Bien qu’elle soit évitable par la vaccination, la grippe saisonnière est responsable annuellement de taux de morbidité et de mortalité élevés. Plusieurs études ont démontré que les facteurs sexuels (gènes et hormones) affectent la susceptibilité des individus aux maladies infectieuses et leur réponse aux vaccins. Toutefois, le sexe est souvent considéré comme une variable de confusion dans les études épidémiologiques, les résultats sont ainsi ajustés pour cette variable, ce qui rend la comparaison entre les deux sexes impossible. Le but de mon mémoire est de synthétiser les preuves existantes sur les différences liées au sexe dans la réponse au vaccin antigrippal. Ceci permettrait d’orienter les recommandations vaccinales qui tiendraient compte du sexe. Par conséquent, nous avons procédé à une revue systématique de la littérature afin d’analyser les données disponibles concernant les différences liées au sexe dans l’immunogénicité, l’efficacité potentielle, l’efficacité réelle et l’innocuité du vaccin contre la grippe saisonnière. Les résultats n’indiquent aucune différence dans l’immunogénicité et l’efficacité réelle du vaccin antigrippal saisonnier entre les sexes. Tandis que les taux de manifestations cliniques inhabituelles (MCI) étaient plus élevés chez les femmes. Enfin, il est nécessaire de disposer de données probantes afin de mieux comprendre les différences liées au sexe dans la réponse au vaccin antigrippal. / Every year, seasonal influenza is an important cause of morbidity and mortality, despite being vaccine-preventable. Several studies have demonstrated that sex factors (genes and hormones) impact individuals’ susceptibility and response to infectious diseases and vaccines. However, most studies do not explicitly assess sex differences in vaccine response despite collecting this data, but rather adjust for sex. The purpose of my dissertation is to synthesize the current evidence on sex differences in response to seasonal influenza vaccine in an attempt to guide sex-specific recommendations in influenza vaccines administration. Therefore, we conducted a systematic review to analyze available evidence on sex differences in immunogenicity, efficacy, effectiveness and/or safety of the seasonal influenza vaccine. Available data show no sex differences in the immunogenicity and effectiveness of seasonal influenza vaccine, while higher rates of adverse events following immunization (AEFIs) seem to occur in females. However, evidence of higher quality is needed to better understand sex differences in response to influenza vaccine.

Bien qu'il s'agisse d'une maladie évitable par la vaccination, la grippe cause annuellement environ 3 à 5 millions de cas de maladie grave et environ 290 000 à 650 000 décès dans le monde. Pour prévenir l'infection et ses complications, la vaccination antigrippale est généralement recommandée pour toutes les personnes de 6 mois et plus. La vaccination annuelle est nécessaire en raison des perpétuels changements antigéniques des virus de la grippe; par conséquent, les souches incluses dans les vaccins antigrippaux sont régulièrement mises à jour. Ainsi, l'efficacité de terrain des vaccins antigrippaux (EV) varie d'une saison à l'autre, ce qui nécessite une surveillance constante pour évaluer l'impact des programmes de vaccination contre la grippe saisonnière au fil du temps. Les données médico-administratives sont une riche source d'informations qui pourraient être exploitées pour estimer l'efficacité réelle des vaccins antigrippaux. De plus, des études récentes ont rapporté que la réponse immunitaire à l'infection grippale et à la vaccination peut être altérée par des expositions antérieures, ce qui pourrait affecter l’efficacité de terrain des vaccins antigrippaux. Cette thèse visait à déterminer si les données médico-administratives fournissent des estimations valables de l'EV et à évaluer l'impact de la vaccination répétée et d’une infection antérieure par les virus de la grippe sur l'EV contre le syndrome d’allure grippale (SAG). Nous avons d'abord effectué une revue systématique de la littérature pour évaluer l'impact de la vaccination antigrippale sur la réduction des visites médicales pour un SAG, des hospitalisations pour un SAG, des hospitalisations pour la grippe confirmée en laboratoire (LCI) et des hospitalisations toutes causes confondues. Nous avons identifié que la spécificité des résultats joue un rôle crucial dans l'estimation de l'EV et que la propension à utiliser des soins de santé peut introduire un biais dans les études d'EV si la propension à consulter pour un