Cerebral cavernous malformations (CCMs) are vascular anomalies of the nervous system mostly located in the brain presenting sporadically or familial. Causes of familial forms are mutations in CCM1 (Krit1), CCM2 (MGC4607) and CCM3 (PDCD10) genes. Sporadic forms with no affected relative most often have only one lesion and no germ line mutations. However, a number of sporadic cases with multiple lesions have been reported and are indeed genetic cases with a de novo mutation or a mutation inherited from an asymptomatic parent. Here, we performed an analysis of regulatory region of CCM genes in 60 sporadic patients, negative for mutations in coding region and intron-exon boundaries and large deletion/duplications in CCM genes by direct sequencing and MLPA. Among 5 variants identified in 851-bp region shared by CCM3 and SERPINI1 genes and acting as asymmetric bidirectional promoter, two polymorphisms c.-639 T > C/rs9853967 and c.-591 T > C/rs11714980 were selected. A case-control study was performed to analyze their possible relationships with sporadic CCMs. Promoter haplotypes activities on CCM3/SERPINI1 genes expression were tested by dual-luciferase assay. No variants were identified in CCM1 and CCM2 regulatory regions. In CCM3/SERPINI1 asymmetric bidirectional promoter 5 variants, 2 of them unknown and 3 corresponding to polymorphisms c.-639 T > C/rs9853967, c.-591 T > C/rs11714980 and c.-359G > A/rs9834676 were detected. While rs9853967 and rs11714980 polymorphisms fall in a critical regulatory fragment outside the minimal promoter in intergenic region, other variants had no effects on transcription factor binding according to RegRNA tool. Case-control study performed on 60 patients and 350 healthy controls showed frequencies of the mutated alleles significantly higher in the control group than in patients. Furthermore, the functional assay showed a significant reduction of CCM3 expression for C-C haplotype even more than for T-C and C-T haplotypes. In SERPINI1 direction, the reduction was not statistically significant. Our data indicated that rs9853967 and rs11714980 polymorphisms could be associated with a protective role in CCM disease.

Purpose: The purpose is to analyze the spatially varying impacts of corruption and public debt as % of GDP (proxies of government failures) on non-performing loans (NPLs) in European countries; comparing two periods: one prior to the crisis of 2007 and another one after that. The authors first modeled the NPLs with an ordinary lest square (OLS) regression and found clear evidence of spatial instability in the distribution of the residuals. As a second step, the authors utilized the geographically weighted regression (GWR) to explore regional variations in the relationship between NPLs and the proxies of “Government failures”.Design/methodology/approach: The authors first modeled the NPL with an OLS regression and found clear evidence of spatial instability in the distribution of the residuals. As a second step, the author utilized the Geographically Weighted Regression (GWR) (Fotheringham et al., 2002) to explore regional variations in the relationship between NPLs and proxies of “Government failures” (corruption and public debt as % of GDP).Findings: The results confirm that corruption and public debt as % of GDP, after the crisis of 2007, have affected significantly on NPLs of the EU countries and the following countries neighboring the EU: Switzerland, Iceland, Norway, Montenegro, and Turkey.Originality/value: In a spatial prospective, unprecedented in the literature, this research focused on the impact of corruption and public debt as % of GDP on NPLs in European countries. The positive correlation, as expected, between public debt and NPLs highlights that fiscal problems in Eurozone countries have led to an important rise of problem loans. The impact of institutional corruption on NPLs reports that the higher the corruption, the higher is the level of NPLs.

Background: The analysis of risk for the population residing and/or working in contaminated areas raises the topic of commuting. In fact, especially in contaminated areas, commuting groups are likely to be subject to lower exposure than residents. Only very recently environmental epidemiology has started considering the role of commuting as a differential source of exposure in contaminated areas. In order to improve the categorization of groups, this paper applies a gravitational model to the analysis of residential risk for workers in the Gela petrochemical complex, which began life in the early 60s in the municipality of Gela (Sicily, Italy) and is the main source of industrial pollution in the local area.Results: A logistic regression model is implemented to measure the capacity of Gela "central location" to attract commuting flows from other sites. Drawing from gravity models, the proposed methodology: a) defines the probability of finding commuters from municipalities outside Gela as a function of the origin's "economic mass" and of its distance from each destination; b) establishes "commuting thresholds" relative to the origin's mass. The analysis includes 367 out of the 390 Sicilian municipalities. Results are applied to define "commuters" and "residents" within the cohort of petrochemical workers. The study population is composed of 5,627 workers. Different categories of residence in Gela are compared calculating Mortality Rate Ratios for lung cancer through a Poisson regression model, controlling for age and calendar period. The mobility model correctly classifies almost 90% of observations. Its application to the mortality analysis confirms a major risk for lung cancer associated with residence in Gela.Conclusions: Commuting is a critical aspect of the health-environment relationship in contaminated areas. The proposed methodology can be replicated to different contexts when residential information is lacking or unreliable; however, a careful consideration of the territorial characteristics ("insularity" and its impact on transportation time and costs, in our case) is suggested when specifying the area of application for the mobility analysis.

In the last few decades, the foreign resident population in Italy has grown considerably, showing a tendency towards a stable settlement. The spatial distribution of this population is an important key to better understanding the integration process in the host society. This paper aims to explore the diachronic evolution of the settlement models of the foreign population and the main ethnic groups usually classified as residents in Italy in the period 2003–2021. Towards this aim, we computed statistical global indices referring to evenness, concentration, and clustering dimension of residential segregation and ad hoc indices that regard territorial dimensions. One of the major novelties of the contribution lies in the attempt to compute these indices not only in reference to the major population group—i.e., the Italians—but also between foreign communities and considering the gender structure. The indices are then synthesised by a multivariate analysis (principal component analysis and cluster analysis). The results of this study show that (a) higher differences in terms of settlement models are found by comparing different minority groups rather than by comparing minorities to Italians; (b) the settlement models of each foreign citizenship remain almost stable over time despite their growth in both absolute and relative terms.