Background: Some dietary patterns have been associated with colorectal cancer (CRC) in observational studies but the findings are inconclusive. The aim of this study is to explore associations between two dietary patterns, derived using different dietary assessment methods, and risk of CRC. Methods: CRC event data for the UK Women’s Cohort Study were obtained from NHS Digital. Adherence scores to the Mediterranean dietary pattern and to the 2007 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations respectively were generated. Cox regression was used to estimate hazard ratios (HRs) for CRC risk, for each score separately, using a cohort approach for food frequency data and a case-cohort design for analyses with food diary data. Agreement between scores derived by the two different assessment methods was assessed by weighted Kappa statistics and the Bland-Altman method. Results: After 17 years, 527 CRC cases were observed. The Mediterranean dietary pattern, assessed using the food frequency questionnaire (FFQ), was associated with a decreased risk of CRC. For a 2-point increment in the Mediterranean diet (MD) score, HR 0.88, 95% CI: 0.78, 0.99; Ptrend = 0.03. No evidence of an association was observed when data from food diaries was used for deriving the dietary pattern: for a 1-unit increment in the MD score, HR 0.94; 95% CI: 0.83 to 1.06; Ptrend 0.32. Similarly, no significant associations were observed between higher adherence to the WCRF/AICR guidelines and risk of CRC. For a 1-unit increment in the WCRF/AICR score, HR 0.92, 95% CI: 0.82, 1.03; Ptrend 0.169 for FFQ data whilst HR 1.01; 95% CI: 0.83, 1.24; Ptrend 0.87 for food diary data. The Bland-Altman method showed higher energy intake by the FFQ in comparison to the food diary and agreement between the two methods was slight for the MD score (Κ=0.15; 95% CI: 0.14, 0.16) and fair for the WCRF/AICR score (Κ=0.38; 95% CI: 0.37, 0.39). Conclusion: The Mediterranean dietary pattern is inversely associated with CRC risk whilst a higher adherence to the WCRF/AICR cancer prevention guidelines did not significantly decrease CRC risk in this cohort of British women.

The domain wall (DW) dynamics of epitaxial and polycrystalline multilayers with perpendicular magnetic anisotropy have been investigated. DC magnetron sputtering was used to deposit different multilayers. The saturation magnetization, anisotropy energies, exchanges stiffness constant, and DW width and energy density were calculated using hard-axis hysteresis loops and change of magnetization with temperature. The evaluated magnetic parameters were used in study of asymmetrical bubble expansion and Brillouin light spectroscopy (BLS) spectra to derive the strength of interfacial Dzyaloshinskii-Moriya interaction (DMI) in the films. Pt\Co\Au_xPt_(1−x) (x = 0, 0.5, 1) epitaxial trilayers with increasing broken inversion symmetry were deposited by sputtering. Zero DMI and no visible current-induced DW motion proven the expected fully symmetrical layers and interfaces in the case of x = 0. Field-induced DW motion (FIDWM) was used to calculate the depinning field, temperature, and velocity. All these material dependent parameters increased with x. They were used to estimate the value of Gilbert damping constant, which was compared to the same value evaluated from full micromagnetic calculations performed in collaboration with Simone Moretti. Larger values of Gilbert damping from FIDWM were attributed to other dissipation mechanisms that happen solely during DW motion. It was shown that DMI and SHE in the multilayers rise with concentration of Au on the top layer. The effect of inserting Ir in the top interface of polycrystalline Pt\Co\Ta films was also investigated through DMI and DW behaviour. It was shown that motion of the left-handed DWs in Pt\Co\Ir(t_Ir)\Ta multilayers (t_Ir = 0.0-2.0 nm) perfectly follows the universal creep and depinning regimes. The depinning related parameters and evaluated DMI did not change significantly for Ir of more than two monolayers. Evaluation of DMI showed that insertion of Ir layer reduces the net DMI of the multilayer, suggesting a negative DMI constant for Ir\Co interfaces. This opposes previous theoretical calculations and experimental studies. The observed anomalies in asymmetrical bubble expansion results could not be explained with the previous simple creep model of DW motion. Including changes of depinning field with in-plane applied field into the dynamics, micromagnetic simulation by Joo-Von Kim could successfully reproduce the experimental data. Finally, to study the DMI of Hf layers with different thicknesses, multilayers of Pt\Co\Hf(t_Hf)\Ta (tHf = 0.0-2.0 nm) were deposited. The magnetic characterization of films showed an approximately 0.7 nm thick magnetic dead-layer in the multilayers. The DMI in these films was again investigated using BLS and asymmetric bubble expansion. The results showed that Hf enhances DMI in the stack, suggesting a positive sign of DMI for the Hf\Co interface, which is opposite to DMI of Pt\Co interfaces. Changing the thickness did not show a significant effect on DMI factor.

