Parameters associated with the detection and quantification of microorganisms (or discrete particles) in water such as the analytical recovery of an enumeration method, the concentration of the microorganisms or particles in the water, the log-reduction achieved using a treatment process, and the sensitivity of a detection method cannot be measured exactly. There are unavoidable random errors in the enumeration process that make estimates of these parameters imprecise and possibly also inaccurate. For example, the number of microorganisms observed divided by the volume of water analyzed is commonly used as an estimate of concentration, but there are random errors in sample collection and sample processing that make these estimates imprecise. Moreover, this estimate is inaccurate if poor analytical recovery results in observation of a different number of microorganisms than what was actually present in the sample. In this thesis, a statistical framework (using probabilistic modelling and Bayes’ theorem) is developed to enable appropriate analysis of microorganism concentration estimates given information about analytical recovery and knowledge of how various random errors in the enumeration process affect count data. Similar models are developed to enable analysis of recovery data given information about the seed dose. This statistical framework is used to address several problems: (1) estimation of parameters that describe random sample-to-sample variability in the analytical recovery of an enumeration method, (2) estimation of concentration, and quantification of the uncertainty therein, from single or replicate data (which may include non-detect samples), (3) estimation of the log-reduction of a treatment process (and the uncertainty therein) from pre- and post-treatment concentration estimates, (4) quantification of random concentration variability over time, and (5) estimation of the sensitivity of enumeration processes given knowledge about analytical recovery. The developed models are also used to investigate alternative strategies that may enable collection of more precise data. The concepts presented in this thesis are used to enhance analysis of pathogen concentration data in Quantitative Microbial Risk Assessment so that computed risk estimates are more predictive. Drinking water research and prudent management of treatment systems depend upon collection of reliable data and appropriate interpretation of the data that are available.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 178-195).

Parameters associated with the detection and quantification of microorganisms (or discrete particles) in water such as the analytical recovery of an enumeration method, the concentration of the microorganisms or particles in the water, the log-reduction achieved using a treatment process, and the sensitivity of a detection method cannot be measured exactly. There are unavoidable random errors in the enumeration process that make estimates of these parameters imprecise and possibly also inaccurate. For example, the number of microorganisms observed divided by the volume of water analyzed is commonly used as an estimate of concentration, but there are random errors in sample collection and sample processing that make these estimates imprecise. Moreover, this estimate is inaccurate if poor analytical recovery results in observation of a different number of microorganisms than what was actually present in the sample. In this thesis, a statistical framework (using probabilistic modelling and Bayes’ theorem) is developed to enable appropriate analysis of microorganism concentration estimates given information about analytical recovery and knowledge of how various random errors in the enumeration process affect count data. Similar models are developed to enable analysis of recovery data given information about the seed dose. This statistical framework is used to address several problems: (1) estimation of parameters that describe random sample-to-sample variability in the analytical recovery of an enumeration method, (2) estimation of concentration, and quantification of the uncertainty therein, from single or replicate data (which may include non-detect samples), (3) estimation of the log-reduction of a treatment process (and the uncertainty therein) from pre- and post-treatment concentration estimates, (4) quantification of random concentration variability over time, and (5) estimation of the sensitivity of enumeration processes given knowledge about analytical recovery. The developed models are also used to investigate alternative strategies that may enable collection of more precise data. The concepts presented in this thesis are used to enhance analysis of pathogen concentration data in Quantitative Microbial Risk Assessment so that computed risk estimates are more predictive. Drinking water research and prudent management of treatment systems depend upon collection of reliable data and appropriate interpretation of the data that are available.

