This project aims to support pharmacovigilance, the science and activities relating to drug-safety and prevention of adverse drug reactions (ADRs). We focus on a specific ADR called QT prolongation, a serious reaction affecting the heartbeat. Our main goal is to group medicinal ingredients that might cause QT prolongation. This grouping can be used in safety analysis and for exclusion lists in clinical studies. It should preferably be ranked according to level of suspected correlation. We wished to create an automated and standardised process. Drug safety-related reports describing patients' experienced ADRs and what medicinal products they have taken are collected in a database called VigiBase, that we have used as source for ingredient extraction. The ADRs are described in free-texts and coded using an international standardised terminology. This helps us to process the data and filter ingredients included in a report that describes QT prolongation. To broaden our project scope to include uncoded data, we extended the process to use free-text verbatims describing the ADR as input. By processing and filtering the free-text data and training a classification model for natural language processing released by Google on VigiBase data, we were able to predict if a free-text verbatim is describing QT prolongation. The classification resulted in an F1-score of 98%. For the ingredients extracted from VigiBase, we wanted to validate if there is a known connection to QT prolongation. The VigiBase occurrences is a parameter to consider, but it might be misleading since a report can include several drugs, and a drug can include several ingredients, making it hard to validate the cause. For validation, we used product labels connected to each ingredient of interest. We used a tool to download, scan and code product labels in order to see which ones mention QT prolongation. To rank our final list of ingredients according to level of suspected QT prolongation correlation, we used a multinomial logistic regression model. As training data, we used a data subset manually labeled by pharmacists. Used on unlabeled validation data, the model accuracy was 68%. Analyzing the training data showed that it was not easily separated linearly explaining the limited classification performance. The final ranked list of ingredients suspected to cause QT prolongation consists of 1086 ingredients.

Les clauses de fin de contrat illustrent l’importance de la liberté contractuelle. La pratique s’est emparée de cette période de l’« après-Contrat » sous le contrôle de la jurisprudence, dans le relatif désintérêt du législateur.Les fins du contrat sont diverses. La fin peut être retardée par le biais de la prorogation du contrat. La fin peut être prématurée : elle peut être une fin brutale et définitive par le biais de la clause résolutoire, la continuité de ce qui était par l’arrivée du terme extinctif, ou encore la venue de quelque chose de nouveau par le biais d’une clause de caducité. La fin peut n’être qu’un passage vers un autre contrat par le biais de la reconduction. Il en ressort un flou théorique nécessitant une construction juridique. Il peut être proposé de scinder le temps de l’après-Contrat en trois temps. Le premier temps, les parties satisfaites de leur relation vont chercher à la faire perdurer. Les clauses de fin de contrat ont alors pour finalité la préservation de la pérennité du lien contractuel entre les parties. La deuxième période porte sur les modes d’extinction du contrat. La sortie de la relation contractuelle est devenue un enjeu important nécessitant le recours à différents mécanismes juridiques tels que la clause de dédit, la condition résolutoire ou encore la clause résolutoire.La troisième période peut être désignée comme la période de liquidation du passé contractuel comprenant deux séries de clauses : celles liquidant le passé contractuel (notamment la clause de non-Concurrence et la clause de confidentialité) et celle s’intéressant à l’avenir post-Contractuel. La fin du contrat doit être distinguée de la clôture de la relation contractuelle désignant la cessation de toutes les obligations post-Contractuelles et de leurs conséquences. Ainsi loin d’être secondaires, ces clauses de fin de contrat composant la période de l’après-Contrat sont fondamentales pour toute relation d’affaires continue. / End-Of-Contract clauses illustrate the significance of contractual freedom. Practice took hold of this “post-Contractual” period under the control of established precedents, in the relative disinterest of lawmakers.The types of contractual ends are diverse. The end may be delayed by means of prolongation of the contract. The end may come prematurely: it may come suddenly and definitively by means of a termination clause, the continuity of that which was by the arrival of the extinctive term, or the arrival of something new by means of a sunset clause. The end may only be a passage to another contract by means of renewal. This results in a lack of theoretical clarity that requires a legal structure. It may be proposed to divide the post-Contractual period into three parts. In the first part, parties satisfied with their relationship will seek to have it continue. The end-Of-Contract clauses thus serve the purpose of preserving the durability of the contractual bond between the parties. The second part involves the manner of termination the contract. Closing the contractual relationship has become an important matter that requires resorting to different legal mechanisms such as the forfeiture clause, the termination condition or the termination clause.The third part may be referred to as the period of liquidation of the contractual past including two series of clauses: those liquidating the contractual past (notably the clause of non-Competition and the clause of confidentiality) and those concerning the post-Contractual future. The end of the contract must be distinguished from the close of the contractual relationship designating the cessation of all post-Contractual obligations and their consequences. Thus, far from being secondary, these end-Of-Contract clauses affecting the post-Contractual period are fundamental for any ongoing business relationship.

