Well-posedness for a class of nonlinear degenerate parabolic equations

In this paper we obtain well-posedness for a class of semilinear weakly degenerate reaction-diffusion systems with Robin boundary conditions. This result is obtained through a Gagliardo-Nirenberg interpolation inequality and some embedding results for weighted Sobolev spaces

Declining partisan representation at the sub-national level: assessing and explaining the strengthening of local lists in Italian municipalities (1995–2014)

In Western democracies political representation at the national level is still dominated by (old and new) political parties. This article shows that, instead, the representative role of parties may have declined at the local level. In Italy, for instance, the average share of municipal seats held by non-partisan councillors has almost tripled in the last 20 years. By using an original data set, this article classifies different types of Italian local lists, assesses their relationship with traditional parties and explains territorial variation in their success. The results suggest that local lists have become substantially stronger in small municipalities, in regions characterised by weak or declining political subcultures and where regionalist parties are absent or irrelevant. Finally, contrary to the expectation that declining partisanship is linked to modernisation processes and direct civic engagement, local lists have achieved their best results in the less developed areas of the country

High Levels of Receptor Tyrosine Kinases in CCM3-Deficient Cells Increase Their Susceptibility to Tyrosine Kinase Inhibition

Cerebral cavernous malformations (CCMs) are vascular malformations that can be the result of the deficiency of one of the CCM genes. Their only present treatment is surgical removal, which is not always possible, and an alternative pharmacological strategy to eliminate them is actively sought. We have studied the effect of the lack of one of the CCM genes, CCM3, in endothelial and non-endothelial cells. By comparing protein expression in control and CCM3-silenced cells, we found that the levels of the Epidermal Growth Factor Receptor (EGFR) are higher in CCM3-deficient cells, which adds to the known upregulation of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in these cells. Whereas VEGFR2 is upregulated at the mRNA level, EGFR has a prolonged half-life. Inhibition of EGFR family members in CCM3-deficient cells does not revert the known cellular effects of lack of CCM genes, but it induces significantly more apoptosis in CCM3-deficient cells than in control cells. We propose that the susceptibility to tyrosine kinase inhibitors of CCM3-deficient cells can be harnessed to kill the abnormal cells of these lesions and thus treat CCMs pharmacologically

Pregnancy Loss in Women with HIV is not Associated with HIV Markers: Data from a National Study in Italy, 2001-2018.

BACKGROUND: There is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. METHODS: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth ( 6522 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses. RESULTS: Among 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio [AOR] per additional year of age: 1.079, 95% confidence interval [CI] 1.046-1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407-4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178-2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage. CONCLUSIONS: Older women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss

Local representative democracy and protest politics:the case of the Five-star Movement

In recent years, protest politics has become a relevant phenomenon in various European countries. Italy has witnessed the rise of the Five-star Movement (M5S), an anti-establishment party, which, at the 2013 general election, obtained one-fourth of the total votes. However, the story of this ‘party-movement’ started at the local level, as a civic network aimed at changing administrative practices in municipal government. By using an original dataset on representation in 671 Italian municipalities from 2010 to 2014, this article aims to explain not only the subnational political success of the M5S but also the challenges and contradictions that a newly formed movement faces in multi-level electoral arenas

Improving diagnosis for rare diseases: the experience of the Italian undiagnosed Rare diseases network

Background For a number of persons with rare diseases (RDs) a definite diagnosis remains undiscovered with relevant physical, psychological and social consequences. Undiagnosed RDs (URDs) require other than specialised clinical centres, outstanding molecular investigations, common protocols and dedicated actions at national and international levels; thus, many "Undiagnosed RDs programs" have been gradually developed on the grounds of a well-structured multidisciplinary approach. Methods The Italian Undiagnosed Rare Diseases Network (IURDN) was established in 2016 to improve the level of diagnosis of persons with URD living in Italy. Six Italian Centres of Expertise represented the network. The National Centre for Rare Diseases at the Istituto Superiore di Sanita coordinates the whole project. The software PhenoTips was used to collect the information of the clinical cases. Results One hundred and ten cases were analysed between March 2016 and June 2019. The age of onset of the diseases ranged from prenatal age to 51 years. Conditions were predominantly sporadic; almost all patients had multiple organs involvements. A total of 13/71 family cases were characterized by WES; in some families more than one individual was affected, so leading to 20/71 individuals investigated. Disease causing variants were identified in two cases and were associated to previously undescribed phenotypes. In 5 cases, new candidate genes were identified, although confirmatory tests are pending. In three families, investigations were not completed due to the scarce compliance of members and molecular investigations were temporary suspended. Finally, three cases (one familial) remain still unsolved. Twelve undiagnosed clinical cases were then selected to be shared at International level through PhenomeCentral in accordance to the UDNI statement. Conclusions Our results showed a molecular diagnostic yield of 53,8%; this value is comparable to the diagnostic rates reported in other international studies. Cases collected were also pooled with those collected by UDNI International Network. This represents a unique example of global initiative aimed at sharing and validating knowledge and experience in this field. IURDN is a multidisciplinary and useful initiative linking National and International efforts aimed at making timely and appropriate diagnoses in RD patients who still do not have a confirmed diagnosis even after a long time

