Background: Drug interactions resulting in adverse drug reactions (ADRs) represent a major health problem both for individuals and society in general. Post-marketing pharmacovigilance reporting databases with compiled individual case safety reports (ICSRs) have been shown to be particularly useful in the detection of novel drug - ADR combinations, though these reports have not been fully used to detect adverse drug interactions. Aim: To explore the potential to identify drug interactions using ICSRs and to develop a method to facilitate the detection of adverse drug interaction signals in the WHO Global ICSR Database, VigiBase. Methods: All six studies included in this thesis are based on ICSRs available in VigiBase. Two studies aimed to characterise drug interactions reported in VigiBase. In the first study we examined if contraindicated drug combinations (given in a reference source of drug interactions) were reported on the individual reports in the database, and in the second study we examined the scientific literature for interaction mechanisms for drug combinations most frequently co-reported as interacting in VigiBase. Two studies were case series analyses where the individual reports were manually reviewed. The two remaining studies aimed to develop a method to facilitate detection of novel adverse drug interactions in VigiBase. One examined what information (referred to as indicators) was reported on ICSRs in VigiBase before the interactions became listed in the literature. In the second methodological study, logistic regression was used to set the relative weights of the indicators to form triage algorithms. Three algorithms (one completely data driven, one semi-automated and one based on clinical knowledge) based on pharmacological and reported clinical information and the relative reporting rate of an ADR with a drug combination were developed. The algorithms were then evaluated against a set of 100 randomly selected case series with potential adverse drug interactions. The algorithm’s performances were then evaluated among DDAs with high coefficients. Results: Drug interactions classified as contraindicated are reported on the individual reports in VigiBase, although they are not necessarily recognised as interactions when reported. The majority (113/123) of drug combinations suspected for being responsible for an ADR were established drug interactions in the literature. Of the 113 drug interactions 46 (41%) were identified as purely pharmacodynamic; 28 (25%) as pharmacokinetic; 18 (16%) were a mix of both types and for 21 (19%) the mechanism have not yet been identified. Suspicions of a drug interaction explicitly noted by the reporter are much more common for known adverse drug interactions than for drugs not known to interact. The clinical evaluation of the triage algorithms showed that 20 were already known in the literature, 30 were classified as signals and 50 as not signals. The performance of the semi-automated and the clinical algorithm were comparable. In the end the clinical algorithm was chosen. At a relevant level, 38% were of the adverse drug interactions were already known in the literature and of the remaining 80% were classified as signals for this algorithm. Conclusions: This thesis demonstrated that drug interactions can be identified in large post-marketing pharmacovigilance reporting databases. As both pharmacokinetic and pharmacodynamic interactions were reported on ICSRs the surveillance system should aim to detect both. The proposed triage algorithm had a high performance in comparison to the disproportionality measure alone.

Faces provide cues for judgments regarding the emotional state of individuals. Using signal-detection methodology and a standardized stimulus set, the overall aim of the present dissertation was to investigate the detection of emotional facial expressions (i.e., angry and happy faces) with neutral expressions as the nontarget stimuli. Study I showed a happy-superiority effect and a bias towards reporting happiness in female faces. As work progressed, questions arose regarding whether the emotional stimuli were equal with regard to perceived strength of emotion, and whether the neutral faces were perceived as neutral. To further investigate the effect of stimulus quality on the obtained findings, Study II was designed such that the facial stimuli were rated on scales of happy-sad, angry-friendly, and emotionality. Results showed that ‘neutral’ facial expressions were not rated as neutral, and that there was a greater perceived distance between happy and neutral faces than between angry and neutral faces. These results were used to adjust the detectability measures to compensate for the varying distances of the angry and happy stimuli from the neutral stimuli in the emotional space. The happy-superiority effect was weakened, while an angry-female disadvantage remained. However, as these results were based upon different participant groups for detection and emotional rating, Study III was designed to investigate whether the results from Studies I and II could be replicated in a design where the same participants performed both tasks. Again, the results showed the non-neutrality of ‘neutral’ expressions and that happiness was more easily detected than anger, as shown in general emotion as well as specific emotion detection. Taken together, the overall results of the present dissertation demonstrate a happy-superiority effect that was greater for female than male faces, that angry-female faces were the most difficult to detect, and a bias to report female faces as happy. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: In press. Paper 2: Manuscript. Paper 3: Manuscript.

