Anti-doping education for coaches: Qualitative insights from national and international sporting and anti-doping organisations

Within anti-doping efforts, an emphasis has been placed on the importance of providing education programmes to key stakeholder groups, including coaches. Yet, very little is known about current coach education provision in the anti-doping domain across countries and sports. Therefore, this study aimed to: 1) establish the current status of antidoping education for coaches; 2) gain an understanding of the system through which antidoping education is provided to coaches; and, 3) explore the opportunities for future education provision. This was done through semi-structured interviews with thirteen individuals responsible for managing anti-doping education within national and international sporting and anti-doping organisations. Most stakeholders acknowledged the importance of providing education programmes for coaches; some already had provision in place and others were in the process of developing programmes. However, the current focus is on sportspeople and the degree to which sporting and anti-doping organisations are able to devise, implement and evaluate anti-doping education programmes for coaches is hindered by the contextual constraints they face. These include a lack of resources and limited interagency coordination, as well as challenges to overcome negative perceptions of ‘anti-doping’ efforts. Taken together, the findings indicate that policy expectations regarding anti-doping education for coaches are not being fully operationalised, and this situation is unlikely to change without: 1) greater direction and regulation of the system through which education is provided; 2) frequent and effective communication and cooperation between Code signatories; and, 3) increased fiscal and human capital investment at every level of the sporting hierarchy. Ultimately, until anti-doping education is shown to be a key priority for decision makers within sporting organisations (i.e., chief executives and board members), it is unlikely to become a central priority for coaches

First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Measurement Properties of Questionnaires Assessing Complementary and Alternative Medicine Use in Pediatrics: A Systematic Review

Complementary and alternative medicine (CAM) is commonly used by children, but estimates of that use vary widely partly due to the range of questionnaires used to assess CAM use. However, no studies have attempted to appraise measurement properties of these questionnaires. The aim of this systematic review was to critically appraise and summarize measurement properties of questionnaires of CAM use in pediatrics.A search strategy was implemented in major electronic databases in March 2011 and conference websites, scientific journals and experts were consulted. Studies were included if they mentioned a questionnaire assessing the prevalence of CAM use in pediatrics. Members of the team independently rated the methodological quality of the studies (using the COSMIN checklist) and measurement properties of the questionnaires (using the Terwee and Cohen criteria).A total of 96 CAM questionnaires were found in 104 publications. The COSMIN checklist showed that no studies reported adequate methodological quality. The Terwee criteria showed that all included CAM questionnaires had indeterminate measurement properties. According to the Cohen score, none were considered to be a well-established assessment, two approached the level of a well-established assessment, seven were promising assessments and the remainder (n = 87) did not reach the score's minimum standards.None of the identified CAM questionnaires have been thoroughly validated. This systematic review highlights the need for proper validation of CAM questionnaires in pediatrics, which may in turn lead to improved research and knowledge translation about CAM in clinical practice

A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation

We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0×10−62 and p = 7.46×10−127, respectively. The IRF4 SNP was also associated with skin color (p = 6.2×10−14), eye color (p = 6.1×10−13), and skin tanning response to sunlight (p = 3.9×10−89). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation

Efficacy of Fumaric Acid Esters in the R6/2 and YAC128 Models of Huntington's Disease

Huntington's disease (HD) is an autosomal dominantly inherited progressive neurodegenerative disease. The exact sequel of events finally resulting in neurodegeneration is only partially understood and there is no established protective treatment so far. Some lines of evidence speak for the contribution of oxidative stress to neuronal tissue damage. The fumaric acid ester dimethylfumarate (DMF) is a new disease modifying therapy currently in phase III studies for relapsing-remitting multiple sclerosis. DMF potentially exerts neuroprotective effects via induction of the transcription factor “nuclear factor E2-related factor 2” (Nrf2) and detoxification pathways. Thus, we investigated here the therapeutic efficacy of DMF in R6/2 and YAC128 HD transgenic mice which mimic many aspects of HD and are characterized by an enhanced generation of free radicals in neurons. Treatment with DMF significantly prevented weight loss in R6/2 mice between postnatal days 80–90. At the same time, DMF treatment led to an attenuated motor impairment as measured by the clasping score. Average survival in the DMF group was 100.5 days vs. 94.0 days in the placebo group. In the histological analysis on day 80, DMF treatment resulted in a significant preservation of morphologically intact neurons in the striatum as well as in the motor cortex. DMF treatment resulted in an increased Nrf2 immunoreactivity in neuronal subpopulations, but not in astrocytes. These beneficial effects were corroborated in YAC128 mice which, after one year of DMF treatment, also displayed reduced dyskinesia as well as a preservation of neurons. In conclusion, DMF may exert beneficial effects in mouse models of HD. Given its excellent side effect profile, further studies with DMF as new therapeutic approach in HD and other neurodegenerative diseases are warranted

Intra-Operative Assessment of Cancer with X-Ray Phase Contrast Computed Tomography

X-ray Phase-Contrast Computed Tomography (PC-CT) increases contrast in weakly attenuating samples, such as soft tissues. In Edge-Illumination (EI) PC-CT, phase effects are accessed from amplitude modulation of the x-ray beam using alternating transmitting and attenuating masks placed prior to the sample and detector. A large field of view PC-CT scanner using this technique was applied to two areas of cancer assessment, namely excised breast and esophageal tissue. For the breast tissue, Wide Local Excisions (WLEs) were studied intra-operatively using PC-CT for the evaluation of tumor removal in breast conservation surgery. Images were acquired in 10 minutes without compromising on image quality, showing this can be used in a clinical setting. Longer, higher resolution PC-CT images were also taken, with analysis showing previously undetected thinning of tumor strands. This would allow a second use of the system for “virtual histopathology”, outside of surgery. For the esophagus samples, tissues were taken from esophagectomy surgery, where the lower part of the esophagus is removed, and the stomach relocated. For the assessment of ongoing therapy, accurate staging of tumors in the removed esophagus is essential, with the current gold standard provided by histopathology. PCCT images were acquired on several samples and compare well with histopathology, with both modalities showing similar features. Examples are shown where staging of tumor penetration is possible with PC-CT images alone, which is hoped will be an important step in performing the imaging and staging intra-operatively