Analytical aspects in doping control: challenges and perspectives

Since the first anti-doping tests in the 1960s, the analytical aspects of the testing remain challenging. The evolution of the analytical process in doping control is discussed in this paper with a particular emphasis on separation techniques, such as gas chromatography and liquid chromatography. These approaches are improving in parallel with the requirements of increasing sensitivity and selectivity for detecting prohibited substances in biological samples from athletes. Moreover, fast analyses are mandatory to deal with the growing number of doping control samples and the short response time required during particular sport events. Recent developments in mass spectrometry and the expansion of accurate mass determination has improved anti-doping strategies with the possibility of using elemental composition and isotope patterns for structural identification. These techniques must be able to distinguish equivocally between negative and suspicious samples with no false-negative or false-positive results. Therefore, high degree of reliability must be reached for the identification of major metabolites corresponding to suspected analytes. Along with current trends in pharmaceutical industry the analysis of proteins and peptides remains an important issue in doping control. Sophisticated analytical tools are still mandatory to improve their distinction from endogenous analogs. Finally, indirect approaches will be discussed in the context of anti-doping, in which recent advances are aimed to examine the biological response of a doping agent in a holistic way.     

Making Visible the Invisible Act of Doping

This paper describes the construction of the visual space of surveillance by the global anti-doping apparatus, it is a space inhabited daily by professional cyclists. Two principal mechanisms of this apparatus will be discussed—the Whereabouts System and the Biological Passport; in order to illustrate how this space is constructed and how it visualises the invisible act of doping. These mechanisms act to supervise and govern the professional cyclist and work to classify them as either clean or dirty in terms of the use of prohibited doping substances or methods. Contrary to the analysis of liberal anti-doping scholars such as Hanstad, Loland and Møller this paper argues that Foucault’s Panopticon paradigm is a useful tool for the analysis of this apparatus. The Whereabouts System and Biological Passport are the instruments by which the anti-doping apparatus intensifies the construction of the space of surveillance in professional sport. This space of surveillance not only locates and makes visible the physical location of each individual cyclist, but it also makes visible their internal bodily functions, in this case the composition and the fluctuations of the composition of their blood. In making the cyclist visible the instruments do not allow the cause of doping, or the event of doping to be known or observed. Rather what they do is cast the body in terms of abnormalities of time, place or blood. In the case of an abnormality of the cyclist’s blood, the cause itself cannot be identified with any certainty, all that is made visible is a suggestion, or a probability, that doping may have occurred. The ultimate effects are twofold—an internalisation and continual monitoring of one’s self as well as by the authorities, and a radical change in the nature and the definition of the offence of doping. No longer is it positive evidence of doping that is punishable, but what becomes punishable is an abnormality, in the cyclist’s location, or their body, which suggests a probability that the invisible act of doping may have occurred. In the course of this process accepted manners of proving an offence by the use of scientific evidence and expert commentary are transformed. The Whereabouts System and the Biological Passport open up a new manner in which the invisible can be visualised. Through the discourse and the attendant commentary of the expert a new alliance between doping and the law is constructed. The result is a redistribution of the way in which the law visualises and treats the symptoms (the signifier) and the signified act of doping. The Whereabouts System and Biological Passport are the instruments by which the anti-doping apparatus intensifies the construction of the space of surveillance in professional sport. This space of surveillance not only locates and makes visible the physical location of each individual cyclist, but it also makes visible their internal bodily functions, in this case the composition and the fluctuations of the composition of their blood. In making the cyclist visible the instruments do not allow the cause of doping, or the event of doping to be known or observed. Rather what they do is cast the body in terms of abnormalities of time, place or blood. In the case of an abnormality of the cyclists’s blood, the cause itself cannot be identified with any certainty, all that is made visible is a suggestion, or a probability, that doping may have occurred. The ultimate effects are twofold—an internalisation and continual monitoring of one’s self as well as by the authorities, and a radical change in the nature and the definition of the offence of doping. No longer is it positive evidence of doping that is punishable, but what becomes punishable is an abnormality, in the cyclist’s location, or their body, which suggests a probability that the invisible act of doping may have occurred. In the course of this process accepted manners of proving an offence by the use of scientific evidence and expert commentary are transformed. The Whereabouts System and the Biological Passport open up a new manner in which the invisible can be visualised. Through the discourse and the attendant commentary of the expert a new alliance between doping and the law is constructed. The result is a redistribution of the way in which the law visualises and treats the symptoms (the signifier) and the signified act of doping     

