No description available.

<p>Akrilamid je toksična hemijska supstanca koja ima vrlo &scaron;iroku primenu u hemijskoj industriji, a 2002. godine otkriveno je njegovo prisustvo u namirnicima bogatim skrobom koje se pripremaju na visokim temperaturama. U poslednjh desetak godina primećen je veliki porast gastrointestinalnih tegoba u ljudskoj populaciji. Cilj istraživanja bio je ispitati patohistolo&scaron;ke promene u tkivu želuca pacova soja Wistar izazvanih peroralnim aplikovanjem akrilamida i na taj način povući paralelu sa mogućim gastrointestinalnim tegobama nastalim kao posledica konzumiranja hrane bogate akrilamidom. U istraživanju je ispitivano 6 grupa od po 5 eksperimentalnih životinja (pacovi soja Wistar). Dve kontrolne grupe kojima je peroralno aplikovana destilovana voda i koje su žrtvovane posle 24h i 72h; dve eksperimentalne kojima je peroralno aplikovan akrilamid u dnevnoj dozi od 25 mg/kg i koje su žrtvovane posle 24h i 72h; dve eksperimentalne grupe kojima je peroralno aplikovan akrilamid u dnevnoj dozi od 50 mg/kg i koje su žrtvovane posle 24h i 72h. Na histolo&scaron;kom materijalu tkiva želuca primenjena je kvalitativna histolo&scaron;ka analiza pod svetlosnim mikroskopom, semikvantitativna procena tipa mucina u epitelnim ćelijama sluznice želuca, prisustvo limfocita i granulocita u sluznici želuca, stereolo&scaron;ka merenja pojedinih kompartmana zida želuca, linearna merenja broja i veličine ganglijskih ćelija u Maissner-ovom i Auerbach-ovom nervnom pleksusu, kao i broj mastocita u lamini propriji sluznice i podsluznici želuca. Dobijene vrednosti merenih parametara su potom statistički obrađene. Nastale promene na tkivu želuca pacova soja Wistar se ogledaju u vidu blagog direktnog o&scaron;tećenja povr&scaron;nog epitela sa propratnom blagom inflamatornom reakcijom i blagom degranulacijom mastocita. U Maissner-ovom i Auerbach-ovom nervnom pleksusu su smanjene volumenske gustine nervnih vlakana i ganglijskih ćelija, kao i broj i veličina ganglijskih ćelija. Direktno toksično delovanje na epitel dovodi do posledične obnove epitela, te je potvrđeno prisustvo nezrelijih oblika mukoproduktivnih ćelija koje sadrže kisele, AB pozitivne mucine. Ispitani inflamatorni i degenerativni parametri pokazuju pozitivnu korelaciju u odnosu na dozu i/ili dužinu ekspozicije akrilamidu. Primena akrilamida peroralno pokazala je da postoje patohistolo&scaron;ke promene na tkivu želuca u vidu direktnog toksičnog o&scaron;tećenja epitela, inflamatorne reakcije i o&scaron;tećenja nervnih pleksusa. Poznavanjem mehanizma delovanja ove toksične materije moguće je primeniti adekvatnu prevenciju u ishrani i izvr&scaron;iti odgovarajući izbor terapijskih metoda.</p> / <p>Acrylamide is a toxic chemical substance with wide implementation in chemical industry. In 2002 it was discovered the presence of acrylamide in foods rich in starch which are prepared at high temperatures. In the last ten years there is a large increase in gastrointestinal illnesses in human population. The aim of this study was to investigate the histopathological changes in the gastric tissue in Wistar rats induced with injection of oral acrylamide and thus draw a parallel with possible gastrointestinal problems arising as a result of the consumption of foods rich in acrylamide. The research was carried out 6 groups of 5 experimental animals (Wistar rats). Two control groups that are orally concomitant application of distilled water and which were sacrificed after 24h and 72h; two experimental groups which are orally administrated acrylamide in a daily dose of 25 mg / kg and that were sacrificed after 24h and 72h; two experimental groups which were orally administrated acrylamide in a daily dose of 50 mg / kg and that were sacrificed after 24h and 72h. On histological gastric tissue material is applied qualitative histological analysis by light microscopy, semi-quantitative assessment of the type of mucin in epithelial cells of the stomach lining, the presence of lymphocytes and granulocytes in gastric mucosa, stereological measurements of individual compartments of the stomach wall, linear measuring the number and size of ganglion cells in the Maissner and Auerbach&#39;s nerve plexus, and the number of mast cells in the lamina propria of the mucosa and in the submucosis of the stomach. Obtained values of measured parameters were statistically processed. Histological changes in the stomach tissue of Wistar rats are seen as a direct slight damage of the surface epithelium, with accompanynig mild inflammatory reaction and the degranulation of mast cells. The Meissner&#39;s and Auerbach&#39;s nerve plexus decreased volume density of nerve fibers and ganglion cells, as well as the number and size of the ganglion cells. Directly toxic effect on epithelium leads to the result of the reconstruction of the epithelium, which is confirmed by the presence of immature form of mucoproductive cells which contain acid, AB positive mucins. Examined inflammatory and degenerative parameters show a positive correlation with respect to dose and / or a time of exposition to acrylamide. Acrylamide oral application revealed that there are histologic changes in the stomach tissue in the form of a direct toxic damage to the epithelium, inflammatory reaction and damage to the nerve plexus. Knowing the mechanism of action of these toxic substances allows to apply adequate prevention in nutrition and make an appropriate choice of therapeutic methods.</p>

