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Background The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. Methods Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine the relapse risk using only the RKD dataset. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. Results Residential latitude was positively correlated (OR 1.41, 95% CI 1.14–1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70–0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57–0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. Conclusion Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, the development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.

Additional file 2: Table S1. Summary statistics of variables used in statistical learning analyses and splines. Figure S1. Pairwise relationships between all variables analyzed in this study. Figure S2. Variable importance plots for random forests. Figure S3. Variable importance in the generalized additive model (GAM) using cubic spline smoothing. Figure S4. Relationship between microbial biomass and benthic cover of calcifying organisms.

Additional file 1: Fig. S1. Flowchart of participant selection for the UKIVAS cohort (1). Fig. S2. Flowchart of participant selection for the RKD cohort (2). Fig. S3. Participant locations at diagnosis for i). UKIVAS and ii). RKD cohort. Shading represents the absolute number of participants recruited to the study in that region, at the time of their diagnosis. Tendency to cluster around vasculitis referral centres is observed. Fig. S4. Distribution of vitD-UVB (kJ/m2) (a and b) and CW-D-UVB (kJ/m2) (c and d) by month and season: CW-D-UVB peaks in late summer and nadirs in winter. Fig. S5. The relationship between latitude (degrees) and a). annual daily average vitD-UVB (kJ/m2, Pearson correlation coefficient (corr) -0.98, p

Funder: Vifor Pharma; Id: http://dx.doi.org/10.13039/501100006484, Objective: COVID‐19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID‐19. We undertook this study to establish the risk factors for severe COVID‐19 outcomes in these patients, including the impact of immunosuppressive therapies. Methods: A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID‐19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death. Results: The cohort included 65 patients with systemic vasculitis who developed COVID‐19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1–14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9–38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes. Conclusion: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID‐19. These data can inform clinical decision‐making relating to the risk of severe COVID‐19 in this vulnerable patient group.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

Additional file 1. The registries survey sheet.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

Polymeric semiconductors exhibit exceptionally long spin lifetimes, and recently observed micrometre spin diffusion lengths in conjugated polymers demonstrate the potential for organic spintronics devices. Weak spin–orbit and hyperfine interactions lie at the origin of their long spin lifetimes, but the coupling mechanism of a spin to its environment remains elusive. Here, we present a systematic study of polaron spin lifetimes in field-effect transistors with high-mobility conjugated polymers as an active layer. We demonstrate how spin relaxation is governed by the charges’ hopping motion at low temperatures, whereas an Elliott–Yafet-like relaxation due to a transient localization of the carrier wavefunctions is responsible for spin relaxation at high temperatures. In this regime, charge, spin and structural dynamics are intimately related and depend sensitively on the local conformation of polymer backbones and the crystalline packing of the polymer chains., * ERC Synergy grant SC2 (no. 610115) * Alexander von Humboldt Foundation * Transregional Collaborative Research Center (SFB/TRR) 173 SPIN+X * Winton Programme for the Physics of Sustainability * Engineering and Physical Sciences Research Council (EPSRC) * Excellence Initiative by the Graduate School Materials Science in Mainz (GSC 266) * European Commission/Région Wallonne (FEDER–BIORGEL project), the Consortium des Équipements de Calcul Intensif (CÉCI), funded by the Fonds National de la Recherche Scientifique (FRS-FNRS) under grant no. 2.5020.11 * Tier-1 supercomputer of the Fédération Wallonie-Bruxelles, infrastructure funded by the Walloon Region under grant agreement n1117545

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

OBJECTIVE: The treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) aims to suppress disease activity and prevent subsequent disease flare. This study sought to explore the association of early disease control with long-term outcomes to validate early disease control as an end point for future clinical trials in AAV. METHODS: Data from 4 European Vasculitis Society inception clinical trials in AAV (1995-2002) and subsequent data on long-term outcomes from the trial data registry were studied. Clinical parameters in patients with AAV at baseline and at 3 and 6 months after diagnosis were assessed to study the long-term risk of death and end-stage renal failure (ESRF). At 6 months, outcomes were defined based on a disease status of either sustained remission (remission by 3 months, sustained to 6 months), late remission (remission after 3 months and by 6 months), relapsing disease (remission by 3 months but relapse by 6 months), or refractory disease (no remission by 6 months). RESULTS: Of the 354 patients with AAV who were followed up for a median of 5.7 years, 46 (13%) developed ESRF, 66 (18.6%) died, and 89 (25.1%) had either died or developed ESRF. At 6 months, predictors of the composite end point of death or ESRF were as follows: age (hazard ratio [HR] 1.02, 95% confidence interval [95% CI] 1-1.05; P = 0.012), estimated glomerular filtration rate (HR 0.94, 95% CI 0.92-0.95; P < 0.001), and disease status at 6 months (late remission, HR 2.94, 95% CI 1.1-7.85 [P = 0.031]; relapsing disease, HR 8.21, 95% CI 2.73-24.65 [P < 0.001]; refractory disease, HR 4.89, 95% CI 1.96-12.18 [P = 0.001]). Similar results were observed when these analyses were performed separately for death and for ESRF. CONCLUSION: The results of this study suggest that disease status at 3 and 6 months following the diagnosis of AAV may be predictive of the long-term risk of mortality and ESRF, and therefore these may be valid end points for induction trials in AAV. The current findings need to be validated in a larger data set.

