Background: Seasonal influenza epidemics occur annually in the United States (U.S.) and result in lost workforce productivity, strained healthcare services, and an annual economic burden of $11 billion. While the U.S. has a comprehensive surveillance system, and the Centers for Disease Control and Prevention (CDC) publishes weekly updates on the outlook of seasonal influenza activity (FluView), there is a lack of literature analyzing seasonal influenza peak trends across and within regions of the country over multiple flu seasons. This study aimed to identify trends over time (2005-2015) in the timing and size of seasonal flu outbreak peaks, both across and within Health and Human Services regions. Methods: Secondary data analysis was conducted on U.S. national influenza surveillance data compiled and provided by the CDC. The study includes all persons in the United States (all 50 states, District of Columbia, Puerto Rico, and the U.S. Virgin Islands) who sought healthcare for influenza-like illness (ILI) during the 2005-06 flu season through the 2014-15 season. Trends over time in peak timing and size were assessed overall (across all HHS regions) and within regions. The effect of the dominant subtype of influenza virus circulating on peak timing and size was also assessed. Results: Trends in seasonal influenza outbreaks revealed peaks that occurred earlier over time (p<0.0001) and increased in size over time (p=0.0012). The median peak week did not vary significantly by region (p=0.8541). Also, peak week and peak size were negatively correlated showing that earlier epidemics result in higher ILI rates. The timing of the epidemic differed depending on the dominant subtype circulating (p=0.0337) with subtype 2009 H1N1peaks occurring 3.5 weeks earlier than H1 peaks; however, subtype did not have a significant effect on the size of the epidemic peak (p=0.1984). Conclusion: A significant decrease in peak week and a significant increase in peak size were observed over time, revealing a trend of earlier and more intense seasonal flu peaks. Since earlier epidemics are correlated with higher rates of ILI, anticipating earlier seasonal peaks highlights the importance of vaccination and other flu prevention strategies being utilized early in the flu season.

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Influenza is suspected to be endemic in tropical climates, with peaks during and/or following cold or rainy seasons. To date, only one study has been conducted examining the epidemiology and seasonality of influenza in Uganda. The focus of this analysis is to determine whether a change in the seasonality of influenza can been seen between three distinct regions of Uganda: Central, Northwest, and Western. Secondary data analysis was conducted on surveillance data collected by the Uganda Virus Research Institute (UVRI) between April 2007 to September 2010 from 10 surveillance sites. Surveillance sites were grouped for this analysis into three regions: Central, Northwest, and Western. A total of 3,944 samples were collected and tested for any strain of influenza. The prevalence of influenza over the 4 years of surveillance was 10.1%. The majority of cases came from the Central region (81.7%) and the highest prevalence of influenza-positive samples were collected in the Central region (88.7 cases/1,000 persons). A clear difference in influenza activity was observed during the 2009 H1N1 pandemic. Uganda reported its first case of H1N1 in July 2009 (Relief Web). The Central region experienced its initial flux of influenza activity in July and August 2009 (Figure 1). However, the Northwest region did not experience a flux in activity until October 2009 (Figure 2). Influenza activity in the Central and Northwest regions appear to coincide with colder temperatures and both rainy seasons. The Northwest region was the only region to experience a peak corresponding with warmer weather. Results showed a slight change in the seasonality of influenza between the Central and Northwest regions of Uganda from surveillance data collected between April 2007 and September 2010.

This thesis examines the experience of disability income insurance in Australia from 1980 to 2001. The data underlying the work was generously provided by the Institute of Actuaries of Australia which has collected data from the major companies which have written this business since 1976. The focus in this work is on the claims behaviour of those who have been insured and the implications to be drawn from the observations about that behaviour. This information is intended to be valuable to individual companies as they seek to make decisions about their pricing, underwriting and claims management so as to ensure adequate profitability of this line of business. The work demonstrates the following key conclusions. There have been very radical changes in the characteristics of the business over the period and in the resulting experience. In particular, the claim termination experience has deteriorated dramatically with average claim durations now around twice that at the start of the period, The structure of IAD8993 is no longer representative of the aggregate industry experience. This is particularly so in respect to incidence, where only one of the six characteristics included has its �shape� confirmed by the experience. The other five have statistically significant evidence that their �shape� is not consistent with the experience. For terminations three of the six are confirmed. Many of the additional characteristics examined demonstrate that they are significant predictors of experience. In respect to incidence six of the eight examined were significant. In respect to terminations only two of the eight were significant. There is a material element of seasonality in respect to both incidence and terminations. While the Australian experience is materially better than the corresponding USA experience the worsening experience for medical occupations in the USA should be taken as a warning to Australia of the potential which exists in this occupation subclass. There is a serious body of circumstantial evidence supporting the hypothesis that the experience of disability income insurance is significantly influenced by �state of mind� rather than �state of body�.

