Comparison of normal distribution–based and nonparametric decision limits on the GH‐2000 score for detecting growth hormone misuse (doping) in sport

This paper is motivated by the GH‐2000 biomarker test, though the discussion is applicable to other diagnostic tests. The GH‐2000 biomarker test has been developed as a powerful technique to detect growth hormone misuse by athletes, based on the GH‐2000 score. Decision limits on the GH‐2000 score have been developed and incorporated into the guidelines of the World Anti‐Doping Agency (WADA). These decision limits are constructed, however, under the assumption that the GH‐2000 score follows a normal distribution. As it is difficult to affirm the normality of a distribution based on a finite sample, nonparametric decision limits, readily available in the statistical literature, are viable alternatives. In this paper, we compare the normal distribution–based and nonparametric decision limits. We show that the decision limit based on the normal distribution may deviate significantly from the nominal confidence level or nominal FPR when the distribution of the GH‐2000 score departs only slightly from the normal distribution. While a nonparametric decision limit does not assume any specific distribution of the GH‐2000 score and always guarantees the nominal confidence level and FPR, it requires a much larger sample size than the normal distribution–based decision limit. Due to the stringent FPR of the GH‐2000 biomarker test used by WADA, the sample sizes currently available are much too small, and it will take many years of testing to have the minimum sample size required, in order to use the nonparametric decision limits. Large sample theory about the normal distribution–based and nonparametric decision limits is also developed in this paper to help understanding their behaviours when the sample size is large.     

The trace and major element composition of the leaves of some deciduous trees

Summary The contents of 21 trace and major constitutents in the leaves or leaf blades of three species of deciduous trees, sycamore, horse-chestnut and beech, have been studied at regular intervals throughout the season. The various elements can be grouped into three categories: (A) Co, Ni, Fe, V, Ti, Cr, Pb and Al, (B) Mn, B, Si, Ca, Sr, Ba, and Mg, and (C) Cu, Mo, Zn, P, K, and Na. The Group-A elements, including most of those whose essentiality has not been established, together with Fe, show a fall in concentration in the leaf early in the season, probably as a result of dilution due to increase in dry weight as the absolute amount per leaf rises slightly, followed by steady rise until senescence, when a further fall occurs. In Group B, in which Si Sr, and Ba are considered non-essential, there is a continual rise both in concentration and absolute content until late in the season. In Group C, all the elements of which, except possibly Na, are essential, there is generally a gradual fall followed by a period when the content remains relatively constant, although Na and Zn, together with Pb from Group A, show an unexpected increase at senescence.Group-A elements show a decrease in concentration with height, which can only partly be explained by dilution due to increase in dry weight with height, while Group-B and -C elements are relatively constant at all heights. Results are also presented for some petioles and inflorescences. There does not appear to be any systematic transfer from leaf to inflorescence at any stage of growth. The only elements whose contents could be used systematically for diagnostic purposes appear to be those in Group C, during the midseason period of constant concentration.     

Purification and characterization of an acidic trypsin/subtilisin inhibitor from tortoise egg white

Egg whites of three species of tortoise and turtle have been compared by gel chromatography for inhibitory activity against proteases. The egg white of Geomda trijuga trijuga Schariggar contains trypsin/subtilisin inhibitor while the egg white of Caretta caretta Linn. contains both trypsin and chymotrypsin inhibitors. No protease inhibitory activity has been detected in the egg white of Trionyx gangeticus Cuvier. An acidic trypsin/subtilisin inhibitor has been purified to homogeneity from the egg white of tortoise (G. trijuga trijuga). It is a single polypeptide chain of 100 amino acid residues, having a molecular weight of 11 700. It contains six disulphide bonds and is devoid of methionine and carbohydrate moiety. Its isoelectric point is at pH 5.95 and is stable at 100°C for 4 h at neutral pH. The inhibitor inhibits both trypsin and subtilisin by forming enzyme-inhibitor complexes at a molar ratio close to unity. Their dissociation contants are 7.2·10^?9 M for bovine trypsin adn 5.5·10^?7 M for subtilisin. Chemical modification of amino groups with trinitrobenzene sulfonate has reduced its inhibitory activities against both trypsin and subtilisin, but the loss of its trypsin inhibitory activity is faster than of its subtilisin inhibitory activity. It has independent binding sites for inhibition of trypsin and subtilisin.