Assessing Cumulative Disadvantage against Minority Female Defendants in State Courts

Abstract

Prior sentencing research, especially research on cumulative disadvantage, has mainly focused on the treatment of male defendants. Little attention has been paid to female defendants, particularly minority female defendants. Drawing on the selective chivalry, evil women, and focal concerns perspectives and using data from the 1990–2009 State Court Processing Statistics (SCPS), this paper investigates the impact of race/ethnicity for female defendants across individual and successive stages in the sentencing process. The results indicate that ethnicity does not operate via indirect or direct pathways, and therefore no evidence of cumulative disadvantage against Hispanic female defendants was detected. The results, however, do suggest that race operates through direct and indirect pathways to cause more punitive sentencing outcomes for Black female defendants compared to White female defendants, thus providing evidence of cumulative disadvantage against Black female defendants. Theoretical, research, and policy implications are discussed.     

A steroidomic approach for biomarkers discovery in doping control

Anti-doping authorities have high expectations of the athlete steroidal passport (ASP) for anabolic-androgenic steroids misuse detection. However, it is still limited to the monitoring of known well-established compounds and might greatly benefit from the discovery of new relevant biomarkers candidates. In this context, steroidomics opens the way to the untargeted simultaneous evaluation of a high number of compounds. Analytical platforms associating the performance of ultra-high pressure liquid chromatography (UHPLC) and the high mass-resolving power of quadrupole time-of-flight (QTOF) mass spectrometers are particularly adapted for such purpose. An untargeted steroidomic approach was proposed to analyse urine samples from a clinical trial for the discovery of relevant biomarkers of testosterone undecanoate oral intake. Automatic peak detection was performed and a filter of reference steroid metabolites mass-to-charge ratio (m/z) values was applied to the raw data to ensure the selection of a subset of steroid-related features. Chemometric tools were applied for the filtering and the analysis of UHPLC-QTOF-MS(E) data. Time kinetics could be assessed with N-way projections to latent structures discriminant analysis (N-PLS-DA) and a detection window was confirmed. Orthogonal projections to latent structures discriminant analysis (O-PLS-DA) classification models were evaluated in a second step to assess the predictive power of both known metabolites and unknown compounds. A shared and unique structure plot (SUS-plot) analysis was performed to select the most promising unknown candidates and receiver operating characteristic (ROC) curves were computed to assess specificity criteria applied in routine doping control. This approach underlined the pertinence to monitor both glucuronide and sulphate steroid conjugates and include them in the athletes passport, while promising biomarkers were also highlighted.     

The ideal subject distance for passport pictures

In an age of global combat against terrorism, the recognition and identification of people on document images is of increasing significance. Experiments and calculations have shown that the camera-to-subject distance - not the focal length of the lens - can have a significant effect on facial proportions. Modern passport pictures should be able to function as a reference image for automatic and manual picture comparisons. This requires a defined subject distance. It is completely unclear which subject distance, in the taking of passport photographs, is ideal for the recognition of the actual person. We show here that the camera-to-subject distance that is perceived as ideal is dependent on the face being photographed, even if the distance of 2m was most frequently preferred. So far the problem of the ideal camera-to-subject distance for faces has only been approached through technical calculations. We have, for the first time, answered this question experimentally with a double-blind experiment. Even if there is apparently no ideal camera-to-subject distance valid for every face, 2m can be proposed as ideal for the taking of passport pictures. The first step would actually be the determination of a camera-to-subject distance for the taking of passport pictures within the standards. From an anthropological point of view it would be interesting to find out which facial features allow the preference of a shorter camera-to-subject distance and which allow the preference of a longer camera-to-subject distance.     

