Global Citizenship and the Ethical Challenges of ‘Sport for Development and Peace’

Recent years have seen increased recognition, promotion and institutionalization of the role of sport and physical activity amidst struggles for just and sustainable development on an international scale. This paper explores the ways in, and extent to, which global citizenship – the idea that humans are citizens of the world with global rights and responsibilities – underpins this institutionalization and popularity of Sport for Development and Peace (SDP). These connections are then used to put forth a series of critical and ethical complications regarding the mobilization of sport towards meeting international development goals. In particular, the paper argues that any progressive and ethical invocation of sport as a means of supporting sustainable development depends more on the ways in which global citizenship is interpreted and acted upon by SDP stakeholders than it does on the global popularity of sport as an entry into the field or context of international development

Mining expressed sequence tags identifies cancer markers of clinical interest

BACKGROUND: Gene expression data are a rich source of information about the transcriptional dis-regulation of genes in cancer. Genes that display differential regulation in cancer are a subtype of cancer biomarkers. RESULTS: We present an approach to mine expressed sequence tags to discover cancer biomarkers. A false discovery rate analysis suggests that the approach generates less than 22% false discoveries when applied to combined human and mouse whole genome screens. With this approach, we identify the 200 genes most consistently differentially expressed in cancer (called HM200) and proceed to characterize these genes. When used for prediction in a variety of cancer classification tasks (in 24 independent cancer microarray datasets, 59 classifications total), we show that HM200 and the shorter gene list HM100 are very competitive cancer biomarker sets. Indeed, when compared to 13 published cancer marker gene lists, HM200 achieves the best or second best classification performance in 79% of the classifications considered. CONCLUSION: These results indicate the existence of at least one general cancer marker set whose predictive value spans several tumor types and classification types. Our comparison with other marker gene lists shows that HM200 markers are mostly novel cancer markers. We also identify the previously published Pomeroy-400 list as another general cancer marker set. Strikingly, Pomeroy-400 has 27 genes in common with HM200. Our data suggest that a core set of genes are responsive to the deregulation of pathways involved in tumorigenesis in a variety of tumor types and that these genes could serve as transcriptional cancer markers in applications of clinical interest. Finally, our study suggests new strategies to select and evaluate cancer biomarkers in microarray studies

The Tyrphostin Agent AG490 Prevents and Reverses Type 1 Diabetes in NOD Mice

<div><h3>Background</h3><p>Recent studies in the NOD (non-obese diabetic) mouse model of type 1 diabetes (T1D) support the notion that tyrosine kinase inhibitors have the potential for modulating disease development. However, the therapeutic effects of AG490 on the development of T1D are unknown.</p> <h3>Materials and Methods</h3><p>Female NOD mice were treated with AG490 (i.p, 1 mg/mouse) or DMSO starting at either 4 or 8 week of age, for five consecutive week, then once per week for 5 additional week. Analyses for the development and/or reversal of diabetes, insulitis, adoptive transfer, and other mechanistic studies were performed.</p> <h3>Results</h3><p>AG490 significantly inhibited the development of T1D (p = 0.02, p = 0.005; at two different time points). Monotherapy of newly diagnosed diabetic NOD mice with AG490 markedly resulted in disease remission in treated animals (n = 23) in comparision to the absolute inability (0%; 0/10, p = 0.003, Log-rank test) of DMSO and sustained eugluycemia was maintained for several months following drug withdrawal. Interestingly, adoptive transfer of splenocytes from AG490 treated NOD mice failed to transfer diabetes to recipient NOD.<em>Scid</em> mice. CD4 T-cells as well as bone marrow derived dendritic cells (BMDCs) from AG490 treated mice, showed higher expression of Foxp3 (p<0.004) and lower expression of co-stimulatory molecules, respectively. Screening of the mouse immune response gene arrary indicates that expression of costimulaotry molecule Ctla4 was upregulated in CD4+ T-cell in NOD mice treated with AG490, suggesting that AG490 is not a negative regulator of the immune system.</p> <h3>Conclusion</h3><p>The use of such agents, given their extensive safety profiles, provides a strong foundation for their translation to humans with or at increased risk for the disease.</p> </div

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Sport and international development : mainstreaming sport in development studies; workshop report

This report summarizes a workshop that included scholars, researchers, practitioners, activists and students from both development studies and sport studies. It indicates that ‘Sport for Development and Peace’ (SDP) is well positioned, and would benefit from a commitment to partnership between the disparate fields of sport studies and development studies. Six ways sport is used in development are: as a means of conflict resolution and social cohesion; building physical, social and community infrastructure; supporting economic development and capacity; fostering awareness of social issues related to inequality; empowering traditionally marginalized groups; and improving the physical and psychological health of individuals and communities

The media construction of Simon Whitfield : producing a Canadian Olympic champion

This thesis analyzes the media coverage and marketing of the Canadian Olympic athlete Simon Whitfield. Whitfield, a 25 year-old from Kingston Ontario, won the first ever gold medal in the Olympic men's triathlon at the 2000 Sydney Games. The victory propelled him to the status of Canadian celebrity and afforded him increased commercial opportunities including corporate sponsorships and product endorsements. This research combined two methodologies: 1) a textual analysis of Canadian media coverage of Whitfield and a keyword search of the coverage, and 2) interviews with five Canadian sports journalists that covered Whitfield and four marketing representatives from companies that sponsored Whitfield or employed him as a product endorser. Whitfield was also interviewed to provide an athlete's perspective on the media production and marketing processes. The results revealed thematic consistencies in the Canadian media coverage of Whitfield, particularly with respect to Canadian national identity, the value of an Olympic gold medal and Whitfield's status as a Canadian hero. These results support previous research that found recurring themes of athletic heroism and myths of Canadian nationalism in the production of Canadian sports media (MacNeill, 1996, Gruneau, 1989). Interviews with journalists confirmed the observed elements of the Whitfield story - his Canadian identity, gold medal victory, heroic performance, as well as other features (genuine personality, athletic good looks) - that made him newsworthy. Covering these attributes of Whitfield helped newsmakers to produce news that was attractive to audiences, and maintained circulation, viewership, and ad ratings, strengthening the media "audience commodity" (Sparks, 1992). Interviews with marketers revealed that Whitfield was commercially attractive because the meanings associated with his media image could be attached to brands through the endorsement and sponsorship process in order to improve brand equity, the value that consumers attribute to a brand of product or service (Keller, 1993). The results support a model of celebrity product endorsement based on the transfer of meanings from the endorser to the product and subsequently, to the consumer (McCracken, 1989). Overall, the results suggest intertextual linkages between media production and marketing as they relate to celebrity athletes in Canada. Whitfield's positive media image was understood to impact his marketability and contributed to a "vortex of publicity" (Wernick, 1991) by linking stages along the promotional chain.Education, Faculty ofKinesiology, School ofGraduat