Menschliche Systeme werden seit einiger Zeit modelliert und analysiert auf der Basis der Theorie komplexer Netzwerke. Dies erlaubt es quantitativ zu untersuchen, welche strukturellen und zeitlichen Merkmale eines Systems Ausbreitungsprozesse beeinflussen, z.B. von Informationen oder von Infektionskrankheiten. Im ersten Teil der Arbeit wird untersucht, wie eine modular-hierarchische Struktur von statischen Netzwerken eine schnelle Verbreitung von Signalen ermöglicht. Es werden neue Heuristiken entwickelt um die Random-Walk-Observablen “First Passage Time” und “Cover Time” auf lokal geclusterten Netzwerken zu ermitteln. Vergleiche mit der Approximation eines gemittelten Mediums zeigen, dass das Auftreten der beobachteten Minima der Observablen ein reiner Netzwerkeffekt ist. Es wird weiterhin dargelegt, dass nicht alle modular-hierarchischen Netzwerkmodelle dieses Phänomen aufweisen. Im zweiten Teil werden zeitlich veränderliche face-to-face Kontaktnetzwerke auf ihre Anfälligkeit für Infektionskrankheiten untersucht. Mehrere Studien belegen, dass Menschen vornehmlich Zeit in Isolation oder kleinen, stark verbundenen Gruppen verbringen, und dass ihre Kontaktaktivität einem zirkadianen Rhythmus folgt. Inwieweit diese beiden Merkmale die Ausbreitung von Krankheiten beeinflussen, ist noch unklar. Basierend auf einem neuen Modell wird erstmals gezeigt, dass zirkadian variierende Netzwerke Trajektorien folgen in einem Zustandsraum mit einer strukturellen und einer zeitlichen Dimension. Weiterhin wird dargelegt, dass mit zunehmender Annäherung der zeitlichen Dimension von System und Krankheit die systemische Infektionsanfälligkeit sinkt. Dies steht in direktem Widerspruch zu Ergebnissen anderer Studien, die eine zunehmende Anfälligkeit vorhersagen, eine Diskrepanz, die auf die Ungültigkeit einer weit verbreiteten Approximation zurückzuführen ist. Die hier vorgestellten Ergebnisse implizieren, dass auf dem Gebiet die Entwicklung neuer theoretischer Methoden notwendig ist. / Human systems have been modeled and analyzed on the basis of complex networks theory in recent time. This abstraction allows for thorough quantitative analyses to investigate which structural and temporal features of a system influence the evolution of spreading processes, such as the passage of information or of infectious diseases. The first part of this work investigates how the ubiquitous modular hierarchical structure of static real-world networks allows for fast delivery of messages. New heuristics are developed to evaluate random walk mean first passage times and cover times on locally clustered networks. A comparison to average medium approximations shows that the emergence of these minima are pure network phenomena. It is further found that not all modular hierarchical network models provide optimal message delivery structure. In the second part, temporally varying face-to-face contact networks are investigated for their susceptibility to infection. Several studies have shown that people tend to spend time in small, densely-connected groups or in isolation, and that their connection behavior follows a circadian rhythm. To what extent both of these features influence the spread of diseases is as yet unclear. Therefore, a new temporal network model is devised here. Based on this model, circadially varying networks can for the first time be interpreted as following trajectories through a newly defined systemic state space. It is further revealed that in many temporally varying networks the system becomes less susceptible to infection when the time-scale of the disease approaches the time-scale of the network variation. This is in direct conflict with findings of other studies that predict increasing susceptibility of temporal networks, a discrepancy which is attributed to the invalidity of a widely applied approximation. The results presented here imply that new theoretical advances are necessary to study the spread of diseases in temporally varying networks.

A substantial number of employees in South Africa may soon be out of work as the result of their HIV-positive status. The dismissal of an infected employee may be motivated by the fact that he is considered to be incompetent or incapable of doing the work for which he was employed. Customers and fellow employees may refuse to deal with an infected employee, with the result that the employee is dismissed for economic reasons. The nature of the undertaking's activities may be such that the presence of an infected employee constitutes a health risk. For the purposes of carrying out his duty to create and maintain safe working conditions, the employer dismisses the employee. The employer may even force the infected employee to resign. Measures should be taken to improve the situation of infected employees. They include educating employers and employees about the transmission of the human immunodeficiency virus. / Mercentile Law / LL. M.

