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Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain–hindbrain malformation known as the ‘molar tooth sign’. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci. We previously identified the INPP5E gene as causative of JSRD in seven families linked to the JBTS1 locus, yet the phenotypic spectrum and prevalence of INPP5E mutations in JSRD and MKS remain largely unknown. To address this issue, we performed INPP5E mutation analysis in 483 probands, including 408 JSRD patients representative of all clinical subgroups and 75 MKS fetuses. We identified 12 different mutations in 17 probands from 11 JSRD families, with an overall 2.7% mutation frequency among JSRD. The most common clinical presentation among mutated families (7/11, 64%) was Joubert syndrome with ocular involvement (either progressive retinopathy and/or colobomas), while the remaining cases had pure JS. Kidney, liver and skeletal involvement were not observed. None of the MKS foetuses carried INPP5E mutations, indicating that the two ciliopathies are not allelic at this locus., peer-reviewed

Pontine Tegmental Cap Dysplasia (PTCD) is a recently described, rare disorder characterized by a peculiar cerebellar and brainstem malformation. Nineteen patients have been reported to date, of which only one in the adolescent age, and data on the clinical, cognitive and behavioural outcome of this syndrome are scarce. Here we describe three adolescent patients with PTCD. All presented bilateral deafness and multiple cranial neuropathies, variably associated with skeletal, cardiac and gastro-intestinal malformations. Feeding and swallowing difficulties, that are often causative of recurrent aspiration pneumonias and death in the first years of life, completely resolved with age in all three patients. Neuropsychological assessment showed borderline to moderate cognitive impairment, with delay in adaptive functioning, visual-spatial and language deficits. Two of three patients also showed mild behavioural problems, although their overall socialization abilities were well preserved. Cochlear implantation in two patients significantly improved their relational and learning abilities. Fibre tractography confirmed the abnormal bundle of transversely oriented fibres forming the typical pontine "tegmental cap" and absence of decussation of the superior cerebellar peduncles, supporting the hypothesis that PTCD results from abnormal axonal guidance and/or migration. These data indicate that PTCD may have a favourable long-term outcome, with borderline cognitive deficit or even normal cognition and partially preserved speech.

With the enforcement of the Water Framework Directive 2000/60/EC (WFD), policy makers are required to pursue the improvement of the use efficiency of the water resources in the agricultural sector. For this purpose, we suggest a methodology to perform an ex-ante analysis of the efficiency of water pricing policies, based on a two stage DEA technique, by which it is possible to disaggregate the technical and the ecological efficiency of the policy. According to our results, we found that, coherently with the WFD principles, the direct pricing methods show the highest levels of efficiency. However, we have also found that some indirect pricing methods show relatively high levels of efficiency. Therefore, since the high cost for the management and implementation of water measurement devices required to apply the volumetric methods, indirect pricing methods might still be preferable.

With the enforcement of the Water Framework Directive 2000/60/EC (WFD), policy makers are required to pursue the improvement of the use efficiency of the water resources in the agricultural sector. For this purpose, we suggest a methodology to perform an ex-ante analysis of the efficiency of water pricing policies, based on a two stage DEA technique, by which it is possible to disaggregate the technical and the ecological efficiency of the policy. According to our results, we found that, coherently with the WFD principles, the direct pricing methods show the highest levels of efficiency. However, we have also found that some indirect pricing methods show relatively high levels of efficiency. Therefore, since the high cost for the management and implementation of water measurement devices required to apply the volumetric methods, indirect pricing methods might still be preferable.

In the last decades, problems related to environmental protection have become more and more important, involving a growing number of economic and social actors. The new role played by agriculture in this context requires not only innovations concerning policy instruments, but also an evolution of tools, such as those for environmental accounting and assessment, able to support the analysis of choices in a complex economic and technological context, characterised by a number of heterogeneous objectives. This paper illustrates a model (AGRI-ECO-AUDIT) set up with the aim of supporting decision making concerning the application of Reg. (EEC) 2078/92 in Emilia-Romagna (Italy). The aim is to verify the possible contribution of environmental accounting to environmental protection and improvement in agriculture and to identify policy strategies for the exploitation of such potentialities in order to improve agricultural and agri-environmental policies. The case study discussed here shows that the use of accounting tools for measuring and evaluating the multidimensional impact of policies and farming practices on the environment can improve considerably the information available for the decision maker, allowing a higher effectiveness of agri-environmental policy measures.

To determine the prevalence of antibodies against HCV in monoclonal gammopathies with and without cryoglobulinemic activity.201 patients were divided into two groups: (I) 94 patients with monoclonal gammopathies with cryoglobulinemic activity, and (II) 107 with monoclonal gammopathies without cryoglobulinemic activity. Cryoglobulins were characterized by immunofixation; HCVAb were detected using second-generation ELISA and RIBA methods; in 38 cases the presence of HCV in peripheral blood mononuclear cells was evaluated by PCR.The HCVAb prevalence, as evaluated by RIBA, in Group I was 69.1% while in Group II it was only 14.9%. Histological and immunohistochemical study of the bone marrow in Group I patients frequently showed signs of nodular B-cell clonal expansion.Our data confirm the existence of a close correlation between HCV infection and the monoclonal gammopathies with cryoglobulinemic activity. HCV-positive cryoglobulinemic is characterized by self-limiting IgM monoclonal expansion associated with histological aspects of bone marrow lymphoid nodules that do not expand in the course of the disease like classic evolving lymphoproliferative processes.