During 2007 the UK experienced outbreaks of three notifiable exotic livestock diseases; Foot and Mouth Disease (FMD), Highly Pathogenic Avian Influenza (HPAI) and bluetongue. Large epidemics of any of these diseases would have a serious impact on animal welfare, farming, food production and the economy. In light of this, understanding holdings which are most likely to acquire and spread infection and being able to identify areas at higher risk of an epidemic is valuable when preparing for and managing an epidemic. This thesis uses a spatial epidemiological framework and the detailed disease and demographic data from the 2001 Great Britain (GB) FMD epidemic to develop static models of the risk of FMD susceptibility and transmission. These models are used to develop maps of FMD risk. These methods are then applied to the outbreak of FMD in 2007. The inputs for this analysis comprised a set of data relating to the farms diagnosed with FMD and farms culled as part of the disease control measures. The cleaning of these data is described and data which were estimated relating to dates of infection and putative sources of infection are evaluated. The distribution of farm holdings and animals is taken from the June 2000 GB agricultural census, off-fields of farms in the agricultural census are recorded in other datasets and these have been identified and linked to census holdings. A model of holding level susceptibility is developed using both farm level variables and measures of animal numbers in the locality of the holding as well as the distance to the nearest farm infected before the ban on animal movements (seeds). The overall fit of the model was very good with an area under the Receiver Operator Characteristic (ROC) curve of 0.91. A further model was developed to describe the risk of FMD transmission. However, due to incompleteness of transmission data, this was a model of the risk of finding a subsequent Infected Premises (IP) within 3km of an IP. Risk factors were a combination of holding level variables and locality measures as well as data relevant to the infection, such as infectious period and the species initially infected. The area under the ROC curve for this model was 0.71, which is regarded as an acceptable fit. Geographical barriers to FMD transmission were investigated using a case-control methodology, linear barriers comprising rivers and railways had a significant protective effect with respect to disease transmission (odds ratio = 0.54, 95% CIs = 0.30,0.96, p=0.038). Modelled values for the transmission and susceptibility models were transformed to a raster surface in ESRI ArcMap for both the disease as it was seeded in the 2001 epidemic and a non-specific background risk surface independent of the distribution of seeds. A risk map generated for the outbreak of FMD in Surrey in August 2007 suggested that there was little risk of a large outbreak in Surrey. Potential disease introductions through livestock movements from Surrey into Scotland were identified and these suggested that if the disease were introduced into Scotland there was great danger of substantial local spread. These methods described in this thesis have been used to map risk of FMD and subsequently applied to inform the risk presented by a different outbreak of FMD. The study underlines the value of detailed data both disease and demographic, for epidemic management. Similar methods could and should be applied to other infectious diseases threats of livestock such as HPAI and bluetongue.

The usual approach to the study of signaling pathways in biological systems is to assume that high numbers of cells and of perfectly mixed molecules within cells are involved. To study the temporal evolution of the system averaged over the cell population, ordinary differential equations are usually used. However, this approach has been shown to be inadequate if few copies of molecules and/or cells are present. In such situation, a stochastic or a hybrid stochastic/deterministic approach needs to be used. Moreover, considering a perfectly mixed system in cases where spatial effects are present can be an over-simplifying assumption. This can be corrected by adding diffusion terms to the ordinary differential equations describing chemical reactions and proliferation kinetics. However, there exist cases in which both stochastic and spatial effects have to be considered. We study the relevance of differential equations, stochastic Gillespie algorithm, and deterministic and stochastic reaction-diffusion models for the study of important biological processes, such as viral infection and early carcinogenesis. To that end we have developed two optimized libraries of C functions for R (r-project.org) to simulate biological systems using Petri Nets, in a pure deterministic, pure stochastic, or hybrid deterministic/stochastic fashion, with and without spatial effects. We discuss our findings in the terms of specific biological systems including signaling in innate immune response, early carcinogenesis and spatial spread of viral infection.

The outbreak of the coronavirus disease 2019 (COVID-19) has seen the world scramble for effective countermeasures to limit infection spread in society. Understanding how infection spreads in places where strangers meet in relatively high numbers and proximity to one another is especially important. Supermarkets are one such place where strangers inevitably gather in close proximity indoors. In particular, the checkout area where people queue up to pay tends to be densely populated, making it especially hazardous. One approach to understanding the infection spread is to use agent-based computer simulations to model different scenarios. This paper describes one such simulation of a supermarket checkout area using the Unity 3D engine, including the effect of checkout types and quantity, customer load and COVID-19 countermeasures, i.e., masking and distancing, on infection spread. Using the results from one default scenario and eleven variations, the relative impact of aforementioned factors on exposure in the simulation is discussed. Results indicate that for this simulation the most important factor is preventing queue buildup via having sufficient customer throughput capacity, with potent effects also resulting from operating service registers in such a way that the distance between each queue is maximized as well as increasing distances between agents within queues. Including a self-checkout area was found to be a viable approach to reducing queue times and consequently exposure rates. Comparatively, masking did not yield as notable reductions in exposure rates in the simulation. Similarities in exposure patterns to previous work in the context of supermarkets are discussed, as well as limitations of simulations in capturing the real world. / Utbrottet av coronavirus disease 2019 (COVID-19) föranledde införandet av smittskyddsåtgärder världen över i ett försök att begränsa smittspridningen i samhället. Särskilt viktigt är att förstå hur smittspridning äger rum i trånga utrymmen där ett förhållandevis stort antal främmande människor samlas. Ett exempel på en inomhusmiljö där stora folksamlingar oundvikligen uppstår är mataffärer, där kassaområdena är högriskområden för smittspridning eftersom kunder köar för att betala i dessa områden. Ett tillvägagångssätt för att erhålla kunskap kring smittspridning är att använda agentbaserade datorsimuleringar för att modellera olika scenarion. Den här publikationen beskriver en sådan simulering av en mataffärs kassaområde i spelmotorn Unity 3D. Simuleringen används för att undersöka betydelsen av kassaområdets utformning för smittspridningen, samt inverkan av besökstryck och smittskyddsåtgärder, härvidlag användning av munskydd och social distansering. Som diskussionsunderlag för att fastställa vilken effekt dessa faktorer har på smittspridningen används ett grundscenario och elva simuleringsvarianter. Resultaten visar att den enskilt viktigaste faktorn i denna simulering är att hålla tillräckligt många kassor öppna, vilket förhindrar kötillväxt. Att hålla maximalt avstånd mellan öppna kassor, samt anamma social distansering mellan köande agenter bidrar också påtagligt till minskad smittspridning. Vidare förefaller inkludering av självskanningskassor vara ett effektivt tillvägagångssätt för att minska kötid och därmed även smittspridning. Användande av munskydd har jämförelsevis en mindre påtaglig effekt i simuleringen. I publikationen diskuteras även likheter i exponeringsmönster gentemot tidigare forskning rörande simulering av smittspridning i mataffärskontext, samt vilka begränsningar simuleringar kan uppvisa när det kommer till att replikera verkligheten.