Thesis (Ph.D.)--University of Delaware, 2005. / Principal faculty adviser: Xiang-Gen Xia, Dept. of Electrical & Computer Engineering. Includes bibliographical references.

A ocorrência de um estímulo auditivo imediatamente antes de um estímulo alvo visual reduz o tempo de reação em dezenas de milisegundos, um efeito atribuído a atenção temporal automática. O presente estudo investigou se este efeito é resultante de uma facilitação de mecanismos sensoriais. Dois experimentos foram realizados. No primeiro, foi realizada uma tarefa de tempo de reação simples por meio da resposta a estímulos alvos visuais com variações em sua detectabilidade. Esperava-se que o tamanho do efeito facilitador pudesse aumentar com o aumento da dificuldade de detecção do alvo. No segundo experimento foi realizada uma tarefa de acurácia. Os dados foram analisados pela teoria de detecção de sinais. Esperava-se que o estímulo precedente possibilitasse o aumento da detectabilidade do alvo e redução do critério de resposta. No primeiro experimento, não houve influência do estímulo precedente no aumento da detectabilidade do alvo. Os resultados do segundo experimento indicaram haver influência do estímulo precedente no aumento da detectabilidade do alvo e redução do critério pra a resposta. Esses resultados reforçam a teoria de que a atenção temporal automática facilita o processamento sensorial. / The occurrence of an auditory stimulus immediately before a visual target stimulus shortens reaction time by tens of milliseconds, an effect attributed to automatic temporal expectation. The present study investigated whether this effect results from a facilitation of sensory mechanisms. Two experiments were performed. In the first one the volunteers performed a simple reaction time task. They responded to visual targets which differ in detectability. It was expected that the size of the facilitatory effect would increase with the difficulty of target detection. In the second experiment the volunteers performed an accuracy task. Its data were analyzed on basis of signal detection theory. It was expected that the warning stimulus would increase the detectability of the target and lower the criterion to respond. The results of the first experiment did not indicate any influence of target detectability. The results of the second experiment indicate that both the detectability of the target and the criterion to respond were affected by the warning stimulus. These results provide support to the idea that automatic temporal expectancy facilitates sensory processing.

Orientador: Elnatan Chagas Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-13T16:12:21Z (GMT). No. of bitstreams: 1 Fernandes_AlecioPontes_M.pdf: 6269465 bytes, checksum: 0d2b04f6049ffb1685b947932894c75d (MD5) Previous issue date: 2009 / Resumo: Giroscópios são dispositivos usados para medir rotação angular, sendo extensivamente empregados em sistemas de guiamento, navegação e estabilização. Entre os diversos tipos de giroscópios, o IFOG (Giroscópio Interferométrico a Fibra Óptica) baseado no efeito de Sagnac é uma das soluções mais interessante, dada sua alta sensibilidade, resolução, ausência de partes móveis, confiabilidade, tamanho compacto e imunidade a interferências eletromagnéticas. Este trabalho descreve a implementação de um circuito digital de demodulação para IFOGs operando em malha aberta utilizando a técnica de zero-crossing (cruzamento em zero). A técnica implementada no circuito eletrônico descrito neste trabalho emprega um clock quase-síncrono para processamento, o que leva a um esquema de demodulação digital preciso, simples e de baixo custo. O circuito de demodulação proposto foi testado em laboratório, utilizando um sinal de giroscópio emulado. Os resultados experimentais medidos no protótipo mostraram que a resolução final do circuito de detecção é 1000 vezes melhor que a resolução possível de se alcançar em um demodulador zero-crossing digital convencional com clock síncrono / Abstract: Gyroscopes are devices used to measure angular orientation, being extensively employed for guidance, navigation and stabilization. Among the many types of gyroscopes, IFOG (Interferometer Fiber Optic Gyroscope), based on Sagnac effect, is the most interesting solution due to its high sensitivity, resolution, reliability, small size and EMI immunity. The present work describes a digital electronic circuit implementation for open-loop IFOGs using zero-crossing demodulation techniques. The technique used in the electronic circuit described in this work employs a quasi-synchronous clock for signal processing which leads to an accurate, simple and low cost digital demodulation scheme. The experimental results of the prototype showed that the final detection resolution is 1000 times better than one achieved by the conventional synchronous clock zero-crossing digital demodulator / Mestrado / Eletrônica, Microeletrônica e Optoeletrônica / Mestre em Engenharia Elétrica