This thesis examines returns around earnings announcements for companies with seasonality in earnings. Earnrank is used as a measure of seasonality where earnrank for a company is calculated quarterly by taking last five years of earnings data, ranking them and taking the average of the ranks for the respective quarter. For seasonal firms, we find robust evidence that abnormal returns are created when such firms announce their earnings for the highest seasonality quarter as measured by their earnrank. Additionally, the results were consistent for different time periods and abnormal returns were found to increase over time. We also performed the analysis industry-wise and found significant difference in returns for most and least seasonal firms in Manufacturing, Financial and Construction sectors. The results for Construction sector is in conflict to our hypothesis and require further exploration. We also study which kind of firms exhibit seasonality and found evidence for high seasonality in large firms, value firms, old firms, firms with lower turnover and firms with lower accruals. Lastly, we studied factors determining abnormal returns relative to the four-factor model and found size to be a significant explanatory variable. The long-short portfolio based on seasonality generated an alpha of 62 basis points per month. / Master of Science

L'omniprésence des horloges circadiennes à travers une vaste gamme de taxons démontre la valeur adaptative de connaître l'heure du jour. Ces horloges permettent aux organismes de synchroniser leurs processus biologiques quotidiens à des environnements externes et internes changeants. Dans mon projet de doctorat, j'ai utilisé la drosophile comme système modèle pour étudier les bases neurales de l'adaptation saisonnière de l'activité quotidienne par l'horloge. Chez la drosophile, l'horloge cérébrale régulant l'activité locomotrice, suivant un modèle bimodale, fonctionne comme un réseau multi-oscillateurs. Deux ensembles distincts de neurones contrôlent l'activité du matin et l’activité du soir quotidiennement. Les neurones contribuant à l'activité du soir sont nombreux (oscillateurs E : 6 LNds, 1 sLNv et environ 12 à 15 DN1ps dans chaque hémisphère) et très divers en termes de localisations anatomiques, de motifs de projection, de neurochimie et de modalités photoréceptives. Mon travail indique que les différents oscillateurs E possèdent également des activités fonctionnelles distinctes dans le réseau neuronal d'horloge. J’ai démontré que seulement 2 paires d'oscillateurs E (ITP + CRY +) sur environ 150 neurones d'horloge sont suffisantes pour l'activité d'anticipation du soir. La dissection génétique de divers sous-ensembles d'oscillateurs du soir indique que non seulement ces deux paires de neurones sont suffisantes pour l'activité du soir, mais également qu'elles sont fonctionnellement supérieures aux autres oscillateurs du soir. Par conséquent, une hiérarchie opérationnelle existe parmi les oscillateurs du soir dans lesquels les neurones oscillateurs ITP + CRY + (dorénavant, ITP E) occupent l'échelon le plus élevé. J’ai par ailleurs démontré que cette hiérarchie est plutôt flexible, et que les partenaires de cette relation hiérarchique changent de rôle en fonction des entrées neuropeptidergiques (à savoir, le PDF). Les comportement et les réponses calciques des divers neurones du soir suggèrent que le PDF et les signaux saisonniers agissent sur un cadre fonctionnel, dans lequel certains neurones construisent l'activité du soir en augmentant l’activité en fin de journée et que d'autres neurones y contribuent en inhibant l'activité du début d'après-midi. Mise à part le PDF, les indices saisonniers, tels que la durée du jour, l'intensité lumineuse et la température, déterminent la pondération fonctionnelle parmi les oscillateurs du soir. Les signaux saisonniers influencent différents oscillateurs pour remplir la même fonction sous différentes saisons. Les oscillateurs ITP E sont recrutés principalement dans des conditions hivernales, tandis que les oscillateurs non-ITP E contribuent davantage dans des conditions semblables à celles de l'été. Ce recrutement biaisé d'oscillateurs se produit en partie via la