Introduction

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Aedes Anphevirus: an insect-specific virus distributed worldwide in Aedes aegypti mosquitoes that has complex interplays with Wolbachia and dengue virus infection in cells

Insect specific viruses (ISVs) of the yellow fever mosquito Aedes aegypti have been demonstrated to modulate transmission of arboviruses such as dengue virus (DENV) and West Nile virus by the mosquito. The diversity and composition of the virome of Ae. aegypti, however, remains poorly understood. In this study, we characterised Aedes anphevirus (AeAV), a negative-sense RNA virus from the order Mononegavirales. AeAV identified from Aedes cell lines were infectious to both Ae. aegypti and Aedes albopictus cells, but not to three mammalian cell lines. To understand the incidence and genetic diversity of AeAV, we assembled 17 coding-complete and two partial genomes of AeAV from available RNA-Seq data. AeAV appears to transmit vertically and be present in laboratory colonies, wild-caught mosquitoes and cell lines worldwide. Phylogenetic analysis of AeAV strains indicates that as the Ae. aegypti mosquito has expanded into the Americas and Asia-Pacific, AeAV has evolved into monophyletic African, American and Asia-Pacific lineages. The endosymbiotic bacterium Wolbachia pipientis restricts positive-sense RNA viruses in Ae. aegypti. Re-analysis of a small RNA library of Ae. aegypti cells co-infected with AeAV and Wolbachia produces an abundant RNAi response consistent with persistent virus replication. We found Wolbachia enhances replication of AeAV when compared to a tetracycline cleared cell line, and AeAV modestly reduces DENV replication in vitro. The results from our study improve understanding of the diversity and evolution of the virome of Ae. aegypti and adds to previous evidence that shows Wolbachia does not restrict a range of negative strand RNA viruses. IMPORTANCE: The mosquito Aedes aegypti transmits a number of arthropod-borne viruses (arboviruses) such as dengue virus and Zika virus. Mosquitoes also harbour insect-specific viruses that may affect replication of pathogenic arboviruses in their body. Currently, however, there are only a handful of insect-specific viruses described from Ae. aegypti in the literature. Here, we characterise a novel negative strand virus, Aedes anphevirus (AeAV). Meta-analysis of Ae. aegypti samples showed that it is present in Ae. aegypti mosquitoes worldwide and is vertically transmitted. Wolbachia transinfected mosquitoes are currently being used in biocontrol as they effectively block transmission of several positive sense RNA viruses in mosquitoes. Our results demonstrate that Wolbachia enhances the replication of AeAV and modestly reduces dengue virus replication in a cell line model. This study expands our understanding of the virome in Ae. aegypti as well as providing insight into the complexity of the Wolbachia virus restriction phenotype

Strategies to manage postpartum haemorrhage

Postpartum haemorrhage (PPH) is a global problem and the solutions to reducing it are complex. This thesis uses a mixture of research methods to investigate strategies that might improve the burden of blood loss following childbirth. The main findings are: 1. The use of contraception medication prior to pregnancy warrants further research as progesterone only contraception in particular might be associated with an increase in the risk of subsequent PPH; 2. The use of antidepressant medication during late pregnancy does not appear to increase the risk of PPH; 3. Following childbirth, a preventative uterotonic drug may not need to be given immediately; a delay of up to 5 minutes does not appear to increase the risk of bleeding; 4. There is little evidence to recommend the use of oxytocin, carbetocin, or misoprostol over each other for use as a first line drug to treat PPH; 5. Less than half of patients who had a PPH of 500mL received treatment uterotonic medication; 6. There is no appreciable long-term effect of PPH on mental health, but there is an increased risk of developing postnatal depression and post traumatic stress disorder; 7. There is no appreciable effect of PPH on cardiovascular health

Wolbachia endosymbiont of the horn fly Haematobia irritans irritans: a supergroup A strain with multiple horizontally acquired cytoplasmic incompatibility genes

The horn fly, Haematobia irritans irritans, is a hematophagous parasite of livestock distributed throughout Europe, Africa, Asia, and the Americas. Welfare losses on livestock due to horn fly infestation are estimated to cost between USD 1-2.5 billion annually in North America and Brazil. The endosymbiotic bacterium Wolbachia pipientis is a maternally inherited manipulator of reproductive biology in arthropods and naturally infects laboratory colonies of horn flies from Kerrville, USA and Alberta, Canada, but has also been identified in wild-caught samples from Canada, USA, Mexico and Hungary. Re-assembly of PacBio long-read and Illumina genomic DNA libraries from the Kerrville H. i. irritans genome project allowed for a complete and circularised 1.3 Mb Wolbachia genome (wIrr). Annotation of wIrr yielded 1249 coding genes, 34 tRNAs, three rRNAs, and five prophage regions. Comparative genomics and whole genome Bayesian evolutionary analysis of wIrr compared to published Wolbachia genomes suggests that wIrr is most closely related to and diverged from Wolbachia supergroup A strains known to infect Drosophila spp. Whole-genome synteny analyses between wIrr and closely related genomes indicates that wIrr has undergone significant genome rearrangements while maintaining high nucleotide identity. Comparative analysis of the cytoplasmic incompatibility (CI) genes of wIrr suggests two phylogenetically distinct CI loci and acquisition of another CifB homolog from phylogenetically distant supergroup A Wolbachia strains suggesting horizontal acquisition of these loci. The wIrr genome provides a resource for future examination of the impact Wolbachia may have in both biocontrol and potential insecticide resistance of horn flies

Comparative analysis of genome-encoded viral sequences reveals the evolutionary history of flavivirids (family Flaviviridae)

