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Rabies is a viral disease caused by the rabies lyssavirus (RABV). Despite effective rabies vaccines for humans and animals, this disease continues to pose a major public health challenge, causing an estimated 59 000 human deaths each year, over 99% of which are caused by the domestic dog (Canis familiaris). Current methods of dog population management used in rabies control programs are ineffective. Surgical sterilisation does not reach enough of the dog population to curb population densities and contraceptives need to be administered at a specific phase in the oestrous cycle or cause a range of side effects. Immunocontraception in dogs would allow rabies vaccination coverage to be maintained, in turn reducing the burden of rabies on public health. The aim of this study was to develop an immunocontraceptive vaccine for dogs capable of eliciting a stronger immune response than that of previously constructed vaccines allowing for effective dog population management and allowing rabies vaccination coverage to be maintain, in turn reducing the burden of rabies on public health. By stabilising the dog population size, the 70% vaccination coverage required to interrupt rabies transmission within a population can be maintained. The immunocontraceptive vaccine constructed in this study contained two reproductive hormones, namely GnRH and kisspeptin, in the hope of eliciting a stronger contraceptive effect than either of these could produce alone, as well as the partial tetanus toxoid gene as an immune stimulant. The nucleic acid GnRH, kisspeptin and partial tetanus toxoid gene (GKT) insert fragment was PCR amplified from a DNA construct (pVAC-GKT) and was cloned into the adenoviral vector using In-fusion cloning technology. Transfection of pAdeno-X 293 cells was confirmed using green fluorescent microscopy and expression of the Ad-GKT mRNA in cell culture was confirmed using real-time RT-PCR. The antigenicity of the Ad-GKT construct was evaluated using female Swiss Webster mice. An indirect ELISA was used to detect seroconversion of the GnRH and Kisspeptin insert fragments. The Ad-GKT construct was successful in eliciting an immune response against GnRH and kisspeptin. Future research should include a comparative study to determine the antigenicity of the Ad-GnRH1 and Ad-GKT constructs in a canine trial for potential use in rabies control programs. / Dissertation (MSc (Microbiology))--University of Pretoria, 2021. / The Poliomyelitis Research Foundation grant (19/89). University of Pretoria postgraduate masters research bursary. Technology Innovation Agency Seed Fund. National Research Foundation grant (122016). / Microbiology and Plant Pathology / MSc (Microbiology) / Restricted

THESIS ABSTRACT

Decision makers' conflicts about the validity of a single simulation model and inefficiencies of existing response matrix methods (RMM) hinder adopting successful groundwater management plans. We speed up the process by proposing a hybrid RMM that is most efficient for situations in which optimizable stimuli can vary through consecutive periods of uniform duration interspersed with periods of different duration. We use the hybrid RMM within Simulation-Optimization (S-O) models to develop optimal water management strategies. For the tested problems, the hybrid RMM requires as much or 63-89% less computation time than other RMMs. Second, we propose Multi-Conceptual Model Optimization (MCMO) that can help stakeholders reach a compromise strategy instead of agreeing on the validity of a single model. MCMO computes optimal strategies that simultaneously satisfy analogous constraints and bounds in multiple numerical models differing by more than parameter values. Applying MCMO to Cache Valley (Utah, USA) reveals that protecting local ecosystem limits the increased groundwater pumping to satisfy only 40% of projected water demand increase using two models. To successfully and sustainably manage Cache Valley aquifer, we evaluate sustained yield strategies (SYS) and quantify the resilience of a computed SYS. We maximize the number of new residents who can have their indoor and outdoor uses satisfied, subject to constraints on aquifer-surface waters conditions, and limiting new residents to projected increases in population (PIiP). furthermore, we examine the effect of optimization approach and sequiencing, temporally-lagged spatially distributed return flow that is a function of optimal groundwater use, and the acceptability time evaluation on the optimal yield strategy. Cache Valley aquifer can sustainably satisfy the outdoor water demand of 74%-83% and the indoor water demand of 83%-100% of the PIiP. We quantify deterministic resilience Rd(A,T,SV)=P to evaluate how completely an aquifer condition (SV) recovers after the end of climatic anomaly (A), by recovery time (T). Simulation predicts that Cache Valley aquifer system resiliences to a 2-year drought are Rd(2YD, 3 yrs, Overall) = 93% and Rd (2YD,≥8,Overall) ≥ 95%. Proportionally reducing pumping rates by 25% through the time horizon of the simulation increases the overall resilience to 96% within 3 years.

