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Psoriasis is a chronic multifactorial skin disorder with an immune basis. It is characterized by patches of skin that are usually red, flaky and crusty, and that often release silvery scales. The patches appear predominantly on the elbows, knees, scalp and lower back, although they may also appear on other body areas and severity may be variable. The majority of patients (about 90%) present small patches known as “plaque psoriasis”. The roles of environmental triggers such as stress, mechanical trauma and streptococcal infections are well described in psoriasis onset, but much effort is still needed to unravel the genetic component. The principal aim of this study was to use a next-generation sequencing technologies-based approach together with a 96 customized multigene panel in the attempt to determine if there are germline alterations that can explain the onset of the disease, and thus to find associations between genotypes and phenotypes. To this aim, we analyzed a family in which the mother showed mild psoriasis, and her 31-year-old daughter had suffered from psoriasis for several years, whereas an unaffected sister served as a negative control. We found variants already associated directly to psoriasis in the TRAF3IP2 gene, and interestingly we found a missense variant in the NAT9 gene. The use of multigene panels in such a complex pathology such as psoriasis can be of great help in identifying new susceptibility genes, and in being able to make early diagnoses especially in families with affected subjects.

CXCL1, a functional murine orthologue of the human chemokine CXCL8 (IL-8), and its CXCR1 and CXCR2 receptors were investigated in a murine model of acquired epilepsy developing following status epilepticus (SE) induced by intra-amygdala kainate. CXCL8 and its receptors were also studied in human temporal lobe epilepsy (TLE). The functional involvement of the chemokine in seizure generation and neuronal cell loss was assessed in mice using reparixin (formerly referred to as repertaxin), a non-competitive allosteric inhibitor of CXCR1/2 receptors. We found a significant increase in hippocampal CXCL1 level within 24 h of SE onset that lasted for at least 1 week. No changes were measured in blood. In analogy with human TLE, immunohistochemistry in epileptic mice showed that CXCL1 and its two receptors were increased in hippocampal neuronal cells. Additional expression of these molecules was found in glia in human TLE. Mice were treated with reparixin or vehicle during SE and for additional 6 days thereafter, using subcutaneous osmotic minipumps. Drug-treated mice showed a faster SE decay, a reduced incidence of acute symptomatic seizures during 48 h post-SE, and a delayed time to spontaneous seizures onset compared to vehicle controls. Upon reparixin discontinuation, mice developed spontaneous seizures similar to vehicle mice, as shown by EEG monitoring at 14 days and 2.5 months post-SE. In the same epileptic mice, reparixin reduced neuronal cell loss in the hippocampus vs vehicle-injected mice, as assessed by Nissl staining at completion of EEG monitoring. Reparixin administration for 2 weeks in mice with established chronic seizures, reduced by 2-fold on average seizure number vs pre-treatment baseline, and this effect was reversible upon drug discontinuation. No significant changes in seizure number were measured in vehicle-injected epileptic mice that were EEG monitored in parallel. Data show that CXCL1-IL-8 signaling is activated in experimental and human epilepsy and contributes to acute and chronic seizures in mice, therefore representing a potential new target to attain anti-ictogenic effects.

Stabilization projects of rock masses cannot be performed without a proper geomechanical characterization. The classical approaches, due to logistic issues, typically are not able to cover extensively the areas under study. Geo-structural analysis on point cloud from terrestrial laser scanning and photogrammetry from unmanned aerial vehicles are valid tools for analysis of discontinuity systems. Such methodologies provide reliable data even in complex environmental settings (active cliffs) or at inaccessible sites (excavation fronts in tunnels), offering advantages in terms of both safety of the operators and economic and time issues. We present the implementation of these techniques at a tuff cliff over the Santa Caterina beach (Campania) and at the main entrance of Castellana Caves (Apulia). In the first case study, we also perform an integration of the two techniques. Both sites are of significant tourist and economic value, and present instability conditions common to wide areas of southern Italy: namely, retrogressive evolution of active cliffs along the coast, and instability at the rims of natural and/or artificial sinkholes. The results show the reliability of the data obtained through semi-automatic methods to extract the discontinuity sets from the point clouds, and their agreement with data collected in the field through classical approaches. Advantages and drawbacks of the techniques are illustrated and discussed.

Summary We analyzed MBL2 gene variants in two cohorts of centenarians, octo-nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose-binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population from the same geographic area. Furthermore, serum MBL concentration (also after normalization to serum albumin) was significantly lower in centenarians and in octo- and nonagenarians as compared to the general population, suggesting that intermediate MBL haplotype/activity may be protective. We also demonstrated that in vitro MBL protein bound to senescent IMR90 fibroblasts thereby causing cell lysis, but not to other types of cycle-arrested cells not in senescence. This implicates a novel role of MBL in the clearance of senescent cells.

