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Purpose: Internationally adopted variant interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) are generic and require disease-specific refinement. Here we developed CardioClassifier ( http://www.cardioclassifier.org ), a semiautomated decision-support tool for inherited cardiac conditions (ICCs)., Methods: CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules., Results: We benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules. A generic annotation tool identified fewer than half as many clinically actionable variants (64/219 vs. 156/219, Fisher's P = 1.1  ×  10 -18 ), with important false positives, illustrating the critical importance of disease and gene-specific annotations. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data., Conclusion: CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.

In three experiments with sixty 3- and 6-month-olds, we examined whether operant and visual-preference measures of retention are equivalent. Infants learned to move a mobile by kicking and then received a paired-comparison test with the familiar (training) mobile and a novel one. Kicking above baseline was the direct measure of retention, and longer looking at the novel mobile was the visual-preference or inferred measure. Retention was tested 1 day after training (Experiment 1) or reactivation (Experiment 2) and immediately or 4 days after training (Experiment 3). Despite differences in age and retention interval, infants consistently exhibited retention on the operant measure, but not on the visual-preference measure. These data reveal that the two measures of retention are not equivalent. When expectations are associated with a particular stimulus, infants indicate retention directly and robustly, rarely looking longer at a novel test stimulus. This result is not limited to operant situations., (Copyright 2001 John Wiley & Sons, Inc.)

This research examined whether an expanding training series protracts retention for infants as it does for children and adults. In three sessions spanning an 8-day period, 3-month-olds learned to move a crib mobile by kicking. Intersession intervals were either constant (1 or 4 days) or progressively expanding (average ISI = 4 days). The expanding-series group exhibited significant retention on a delayed recognition test 3 weeks after training was over, but the two constant-series groups exhibited none. Although the 1-day constant-series group remembered after 1 week, the 4-day constant-series group did not. Surprisingly, a reactivation treatment administered 4 weeks after training was over was ineffective whether infants were trained, reminded, and tested in a distinctive context or not. These results demonstrate that the retention advantage afforded by programming training sessions in an expanding series extends to infants and suggest that the upper limit on reactivation is timed from initial encoding and not from the point of forgetting.

Discontinuous vertical gel electrophoresis was applied to samples of root canal aspirate, periapical blood, and control blood from twelve periapical lesions. The periapical sample from ten of the twelve lesions showed an additional band in the alpha 1 globulin area which was not present in the control. By means of Grabbar-Williams immunoelectrophoresis to specific antisera, the band was subsequently identified as alpha 1 antitrypsin. The results suggest that the regulation of proteolytic activity afforded by alpha 1 antitrypsin plays an important role in the pathogenesis of periapical lesions.