The sequencing of the human genome revealed that the number of genes does not explain why humans are different from other organisms like mice and dogs. Instead, it is how genes interact with each other and the environment that separates us from other organisms. This motivates the study of genetic networks and, consequently, my research. My work delves into the roles that simple genetic networks play in a cell and explores the biotechnological aspects of how to uncover such genes and their interactions in experimental models. / Cells must respond to the extracellular environment to contract, migrate, and live. Cells, however, are subject to stochastic fluctuations in protein concentrations. I investigate how cells make important decisions such as gene transcription based on noisy measurements of the extracellular environment. I propose that genetic networks perform Bayesian inference as a way to consider the probabilistic nature of these measurements and make the best decision. With mathematical models, I show that allosteric repressors and activators can correctly infer the state of the environment despite fluctuating concentrations of molecules. Viewing transcriptional networks as inference modules explains previous experimental data. I also discover that the particular inference problem determines whether repressors or activators are better. / Next, I explore the genetic underpinnings of two canine models of atrial fibrillation: atrial tachypacing and ventricular tachypacing. Using Affymetrix microarrays, I find that the genetic signatures of these two models are significantly different both in magnitude and in class of genes expressed. The ventricular tachypacing model has thousands of transcripts differentially expressed with little overlap between 24 hours and 2 weeks, suggesting independent mechanisms. The atrial tachypacing model demonstrates an adaptation as the number of genes found changed decreases with increasing time to the point that no genes are changed at 6 weeks. I use higher level analysis to find that extracellular matrix components are among the most changed in ventricular tachypacing and that genes like connective tissue growth factor may be responsible. / Finally, I generalize the main problem of microarray analysis into an evaluation problem of choosing between two competing options based on the scores of many independent judges. In this context, I rediscover the voting paradox and compare two different solutions to this problem: the sum rule and the majority rule. I find that the accuracy of a decision depends on the distribution of the judges' scores. Narrow distributions are better solved with a sum rule, while broad distributions prefer a majority rule. This finding motivates a new algorithm for microarray analysis which outperforms popular existing algorithms on a sample data set and the canine data set examined earlier. A cost analysis reveals that the optimal number of judges depends on the ratio of the cost of a wrong decision to the cost of a judge.

Diss. (sammanfattning) Umeå : Univ., 2008. / Härtill 5 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed on June 23, 2009). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (p. 164-170).

OBJETIVO: Comparar a eficácia e a tolerabilidade dos fármacos antiepiléticos (FAE) no tratamento em monoterapia de pacientes com epilepsia focal ou generalizada. MÉTODOS: Uma revisão sistemática foi realizada por meio da busca nas bases de dados eletrônicas Pubmed, Scopus, Web of Science e Cochrane Register of Controlled Trials. Foram incluídos os ensaios clínicos controlados com pacientes com epilepsia, em tratamento com FAE, via oral, em monoterapia, e que avaliaram o número de pacientes que atingiram a remissão das crises epilépticas, que interromperam o tratamento devido à ineficácia terapêutica ou à ocorrência de reações adversas (RAM) intoleráveis. Meta-análises de comparação de múltiplos tratamentos foram realizadas por meio do modelo bayesiano de efeitos randômicos que permitiu o cálculo do Odds Ratio meta-analítico para os FAE estudados. Também foi realizado um ranqueamento da probabilidade de cada FAE ser a melhor opção em eficácia e tolerabilidade. RESULTADOS E CONCLUSÕES: A busca identificou 18874 publicações, no entanto apenas 71 estudos foram selecionados, compreendendo 17555 pacientes com epilepsia. Vinte e nove estudos apresentaram os desfechos de eficácia no tratamento de crises focais, 19 em crises generalizadas e 58 apresentaram dados de tolerabilidade. Nesses estudos, 15 FAE foram avaliados. No tratamento das crises focais, os FAE de nova geração levetiracetam (LEV), lamotrigina (LTG), oxcarbazepina, sultiame e topiramato (TPM) demonstraram possuir eficácia equivalente à carbamazepina (CBZ), clobazam e valproato (VPA). No entanto, a CBZ apresentou o pior perfil de tolerabilidade devido à grande probabilidade do paciente abandonar o tratamento devido à RAM intoleráveis. Quanto ao tratamento das crises