Master of Arts / Department of Geography / J. M. Shawn Hutchinson / Prairie dogs (Cynomys spp.) are social, ground-dwelling rodents native to North American short- and mixed-grass prairie. They are also the main prey of the Federally-endangered black-footed ferret (Mustela nigripes). At the same time, prairie dog colonization is highly opposed by most agricultural landowners. Therefore nonlethal population management techniques must be investigated. This paper presents the results of research on the effectiveness of ungrazed vegetative barriers composed of native plants at limiting prairie dog dispersal away from a ferret reintroduction site in northwest Kansas. Data was collected on barrier quality and condition as well as estimates of population densities of immigrant prairie dogs, dispersing through the vegetative barrier to reoccupy previously extirpated colonies on properties surrounding the ferret reintroduction site. Using strip transects and aboveground visual counts to estimate population densities and visual obstruction ranking techniques to sample barrier condition, statistical analysis of the data indicated that while barrier condition increased over time, it was not effective at limiting prairie dog emigration from the black-footed ferret reintroduction site.

Este estudo integrou sistemas de informação geográfica e métodos analíticos geoespaciais baseados em modelos de acessibilidade espacial e de locação-alocação com o objetivo de aprimorar o planejamento espacial de diferentes programas de saúde pública em áreas urbanas. Para estimar a acessibilidade espacial foi desenvolvido o modelo de três passos de área de influência flutuante (E3SFCA - Enhancement three-step floating catchment área) baseado em uma função Gaussiana, considerando um coeficiente de atrito e distâncias ao longo de uma rede de transporte, utilizando o algoritmo de Dijkstra. A metodologia foi aplicada e validada usando os programas de vacinação contra a raiva e de esterilização para cães e gatos da cidade de Bogotá, Colômbia. A escolha do método de cálculo da distância resolveu o problema de superestimação associado com a metodologia clássica que aplica zonas buffer em torno dos locais de serviço baseado em uma distância Euclideana. Em geral, não se encontrou uma adequada acessibilidade espacial aos dois programas. As zonas norte, central e periférica da cidade revelaram baixa ou nula acessibilidade aos serviços. Para determinar a alocação e realocação efetiva dos programas foram utilizados os problemas de máxima cobertura com demanda finita e de p-mediana ou de mínima impedância. A realocação proposta pelo modelo de máxima cobertura forneceu uma melhor distribuição dos serviços nas áreas mais povoadas com cães e gatos e garantiu uma acessibilidade espacial potencial a estes programas. O desenvolvimento deste trabalho pode trazer benefícios diretos para a sociedade em geral auxiliando no planejamento estratégico e melhorando a efetividade das ações públicas em áreas urbanas da América Latina. / This study integrated geographic information systems and geospatial analytical methods based on spatial accessibility and location-allocation models in order to improve the spatial planning of different public health programs in urban areas. To estimate the spatial accessibility, a Gaussian-based three-step oating catchment area (E3SFCA) method was developed, including a friction coeffcient and using distances along a street network based on Dijkstra\'s algorithm. The methodology was applied and valiated using the rabies vaccination and sterilization programs for dogs and cats in the city of Bogotá, Colombia. The choice of the distance calculation method solve the overestimation associated with the classic methodology that applies buffer zones around vaccination sites based on Euclidean (straight-line) distance. In general it was not observed an adequate spatial accessibility to both programs. The zones north, central and peripheral of the city revealed low or no access to services. To determine the effective allocation or reallocation of these programs the maximum coverage with finite demand and the p-median or minimum impedance problems were used. The relocation proposed by the maximum coverage model provided a better distribution of the services in the most populated areas and proportioned a potential spatial accessibility to these programs. The development of this work can provide direct benefits to society assisting in the strategic planning and improving the effectiveness of public policies in urban areas of Latin America.

