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Mutations in the ganglioside-induced differentiation associated-protein 1 (GDAP1) gene have been associated with both autosomal recessive (AR) and dominant (AD) Charcot-Marie-Tooth (CMT) axonal neuropathy. The relative frequency of heterozygous, dominant mutations in Italian CMT is unknown. We investigated the frequency of dominant mutations in GDAP1 in a cohort of 109 axonal Italian patients by sequencing genomic DNA and search for copy number variations. We also explored correlations with clinical features. All cases had already been tested for variants in common axonal AD genes. Eight patients (7.3%) harbored five already reported heterozygous mutations in GDAP1 (p.Arg120Gly, p.Arg120Trp, p.His123Arg, p.Gln218Glu, p.Arg226Ser). Mutations had different penetrances in the families; the onset of symptoms is in the first decade and progression is slower than usually seen in GDAP1-related AR-CMT. We show that the relative frequency of mutations in GDAP was slightly higher than those observed in MFN2 and MPZ (7.3% vs 6.3% and 5.0%). The relatively milder clinical features and the quite indolent course observed are relevant for prognostic assessment. On the basis of our experience and the data reported here, we suggest GDAP1 as the first gene that should be analysed in Italian patients affected by CMT2.

Item does not contain fulltext AIM: Lamivudine is used as first line therapy in HIV-infected children. Yet, like many other paediatric drugs, its dose rationale has been based on limited clinical data, without thorough understanding of the effects of growth on drug disposition. Here we use lamivudine to show how a comprehensive population pharmacokinetic model can account for the influence of demographic covariates on exposure (i.e. AUC and Cmax ). METHODS: Data from three paediatric trials were used to describe the pharmacokinetics across the overall population. Modelling was based on a non-linear mixed effects approach. A stepwise procedure was used for covariate model building. RESULTS: A one compartment model with first order elimination best described the pharmacokinetics of lamivudine in children. The effect of weight on clearance (CL) and volume of distribution (V) was characterized by an exponential function, with exponents of 0.705 and 0.635, respectively. For a child with median body weight (17.6 kg), CL and V were 16.5 (95% CI 15.2, 17.7) l h(-)(1) and 46.0 (95% CI 42.4, 49.5) l, respectively. There were no differences between formulations (tablet and solution). The predicted AUC(0,12 h) after twice daily doses of 4 mg kg(-)(1) ranged from 4.44 mg l(-)(1) h for children 30 kg. CONCLUSIONS: The use of meta-analysis is critical to identify the correct covariate-parameter relationships, which must be assessed before a model is applied for predictive purposes (e.g. defining dosing recommendations for children). In contrast to prior modelling efforts, we show that the covariate distribution in the target population must be considered.

Southwestern Sicily is an area of infrequent seismic activity. Only an earthquake occurred in the Belice valley on 13 January 1968 is reported in the historic earthquake catalogues (see e.g. [1]) as severe event, that is characterized by moderate-high energy (M=6.5) and significant epicentral and local macroseismic intensities (Io=X and I=VII-VIII of the MCS scale). Nevertheless, some studies (e.g. [2]) suggest that probably at least two earthquakes struck this area, between the fourth century B.C. and the early Middle Ages, with energy able to damage and produce collapse in some temples of Selinunte. In this framework, we propose the use of non-invasive approaches in geoarchaeology for detecting and measuring structural damages in walls and foundations of Selinunte Acropolis, in order to identify any effects due to historic earthquakes. The methodology consists of an integration of landscape analysis, remote sensing and geophysical methods useful for dating important ancient seismic events. The intents of this multidisciplinary research are: 1) the detailed analysis of the most important structures and the landscape, also to assess kinematics behaviour of the masonry segments and their defects (cracks, disintegration of the original mortar, replacement of ashlars, etc.) and 2) the analysis of the seismic site response in order to assess potential amplification phenomena on the ground motion. The preliminary results seem to show significant residuals on the walls on the East side of the Acropolis, where also the geological and stratigraphical setting provide amplification effects in correspondence of frequency range typical of the earthquakes and for manmade structures.

Southwestern Sicily is an area of infrequent seismic activity; however, some studies carried out in the archaeological Selinunte site suggest that, between the fourth century BC and the early Middle Ages, probably at least two earthquakes strucked this area with enough energy to damage and cause the collapse and kinematics of much of the architecture of Selinunte. Take into account that, in 2008, a noninvasive archaeological prospection and traditional data gathering methods along the Acropolis north fortifications were carried out. Following these first studies, after about 10 years, a new geophysical campaign was carried out. This second campaign benefited from the application of modern technologies for the acquisition and processing of the point cloud data on the northern part of the Acropolis, like terrestrial laser scanning and unmanned aerial vehicle photogrammetry. In this paper, we present the application of these techniques and a strategy for their integration for the 3D modelling of buildings and cultural heritages. We show how the integration of data acquired independently by these two techniques is an added value able to overcome the intrinsic limits of the individual techniques. The application to Selinunte's Acropolis allowed it to highlight and measure with high accuracy fractures, dislocation, inclinations of walls, depressions of some areas and other interesting observations, which may be important starting points for future investigations.

In view of direct inkjet printing of low-cost sensors, we describe here the thermal printing of a thin film of a commercially available conjugated polymer (poly(3,4-ethylenedioxythiophene):polystyrene sulfonic acid, PEDOT:PSS). The printed film has been investigated by optical microscopy, AFM and cyclic voltammetry. The results have been compared to the ones obtained for a continuous film of the same polymer deposed by spin-coating. No appreciable differences were noted between the electrochemical behaviour of the two samples, indicating that the thermal printing of the polymer did not alter appreciably the material properties. Our findings indicate that the thermal printing route may be then a good alternative for the controlled deposition of thin films of conjugated polymers.