generalizadas, a LTG, LEV e TPM são tão eficazes quanto o VPA para o tratamento de crises generalizadas tônico-clônicas, tônicas e clônicas. O VPA e a etosuximida constituem as melhores opções para o tratamento de crises de ausências, enquanto que a LTG mostrou-se menos eficaz. Para o tratamento de crises mioclônicas e espasmos infantis mais ensaios clínicos randomizados são necessários para fornecer boas evidências que possam guiar a decisão clínica dos profissionais de saúde. Dentre os FAE com perfil de eficácia adequado, a LTG destacou-se pela menor probabilidade de manifestar RAM intoleráveis. / OBJECTIVE: To compare the efficacy and tolerability of the antiepileptic drugs (AED) in monotherapy of patients with focal or generalized epilepsy. METHODS: A systematic review was in the Medline/Pubmed, Scopus, Web of Science and Cochrane Register of Controlled Trials databases. We included randomized clinical trials of patients with epilepsy treated with oral monotherapy AED, which evaluated number of patients becoming seizure free at the maintenance treatment period; number of patients which withdrawals from the study because of therapeutic inefficacy and number of patients which withdrawals from the study because of intolerable adverse reaction. Network meta-analyses were performed using Bayesian random effects model. We also carried out a ranking of the probability of each AED be the best option in the efficacy and tolerability outcomes. Sensitivity analyses were conducted in order to check the robustness of the results. RESULTS AND CONCLUSIONS: The research identified 18,874 publications, but only 71 studies were selected, comprising 17555 patients with epilepsy.Twenty-nine trials showed the efficacy outcomes in the treatment of focal seizures, 19 in generalized seizures and 58 showed tolerability data. In the treatment of focal seizures, levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine, sultiame and topiramate (TPM) have demonstrated equivalent efficacy to carbamazepine (CBZ), clobazam and valproate (VPA). LTG, LEV and TPM are as effective as the VPA for the treatment of generalized tonic-clonic, tonic and clonic seizures. VPA and ethosuximide are the best options for the treatment of absence seizures, whereas LTG was less effective. For the treatment of myoclonic seizures and infantile spasms, more randomized clinical trials are needed to provide good evidence to guide the clinical decision of health professionals. Among the AED with adequate efficacy profile, LTG stands out as the AED with the best tolerability profile, suggesting it may be the best option for the treatment of patients with epilepsy.

OBJETIVO: Comparar a eficácia e a tolerabilidade dos fármacos antiepiléticos (FAE) no tratamento em monoterapia de pacientes com epilepsia focal ou generalizada. MÉTODOS: Uma revisão sistemática foi realizada por meio da busca nas bases de dados eletrônicas Pubmed, Scopus, Web of Science e Cochrane Register of Controlled Trials. Foram incluídos os ensaios clínicos controlados com pacientes com epilepsia, em tratamento com FAE, via oral, em monoterapia, e que avaliaram o número de pacientes que atingiram a remissão das crises epilépticas, que interromperam o tratamento devido à ineficácia terapêutica ou à ocorrência de reações adversas (RAM) intoleráveis. Meta-análises de comparação de múltiplos tratamentos foram realizadas por meio do modelo bayesiano de efeitos randômicos que permitiu o cálculo do Odds Ratio meta-analítico para os FAE estudados. Também foi realizado um ranqueamento da probabilidade de cada FAE ser a melhor opção em eficácia e tolerabilidade. RESULTADOS E CONCLUSÕES: A busca identificou 18874 publicações, no entanto apenas 71 estudos foram selecionados, compreendendo 17555 pacientes com epilepsia. Vinte e nove estudos apresentaram os desfechos de eficácia no tratamento de crises focais, 19 em crises generalizadas e 58 apresentaram dados de tolerabilidade. Nesses estudos, 15 FAE foram avaliados. No tratamento das crises focais, os FAE de nova geração levetiracetam (LEV), lamotrigina (LTG), oxcarbazepina, sultiame e topiramato (TPM) demonstraram possuir eficácia equivalente à carbamazepina (CBZ), clobazam e valproato (VPA). No entanto, a CBZ apresentou o pior perfil de tolerabilidade devido à grande probabilidade do paciente abandonar o tratamento devido à RAM intoleráveis. Quanto ao tratamento das crises generalizadas, a LTG, LEV e TPM são tão eficazes quanto o VPA para o tratamento de crises generalizadas tônico-clônicas, tônicas e clônicas. O VPA e a etosuximida constituem as melhores opções para o tratamento de crises de ausências, enquanto que a LTG mostrou-se menos eficaz. Para o tratamento de crises mioclônicas e espasmos infantis mais ensaios clínicos randomizados são necessários para fornecer boas evidências que possam guiar a decisão clínica dos profissionais de saúde. Dentre os FAE com perfil de eficácia adequado, a LTG destacou-se pela menor probabilidade de