SAG est influencée par le statut vaccinal, mais également si la capacité à capturer le statut vaccinal et l’issue (SAG) est tributaire de la propension à consulter. Par la suite, nous avons constaté que les courbes d'incidence des consultations médicales liées à un SAG spécifique, dérivées des codes de diagnostic clinique spécifiques à l'infection grippale, étaient très similaires aux données de surveillance des Centers for Disease Control and Prevention (CDC) des États-Unis pour le LCI, suggérant ainsi qu'il est plus approprié d'utiliser la définition de SAG spécifique à l’infection grippale pour une surveillance des cas de grippe plutôt qu'une définition large du SAG, lorsque seuls les codes de diagnostic clinique sont disponibles pour l'évaluation de l’infection grippale. Ensuite, l'efficacité de terrain des vaccins antigrippaux de 2018-2019 à prévenir les consultations médicales pour un SAG (spécifique à l’infection grippale) a été évaluée dans une cohorte d'individus américains ayant au moins un enregistrement pertinent par année, entre 2015 et 2019, dans leur dossier de santé électronique (DSE). Les rapports de cotes ajustés (aOR) ont été dérivés de modèles de régression logistique multivariés et les EVs ajustées ont été calculées à l'aide de 100x(1-aOR). Les estimations d’EVs dérivées des données médico-administratives étaient toutes plus petites que celles rapportées par les CDC américains, suggérant ainsi que l’utilisation secondaire de ces données médico-administratives a mené à une sous-estimation de l’EV probablement due à des biais de détection et de mauvaise classification corrélés avec la propension à utiliser des soins de santé. Lorsque les EVs sont stratifiées sur le nombre de visites médicales, les estimations d'EVs et la couverture vaccinale augmentent avec le nombre de visites médicales, atteignant des estimations similaires à celles obtenues par les CDC américains et la couverture vaccinale nationale des États-Unis pour les personnes ayant au moins 6 visites médicales lors des 12 mois précédents. Les résultats suggèrent ainsi que l'utilisation secondaire des données médico-administratives ne permet pas de produire des estimations valables de l’efficacité de terrain des vaccins antigrippaux, et ce, en l’absence de données complètes sur la vaccination et l'infection grippale. Cependant, ces données médico-administratives ont le potentiel d'évaluer l'efficacité de terrain des vaccins antigrippaux dans les populations considérées à haut risque de complications à la suite de l'infection, ce qui est difficile à faire avec une surveillance active, ainsi que dans les populations ayant des conditions de santé nécessitant un suivi médical soutenu; car la probabilité que le statut vaccinal et/ou l’infection grippale soient déclarés dans les données médico-administratives augmente avec le nombre de contacts avec le système de santé. Enfin, l'efficacité de terrain des vaccins antigrippaux de 2018-2019 à prévenir le SAG a été estimée en fonction de l’historique de la vaccination antigrippale et des antécédents de SAG chez les utilisateurs fréquents de soins de santé. Bien que l'EV semble diminuer avec l’augmentation du nombre de vaccinations précédentes, la vaccination antigrippale lors de la saison en cours offre probablement une protection contre le SAG, quels que soient les antécédents de vaccination, en particulier chez les enfants. Néanmoins, les antécédents de SAG pourraient atténuer l'effet négatif d'une vaccination antérieure sur l'EV, probablement en raison d’une immunité naturelle liée à l’infection grippale. Même si une vaccination antérieure peut atténuer l'EV de la saison en cours dans certaines circonstances, cet effet d'interférence est imprévisible et les antécédents de vaccination ou d'infection ne devraient pas influencer la décision de se faire vacciner contre la grippe. Jusqu'à ce que des vaccins antigrippaux universels efficaces soient disponibles et éliminent la nécessité d'une vaccination annuelle, la recommandation actuelle de la vaccination annuelle contre la grippe reste un bon moyen de se protéger et ainsi protéger les autres de l’infection et de ses complications, principalement pour les personnes à haut risque de complications. / Although a vaccine-preventable disease, influenza causes annually approximately 3 to 5 million cases of severe illness and about 290 000 to 650 000 deaths worldwide. To prevent the infection and its complications, influenza vaccination is recommended for all individuals 6 months and older. Annual vaccination is necessary because of continual antigenic changes