Enhanced interpretation of newborn screening results without analyte cutoff values

A collaboration among 157 newborn screening programs in 47 countries has lead to the creation of a database of 705,333 discrete analyte concentrations from 11,462 cases affected with 57 metabolic disorders, and from 631 heterozygotes for 12 conditions. This evidence was first applied to establish disease ranges for amino acids and acylcarnitines, and clinically validate 114 cutoff target ranges. Objective: To improve quality and performance with an evidence-based approach, multivariate pattern recognition software has been developed to aid in the interpretation of complex analyte profiles. The software generates tools that convert multiple clinically significant results into a single numerical score based on overlap between normal and disease ranges, penetration within the disease range, differences between specific conditions, and weighted correction factors. Design: Eighty-five on-line tools target either a single condition or the differential diagnosis between two or more conditions. Scores are expressed as a numerical value and as the percentile rank among all cases with the condition chosen as primary target, and are compared to interpretation guidelines. Tools are updated automatically after any new data submission (2009- 2011: 5.2 new cases added per day on average). Main outcome measures: Retrospective evaluation of past cases suggest that these tools could have avoided at least half of 277 false positive outcomes caused by carrier status for fatty acid oxidation disorders, and could have prevented 88% of false negative events caused by cutoff 7 values set inappropriately. In Minnesota, their prospective application has been a major contributing factor to the sustained achievement of a false positive rate below 0.1% and a positive predictive value above 60%. Conclusions: Application of this computational approach to raw data could make cutoff values for single analytes effectively obsolete. This paradigm is not limited to newborn screening and is applicable to the interpretation of diverse multi-analyte profiles utilized in laboratory medicine. Abstract wor

Has the Historian’s craft gone digital? Some observations from France

Since the end of the 1980s the historiographical context has changed considerably. Over the course of the last ten years, we have reached the “digital age” and computers as well as resources available via the Internet have become indispensable tools for all researchers. Be it for the stage of documentation or for actual writing, we are now living and working in a context where historians can no longer completely refuse all IT tools. As long as there are no solid, durable, large-scale training efforts to equip all historians with the skills to use the new and old IT tools, their potential is necessarily limited. While there have been studies on “researchers” in general and also on political scientists in particular, there has, to our knowledge, been no scientific study which would allow us to reach conclusions on the use of IT tools and digital resources by French historians. It is thus difficult to reach conclusions on a larger scale and we have decided to base our analysis on our own experience in order to consider what could be the transformations of the historian’s craft in the digital age. We will thus proceed first to a series of conclusions based on our activities in mediation (teaching and blogging), before proposing a typology of the principal evolutions. We will conclude with a certain number of propositions as far as training of historians is concerned