William Van Milderet, Bishop

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Co-Occurrence of Anaerobic Bacteria in Colorectal Carcinomas

Background Numerous cancers have been linked to microorganisms. Given that colorectal cancer is a leading cause of cancer deaths and the colon is continuously exposed to a high diversity of microbes, the relationship between gut mucosal microbiome and colorectal cancer needs to be explored. Metagenomic studies have shown an association between Fusobacterium species and colorectal carcinoma. Here, we have extended these studies with deeper sequencing of a much larger number (n = 130) of colorectal carcinoma and matched normal control tissues. We analyzed these data using co-occurrence networks in order to identify microbe-microbe and host-microbe associations specific to tumors. Results We confirmed tumor over-representation of Fusobacterium species and observed significant co-occurrence within individual tumors of Fusobacterium, Leptotrichia and Campylobacter species. This polymicrobial signature was associated with over-expression of numerous host genes, including the gene encoding the pro-inflammatory chemokine Interleukin-8. The tumor-associated bacteria we have identified are all Gram-negative anaerobes, recognized previously as constituents of the oral microbiome, which are capable of causing infection. We isolated a novel strain of Campylobacter showae from a colorectal tumor specimen. This strain is substantially diverged from a previously sequenced oral Campylobacter showae isolate, carries potential virulence genes, and aggregates with a previously isolated tumor strain of Fusobacterium nucleatum. Conclusions A polymicrobial signature of Gram-negative anaerobic bacteria is associated with colorectal carcinoma tissue

Hydrogen isotope exchange with highly active iridium(I) NHC/phosphine complexes : a comparative counter-ion study

Herein we present a range of substrates that undergo hydrogen isotope exchange with an iridium(I) NHC/phosphine complex bearing the less coordinating tetrakis[3,5-bis(trifluoromethyl)phenyl]borate counterion, and compare these with labelling using the equivalent, more established hexafluorophosphate complex. The changes in reactivity and selectivity of these complexes in a series of solvents are examined

My neighbourhood: Studying perceptions of urban space and neighbourhood with moblogging

We describe a novel methodology that examines perceptions of urban space, and present a study using this methodology that explores people’s perceptions of their neighbourhood. Previous studies of spatial cues have involved a variety of tasks such as pointing and sketching to externalise participants’ internal spatial maps. Our methodology extends these approaches by introducing mobile technologies alongside traditional materials and tasks. Participants use mobile phones to carry out self-guided neighbourhood tours. We collected rich qualitative data from 15 participants during two workshops and a self-directed neighbourhood tour. Our study highlights the use of public and private landmarks, differences in spatial maps of rural versus urban dwellers, and individual variance in orientation strategies. These themes suggest guidelines for the design of technologies with personalised spatial profiles

Devolving the heartland: making up a new social policy for the 'South East'

Devolution appears to challenge the traditional regional and national hierarchies of the UK, but in practice the dominance of the South East of England has been maintained through active state intervention. As social welfare has increasingly been redefined through economic success and access to the labour market, the focus of social policy has shifted accordingly. In this context the South East has been re-imagined not as a symbol of inequality and a potential source of redistribution, but rather as driver of economic prosperity and 'national' (UK) well-being

‘All hands-on deck’, working together to develop UK standards for public involvement in research

Background: Public involvement in research is an established part of the research process in the UK, however there remain questions about what good public involvement in research looks and feels like. Until now public involvement practitioners, researchers and members of the public have looked for answers in examples shared across networks, published case studies, guidance and research articles. Pulling these strands together, the UK Standards for Public Involvement provides six statements (standards) about public involvement in research. They were produced by a partnership of organisations from Scotland, Northern Ireland, Wales and England with contributions from involvement practitioners, public partners, researchers and research funders. Main body: Each standard has reflective questions, which are designed to encourage standard users to use approaches and behaviours that improve involvement, over time. The standards are designed to be used as a practical tool, and reflect the agreed hallmarks of good public involvement in research for example, flexibility in approaches used, shared learning, and mutual respect. The standards development process is described from the initial idea and scoping, via the appraisal of existing standard sets and integration of values and principles in public involvement in research. The collaborative writing process of and consultation on the draft standard set is described, together with what changed as a result of feedback. The initiation of a year-long testing programme with forty participating research organisations, the experiential feedback and the resulting changes to the standards is summarised. Conclusion: This commentary paper describes, in some detail, a process to develop a set of six standards for public involvement in research in the UK. Producing a complex, national public involvement initiative is not without its challenges, and in supplementary material partnership members reflect on and share their experiences of standards development. The next phase of integration and implementation is explored with concluding comments from those that tested and helped improve the standards

A consideration of the challenges involved in supervising international masters students

This paper explores the challenges facing supervisors of international postgraduate students at the dissertation stage of the masters programme. The central problems of time pressure, language difficulties, a lack of critical analysis and a prevalence of personal problems among international students are discussed. This paper makes recommendations for the improvement of language and critical thinking skills, and questions the future policy of language requirements at HE for international Masters students

ALEGRA-MHD : version 4.6

ALEGRA is an arbitrary Lagrangian-Eulerian finite element code that emphasizes large distortion and shock propagation in inviscid fluids and solids. This document describes user options for modeling resistive magnetohydrodynamic, thermal conduction, and radiation emission effects

First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial)

Background: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use.Patients and methods: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.Results: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids.Conclusions: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer