BACKGROUND In elite sports, the growing availability of doping substances identical to those naturally produced by the human body seriously limits the ability of drug-testing regimes to ensure fairness and protection of health. CONTENT The Athlete Biological Passport (ABP), the new paradigm in testing based on the personalized monitoring of biomarkers of doping, offers the enormous advantage of being independent of this endless pharmaceutical race. Doping triggers physiological changes that provide physiological enhancements. In the same way that disease-related biomarkers are invaluable tools that assist physicians in the diagnosis of pathology, specifically selected biomarkers can be used to detect doping. SUMMARY The ABP is a new testing paradigm with immense potential value in the current climate of rapid advancement in biomarker discovery. In addition to its original aim of providing proof of a doping offense, the ABP can also serve as a platform for a Rule of Sport, with the presentation before competition of the ABP to objectively demonstrate that the athlete will participate in a healthy physiological condition that is unaltered by performance-enhancing drugs. Finally, the decision-support system used today for the biological monitoring of world top-level athletes can also be advantageously transferred to other areas of clinical practice to reach the goal of personalized medicine.

In the fight against doping, disciplinary sanctions have up to now been primarily based on the discovery of an exogenous substance in a biological fluid of the athlete. However, indirect markers of altered erythropoiesis can provide enough evidence to differentiate between natural variations and blood doping. Forensic techniques for the evaluation of the evidence, and more particularly Bayesian networks, allow antidoping authorities to take into account firstly the natural variations of indirect markers - through a mathematical formalism based on probabilities - and secondly the complexity due to the multiplicity of causes and confounding effects - through a distributed and flexible graphical representation. The information stored in an athlete's biological passport may be then sufficient to launch a disciplinary procedure against the athlete. The strength of the passport is that it relies on a statistical approach based on sound empirical testing on large populations and justifiable protocols. Interestingly, its introduction coincides with the paradigm shift that is materializing today in forensic identification science, from archaic assumptions of absolute certainty and perfection to a more defensible empirical and probabilistic foundation.

Using numerical simulations we investigate how overall dimensions of random knots scale with their length. We demonstrate that when closed non-self-avoiding random trajectories are divided into groups consisting of individual knot types, then each such group shows the scaling exponent of Ϸ0.588 that is typical for self-avoiding walks. However, when all generated knots are grouped together, their scaling exponent becomes equal to 0.5 (as in non-self-avoiding random walks). We explain here this apparent paradox. We introduce the notion of the equilibrium length of individual types of knots and show its correlation with the length of ideal geometric representations of knots. We also demonstrate that overall dimensions of random knots with a given chain length follow the same order as dimensions of ideal geometric representations of knots.

We developed a test that compares sequential measurements of a biomarker against previous readings performed on the same individual. A probability mass function expresses prior information on interindividual variations of intraindividual parameters. Then, the model progressively integrates new readings to more accurately quantify the characteristics of the individual. This Bayesian framework generalizes the two main approaches currently used in forensic toxicology for the detection of abnormal values of a biomarker. The specificity is independent of the number n of previous test results, with a model that gradually evolves from population-derived limits when n = 0 to individual-based cutoff thresholds when n is large. We applied this model to detect abnormal values in an athlete's steroid profile characterized by the testosterone over epitestosterone (T/E) marker. A cross-validation procedure was used for the estimation of prior densities as well as model validation. The heightened sensitivity/specificity relation obtained on a large data set shows that longitudinal monitoring of an athlete's steroid profile may be used efficiently to detect the abuse of testosterone and its precursors in sports. Mild assumptions make the model interesting for other areas of forensic toxicology.

tHb-mass shows very low individual oscillations during a training year (<6%), and these oscillations are below the expected changes in tHb-mass due to Herythropoetin (EPO) application or blood infusion (approximately 10%). The high stability of tHb-mass over a period of 1 year suggests that it should be included in an athlete's biological passport and analyzed by recently developed probabilistic inference techniques that define subject-based reference ranges.

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BACKGROUND No reliable estimate of the prevalence of doping in elite sports has been published. Since 2001, the international governing body for athletics has implemented a blood-testing program to detect altered hematological profiles in the world's top-level athletes. METHODS A total of 7289 blood samples were collected from 2737 athletes out of and during international athletic competitions. Data were collected in parallel on each sample, including the age, sex, nationality, and birth date of the athlete; testing date; sport; venue; and instrument technology. Period prevalence of blood-doping in samples was estimated by comparing empirical cumulative distribution functions of the abnormal blood profile score computed for subpopulations with stratified reference cumulative distribution functions. RESULTS In addition to an expected difference between endurance and nonendurance athletes, we found nationality to be the major factor of heterogeneity. Estimates of the prevalence of blood doping ranged from 1% to 48% for subpopulations of samples and a mean of 14% for the entire study population. Extreme cases of secondary polycythemia highlighted the health risks associated with blood manipulations. CONCLUSIONS When applied at a population level, in this case the population of samples, hematological data can be used to estimate period prevalence of blood doping in elite sports. We found that the world's top-level athletes are not only heterogeneous in physiological and anthropometric factors but also in their doping behavior, with contrasting attitudes toward doping between countries. When applied at the individual level, the same biomarkers, as formalized in the Athlete Biological Passport paradigm, can be used in analysis of the observed different physiological characteristics and behavioral heterogeneities.