Understanding participation and non-participation in sport amongst Black and minority ethnic groups in Wales

Like the other home nation sports councils, Sport Wales has a responsibility to increase participation, improve sporting performance and raise standards in sport and physical recreation. For some time the sports councils in the UK have been concerned that people from Black and minority ethnic (BME) groups may not be getting as much from sport as they might (e.g. the Sports Equity Index (Sport England, 2001)). The concern with increasing participation is multidimensional: it might serve to recruit new talent; allows sectors of society to enjoy what are thought to be the benefits of sport; and in so doing help to unite the nation. However, as recognised by the Equality Impact Assessment that was conducted by Sport Wales, there has been a shortage of research around sport participation by Black and minority ethnic communities. Thus, the current research is closely aligned with the aim of increasing participation and understanding non-participation. The research also addresses the identified need for further investigation into identified differences in participation between different equalities groups. This project, commissioned by Sport Wales, has been undertaken by the Institute for Sport, Physical Activity and Leisure (ISPAL) in conjunction with Ecorys. It is a response to the strategy, action plans and operational plans of Sport Wales that embrace diversity and inclusiveness. These policy and operational documents consider ethnicity alongside other protected characteristics and a concern to address poverty and deprivation by operating in conjunction with other agencies. The research reported here will help to establish what resonance people in Black and minority ethnic groups have with the goal of ensuring ‘a thriving sporting community, where all individuals feel safe, welcome and free from discrimination’ (Sport Wales, Equality And Diversity Operational Action Plan)

Survival Analysis of F98 Glioma Rat Cells Following Minibeam or Broad-Beam Synchrotron Radiation Therapy

Background: In the quest of a curative radiotherapy treatment for gliomas new delivery modes are being explored. At the Biomedical Beamline of the European Synchrotron Radiation Facility (ESRF), a new spatially-fractionated technique, called Minibeam Radiation Therapy (MBRT) is under development. The aim of this work is to compare the effectiveness of MBRT and broad-beam (BB) synchrotron radiation to treat F98 glioma rat cells. A dose escalation study was performed in order to delimit the range of doses where a therapeutic effect could be expected. These results will help in the design and optimization of the forthcoming in vivo studies at the ESRF. Methods: Two hundred thousand F98 cells were seeded per well in 24-well plates, and incubated for 48 hours before being irradiated with spatially fractionated and seamless synchrotron x-rays at several doses. The percentage of each cell population (alive, early apoptotic and dead cells, where either late apoptotic as necrotic cells are included) was assessed by flow cytometry 48 hours after irradiation, whereas the metabolic activity of surviving cells was analyzed on days 3, 4, and 9 post-irradiation by using QBlue test. Results

Treatment outcome of extra-pulmonary tuberculosis in Finland: a cohort study

<p>Abstract</p> <p>Background</p> <p>We investigated the treatments given, the outcome and the patient- and treatment-system dependent factors affecting treatment outcome in a national two-year cohort of culture-verified extra-pulmonary tuberculosis cases in Finland.</p> <p>Methods</p> <p>Medical records of all cases in 1995 - 1996 were abstracted to assess treatment and outcome, using the European recommendations for outcome monitoring. For risk factor analysis, outcome was divided into three groups: favourable, death and other unfavourable. Predictors of unfavourable outcome were assessed in univariate and multivariate analysis.</p> <p>Results</p> <p>In the study cohort of 276 cases, 116 (42.0%) were men and 160 (58.0%) women. The mean age was 65.7 years. A favourable outcome was achieved in 157/276 (56.9%) cases, consisting of those cured (8.0%) and treatment completed (48.9%). Death was the outcome in 17.4% (48/276) cases, including cases not treated. Other unfavourable outcomes took place in 45 (16.3%) cases. Significant independent risk factors for death in multinomial logistic regression model were male sex, high age, immunosuppression, any other than a pulmonary specialty being responsible at the end of the treatment and other than standard combination of treatment. For other unfavourable treatment outcomes, significant risk factor was treatment with INH + RIF + EMB/SM. Deep site of TB was inversely associated with the risk of other unfavourable outcome.</p> <p>Conclusions</p> <p>The proportion of favourable outcome was far below the goal set by the WHO. Age and comorbidities, playing an important role in treatment success, are not available in routine outcome data. Therefore, comparisons between countries should be made in cohort analyses incorporating data on comorbidities.</p

