Clinical and Genotypical Features of False-Negative Patients in 26 Years of Cystic Fibrosis Neonatal Screening in Tuscany, Italy.

Cystic fibrosis (CF) is a life-threatening and common genetic disorder. Cystic fibrosis newborn screening (CF NBS) has been implemented in many countries over the last 30 years, becoming a widely accepted public health strategy in economically developed countries. False-negative (FN) cases can occur after CF NBS, with the number depending on the method. We evaluated the delayed diagnosis of CF, identifying the patients who had false-negative CF NBS results over 26 years (1992-2018) in Tuscany, Italy. The introduction of DNA analysis to the newborn screening protocol improved the sensitivity of the test and reduced the FNs. Our experience showed that, overall, at least 8.7% of cases of CF received FNs (18 cases) and were diagnosed later, with an average age of 6.6 years (range: 4 months to 22 years). Respiratory symptoms and salt-loss syndrome (metabolic hypochloremic alkalosis) are suggestive symptoms of CF and were commons events in FN patients. In Tuscany, a region with a high CFTR allelic heterogeneity, the salt-loss syndrome was a common event in FNs. Therefore, we provided evidence to support the claim that the FN patients had CFTR mutations rarer compared with the true-positive cases. We underline the importance of vigilance toward clinical manifestations suggestive of CF on the part of the primary care providers and hospital physicians in a region with an efficient newborn screening program

Where Does Europe End? Christian Democracy and the Expansion of Europe *

In this article, we argue that an analysis of the conflict around the nature and limits of European integration that arose between Catholic and Protestant Christian Democrats in the post-war era can shed new light on the expansionary dynamics that gradually came to characterize the project of European integration. Catholic Christian Democrats framed the unification of Europe as a relatively exclusionary cultural-civilizational endeavour, while Protestant Christian Democrats favoured a more inclusive conception of Europe that prioritised free trade over cultural homogeneity. Focusing specifically on Germany, we suggest that the eventual resolution of the intra-party struggle between the two camps in the early 1970s was a crucial enabler for including more and more countries into the European project. For it was only thereafter that Catholic Christian Democrats began supporting the expansion of European integration beyond the core Europe of the original Six, with geopolitical concerns gradually crowding out cultural ones.