modulation des niveaux de PDF par des indices saisonniers.Même s'il existe de nombreux oscillateurs E dans le circuit neuronal circadien, leur pertinence fonctionnelle est définie par des stimuli externes (indices saisonniers) et internes (neuropeptides) grâce au recrutement de différents oscillateurs.En résumé, mon étude de doctorat tente de fournir une explication plausible sur la manière dont l'adaptation saisonnière de l'horloge circadienne est réalisée au niveau neuronal. Mes résultats supportent l'idée que le recrutement d'oscillateurs, contrôlé par l'environnement, facilite l'ajustement saisonnier sculpté par l'horloge circadienne multi-oscillateurs.LNd: dorsal-lateral neuronssLNv: small ventral-lateral neuronsDN1p: dorsal neurons 1 (posterior)ITP: Ion Transport PeptideCRY: CryptochromePDF: Pigment Dispersing Factor / The ubiquity of circadian clocks across a vast range of taxa signifies the adaptive value of knowing the time of the day. These clocks enable organisms to synchronize their daily biological processes to changing external and internal environments. In my PhD project, I used Drosophila as a model system to test hypotheses regarding the neural basis of the seasonal adaptation of the clock-driven daily activity pattern. In Drosophila, the brain clock regulating bimodal locomotor activity functions as a multi-oscillator network. Two distinct sets of neurons control morning and evening bouts of daily locomotor activity. Neurons contributing to the evening activity (E oscillators; 6 LNds, 1 sLNv and around 12 to 15 DN1ps in each hemisphere) are numerous and quite diverse within themselves in terms of their anatomical loci, projection patterns, neurochemistry, and photoreceptive modalities. My work indicates that the different E oscillators also possess distinct functional loci in the clock neuronal network. I show that only 2 pairs of E oscillators (ITP+ CRY+) out of around 150 clock neurons are sufficient for the evening anticipatory activity. Genetic dissection of various evening oscillator subsets further indicates that not only these two pairs of neurons are sufficient for the evening activity, but also, they are functionally superior to other evening oscillators in their contribution to the evening activity. Hence, an operational hierarchy exists among the evening oscillators in which the ITP+ CRY+ (henceforth, ITP E) oscillator neurons inhabit the highest rung. I further show that this hierarchy is rather flexible, and the partners of this hierarchical relationship switch roles depending on neuropeptidergic inputs (namely, PDF). Studying behavior and calcium responses in diverse evening neurons suggest that PDF and seasonal cues act on a functional framework of E neurons in which some build evening activity by promotion of activity in the later parts of the day and while others, by inhibiting activity in the earlier afternoon. Alongside PDF, seasonal cues such as day-length, light intensity and temperature, determine the functional weightage among evening oscillators. Specific seasonal cues recruit different oscillators to carry out the same function under different seasons. ITP E oscillators are recruited mostly by winter-like conditions whereas non- ITP E oscillators contribute more under summer-like conditions. This biased recruitment of oscillators partly occurs via modulation of the PDF levels by seasonal cues. Even though there are numerous E oscillators in the brain circadian circuit, their functional relevance is defined by external (seasonal cues) and internal (neuropeptides) environments through conditional oscillator recruitment. In summary, my PhD study attempts to provide a plausible explanation of how seasonal adaptation of the circadian clock and the behaviours that it times, is achieved at the neural level. My results support the idea that environmentally gated recruitment of oscillators facilitates seasonal adjustment of the daily activity pattern sculpted by the multi-oscillator circadian clock.LNd: dorsal-lateral neuronssLNv: small ventral-lateral neuronsDN1p: dorsal neurons 1 (posterior)ITP: Ion Transport PeptideCRY: CryptochromePDF: Pigment Dispersing Factor

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