The flavivirids (family Flaviviridae) are a group of positive-strand RNA viruses that pose serious risks to human and animal health on a global scale. Here we use flavivirid-derived DNA sequences, identified in animal genomes, to reconstruct the long-term evolutionary history of family Flaviviridae. We demonstrate that flavivirids are >100 million years old and show that this timing can be combined with dates inferred from co-phyletic analysis to produce a cohesive overview of their evolution, distribution and diversity wherein the main flavivirid subgroups originate in early animals and broadly co-diverge with major animal phyla. In addition, we reveal evidence that the ‘classical flaviviruses’ of vertebrates, most of which are transmitted via blood-feeding arthropod vectors, originally evolved in hematophagous arachnids and later acquired the capacity to be transmitted by insects. Our findings imply that the biological properties of flavivirids have been acquired gradually over the course of animal evolution. Thus, broad-scale comparative analysis will likely reveal fundamental insights into their biology. We therefore published our results via an open, extensible, database (Flavivirid-GLUE), which we constructed to facilitate the wider utilisation of genomic data and evolution-related domain knowledge in flavivirid research

Teaching and learning in the outdoors:The current state of outdoor learning in schools in Wales

This report presents the findings of a study investigating the knowledge of, access to and purposes for, outdoor learning in Wales. Outdoor learning played a significant role in the health and wellbeing of children and young people during the Covid-19 pandemic (Sefton, 2021) and a previous WG commissioned report found that during, between, and directly subsequent to Covid-19 lockdowns, ‘outdoor learning played an increased role, both in and out of school, in supporting physical and mental wellbeing’ (French, Horder, Jones, Parry, Mahoney, Moody and Rhys-Jones, 2021, p. 79). With the importance of outdoor learning as a pedagogical approach that has both physical and cognitive benefits having been established, the current study attempted to provide an indication of how outdoor learning was being utilised in schools across Wales. The research utilised a small convenience sample to provide indicative findings of the frequency, type of activity and purposes of activity undertaken by schools. The study deployed a survey-based data capture instrument and research design based on an effective methodology from three studies conducted in Scotland (commissioned by Scottish Government), commencing in the late 2000s through to 2018. The data collection instrument was modified to suit the Welsh context in terms of school types and provision, and in light of the transitional period between the previous iteration of, and the current Curriculum for Wales. The study found that amongst the schools surveyed, sessions ranged in duration from 30 mins to full days (6 hours), with groups ranging from 4 children to 29. There were between 1 and 4 adults supervising the children during these sessions who were teachers and teaching assistants, associate teachers (a term frequently used by ITE partnerships to describe student teachers) or outdoor instructors. The main purposes of the sessions were to develop teamworking skills, and to draw direct links with the Curriculum for Wales. Fewer sessions were delivered for the specific purposes of extra-curricular health and well-being or to experience nature and a sense of place (cynefin), and there were very few sessions reported for the purpose of field work, being creative, adventure or to study or conserve local heritage or learn about Wales. The main stated curriculum links were to the health and well-being and language literacy and communication areas of learning and experience. There were very few sessions with clear links to recognised award schemes such as the John Muir Award. The reported impact of the sessions on the children and young people concerned was primarily concerned with developing personal choice and overcoming challenge.Other findings concerned the challenges of collecting data by the research team resulting from the over-researching of practitioners during challenging times (still during the Covid-19 recovery period for instance) and the plethora of similar projects that also utilised existing HEI/school networks so the same schools are routinely asked to contribute. The report concluded that the timing of data collection came at a time of year when the weather in Wales requires more protective clothing to remain comfortable and thus there were potentially fewer episodes of outdoor learning than might have been expected from the literature review, and that whilst outdoor learning was valued by the schools that engaged in the survey, the sample size was very small and therefore findings are indicative rather than generalised across Wales. The project timing and scale were constrained by the timescale of the commission, but did highlight that there is still a lack of clarity concerning a definition of outdoor learning. Between the completion of this study and the submission of this report, definitions of outdoor learning, adventure education and outdoor education (specific to the Welsh educational context) have been suggested in the presentation to the Outdoor Activity Sector Senedd Cross Party Group on 28th September 2022.<br/

No evidence of SARS-CoV-2 reverse transcription and integration as the origin of chimeric transcripts in patient tissues

No abstract available

Genetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis

Download PDFPDF Urology Protocol Genetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis Joseph M Norris1, Benjamin S Simpson1, Marina A Parry2, Clare Allen3, Rhys Ball4, Alex Freeman4, Daniel Kelly5, Alex Kirkham3, Veeru Kasivisvanathan1, Hayley C Whitaker1, Mark Emberton1 Author affiliations Abstract Introduction The introduction of multiparametric MRI (mpMRI) has enabled enhanced risk stratification for men at risk of prostate cancer, through accurate prebiopsy identification of clinically significant disease. However, approximately 10%–20% of significant prostate cancer may be missed on mpMRI. It appears that the genomic basis of lesion visibility or invisibility on mpMRI may have key implications for prognosis and treatment. Here, we describe a protocol for the first systematic review and novel bioinformatic analysis of the genomic basis of prostate cancer conspicuity on mpMRI. Methods and analysis A systematic search of MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included papers will be full text articles, written between January 1980 and December 2019, comparing molecular characteristics of mpMRI-visible lesions and mpMRI-invisible lesions at the DNA, DNA-methylation, RNA or protein level. Study bias and quality will be assessed using a modified Newcastle-Ottawa score. Additionally, we will conduct a novel bioinformatic analysis of supplementary material and publicly available data, to combine transcriptomic data and reveal common pathways highlighted across studies. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist. Ethics and dissemination Ethical approval will not be required, as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences

Genetic landscape of prostate cancer conspicuity on multiparametric magnetic resonance imaging: a systematic review and bioinformatic analysis

Context Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. Objective To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. Evidence acquisition We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. Evidence synthesis We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. Conclusions Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. Patient summary Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility