Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid : community-based randomized clinical trial in Italy and the Netherlands

Background: In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear.Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open.The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae.Methods/Design: This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information.We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis.Discussion: The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes.Trial registration: Italian trial: ClinicalTrials.gov Identifier: NCT01244347.Dutch trial: Dutch Trial Register ID: NTR3161

INVESTIGATING THE COMPUTATION OF SCALAR IMPLICATURES IN ITALIAN CHILDREN WITH DYSLEXIA: THE ROLE OF QUANTIFIER PROPERTIES

This paper investigates scalar implicatures (SIs) computation in dyslexia focusing on the role of the quantifier's semantic properties. We developed two protocols, a Statement Evaluation Task (SET) and a Truth Value Judgement Task, using two Italian quantifiers, alcuni (a cardinality quantifier) and qualche (a proportional quantifier), both corresponding to the English 'some'. The tasks were administered on 18 dyslexic children (10.6 y.o.), 18 age-matched controls (10.7 y.o.) and 18 adults (24.5 y.o.). Unlike the other groups, dyslexics showed a higher tendency to avoid the derivation of a SI. We propose that this is due to the processing limitations characterizing dyslexia and to the high cognitive costs imposed by SIs computation, especially in the SET, which, requiring access to encyclopaedic knowledge, is more cognitively demanding. Furthermore, in this task all groups showed longer latencies when the SI was licensed by alcuni: we propose that this is related to the semantic properties of this quantifier, whose interpretation requires the introduction of a new discourse referent corresponding to the intersection between two sets and associated with a specific cardinality property (at least two). This step increases the processing costs of implicature computation, exerting an effect that becomes tangible when the processing demands of the task are higher

The interplay of lithology, tectonics and climate in the morphology of Corsica

The morphology of the landscape on the island of Corsica in the western Mediterranean is transient with clear topographic asymmetry. The geology of the island can be divided into two units – Hercynian Corsica and Alpine Corsica, with contrasting lithology, climate and structural controls between them. Here, topographic analysis is used to assess the influence of each of these factors on landscape form. Disequilibrium in the landscape is illustrated by analysing chi and Gilbert metrics which indicate active drainage divide migration, along with a new metric that quantifies tributary heights above the main stem channel. Climate in the region has fluctuated dramatically from the Messinian salinity crisis through to Quaternary glaciation. However, analysis of the size and distribution of knickpoints across the island does not reflect specific base-level changes. Instead, basement structures control valley orientation and conditioning of the landscape by glaciation exerts strong controls on drainage evolution

Relationship between the intrahepatic expression of 'e' and 'c' epitopes of the nucleocapsid protein of hepatitis B virus and viraemia.

The relationship between hepatitis B viraemia and intrahepatic HBV nucleocapsid proteins (HBcAg and HBeAg) was studied in 18 patients with chronic hepatitis B. Monoclonal antibodies (MoABs) were obtained in BALB/c mice primed with recombinant HBV nucleocapsid proteins. Four MoABs reacting with recombinant proteins gave positive results in competitive assays. Two reacted as anti-HBc and two as anti-HBe. One of them showed a strong affinity for the cytoplasmic, membrane-bound antigen (P23e) of infected hepatocytes while the latter showed a higher specificity for serum HBeAg than for the intrahepatic antigen. Anti-HBc MoABs had a staining capacity for liver cell nuclei comparable with that of polyclonal antibodies. Overall the anti-HBc MoABs stained the liver cell nuclei in 86% of cases, while anti-HBe MoABs stained in 58% of cases. The hepatocyte cytoplasm was stained by anti-HBc MoABs and anti-HBe MoABs in 64% and 72% of cases respectively. Not one of 12 control liver biopsies was stained. Viraemia (HBV-DNA) was measured by dot blot hybridization and was correlated with the number of hepatocytes containing the nucleocapsid antigen. The highest levels of HBV-DNA (greater than 10(8) genomes/ml) were detected in patients with prevalent nuclear staining while the lowest ones were observed in those with prevalent cytoplasmic expression of this antigen. The application of anti-HBV-nucleocapsid MoABs in diagnostics requires careful scrutiny since some are specific for the circulating antigen while others show a higher affinity for the intrahepatic antigen