Letter from the Editer

The Notre Dame Journal of International and Comparative Law, Volume 8, Issue 2 (2018)

Fairness at a Price: Protecting the Integrity of Athletic Competitions at the Expense of Female Athletes

Ever since women were allowed to compete in the Olympics, they have been subjected to some form of gender verification. Initially, the International Olympic Committee (IOC) and International Amateur Athletic Federation (IAAF) required female athletes to present certificates from their doctors confirming that they were in fact women. In 1966, the IOC and the IAAF “decided they couldn’t trust individual nations to certify femininity, and instead implemented a mandatory genital check of every woman competing at international games.” This process was dubbed the “nude parades”. In response to the overwhelming disapproval of such examination, the IOC and IAAF began implementing the Chromatin Test. This test also faced intense criticism and was disposed of in 1999. Even though the IOC and the IAAF have abandoned universal compulsory gender examination, these organizations seem to have continued interest in policing gender. In 2011, the IAAF developed a new policy dubbed as the “Hyperandrogenism Regulation” that focused on female athletes with elevated levels of androgen. The IOC, in 2012 adopted a similar policy. This Note will evaluate the discriminatory and scientific issues surrounding gender verification examinations. For a better understanding of gender verification examinations, Part I of this Note will briefly outline the history of gender verification examinations. Part II will discuss the problems with the various tests that the IOC and IAAF have adopted throughout the years. More specifically, it will discuss the discriminatory effect of each type of gender verification procedure, and the scientific shortcomings of each. Part III will discuss the legal implications of the Testosterone Test which is currently implemented by the IOC and the IAAF under the “Hyperandrogenism Regulations.” Finally, Part IV will call for the elimination of gender testing

Letter from the Editor

The Notre Dame Journal of International and Comparative Law, Volume 8, Issue 1 (2018)

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Fairness at a Price: Protecting the Integrity of Athletic Competitions at the Expense of Female Athletes

Ever since women were allowed to compete in the Olympics, they have been subjected to some form of gender verification. Initially, the International Olympic Committee (IOC) and International Amateur Athletic Federation (IAAF) required female athletes to present certificates from their doctors confirming that they were in fact women. In 1966, the IOC and the IAAF “decided they couldn’t trust individual nations to certify femininity, and instead implemented a mandatory genital check of every woman competing at international games.” This process was dubbed the “nude parades”. In response to the overwhelming disapproval of such examination, the IOC and IAAF began implementing the Chromatin Test. This test also faced intense criticism and was disposed of in 1999. Even though the IOC and the IAAF have abandoned universal compulsory gender examination, these organizations seem to have continued interest in policing gender. In 2011, the IAAF developed a new policy dubbed as the “Hyperandrogenism Regulation” that focused on female athletes with elevated levels of androgen. The IOC, in 2012 adopted a similar policy. This Note will evaluate the discriminatory and scientific issues surrounding gender verification examinations. For a better understanding of gender verification examinations, Part I of this Note will briefly outline the history of gender verification examinations. Part II will discuss the problems with the various tests that the IOC and IAAF have adopted throughout the years. More specifically, it will discuss the discriminatory effect of each type of gender verification procedure, and the scientific shortcomings of each. Part III will discuss the legal implications of the Testosterone Test which is currently implemented by the IOC and the IAAF under the “Hyperandrogenism Regulations.” Finally, Part IV will call for the elimination of gender testing

Letter from the Editor

The Notre Dame Journal of International and Comparative Law, Volume 8, Issue 1 (2018)

Letter from the Editor

The Notre Dame Journal of International and Comparative Law, Volume 8, Issue 1 (2018)

Patient-Reported Outcomes in First-Line Antiretroviral Therapy: Results From NEAT001/ANRS143 Trial Comparing Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine or Raltegravir

Background: There are few data comparing patient-reported outcomes (PROs) in randomized trials of initial antiretroviral therapy. We present results from a substudy of the NEAT001/ ANRS143 trial. Methods: The randomized trial compared first-line DRV/r 800/100 mg once daily plus RAL 400 mg twice daily and DRV/r plus TDF/ FTC 245/200 mg once daily. Changes in PROs were assessed with 3 questionnaires: EuroQoL 5 domains (EQ-5D), Center for Epidemiologic Studies Depression (CES-D) scale, and HIV Treatment Satisfaction Questionnaire. Major depressive disorder (MDD) was defined as CES-D $16. General estimating equations were used to model change over 96 weeks in PROs from baseline. Results: Of the 805 participants, 797 (99substudy. Baseline PRO data were similar for the 2 randomized groups. Health status improved over time with a mean increase in EQ-5D visual analogue scale (VAS) of 8.0 by W96 [95to 9.4; P, 0.001], and no statistically significant differences between groups (difference of 0.3 on VAS score (95global P value$ 0.05 for all domains over follow-up). There was no significant difference between groups on CES-D [difference of 20.1 (95% CI: 21.3 to 1.1); P = 0.9], or MDD during follow-up, adjusted for baseline MDD (odds ratio = 0.98, 95% CI: 0.82 to 1.18; P = 0.9). RAL + DRV/r group had lower level of convenience (P = 0.03) and fitted less well into patients’ lifestyle (P = 0.007) than the TDF/FTC + DRV/r regimen, and was associated with lower treatment satisfaction [median score: 53 RAL + DRV/r vs 55 TDF/FTC + DRV/r (P = 0.001)]. Conclusion: PROs improved after starting antiretroviral therapy, with no statistically significant difference between groups. The lower satisfaction with RAL + DRV/r may be explained by twicedaily administration

Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response : a sub-study of the NEAT001/ANRS143 randomized trial

OBJECTIVES: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. METHODS: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. RESULTS: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P < 0.001). No significant relationship was demonstrated between darunavir AUC0-24 or C24 and time to virological failure [HR (95% CI): 2.28 (0.53-9.80), P = 0.269; and 1.82 (0.61-5.41), P = 0.279, respectively]. CONCLUSIONS: Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity