Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 5 uppsatser.

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Made available in DSpace on 2016-06-02T20:04:51Z (GMT). No. of bitstreams: 1 4040.pdf: 1510214 bytes, checksum: 7dfe4542c20ffa8a47309738bc22a922 (MD5) Previous issue date: 2011-12-16 / Financiadora de Estudos e Projetos / The application of a gold standard reference test in all or part of the sample under investigation is often not feasible for the majority of diseases affecting humans, either by a lack of consensus on which testing may be considered a gold standard, the high level of invasion of the gold standard technique, the high cost of financially large-scale application, or by ethical questions, so to know the performance of existing tests is essential for the process of diagnosis of these diseases. In statistical modeling aimed to obtain robust estimates of the prevalence of the disease (x ) and the performance parameters of diagnostic tests (sensitivity (Se) and specificity (Sp)), various strategies have been considered such as the stratification of the population, the relaxation of the assumption of conditional independence, the inclusion of covariates, the verification type (partial or total) and the techniques to replace the gold standard. In this thesis we propose a new structure of stratification of the population considering both the prevalence rates and the parameters of test performance among the different strata (EHW). A Bayesian latent class modeling to estimate these parameters was developed for the general case of K diagnostic tests under investigation, relaxation of the assumption of conditional independence according to the formulations of the fixed effect (FECD) and random (RECD) with dependent order (h _ k) and M covariates. The application of models to two data sets about the performance evaluation of diagnostic tests used in screening for Chagas disease in blood donors showed results consistent with the sensitivity studies. Overall, we observed for the structure of stratification proposal (EHW) superior performance and estimates closer to the nominal values when compared to the structure of stratification when only the prevalence rates are different between the strata (HW), even when we consider data set with rates of Se, Sp and x close among the strata. Generally, the structure of latent class, when we have low or high prevalence of the disease, estimates of sensitivity and specificity rates have higher standard errors. However, in these cases, when there is high concordance of positive or negative results of the tests, the error pattern of these estimates are reduced. Regardless of the structure of stratification (EHW, HW), sample size and the different scenarios used to model the prior information, the model of conditional dependency from the FECD and RECD had, from the information criteria (AIC, BIC and DIC), superior performance to the structure of conditional independence (CI) and to FECD with improved performance and estimates closer to the nominal values. Besides the connection logit, derived from the logistic distribution with symmetrical shape, find in the link GEV, derived from the generalized extreme value distribution which accommodates symmetric and asymmetric shapes, a interesting alternative to construct the conditional dependence structure from the RECD. As an alternative to the problem of identifiability, present in this type of model, the criteria adopted to elicit the informative priors by combining descriptive analysis of data, adjustment models from simpler structures, were able to produce estimates with low standard error and very close to the nominal values. / Na área da saúde a aplicação de teste de referência padrão ouro na totalidade ou parte da amostra sob investigação é, muitas vezes, impraticável devido à inexistência de consenso sobre o teste a ser considerado padrão ouro, ao elevado nível de invasão da técnica, ao alto custo da aplicação em grande escala ou por questões éticas. Contudo, conhecer o desempenho dos testes é fundamental no processo de diagnóstico. Na modelagem estatística voltada à estimação da taxa de prevalência da doença (x ) e dos parâmetros de desempenho de testes diagnósticos (sensibilidade (S) e especificidade (E)), a literatura tem explorado: estratificação da população, relaxamento da suposição de independência condicional, inclusão de covariáveis, tipo de verificação pelo teste padrão ouro e técnicas para substituir o teste padrão ouro inexistente ou inviável de ser aplicado em toda a amostra. Neste trabalho, propomos uma nova estrutura de estratificação da população considerando taxas de