of influenza viruses; hence, vaccine compositions are regularly updated. Consequently, vaccine effectiveness (VE) varies between seasons requiring ongoing measurement to assess the impact of seasonal influenza vaccination programs over time. Administrative healthcare databases are a rich source of information that could be leveraged to estimate real-world influenza VE. Recent studies have reported that immunologic response to influenza infection and vaccination may be altered by previous exposures. This thesis aimed to determine if administrative healthcare data provide accurate VE estimates and to evaluate the impact of repeated vaccination and previous infection on VE against medically attended influenza-like illness (MA-ILI). We first performed a systematic review of the literature to evaluate the impact of influenza vaccination to reduce outpatient visits for influenza-like illness (ILI), hospitalization for ILI, hospitalization for lab-confirmed influenza (LCI) and all-cause hospitalization. We identified that outcome specificity plays a crucial role in VE estimate and healthcare seeking behaviour can bias VE estimates if the propensity to seek care for ILI is influenced by vaccination status, but also if the ability to capture patients’ vaccination status and/or ILI is dependent on their propensity to seek care. Subsequently, we found that the incidence curves of influenza-related medical encounters, derived from clinical diagnostic codesspecific to influenza infection, were very similar to the United States (U.S.) Centers for Disease Control and Prevention (CDC) surveillance data for LCI; suggesting that it is more appropriate to use influenza case definition for specific surveillance rather than a broad ILI definition, when only clinical diagnostic codes are available for the evaluation of influenza. Then, the 2018-2019 influenza vaccine effectiveness against medically attended influenza-like illness (MA-ILI) was evaluated in a cohort of U.S. individuals who had at least one relevant record per year between 2015 and 2019 in their electronic medical record (EMR). Adjusted odds ratios (aORs) were derived from multivariate logistic regression models and adjusted VE (aVEs) were calculated using 100x(1-aORs). Estimated aVEs derived from administrative healthcare data were all lower than CDC-reported VE; results suggested that the secondary use of these administrative healthcare data led to an underestimation of influenza VE, likely due to detection and misclassification biases, correlated with healthcare seeking behaviour. When stratified by the number of primary care visits, aVE estimates and vaccine coverage increased with the number of primary care visits, reaching estimates similar to those obtained by the U.S. CDC and U.S. national vaccination coverage among those with at least 6 primary care visits in the previous 12 months. Results suggested that the secondary use of these administrative healthcare data cannot produce accurate influenza VE without comprehensive influenza vaccination and infection data. However, these databases have the potential to assess influenza VE in populations considered at high risk of complications following the infection, which is not easily achievable with active surveillance, as well as in populations with health conditions requiring constant medical follow-up since probabilities that vaccination and/or infection status are reported in administrative healthcare data increase with the number of contacts with the healthcare system. Finally, the 2018-2019 aVE against MA-ILI was estimated by previous vaccination status and previous history of MA-ILI in frequent healthcare users. Although VE appeared to decrease in relation to increasing numbers of previous influenza vaccinations, current season vaccination likely provides protection against MA-ILI regardless of vaccination history, especially in children. Nevertheless, previous MA-ILI could mitigate the negative effect of prior influenza vaccination on VE likely via infection-induced immunity. Even if prior influenza vaccination may attenuate current season VE in some circumstances, this interference effect is unpredictable and previous vaccination or infection history should not influence the decision to get vaccinated against influenza. Until effective universal influenza vaccines are available and eliminate the need for annual vaccination, the current recommendation for annual influenza vaccination remains important to protect ourselves and others from influenza infection and its complications, particularly in at-risk populations.

