, Melissa Yssel, MB ChB, FC Path(SA) Chem 139, and Wendy M. Zakowicz, BS 79 Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration.

Purpose: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. Methods: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. Results: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events. Conclusions: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%

1. This study was to determine the effects of strain, age of the maternal flock and sex on morphological characteristics and composition of tibial bone of broilers from hatch to 48 d of age. 2. A total of 600 chicks was obtained from 2 strains of broiler breeder flocks (150/chicks/strain/maternal age). Maternal flock age was classified as young (32 to 35 weeks of age) or old (56 to 58 weeks of age). Birds were reared under standard feeding and lighting regimes. 3. On day 1, 16, 32 and 48, twelve birds were selected at random from each maternal group, strain and sex and killed. The wet bone weight and volume were measured. Morphological characteristics of tibia were determined using radiography. Bone breaking strength was tested. Tibia dry matter, ash content, mineral density and collagen level were determined. 4. A quadratic increase occurred with increase in age of broilers for all variables, except proximal width, medial cortex thickness and distal condyle width which increased in a linear manner. 5. Maternal age had a significant effect only on the variably measured at the time of hatch. On day of hatch bone weight, ash content and bone volume were affected by maternal age, but the extent of this also depended on the strain. 6. The differences observed between strains for bone anatomy and bone mineralisation during the rapid growth period of 16 d were not significant at later ages, with the exception of bone volume. Differences between sexes were evident from 16 to 49 d of age with females having lower values.

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Summary:The aim of this study was to observe membrane injury and to investigate the mechanism of antioxidant defence Systems against acute ethanol toxicity. Erythrocyte Superoxide dismutase and Na" 1 ", K^-ATPase activities were significantly decreased and catalase levels were significantly increased one hour after ethanol intoxication of male swiss albino rats. These data demonstrated that Superoxide dismutase and catalase are susceptible to lipid peroxidation and that these enzymes protect tissues from free radicals. The possible mechanism involved in Na + , K + -ATPase and Ca 2 " 1 "-ATPase Inhibition are discussed in relation to the development of ethanol toxicity and the role of lipid peroxidative processes.