Bibliography / Thesis (MScMedSc (Pathology. Medical Virology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: In just 25 years since the first reported cases in 1981, the number of Human Immunodeficiency virus (HIV) infected people has risen to 65 million, and over 25 million have died of acquired immunodeficiency syndrome (AIDS). Sub-Saharan Africa accounts for 67% of all people living with HIV and 72% of deaths in this region were AIDS related. Tuberculosis (TB) is one of the most common opportunistic infections in AIDS patients, particularly in developing countries, where 60 - 70% of TB cases occur in HIV-1-infected persons. HIV-1 is a high risk factor for the development of TB, the reactivation of a latent Mycobacterium tuberculosis infection and also progressive TB. CD8+ Cytotoxic T Lymphocytes (CTL) are pivotal in the host immune response to HIV infection. CTL are associated with resolution of acute infection and with reduction in viral load. Studies in macaques and humans indicate the importance of CTL in the control of HIV infection, where reduction in CD8+ T cell number has been correlated with progression to AIDS. The current study was a cross-sectional descriptive study of CD8+ T cells of HIV+ adult South Africans with and without TB co-infection (TB disease). The cohort consisted of anti-retroviral therapy (ART) naive patients and all CTL analyses were carried out on peripheral blood mononuclear cells (PBMCs). A total of 60 South African adults from the Western Cape were utilized in this study, including 15 healthy controls; 30 HIV+TB-individuals and 15 HIV+TB+ individuals. Expression of phenotypic, activation and functional markers were investigated by flow cytometry with the use of fluorochomeconjugated antibodies. The markers examined included the novel activation marker CD137, the CTL associated markers Perforin, Granzyme A, CD107a/b, Fas (CD95), and FasL (CD95L), intracellular cytokines IFN-y and TNF-a and the chronic HIV CTL dysfunction marker PD-1. HIV infection alone was associated with increased baseline expression of TNF-a, Perforin, Granzyme A, PD-1, Fas (CD95), and FasL (CD95L), but not CD137(4-1BB) or IFN-y as compared to uninfected controls. TB co-infection resulted in further increased baseline expression of TNF-a, perforin, PD-1, FasL (CD95L), as well as increased IFN-y. HIV-1 antigen (gag)-specific stimulation in vitro indicated that in HIV infection was associated with antigen-specific upregulation of activation and cytotoxicity markers CD137, IFN-y, TNF-a, Fas, FasL and CD107a/b. In TB co-infection a reduction in antigen-specific degranulation (CD107a/b up-regulation) and also Fas and FasL expression was observed. TB co-infection (in the form of active pulmonary TB) reduced antigen-specific CTL functional activity, but simultaneously there was an association with increased baseline PD-1 expression and also cytolytic marker expression (Fas, FasL, TNF-a). These cytolytic markers could be involved in non-antigen-specific bystander target cell death. The expression of the co-stimulatory molecule CD137 appeared to correlate with interferon-y production and levels of degranulation, confirming its usefulness as a putative surrogate marker of functional responsiveness. These data indicate that in addition to impacting on CD4 T cell function, TB co-infection leads to higher baseline expression of CTL-associated markers, but to dysfunctional antigen-specific CTL responses. / AFRIKAANSE OPSOMMING: Slegs vyf en twintig jaar na die eerste berigte van die menslike immuniteitsgebrekvirus (MIV) in 1981, het die getal MIV-geinfekteerde individue gestyg tot 65 miljoen en het meer as 25 miljoen mense alreeds gesterf aan die verworwe immuniteitsgebrek sindroom (VIGS). Sub Sahara Afrika maak 67% uit van alle HIV gevalle en het `n MIVverwante doodsyfer van 72%. Een van die algemeenste opportunistiese infeksies in VIGS pasiente is Tuberkulose (TB). In ontwikkelende lande, veral, kom 60-70% van TB gevalle voor in MIV-1 geinfekteerde individue. MIV-1 is `n hoe risiko faktor vir die ontwikkeling van TB, die heraktivering van latente Mycobacterium tuberculosis infeksie en progressiewe TB. Die CD8+ sitotoksiese T Limfosiete (STL) se immuun reaksie teen `n MIV infeksie is noodsaaklik en word geassosieer met `n resolusie van die akute infeksie en `n afname in viruslading. Studies in die mens en macaque het getoon dat sitotoksiese T limfosiete belangrik is vir die beheer van MIV infeksies aangesien die afname in CD8+ sel getalle korreleer met die verloop tot VIGS. Hierdie deursnit-beskrywende studie het