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Background Over the past decade the nursing profession has seen a significant shortage of nurses to meet the ever-increasing demands of the National Health Service (NHS). This has placed recruitment and retention at the forefront of political agendas. In order to meet increasing demand, health boards need to explore new avenues of working especially for remote and rural practice. A group of nurses are at the forefront of patient care and who's role incorporates working in some of the harshest environments across the UK. These nurses work on remote and rural islands known locally as non-doctor islands (NDI). These islands are unique to Northern Scotland and cover three health boards, NHS Orkney, NHS Shetland and NHS Highland. These nurses provide 24-hour cover 365 days a year with a diverse skill set that covers primary, secondary and emergency care. This study will explore the factors that influence nurse's decisions to live and work on the NDIs and furthermore the factors that keep them in post. Aims and Objectives The overall aim of this study is to understand the life history and career events that influence the trajectory of nurses who work on non-doctor islands across Northern Scotland. To furthermore understand the career journey of nurses and what influences their decision-making process to work on non-doctor islands. To understand the experiences of nurses who work on non-doctor islands and to understand the reasons nurses, remain or leave their employment on non-doctor islands. Methods This research explored the life history of eleven nurses who work and live on the NDIs. The aim of which is to understand the factors that influence their overall recruitment and retention to the islands. What makes this research unique is the use of a life history methodology. This methodology is used to underpin semi-structured interviews of the nurses, taking them back to their early childhood memoirs and mapping their career and life journeys to the present day. Results The results show that childhood support networks form an important aspect in their early childhood experiences. It is these experiences where we see the emergence and recurring life history themes of independence, resilience and teamwork. The pathways into nursing were fostered by first-hand experiences of caring and that of family role models. Today we see nurses that form part of the wider island community who have clinical autonomy and work life balance. The move to a non-doctor island for many is their final steppingstone before retirement. Conclusion This research has identified the factors that influence nurse recruitment and retention to NDIs. The use of a life history methodology has facilitated an insight into the life history of the participants from their early childhood memories to the present day.

Acanthamoeba species have been found to be facultative, opportunistic, protozoan, parasites. They are found ubiquitously in the environment. Acanthamoeba species are emerging pathogens causing a severe corneal infection called Acanthamoeba keratitis (AK) in immunocompetent individuals normally associated with contact lens wearers, which may result in blindness. Many drugs used to treat Acanthamoeba infections are poorly effective because they can induce encystation and/or fail to eliminate cysts, so more reliable and effective therapies are required. To this end, the studies described herein demonstrate the ability of Acanthamoeba unlike its mammalian host to synthesise histidine and lysine. Thus growth of Acanthamoeba spp. was restricted by 3-amino-1, 2, 4-triazole (3AT) (IC50 125μM), an inhibitor of imidazoleglycerol-phosphate dehydratase (IGPD) (EC 4.2.1.19) a key enzyme for de novo histidine biosynthesis. The addition of histidine was able to ablate the effects of 3AT in a dose dependent manner when added to cultures, indicating that 3AT was specifically acting on histidine biosynthesis. 3AT had minimal cytotoxicity to a prostate cancer cell line (PC3-luc) at concentrations that restrict the growth of Acanthamoeba. Bioinformatic analysis demonstrated that Acanthamoeba has the full complement of enzymes necessary for histidine biosynthesis. The complete coding sequence for a novel multifunctional gene, histidinol dehydrogenase (EC 1.1.1.23) and IGPD (EC 4.2.1.19) have both been amplified from A. castellanii and A. polyphaga cDNA, both have been cloned and sequenced. The gene encoding histidinol dehydrogenase from Acanthamoeba has been found to encode several enzymes including imidazoleglycerol phosphate synthase, phosphoribosyl-formimino-5-amino-1-imidazole-carboxyamide ribotide isomerase, phosphoribosyl-AMP cyclohydrolase, phosphoribosyl-ATP pyrophosphatase, histidinol dehydrogenase and ATP Phosphoribosyltransferase. An experimental compound (C348) previously demonstrated to inhibit IGPD of plant species was found to restrict the growth of Acanthamoeba (IC50 305nM). This inhibition was also ablated with the addition of exogenous histidine when added to the medium. C348 showed no cytotoxicity effects to the PC3-luc at concentrations restricting the growth of Acanthamoeba species.

Lag phase is a period of bacterial adaptation that occurs prior to cell division. The aim of this project was to characterise the processes used by Salmonella enterica serovar Typhimurium to escape from lag phase, and determine whether these processes are dependent on the bacterial ‘physiological history’. The lag phase transcriptomic response at 25 °C of stationary phase cells that had been held for twelve days at 2 °C was compared with that of stationary phase cells not subjected to this cold storage treatment. Cold-stored cells showed significant changes in expression of 78 % genes during lag phase, with 875 genes altering their expression ≥2-fold within the first four minutes of inoculation into fresh medium. Functional categories of genes that were significantly up-regulated included those encoding systems involved with metal ion uptake, stress resistance, phosphate uptake, ribosome synthesis and cellular metabolism. Genes in the OxyR regulon were induced earlier in cold-stored cells, a response coupled with a delay in the expression of Fe2+ acquisition genes, and down-regulation of genes encoding central metabolic enzymes. Together, these findings with physiological tests demonstrated that Salmonella held in cold storage exhibited an increased sensitivity to oxidative stress in midlag phase, although the lag time was not increased. Despite an oxidative stress response at the transcriptomic level during lag phase under both experimental conditions, deletion of the OxyR and SoxRS systems did not lead to an increased lag time during aerobic growth at 25 °C. The intracellular concentration of metal ions was quantified using ICP-MS, and changes observed during lag phase confirmed the transcriptomic data. Metal ions specifically accumulated during lag phase included Mn2+, Fe2+, Cu2+ and Ca2+, with the latter being the most abundant metal ion. The intracellular concentration of Zn2+ and Mg2+ remained the same as for stationary phase cells, and Ni2+, Mo2+ and Co2+ were expelled from the cell during lag phase. Metal homeostasis was determined to be a critical process, highlighted by growth in the presence of a chelator causing an extended lag time. Overall, lag phase was found to be a robust and reproducible adaptation period which was not perturbed by the mutagenesis approaches utilised in this study.