Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Hand gesture-based interactive puppetry system to assist storytelling for children

© 2016 The Author(s)Digital techniques have been used to assist narrative and storytelling, especially in many pedagogical practices. With the rapid development of HCI techniques, saturated with digital media in their daily lives, young children, demands more interactive learning methods and meaningful immersive learning experiences. In this paper, we propose a novel hand gesture-based puppetry storytelling system which provides a more intuitive and natural human computer interaction method for young children to develop narrative ability in virtual story world. Depth motion sensing and hand gestures control technology is utilized in the implementation of user-friendly interaction. Young players could intuitively use hand gestures to manipulate virtual puppet to perform story and interact with different items in virtual environment to assist narration. Based on the result of the evaluation, this novel digital storytelling system shows positive pedagogical functions on children’s narrating ability as well as the competencies of cognitive and motor coordination. The usability of the system is preliminary examined in our test, and the results which showed that young children can benefit from playing with Puppet Narrator

Attitudes towards Human Papillomavirus vaccination among African parents in a city in the north of England: A qualitative study.

Background: Human papillomavirus (HPV) is sexually transmitted and has been conclusively linked to cervical cancer and genital warts. Cervical cancer is attributed to approximately 1100 deaths annually in UK, and is the second most common female cancer globally. It has been suggested that black African women are more predisposed to HPV infection and cervical cancer. A vaccine has been developed to reduce HPV infection, and in the UK, has been offered to 12-13 year old adolescent girls through schools as part of their childhood immunization programme since 2008. Upon programme initiation, it was noted that vaccine uptake was lower in schools where girls from ethnic minority groups were proportionately higher. Objectives: The study’s objectives were to explore factors influencing UK based African parents’ acceptance or decline of the HPV vaccine, whether fathers and mothers share similar views pertaining to vaccination and any interfamily tensions resulting from differing views. Methodology: A qualitative study was conducted with five African couples residing in north England. Face to face semi-structured interviews were carried out. Participants were parents to at least one daughter aged between 8 and 14 years. Recruitment was done through purposive sampling using snowballing. Results: HPV and cervical cancer awareness was generally low, with awareness lower in fathers. HPV vaccination was generally unacceptable among the participants, with fear of promiscuity, infertility and concerns that it’s still a new vaccine with yet unknown side effects cited as reasons for vaccine decline. There was HPV risk denial 3 as religion and good cultural upbringing seemed to result in low risk perceptions, with HPV and cervical cancer generally perceived as a white person’s disease. Religious values and cultural norms influenced vaccine decision-making, with fathers acting as the ultimate decision makers. Current information about why the vaccine is necessary was generally misunderstood. Conclusion: Tailored information addressing religious and cultural concerns may improve vaccine acceptability in African parents

Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems

Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change

Applying Bayesian model averaging for uncertainty estimation of input data in energy modelling

Background Energy scenarios that are used for policy advice have ecological and social impact on society. Policy measures that are based on modelling exercises may lead to far reaching financial and ecological consequences. The purpose of this study is to raise awareness that energy modelling results are accompanied with uncertainties that should be addressed explicitly. Methods With view to existing approaches of uncertainty assessment in energy economics and climate science, relevant requirements for an uncertainty assessment are defined. An uncertainty assessment should be explicit, independent of the assessor’s expertise, applicable to different models, including subjective quantitative and statistical quantitative aspects, intuitively understandable and be reproducible. Bayesian model averaging for input variables of energy models is discussed as method that satisfies these requirements. A definition of uncertainty based on posterior model probabilities of input variables to energy models is presented. Results The main findings are that (1) expert elicitation as predominant assessment method does not satisfy all requirements, (2) Bayesian model averaging for input variable modelling meets the requirements and allows evaluating a vast amount of potentially relevant influences on input variables and (3) posterior model probabilities of input variable models can be translated in uncertainty associated with the input variable. Conclusions An uncertainty assessment of energy scenarios is relevant if policy measures are (partially) based on modelling exercises. Potential implications of these findings include that energy scenarios could be associated with uncertainty that is presently neither assessed explicitly nor communicated adequately

Child categorization

Categorization is a process that spans all of development, beginning in earliest infancy yet changing as children's knowledge and cognitive skills develop. In this review article, we address three core issues regarding childhood categorization. First, we discuss the extent to which early categories are rooted in perceptual similarity versus knowledge-enriched theories. We argue for a composite perspective in which categories are steeped in commonsense theories from a young age but also are informed by low-level similarity and associative learning cues. Second, we examine the role of language in early categorization. We review evidence to suggest that language is a powerful means of expressing, communicating, shaping, and supporting category knowledge. Finally, we consider categories in context. We discuss sources of variability and flexibility in children's categories, as well as the ways in which children's categories are used within larger knowledge systems (e.g., to form analogies, make inferences, or construct theories). Categorization is a process that is intrinsically tied to nearly all aspects of cognition, and its study provides insight into cognitive development, broadly construed. WIREs Cogn Sci 2011 2 95–105 DOI: 10.1002/wcs.96 For further resources related to this article, please visit the WIREs websitePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78491/1/96_ftp.pd

Southern Ocean pteropods at risk from ocean warming and acidification

Early life stages of marine calcifiers are particularly vulnerable to climate change. In the Southern Ocean aragonite undersaturation events and areas of rapid warming already occur and are predicted to increase in extent. Here, we present the first study to successfully hatch the polar pteropod Limacina helicina antarctica and observe the potential impact of exposure to increased temperature and aragonite undersaturation resulting from ocean acidification (OA) on the early life stage survival and shell morphology. High larval mortality (up to 39%) was observed in individuals exposed to perturbed conditions. Warming and OA induced extensive shell malformation and dissolution, respectively, increasing shell fragility. Furthermore, shell growth decreased, with variation between treatments and exposure time. Our results demonstrate that short-term exposure through passing through hotspots of OA and warming poses a serious threat to pteropod recruitment and long-term population viability

Extra-pair parentage and personality in a cooperatively breeding bird

Why so much variation in extra-pair parentage occurs within and among populations remains unclear. Often the fitness costs and benefits of extra-pair parentage are hypothesised to explain its occurrence; therefore, linking extra-pair parentage with traits such as personality (behavioural traits that can be heritable and affect reproductive behaviour) may help our understanding. Here, we investigate whether reproductive outcomes and success are associated with exploratory behaviour in a natural population of cooperatively breeding Seychelles warblers (Acrocephalus sechellensis) on Cousin Island. Exploratory behaviour correlates positively with traits such as risk-taking behaviour and activity in other wild bird species and might promote extra-pair mating by increasing the rate at which potential extra-pair partners are encountered. We therefore predicted that fast-exploring individuals would have more extra-pair offspring. There is also a potential trade-off between pursuing extra-pair parentage and mate guarding in males. We therefore also predicted that fast-exploring males would be more likely to pursue extra-pair parentage and that this would increase the propensity of their mate to gain extra-pair parentage. We found that neither the total number of offspring nor the number of extra-pair offspring were associated with a male’s or female’s exploratory behaviour. However, there was a small but significant propensity for females to have extra-pair fertilisations in pairs that were behaviourally disassortative. Overall, we conclude that, due to the small effect size, the association between exploratory behaviour and extra-pair paternity is unlikely to be biologically relevant. Significance statement: True genetic monogamy is rare, even in socially monogamous systems, and multiple factors, such as behaviour, social structure, morphology and physiology, determined by the biological system can cause variation in extra-pair parentage (EPP). Therefore, investigating the inherent differences in these factors among individuals could be informative. We investigated whether reproductive outcomes/success are associated with differences in the propensity to explore novel environments/objects in a promiscuous, island-dwelling cooperatively breeding bird, the Seychelles warbler. Our results showed that exploratory behaviour was not associated with the number of offspring produced by an individual, and thus the long-term fitness consequences of different exploratory tendencies did not differ. We also found that the propensity to engage in EPP in females was higher in dissimilar behavioural pairs, but due to the small effect size, we hesitate to conclude that there are personality-dependent mating outcomes in the population