die CD8+ T selle van MIV+ volwasse Suid-Afrikaners, met of sonder`n TB mede-infeksie, ondersoek. STL analise is gedoen op die perifere bloed mono-nuklere selle (PBMS) van pasiente wat geen teen-retrovirale terapie (TRT) ontvang het nie. `n Totaal van sestig Suid-Afrikaanse volwassenes van die Wes-Kaap het deelgeneem aan die studie wat 15 gesonde kontroles; 30 MIV+TBen 15 MIV+TB+ individue ingesluit het. Die uitdrukking van fenotipiese, aktiverings en funksionele merkers is ondersoek deur middel van vloeisitometrie en fluorochroomgekonjugeerde teenliggaampies. Laasgenoemde het ingesluit die nuwe aktiversingsmerker CD 137, die STL geassosieerde merkers Perforien en Gransiem A, CD 107a/b, Fas (CD95) en FasL (CD95L), intrasellulere sitokiene IFN-y en TNF-a en PD-1, die merker vir chroniese MIV CTL disfunksie. Daar is gevind dat `n TB mede-infeksie (in die vorm van aktiewe pulmonere TB) die antigeen-spesifieke STL funksie verlaag en terselftertyd `n verhoging in die uitdrukking van PD-1 en sitolitiese merkers (Fas, FasL, TNF-a) bewerkstellig. Hierdie sitolitiese basislyn merkers is moontlik betrokke by die dood van nie-antigeen-spesifieke omstander teiken selle. Die uitdrukking van die mede-stimulatoriese molekule CD 137 blyk om te korreleer met die produksie van STL IFN-y en die vlakke van degranulasie. Dit bevestig die merker se bruikbaarheid as `n gewaande surrogaat merker vir funksionele reaksies. Die data toon verder dat `n TB mede-infeksie nie net `n effek het op die CD4 T sel funksie nie, dit lei ook tot `n verhoogde basislyn uitdrukking van STLgeassosieerde merkers, maar met disfunksionele antigeen-spesifieke STL reaksies. Hierdie studie het bepaal dat `n MIV infeksie verbind word met `n toename in die basislyn uitdrukking van TNF-a, Perforien, Gransiem A, PD-1, Fas (CD95) en FasL (CD95L). Dit is egter nie die geval wanneer die uitdrukking van CD 137 (4-1BB) of IFN-y vergelyk word met nie-geinfekteerde kontroles. `n TB mede-infeksie het `n verdere toename in die uitdrukking van TNF-a, Perforien, PD-1, FasL (CD95L) getoon, asook `n verhoging in IFN-y vanaf die basislyn. In vitro MIV-1 antigeen (gag)-spesifieke stimulasies het aangedui dat `n MIV infeksie met die antigeen-spesifieke op-regulasie van aktiverings en sitotoksiese merkers CD137, IFN-y, TNF-a, Fas, FasL en CD107a/b geassosieer word. In `n TB mede-infeksie, is `n verlaging van antigeen-spesifieke degranulasie (CD 107a/b op-regulasie) asook die uitdrukking van Fas en FasL waargeneem. / The Poliomyelitis Research Foundation / The National Health Laboratory Service

Le complexe Burkholderia cepacia (Bcc) englobe 17 espèces retrouvées dans les infections pulmonaires d'individus atteints de mucoviscidose. Les bactéries de ce complexe sont présentes dans les sols, la rhizosphère de grandes cultures, les eaux usées et peuvent également être rencontrées dans le cadre d'infections nosocomiales. En France, les espèces B. multivorans et B. cenocepacia (Bcen) sont les espèces majoritaires au niveau des infections de patients atteints de mucoviscidose. Divers clones épidémiques ont été décrits au sein de l’espèce Bcen dont le clone ET12 associé au "syndrome cepacia". En 2004, une épidémie nosocomiale impliquant un clone du Bcc est survenue dans un hôpital de l’Ain. Durant ce travail, l’origine de ce clone (B&B), sa classification au sein du Bcc et certains phénomènes génétiques liés à son émergence ont été étudiés. Cela a permis d’identifier ce clone comme appartenant à l’espèce Bcen et une forte proximité de celui-ci avec la lignée ET12. L’étude des facteurs transcriptionnels de la famille σ70 au sein du Bcc a mis en évidence une structure génétique similaire entre la lignée ET12 et ce clone, mais différente de celle observée chez les autres espèces du Bcc. L’analyse d’éléments génétiques répétés de la famille des séquences d’insertion (IS) a cependant permis d’observer une organisation génomique distincte de la lignée ET12. Celle-ci a été reliée à des phénomènes d’instabilité génétique notamment à des phénomènes d’acquisition d’éléments génétiques mobiles de type îlot génomique. L’ensemble de ce travail a permis de caractériser un ensemble de phénomènes génétiques pouvant expliquer l’émergence de clones épidémiques tels que le clone B&B. / The Burkholderia cepacia complex (Bcc) comprises 17 species found in lung infections of individuals with cystic fibrosis. The bacteria of this complex are present in the soil, the rhizosphere of field crops, wastewater and may also be encountered in nosocomial infections. In France, the B. multivorans and B. cenocepacia