O manejo populacional de cães e gatos é um conjunto de estratégias para controlar e prevenir problemas relacionados com o convívio entre esses animais e os seres humanos. Nesta tese é proposto um fluxo de trabalho baseado em métodos quantitativos, para auxiliar o planejamento, implementação e monitoramento de programas de manejo populacional de animais de companhia. Ao seguir o fluxo de trabalho é possível coletar dados para caracterizar populações, analisar esses dados para propor intervenções e avaliar o efeito das intervenções. A proposta foi baseada na articulação de cinco pesquisas. Na primeira pesquisa foi implementado de um desenho amostral complexo para caracterizar a população de cães e gatos domiciliados de Votorantim, São Paulo. Na segunda pesquisa que foi baseada nos dados levantados na primeira, foram usadas análises de correspondências múltiplas para identificar perfis de opiniões públicas em relação ao abandono de cães e gatos. Na terceira pesquisa foi avaliada a validade do desenho amostral usado na primeira pesquisa, mediante simulações estocásticas. Na quarta pesquisa foi desenvolvido um modelo matemático de manejo populacional que permite priorizar as intervenções de acordo com o efeito que produzem. Na quinta pesquisa foi desenvolvido um modelo matemático para avaliar a eficiência do controle reprodutivo realizado com contraceptivos de efeito reversível. Os modelos das duas últimas pesquisas foram baseados em sistemas acoplados de equações diferenciais e em análises de sensibilidade global e local. A proposta foi implementada em um software de código aberto, o pacote do R capm, que pode ser incorporado na rotina de trabalho dos setores envolvidos no manejo populacional de animais de companhia / Dog and cat population management is a set of strategies to control and prevent problems related with the coexistence between those animals and human beings. In this thesis it is proposed a work-fiow based on quantitative methods to support the planning, implementation and mo- nitoring of companion animal population management programs. Following the work-fiow, it is possible to collecf data to characterize populations, analyze that data to propose interventions and assess the effect of interventions. The proposal was based on the articulation of five rese- arches. In the first research, a complex sampling design was implemented to characterize the owned dog and cat populations of Votorantim, São Paulo. In the second research, which was based on data from the first one, public opinion profiles regarding dog and cat abandonment were identified using multiple correspondence analysis. In the third research, the validity of the sampling design used in the first research was assessed through stochastic simulations. In the fourth research, a mathematical model of population management was developed. With that model, it is possible to prioritize interventions according to the effect they produce. In the fifth research, a mathematical model was developed to assess the efficiency of reproductive control based on contraceptives with reversible effect. The models of the last two researches were based on systems of coupled differential equations, and on global and local sensitivity analysis. The proposal was implemented in an open source software, the R package capm, that can be incorporated in the working routine of sectors involved with companion animal population management

Este estudo integrou sistemas de informação geográfica e métodos analíticos geoespaciais baseados em modelos de acessibilidade espacial e de locação-alocação com o objetivo de aprimorar o planejamento espacial de diferentes programas de saúde pública em áreas urbanas. Para estimar a acessibilidade espacial foi desenvolvido o modelo de três passos de área de influência flutuante (E3SFCA - Enhancement three-step floating catchment área) baseado em uma função Gaussiana, considerando um coeficiente de atrito e distâncias ao longo de uma rede de transporte, utilizando o algoritmo de Dijkstra. A metodologia foi aplicada e validada usando os programas de vacinação contra a raiva e de esterilização para cães e gatos da cidade de Bogotá, Colômbia. A escolha do método de cálculo da distância resolveu o problema de superestimação associado com a metodologia clássica que aplica zonas buffer em torno dos locais de serviço baseado em uma distância Euclideana. Em geral, não se encontrou uma adequada acessibilidade espacial aos dois programas. As zonas norte, central e periférica da cidade revelaram baixa ou nula acessibilidade aos serviços. Para determinar a alocação e realocação efetiva dos programas foram utilizados os problemas de máxima cobertura com demanda finita e de p-mediana ou de mínima impedância. A realocação proposta pelo modelo de máxima cobertura forneceu uma melhor distribuição dos serviços nas áreas mais povoadas com cães e gatos e garantiu uma acessibilidade espacial potencial a estes programas. O desenvolvimento deste trabalho pode trazer benefícios diretos para a sociedade em geral auxiliando no planejamento estratégico e melhorando a efetividade das ações públicas em áreas urbanas da América Latina. / This study integrated geographic information systems and geospatial analytical methods based on spatial accessibility and location-allocation models in order to improve the spatial planning of different public health programs in urban areas. To estimate the spatial accessibility, a Gaussian-based three-step oating catchment area (E3SFCA) method was developed, including a friction coeffcient and using distances along a street network based on Dijkstra\'s algorithm. The methodology was applied and valiated using the rabies vaccination and sterilization programs for dogs and cats in the city of Bogotá, Colombia. The choice of the distance calculation method solve the overestimation associated with the classic methodology that applies buffer zones around vaccination sites based on Euclidean (straight-line) distance. In general it was not observed an adequate spatial accessibility to both programs. The zones north, central and peripheral of the city revealed low or no access to services. To determine the effective allocation or reallocation of these programs the maximum coverage with finite demand and the p-median or minimum impedance problems were used. The relocation proposed by the maximum coverage model provided a better distribution of the services in the most populated areas and proportioned a potential spatial accessibility to these programs. The development of this work can provide direct benefits to society assisting in the strategic planning and improving the effectiveness of public policies in urban areas of Latin America.