[pt] A pesquisa recorda as três maiores pandemias da Era Cristã: a Peste Justiniana, no século VI, a Peste Negra, no século XIV e a Gripe Espanhola, no século XX. Investiga-se em cada moléstia a natureza da doença, sua origem, sintomas, percursos e impactos. Enfatiza-se a maneira como a Igreja atravessou cada período pandêmico, revelando suas crenças e interpretações para as pragas, a forma como tentava afastar o mal e a assistência que fornecia aos enfermos e enlutados. A pesquisa revela ainda se os cristãos amadureceram suas respostas às crises, se aspectos litúrgicos foram adaptados e se interpretações escatológicas sofreram alguma alteração. Seguindo a ordem cronológica em que as pestilências se sucederam, dedica-se o primeiro capítulo ao estudo da Peste Justiniana, revelando, por exemplo, como o contexto geográfico e social da época contribuía para a disseminação de doenças. A pesquisa avança até a Baixa Idade Média, quando Europa, Ásia e África são assoladas pela Peste Negra, e mostra, entre outras coisas, as frustrantes tentativas médicas e religiosas de lidar com a praga. Finalmente, o último capítulo explora a maior pandemia da história, a Gripe Espanhola, dissertando sobre sua alta letalidade e a maneira diversa como os cristãos oriundos de diferentes denominações reagiram. / [en] The research recalls the three greatest pandemics of the Christian Era: the Jus-tinian Plague, in the 6th century, the Black Death, in the 14th century and the Spanish Flu, in the 20th century. The nature of the disease, its origin, symptoms, routes and impacts are investigated in each sickness. It emphasizes how the Church went through each pandemic period, revealing its beliefs and interpretations for the plagues, the way it tried to ward off evil and the assistance it provided to the sick and mourning. The survey also reveals whether Christians have matured their responses to crises, whether liturgical aspects have been adapted and whether eschatological interpretations have undergone any changes. Following the chronological order in which the pestilences followed one another, the first chapter is devoted to the study of the Justinian Plague, revealing, for example, how the geographic and social context of the time contributed to the spread of diseases. The research advances to the Late Middle Ages, when Europe, Asia and Africa were ravaged by the Black Death, and shows, among other things, the frustrating medical and religious attempts to deal with the plague. Finally, the last chapter explores the greatest pandemic in history, the Spanish Flu, discussing its high lethality and the diverse way in which Christians from different denominations reacted.

Die Tetrapyrrolbiosynthese (TBS) führt zu wichtigen Endprodukten wie Häm und Chlorophyll. Das gemeinsame Vorstufenmolekül aller Tetrapyrrole ist die 5-Aminolävulinsäure (ALA), die in Pflanzen über den C5-Weg aus Glutamat synthetisiert wird. Das erste spezifische Enzym der ALA-Synthese und somit auch der TBS ist die Glutamyl-tRNA Reduktase (GluTR). Sie unterliegt als Schlüsselenzym einer strengen Regulation. Aufgrund der unterschiedlichen Expression der HEMA-Gene in Arabidopsis wird ein differenzieller Beitrag der GluTR-Isoformen zu den Endprodukten der TBS vermutet. Analysen von knockout-Mutanten gaben Aufschluss darüber, inwiefern die Isoformen den Verlust des jeweils anderen kompensieren können. Die knockout-Mutante von HEMA1 zeigte einen blassgrünen Phänotyp, war nicht mehr in der Lage photoautotroph zu wachsen und demonstrierte eine essentielle Rolle der GluTR1 gegenüber GluTR2, wohingegen hema2-Mutanten einen wildtypartigen Phänotyp aufzeigten. Die Bedeutung der N-terminalen GluTR-Domäne in der posttranslationalen Regulation der ALA-Synthese wurde durch BiFC-Analysen und Komplementationsversuche aufgeklärt. BiFC-Analysen zeigten eine Interaktion der N-terminalen Domäne der GluTR1 mit Proteinen der Clp Proteasen und dem GluTR-Bindeprotein (GBP). Veränderte GluTR-Stabilitäten in gbp-Mutanten lassen eine schützende Funktion des GBP gegenüber dem Abbau des Proteins postulieren. Die Expression einer N-terminal verkürzten GluTR1 komplementierte hema1-Mutanten vollständig. Die in diesen Pflanzen und in clp-Mutanten beobachteten erhöhten GluTR1-Proteinstabilitäten im Dunkeln lassen einen Abbau der GluTR durch Clp Proteasen vermuten, bei dem der N-Terminus des Enzyms für die Substraterkennung notwendig zu sein scheint. Die Detektion von erhöhten Pchlid-Mengen als Folge der erhöhten Proteinstabilität in Linien, die die verkürzte GluTR1 exprimierten, demonstriert erstmals die Bedeutung einer kontrollierten Proteolyse der GluTR in der Regulation