prevalências e parâmetros de desempenho diferentes entre os estratos (HWE). Apresentamos uma modelagem bayesiana de classe latente para o caso geral de K testes diagnósticos sob investigação, relaxamento da suposição de independência condicional segundo as formulações de efeito fixo (DCEF) e efeito aleatório (DCEA) com dependência de ordem (h _ K) e inclusão de M covariáveis. A aplicação dos modelos a dois conjuntos de dados sobre avaliação do desempenho de testes diagnósticos utilizados na triagem da doença de Chagas em doadores de sangue apresentou resultados coerentes com os estudos de sensibilidade. Observamos, para a estrutura de estratificação proposta, HWE, desempenho superior e estimativas muito próximas dos valores nominais quando comparados à estrutura de estratificação na qual somente as taxas de prevalências são diferentes entre os estratos (HW), mesmo quando consideramos dados com taxas de S, E e x muito próximas entre os estratos. Geralmente, na estrutura de classe latente, quando temos baixa ou alta prevalência da doença, as estimativas das sensibilidades e especificidades apresentam, respectivamente, erro padrão mais elevado. No entanto, quando há alta concordância de resultados positivos ou negativos, tal erro diminui. Independentemente da estrutura de estratificação (HWE, HW), do tamanho amostral e dos diferentes cenários utilizados para modelar o conhecimento a priori, os modelos de DCEF e de DCEA apresentaram, a partir dos critérios de informação (AIC, BIC e DIC), desempenhos superiores à estrutura de independência condicional (IC), sendo o de DCEF com melhor desempenho e estimativas mais próximas dos valores nominais. Além da ligação logito, derivada da distribuição logística com forma simétrica, encontramos na ligação VEG , derivada da distribuição de valor extremo generalizada a qual acomoda formas simétricas e assimétricas, interessante alternativa para construir a estrutura de DCEA. Como alternativa ao problema de identificabilidade, neste tipo de modelo, os critérios para elicitar as prioris informativas, combinando análise descritiva dos dados com ajuste de modelos de estruturas mais simples, contribuíram para produzir estimativas com baixo erro padrão e muito próximas dos valores nominais.

Made available in DSpace on 2016-06-02T20:06:03Z (GMT). No. of bitstreams: 1 2711.pdf: 1912872 bytes, checksum: 297e56759e248cb7127eae6094c0d821 (MD5) Previous issue date: 2009-03-03 / Financiadora de Estudos e Projetos / Diagnostic tests are methods capable of indicating the presence or absence of a disease, with a probability of error. The performance of a diagnostic test can be verified by some indicator, as: the specificity, the sensitivity and the ROC curve. A graph of the specificity complement versus sensitivity is called as ROC curve. The ROC curve demonstrates the test s ability to discriminate the different disease diagnosis, therefore it is a graphical tool that is used to assess the performance of a test. We define three types of confidence regions around the ROC curve: the punctual, the regional and the global. In some instances, depending on the clinical needs, the decision is taken under an specific region of the ROC curve. We review some procedures for estimating confidence region for the ROC curve and we propose two new methods (optimized averages and averages thresholds optimized) to estimating that region. We use the bootstrap method to search for a confidence region around the ROC curve. Using numerical examples, we apply the methods an compare their performance. / Testes diagnósticos são métodos capazes de indicar a presença ou ausência de uma doença, com uma probabilidade de erro. O desempenho de um teste diagnóstico pode ser verificado por algum indicador, como: a especificidade, a sensibilidade e a curva ROC. Um gráfico do complemento da especificidade versus sensibilidade é chamado de curva ROC. A curva ROC demonstra a habilidade do teste em discriminar os diferentes diagnósticos da doença, logo é uma ferramenta gráfica que serve para avaliar o desempenho de um teste. Definimos três tipos de regiões de confiança em torno da curva ROC: as pontuais, as regionais e as globais. Em algumas situações, de acordo com a necessidade do clínico, uma decisão é tomada sobre uma determinada região específica da curva ROC. Revisamos alguns procedimentos para estimar a região de confiança para a curva ROC e propomos dois novos métodos (médias otimizadas e médias limiares otimizadas) para estimar essa região. Usamos o método bootstrap para buscar uma região de confiança em torno da curva ROC. Usando exemplos numéricos, aplicamos os métodos para comparar seus desempenhos.