Sentencing Recommendations by Probation Officers and Judges: An Examination of Adult Offenders Across Gender

Connecting the courtroom workgroup model with attributions and stereotyping based on the focal concerns perspective and gender sentencing literature, the present study investigates the extent to which probation officer recommendations influence judicial sentencing, and whether the gender of the offender further conditions this relationship. Results from logistic and ordinary least squares regression indicate that there is concordance between probation officer recommendations and sentencing by judges. Offender gender has both direct and indirect effects on judicial sentencing through its relationship with probation officer recommendations, and Black males tend to receive lengthier sentences than other race/gender counterparts. These findings provide evidence that probation officer recommendations are an important part of the sentencing process and offer additional insight on how extralegal factors such as gender and race impact criminal justice decision making.     

Prospects for determining age from human soft tissues (a morphometric study)

Biometric studies of the aorta, endocrine glands (testes, prostate, and thyroid), and x-ray examination of the hands from 427 corpses of men and women aged 17-89 years helped formulate equations of paired and multiple linear regression for the diagnosis of age. The difference between biological and passport age is significant if the diagnosis is made on the basis of a single object or single sign. Complex use of several objects described by many signs is recommended; in this case the confidence intervals is no more than +/- 4.09 years.     

略论晚清政府关于来华外国人内地游历的执照制度

晚清时期,国门初开,护照制度开始实行。一般来说,护照是一个政府控制入境外国人的最基本、最有效的行政手段,本文拟对晚清政府关于来华外国人所持游历执照的政策作一概述,包括游历执照的分类、主要内容和实施的成效情况。此种游历执照,亦称"护照",但与现代意义上的"护照"有很大区别,是专门注明前往内地游历的通行证件,也起证明持照人身份的作用。     

Is there a place for hair analysis in doping controls?

The actual antidoping control rules applied in sports (as established by the International Olympic Committee and the International Sport Federations) state that a positive case is chemically established by the unequivocal detection of a forbidden parent molecule and/or any of its metabolite(s) in urine, no matter the amounts which were administered and when the drug was taken. Screening is accomplished most of the time by using GC-MS procedures. These have been optimized to detect most if not all of the forbidden compounds which are put on a list. Recently, attempts have been made on scalp hair to demonstrate the value of this matrix as a possible means for differentiating between therapeutic use and doping abuse. In particular, GC-mass selective detector and GC-high resolution MS were successfully applied to treated animals and body-builders for anabolic agents (steroids and beta-2-agonists) at high sensitivity detection (low ng/g level). Naturally occurring molecules, like testosterone and its metabolites, could also be differentiated from their synthetic counterparts. Positive cases are more often challenged in courts and retrospectivity in time of the drug(s) intake is becoming an important issue for evaluating the responsibility of the person. This is can be based on hair analyses if the drugs have been taken at regular intervals. Stimulants and narcotics are often used in sports like drug of abuse in the ordinary social contexts. On the other hand, anabolic agents, when taken to improve the physical performances, follow complex regimens with the mixing of various formulas and dosages. Scalp hair references ranges for these as well as for endogenous substances still wait to be established statistically for competing, well-trained athletes. The incorporation rate into blond or gray hair is poorer than that of dark colored hair raising the question of individuals equality against the controls, a very important matter of concern for the sport's governing bodies. The frequency of hair cutting and short hair cuts necessary to gain speed in specific sports like swimming are other critical factors. On the other hands, irregular hair growth, associated with the washout effect through multiple washing and staining processes over expanded time intervals can cause concentrating or diluting effects. So far, a minority of prohibited substances could be detected in scalp hair with the sensitivity and specificity required in the context of the sport's activities. From the above, clear limitations of the usefulness of hair analysis in doping control analysis are obvious until a lot more data relevant to this particular field have been collected.     

