Corruption, growth and ethnic fractionalization: a theoretical model

This paper analyzes the existing relationship between ethnic fractionalization, corruption and the growth rate of a country. We provide a simple theoretical model. We show that a nonlinear relationship betweenfractionalization and corruption exists: corruption is high in homogeneous or very fragmented countries, but low where fractionalization is intermediate. In fact, when ethnic diversity is intermediate, constituencies act as a check and balance device to limit ethnically-based corruption. Consequently, the relationship between fractionalization and growth rate is also non-linear: growth is high in the middle range of ethnic diversity, low in homogeneous or very fragmented countries

An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes

The Endoplasmatic Reticulum Aminopeptidases ERAP1 and ERAP2 are implicated in a variety of immune and non-immune functions. Most studies however have focused on their role in shaping the HLA class I peptidome by trimming peptides to the optimal size. Genome Wide Association Studies highlighted non-synonymous polymorphisms in their coding regions as associated with several immune mediated diseases. The two genes lie contiguous and oppositely oriented on the 5q15 chromosomal region. Very little is known about the transcriptional regulation and the quantitative variations of these enzymes. Here, we correlated the level of transcripts and proteins of the two aminopeptidases in B-lymphoblastoid cell lines from 44 donors harbouring allelic variants in the intergenic region between ERAP1 and ERAP2. We found that the presence of a G instead of an A at SNP rs75862629 in the ERAP2 gene promoter strongly influences the expression of the two ERAPs with a down-modulation of ERAP2 coupled with a significant higher expression of ERAP1. We therefore show here for the first time a coordinated quantitative regulation of the two ERAP genes, which can be relevant for the setting of specific therapeutic approaches

AIF-1 gene does not confer susceptibility to Behçet's disease: Analysis of extended haplotypes in Sardinian population

Background BehcEet's disease (BD) is a polygenic immune-mediated disorder characterized by a close association with the HLA-B∗51 allele. The HLA region has a strong linkage disequilibrium (LD) and carries several genetic variants (e.g. MIC-A, TNF-α genes) identified as associated to BD because of their LD with HLA-B∗51. In fact, the HLA-B∗51 is inherited as part of extended HLA haplotypes which are well preserved in patients with BD. Sardinian population is highly differentiated from other Mediterranean populations because of a distinctive genetic structure with very highly preserved HLA haplotypes. Patients and methods In order to identify other genes of susceptibility to BD within the HLA region we investigated the distribution of human Allograft Inflammatory Factor-1 (AIF-1) gene variants among BD patients and healthy controls from Sardinia. Six (rs2736182; rs2259571; rs2269475; rs2857597; rs13195276; rs4711274) AIF-1 single nucleotide polymorphisms (SNPs) and related extended haplotypes have been investigated as well as their LD within the HLA region and with HLA-B∗51. Overall, 64 BD patients, 43 HLA-B∗51 positive healthy controls (HC) and 70 random HC were enrolled in the study. Results HLA-B∗51 was the only allele with significantly higher frequency (pc = 0.0021) in BD patients (40.6%) than in HC (9.8%). The rs2259571TAIF-1 variant had a significantly reduced phenotypic, but not allelic frequency in BD patients (72.1%; pc = 0.014) compared to healthy population (91.3%). That was likely due to the LD between HLA-B∗51 and rs2259571G(pc= 9E-5), even though the rs2259571Gdistribution did not significantly differ between BD patients and HC. Conclusion No significant difference in distribution of AIF-1 SNPs haplotypes was observed between BD patients and HC and between HLA-B∗51 positive BD patients and HLA-B∗51 positive HC. Taken together, these results suggest that AIF-1 gene is not associated with susceptibility to BD in Sardinia

Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis

Background. Ankylosing Spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of HLA-B27 alleles. HLA-E are non-classical MHC class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis. Objectives: To analyze the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27 positive AS patients and healthy controls (HC) bearing the AS-associated, B*2705 and the non-AS-associated, B*2709 allele. Methods: The level of surface expression of HLA-E molecules on CD14 positive peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27 negative HC, using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C were also measured on CD3-CD56+ NK cells. Results. HLA-E expression in CD14 positive cells was significantly higher in AS patients (587.0 IQR 424-830) compared to B*2705 HC (389 IQR 251.3-440.5, p=0.0007), B*2709 HC (294.5 IQR 209.5-422, p=0.0004) and HLA-B27 negative HC (380 IQR 197.3-515.0, p=0.01). A higher number of NK cells expressing NKG2A compared to NKG2C was found in all cohort analysed as well as a higher cell surface density. Conclusion: The higher surface level of HLA-E molecules in AS patients compared to HC, concurrently with a prevalent expression of NKG2A, suggests that the crosstalk between these two molecules might play a role in AS pathogenesis accounting for the previously reported association between HLA-E and AS

correlation between fissured fibrous cap and contrast enhancement preliminary results with the use of cta and histologic validation

BACKGROUND AND PURPOSE: Previous studies demonstrated that carotid plaques analyzed by CTA can show contrast plaque enhancement. The purpose of this preliminary work was to evaluate the possible association between the fissured fibrous cap and contrast plaque enhancement. MATERIALS AND METHODS: Forty-seven consecutive (men = 25; average age = 66.8 ± 9 years) symptomatic patients studied by use of a multidetector row CT scanner were prospectively analyzed. CTA was performed before and after contrast and radiation doses were recorded; analysis of contrast plaque enhancement was performed. Patients underwent carotid endarterectomy en bloc; histologic sections were prepared and evaluated for fissured fibrous cap and microvessel attenuation. The Mann-Whitney test was performed to evaluate the differences between the 2 groups. A multiple logistic regression analysis was performed to assess the effect of fissured fibrous cap and microvessel attenuation on contrast plaque enhancement. Receiver operating characteristic curve and area under the curve were also calculated. RESULTS: Twelve patients had fissured fibrous cap. In 92% (11/12) of fissured fibrous cap–positive plaques, we found contrast plaque enhancement, whereas in 69% (24/35) of the plaques without fissured fibrous cap contrast plaque enhancement was found. The Mann-Whitney test showed a statistically significant difference between the contrast enhancement in plaques with fissured fibrous cap (Hounsfield units = 22.6) and without fissured fibrous cap (Hounsfield units = 12.9) ( P = .011). On the regression analysis, both fissured fibrous cap and neovascularization were associated with contrast plaque enhancement ( P = .0366 and P = .0001). The receiver operating characteristic curve confirmed an association between fissured fibrous cap and contrast plaque enhancement with an area under the curve of 0.749 ( P = .005). CONCLUSIONS: The presence of fissured fibrous cap is associated with contrast plaque enhancement. Histologic analysis showed that the presence of fissured fibrous cap is associated with a larger contrast plaque enhancement compared with the contrast plaque enhancement of plaques without fissured fibrous cap

POS0758 DOES EXPERIENCE IN SYSTEMIC LUPUS ERYTHEMATOSUS INFLUENCE THE PHYSICIAN GLOBAL ASSESSMENT SCORING? A CROSS-SECTIONAL STUDY ON TWO EUROPEAN COHORTS