Additional file 2. LQ1 questionnaire, LQ2 questionnaire, LQ3 questionnaire and supplementary skin cancer questionnaire used in USRT

Additional file 1 Table S1. Categories for variables used to define person-year table. Supplementary statistical methods. Table S2. Curvature in exposure response of relative risk of basal cell carcinoma (BCC) with UVR cumulative radiant exposure, using AVGLO and NASA TOMS measures of UVR among 63,912 white technologists. Table S3. Modification by age of excess absolute risk and excess relative risk of basal cell carcinoma (BCC) in relation to ultraviolet radiation (UVR) cumulative radiant exposure. Table S4. Excess absolute risk (+ 95% CI) for AVGLO and NASA TOMS data. Figure S1. Cumulative potential UVR radiant exposure, derived from AVGLO and from NASA TOMS data, by age: (a) age 20 years, (b) age 40 years, (c) age 60 years, and (d) age 80 years. Reproduced from Little et al. [20].

Corals and humans represent two extremely disparate metazoan lineages and are therefore useful for comparative evolutionary studies. Two lipid-based molecules that are central to human immunity, platelet-activating factor (PAF) and Lyso-PAF were recently identified in scleractinian corals. To identify processes in corals that involve these molecules, PAF and Lyso-PAF biosynthesis was quantified in conditions known to stimulate PAF production in mammals (tissue growth and exposure to elevated levels of ultraviolet light) and in conditions unique to corals (competing with neighbouring colonies over benthic space). Similar to observations in mammals, PAF production was higher in regions of active tissue growth and increased when corals were exposed to elevated levels of ultraviolet light. PAF production also increased when corals were attacked by the stinging cells of a neighbouring colony, though only the attacked coral exhibited an increase in PAF. This reaction was observed in adjacent areas of the colony, indicating that this response is coordinated across multiple polyps including those not directly subject to the stress. PAF and Lyso-PAF are involved in coral stress responses that are both shared with mammals and unique to the ecology of cnidarians.

Holobionts are assemblages of microbial symbionts and their macrobial host. As extant representatives of some of the oldest macro-organisms, corals and algae are important for understanding how holobionts develop and interact with one another. Using untargeted metabolomics, we show that non-self interactions altered the coral metabolome more than self-interactions (i.e. different or same genus, respectively). Platelet activating factor (PAF) and Lyso-PAF, central inflammatory modulators in mammals, were major lipid components of the coral holobionts. When corals were damaged during competitive interactions with algae, PAF increased along with expression of the gene encoding Lyso-PAF acetyltransferase; the protein responsible for converting Lyso-PAF to PAF. This shows that self and non-self recognition among some of the oldest extant holobionts involve bioactive lipids identical to those in highly derived taxa like humans. This further strengthens the hypothesis that major players of the immune response evolved during the pre-Cambrian.

One of the biggest problems in current distributed systems is that presented by one machine attempting to determine the liveness of another in a timely manner. Unfortunately, the symptoms exhibited by a failed machine can also be the result of other causes, e.g., an overloaded machine or network which drops messages, making it impossible to detect a machine failure with cetainty until that machine recovers. This is a well understood problem and one which has led to a large body of research into failure suspectors: since it is not possible to detect a failure, the best one can do is suspect a failure and program accordingly. However, one machine's suspicions may not be the same as another's; therefore, these algorithms spend a considerable effort in ensuring a consistent view among all available machines of who is suspects of being failed. This paper describes a thought experiment on how quantum mechanics may be used to provide a failure detector that is guaranteed to give both accurate and instantaneous information about the liveness of machines, no matter the distances involved.

The purpose for this thesis, "A Pavilion for Time", is to allow an unhindered exploration of phenomenological time. It is to go beyond, to transcend a convention towards empiricism. The result is an uncritical state, unhindered, uncluttered, a place of pure perception, an existential autoclave. As a phenomenological exploration with architecture as the vehicle, this project investigates time as experienced. It is a heuristic excercise. Its goal is to encourage or rather enhance an understanding of phenomenological time. This thesis does not attempt to answer the question "What is time?" but rather, with architecture, examines the question "How do we, as cognizant human beings, exist with time?" Master of Architecture

Background: Risks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear. Objectives: We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation. Methods: A nested case–control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986–2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose. Results: We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews less than 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = –0.47 (95% CI: less than –0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure. Conclusions: Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive.