manifestar RAM intoleráveis. / OBJECTIVE: To compare the efficacy and tolerability of the antiepileptic drugs (AED) in monotherapy of patients with focal or generalized epilepsy. METHODS: A systematic review was in the Medline/Pubmed, Scopus, Web of Science and Cochrane Register of Controlled Trials databases. We included randomized clinical trials of patients with epilepsy treated with oral monotherapy AED, which evaluated number of patients becoming seizure free at the maintenance treatment period; number of patients which withdrawals from the study because of therapeutic inefficacy and number of patients which withdrawals from the study because of intolerable adverse reaction. Network meta-analyses were performed using Bayesian random effects model. We also carried out a ranking of the probability of each AED be the best option in the efficacy and tolerability outcomes. Sensitivity analyses were conducted in order to check the robustness of the results. RESULTS AND CONCLUSIONS: The research identified 18,874 publications, but only 71 studies were selected, comprising 17555 patients with epilepsy.Twenty-nine trials showed the efficacy outcomes in the treatment of focal seizures, 19 in generalized seizures and 58 showed tolerability data. In the treatment of focal seizures, levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine, sultiame and topiramate (TPM) have demonstrated equivalent efficacy to carbamazepine (CBZ), clobazam and valproate (VPA). LTG, LEV and TPM are as effective as the VPA for the treatment of generalized tonic-clonic, tonic and clonic seizures. VPA and ethosuximide are the best options for the treatment of absence seizures, whereas LTG was less effective. For the treatment of myoclonic seizures and infantile spasms, more randomized clinical trials are needed to provide good evidence to guide the clinical decision of health professionals. Among the AED with adequate efficacy profile, LTG stands out as the AED with the best tolerability profile, suggesting it may be the best option for the treatment of patients with epilepsy.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-02-18T14:22:58Z No. of bitstreams: 1 marcelosoaressalomao.pdf: 5275463 bytes, checksum: bd084577d98f83eca225c7117c8ee332 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-02-26T13:31:33Z (GMT) No. of bitstreams: 1 marcelosoaressalomao.pdf: 5275463 bytes, checksum: bd084577d98f83eca225c7117c8ee332 (MD5) / Made available in DSpace on 2016-02-26T13:31:33Z (GMT). No. of bitstreams: 1 marcelosoaressalomao.pdf: 5275463 bytes, checksum: bd084577d98f83eca225c7117c8ee332 (MD5) Previous issue date: 2014-08-16 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Nesse trabalho apresentamos o Paradoxo de Monty Hall e seus aspectos lúdicos como uma oportunidade de cativar o educando para o estudo das probabilidades. Oferecendo assim a oportunidade de trabalhar no universo da educação básica o ensino de probabilidade na sala de aula através de atividades em forma de jogos. Apesar da dificuldade do assunto na Educação Básica, os professores que lerem o trabalho poderão aproveitar algumas dessas ideias e transformá-las em conhecimento aos seus educandos. Primeiramente apresentamos um breve resumo teórico sobre probabilidade, um pouco da história do Monty Hall paradox e algumas soluções formais e experimentais. Para as atividades, há simulações do problema com variantes do números de portas proporcionando desenvolver no aluno as habilidades como: experimentação, abstração, modelagem. Com o intuito de fazer uso de recursos computacionais apresentamos uma sugestão de atividade com a utilização de um software de fácil acesso e manuseio. Isso se sustenta, pois com aumento de cursos tecnológicos e a presença maior da informática no cotidiano do educando é imperativo o emprego dessa interdisciplinaridade. / We present the Monty Hall Paradox and its entertaining aspects as a chance to engage the student to the study of probability. Thus offering the opportunity to work in the world of basic education by teaching probability in the level of classroom through activities in the form of games. Despite of the difficulty of the subject at the Basic Education, it is expected that teachers who read the work will take some of these ideas and turn them into knowledge to their students. First, we present a brief overview of theoretical probability, a little history of the Monty Hall paradox and some formal and experimental solutions. For activities, there are simulations of the problem with varying numbers of ports providing the development of student skills such as experimentation, abstraction, and modeling. In order to make use of computational resources we present a suggested activity with the use of software for easy access and handling. This is sustained, because with increased technological courses and the increased presence of computers in daily life of the student it is imperative the employment of this interdisciplinarity.