This master´s thesis deals with influence of mica content on the electrical properties of electrical insulating varnishes, particularly in the polyester resin Dolphon XL 2102. It focuses on diagnostic methods and testing the properties of electroinsulating varnishes. Examines the potential benefits of micronised mica in order to achieve better electrical insulation properties of the system compared to the matrix. The composite material consists of polyester resin Dolphon XL 2102, which is modified different mass percentage of micronized mica. The results of this project are frequency dependencies of real and imaginary parts of complex permitivity of varnish component.

Objectif : La bronchopneumonie infectieuse (BPI) est une affection des voies respiratoires inférieures due à l’interaction entre des agents microbiens, des facteurs environnementaux et des facteurs propres à l’individu. Malgré des années de recherche, la BPI reste prévalente en élevage de génisses de remplacement et de veaux lourds engendrant des pertes économiques majeures et une forte consommation d’antibiotiques dans ces élevages. Le score clinique respiratoire diagnostique (SCRD), l’auscultation thoracique, l’échographie thoracique et la radiographie thoracique sont des tests couramment utilisés pour détecter la BPI. Cependant, leurs performances diagnostiques actuelles à savoir : leurs facultés à détecter les veaux malades (sensibilité; Se) et leurs facultés à détecter les veaux non malades (spécificité; Sp) sont sous-optimales pour détecter adéquatement les veaux de race laitière nécessitant d’être traités avec des antibiotiques et/ou des anti-inflammatoires. L’objectif général de cette thèse était donc d’améliorer les stratégies de détection du statut actif de la BPI, statut nécessitant un traitement (d’antibiotiques et/ou d’anti-inflammatoires), afin, d’une part, de mieux diagnostiquer les veaux malades, diminuer les impacts économiques de la maladie et améliorer le bien-être des veaux ; et d’autre part, favoriser l’emploi judicieux des antibiotiques en traitant uniquement les veaux qui en ont besoin. Pour répondre à cet objectif général, 3 sous-objectifs spécifiques ont été définis : (1) développer un SCRD, en identifiant et validant les signes cliniques avec une bonne répétabilité interopérateurs pour diagnostiquer le statut actif de la BPI à l’échelle individuelle et populationnelle; (2) Améliorer les stratégies diagnostiques des tests d’imagerie médicale en comparant l’échographie et la radiographie thoracique pour détecter les lésions pulmonaires et le statut actif de la BPI; (3) Améliorer l’échographie thoracique en standardisant la technique (ajout ou non du lobe crânial droit) et l’interprétation (seuil de profondeur) afin d’en optimiser ces performances pour détecter le statut actif de la BPI. Méthodes : (1) 800 veaux lourds de 80 lots ont été filmés à l’aide d’une caméra portative lors de leur évaluation clinique. Différentes séquences vidéo ont été aléatoirement sélectionnées et soumises à un panel d’évaluateur constitué de producteurs de veaux lourds, techniciens et médecins vétérinaires. La variabilité interopérateurs de chaque signe clinique a été évaluée. Les signes cliniques ayant la meilleure répétabilité ont été retenus pour le développement et la validation d’un SCRD en utilisant un modèle bayésien d’analyse de classe latente. Enfin, des stratégies diagnostiques des BPI au niveau populationnel ont été développées; (2) 50 veaux hospitalisés ont reçu une échographie et une radiographie thoracique. La tomodensitométrie thoracique (CT scan) a été utilisé comme gold standard pour vérifier les individus positifs à l’un des deux tests. Les performances des deux tests ont été comparées pour détecter d’abord les lésions pulmonaires en comparant avec les résultats du CT scan, puis le statut actif de la BPI défini par trois experts; (3) la Se et la Sp pour diagnostiquer le statut actif de BPI de différents sites d’échographie thoracique et différents seuils de profondeur de consolidation pulmonaire ont été évalués à l’aide de modèles utilisant une analyse bayésienne à classe latente dans une population de génisse de remplacement et une population de veaux lourds. Résultats : (1) La position des oreilles et la toux induite étaient les signes