species are the major species in infections of cystic fibrosis patients. Various epidemic clones have been described within the B. cenocepacia species whose ET12 clone associated with "cepacia syndrome". In 2004, a nosocomial outbreak involving a clone of Bcc occurred in a French hospital. During this outbreak, origin of this clone (B&B clone), its classification within the Bcc and several genetic events associated with its emergence have been studied. These investigations have identified this clone as belonging to the species B. cenocepacia with a strong proximity with the ET12 lineage. The study of transcriptional factors of σ70 family within the Bcc has revealed a similar genetic structure between the ET12 lineage and this clone, but different from that observed in other species of Bcc. Analysis of genetic elements repeated family of insertion sequences (IS), however, allowed to observe a distinct genomic organization of the ET12 lineage. It has been linked to phenomen of genetic instability including acquisition of mobile genetic elements like genomic island (GI). All of this work has helped to characterize a set of genetic events may explain the emergence of epidemic clones such as clone B&B.

Les écosystèmes forestiers méditerranéens présentent des espèces d'arbres vivant en limite sud de leur aire de répartition sensibles aux stress climatiques et des espèces vivant au coeur de leur aire de répartition et a priori adaptées à ces mêmes stress. Ces contrastes interrogent sur la diversité potentielle des mécanismes régulant la dynamique des populations de leurs parasites, et en retour l'impact des parasites sur la dynamique de leurs hôtes. Les scolytes constituent un bon modèle pour l'étude de ces interactions hôte-parasite car ils alternent des phases endémiques et épidémiques. Nous avons développé une approche pluridisciplinaire couplant la caractérisation de traits écophysiologiques et dendrométriques impliqués dans la résistance des populations d'arbres aux attaques de scolytes avec la caractérisation de facteurs écologiques clés pour la démographie des scolytes. Chez le pin d'Alep, T. destruens est présent à un niveau endémique mais des attaques subsistent dans des patchs d'arbres formés par des arbres attaqués et morts suite aux attaques, des arbres attaqués qui ont résisté et des arbres non attaqués. Des stratégies de dispersion locale différentes selon les deux grandes phases du cycle de T . destruens semblent favoriser l'exploitation d'une ressource peu abondante. Chez le sapin pectiné, nous avons montré qu'une communauté abondante de scolytes s'attaque à des arbres déjà affaiblis par des sécheresses répétées et présentant un mauvais état sanitaire et une croissance en baisse. Ces deux écosystèmes forestiers permettent de mieux appréhender les mécanismes impliqués dans les interactions plantes-insectes dans un contexte de changement global. / Mediterranean forest ecosystems have both trees living in their southern range and being sensitive to climatic stress and tree species living in the core of their range and being non sensitive to the same stress. These contrasts in tree populations questioned about potential contrasts in their interrelationships with their parasites and on the impact of that parasites have on their host in turn. Bark beetles are a relevant model to study such host-parasite interactions because they alternate endemic and epidemic phases. We developed a multidisciplinary approach combining the characterization of ecophysiological and dendrometrical traits involved in resistance of tree populations to bark beetle attacks with this assessment of key ecological factors involved in bark beetles demography. We focused on the two following contrasted Mediterranean ecosystems in South-Eastern France: a healthy Aleppo pine interacting with a bark beetle population at an endemic state and a declining population of the Silver fir interacting with a bark beetle community at an epidemic state. Our results suggested that this Aleppo pine population, the pine shoot beetle T. destruens showed low abundance levels. All attacks remained in patches formed by dead trees following the attacks. T. destruens dispersal strategies seem to favor the exploitation of a scarce resource. On silver fir, we showed a bark beetle community attacking trees already weakened by repeated droughts and with poor health status and low growth. The study of these two contrasted forest ecosystems allowed us to shed some critical light on the mechanisms involved in plant-insect interactions in the context of global change.