Table S1. List of target genes sequenced by targeted deep sequencing. Table S2. Mutations in Exposed and Unexposed Cases. Table S3. Copy Number Aberrations (CNA) in Exposed and Unexposed Cases. (DOCX 311Â kb)

Table S1. List of target genes sequenced by targeted deep sequencing. Table S2. Mutations in Exposed and Unexposed Cases. Table S3. Copy Number Aberrations (CNA) in Exposed and Unexposed Cases. (DOCX 311Â kb)

Background Chronic lymphocytic leukemia (CLL) was the predominant leukemia in a recent study of Chornobyl cleanup workers from Ukraine exposed to radiation (UR-CLL). Radiation risks of CLL significantly increased with increasing bone marrow radiation doses. Current analysis aimed to clarify whether the increased risks were due to radiation or to genetic mutations in the Ukrainian population. Methods A detailed characterization of the genomic landscape was performed in a unique sample of 16 UR-CLL patients and age- and sex-matched unexposed general population Ukrainian-CLL (UN-CLL) and Western-CLL (W-CLL) patients (n = 28 and 100, respectively). Results Mutations in telomere-maintenance pathway genes POT1 and ATM were more frequent in UR-CLL compared to UN-CLL and W-CLL (both p

Corals and humans represent two extremely disparate metazoan lineages and are therefore useful for comparative evolutionary studies. Two lipid-based molecules that are central to human immunity, platelet-activating factor (PAF) and Lyso-PAF were recently identified in scleractinian corals. To identify processes in corals that involve these molecules, PAF and Lyso-PAF biosynthesis was quantified in conditions known to stimulate PAF production in mammals (tissue growth and exposure to elevated levels of ultraviolet light) and in conditions unique to corals (competing with neighbouring colonies over benthic space). Similar to observations in mammals, PAF production was higher in regions of active tissue growth and increased when corals were exposed to elevated levels of ultraviolet light. PAF production also increased when corals were attacked by the stinging cells of a neighbouring colony, though only the attacked coral exhibited an increase in PAF. This reaction was observed in adjacent areas of the colony, indicating that this response is coordinated across multiple polyps including those not directly subject to the stress. PAF and Lyso-PAF are involved in coral stress responses that are both shared with mammals and unique to the ecology of cnidarians.

Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome.

Essentials 1. An emergency department attendance represents an opportunity to set goals for care during the attendance and beyond. 2. End of life discussions and advance care planning assist early decision making about treatment goals and end of life care. 3. Knowledge of the law assists decision making at the end of life. 4. Not all dying patients require the skill set of a palliative care specialist but every dying patient will benefit from a palliative approach. 5. Palliative care does not preclude active treatment where the intent is understood by patient and family. 6. Failure to diagnose dying can compromise patient care. 7. The emergency department should foster close relationships with local specialist palliative care providers to improve and ensure timely access for patients and families and so that emergency staff have access to the knowledge and skills provided.

1. An emergency department attendance represents an opportunity to set goals for care during the attendance and beyond. 2. End of life discussions and advance care planning assist early decision-making about treatment goals and end of life care. 3. Knowledge of the law assists decision-making at the end of life. 4. Not all dying patients require the skill set of a palliative care specialist but every dying patient will benefit from a palliative approach. 5. Palliative care does not preclude active treatment where the intent is understood by patient and family. 6. Failure to diagnose dying can compromise patient care. 7. The emergency department should foster close relationships with local specialist palliative care providers to improve and ensure timely access for patients and families and so that emergency staff have access to the knowledge and skills provided.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in many developing and developed countries. This dissertation proposes a framework for gaining a greater understanding of the inflammatory process that is thought to result in the development of atherosclerosis and effects of radiation on the subsequent cardiovascular disease through statistical analysis and mathematical modelling of this process. The potential effect of low dose radiation in atherosclerotic initiation and progression is assessed utilising data on inflammatory markers and plaque development generated by European and Canadian researchers collected as part of the EU NOTE Project. Following suggestions from previous in vitro and in vivo experimental data, the hypothesis under consideration is that at low doses and dose rates there is a largely antiinflammatory response. Implications of this for induction of atherosclerosis after low dose and low dose-rate exposure are assessed. Two and three dimensional reaction-diffusion models of the cardiovascular system are constructed. These are used to assess perturbations of equilibrium and non-equilibrium states. Inferences for low dose mechanisms in the light of much biological and epidemiological data are considered. Chapter 1 serves as an introduction, describing the aetiology of atherosclerosis, a complex disease with many routes to initiation and progression, as well as environmental, biochemical, genetic and mechanical risk factors. This chapter surveys the extensive literature on the subject. Effects of radiation and mechanisms of cardiovascular injury are likewise assessed and the findings from various epidemiological and animal studies along with statistical considerations are discussed. Chapter 2 gives an overview of mathematical models of cardiovascular disease, and how they may illuminate the structure and evolution of CVD from various perspectives; this chapter outlines challenges in using mathematics as a tool for analysing this complex process. Chapter 3 proposes a spatial reaction diffusion model for atherosclerosis and provides a general framework for modelling early stage disease. Numerical implementation of the equations is performed based on parameter values derived from the biological and epidemiological literature. Chapter 4 considers the association between low dose radiation, inflammation and plaque development and progression by conducting statistical analysis utilising data on ApoE-null, ApoE-heterozygote and wild-type mice and discussing the biological pathways. Chapter 5 concludes. Certain auxiliary figures and tables (largely relating to chapters3 and 4) are presented in the appendix, while definitions for various biological and statistical terms utilized throughout are provided in the glossary at the end.