cliniques de BPI les plus répétables. Le SCRD développé et validé consiste à évaluer ces deux signes cliniques ainsi que la température rectale (anormale T≥ 39.5◦C) sur 10 veaux d’un lot, deux semaines après leur arrivée en parc d’engraissement. La présence de 3 veaux avec deux de ces prédicteurs implique que le lot a 94 % de chance d’avoir une prévalence du statut actif de BPI ≥ 0.10. Avec moins de 3 veaux, le lot à 95 % de chance de ne pas avoir une prévalence ≥ 0.10; (2) Pour détecter les lésions pulmonaires, les Se et Sp de l’échographie thoracique étaient de 0,81 (intervalle de crédit bayésien à 95 % (ICB95%): 0,65; 0,92) et 0,90 (ICB95 %: 0,81; 0,96), respectivement. Les Se et Sp de la radiographie thoracique étaient de 0,86 (ICB95%: 0,62; 0,99) et 0,89 (ICB95%: 0,67; 0,99), respectivement. Pour détecter le statut actif de la BPI, les Se et Sp de l’échographie thoracique étaient de 0,84 (intervalle de confiance à 95% (IC95%): 0,60; 0,97) et 0,74 (IC95 %: 0,57; 0,86), respectivement. La Se et Sp de la radiographie thoracique étaient de 0,89 (IC95%: 0,67; 0,99) et 0,58 (IC95%: 0,39; 0,75), respectivement. Aucune différence n’était présente entre les deux tests pour détecter les lésions pulmonaires ou le statut actif de BPI; (3) La détection échographique de lésions de consolidation pulmonaire des sites caudaux au cœur avec une profondeur ≥ 3 cm conclut à la présence du statut actif de BPI avec une Se de 0,89 (ICB95%: 0,55; 1,00) et une Sp de 0,95 (ICB95%: 0,92; 0,98). Conclusion : Dans cette thèse, nous avons amélioré les stratégies diagnostiques pour détecter les veaux à traiter de BPI. L’utilisation de ces résultats pour élaborer des algorithmes décisionnels devrait ultimement permettre de diminuer les pertes économiques et de raffiner l’utilisation d’antibiotiques. / Objectives: Infectious bronchopneumonia (BPI) is the infection of the lower respiratory tract implying an interaction between microbial agents, environment, and host. Despite decades of research, BPI remains omnipresent in dairy and veal calves, responsible for major economic losses and antimicrobial consumption. Clinical respiratory scoring system (CRSC), lung auscultation, thoracic ultrasonography, and thoracic radiography are the most popular tests used to detect BPI in calves. However, the sensitivity (Se) (i.e., faculty to detect sick calves) and the specificity (Sp) (i.e., faculty to detect healthy calves) are suboptimal to accurately detecting dairy and veal calves to treat. Our main objective was to improve the diagnostic strategies to detect active BPI (BPI status needed a treatment) in order to: firstly, better diagnose sick calves, reduce BPI economic losses and improve calves’ welfare; secondly, reduce antimicrobial consumption by treating only calves that need it. For this purpose, three sub-objectives have been defined: (1) develop and validate a CRSC including inter-operator reliable respiratory clinical signs to detect active BPI at calf-level and group level; (2) compare thoracic ultrasonography and thoracic radiography to detect lung lesions and active BPI; (3) standardize thoracic ultrasonography technique (sites to ultrasound) and interpretation (lung consolidation depth threshold) to promote thoracic ultrasonography Se and Sp to detect active BPI. Methods: (1) 800 veal calves from 80 batches were filmed with a portative camera during their clinical exam. Videos were randomly selected and assessed by producers, technicians, and veterinarians. The reliability of each respiratory clinical sign was assessed. The most reliable respiratory clinical signs were kept in order to develop and validate a CRSC using latent class Bayesian analysis. Batch-level diagnostic strategies were developed; (2) Fifty hospitalized calves underwent thoracic ultrasonography and thoracic radiography. Thoracic tomography (CT scan) was used as a gold standard to check positive calves on one of both tests. Se and Sp of both tests were compared to detect lung lesions and active BPI defined by three experts; (3) Se and Sp of different ultrasound sites and different lung consolidation depth thresholds were estimated to detect active BPI using latent class Bayesian analysis in both dairy calves and veal calves’ populations. Results: (1) Ear droop/head tilt and induced