千年以來，人類不斷遭遇各種疫病的侵襲，流行速度更勝戰火蔓延，影響整體人類重大，然而隨著醫學知識的進步與衛生環境的改善，許多傳染病已經受到控制乃至根絕，但是生活周遭仍然面臨諸多威脅生命健康的潛藏危機，如果稍有疏失或不慎，傳染病不僅對於人體造成傷害，甚至恐將危害社會、經濟和政治層面，而近年的SARS、H1N1等流行病毒皆造成全球恐慌。 防疫工作重點在於及早掌握疫情趨勢以利制定相關因應政策，目前各國對於傳染病的掌握主要透過層層監測系統與歷史平均，藉以判斷該年特定傳染病流行與散佈程度。這些方法受到各種人為與環境因素影響，導致推估疫情成效有限之外，同時所得資料無法直接反應未來疫情，因此導致各國相關單位逐漸嘗試其他預測方法。 近年應用預測市場機制預測疫情模式引起公衛領域的重視，相關學術期刊與著名雜誌相繼介紹此一新興模式，同時肯定其在預測傳染病方面的成效與貢獻，而美國和台灣政府部門先後透過此項機制改善現有防疫體系的不足。那麼，預測市場用以預測疫情的成效是否確實如同其在眾多領域取得的成效一樣出眾？鑑於前述問題，本研究分別透過質化與量化的方式發掘公衛、醫學或流病學等其他領域對於「傳染病預測市場」是否能夠成為有效的預測機制或是成為常規的參考方法，結果證實使用的疾管局人員與參與的專業醫事人員認為「傳染病預測市場」確實可以應用於我國疫情預測的層面，但是兩者意見具有程度的差異。 / For centuries, the spread of various diseases damage countless human beings, which surpass wars in the world. Those diseases not only endanger people’s life, but also invade the other dimensions, including society, economic and politics. With the advancement of medical knowledge and the improvement of public health, many infectious diseases have been brought under control and even eradicated. But humans still face and experience threats from pandemic viruses such as SARS and H1N1 constantly. Epidemic prevention work focuses on understanding the variation of situation as soon as possible. Then governments can set up suitable decisions and policies based on epidemic situation. Though the monitoring system and the historical average are the mainstream to control the trends of infections for related departments, scientists believe that the two methods are subject to humans and environmental factors. In other words, it is difficult to draw effective information and direct response of the future trends from present methods. And it leads to national units gradually try other epidemic forecasting methods. In recent years, using prediction markets to predict flu causes the attention of public health. Thus academic journals and well-known magazines not only introduce this application but approve its effectiveness and contribution in predicting infectious diseases. The departments of US and Taiwan have tried to improve the deficiencies of the existing prevention system through prediction markets. Is this application really as successful as PM in many issues and fields? To response the question, this research intends to through qualitative and quantitative ways respectively to explore the evaluations on Epidemic Prediction Markets behind public health, medical, epidemiology, etc. The result confirms that CDC staff and health workers identify the feasibility of Epidemic Prediction Markets, but with the degree of variation.