der ALA-Synthese. / In plants 5-aminolevulinic acid (ALA) is the common precursor of all tetrapyrrols and formed from glutamate via the C5 pathway. Glutamyl-tRNA reductase (GluTR) is the initial enzyme of ALA synthesis and thus tetrapyrrole biosynthesis (TBS). The most important control point of the TBS is the synthesis of ALA and GluTR is the key enzyme, that is tightly regulated. Due to the different expression of HEMA genes in Arabidopsis, a differential contribution to endproducts of the TBS is proposed for GluTR isoforms. Analysis of knockout mutants gave some indications of how the isoforms can compensate each other. I introduced a new knockout mutant of HEMA1 that was pale-green and not able to grow photoautotrophically, indicating that the remaining GluTR2 does not sufficiently compensate ALA synthesis for the extensive needs of chlorophyll. In contrast, hema2 mutants were wild-type-like. The function of the N-terminal region of GluTR1 in posttranslational regulation has been analyzed by BiFC analysis and complementation experiments of hema1. BiFC analysis showed an interaction of the N-terminal region of GluTR1 with the GluTR binding protein (GBP) and with proteins of the Clp proteases. Mutants of GBP revealed a decreased GluTR1 stability during the dark period, indicating a protective role of GBP against proteolysis of GluTR1 in darkness. The expression of a GluTR1 lacking the N-terminal amino acid residues successfully complemented hema1. These plants as well as clp mutants revealed an increased GluTR1 stability in darkness, suggesting a degradation of the protein through Clp proteases. Thereby, the N-terminal region of GluTR1 seems to be necessary for the recognition by Clp proteins. The observed high amount of truncated GluTR1 in transformed hema1 mutants was caused by the increased GluTR1 stability and lead to an accumulation of Pchlide in prolonged dark periods, demonstrating the importance of a controlled proteolysis of GluTR in the regulation of ALA synthesis.

Introduction: Epidemiological studies have indicated that 5-38% of influenza like illnesses (ILI) develop into severe disease due to, among others, factors such as; underlying chronic diseases, age, pregnancy, and viral mutations. There are suggestions that dual or multiple virus infections may affect disease severity. This study investigated the association between co-infection between influenza A viruses and other respiratory viruses and disease severity. Methodology: Datum for samples from North West England tested between January 2007 and June 2012 was analysed for patterns of co-infection between influenza A viruses and ten respiratory viruses. Risk of hospitalization to a general ward ICU or death in single versus mixed infections was assessed using multiple logistic regression models. Results: One or more viruses were identified in 37.8% (11,715/30,975) of samples, of which 10.4% (1,214) were mixed infections and 89.6% (10,501) were single infections. Among patients with influenza A(H1N1)pdm09, co-infections occurred in 4.7% (137⁄2,879) vs. 6.5% (59⁄902) in those with seasonal influenza A virus infection. In general, patients with mixed respiratory virus infections had a higher risk of admission to a general ward (OR: 1.43, 95% CI: 1.2 – 1.7, p = <0.0001) than those with a single infection. Co-infection between seasonal influenza A viruses and influenza B virus was associated with a significant increase in the risk of admission to ICU/ death (OR: 22.0, 95% CI: 2.21 – 219.8 p = 0.008). RSV/seasonal influenza A viruses co-infection also associated with increased risk but this was not statistically significant. For the pandemic influenza A(H1N1)pdm09 virus, RSV and AdV co-infection increased risk of hospitalization to a general ward, whereas Flu B increased risk of admission to ICU/ death, but none of these were statistically significant. Considering only single infections, RSV and hPIV1-3 increased risk of admission to a general ward (OR: 1.49, 95% CI: 1.28 – 1.73, p = <0.0001 and OR: 1.34, 95% CI: 1.003 – 1.8, p = 0.05) and admission to ICU/ death (OR: 1.5, 95% CI: 1.20 – 2.0, p = <0.0001 and OR: 1.60, 95% CI: 1.02 – 2.40, p = 0.04). Conclusion: Co-infection is a significant predictor of disease outcome; there is insufficient public health data on this subject as not all samples sent for investigation of respiratory virus infection are tested for all respiratory viruses. Integration of testing for respiratory viruses’ co-infections into routine clinical practice and R&D on integrated drugs and vaccines for influenza A&B, RSV, and AdV, and development of multi-target diagnostic tests is encouraged.