cough were the most reliable respiratory clinical signs. The CRSC developed and validated implies assessing those clinical signs with rectal temperature (abnormal T≥ 39.5◦C) in 10 calves from a batch at two weeks after arriving at the fattening unit. Having two abnormal characteristics of those predictors in three calves implies that a batch has 94% of having an active BPI prevalence ≥ 0.10. A batch with <3 positive calves on 10 has 95% of not having an active BPI prevalence ≥ 0.10; (2) For detecting lung lesions, the Se and Sp of thoracic ultrasonography were 0.81 (95% Bayesian credible interval (95%BCI): 0.65; 0.92) and 0.90 (95%BCI: 0.81; 0.96), respectively. The Se and Sp of thoracic radiography were 0.86 (95%BCI: 0.62; 0.99) and 0.89 (95%BCI: 0.67; 0.99), respectively. For detecting active BPI, the Se and Sp of thoracic ultrasonography were 0.84 (95% confidence interval (95%CI): 0.60; 0.97) and 0.74 (95%CI: 0.57; 0.86), respectively. The Se and Sp of thoracic radiography were 0.89 (95%CI: 0.67; 0.99) and 0.58 (95%CI: 0.39; 0.75), respectively. There was no difference between both tests to detect both lung lesions and active BPI; (3) Thoracic ultrasonography of the sites caudal of the heart with a depth lung consolidation ≥ 3 cm has a Se of 0.89 (95%BCI: 0.55; 1.00) and a Sp of 0.95 (95%BCI: 0.92; 0.98). Conclusion: We improved diagnostic strategies to detect active BPI in this thesis. Using our results to elaborate decisional algorithms would reduce economic losses and antimicrobial consumption of BPI in dairy and veal calves.

Yes / Background: Tuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results. However, these connected diagnostics and readily available test results are not used to their full capacity, as we have yet to capitalize on fully understanding the relationship between test results and specific rpoB mutations to elucidate its potential application to real-time surveillance. Objective: We aimed to validate and analyze RDT data in detail, and propose the potential use of connected diagnostics and associated test results for real-time evaluation of RR-TB transmission. Methods: We selected 107 RR-TB strains harboring 34 unique rpoB mutations, including 30 within the rifampicin resistance–determining region (RRDR), from the Belgian Coordinated Collections of Microorganisms, Antwerp, Belgium. We subjected these strains to Xpert MTB/RIF, GenoType MTBDRplus v2.0, and Genoscholar NTM + MDRTB II, the results of which were validated against the strains’ available rpoB gene sequences. We determined the reproducibility of the results, analyzed and visualized the probe reactions, and proposed these for potential use in evaluating transmission. Results: The RDT probe reactions detected most RRDR mutations tested, although we found a few critical discrepancies between observed results and manufacturers’ claims. Based on published frequencies of probe reactions and RRDR mutations, we found specific probe reactions with high potential use in transmission studies: Xpert MTB/RIF probes A, Bdelayed, C, and Edelayed; Genotype MTBDRplus v2.0 WT2, WT5, and WT6; and Genoscholar NTM + MDRTB II S1 and S3. Inspection of probe reactions of disputed mutations may potentially resolve discordance between genotypic and phenotypic test results. Conclusions: We propose a novel approach for potential real-time detection of RR-TB transmission through fully using digitally linked TB diagnostics and shared repository of test results. To our knowledge, this is the first pragmatic and scalable work in response to the consensus of world-renowned TB experts in 2016 on the potential of diagnostic connectivity to accelerate efforts to eliminate TB. This is evidenced by the ability of our proposed approach to facilitate comparison of probe reactions between different RDTs used in the same setting. Integrating this proposed approach as a plug-in module to a connectivity platform will increase usefulness of connected TB diagnostics for RR-TB outbreak detection through real-time investigation of suspected RR-TB transmission cases based on epidemiologic linking. / KCN was supported by Erasmus Mundus Joint Doctorate Fellowship grant 2016-1346, and BCdJ, LR, and CJM were supported by European Research Council-INTERRUPTB starting grant 311725.