Cette thèse traite de processus de détérioration en théorie du risque et en biomathématique. En théorie du risque, le processus de détérioration étudié est celui des sinistres supportés par une compagnie d'assurance. Le premier chapitre examine la distribution de Markov-Polya comme loi possible pour modéliser le nombre de sinistres et établit certains liens avec la famille de lois de Katz/Panjer. Nous construisons la loi de Markov-Polya sur base d'un modèle de survenance des sinistres et nous montrons qu'elle satisfait une récurrence élégante. Celle-ci permet notamment de déduire un algorithme efficace pour la loi composée correspondante. Nous déduisons la famille de Katz/Panjer comme famille limite de la loi de Markov-Polya. Le second chapitre traite de la famille dite "Lagrangian Katz" qui étend celle de Katz/Panjer. Nous motivons par un problème de premier passage son utilisation comme loi du nombre de sinistres. Nous caractérisons toutes les lois qui en font partie et nous déduisons un algorithme efficace pour la loi composée. Nous examinons également son indice de dispersion ainsi que son comportement asymptotique. Dans le troisième chapitre, nous étudions la probabilité de ruine sur horizon fini dans un modèle discret avec taux d'intérêt positifs. Nous déterminons un algorithme ainsi que différentes bornes pour cette probabilité. Une borne particulière nous permet de construire deux mesures de risque. Nous examinons également la possibilité de faire appel à de la réassurance proportionelle avec des niveaux de rétention égaux ou différents sur les périodes successives. Dans le cadre de processus épidémiques, la détérioration étudiée consiste en la propagation d'une maladie de type SIE (susceptible - infecté - éliminé). La manière dont un infecté contamine les susceptibles est décrite par des distributions de survie particulières. Nous en déduisons la distribution du nombre total de personnes infectées à la fin de l'épidémie. Nous examinons en détails les épidémies dites de type Markov-Polya et hypergéométrique. Nous approximons ensuite cette loi par un processus de branchement. Nous étudions également un processus de détérioration similaire en théorie de la fiabilité où le processus de détérioration consiste en la propagation de pannes en cascade dans un système de composantes interconnectées.

Complex networks have been used to represent the fundamental structure of a multitude of complex systems from various fields. In the network representation, the system is reduced to a set of nodes and links that denote the elements of the system and the connections between them respectively. Complex networks are commonly adaptive such that the structure of the network and the states of nodes evolve dynamically in a coupled fashion. Adaptive networks lead to peculiar complex dynamics and network topologies, which can be investigated by moment-closure approximations, a coarse-graining approach that enables the use of the dynamical systems theory. In this thesis, I study several contact processes in adaptive networks that are defined by the transmission of node states. Employing moment-closure approximations, I establish analytical insights into complex phenomena emerging in these systems. I provide a detailed analysis of existing alternative moment-closure approximation schemes and extend them in several directions. Most importantly, I consider developing analytical approaches for models with complex update rules and networks with complex topologies. I discuss four different contact processes in adaptive networks. First, I explore the effect of cyclic dominance in opinion formation. For this, I propose an adaptive network model: the adaptive rock-paper-scissors game. The model displays four different dynamical phases (stationary, oscillatory, consensus, and fragmented) with distinct topological and dynamical properties. I use a simple moment-closure approximation to explain the transitions between these phases. Second, I use the adaptive voter model of opinion formation as a benchmark model to test and compare the performances of major moment-closure approximation schemes in the literature. I provide an in-depth analysis that leads to a heightened understanding of the capabilities of alternative approaches. I demonstrate that, even for the simple adaptive voter model, highly sophisticated approximations can fail due to special dynamic correlations. As a general strategy for targeting such problematic cases, I identify and illustrate the design of new approximation schemes specific to the complex phenomena under investigation. Third, I study the collective motion in mobile animal groups, using the conceptual framework of adaptive networks of opinion formation. I focus on the role of information in consensus decision-making in populations consisting of individuals that have conflicting interests. Employing a moment-closure approximation, I predict that uninformed individuals promote democratic consensus in the population, i.e. the collective decision is made according to plurality. This prediction is confirmed in a fish school experiment, constituting the first example of direct verification for the predictions of adaptive network models. Fourth, I consider a challenging problem for moment-closure approximations: growing adaptive networks with strongly heterogeneous degree distributions. In order to capture the dynamics of such networks, I develop a new approximation scheme, from which analytical results can be obtained by a special coarse-graining procedure. I apply this analytical approach to an epidemics problem, the spreading of a fatal disease on a growing population. I show that, although the degree distribution has a finite variance at any finite infectiousness, the model lacks an epidemic threshold, which is a genuine adaptive network effect. Diseases with very low infectiousness can thus persist and prevail in growing populations.

