Genetic structure and colonisation history of European and UK population of Gammarus pulex

The structure of populations has been studied for many years and there have been three main factors that have been suggested as the cause for present-day distributions of species, those being environment, biology and history. With the use of molecular data and advanced phylogeographic approaches it is now possible to distinguish between the main causes of population structuring. The present study considers the extent of population structure in G. pulex on regional (UK) and large geographic (Europe) scales using studies of molecular genetic (allozymes, mtDNA sequencing and microsatellites) and morphological variation.Molecular analysis of Gammarus pulex in Europe revealed more diversity than previously thought. This was thought to be a consequence of two separate waves of colonisation after the formation of the major drainages in the Miocene. The UK appears to have been colonised once from either the Elbe, Mosel and Rhine drainages separately or cumulatively across the drainage basins late in the Pleistocene before a land bridge connection to mainland Europe was submerged. Limited molecular variation in the UK is thought to be a result of reduced genetic variation in the colonising individuals. This in turn was caused by repeated founder events during population expansion and contraction from European refugia.A detailed analysis of a transplantation experiment in 1950 in the Isle of Man revealed little genetic impoverishment of the introduced population when compared to the source. In contrast, morphological variation increased in the introduced population. Unlike in mainland Europe there was no historical explanation for the diversity recorded (as the introduced population was so young) and, in the absence of fragmentation, speciation and colonisation the contemporary forces of gene flow, selection and limited genetic drift are thought to be the determining factors in population structure

‘Walking ... just walking’: how children and young people’s everyday pedestrian practices matter

In this paper we consider the importance of ‘walking… just walking’ for many children and young people’s everyday lives. We will show how, in our research with 175 9-16-year-olds living in new urban developments in south-east England, some particular (daily, taken-for-granted, ostensibly aimless) forms of walking were central to the lives, experiences and friendships of most children and young people. The main body of the paper highlights key characteristics of these walking practices, and their constitutive role in these children and young people’s social and cultural geography. Over the course of the paper we will argue that ‘everyday pedestrian practices’ (after Middleton 2010, 2011) like these require us to think critically about two bodies of geographical and social scientific research. On one hand, we will argue that the large body of research on children’s spatial range and independent mobility could be conceptually enlivened and extended to acknowledge bodily, social, sociotechnical and habitual practices. On the other hand, we will suggest that the empirical details of such practices should prompt critical reflection upon the wonderfully rich, multidisciplinary vein of conceptualisation latterly termed ‘new walking studies’ (Lorimer 2011). Indeed, in conclusion we shall argue that the theoretical vivacity of walking studies, and the concerns of more applied empirical approaches such as work on children’s independent mobility, could productively be interrelated. In so doing we open out a wider challenge to social and cultural geographers, to expedite this kind of interrelation in other research contexts

Children Living in Sustainable Built Environments: New Urbanisms, New Citizens

Urban living has dramatically changed over the past generation, refashioning children’s relationships with the towns and cities in which they live, and the modes of living within them. Focusing on the global shift in urban planning towards sustainable urbanism - from master planned ‘sustainable communities’, to the green retrofitting of existing urban environments - Children Living in Sustainable Built Environments offers a critical analysis of the challenges, tensions and opportunities for children and young people living in these environments. Drawing upon original data, Children Living in Sustainable Built Environments demonstrates how the needs, interests and participation of children and young people often remain inferior to the design, planning and local politics of new urban communities. Considering children from their crucial role as residents engaging and contributing to the vitalities of their community, to their role as consumers using and understanding sustainable design features, the book critically discusses the prospects of future inclusion of children and young people as a social group in sustainable urbanism. Truly interdisciplinary, Children Living in Sustainable Built Environments forms an original theoretical and empirical contribution to the understanding of the everyday lives of children and young people and will appeal to academics and students in the fields of education, childhood studies, sociology, anthropology, human geography and urban studies, as well as policy-makers, architects, urban planners and other professionals working on sustainable urban designs. Drawing upon original data, Children Living in Sustainable Built Environments demonstrates how the needs, interests and participation of children and young people often remain inferior to the design, planning and local politics of new urban communities. Considering children from their crucial role as residents engaging and contributing to the vitalities of their community, to their role as consumers using and understanding sustainable design features, the book critically discusses the prospects of future inclusion of children and young people as a social group in sustainable urbanism. Truly interdisciplinary, Children Living in Sustainable Built Environments forms an original theoretical and empirical contribution to the understanding of the everyday lives of children and young people and will appeal to academics and students in the fields of education, childhood studies, sociology, anthropology, human geography and urban studies, as well as policy-makers, architects, urban planners and other professionals working on sustainable urban designs

Evolution and rapid spread of a reassortant A(H3N2) virus that predominated the 2017-2018 influenza season

The 2017-2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus's North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70 per cent of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, hemagglutination inhibition assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016-2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segmentsa virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics

Anticancer phototherapy using activation of E-combretastatins by two-photon–induced isomerization

The photoisomerization of relatively nontoxic E-combretastatins to clinically active Z-isomers is shown to occur in solution through both one- and two-photon excitations at 340 and 625 nm, respectively. The photoisomerization is also demonstrated to induce mammalian cell death by a two-photon absorption process at 625 nm. Unlike conventional photodynamic therapy (PDT), the mechanism of photoisomerization is oxygen- independent and active in hypoxic environments such as in tumors. The use of red or near-infrared (NIR) light for two-photon excitation allows greater tissue penetration than conventional UV one-photon excitation. The results provide a baseline for the development of a novel phototherapy that overcomes nondiscriminative systemic toxicity of Z-combretastatins and the limitations of PDT drugs that require the presence of oxygen to promote their activity, with the added benefits of two-photon red or NIR excitation for deeper tissue penetration

Leadership course evaluation with patient and public involvement

Executive Summary1. This project had two components, the evaluation of a Developing and Enhancing Leadership and Management Skills programme delivered to 150 frontline supervisory and senior managers in North Bristol NHS Trust and the implementation of guidelines for Patient and Public Involvement (PPI) in research.2. Evaluation data were collected through three knowledge café events engaging 36 staff. These events were used to facilitate and record meaningful conversations that were focused around five questions. Follow-up interviews were conducted with a further 15 staff.3. The PPI guidelines were applied throughout the project and the experiences of the two service users involved were recorded through ongoing dialogue and review of guideline implementation.4. Data from the events and interviews suggested the programme had benefits for staff. These included the development of new insights and better understanding of the roles and experiences of other leaders in the Trust. Immediate and sustained outcomes were also reported for the individuals and organisation. Staff felt that they moved forward professionally and had insight into the “bigger picture”. They also welcomed delivery from external facilitators who had a refreshing approach.5. Staff were also able to demonstrate new learning. In particular the programme had changed their approach to handling leadership issues and their use of tools and skills. Managers reported taking a different approach to the management of more challenging situations, planning responses rather than reacting and encouraging problem-solving and reflection in staff.6. Staff reflected on a number of issues that affected their ability to apply learning in practice. They commented on the need for a learning culture, with a strategy to support the implementation of new learning. They felt senior managerial support with the implementation of change was crucial. Having the time to implement learning was important and access to ongoing support to implement change would also be helpful, through perhaps knowledge café events or supervision and coaching.7. The service users found their involvement in this research to be largely positive, though there is a need to ensure all academics are attuned to the needs of service users engaged in projects.8. A number of recommendations emerged, such as: continue to include a wide range of staff in the same programme to allow sharing of expertise; consider delivering to an even wider range of staff including team leaders; maintain external consultancy role in delivery; consider post-course follow-up and include this in the initial contracting. There was also a recommendation that the organisation undertake internal reflections that explore the current learning culture and identify ways of supporting staff to implement learning in practice.9. The UWE guidelines for PPI in research were evaluated as being fit for purpose and could usefully guide service user and carer involvement in a range of evaluation and research projects

The causes and consequences of changes in virulence following pathogen host shifts.

Emerging infectious diseases are often the result of a host shift, where the pathogen originates from a different host species. Virulence--the harm a pathogen does to its host-can be extremely high following a host shift (for example Ebola, HIV, and SARs), while other host shifts may go undetected as they cause few symptoms in the new host. Here we examine how virulence varies across host species by carrying out a large cross infection experiment using 48 species of Drosophilidae and an RNA virus. Host shifts resulted in dramatic variation in virulence, with benign infections in some species and rapid death in others. The change in virulence was highly predictable from the host phylogeny, with hosts clustering together in distinct clades displaying high or low virulence. High levels of virulence are associated with high viral loads, and this may determine the transmission rate of the virus.BL and FMJ are supported by a NERC grant (NE/L004232/1), a European Research Council grant (281668, DrosophilaInfection), a Junior Research Fellowship from Christ’s College, Cambridge (BL) and a Royal Society University Research Fellowship (FMJ). JDH is supported by a Royal Society University Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004728

Augur: a bioinformatics toolkit for phylogenetic analyses of human pathogens

The analysis of human pathogens requires a diverse collection of bioinformatics tools. These tools include standard genomic and phylogenetic software and custom software developed to handle the relatively numerous and short genomes of viruses and bacteria. Researchers increasingly depend on the outputs of these tools to infer transmission dynamics of human diseases and make actionable recommendations to public health officials (Black et al., 2020; Gardy et al., 2015). In order to enable real-time analyses of pathogen evolution, bioinformatics tools must scale rapidly with the number of samples and be flexible enough to adapt to a variety of questions and organisms. To meet these needs, we developed Augur, a bioinformatics toolkit designed for phylogenetic analyses of human pathogens