In this thesis we develop several kinds of latent variable models in order to address three types of bio-statistical problem. The three problems are the treatment effect of carcinogens on tumour development, spatial interactions between plant species and motor unit number estimation (MUNE). The three types of data looked at are: highly heterogeneous longitudinal count data, quadrat counts of species on a rectangular lattice and lastly, electrophysiological data consisting of measurements of compound muscle action potential (CMAP) area and amplitude. Chapter 1 sets out the structure and the development of ideas presented in this thesis from the point of view of: model structure, model selection, and efficiency of estimation. Chapter 2 is an introduction to the relevant literature that has in influenced the development of this thesis. In Chapter 3 we use the EM algorithm for an application of an autoregressive hidden Markov model to describe longitudinal counts. The data is collected from experiments to test the effect of carcinogens on tumour growth in mice. Here we develop forward and backward recursions for calculating the likelihood and for estimation. Chapter 4 is the analysis of a similar kind of data using a more sophisticated model, incorporating random effects, but estimation this time is conducted from the Bayesian perspective. Bayesian model selection is also explored. In Chapter 5 we move to the two dimensional lattice and construct a model for describing the spatial interaction of tree types. We also compare the merits of directed and undirected graphical models for describing the hidden lattice. Chapter 6 is the application of a Bayesian hierarchical model (MUNE), where the latent variable this time is multivariate Gaussian and dependent on a covariate, the stimulus. Model selection is carried out using the Bayes Information Criterion (BIC). In Chapter 7 we approach the same problem by using the reversible jump methodology (Green, 1995) where this time we use a dual Gaussian-Binary representation of the latent data. We conclude in Chapter 8 with suggestions for the direction of new work. In this thesis, all of the estimation carried out on real data has only been performed once we have been satisfied that estimation is able to retrieve the parameters from simulated data. Keywords: Amyotrophic lateral sclerosis (ALS), carcinogens, hidden Markov models (HMM), latent variable models, longitudinal data analysis, motor unit disease (MND), partially ordered Markov models (POMMs), the pseudo auto- logistic model, reversible jump, spatial interactions.

Made available in DSpace on 2016-06-02T20:06:06Z (GMT). No. of bitstreams: 1 4336.pdf: 1594022 bytes, checksum: ff2370b4d516b9cdf6dd6da3be557c42 (MD5) Previous issue date: 2012-03-16 / Financiadora de Estudos e Projetos / Experiments involving chemical induction of carcinogens in animals are common in the biological area. Interest in these experiments is, in general, evaluating the chemopreventive effect of a substance in the destruction of damaged cells. In this type of study, two variables of interest are the number of induced tumors and their development times. We explored the use of statistical model proposed by Kokoska (1987) for the analysis of experimental data of chemoprevention of cancer in animals. We flexibility the Kokoska s model, subsequently used by Freedman (1993), whereas for the variable number of tumors induced Conway-Maxwell Poisson (COM-Poisson) distribution. This distribution has demonstrated efficiency due to its great flexibility, when compared to other discrete distributions to accommodate problems related to sub-dispersion and super-dispersion often found in count data. The purpose of this paper is to adapt the theory of long-term destructive model (Rodrigues et al., 2011) for experiments chemoprevention of cancer in animals, in order to evaluate the effectiveness of cancer treatments. Unlike the proposed Rodrigues et al. (2011), we formulate a model for the variable number of detected malignant tumors per animal, assuming that the probability of detection is no longer constant, but dependent on the time step. This is an extremely important approach to cancer chemoprevention experiments, because it makes the analysis more realistic and accurate. We conducted a simulation study, in order to evaluate the efficiency of the proposed model and to verify the asymptotic properties of maximum likelihood estimators. We also analyze a real data set presented in the article by Freedman (1993), to demonstrate the efficiency of the COM-Poisson model compared to results obtained by him with the Poisson and Negative Binomial distributions. / Experimentos que envolvem a indução química de substâncias cancerígenas em animais são comuns na área biológica. O interesse destes experimentos é, em geral, avaliar o efeito de uma substância quimiopreventiva na destruição das células danificadas. Neste tipo de estudo, duas variáveis de interesse são o número de tumores induzidos e seus tempos de desenvolvimento. Exploramos o uso do modelo estatístico proposto por Kokoska (1987) para a análise de dados de experimentos de quimioprevenção de câncer em animais. Flexibilizamos o modelo de Kokoska (1987), posteriormente utilizado por Freedman (1993), considerando para a variável número de tumores induzidos a distribuição Conway-Maxwell Poisson (COM-Poisson). Esta distribuição tem demonstrado eficiência devido à sua grande flexibilidade, quando comparada a outras distribuições discretas, para acomodar problemas relacionados à subdispersão e sobredispersão encontrados frequentemente em dados de contagem. A proposta deste trabalho consiste em adaptar a teoria de modelo destrutivo de longa duração (Rodrigues et al., 2011) para experimentos de quimioprevenção do câncer em animais, com o propósito de avaliar a eficiência de tratamentos contra o câncer. Diferente da proposta de Rodrigues et al. (2011), formulamos um modelo para a variável número de tumores malignos detectados por animal, supondo que sua probabilidade de detecção não é mais constante, e sim dependente do instante de tempo. Esta é uma abordagem extremamente importante para experimentos quimiopreventivos de câncer, pois torna a análise mais realista e precisa. Realizamos um estudo de simulação com o propósito de avaliar a eficiência do modelo proposto e verificar as propriedades assintóticas dos estimadores de máxima verossimilhança. Analisamos também um conjunto de dados reais apresentado no artigo de Freedman (1993), visando demonstrar a eficiência do modelo COM-Poisson em relação aos resultados por ele obtidos com as distribuições Poisson e Binomial Negativa.