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Sökning: WFRF:(Mahler G.) > Tidskriftsartikel

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  • Stinton, L. M., et al. (författare)
  • PR3-ANCA: A Promising Biomarker in Primary Sclerosing Cholangitis (PSC)
  • 2014
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients. Methods: A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF. Results: When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes. Conclusion: PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.
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  • Bentow, C., et al. (författare)
  • International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies
  • 2016
  • Ingår i: Lupus. - : SAGE PUBLICATIONS LTD. - 0961-2033 .- 1477-0962. ; 25:8, s. 864-872
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Patients and methods: A total of 1431 samples (SLE, n=843; disease controls, n=588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n=566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off ofamp;gt;4 was used to define active disease. Results: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (pamp;lt;0.0001) in active SLE (SLEDAI-2Kamp;gt;4; n=232; median value 83.0IU/mL) versus the inactive patients (n=573; median value 22.3IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearmans rho=0.44, pamp;lt;0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. Conclusions: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.
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  • de La Vieuville, G., et al. (författare)
  • Faint end of the z similar to 3-7 luminosity function of Lyman-alpha emitters behind lensing clusters observed with MUSE
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 628
  • Tidskriftsartikel (refereegranskat)abstract
    • Contact. This paper presents the results obtained with the Multi-Unit Spectroscopic Explorer (MUSE) at the ESOVery Large Telescope on the faint end of the Lyman-alpha luminosity function (LF) based on deep observations of four lensing clusters. The goal of our project is to set strong constraints on the relative contribution of the Lyman-alpha emitter (LAE) population to cosmic reionization.Aims. The precise aim of the present study is to further constrain the abundance of LAEs by taking advantage of the magnification provided by lensing clusters to build a blindly selected sample of galaxies which is less biased than current blank field samples in redshift and luminosity. By construction, this sample of LAEs is complementary to those built from deep blank fields, whether observed by MUSE or by other facilities, and makes it possible to determine the shape of the LF at fainter levels, as well as its evolution with redshift.Methods. We selected a sample of 156 LAEs with redshifts between 2.9 <= z <= 6.7 and magnification-corrected luminosities in the range 39 less than or similar to log L-Ly alpha [erg s(-1)] less than or similar to 43. To properly take into account the individual differences in detection conditions between the LAEs when computing the LF, including lensing configurations, and spatial and spectral morphologies, the non-parametric 1/V-max method was adopted. The price to pay to benefit from magnification is a reduction of the effective volume of the survey, together with a more complex analysis procedure to properly determine the effective volume V-max for each galaxy. In this paper we present a complete procedure for the determination of the LF based on IFU detections in lensing clusters. This procedure, including some new methods for masking, effective volume integration and (individual) completeness determinations, has been fully automated when possible, and it can be easily generalized to the analysis of IFU observations in blank fields.Results. As a result of this analysis, the Lyman-alpha LF has been obtained in four different redshift bins: 2.9 < z < 6; 7, 2.9 < z < 4.0, 4 : 0 < z < 5.0; and 5 : 0 < z < 6.7 with constraints down to log L-Ly alpha = 40.5. From our data only, no significant evolution of LF mean slope can be found. When performing a Schechter analysis also including data from the literature to complete the present sample towards the brightest luminosities, a steep faint end slope was measured varying from alpha = -1.69(-0.08)(+0.08) to alpha = -1.87(-0 .12)(+0.12) between the lowest and the highest redshift bins.Conclusions. The contribution of the LAE population to the star formation rate density at z similar to 6 is less than or similar to 50% depending on the luminosity limit considered, which is of the same order as the Lyman-break galaxy (LBG) contribution. The evolution of the LAE contribution with redshift depends on the assumed escape fraction of Lyman-alpha photons, and appears to slightly increase with increasing redshift when this fraction is conservatively set to one. Depending on the intersection between the LAE/LBG populations, the contribution of the observed galaxies to the ionizing flux may suffice to keep the universe ionized at z similar to 6.
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  • Khaleva, E, et al. (författare)
  • Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
  • 2023
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
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  • Khaleva, E, et al. (författare)
  • Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
  • 2023
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
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  • Thai, T. T., et al. (författare)
  • Probing the faint-end luminosity function of Lyman-alpha emitters at 3 < z < 7 behind 17 MUSE lensing clusters
  • 2023
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 678
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. This paper presents a study of the galaxy Lyman-alpha luminosity function (LF) using a large sample of 17 lensing clusters observed by the Multi Unit Spectroscopic Explorer (MUSE) at the ESO Very Large Telescope (VLT). The magnification resulting from strong gravitational lensing by clusters of galaxies and MUSE spectroscopic capabilities allows for blind detections of LAEs without any photometric pre-selection, reaching the faint luminosity regime.Aims. The present work aims to constrain the abundance of Lyman-alpha emitters (LAEs) and quantify their contribution to the total cosmic reionization budget.Methods. We selected 600 lensed LAEs behind these clusters in the redshift range of 2.9 < z < 6.7, covering four orders of magnitude in magnification-corrected Ly-α luminosity (39.0 < log(L)[erg s−1] < 43.0). These data were collected behind lensing clusters, indicating an increased complexity in the computation of the LF to properly account for magnification and dilution effects. We applied a non-parametric Vmax method to compute the LF to carefully determine the survey volume where an individual source could have been detected. The method used in this work follows the recipes originally developed in previous works, with some improvements to better account for the effects of lensing when computing the effective volume.Results. The total co-moving volume at 2.9 < z < 6.7 in the present survey is ∼50 103 Mpc3. Our LF points in the bright end (log(L) [erg s−1] > 42) are consistent with those obtained from blank field observations. In the faint luminosity regime, the density of sources is well described by a steep slope, α ∼ −2 for the global redshift range. Up to log(L) [erg s−1] ∼ 41, the steepening of the faint end slope with redshift, suggested in earlier works, is observed, but the uncertainties are still large. A significant flattening is observed towards the faintest end, for the highest redshift bins, namely, log(L)[erg s−1] < 41.Conclusions. When taken at face value, the steep slope at the faint-end causes the star formation rate density (SFRD) to dramatically increase with redshift, implying that LAEs could play a major role in the process of cosmic reionization. The flattening observed towards the faint end for the highest redshift bins still requires further investigation. This turnover is similar to the one observed for the UV LF at z ≥ 6 in lensing clusters, with the same conclusions regarding the reliability of current results. Improving the statistical significance of the sample in this low-luminosity high-redshift regime is a difficult endeavour that may lead to potentially valuable leads in understanding the process of reionization.
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  • Choi, MY, et al. (författare)
  • The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients
  • 2017
  • Ingår i: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 26:10, s. 1051-1059
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7–8.8%), while only 1.1% (95% CI: 0.6–1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-β2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0–2.8%) and was associated with musculoskeletal activity and anti-β2 glycoprotein 1 autoantibodies. However, ‘monospecific’ anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.
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