This Diploma thesis deals with some aspects of four chosen Czech daily newspapers referring about the outbreak and early development of events connected with one of the latest significant global crisis - the swine flu, which had broken out in 2009. The theoretical part of the thesis deals with some characteristics of crisis and basic concepts, which might be associated with their media coverage. In the practical part, it deals with the way, how the Czech dailies covered first two weeks of spreading of the disease. At the beginning, the thesis introduces a quantitative profile of the analyzed sample and shows both physical and verbal range of it. The second part is focused on the main topics, which were chosen by all daily newspapers to refer about the swine flu. Those, which did not make it to the main thematic line presented before, are also shortly mentioned in the chapter. In the third part, the thesis follows the main motives appearing in the images that accompanied the news with the chosen topic and also discovers how the disease was "objectified". Finally, language analysis discovering some specific subjective language characteristics referring to a potential personal opinion included by individual authors, or the way how the authors dealt with the coverage of the potential future development...

Fin avril 2009, un nouveau virus grippal A/H1N1 d'origine porcine émerge dans le monde causant la première pandémie grippale du XXIème siècle. Les différents travaux présentés dans cette thèse retracent la gestion de cette situation au laboratoire de virologie des hôpitaux publics de Marseille. D'avril 2009 à avril 2010, nous avons analysé plus de 13 000 prélèvements issus de cas suspects. Nous avons dû adapter continuellement les moyens mis en œuvre pour effectuer le diagnostic et la mise en place d'une stratégie 'Point of Care' s'est avérée très utile. Nos résultats montrent que l'usage des tests rapides en complément de la RT-PCR en temps réel permet de réduire significativement le délai de rendu des résultats pour les patients infectés. Les données épidémiologiques sur les nombreux cas suspects dépistés ont également permis d'obtenir en temps réel des informations précieuses sur l'épidémiologie de cette pandémie comme l'estimation de l'incidence par classe d'âge, la proportion de patients hospitalisés et la mortalité. Enfin, nous avons réalisé une étude de séroprévalence qui montre qu'environ 12% de la population française a été infectée par ce nouveau virus en 2009-2010 et que les taux d'attaque les plus élevés ont été observés chez les enfants et les jeunes adultes. / In late April 2009, a new swine-origin A/H1N1 Influenza virus emerged and spread rapidly worldwide causing the first influenza pandemic of the 21st century. This work describes how we coped with this emergency situation in the virology laboratory of Marseille public hospitals. From April 2009 to April 2010, we analyzed more than 13,000 samples from suspected cases. We needed to adapt continuously the organization to maintain diagnostic capacity and the implementation of a point of care strategy revealed very useful to achieve this goal. Our results support the use of rapid Influenza detection tests in combination with real-time RT-PCR because it reduces significantly the delay from sample to result for positive cases, thus giving the opportunity to improve patient management. Epidemiological data from all suspected cases tested allowed us to obtain timely precious information about the epidemiology of this pandemic as the estimation of (i) the incidence by age group, (ii) the rate of hospitalization and (iii) the mortality rate among tested patients. Finally, we set up a serological study and showed that around 12% of the French population had been infected by this new virus in 2009-2010 with higher attack rates observed in children and young adults.