One of the fundamental features that separates quantum physics from classical physics is the idea of quantum superposition, also known as coherence. This thesis concentrates on understanding quantum coherence in the mathematical framework of resource theories, viewing it both as a resource to be harnessed and as a way to quantitatively characterise quantum states in contrast to classical states. We first examine the type of coherence resource theory which has emerged recently to cope with general settings where the physical nature of the medium encoding information is not crucial, such as computation. We identify the set of quantum processes in which coherence is neither created nor used, and use these to provide a physically motivated resource theory pictured in terms of interferometry. Using the same concepts, we then find connections between coherence and discord, a type of quantum correlation. In particular, we show how coherence can be used to generate discord, and explore basis-dependent discord as an intermediate quantity. The second part of the thesis applies the resource theory framework to quantify quantum macroscopicity, taken here to mean the extent to which coherence exists in a system on a macroscopic scale. We find the appropriate type of resource theory for this purpose, giving criteria for good measures of macroscopic coherence. We use these criteria to evaluate some previously proposed measures and highlight the role of the quantum Fisher information. Next, we build up measures based on the concept of macroscopic distinguishability and use them to show that macroscopic quantum states are fragile to noise induced by interaction with an environment. Finally, we apply measures based on the Fisher information to a range of experiments involving mechanical degrees of freedom, in order to compare their macroscopicity.

Human activity has had a profound negative impact on the structure and function of the earth’s ecosystems. However, with a growing awareness of the value of the services provided by intact ecosystems, restoration of degraded land is increasingly used as a means of reviving ecosystem function. Upland landscapes offer an excellent example of an environment heavily modified by human land use. Agriculture has been the key driver of ecosystem change, but as upland habitats such as peatlands can provide a number of highly valuable services, future change may focus on restoration in order to regain key ecosystem processes. However, as pastoral farming continues to dominate upland areas, ecosystem restoration has the potential to conflict with existing land use. This thesis attempts to assess differences in the agricultural productivity of the different habitat types present in upland pastures. Past and present land use have shaped the distribution of different upland habitat types, and future changes associated with ecosystem restoration are likely to lead to further change in vegetation communities. Three key contributors to agricultural productivity are examined. Firstly, variation in the nutritional quality of different upland habitats is assessed, in order to understand their value for grazing animals. Secondly, levels of livestock use in different habitats are compared in order to identify areas of particular importance for grazing. Finally, parasite populations are measured in different habitats in order provide an indication of which habitats pose the greatest potential risk of infection. It is shown that these factors appear to differ between habitats, meaning that agricultural productivity may show spatial variation in upland pastures. However, it appears that peatland restoration might have a negligible impact on farming in upland pastures due to apparent minor differences in the agricultural productivity of the habitats most likely to be affected.

