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- 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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- Nordin, Annika, et al.
(författare)
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Troponin I and echocardiography in patients with systemic sclerosis and matched population controls
- 2017
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 46:3, s. 226-235
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Cardiac manifestations in systemic sclerosis (SSc) are associated with poor prognosis. Few studies have investigated cardiac troponins in SSc. We studied the relationships between echocardiographic abnormalities, cardiac biomarkers, and disease manifestations in a population-based cohort of patients with SSc and controls.METHOD: The study comprised 110 patients with SSc and 105 age- and sex-matched population-based controls. We examined ventricular function, heart valves, and estimated pulmonary arterial pressure (ePAP) by echocardiography in all participants. Disease characteristics, manifest ischaemic heart disease (IHD), and measurements of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were tabulated.RESULTS: NT-proBNP and hs-cTnI levels were higher in SSc patients than controls. Both NT-proBNP and hs-cTnI were associated with the presence of echocardiographic abnormalities. Forty-four SSc patients and 23 control subjects had abnormal echocardiograms (p = 0.002). As a group, SSc patients had lower (but normal) left ventricular ejection fraction (LVEF, p = 0.02), more regional hypokinesia (p = 0.02), and more valve regurgitations (p = 0.01) than controls. Thirteen patients and four controls had manifest IHD. Decreased right ventricular (RV) function (n = 7) and elevated ePAP (n = 15) were exclusively detected among SSc patients.CONCLUSIONS: Both NTproBNP and hs-cTnI were associated with echocardiographic abnormalities, which were more prevalent in SSc patients than in controls. Our results thus suggest that hs-cTnI could be a potential cardiac biomarker in SSc. Low RV function and signs of pulmonary hypertension (PH) were uniquely found in the SSc group. SSc patients had more valve regurgitation than controls, an observation that warrants more clinical attention.
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- Bergwall, Lovisa, et al.
(författare)
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Amplification of the Melanocortin-1 Receptor in Nephrotic Syndrome Identifies a Target for Podocyte Cytoskeleton Stabilization
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The melanocortin-1 receptor (MC1R) in podocytes has been suggested as the mediator of the ACTH renoprotective effect in patients with nephrotic syndrome with the mechanism of action beeing stabilization of the podocyte actin cytoskeleton. To understand how melanocortin receptors are regulated in nephrotic syndrome and how they are involved in restoration of filtration barrier function, melanocortin receptor expression was evaluated in patients and a rat model of nephrotic syndrome in combination with cell culture analysis. Phosphoproteomics was applied and identified MC1R pathways confirmed using biochemical analysis. We found that glomerular MC1R expression was increased in nephrotic syndrome, both in humans and in a rat model. A MC1R agonist protected podocytes from protamine sulfate induced stress fiber loss with the top ranked phoshoproteomic MC1R activated pathway beeing actin cytoskeleton signaling. Actin stabilization through the MC1R consisted of ERK1/2 dependent phosphorylation and inactivation of EGFR signaling with stabilization of synaptopodin and stressfibers in podocytes. These results further explain how patients with nephrotic syndrome show responsiveness to MC1R receptor activation by decreasing EGFR signaling and as a consequence restore filtration barrier function by stabilizing the podocyte actin cytoskeleton.
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- Frodlund, Martina, et al.
(författare)
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Immunoglobulin A anti-phospholipid antibodies in Swedish cases of systemic lupus erythematosus : associations with disease phenotypes, vascular events and damage accrual
- 2018
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Ingår i: Clinical and Experimental Immunology. - : WILEY. - 0009-9104 .- 1365-2249. ; 194:1, s. 27-38
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-(2)-glycoprotein-I (anti-(2)GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-(2)GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n=100), primary Sjogren's syndrome (n=50) and blood donors (n=507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-(2)GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and 1 aCL/anti-(2)GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-(2)GPI, 34 (6%) being seronegative regarding IgG/IgM anti-(2)GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-(2)GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-(2)GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR)=021, 95% confidence interval (CI)=006-072) and photosensitivity (OR=019, 95% CI=005-072). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.
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- Idborg, Helena, et al.
