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

Precision measurement of the ratio of the Lambda(0)(b) to (B)over-bar(0) lifetimes

The LHCb measurement of the lifetime ratio of the Lambda(0)(b) baryon to the (B) over bar (0) meson is updated using data corresponding to an integrated luminosity of 3.0 fb(-1) collected using 7 and 8 TeV centre-of-mass energy pp collisions at the LHC. The decay modes used are Lambda(0)(b) -> J/psi pK(-) and (B) over bar (0) -> J/psi pi K-+(-), where the pi K-+(-) mass is consistent with that of the (K) over bar*(0)(892) meson. The lifetime ratio is determined with unprecedented precision to be 0.974 +/- 0.006 +/- 0.004, where the first uncertainty is statistical and the second systematic. This result is in agreement with original theoretical predictions based on the heavy quark expansion. Using the current world average of the (B) over bar (0) lifetime, the Lambda(0)(b) lifetime is found to be 1.479 +/- 0.009 +/- 0.010 ps. (C) 2014 The Authors. Published by Elsevier B.V

A study of CP violation in B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays with D -> (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes B-+/- -> [(KSK +/-)-K-0 pi(-/+)](D)h(+/-) and B-+/- -> [(KSK +/-)-K-0 pi(-/+)](D)h(+/-), where h labels a K or pi meson and D labels a D-0 or (D) over bar (0) meson, is performed. The analysis uses the LHCb data set collected in pp collisions, corresponding to an integrated luminosity of 3 fb(-1). The analysis is sensitive to the CP-violating CKM phase gamma through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of gamma using other decay modes. (C) 2014 The Authors. Published by Elsevier B.V