular complications and organ damage in SLE. This article is protected by copyright. All rights reserved.
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| 13. |
- Vikerfors, Anna, et al.
(författare)
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Clinical manifestations and anti-phospholipid antibodies in 712 patients with systemic lupus erythematosus : evaluation of two diagnostic assays
- 2013
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 34:5, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo evaluate the agreement and performance of two tests for aPLs with regard to association with manifestations of the APS in patients with SLE.MethodsWe investigated 712 SLE patients and 280 population controls. Cardiolipin and β2 glycoprotein-I antibodies were measured with routine ELISA and a new automated method. Three positivity cut-offs (99%, 90% of controls and recommended cut-off by manufacturers) were used. Associations with previous thrombotic events, thrombocytopenia and, in a subgroup of patients, obstetric morbidity (n = 296) were evaluated. Results were compared with the LA test, performed in 380 patients.ResultsInter-test agreement was moderate (demonstrated by κ-values 0.16–0.71). Performance of the two tests was similar: at the 99th percentile cut-off, sensitivity for any thrombotic event ranged from 3.7% to 24.8%, while specificity was 84.7–97.7%. Regardless of assay, IgG isotypes were associated with venous thrombosis and ischaemic cerebrovascular disease, whereas aPLs of IgM isotype were weakly associated with ischaemic heart disease. Associations were greatly affected by aPL level. LA performed better than the specific aPL tests. LA was associated with any thrombotic event, odds ratio 5.4 (95% CI 3.1, 9.4), while the specific aPL tests ranged from non-significant to an odds ratio of 1.9 (95% CI 1.03, 3.4) using criteria cut-off. LA was also convincingly associated with other APS manifestations.ConclusionIn relation to thrombotic manifestations, there was moderate agreement but no clear advantages when comparing a routine aPL ELISA with an automated method. APL isotype and titre as well as LA positivity are important for risk assessment in SLE patients.
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| 14. |
- Wigren, Maria, et al.
(författare)
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Cardiovascular disease in systemic lupus erythematosus is associated with increased levels of biomarkers reflecting receptor-activated apoptosis
- 2018
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 270, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: There is convincing evidence that adaptive immune responses affect the development of atherosclerosis and thrombosis and several autoimmune diseases are associated with increased cardiovascular risk. However, our understanding of the underlying mechanisms remains limited. We investigated how biomarkers reflecting four aspects of autoimmunity: apoptosis, inflammation, tissue degradation and repair, associate with cardiovascular disease (CVD) in subjects with systemic lupus erythematosus (SLE). Methods: We investigated 484 well-characterized SLE patients, 69 of whom had CVD (coronary artery disease, cerebrovascular disease or peripheral artery disease), and 253 controls. Occurrence of carotid plaques was investigated with ultrasound. Plasma levels of biomarkers reflecting apoptosis (Fas, TNF receptor 1, TRAIL receptor 2), inflammation (IL-6, IL-8, monocyte chemotactic protein-1), tissue degradation (matrix metalloproteinase (MMP)-1, MMP-3, MMP-7), and tissue repair (platelet-derived growth factor, epidermal growth factor and stem cell factor) were analyzed by Proximity Extension Assay. Results: Subjects with SLE had markedly elevated plasma levels of biomarkers reflecting apoptosis, inflammation and tissue degradation as compared to controls. SLE patients with CVD had higher levels of Fas, TNF receptor 1, TRAIL receptor 2, MMP-1 and -7 than those without CVD. The same associations were found for the presence of a carotid plaque. When controlling for the factors included in the Framingham risk score, all biomarkers except MMP-1 remained associated with the presence of a carotid plaque, while only TRAIL receptor 2 levels remained significantly associated with CVD. Conclusions: Our findings argue that the cardiovascular risk in SLE is associated with increased cell death by apoptosis and tissue degradation.
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