Candida albicans is a commensal fungal pathogen that grows in yeast and hyphal forms in the human gut. C. albicans causes mucosal and cutaneous diseases that can result in significant mortality following systematic infections and it also exhibits drug resistance. Zebrafish have been an excellent model to investigate C. albicans infections because of their transparency and the availability of many transgenic lines. However, there is a limitation in using zebrafish as a model because the fish embryos cannot survive at 37°C therefore it is not suitable for studying Candida infections at physiological relevant human body temperature. In this thesis, the normal embryonic development of Arabian killifish (A. dispar) is investigated, revealing that embryogenesis was divided into 32 stages based on diagnostic patterns of development. A. dispar can also found to tolerate a wide range of temperatures and salinities. This suggests that A. dispar could be developed as a novel model to investigate host-pathogen interactions. The tolerance of A. dispar to high temperatures may in part be attributable to brown pigment cells with a highly fluorescent character that may have developed to allow the fish to adapt to live within extreme environmental conditions with strong sunlight and a wide range of temperatures (Chapter 3). In terms of Candida infections, this study examined A. dispar as a model to test C. albicans pathogenicity. The survival of A. dispar embryos following Candida infection showed a dose dependent relationship. We also found that A. dispar can survive longer than zebrafish after infection. Furthermore, C. albicans cells were observed to undergo a transition from yeast to hyphae at 37°C. An investigation of the ability of mutant strains of C. albicans with defects in cell wall mannosylation revealed a significant impact on virulence, host mortality, and the fishes’ immune response. The present study found that although the deletion of O- and N-mannan from the cell wall of C. albicans, affected fungal burden (attenuation), and the survival of the infected embryos per se was significantly decreased in the infections of the mutant strains compared to the WT. This data confirms the importance of the mannosylation state of the cell wall in triggering an immune recognition event (Chapter 4). A. dispar is also shown to be suitable for studying the effectiveness of 3 | P a g e antifungals. Fluconazole treatment of infected embryos and eggs promoted greater rates of survival at high doses, alongside a significant reduction of C. albicans CFUs (Chapter 4). When looking at the Candida-host interaction, we directly observed phagocytosed yeast cells within macrophages. Various detection methods were used to follow macrophages and neutrophils including Western blotting, immunostaining and histological staining (Sudan black and FITC-tyramide) allowing the monitoring of the time course of the immune cells. A biphasic response of macrophages was detected by L-plastin Western blotting, suggesting activation of two different type of macrophage: activated macrophage (M1) and alternative macrophage (M2). We also assayed reactive oxygen species (ROS) within infected embryos using a fluorescent probe (H2DCFDA), revealing the accumulation of the fluorescent probe at the sites of infection. Quantitative and qualitative analyses of the oxidative and immune response using the H2DCFDA and qPCR were also accomplished within A. dispar embryos after infection with both the WT and mutant strains of Candida albicans (WT, pmr1∆, mnt1-mnt2∆, and och1∆). The results confirmed that the mutant strains did not activate a host oxidative stress response nor immune cell accumulation when compared to WT, suggesting that the immune response is less activated against these mutants. Finally, a new transgenic line of A. dispar fish was developed using Betaactin-DsR-LoxP-GFP. The new transgenic A. dispar is suggested to be an ideal model for real time observation of host-pathogen interactions and for investigation of molecular functions of the immune response. Overall these results improve our understanding of the use of a new transparent fish model to study fungal pathogenesis and demonstrates the potential advantages of using this species in future studies of bacterial, fungal and viral pathogens at a physiologically relevant temperature for human infection. Such a model could lead us to investigate in more depth the key interactions between pathogens and their host and permit the screening and development of new antifungal therapies (that might target the pathogens directly or target the host immune system).

Plants deploy two key active defensive strategies to combat microbial pathogens; (i) Recognition of Pathogen-Associated Molecular Patterns (PAMPs) by extracellular surface receptors leading to the activation of PAMP-Triggered Immunity (PTI); (ii) Recognition of pathogen effector activity, usually intracellularly, by host Resistance (R) proteins leading to Effector-Triggered Immunity (ETI). ETI is characterised by a rapid localised Hypersensitive Response (HR). HR induces Systemic Acquired Resistance (SAR) through the production of an inducible immune signal(s), leading to broad spectrum systemic resistance. I investigated the earliest events associated with SAR signalling using plant electrophysiology, SAR mutants and a unique promoter-luciferase fusion that captures early systemic transcriptional events associated with ETI. We describe the transcriptional dynamics of A70 (At5g56980), a gene of unknown function (Truman et al. 2007), in local and systemic tissue following challenge with different elicitors and virulent or avirulent pathogen challenges. We provide evidence that A70 responds to a jasmonate (JA) related signal that is rapidly generated following ETI recognition. We further evaluate A70::LUC reporter activity in response to JA stimulus and correlate activity with histological expression of a JA repressor reporter (JAZ10::GUS) and A70::GFP reporter in systemically responding leaves following avirulent pathogen challenges. Finally, we examine changes in electrophysiological signals following ETI in local and systemic leaves. Focussing on events underpinning initiation, propagation and perception of SAR-inducing signals within the first 6-8 h of pathogen challenge we provide new insight into the integrated signalling mechanisms, dynamics and connectivity underpinning systemic immune responses. We conclude that there are multicomponent signals that link ETI induced transcriptional and electrical signals, with a COI1 receptor dependent propagative transcriptional wave the leads to rapid temporal spatial activation of jasmonate responsive genes in systemic responding leaves.

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