O manejo populacional de cães e gatos é um conjunto de estratégias para controlar e prevenir problemas relacionados com o convívio entre esses animais e os seres humanos. Nesta tese é proposto um fluxo de trabalho baseado em métodos quantitativos, para auxiliar o planejamento, implementação e monitoramento de programas de manejo populacional de animais de companhia. Ao seguir o fluxo de trabalho é possível coletar dados para caracterizar populações, analisar esses dados para propor intervenções e avaliar o efeito das intervenções. A proposta foi baseada na articulação de cinco pesquisas. Na primeira pesquisa foi implementado de um desenho amostral complexo para caracterizar a população de cães e gatos domiciliados de Votorantim, São Paulo. Na segunda pesquisa que foi baseada nos dados levantados na primeira, foram usadas análises de correspondências múltiplas para identificar perfis de opiniões públicas em relação ao abandono de cães e gatos. Na terceira pesquisa foi avaliada a validade do desenho amostral usado na primeira pesquisa, mediante simulações estocásticas. Na quarta pesquisa foi desenvolvido um modelo matemático de manejo populacional que permite priorizar as intervenções de acordo com o efeito que produzem. Na quinta pesquisa foi desenvolvido um modelo matemático para avaliar a eficiência do controle reprodutivo realizado com contraceptivos de efeito reversível. Os modelos das duas últimas pesquisas foram baseados em sistemas acoplados de equações diferenciais e em análises de sensibilidade global e local. A proposta foi implementada em um software de código aberto, o pacote do R capm, que pode ser incorporado na rotina de trabalho dos setores envolvidos no manejo populacional de animais de companhia / Dog and cat population management is a set of strategies to control and prevent problems related with the coexistence between those animals and human beings. In this thesis it is proposed a work-fiow based on quantitative methods to support the planning, implementation and mo- nitoring of companion animal population management programs. Following the work-fiow, it is possible to collecf data to characterize populations, analyze that data to propose interventions and assess the effect of interventions. The proposal was based on the articulation of five rese- arches. In the first research, a complex sampling design was implemented to characterize the owned dog and cat populations of Votorantim, São Paulo. In the second research, which was based on data from the first one, public opinion profiles regarding dog and cat abandonment were identified using multiple correspondence analysis. In the third research, the validity of the sampling design used in the first research was assessed through stochastic simulations. In the fourth research, a mathematical model of population management was developed. With that model, it is possible to prioritize interventions according to the effect they produce. In the fifth research, a mathematical model was developed to assess the efficiency of reproductive control based on contraceptives with reversible effect. The models of the last two researches were based on systems of coupled differential equations, and on global and local sensitivity analysis. The proposal was implemented in an open source software, the R package capm, that can be incorporated in the working routine of sectors involved with companion animal population management

A presente pesquisa partiu de uma etnografia realizada na região conhecida como Cracolândia no centro de São Paulo, considerada a mais famosa territorialidade de uso de crack no país. Alvo de intervenções estatais desde seu surgimento, nos anos 1990, essa territorialidade continua no centro de muitos programas e instituições. Em 2012, com o conflito erguido em torno da Operação Sufoco, há, no entanto, uma mudança nas formas de gestão desse espaço: de uma racionalidade de dispersão, que visava impedir o agrupamento de usuários de crack por meio do uso da força, para uma lógica de governo que precisa desse espaço concentrado para executar seus programas. Minha hipótese é que a fixação territorial combinada a essa malha concentrada de programas e instituições assistenciais acabou por construir um campo de gravitação em torno da Cracolândia, de modo a atrair pessoas com trajetórias muito diferentes mas que se encontram ali por terem uma vida errante. A partir do percurso de uma jovem que conheci durante a pesquisa, argumento que o Estado produz espaços e territorialidades como a Cracolândia, ao induzir e condicionar o movimento de diversos sujeitos. Como a personagem dessa pesquisa evidencia, sua circulação é incessante e ilegível, como na imagem do labirinto, mas guiada por uma racionalidade de buscar um local seguro das investidas policiais para estabelecer suas malocas e modos de vida, e onde há concentração de recursos e possibilidades. Dessa forma, a Cracolândia só faz sentido dentro de uma experiência urbana mais ampla, o que envolve outros espaços não contingentes territorialmente. / This research started from an ethnography in the region known as Cracolândia in downtown of São Paulo, considered the most famous crack use of territoriality in the country. Target of state interventions since its inception in the 1990s, this territoriality remains at the heart of many programs and institutions. In 2012, the conflict erected around the operation Suffocation, there is, however, a change in the forms of management of this space: a rationality dispersion, which was intended to prevent the grouping of crack users through the use of force, to a logic of government that needs this concentrated space to run their programs. My hypothesis is that the territorial fixation combined with this concentrated mesh programs and charitable institutions eventually build a gravitational field around the Cracolândia in order to attract people with very different paths but they are there to have a wandering life. From the journey of a young man I met during the research, I argue that the state produces spaces and territoriality as Cracolândia, to induce and influence the movement of various subjects. As the character of this research shows, their movement is unceasing and unreadable, as the labyrinth image, but guided by a rationality to seek a safe place police invested to establish their \"huts\" and ways of life, and where there is a concentration of resources and possibilities. Thus, Cracolândia only makes sense within a broader urban experience, which involves other spaces not contingent territorially.