Frequency dependance of electromechanical properties of PZN-xPT single crystals

In this paper, the frequency behaviour of electro-mechanical properties of PZN-xPT single crystals with compositions close to the morphotropic phase boundary is studied at frequencies up to 100MHz. Properties are deduced from the fit of the electrical input impedance, theoretically calculated with the KLM equivalent circuit model, to experimental data. To measure the electrical impedance of a crystal, its surfaces have first to be metallized. For very thin samples, this metallization may influence the resonances and alter the property identification. A theoretical study is thus performed to quantify the influence of the electrodes on the crystal vibrations. The results show that, even for high frequencies, their effects are negligible. In a second part, the evolution with frequency of the single crystal characteristics is studied. The properties are obtained in a frequency bandwidth centered on the resonances, from the fundamental to the 21(th) harmonic. The study shows the stability of the electromechanical properties versus the frequency. Finally, the mechanical and dielectric loss tangents are quantified

Economic evaluation of health consequences of prenatal methylmercury exposure in France

<p>Abstract</p> <p>Background</p> <p>Evidence of a dose–response relationship between prenatal exposure to methylmercury (MeHg) and neurodevelopmental consequences in terms of IQ reduction, makes it possible to evaluate the economic consequences of MeHg exposures.</p> <p>Objective</p> <p>To perform an economic evaluation of annual national benefits of reduction of the prenatal MeHg exposure in France.</p> <p>Methods</p> <p>We used data on hair-Hg concentrations in French women of childbearing age (18–45 years) from a national sample of 126 women and from two studies conducted in coastal regions (n = 161and n = 503). A linear dose response function with a slope of 0.465 IQ point reduction per μg/g increase in hair-Hg concentration was used, along with a log transformation of the exposure scale, where a doubling of exposure was associated with a loss of 1.5 IQ points. The costs calculations utilized an updated estimate of €₂₀₀₈ 17,363 per IQ point decrement, with three hypothetical exposure cut-off points (hair-Hg of 0.58, 1.0, and 2.5 μg/g).</p> <p>Results</p> <p>Because of higher exposure levels of women in coastal communities, the annual economic impacts based on these data were greater than those using the national data, i.e. € 1.62 billion (national), and € 3.02 billion and € 2.51 billion (regional), respectively, with the linear model, and € 5.46 billion (national), and € 9.13 billion and € 8.17 billion (regional), with the log model, for exposures above 0.58 μg/g.</p> <p>Conclusions</p> <p>These results emphasize that efforts to reduce MeHg exposures would have high social benefits by preventing the serious and lifelong consequences of neurodevelopmental deficits in children.</p

Integrated clinical and omics approach to rare diseases: novel genes and oligogenic inheritance in holoprosencephaly

Kim et al. identify novel genes and disease pathways in the forebrain developmental disorder holoprosencephaly, and show that many cases involve oligogenic inheritance. The findings underline the roles of Sonic Hedgehog and primary cilia in forebrain development, and show that integrating clinical phenotyping into genetic studies can uncover relevant mutations.Holoprosencephaly is a pathology of forebrain development characterized by high phenotypic heterogeneity. The disease presents with various clinical manifestations at the cerebral or facial levels. Several genes have been implicated in holoprosencephaly but its genetic basis remains unclear: different transmission patterns have been described including autosomal dominant, recessive and digenic inheritance. Conventional molecular testing approaches result in a very low diagnostic yield and most cases remain unsolved. In our study, we address the possibility that genetically unsolved cases of holoprosencephaly present an oligogenic origin and result from combined inherited mutations in several genes. Twenty-six unrelated families, for whom no genetic cause of holoprosencephaly could be identified in clinical settings [whole exome sequencing and comparative genomic hybridization (CGH)-array analyses], were reanalysed under the hypothesis of oligogenic inheritance. Standard variant analysis was improved with a gene prioritization strategy based on clinical ontologies and gene co-expression networks. Clinical phenotyping and exploration of cross-species similarities were further performed on a family-by-family basis. Statistical validation was performed on 248 ancestrally similar control trios provided by the Genome of the Netherlands project and on 574 ancestrally matched controls provided by the French Exome Project. Variants of clinical interest were identified in 180 genes significantly associated with key pathways of forebrain development including sonic hedgehog (SHH) and primary cilia. Oligogenic events were observed in 10 families and involved both known and novel holoprosencephaly genes including recurrently mutated FAT1, NDST1, COL2A1 and SCUBE2. The incidence of oligogenic combinations was significantly higher in holoprosencephaly patients compared to two control populations (P < 10(9)). We also show that depending on the affected genes, patients present with particular clinical features. This study reports novel disease genes and supports oligogenicity as clinically relevant model in holoprosencephaly. It also highlights key roles of SHH signalling and primary cilia in forebrain development. We hypothesize that distinction between different clinical manifestations of holoprosencephaly lies in the degree of overall functional impact on SHH signalling. Finally, we underline that integrating clinical phenotyping in genetic studies is a powerful tool to specify the clinical relevance of certain mutations.Molecular Technology and Informatics for Personalised Medicine and Healt