The double or even triple dividend hypothesis of green tax reforms has been a major issue of dispute in both the scientific community and the political arena during the last decade. Theoretical analysis has provided a number of important qualitative insights to the debate but lacks of actual policy relevance due to very restrictive assumptions. Applied research that takes the step from stylized analytical to complex numerical models usually comes as a blackbox to non-expert modelers. This paper aims at bridging the gap between stylized theoretical work and numerical analysis. We develop a flexible, interactive simulation model which is accessible under http://brw.zew.de. Users can specify their own green tax reforms and evaluate the induced economic and environmental effects. Based on illustrative simulations, we demonstrate the usefulness of our do-it-yourself approach for a better understanding of the double (triple) dividend hypothesis.

Knowledge of the geometrical and structural setting of rock masses is crucial to evaluate the stability and to design the most suitable stabilization works. In this work we use the Terrestrial Laser Scanning (TLS) at the site of the Grave of the Castellana Caves, a famous show cave in southern Italy. The Grave is the natural access to the cave system, produced by collapse of the vault, due to upward progression of instabilities in the carbonate rock masses. It is about 55-m high, bell-shaped, with maximum width of 120 m. Aim of the work is the characterization of carbonate rock masses from the structural and geo-mechanical standpoints through the use of innovative survey techniques. TLS survey provides a product consisting of millions of geo-referenced points, to be managed in space, to become a suitable database for the morphological and geological-structural analysis. Studying by means of TLS a rock face, partly inaccessible or located in very complex environments, allows to investigate slopes in their overall areal extent, thus offering advantages both as regards safety of the workers and time needed for the survey. In addition to TLS, the traditional approach was also followed by performing scanlines surveys along the rims of the Grave, following the ISRM recommendations for characterization of discontinuity in rock masses. A quantitative comparison among the data obtained by TLS technique and those deriving from the classical geo-mechanical survey is eventually presented, to discuss potentiality of drawbacks of the different techniques used for surveying the rock masses.

The paper deals with the distributional and efficiency consequences of debt reduction in Italy. A reduction of the deficit from six to three percent of GDP is financed by the so-called Eurotax (introduced temporarily or permanently) combined with an adjustment of consumption taxes or public transfers. The quantitative analysis is based on a dynamic simulation model of the Auerbach-Kotlikoff type, which distinguishes between five lifetime income classes within each age cohort. Our simulation results indicate that debt reduction increases the welfare of future generations between 1 and 2% of lifetime resources and that consumption taxes are preferable to the Eurotax on allocative grounds.

Our paper deals with the welfare and employment effects of green tax reforms. In the first part we develop a flexible, interactive simulation model which is accessible under http://brw.zew.de. Users can specify their own green tax reforms or emission quotas and quantify welfare and employment effects. He or she can choose between different model variants, e. g. closed or small open economies with or without unemployment. In the second part we describe the numerical model specifications and explain some simulation calculations by means of examples. Some exercises for classroom use are available on the above mentioned web-site.

This paper complements and extends an article by FELDER and SCHLEINIGER (FS) previously published in this journal. We show that the results of FS depend crucially on parameter values. Furthermore we perform simulations of optimal tax reforms in the context of the FS-framework, differentiating between public finance and ecological aspects. More generally, our paper stresses the need for more economic reasoning in computational economics.

This paper shows that increases in direct tax progression tend to reduce wages and increase welfare and employment, even in a model allowing for labour supply effects. The employment effect is reversed when benefit levels are low, however. The model shows the different impacts on full- and part-time workers, and on men and women. An a.g.e. model for the UK is also simulated, with an efficiency wage sector with training costs generating unemployment effects.

A prospective study of 1004 consecutive deliveries was carried out to investigate the effect of passive smoking during pregnancy on a set of perinatal parameters. The data set was a cooperative study involving 11 Italian cities, distributed nationally. The study group was divided in three categories according to the mother's cigarette smoke exposure during pregnancy, ie, not smokers, passive smokers, direct smokers. Potential confounders, including paternal characteristics, were adjusted for by multiple linear regression analysis. A mean reduction of 16 g (p less than 0.07) in birthweight and a decrease in birth length of 0.05 cm (p less than 0.08) were found for each hour of antenatal passive smoke exposure. No or slight effects were reported for the other perinatal parameters considered.