No / To build an early warning score (EWS) based exclusively on routinely undertaken laboratory tests that might provide early discrimination of in-hospital death and could be easily implemented on paper. Using a database of combined haematology and biochemistry results for 86,472 discharged adult patients for whom the admission specialty was Medicine, we used decision tree (DT) analysis to generate a laboratory decision tree early warning score (LDT-EWS) for each gender. LDT-EWS was developed for a single set (n=3496) (Q1) and validated in 22 other discrete sets each of three months long (Q2, Q3...Q23) (total n=82,976; range of n=3428 to 4093) by testing its ability to discriminate in-hospital death using the area under the receiver-operating characteristic (AUROC) curve. The data generated slightly different models for male and female patients. The ranges of AUROC values (95% CI) for LDT-EWS with in-hospital death as the outcome for the validation sets Q2-Q23 were: 0.755 (0.727-0.783) (Q16) to 0.801 (0.776-0.826) [all patients combined, n=82,976]; 0.744 (0.704-0.784, Q16) to 0.824 (0.792-0.856, Q2) [39,591 males]; and 0.742 (0.707-0.777, Q10) to 0.826 (0.796-0.856, Q12) [43,385 females]. CONCLUSIONS: This study provides evidence that the results of commonly measured laboratory tests collected soon after hospital admission can be represented in a simple, paper-based EWS (LDT-EWS) to discriminate in-hospital mortality. We hypothesise that, with appropriate modification, it might be possible to extend the use of LDT-EWS throughout the patient's hospital stay.

The objectives of this study were to provide a detailed biopsychosocial description of the characteristics of a sample of 100 individuals screened and referred by the National Responsible Gaming Programme helpline for their outpatient treatment programme over an eighteen month period, and, importantly, to measure the success of this specific treatment programme at set intervals, up to a one year follow-up period. While 80% of the sample did not relapse during the six-week treatment programme, the number of treatment seekers without any gambling relapses during each follow-up period declined, and those falling back into gambling increased as time went on. After one year 47% of treatment seekers managed not to revert back to gambling &#8211; total abstinence. A further 28% reported having relapsed once or twice or that their gambling was controlled. 25% of treatment seekers reported that they reverted back to gambling fulltime which leaves the success rate of the treatment at 75%. Treatment seekers reported an overall reduction in gambling participation, debt and expenditure and an overall improvement in social and vocational functioning. There is evidence in this study to support the perspective that pathological gambling is a multidimensional disorder and that certain sub-groups of gamblers have distinct gambling behaviour. / Psychology / M.Soc.Sc.

A carefully constructed set of 16 graphical tasks related to key biochemistry concepts was designed and administered to a group of 82 students in their final year of B.Sc. study. The test mean score of 48,3% ( 12,1) was low and characterised by gender and ethnic differences. There was a moderate linear relationship between biochemistry grades obtained by the students over two years of study and their graphical literacy (r = 0,433). The majority of the students exhibited slope/height confusion and only seven students (8,5%) were able to answer the two items corresponding to Kimura‘s Level F, the most complex and difficult level of graphical literacy. Eye tracking data gave valuable insights into different strategies used by students while interpreting graphs and is a valuable tool for assessing graphical literacy. These findings confirmed other studies where researchers have found a widespread lack of graph comprehension among biological science students. / Institute of Science and Technology Education / M. Sc. (Science Education)