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The presence of naturally occurring asbestos (NOA) in many areas worldwide requires an enhanced geological risk evaluation to ensure workplace safety from asbestos during large construction projects. Due to the complexity of the geological risk definition, health and safety regulations for working with asbestos-bearing materials are often not enforceable in NOA settings. Therefore, to correctly estimate the risk of NOA in these scenarios, new procedures are urgently needed to provide (1) a detailed geological model representative of the possible presence of the asbestos, (2) representative sampling, and (3) a reliable quantitative determination of asbestos content in rocks. This work aims to discuss the improvements on the two latter points specifically developed during the design of the “Gronda di Genova” project, a 50-km-long tunnel bypass partially designed in the NOA-bearing meta-ophiolites of the Ligurian Alps and ophiolites of the northern Apennines in Italy. Implementation of Gy's theory on sampling was used to maintain statistical validity during sample processing from the primary sample to the analytical sample and is here described. The scanning electron microscopy/energy dispersive spectroscopy procedure for the quantification of NOA was improved with an error analysis delivering the minimum number of fibers to be measured to achieve the best analytical results.

Asbestos may constitute a severe health risk when meta-ophiolites are excavated for large infrastructural projects. For public acceptance, a reliable estimation of the content of Naturally Occurring Asbestos (NOA) is necessary for the design of construction sites, workers' safety and spoil management. In the framework of a research project supporting the final design of a highway tunnel system in NW Italy, SEM-EDS (Scanning Electron Microscopy – Energy-Dispersive Spectrometry) quantitative analyses were performed to provide a direct NOA content estimation by counting and weighing the asbestos fibers in the rocks, after a chemical and geometrical characterization. The direct NOA content estimation was compared with an indirect estimation obtained through a fracture network modeling based on a structural survey on a selected outcrop and statistical analysis of a relative digital image. The fracture intensity, inferred from the fracture network model, was multiplied by coefficients deriving from the semi-quantitative estimation of the geological relations between asbestos mineral occurrence and fracture size, thickness and distribution. A good agreement between the indirect NOA estimation and the average result of the SEM-EDS analysis was obtained. Thus, the statistical analysis of the fracture network may represent a valuable support to the SEM-EDS quantitative analysis based on mineral fibers counting. However, the quality of the indirect NOA estimation depends on the postulates for inferring the coefficients describing the distribution and occurrence of the asbestos minerals within the fractures. This Note discusses the above-mentioned issues, as well as those concerning the procedure for a representative sampling of NOA-bearing rocks and fractures.

Naturally-Occurring Asbestos (NOA) may constitute a severe health risk when metamorphic rocks are excavated for large infrastructure projects. For public acceptance, a reliable assessment of the content of NOA is necessary for the design of the construction site, workers’ safety, and spoil management. Direct measurements of NOA content can be made by SEM-EDS analyses on an adequate number of samples. Such measurements are sufficiently precise but questions about the representativity of the samples may arise, especially when the rock units are structurally and lithologically complex. Therefore, in order to corroborate the direct assessments, alternative and indirect assessments can be performed by measuring the fracture volumetric porosity, provided that almost all the NOA is deposited as veins in the fractures of the rock mass. Statistical sampling and inference procedures can be applied to derive such an index. In this paper, an indirect assessment of NOA is reported and compared with the assessment obtained by direct measurements. The application is to a metamorphic rock formation through which a tunnel is to be driven as part of the ”Gronda di Genova” highway development in Genoa, Italy. Even though significant approximations are made, the indirect assessment is relatively close to the direct measurement.

For a reliable evaluation of the geo-environmental risk due to naturally occurring asbestos (NOA) during rock excavation of large infrastructure projects, a proper procedure is needed. First, it is necessary to provide a detailed geological model tailored to the NOA-related issues that should drive the rock sampling procedures in order to obtain a representative sampling. The sampling procedures should take into account lithological variability and relative spatial distributions of the rock units. The geological model for NOA should be thus constrained by the main NOA petrofacies occurring in a given geotectonic context, which take into consideration both the mineralogical and structural features, and the identification of NOA homogeneous zones in which the NOA petrofacies are distributed. In this paper, some geo-environmental problems faced during the excavation, in meta-ophiolites, of a long highway tunnel are described. The geological model of the complex setting of the tunnel area (northern Italy, Alps-Apennines junction) is described, focusing on how the NOA-related problems were addressed to allow reliable and detailed estimations of NOA contents for each NOA homogeneous zone and the relevant tunnel layout segment.