Στόχος της παρούσης διπλωματικής εργασίας είναι να μελετηθεί η Ταχεία Διάχυση Αρνητικών Χρηματοοικονομικών Συμβάντων (financial contagion) όπως αυτή παρουσιάζεται στην βιβλιογραφία καθώς επίσης οι αιτίες, οι τρόποι διάχυσης και οι τρόποι μέτρησης της. Όσον αφορά στο εφαρμοσμένο κομμάτι της υπάρχουσας βιβλιογραφίας εξετάζεται το μέρος αυτής το οποίο αφορά στην εξέταση της Ταχείας Διάχυσης Αρνητικών Χρηματοοικονομικών Συμβάντων με μοντέλα περιορισμένης εξαρτημένης μεταβλητής. Γίνεται εκτενέστερη ανάλυση στο multinomial logit μοντέλο το οποίο φανερώνει την πιθανότητα εμφάνισης ενός ενδεχομένου σε σχέση με τις επεξηγηματικές μεταβλητές που επιλέγονται. Στα πλαίσια της εργασίας αυτής γίνεται και μια εμπειρική εφαρμογή ενός τέτοιου μοντέλου με δεδομένα που αφορούν την Ελληνική Χρηματιστηριακή Αγορά με σκοπό να δειχθεί αν οι χαμηλές αποδόσεις ορισμένων υποδεικτών του Γενικού Δείκτη Τιμών επηρεάζουν την πιθανότητα εμφάνισης ταυτόχρονων κοινών υπερβάσεων στις αποδόσεις (coexceedances) και άλλων υποδεικτών. / The aim of this thesis is to study the rapid dissemination Negative Financial Events (financial contagion) as presented in the literature as well as the causes, ways and methods of diffusion measurement. As far as the applied part of the existing literature is concerned, it is examined the part which concerns the examination of the Rapid Diffusion of Negative Financial Events (financial contagion) with limited dependent variable models. There is extensive analysis of the multinomial logit model. As part of this work it is presented an empirical application of such a model with data from the Greek stock market in order to indicate whether the low returns of certain subindices of the General Price Index affect the likelihood of simultaneous joint excesses in returns (coexceedances) of other subindices .

Made available in DSpace on 2014-07-29T16:17:38Z (GMT). No. of bitstreams: 1 Leandro Carvalho Damacena Neto.pdf: 5860174 bytes, checksum: d2948cd4bdd56c4fd40f454247f3de60 (MD5) Previous issue date: 2011-03-11 / Research on the Spanish flu in Goiás aimed to understand the impacts and meanings which accounted for the population. We analyze its symptoms Spanish flu, as well as highlight the imprecision of medicine to define and characterize it, the multiple symptoms diagnosed and the variety of treatments and therapeutic measures. For this, the research is anchored in the records of the press Goiás, in the context of 1918/1919 were lodged with the population and called Advice to people: that is, they were indications of health authorities to combat the Spanish flu. More than a biological problem, the Spanish flu became a social problem, and as such has been analyzed here, from its social representation - ie, the disease constituted a problem that requires an explanation by the company attacked, it is imperative that has a social and cultural. Historicize diseases is one of the ways to understand a society. / A pesquisa sobre a gripe espanhola em Goiás teve como principal objetivo compreender os impactos e os significados que representou para a população. Buscamos analisar a sintomatologia da doença de gripe espanhola, bem como ressaltar a imprecisão da medicina ao defini-la e caracterizá-la, os múltiplos sintomas diagnosticados e a variedade de tratamentos e medidas terapêuticas. Para tanto, a pesquisa ancorou-se nos registros da imprensa goiana, que, no contexto de 1918/1919, foram dirigidos à população e denominados Conselhos ao povo;ou seja, eram indicações das autoridades sanitárias para o combate da gripe espanhola. Mais que um problema biológico, a gripe espanhola se tornou um problema social, e como tal foi aqui analisada, a partir da sua representação social ou seja, a doença constituiu-se um problema que exige uma explicação pela sociedade atacada; é imperativo que tenha sentido social e cultural. Historicizar as doenças é um dos caminhos para se compreender uma sociedade.

The 1st and 2nd order Lee–Carter methods were compared with the Hyndman–Ullah method in regards to goodness of fit and forecasting ability of mortality rates. Swedish population data was used from the Human Mortality Database. The robust estimation property of the Hyndman–Ullah method was also tested with inclusion of the Spanish flu and a hypothetical scenario of the COVID-19 pandemic. After having presented the three methods and making several comparisons between the methods, it is concluded that the Hyndman–Ullah method is overall superior among the three methods with the implementation of the chosen dataset. Its robust estimation of mortality shocks could also be confirmed.