论录像证据可采的基本法理

录像材料再现案件事实能力的优势和劣势都同样明显,这决定了录像证据有着较为特殊的可采性规则。美国、英国、加拿大和日本的立法例表明,录像证据可采有三个基本法理,即录像证据与录音证据的可采性规则不一致;影响录像证据可采性的特定因素是形式真实性要件;不同表现形式的录像证据可采性规则不同。我国有关录像证据的规定存在诸多问题,应当按照上述法理加以完善。     

Injuries of the occipital condyles in fatal traffic accidents

Among 600 deaths of traffic accidents we found injuries of the occipital condyles in 10 cyclists, 12 car drivers and 3 pedestrians. In most cases the collision speed ranged from 70 to 100 km/h. In 18 cases of direct head impact the more severe injury was on the opposite side, in 4 cases of indirect side impact (whiplash injury) on the same side. Most types of fractures were 12 horizontal disconnections and 4 fractures of the inner edges. In 9 cases the condyle fractures were on one side, in 16 cases on both sides.     

论国际海事条约在中国的适用方式

国际海事条约的适用方式是指一国如何援引国际海事条约处理具体问题的方式,包括直接适用和间接适用.目前,中国采用直接适用还是间接适用的方式适用国际海事条约尚无定论,必须结合国际海事条约自身的特点,分析其在中国国内适用的局限性,深入剖析中国采用直接适用方式和间接适用方式的利弊,才能够减少司法中的矛盾和混乱,弥补中国海事立法的不足,促进海事立法的完善.     

An Examination of First and Second Generation Immigrant Offending Trajectories

The myth of the criminal immigrant has permeated public and political debate for much of this nation's history and persists despite growing evidence to the contrary. Crime concerns are increasingly aimed at the indirect impact of immigration on crime highlighting the criminal pursuits of the children of immigrants. Adding to extant knowledge on the immigration-crime nexus, this research asks whether immigrants are differentially involved in crime by examining immigrant offending histories (prevalence, frequency, seriousness, persistence, and desistance) from early adolescence to young adulthood. Particular attention is afforded to the influence of various sources of heterogeneity including: generational and nativity status, and crime type. Results suggest that the myth remains; trajectory analyses reveal that immigrants are no more crime-prone than the native-born. Foreign-born individuals exhibit remarkably low levels of involvement in crime across their life course. Moreover, it appears that by the second generation, immigrants have simply caught up to their native-born counterparts in respect to their offending. Implications of the findings for theory and future research are discussed.     

Battered woman syndrome evidence in the courtroom

The use of battered woman syndrome evidence has been advocated in trials of battered women who assault or kill their abusers. The present article reviews existing legal and psychological literature addressing the use of this form of expert testimony. As the review will indicate, there are, at present, substantial gaps in our knowledge about its scientific status and its impact on legal proceedings. The goal of the article is to highlight some of the central concerns surrounding the use of bettered woman syndrome evidence and to encourage additional research on the subject.Thanks are extended to R. Lalonde for comments on earlier versions of this paper.     

The interaction of international institutions from a social network perspective

The literature increasingly acknowledges that international institutions do not exist in isolation, but regularly interact with each other. This interplay might induce influence, affecting institutions’ development and performance. The following research adds to this debate by systematically analyzing the quantitative evidence on how institutional interaction drives institutional design from a network perspective. Using dyadic cross-sectional data on international environmental agreements in 1952–2000, the authors find support for their theoretical argument that regimes’ similarity in design as captured by their degree of legalization strongly depends on institutions’ interaction. However, while “soft law” disseminates between regimes that are well connected through direct or indirect links, this does not apply to “hard law.” The authors explain this divergence with states’ concerns about binding-law commitments and sovereignty costs associated with the latter. This research may have important implications for studies of international institutions and of network analysis in general.     

