School of Mathematics and Statistics - Research Publications
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ItemEvaluation of blood parameters by linear discriminant models for the detection of testosterone administration(WILEY, 2021-07)The steroidal module of the Athlete Biological Passport (ABP) has been used since 2014 for the longitudinal monitoring of urinary testosterone and its metabolites to identify samples suspicious for the use of synthetic forms of Endogenous Anabolic Androgenic Steroids (EAAS). Multiple recent studies have suggested that monitoring of blood parameters may provide enhanced detectability of exogenous testosterone administration. Transdermal and intramuscular testosterone administration studies were carried out in 15 subjects, and the effect on blood steroidal levels, hematological parameters, and gonadotropins was evaluated. Serum testosterone and dihydrotestosterone levels increased while gonadotropin levels were suppressed after administration. A modest increase in reticulocytes was also observed. The blood parameters that were responsive to the administrations were combined into several linear discriminant models targeting both administration (on) and washout (off) phases. The models were effective in detecting the large dose intramuscular administration but were less successful in the detection of the lower dose transdermal application. The blood profiling models may provide complementary value but do not appear to be substantially more advantageous than longitudinal urinary profiling.
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ItemThe athlete's hematological response to hypoxia: A meta-analysis on the influence of altitude exposure on key biomarkers of erythropoiesis(WILEY, 2018-01)Altitude training is associated with changes in blood markers, which can confound results of the Athlete?s Biological Passport (ABP). This meta-analysis aims to describe the fluctuations during- and post-altitude in key ABP variables; hemoglobin concentration ([Hb]), square-root transformed reticulocyte percentage (sqrt(retic%)) and the OFF-score. Individual de-identified raw data were provided from 17 studies. Separate linear mixed effects analyses were performed for delta values from baseline for [Hb], sqrt(retic%) and OFF-score, by altitude phase (during and post). Mixed models were fitted with the hierarchical structure: study and subject within study as random effects. Delta values as response variables and altitude dose (in kilometer hours; km.hr = altitude (m) / 1000 x hours), sex, age, protocol and baseline values as fixed effects. Allowances were made for potential autocorrelation. Within two days at natural altitude [Hb] rapidly increased. Subsequent delta [Hb] values increased with altitude dose, reaching a plateau of 0.94 g/dL [95%CI (0.69, 1.20)] at ~1000 km.hr. Delta sqrt(retic%) and OFF-score were the first to identify an erythrocyte response, with respective increases and decreases observed within 100 to 200 km.hr. Post-altitude, [Hb] remained elevated for two weeks. Delta sqrt(retic%) declined below baseline, the magnitude of change was dependent on altitude dose. Baseline values were a significant covariate (p<0.05). The response to altitude is complex resulting in a wide range of individual responses, influenced primarily by altitude dose and baseline values. Improved knowledge of the plausible hematological variations during- and post-altitude provides fundamental information for both the ABP expert and sports physician.
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ItemAltitude training and haemoglobin mass from the optimised carbon monoxide rebreathing method determined by a meta-analysis(BMJ PUBLISHING GROUP, 2013-12)OBJECTIVE: To characterise the time course of changes in haemoglobin mass (Hbmass) in response to altitude exposure. METHODS: This meta-analysis uses raw data from 17 studies that used carbon monoxide rebreathing to determine Hbmass prealtitude, during altitude and postaltitude. Seven studies were classic altitude training, eight were live high train low (LHTL) and two mixed classic and LHTL. Separate linear-mixed models were fitted to the data from the 17 studies and the resultant estimates of the effects of altitude used in a random effects meta-analysis to obtain an overall estimate of the effect of altitude, with separate analyses during altitude and postaltitude. In addition, within-subject differences from the prealtitude phase for altitude participant and all the data on control participants were used to estimate the analytical SD. The 'true' between-subject response to altitude was estimated from the within-subject differences on altitude participants, between the prealtitude and during-altitude phases, together with the estimated analytical SD. RESULTS: During-altitude Hbmass was estimated to increase by ∼1.1%/100 h for LHTL and classic altitude. Postaltitude Hbmass was estimated to be 3.3% higher than prealtitude values for up to 20 days. The within-subject SD was constant at ∼2% for up to 7 days between observations, indicative of analytical error. A 95% prediction interval for the 'true' response of an athlete exposed to 300 h of altitude was estimated to be 1.1-6%. CONCLUSIONS: Camps as short as 2 weeks of classic and LHTL altitude will quite likely increase Hbmass and most athletes can expect benefit.
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ItemWithin-Subject Variation in Hemoglobin Mass in Elite Athletes(LIPPINCOTT WILLIAMS & WILKINS, 2012-04)UNLABELLED: Illicit autologous blood transfusion to improve performance in elite sport is currently undetectable, but the stability of longitudinal profiles of an athlete's hemoglobin mass (Hbmass) might be used to detect such practices. PURPOSE: Our aim was to quantify within-subject variation of Hbmass in elite athletes, and the effects of potentially confounding factors such as reduced training or altitude exposure. METHODS: A total of 130 athletes (43 females and 87 males) were measured for Hbmass an average of six times during a period of approximately 1 yr using carbon monoxide rebreathing. Linear mixed models were used to quantify within-subject variation of Hbmass and its associated analytical and biological components for males and females, as well as the effects of reduced training and moderate altitude exposure in certain athletes. RESULTS: The maximum within-subject coefficient of variation (CV) for Hbmass was 3.4% for males and 4.0% for females. The analytical CV was ~2.0% for both males and females, and the long-term biological CV, after allowing for analytical variation, was 2.8% for males and 3.5% for females. On average, self-reported reduced training resulted in a 2.8% decrease in Hbmass and altitude exposure increased Hbmass by 1.5% to 2.9%, depending on the duration and type of exposure. CONCLUSIONS: The within-subject CV for Hbmass of ~4% indicates that athletes may experience changes up to ~20% with a 1-in-1000 probability. Changes of this magnitude for measures taken a few months apart suggest that Hbmass has a limited capacity to detect autologous blood doping. However, changes in Hbmass may be a useful indicator when combined with other measures of blood manipulation.
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ItemExponential random graph (p*) models for affiliation networks(ELSEVIER SCIENCE BV, 2009-01)