102 research outputs found
The dynamics of expertise acquisition in sport : the role of affective learning design
Objectives: The aim of this position paper is to discuss the role of affect in designing learning experiences to enhance expertise acquisition in sport. The design of learning environments and athlete development programmes are predicated on the successful sampling and simulation of competitive performance conditions during practice. This premise is captured by the concept of representative learning design, founded on an ecological dynamics approach to developing skill in sport, and based on the individual-environment relationship. In this paper we discuss how the effective development of expertise in sport could be enhanced by the consideration of affective constraints in the representative design of learning experiences. Conclusions: Based on previous theoretical modelling and practical examples we delineate two key principles of Affective Learning Design: (i) the design of emotion-laden learning experiences that effectively simulate the constraints of performance environments in sport; (ii) recognising individualised emotional and coordination tendencies that are associated with different periods of learning. Considering the role of affect in learning environments has clear implications for how sport psychologists, athletes and coaches might collaborate to enhance the acquisition of expertise in sport.</p
Wine and other alcohol consumption and risk of ovarian cancer in the California Teachers Study cohort
OBJECTIVE: Whether alcohol consumption influences ovarian cancer risk is unclear. Therefore, we investigated the association between alcohol intake at various ages and risk of ovarian cancer. METHODS: Among 90,371 eligible members of the California Teachers Study cohort who completed a baseline alcohol assessment in 1995–1996, 253 women were diagnosed with epithelial ovarian cancer by the end of 2003. Multivariate Cox proportional hazards regression analysis was performed to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Consumption of total alcohol, beer, or liquor in the year prior to baseline, at ages 30–35 years, or at ages 18–22 years was not associated with risk of ovarian cancer. Consumption of at least one glass per day of wine, compared to no wine, in the year before baseline was associated with increased risk of developing ovarian cancer: RR = 1.57 (95% CI 1.11–2.22), P(trend) = 0.01. The association with wine intake at baseline was particularly strong among peri-/post-menopausal women who used estrogen-only hormone therapy and women of high socioeconomic status. CONCLUSIONS: Alcohol intake does not appear to affect ovarian cancer risk. Constituents of wine other than alcohol or, more likely, unmeasured determinants of wine drinking were associated with increased risk of ovarian cancer
Complete In Vitro Life Cycle of Trypanosoma congolense: Development of Genetic Tools
Trypanosoma congolense is a parasite responsible for severe disease of African livestock. Its life cycle is complex and divided into two phases, one in the tsetse fly vector and one in the bloodstream of the mammalian host. Molecular tools for gene function analyses in parasitic organisms are essential. Previous studies described the possibility of completing the entire T. congolense life cycle in vitro. However, the model showed major flaws including the absence of stable long-term culture of the infectious bloodstream forms, a laborious time-consuming period to perform the cycle and a lack of genetic tools. We therefore aimed to develop a standardized model convenient for genetic engineering. We succeeded in producing long-term cultures of all the developmental stages on long-term, to define all the differentiation steps and to finally complete the whole cycle in vitro. This improved model offers the opportunity to conduct phenotype analyses of genetically modified strains throughout the in vitro cycle and also during experimental infections
The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes
The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13-14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13-14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.The METABRIC project was funded by Cancer Research UK, the British Columbia Cancer Foundation and Canadian Breast Cancer Foundation BC/Yukon. This sequencing project was funded by CRUK grant C507/A16278 and Illumina UK performed all the sequencing. The authors also acknowledge the support of the University of Cambridge, Hutchinson Whampoa, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre, the Centre for Translational Genomics (CTAG) Vancouver and the BCCA Breast Cancer Outcomes Unit. We thank the Genomics, Histopathology, and Biorepository Core Facilities at the Cancer Research UK Cambridge Institute, and the Addenbrooke’s Human Research Tissue Bank (supported by the National Institute for Health Research Cambridge Biomedical Research Centre).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1147
Lack of Association of Interferon Regulatory Factor 1 with Severe Malaria in Affected Child-Parental Trio Studies across Three African Populations
Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs) across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi). No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia) was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria
Risk Factors for and Clinical Outcome of Congenital Cytomegalovirus Infection in a Peri-Urban West-African Birth Cohort
BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide. Epidemiology and clinical outcomes are known to vary with socio-economic background, but few data are available from developing countries, where the overall burden of infectious diseases is frequently high. METHODOLOGY/PRINCIPAL FINDINGS: As part of an ongoing birth cohort study in The Gambia among term infants, urine samples were collected at birth and tested by PCR for the presence of CMV DNA. Risk factors for transmission and clinical outcome were assessed, including placental malaria infection. Babies were followed up at home monthly for morbidity and anthropometry, and at one year of age a clinical evaluation was performed. The prevalence of congenital CMV infection was 5.4% (40/741). A higher prevalence of hepatomegaly was the only significant clinical difference at birth. Congenitally infected children were more often first born babies (adjusted odds ratio (OR) 5.3, 95% confidence interval (CI) 2.0-13.7), more frequently born in crowded compounds (adjusted OR 2.9, 95%CI 1.0-8.3) and active placental malaria was more prevalent (adjusted OR 2.9, 95%CI 1.0-8.4). These associations were corrected for maternal age, bed net use and season of birth. During the first year of follow up, mothers of congenitally infected children reported more health complaints for their child. CONCLUSIONS/SIGNIFICANCE: In this study, the prevalence of congenital CMV among healthy neonates was much higher than previously reported in industrialised countries, and was associated with active placental malaria infection. There were no obvious clinical implications during the first year of life. The effect of early life CMV on the developing infant in the Gambia could be mitigated by environmental factors, such as the high burden of other infections.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe
AFCo1, a meningococcal B-derived cochleate adjuvant, strongly enhances antibody and T-cell immunity against Plasmodium falciparum merozoite surface protein 4 and 5
<p>Abstract</p> <p>Background</p> <p>Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP), to boost the immune response against two <it>Plasmodium falciparum </it>antigens, merozoite surface protein 4 (MSP4) and 5 (MSP5), was evaluated.</p> <p>Methods</p> <p>Complete Freund's adjuvant (CFA), which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH), T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline.</p> <p>Results</p> <p>AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses.</p> <p>Conclusion</p> <p>Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.</p
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