Background:The Physician Global Assessment (PGA) is an outcome instrument based on physician judgement of disease activity in patients with Systemic Lupus Erythematosus (SLE). Due to the subjectivity of the score and lack of standardization, the PGA could represent a source of heterogeneity, because the same manifestations could be rated differently by physicians with different backgrounds (1).Objectives:The purpose of this study was to evaluate the inter-rater reliability of PGA between a rheumatology trainee and rheumatologists expert in SLE from 2 european countries.Methods:SLE patients classified according to SLICC 2012 criteria were enrolled between May 2019 and December 2019 during a SLEuro traineeship program. Demographic, clinical (SLEDAI-2k, PGA), serological and ongoing medication data were collected. PGA was evaluated before (pre-lab) and after (post-lab) knowledge of laboratory exams, using a Visual Analogue Scale (VAS) ranging from 0 to 3, anchored at point 1 (mild), 2 (moderate) and 3 (severe activity). A trainee in Rheumatology (EC) and three rheumatologists experts in SLE (LA, MP, FS) independently scored the PGA for each patient.The trainee preliminarily received a standardization training with her tutor (MP), consisting of a shared discussion about 10 consecutive SLE outpatients to increase reliability in PGA scoring.Inter-rater reliability was analysed using the intraclass correlation coefficient (ICC) with a two-way single-rating model (2,1); 95% confidence interval (CI) was calculated.Results:Fifty-seven patients (86% female) affected from SLE (29 belonging to a French cohort and 28 to an Italian cohort) with a mean (SD) age 43.2 (15.9) years and a median [IQR] disease duration 6.4 [2.0-15.4] years were enrolled. Clinical features are presented in table 1. Pre-lab PGA scores were obtained from all patients and ranged from 0 to 2.3; post-lab PGA scores were obtained from 51 patients and ranged from 0 to 2.9. Inter-rater reliability of the PGA among the trainee was good to excellent for each lupus expert comparison: a) pre-lab PGA ICC 0.94, 95% CI 0.87-0.97; post-lab PGA ICC 0.94, 95% CI 0.87-0.97 (MP); b) pre-lab PGA ICC 0.84, 95% CI 0.63-0.93; post-lab PGA ICC 0.96 CI 0.88-0.99 (LA); c) pre-lab PGA ICC 0.91, 95% CI 0.65-0.98; post-lab PGA ICC 0.91, 95% CI 0.65-0.98 (FS).Conclusion:After an adequate standardization, PGA scoring reaches good to excellent reliability between trainee and experts.References:[1]Chessa E, Piga M, Floris A, Devilliers H, Cauli A, Arnaud L. Use of Physician Global Assessment in systemic lupus erythematosus: a systematic review of its psychometric properties. Rheumatology (Oxford). 2020 Dec 1;59(12):3622-3632.Clinical DataCaucasian44 (77.2%)anti-dsDNA titre (median,IQR)14 (0-75)Hypocomplementemia (n,%)30 (54%)SLEDAI≥6 (n,%)18 (31.6%)SLEDAI (median,IQR)4 (2-6)Flares (n,%)18 (31.6%)Ongoing prednisone treatment (n,%)41 (71.9%)Prednisone dose mg (mean±sd)5 (0 - 8.9)Hydroxychloroquine (n,%)44 (77.2%)Immunosuppressant (n,%)35 (61.4%)Acknowledgements:Elisabetta Chessa gratefully acknowledges the SLEuro European Lupus Society for its financial support in her traineeship in Strasbourg.Disclosure of Interests:None declare

Semiautomated and automated algorithms for analysis of the carotid artery wall on computed tomography and sonography: a correlation study.

Objectives—The purpose of this study was to compare automated and semiautomated algorithms for analysis of carotid artery wall thickness and intima-media thickness on multidetector row computed tomographic (CT) angiography and sonography, respectively, and to study the correlation between them. Methods—Twenty consecutive patients underwent multidetector row CT angiographic and sonographic analysis of carotid arteries (mean age, 66 years; age range, 59–79 years). The intima-media thickness of the 40 carotid arteries was measured with novel and dedicated automated software analysis and by 4 observers who manually calculated the intima-media thickness. The carotid artery wall thickness was automatically estimated by using a specific algorithm and was also semiautomatically quantified. The correlation between groups was calculated by using the Pearson ρ statistic, and scatterplots were calculated. We evaluated intermethod agreement using Bland-Altman analysis. Results—By comparing automated carotid artery wall thickness, automated intima-media thickness, semiautomated carotid artery wall thickness, and semiautomated intima-media thickness analyses, a statistically significant association was found, with the highest values obtained for the association between semiautomated and thickness analyses(Pearson ρ = 0.9; 95% confidence interval, 0.82–0.95; P = 0.0001). The lowest values were obtained for the association between semiautomated intima-media thickness and automated carotid artery wall thickness analyses (Pearson ρ = 0.44; 95% confidence interval, 0.15–0.66; P = 0.0047). In the Bland-Altman analysis, the better results were obtained by comparing the semiautomated and automated algorithms for the study of intima-media thickness, with an interval of –16.1% to +43.6%. Conclusions—The results of this preliminary study showed that carotid artery wall thickness and intima-media thickness can be studied with automated software, although the CT analysis needs to be further improved