Risk factors for poor tuberculosis treatment outcome in Finland: a cohort study

<p>Abstract</p> <p>Background</p> <p>We investigated the patient- and treatment-system dependent factors affecting treatment outcome in a two-year cohort of all treated culture-verified pulmonary tuberculosis (TB) cases to establish a basis for improving outcomes.</p> <p>Methods</p> <p>Medical records of all cases in 1995 – 1996 were abstracted to assess outcome of treatment. Outcome was divided into three groups: favourable, death and other unfavourable. Predictors of unfavourable outcome were assessed in univariate and multivariate analysis.</p> <p>Results</p> <p>Among 629 cases a favourable outcome was achieved in 441 (70.1%), 17.2% (108) died and other unfavourable outcome took place in 12.7% (80). Significant independent risk factors for death were male sex, high age, non-HIV -related immunosuppression and any other than a pulmonary specialty being responsible for stopping treatment. History of previous tuberculosis was inversely associated with the risk of death. For other unfavourable treatment outcomes, significant risk factors were pause(s) in treatment, treatment with INH+RIF+EMB/SM, and internal medicine specialty being responsible at the end of the treatment.</p> <p>Conclusion</p> <p>We observed a significant association with unfavourable outcome for the specialty responsible for treatment being other than pulmonary, but not for the volume of cases, which has implications for system arrangements. Poor outcomes associated with immunosuppression and advanced age, with frequent comorbidity, stress a low threshold of suspicion, availability of rapid diagnostics, and early empiric treatment as probable approaches in attempting to improve treatment outcomes in countries with very low incidence of TB.</p

Characterization of an Nmr Homolog That Modulates GATA Factor-Mediated Nitrogen Metabolite Repression in Cryptococcus neoformans

Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis

Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.

Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence

Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model

<p>Abstract</p> <p>Background</p> <p>Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical rapamycin in a mouse model for TSC-related tumors.</p> <p>Methods</p> <p>0.4% and 0.8% rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.</p> <p>Results</p> <p>Treatment with topical rapamycin improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin.</p> <p>Conclusion</p> <p>Topical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.</p

Transcriptomic analysis of crustacean neuropeptide signaling during the moult cycle in the green shore crab, Carcinus maenas

Abstract Background Ecdysis is an innate behaviour programme by which all arthropods moult their exoskeletons. The complex suite of interacting neuropeptides that orchestrate ecdysis is well studied in insects, but details of the crustacean ecdysis cassette are fragmented and our understanding of this process is comparatively crude, preventing a meaningful evolutionary comparison. To begin to address this issue we identified transcripts coding for neuropeptides and their putative receptors in the central nervous system (CNS) and Y-organs (YO) within the crab, Carcinus maenas, and mapped their expression profiles across accurately defined stages of the moult cycle using RNA-sequencing. We also studied gene expression within the epidermally-derived YO, the only defined role for which is the synthesis of ecdysteroid moulting hormones, to elucidate peptides and G protein-coupled receptors (GPCRs) that might have a function in ecdysis. Results Transcriptome mining of the CNS transcriptome yielded neuropeptide transcripts representing 47 neuropeptide families and 66 putative GPCRs. Neuropeptide transcripts that were differentially expressed across the moult cycle included carcikinin, crustacean hyperglycemic hormone-2, and crustacean cardioactive peptide, whilst a single putative neuropeptide receptor, proctolin R1, was differentially expressed. Carcikinin mRNA in particular exhibited dramatic increases in expression pre-moult, suggesting a role in ecdysis regulation. Crustacean hyperglycemic hormone-2 mRNA expression was elevated post- and pre-moult whilst that for crustacean cardioactive peptide, which regulates insect ecdysis and plays a role in stereotyped motor activity during crustacean ecdysis, was elevated in pre-moult. In the YO, several putative neuropeptide receptor transcripts were differentially expressed across the moult cycle, as was the mRNA for the neuropeptide, neuroparsin-1. Whilst differential gene expression of putative neuropeptide receptors was expected, the discovery and differential expression of neuropeptide transcripts was surprising. Analysis of GPCR transcript expression between YO and epidermis revealed 11 to be upregulated in the YO and thus are now candidates for peptide control of ecdysis. Conclusions The data presented represent a comprehensive survey of the deduced C. maenas neuropeptidome and putative GPCRs. Importantly, we have described the differential expression profiles of these transcripts across accurately staged moult cycles in tissues key to the ecdysis programme. This study provides important avenues for the future exploration of functionality of receptor-ligand pairs in crustaceans