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

CA 15-3 is predictive of response and disease recurrence following treatment in locally advanced breast cancer

BACKGROUND: Primary chemotherapy (PC) is used for down-staging locally advanced breast cancer (LABC). CA 15-3 measures the protein product of the MUC1 gene and is the most widely used serum marker in breast cancer. METHODS: We retrospectively investigated the role of CA 15-3 in conjunction with other clinico-pathological variables as a predictor of response and time to disease recurrence following treatment in LABC. Pre and post primary chemotherapy serum concentrations of CA 15-3 together with other variables were reviewed and related to four outcomes following primary chemotherapy (clinical response, pathological response, time to recurrence and time to progression). Persistently elevated CA 15-3 after PC was considered as consecutively high levels above the cut off point during and after PC. RESULTS: 73 patients were included in this study. Patients received PC (AC or AC-T regimen) for locally advanced breast cancer. 54 patients underwent surgery. The median follow up was 790 days. Patients with high concentrations of CA 15-3 before PC treatment had a poor clinical (p = 0.013) and pathological (p = 0.044) response. Together with Her-2/neu expression (p = 0.009) and tumour lympho-vascular space invasion (LVI) (p = 0.001), a persistently elevated CA 15-3 post PC (p = 0.007) was an independent predictive factor of recurrence following treatment in LABC. CONCLUSION: Elevated CA 15-3 level is predictive of a poor response to chemotherapy. In addition, persistently elevated CA 15-3 levels post chemotherapy in conjunction with lympho-vascular invasion and HER2 status predict a reduced disease free survival following treatment in locally advanced breast cancer

Response of the Human Circadian System to Millisecond Flashes of Light

Ocular light sensitivity is the primary mechanism by which the central circadian clock, located in the suprachiasmatic nucleus (SCN), remains synchronized with the external geophysical day. This process is dependent on both the intensity and timing of the light exposure. Little is known about the impact of the duration of light exposure on the synchronization process in humans. In vitro and behavioral data, however, indicate the circadian clock in rodents can respond to sequences of millisecond light flashes. In a cross-over design, we tested the capacity of humans (n = 7) to respond to a sequence of 60 2-msec pulses of moderately bright light (473 lux) given over an hour during the night. Compared to a control dark exposure, after which there was a 3.5±7.3 min circadian phase delay, the millisecond light flashes delayed the circadian clock by 45±13 min (p<0.01). These light flashes also concomitantly increased subjective and objective alertness while suppressing delta and sigma activity (p<0.05) in the electroencephalogram (EEG). Our data indicate that phase shifting of the human circadian clock and immediate alerting effects can be observed in response to brief flashes of light. These data are consistent with the hypothesis that the circadian system can temporally integrate extraordinarily brief light exposures

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Formation of unique nanocrystalline Cu-In-Se bulk pn homojunctions for opto-electronic devices

Semiconductor pn junctions, integrated in optoelectronic devices require high quality crystals, made by expensive, technically difficult processes. Bulk heterojunction (BHJ) structures offer practical alternatives to circumvent the cost, flexibility and scale-up challenges of crystalline planar pn junctions. Fabrication methods for the current organic or inorganic BHJ structures invariably create interface mismatch and low doping issues. To overcome such issues, we devised an innovative approach, founded on novel inorganic material system that ensued from single-step electrodeposited copper-indium-selenide compounds. Surface analytical microscopies and spectroscopies reveal unusual phenomena, electro-optical properties and quantum effects. They support the formation of highly-ordered, sharp, abrupt 3-dimensional nanoscale pn BHJs that facilitate efficient charge carrier separation and transport, and essentially perform the same functions as crystalline planar pn junctions. This approach offers a low-cost processing platform to create nanocrystalline films, with the attributes necessary for efficient BHJ operation. It allows roll-to-roll processing of flexible devices in simple thin-film form factor.Partial funding for this work is provided by customers of Xcel Energy through a grant from the Renewable Development Fund. The authors gratefully acknowledge sample preparation, analytical contributions and useful discussions with Sharmila Menezes and Yan Li (InterPhases Solar); Senli Guo (Brucker Nano); Terrence McGuckin (Ephemeron Labs); and Nassim Rahimi (HORIBA Scientific). A. Samantilleke acknowledges Prof. L. M. Peter (Bath University, UK) for introducing EER technique