Hair analysis for cocaine: factors in laboratory contamination studies and their relevance to proficiency sample preparation and hair testing practices

Since the introduction in 2001 of a urine-based detection method for recombinant erythropoietin (rHuEPO), transfusion-doping practices have regained interest. To address this problem, an efficient antidoping test designed to obtain direct proof of allogeneic blood transfusion was developed and validated. This test, based on flow cytometry analysis of red blood cell (RBCs) phenotypes, was used to determine the absence or the presence of numerous RBCs populations in a blood sample. A such, it may constitute a direct proof of an abnormal blood population resulting from homologous transfusion. Single-blind and single-site studies were carried out to validate this method as a forensic quality standard analysis and to allow objective interpretation of real cases. The analysis of 140 blood samples containing different percentages (0-5%) of a minor RBCs population were carried on by four independent analysts. Robustness, sensitivity, specificity, precision and stability were assessed. ISO-accredited controls samples were used to demonstrate that the method was robust, stable and precise. No false positive results were observed, resulting in a 100% specificity of the method. Most samples containing a 1.5% minor RBCs population were unambiguously detected, yielding a 78.1% sensitivity. These samples mimicked blood collected from an athlete 3 months after a homologous blood transfusion event where 10% of the total RBCs present in the recipient originated in the donor. The observed false negative results could be explained by differences in antigen expression between the donor and the recipient. False negatives were more numerous with smaller minor RBCs populations. The method described here fulfils the ISO-17025 accreditation and validation requirements. The controls and the methodology are solid enough to determine with certainty whether a sample contains one or more RBCs populations. This variable is currently the best indicator for homologous blood transfusion doping.     

Use of forensic investigations in anti-doping

The fight against doping is mainly focused on direct detection, using analytical methods for the detection of doping agents in biological samples. However, the World Anti-Doping Code also defines doping as possession, administration or attempted administration of prohibited substances or methods, trafficking or attempted trafficking in any prohibited substance or methods. As these issues correspond to criminal investigation, a forensic approach can help assessing potential violation of these rules. In the context of a rowing competition, genetic analyses were conducted on biological samples collected in infusion apparatus, bags and tubing in order to obtain DNA profiles. As no database of athletes' DNA profiles was available, the use of information from the location detection as well as contextual information were key to determine a population of suspected athletes and to obtain reference DNA profiles for comparison. Analysis of samples from infusion systems provided 8 different DNA profiles. The comparison between these profiles and 8 reference profiles from suspected athletes could not be distinguished. This case-study is one of the first where a forensic approach was applied for anti-doping purposes. Based on this investigation, the International Rowing Federation authorities decided to ban not only the incriminated athletes, but also the coaches and officials for 2 years.     

Forensic identification science evidence since Daubert: Part II--judicial reasoning in decisions to exclude forensic identification evidence on grounds of reliability

Many studies regarding the legal status of forensic science have relied on the U.S. Supreme Court's mandate in Daubert v. Merrell Dow Pharmaceuticals Inc., and its progeny in order to make subsequent recommendations or rebuttals. This paper focuses on a more pragmatic approach to analyzing forensic science's immediate deficiencies by considering a qualitative analysis of actual judicial reasoning where forensic identification evidence has been excluded on reliability grounds since the Daubert precedent. Reliance on general acceptance is becoming insufficient as proof of the admissibility of forensic evidence. The citation of unfounded statistics, error rates and certainties, a failure to document the analytical process or follow standardized procedures, and the existence of observe bias represent some of the concerns that have lead to the exclusion or limitation of forensic identification evidence. Analysis of these reasons may serve to refocus forensic practitioners' testimony, resources, and research toward rectifying shortfalls in these areas.     

Current strategic approaches for the detection of blood doping practices

Aerobic sport performance may be strongly influenced by the number of red blood cells available for transport and delivery of oxygen from lungs to muscles. Often, athletes search for an acute increase in red blood cells by means of blood transfusions. This paper reviews the possibilities for detecting such prohibited practice. Flow cytometry methods are able to detect a double population of red blood cell membrane surface antigens, thus revealing an allogeneic transfusion. Other ingenious approaches for total hemoglobin mass measurements or to test for the metabolites of blood bag plasticizers in urine are new trends for facing the detection of autologous transfusions. Steady increase of red blood cell number may be obtained also by erythropoietic stimulant agents such as erythropoietin, analogs and mimetics. The challenge of detecting those substances has stimulated the development of indirect markers of altered erythropoiesis, leading to the consequent development of the hematological blood passport approach, which is gaining legal acceptance.