In this work, our goal is to prove results on prolongation of solutions, uniform boundedness of solutions, uniform stability as well uniform asymptotic stability (in the classical sense of Lyapunov) for measure differential equations and for dynamic equations on time scales. In order to get our results, we employ the theory of generalized ODEs, since these equations encompass measure differential equations and dynamic equations on time scales. Therefore, to get our results, we start by proving the expected result for abstract generalized ODEs. Then, using the correspondence between the solutions of these equations and the solutions of measure differential equations (see [38]), we extend all the results to these the latter. After that, using the correspondence between the solutions of measure differential equations and the solutions of dynamic equations on time scales (see [21]), we extend all the results to these last equations. Finally, we investigate autonomous generalized ODEs and show that these equations do not enlarge the class of classical autonomous ODEs, even when we consider a more general class of functions as right-hand sides. All the new results presented in this work are contained in papers [16, 17, 18, 19]. / Neste trabalho, nosso objetivo e provar resultados sobre prolongamento de soluções, limitação uniforme de soluções, estabilidade uniforme e estabilidade uniforme assintótica (no sentido clássico de Lyapunov) para equações diferenciais em medida e para equações dinâmicas em escalas temporais. A fim de obter os nossos resultados, empregamos a teoria de EDOs generalizadas, uma vez que estas equações abrangem equações diferenciais em medida e equações dinâmicas em escalas temporais. Portanto, para obter nossos resultados, vamos começar por provar, os resultados que queremos para EDOs generalizadas abstratas. Em seguida, usando a correspondência entre as soluções de EDOs generalizadas e soluções de equações diferenciais em medida (ver [38]), estenderemos os resultados para estas ultimas equações. Depois disso, usando a correspondência entre as soluções de equações diferenciais em medida e as soluções de equações dinâmicas em escalas temporais (ver [21]), estenderemos todos os resultados para estas ultimas equações. Finalmente, investigamos EDOs generalizadas autônomas e mostramos que estas equações não aumentam a classe de EDOs autônomas clássicas, mesmo quando consideramos uma classe mais geral de funções nos lados direitos das equações. Os novos resultados encontrados estão contidos em [16, 17, 18, 19].

In this work, our goal is to prove results on prolongation of solutions, uniform boundedness of solutions, uniform stability as well uniform asymptotic stability (in the classical sense of Lyapunov) for measure differential equations and for dynamic equations on time scales. In order to get our results, we employ the theory of generalized ODEs, since these equations encompass measure differential equations and dynamic equations on time scales. Therefore, to get our results, we start by proving the expected result for abstract generalized ODEs. Then, using the correspondence between the solutions of these equations and the solutions of measure differential equations (see [38]), we extend all the results to these the latter. After that, using the correspondence between the solutions of measure differential equations and the solutions of dynamic equations on time scales (see [21]), we extend all the results to these last equations. Finally, we investigate autonomous generalized ODEs and show that these equations do not enlarge the class of classical autonomous ODEs, even when we consider a more general class of functions as right-hand sides. All the new results presented in this work are contained in papers [16, 17, 18, 19]. / Neste trabalho, nosso objetivo e provar resultados sobre prolongamento de soluções, limitação uniforme de soluções, estabilidade uniforme e estabilidade uniforme assintótica (no sentido clássico de Lyapunov) para equações diferenciais em medida e para equações dinâmicas em escalas temporais. A fim de obter os nossos resultados, empregamos a teoria de EDOs generalizadas, uma vez que estas equações abrangem equações diferenciais em medida e equações dinâmicas em escalas temporais. Portanto, para obter nossos resultados, vamos começar por provar, os resultados que queremos para EDOs generalizadas abstratas. Em seguida, usando a correspondência entre as soluções de EDOs generalizadas e soluções de equações diferenciais em medida (ver [38]), estenderemos os resultados para estas ultimas equações. Depois disso, usando a correspondência entre as soluções de equações diferenciais em medida e as soluções de equações dinâmicas em escalas temporais (ver [21]), estenderemos todos os resultados para estas ultimas equações. Finalmente, investigamos EDOs generalizadas autônomas e mostramos que estas equações não aumentam a classe de EDOs autônomas clássicas, mesmo quando consideramos uma classe mais geral de funções nos lados direitos das equações. Os novos resultados encontrados estão contidos em [16, 17, 18, 19].