Identifying previously unknown adverse drug reactions becomes more important as the number of drugs and the extent of their use increases. The aim of this Master’s thesis project was to evaluate the performance of a novel approach for highlighting potential adverse drug reactions, also known as signal detection. The approach was based on deviating time-to-onset patterns and was implemented as a two-sample Kolmogorov-Smirnov test for non-vaccine data in the safety report database, VigiBase. The method was outperformed by both disproportionality analysis and the multivariate predictive model vigiRank. Performance estimates indicate that deviating time-to-onset patterns is not a suitable approach for signal detection for non-vaccine data in VigiBase.

Nous étudions le problème de suivi de cible dans une séquence vidéo sans aucune connaissance préalable autre qu'une référence annotée dans la première image. Pour résoudre ce problème, nous proposons une nouvelle méthode de suivi temps-réel se basant sur à la fois une représentation originale de l’objet à suivre (descripteur) et sur un algorithme adaptatif capable de suivre la cible même dans les conditions les plus difficiles comme le cas où la cible disparaît et réapparait dans le scène (ré-identification). Tout d'abord, pour la représentation d’une région de l’image à suivre dans le temps, nous proposons des améliorations au descripteur de covariance. Ce nouveau descripteur est capable d’extraire des caractéristiques spécifiques à la cible, tout en ayant la capacité à s’adapter aux variations de l’apparence de la cible. Ensuite, l’étape algorithmique consiste à mettre en cascade des modèles génératifs et des modèles discriminatoires afin d’exploiter conjointement leurs capacités à distinguer la cible des autres objets présents dans la scène. Les modèles génératifs sont déployés dans les premières couches afin d’éliminer les candidats les plus faciles alors que les modèles discriminatoires sont déployés dans les couches suivantes afin de distinguer la cibles des autres objets qui lui sont très similaires. L’analyse discriminante des moindres carrés partiels (AD-MCP) est employée pour la construction des modèles discriminatoires. Enfin, un nouvel algorithme d'apprentissage en ligne AD-MCP a été proposé pour la mise à jour incrémentale des modèles discriminatoires / We study the challenging problem of tracking an arbitrary object in video sequences with no prior knowledge other than a template annotated in the first frame. To tackle this problem, we build a robust tracking system consisting of the following components. First, for image region representation, we propose some improvements to the region covariance descriptor. Characteristics of a specific object are taken into consideration, before constructing the covariance descriptor. Second, for building the object appearance model, we propose to combine the merits of both generative models and discriminative models by organizing them in a detection cascade. Specifically, generative models are deployed in the early layers for eliminating most easy candidates whereas discriminative models are in the later layers for distinguishing the object from a few similar "distracters". The Partial Least Squares Discriminant Analysis (PLS-DA) is employed for building the discriminative object appearance models. Third, for updating the generative models, we propose a weakly-supervised model updating method, which is based on cluster analysis using the mean-shift gradient density estimation procedure. Fourth, a novel online PLS-DA learning algorithm is developed for incrementally updating the discriminative models. The final tracking system that integrates all these building blocks exhibits good robustness for most challenges in visual tracking. Comparing results conducted in challenging video sequences showed that the proposed tracking system performs favorably with respect to a number of state-of-the-art methods