Objectives. The aim of this study was to define the features of chronic cryptogenic hepatitis (CCH) in childhood and to investigate whether it is related to hepatitis G virus infection. Methods. Forty-six children (24 males; age range, 1.5 to 17 years) with CCH were studied. CCH was diagnosed when serum alanine aminotransferase concentrations were more than 1.5 times normal for longer than 6 months without any apparent cause of liver disease. Results. No patient had acute symptomatic onset or had received a blood transfusion. Three had undergone minor surgical procedures. All appeared to be healthy during follow-up (median, 4.2 years; range, 1 to 10 years). Hypertransaminasemia was the only aberrant liver function test. Elevated serum alanine aminotransferase values alternated with normal values in 40 children (86.9%). Five children (10.8%) had a spontaneous sustained (>12 months) remission of hypertransaminasemia. Twelve (26%) had laboratory signs of autoimmunity, but none fulfilled the criteria for autoimmune hepatitis. Of 20 children who underwent liver biopsy, 13 (65%) had minimal chronic hepatitis, 4 (20%) had mild chronic hepatitis and 3 (15%) had moderate chronic hepatitis. Serum hepatitis G virus RNA was detected in 2 girls (4%) whose risk factor was a hepatitis G virus-infected mother and a minor surgical procedure, respectively. In 12 families at least 1 other member had chronic liver disease. Conclusions. Childhood CCH seems to be a symptomless disease characterized by isolated hypertransaminasemia with onset during the first 4 years of life and mild to moderate histologic liver lesions. Although the frequency of spontaneous remissions is low, childhood CCH seems, in the short run, to be a nonprogressive disease. Hepatitis G virus does not play a major role in CCH.

Background/Aims: Children with chronic hepatitis C were recently found to have higher rates of sustained response to interferon compared to adults. The aim of this study was to verify the response to interferon using frequent viremia measurements. Methods: Sera from 25 children (13 males; mean age 7.9 years) with chronic hepatitis C, treated with recombinant alpha-2b interferon for 12 months, were tested for liverfunction tests and viremia levels for a median of 27.5 months. Autoantibodies were evaluated during and after interferon. Results: Fifteen patients completed 12 months of interferon; treatment was stopped in 10 other patients. In 11 (44%) patients viremia was undetectable already at the second administration of interferon; one of them remained viremia-free up to the end of follow-up and had persistently normal alanine-amino-transferase levels (complete sustained responder). A complete sustained response was observed only in one other patient, who normalized alanine amino-transferase and cleared viremia from the 3rd month of therapy. Three patients with persistent viremia normalized alanine-aminotransferase from the 3rd week of therapy up to the end of follow-up (biochemical sustained responders). Viremia was undetectable during treatment in four patients, who stopped interferon because of worsening in hypertransaminasemia. Three of these four patients were anti-liver-kidney microsomal type 1-positive. Conclusions: In this study the response rate to interferon was very low and viremia and transaminase findings were often discordant.

Background. Interferon (IFN) is standard therapy for chronic viral hepatitis in children. The aim of this study was to evaluate the side effects of alpha-interferon (IFN) in 94 consecutive children (58 males; age range, 3 to 14 years) affected by chronic viral hepatitis treated with different schedules ranging from 3 to 10 MU and from 3 to 12 months, and the impact of this therapy on health-related quality of life. Methods. Side effects were evaluated with clinical and laboratory examinations and were recorded on a diary card. The health-related quality of life was evaluated with a modified version of the Sickness Impact Profile. Results. All patients experienced at least one adverse reaction to IFN treatment; 80% had more than five side effects.There were no life-threatening reactions. Three children experienced severe reactions (febrile seizure, severe hyper-transaminasemia and relapsing episodes of epistaxis, respectively) that required permanent IFN withdrawal. Another child had a febrile seizure requiring temporary IFN withdrawal. In seven children the neutrophil count fell below 1000/mm 3 and promptly increased when IFN was temporarily discontinued. The remaining children had mild or moderate clinical and/or laboratory adverse reactions. Age, sex, viral etiology of chronic hepatitis and response to therapy were not significantly associated with the appearance of side effects. The pre-IFN health-related quality of life was good in all children; it deteriorated significantly during IFN therapy and returned to basal standards within 3 months after IFN withdrawal. No patient required suspension of IFN therapy because of worsening of health-related quality of life. Conclusion. Children have a low risk of developing severe IFN-induced side effects. Adverse reactions and worsening of health-related quality of life were tolerable and did not seem to be a limiting factor for IFN therapy in young candidates.

Gene-expression programs modulated by transcription factors (TFs) mediate key developmental events. Here, we show that the synthetic transcriptional repressor (TR, ZF6-DB), designed to treat Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP), does not perturb murine retinal development, while maintaining its ability to block Rho expression transcriptionally. To express ZF6-DB into the developing retina, we pursued two approaches, (i) the retinal delivery (somatic expression) of ZF6-DB by Adeno-associated virus (AAV) vector (AAV-ZF6-DB) gene transfer during retinogenesis and (ii) the generation of a transgenic mouse (germ-line transmission, TR-ZF6-DB). Somatic and transgenic expression of ZF6-DB during retinogenesis does not affect retinal function of wild-type mice. The P347S mouse model of RHO-adRP, subretinally injected with AAV-ZF6-DB, or crossed with TR-ZF6-DB or shows retinal morphological and functional recovery. We propose the use of developmental transitions as an effective mode to challenge the safety of retinal gene therapies operating at genome, transcriptional, and transcript levels.