Recent Trends and Perspectives on Defect-Oriented Testing

Electronics employed in modern safety-critical systems require severe qualification during the manufacturing process and in the field, to prevent fault effects from manifesting themselves as critical failures during mission operations. Traditional fault models are not sufficient anymore to guarantee the required quality levels for chips utilized in mission-critical applications. The research community and industry have been investigating new test approaches such as device-aware test, cell-aware test, path-delay test, and even test methodologies based on the analysis of manufacturing data to move the scope from OPPM to OPPB. This special session presents four contributions, from academic researchers and industry professionals, to enable better chip quality. We present results on various activities towards this objective, including device-aware test, software-based self-test, and memory test

Markers of microbial translocation during pregnancy: differences among HIV+ women of African and European provenance.

Introduction: Microbial translocation (MT) markers are indicators of HIV-related immune activation, but reference values are mostly derived from European or North American populations and could be substantially different in populations living in developing countries. Here we evaluate possible differences in MT markers levels in HIV+ pregnant women of different geographical provenance. Methodology: This study is nested within an observational study of pregnant women with HIV in Italy. Women were dichotomized on the basis of provenance in two groups of European (n = 14) and African (n = 26) origin. Soluble CD14, lipopolysaccharide-binding protein (LBP) and intestinal-fatty acid binding protein (I-FABP) were measured in plasma samples collected between the first and second trimester of pregnancy. Results: Demographic and viroimmunological characteristics were similar between groups, although European women were more commonly smokers and HCV-coinfected. Irrespective of origin, LBP plasma levels were positively correlated with I-FABP (r = 0.467, p = 0.004) and sCD14 levels (r = 0.312 p = 0.060). Significantly higher levels of sCD14 (1885 vs. 1208 ng/mL, p = 0.005) LBP (28.5 vs. 25.3 µg/mL, p = 0.050) and I-FABP (573.4 vs. 358.2 pg/mL, p = 0.002) were observed in European compared with African women. A multivariable linear regression analysis, adjusted for smoking and HCV coinfection confirmed the association between sCD14 levels and women provenance (p = 0.03). Conclusions: Our observations indicate significant differences in soluble markers among women of different provenance. In the design and analysis of studies evaluating MT markers, population-specific reference values should be considered

HIV-1 viral load and resistance in genital secretions in patients taking protease-inhibitor-based second-line therapy in Africa

Background: HIV is transmitted primarily through sexual intercourse, and the objective of this study was therefore to assess whether there is occult viral replication and resistance in genital secretions in patients on protease inhibitor (PI)-based second-line therapy. Methods: HIV-infected adults taking ritonavir-boosted lopinavir with either two NRTIs, raltegravir, or as monotherapy for 96 weeks were enrolled at seven clinical sites in Uganda. Viral load (VL) was measured in cervico-vaginal secretions or semen and in a corresponding plasma sample. Genotypic resistance was assessed in genital secretion samples and plasma samples. Results were compared between compartments and with the plasma resistance profile at first-line failure. Results: Of the 111 participants enrolled (91 female, 20 male), 16 (14%) and 30 (27%) had VL >1000 and >40 copies/ml respectively in plasma; 3 (3%) and 23 (21%) had VL >1000 copies/ml and >40 copies/ml respectively in genital secretions. There was 74% agreement between plasma and genital secretion VL classification above/below 40 copies/ml threshold (kappa-statistic=0.29; p=0.001). RT mutations (both NRTI and NNRTI) were detected in genital secretions in 4 patients (similar profile to corresponding plasma sample at first-line failure) and PI mutations were detected in 2 (1 polymorphism with no impact on resistance; 1 with high-level PI resistance). Conclusions: High level (>1000 copies/ml) viral replication and development of new RT or PI resistance in the genital compartment were rare. The risks of transmission arising from resistance evolution in the genital compartment are likely to be low on PI-based second-line therapy