(författare)
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STRATIFICATION OF SLE PATIENTS FOR IMPROVED DIAGNOSIS AND TREATMENT
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 72, s. A80-A80
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background. Systemic autoimmune diseases (SAIDs) affect about 2% of the population in Western countries. Sufficient diagnostic criteria are lacking due to the heterogeneity within diagnostic categories and apparent overlap regarding symptoms and patterns of autoantibodies between different diagnoses. Systemic lupus erythematosus (SLE) is regarded as a prototype for SAIDs and we hypothesise that subgroups of patients with SLE may have different pathogenesis and should consequently be subject to different treatment strategies.Objectives. Our goal is to find new biomarkers to be used for the identification of more homogenous patient populations for clinical trials and to identify sub-groups of patients with high risk of for example cardiovascular events.Methods. In this study we have utilised 320 SLE patients from the Karolinska lupus cohort and 320 age and gender matched controls. The SLE cohort was characterised based on clinical, genetic and serological data and combined by multivariate data analysis in a systems biology approach to study possible subgroups. A pilot study was designed to verify and investigate suggested subgroups of SLE. Two main subgroups were defined: One group was defined as having SSA and SSB antibodies and a negative lupus anticoagulant test (LAC), i.e., a “Sjögren-like” group. The other group was defined as being negative for SSA and SSB antibodies but positive in the LAC test.i.e. an “APS-like” group. EDTA-plasma from selected patients in these two groups and controls were analysed using a mass spectrometry (MS) based proteomic and metabolomic approach. Pathway analysis was then performed on the obtained data.Results. Our pilot study showed that differences in levels of proteins and metabolites could separate disease groups from population controls. The profile/pattern of involved factors in the complement system supported a division of SLE in two major subgroups, although each individual factor was not significantly different between subgroups. Complement factor 2 (C2) and membrane attack complex (MAC) were analysed in the entire cohort with complementary methods and C2 verifies our results while the levels of MAC did not differ between SLE subgroups. The generated metabolomics data clearly separated SLE patients from controls in both gas chromatography (GC)-MS and liquid chromatography (LC)-MS data. We found for example that tryptophan was lower in the SLE patients compared to controls.Conclusions. Our systems biology approach may lead to a better understanding of the disease and its pathogenesis, and assigning patients into subgroups will result in improved diagnosis and better outcome measures of SLE.
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| 24. |
- 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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| 36. |
- Rahbin, N, et al.
(författare)
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Detection and characterization of focal liver lesions with contrast-enhanced ultrasonography in patients with hepatitis C-induced liver cirrhosis
- 2008
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 49:3, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hepatitis C virus (HCV)-associated liver cirrhosis provides a major preneoplastic condition for hepatocellular carcinoma (HCC). Ultrasonography (US) is usually used for screening of HCC, but needs improvement. Purpose: To assess whether use of a second-generation ultrasound contrast agent can improve characterization of focal liver lesions and detection of HCC in HCV-infected patients with liver cirrhosis. Material and Methods: In total, 96 US studies in 49 HCV-infected patients with liver cirrhosis were performed. The patients were first examined with a baseline US. After this, a diagnostic decision was made and recorded. The patients were then re-examined with contrast-enhanced ultrasound (CEUS), and the diagnostic triage was repeated. The patients were followed up for at least 1 year. Results: On baseline US, indeterminate focal lesions were found in 27 examinations. After CEUS, a confident diagnosis of HCC was made in eight of these examinations. In an additional eight US examinations, diagnosis of regenerative/dysplastic noduli was established. In one patient with no detectable focal lesion at baseline examination, an indeterminate malignant lesion was detected with CEUS. This lesion was further investigated with computed tomography and diagnosed as HCC. Conclusion: Our study indicates that the use of CEUS significantly improves diagnostic confidence. CEUS improves the detection of HCC in patients with HCV-induced liver cirrhosis. Also, CEUS makes it possible to rule out malignancy in many cases where baseline US shows indeterminate focal lesions. In low-endemic countries, the use of CEUS in screening for HCC may be considered.
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| 39. |
- Wang, Ning, et al.
(författare)
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Selective IgA deficiency in autoimmune diseases
- 2011
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Ingår i: Molecular Medicine. - Baltimore, Md. : Johns Hopkins University Press. - 1076-1551 .- 1528-3658. ; 17:11-12, s. 1383-
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Forskningsöversikt (refereegranskat)abstract
- Selective IgA deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves' disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) based both on our own, recent, large scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the MHC region has been reported. In addition, non-MHC genes, such as IFIH1 and CLEC16A, are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders.
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