La vidéosurveillance représente l’un des domaines de recherche privilégiés en vision par ordinateur. Le défi scientifique dans ce domaine comprend la mise en œuvre de systèmes automatiques pour obtenir des informations détaillées sur le comportement des individus et des groupes. En particulier, la détection de mouvements anormaux de groupes d’individus nécessite une analyse fine des frames du flux vidéo. Dans le cadre de cette thèse, la détection de mouvements anormaux est basée sur la conception d’un descripteur d’image efficace ainsi que des méthodes de classification non linéaires. Nous proposons trois caractéristiques pour construire le descripteur de mouvement : (i) le flux optique global, (ii) les histogrammes de l’orientation du flux optique (HOFO) et (iii) le descripteur de covariance (COV) fusionnant le flux optique et d’autres caractéristiques spatiales de l’image. Sur la base de ces descripteurs, des algorithmes de machine learning (machines à vecteurs de support (SVM)) mono-classe sont utilisés pour détecter des événements anormaux. Deux stratégies en ligne de SVM mono-classe sont proposées : la première est basée sur le SVDD (online SVDD) et la deuxième est basée sur une version « moindres carrés » des algorithmes SVM (online LS-OC-SVM) / One of the major research areas in computer vision is visual surveillance. The scientific challenge in this area includes the implementation of automatic systems for obtaining detailed information about the behavior of individuals and groups. Particularly, detection of abnormal individual movements requires sophisticated image analysis. This thesis focuses on the problem of the abnormal events detection, including feature descriptor design characterizing the movement information and one-class kernel-based classification methods. In this thesis, three different image features have been proposed: (i) global optical flow features, (ii) histograms of optical flow orientations (HOFO) descriptor and (iii) covariance matrix (COV) descriptor. Based on these proposed descriptors, one-class support vector machines (SVM) are proposed in order to detect abnormal events. Two online strategies of one-class SVM are proposed: The first strategy is based on support vector description (online SVDD) and the second strategy is based on online least squares one-class support vector machines (online LS-OC-SVM)

Orientador: Renato da Rocha Lopes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-18T15:38:37Z (GMT). No. of bitstreams: 1 Simoes_GlaucoCesarCrystalPereira_M.pdf: 1336036 bytes, checksum: 7f787abec0f0f88f41c09ef5dc04d775 (MD5) Previous issue date: 2011 / Resumo: Sistemas de comunicação sem fio com múltiplas antenas atingem altas taxas de transmissão de dados e boa robustez ao desvanecimento do canal de comunicação quando os sinais que trafegam pelo sistema são processados conjuntamente em sua transmissão e/ou em sua recepção. Em geral, as técnicas de detecção de sinais assumem o conhecimento perfeito do canal de comunicações, tanto no transmissor, quanto no receptor do sistema, uma hipótese que nem sempre é válida. Neste sentido, é importante analisar o desempenho do sistema frente a erros de estimação do canal de comunicações. Neste trabalho, esta análise é feita através da comparação do cálculo da probabilidade de erro de símbolos com as taxas de erro de símbolos obtidas através de simulação computacional para o detector zero-forcing, assumindo a utilização dos critérios de detecção linear e através da aplicação da técnica de cancelamento sucessivo de interferências / Abstract: Multiple antenna wireless communication systems achieve high data transmission rates and good robustness to channel fading when signals traveling through the system are jointly processed in their transmitters and/ or receivers. In general, signal detection techniques assume perfect knowledge of the channel state information, in both transmitter and receiver, a hypothesis which is not always valid. In this sense, it is important to analyze is done by the comparison between the calculus of the probability of symbol error and the symbol error rate obtained by computer simulation for the zero-forcing detector, assuming the use of linear criteria detection and by applying the technique of successive interference cancellation / Mestrado / Telecomunicações e Telemática / Mestre em Engenharia Elétrica

As online technology continues to progress, the modes of communication through which content can be shared have exponentially grown. These include advances in navigational options for presenting information and news online. Though the listicle has been around for centuries, the internet has proliferated its growth, as content producers rely on its structure as a vehicle for sharing information. This research shows that in the case of listicles, format had no direct effect on recall, however, participants who had a greater interest in the content showed significantly higher levels of memory sensitivity. This critical finding suggests that news outlets and content producers should concern themselves with ensuring that their content is interesting and relevant to their audience more so than worrying about whether the listicle is in clickable or scrollable form. This first attempt to examine listicles by comparing their navigational difference in terms of recall performance lays a framework for future research on listicles.