An investigation into the effect of salt (sodium chloride) on immunity in patients with kidney disease

The salt (sodium chloride; NaCl) content of a western diet far exceeds the amount that we consumed through most of our evolutionary history. It is accepted that excess sodium intake causes hypertension and cardiovascular disease, but it has been recently shown that sodium also affects immunity, and high salt diets worsen animal models of autoimmune disease. Sodium has been shown to activate multiple immune cells, including Th17 cells, which provide protection from bacterial and fungal infection but which are also implicated in autoimmune disease. The mechanism by which sodium polarises Th17 cells, whether salt depletion has clinical consequences, and if altering sodium balance affects the development of inflammatory kidney diseases are unknown. In this project, I investigate the effect of salt on IL-17 responses and how this is relevant in patients with kidney disease. I demonstrate that NaCl promotes IL-17 responses in both CD4+ (Th17) and CD8+ (Tc17) cells. This effect is mediated by sodium altering calcium flux during T cell activation and may be abrogated by inhibition of the sodium-potassium-chloride (NKCC) transporter and the epithelial sodium channel (ENaC) on immune cells. Patients with inherited salt losing tubulopathies (SLTs) have clinical features of immunodeficiency with increased infections and allergic disease. This is associated with a reduced ratio of circulating Th17:Th2 cells, and Th17 polarisation in SLT patients is impaired compared with controls. I show that SLT patients have reduced sodium stores and that the typical extracellular ionic environment in SLT is inhibitory to Th17 polarisation. Salt supplementation in vitro rescues IL-17 responses in SLT patients. Lastly, I demonstrate that Th17 cells are salt responsive in patients with inflammatory kidney disease despite in vivo immunosuppression. A high salt diet did not alter the development of an animal model of glomerulonephritis, but a low salt diet was a feasible therapeutic intervention in kidney transplant recipients

Bowled out for a duck before picking up a bat: identifying women’s perceived barriers and lived experiences of cricket within the City of Lincoln

Gender inequality in sport has received significant attention from sports development initiatives and sociologists of sport. Gender inequality describes the structuring of aspects of society that favours one gender over another. Feminist academic literature is heavily focused around how the inequality is perpetuated in society (Hargreaves, J. (2000) Heroines of Sport: ‘The politics of difference and identity’. London: Routledge.). The prevalence of gender inequality is reflected in women’s participation levels in typically masculine sports such as cricket. Approximately 0.08% of the female population take part in cricket in the UK, which suggests there are inherent barriers to women’s participation (Sport England, 2011, Active People Survey 2011). This problem is something that has been highlighted as a substantial aim that the legacy of the 2012 London Olympics can help overcome (London Organising Committee of the Olympic and Paralympics games Ltd (2008) Diversity and Inclusion strategy). The present study builds on previous work to increase opportunities for women to participate in cricket (Hibberd et al 2011; ‘Not Just a Boys Game’: Programme evaluation of a multi-agency cricket intervention designed to reduce gender inequity in a city in the East of England.’Paper presented at the student BASES 2011 conference). The principal aim of this study is to investigate the perceived barriers that active women feel prevent or inhibit their participation in cricket. A case study approach will be adopted, focusing on six women’s community and University sports clubs in Lincoln, in conjunction with Lincolnshire Cricket board (LCB). Women will be recruited from an array of social backgrounds, with different abilities, ages and experiences of sport. A mixed method approach utilising both questionnaires and semi-structured group interviews will be employed (Bryman, A. (1988) Quantity and Quality in Social Research. London: Routledge). A theory driven approach to understanding women’s perceived barriers to participation in cricket will be adopted. The project will enable researchers to gain a better understanding of the reasons why women find access to certain sports easier than others. This information will allow researchers to make recommendations for widening participation in women’s cricket, with a view to increasing the viability of women’s participation in cricket locally

Why Do Word Blends with Near-Synonymous Composites Exist and Persist? The Case of Guesstimate, Chillax, Ginormous and Confuzzled

Despite their increasing use, little is known about the purpose of word blends, e.g. chillax, which have near-synonymous composite words (relax and chill). Potential explanations for their existence and persistence include: use in different sentence constructions, to provide unique meaning, and to create interest/identity. Th e current study used a vignette methodology with two-hundred and forty-one students to explore the relevance of such hypotheses for ‘guesstimate’, ‘chillax’, ‘ginormous’, and ‘confuzzled’. Our inconsistent results suggest that the semantics of the word blends may diff er from their composites in very subtle ways. However further work is needed to acknowledge and determine the impact of context upon the use and consequences of these word blends

On regular induced subgraphs of edge-regular graphs.

PhD Thesis.We study edge-regular graphs and their regular induced subgraphs. More precisely, we are interested in vertex partitions of edge-regular graphs into two parts, for which one or both of the parts induce a regular subgraph. We can divide the thesis into three major components, where we focus on di erent subclasses of edge-regular graphs and partitions with varying properties. First we consider regular induced subgraphs of strongly regular graphs. We determine new upper and lower bounds on the order of a d-regular induced subgraph of a strongly regular graph with given parameters. We prove our bounds are at least as good as some well-known bounds for the order of regular induced subgraphs of regular graphs. Further, we nd that our bounds are often better than these well-known bounds. Secondly, we investigate edge-regular graphs which have a partition into a clique and a regular induced subgraph. We rst explore some fundamental properties of these graphs and their parameters. Then we construct new graphs having partitions with previously unseen properties, answering questions found in the literature. Finally, we examine partitions of the Johnson graphs J(n; 3) into two regular induced subgraphs. We use the combinatorial structure and spectrum of J(n; 3) to investigate the local structure of particular partitions in J(n; 3). To study these problems, we use algebraic and computational tools in conjunction with combinatorial arguments. A manual for AGT, a software package developed and used during this thesis, is found in the appendix

Learning Structured Preferences

Learning the preferences of other people is crucial for predict- ing future behavior. Both children and adults make inferences about others’ preferences from sparse data and in situations where the preferences have complex internal structures. We present a computational model of learning structured prefer- ences which integrates Bayesian inference and utility-based models of preference from economics. We experimentally test this model with adult participants, and compare the model to alternative heuristic models