Antibiotic resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE), are an increasing burden on healthcare systems. Hospital acquired infections with these organisms leads to higher morbidity and mortality compared with the sensitive strains of the same species and both VRE and MRSA are on the rise worldwide including in Australian hospitals. Emerging community infectious diseases are also having an impact on hospitals. The Severe Acute Respiratory Syndrome virus (SARS Co-V) was noted for its propensity to spread throughout hospitals, and was contained largely through social distancing interventions including hospital isolation. A detailed understanding of the transmission of these and other emerging pathogens is crucial for their containment. The statistical inference and mathematical models used in this thesis aim to improve understanding of pathogen transmission by estimating the transmission rates of contagions and predicting the impact of interventions. Datasets used for these studies come from the Princess Alexandra Hospital in Brisbane, Australia and Shanxi province, mainland China. Epidemiological data on infection outbreaks are challenging to analyse due to the censored nature of infection transmission events. Most datasets record the time on symptom onset, but the transmission time is not observable. There are many ways of managing censored data, in this study we use Bayesian inference, with transmission times incorporated into the augmented dataset as latent variables. Hospital infection surveillance data is often much less detailed that data collected for epidemiological studies, often consisting of serial incidence or prevalence of patient colonisation with a resistant pathogen without individual patient event histories. Despite the lack of detailed data, transmission characteristics can be inferred from such a dataset using structured HiddenMarkovModels (HMMs). Each new transmission in an epidemic increases the infection pressure on those remaining susceptible, hence infection outbreak data are serially dependent. Statistical methods that assume independence of infection events are misleading and prone to over-estimating the impact of infection control interventions. Structured mathematical models that include transmission pressure are essential. Mathematical models can also give insights into the potential impact of interventions. The complex interaction of different infection control strategies, and their likely impact on transmission can be predicted using mathematical models. This dissertation uses modified or novel mathematical models that are specific to the pathogen and dataset being analysed. The first study estimates MRSA transmission in an Intensive Care Unit, using a structured four compartment model, Bayesian inference and a piecewise hazard methods. The model predicts the impact of interventions, such as changes to staff/patient ratios, ward size and decolonisation. A comparison of results of the stochastic and deterministic model is made and reason for differences given. The second study constructs a Hidden Markov Model to describe longitudinal data on weekly VRE prevalence. Transmission is assumed to be either from patient to patient cross-transmission or sporadic (independent of cross-transmission) and parameters for each mode of acquisition are estimated from the data. The third study develops a new model with a compartment representing an environmental reservoir. Parameters for the model are gathered from literature sources and the implications of the environmental reservoir are explored. The fourth study uses a modified Susceptible-Exposed-Infectious-Removed (SEIR) model to analyse data from a SARS outbreak in Shanxi province, China. Infectivity is determined before and after interventions as well as separately for hospitalised and community symptomatic SARS cases. Model diagnostics including sensitivity analysis, model comparison and bootstrapping are implemented.

New Zealand’s First World War studies have traditionally focused on the soldier and battlefield experiences. ‘The Rural Home Front’ breaks with that tradition and focuses on the lives of people and the local communities that the soldiers left behind in the predominantly rural region of Taranaki in New Zealand. ‘The Rural Home Front’ is essentially a study of the impact and effects of the First World War on rural society. By focusing on topics and themes such as ‘war enthusiasm’, the voluntary spirit of fund raising and recruiting, conscription, attempting to maintain normality during wartime, responses to war deaths, the influenza epidemic, the Armistice and the need to remember, this thesis argues that civilians experienced the Great War, too, albeit differently from that of the soldiers serving overseas.