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Indiana University-Purdue University Indianapolis (IUPUI) / The crossing of Kaplan-Meier survival curves presents a challenge when conducting survival analysis studies, making it unclear whether any of the study groups involved present any significant difference in survival. An approach involving the determination of maximum vertical distance between the curves is considered here as a method to assess whether a survival advantage exists between different groups of patients. The method is illustrated on a dataset containing survival times of patients treated with two cancer treatment regimes, one involving treatment by chemotherapy alone, and the other by treatment with both chemotherapy and radiotherapy.

Grandes avanços tem sido feitos para melhorar a produção de leite, mas estes avanços têm resultado numa queda geral da eficiência reprodutiva. Para se combater esta queda, tem sido seguidos principalmente três caminhos: um relacionado com a vaca, outro com as gametas e outro com o ambiente. Os problemas associados à vaca compreendem os problemas relacionados com a detecção de cio e os problemas hormonais que resultam em baixas taxas de concepção e aumento das mortes embrionárias precoces. Alternativas para melhorar a detecção de cio tem sido procuradas, dentre estas, os medidores de atividade são uma alternativa promissória, porém ainda em desenvolvimento. Com o fim de avaliar a eficiência do uso de medidor de atividade na detecção de cio de vacas leiteiras de alta produção, foram desenvolvidos três experimentos. O primeiro avaliou a eficiência do uso de medidor de atividade na detecção de cio após o período de espera voluntario (PEV), o segundo avaliou a eficiência do uso de medidor de atividade na detecção do cio de retorno após o uso de um protocolo de inseminação artificial a tempo fixo (IATF), o terceiro avaliou a relação custo-benefício da aquisição do aparelho. Na detecção do primeiro cio efetivo após o PEV o medidor de atividade apresentou maior taxa de detecção de cio, comparado com a observação visual de cio. O aparelho mostrou especial avantaja sobre a observação visual de cio na detecção de vacas multíparas de alta produção. No experimento de detecção de cio de retorno após o uso de IATF, o medidor de atividade detectou maior número de animais em menor tempo, porém, as mudanças no padrão de comportamento animal causadas pelos hormônios próprios da sincronização de cio, diminuíram a confiabilidade do sistema automatizado de detecção, ainda assim o numero de animais detectados em cio verdadeiro do sistema automatizado foi superior. Na análise de custo-benefício, a taxa interna de retorno obtida, demonstrou que o medidor de atividade é um investimento rentável o que possibilita sua aquisição. Enquanto aos falsos positivos gerados pelo sistema, sugere-se integrar as indicações feitas pelo sistema automatizado com a experiência dos funcionários das fazendas. / Huge progress has been made to improve the milk yield, but these advances have resulted in a general decrease of reproductive efficiency. Three main ways have been taken to combat this decrease: one related to the cow, another with the gametes and the lasts related with the environment. The problems associated with cow comprehend the estrous detection problems and the hormonal disorders that results in low conception rates and increases the early embryonic deaths. Alternatives to improve the heat detection has been developed. Among them, the activity meters are a promissory alternative, but still in development. Three experiments were developed in order to assess the efficiency of use of an activity meter in the estrous detection of high producing dairy cows. The first assessed the efficiency of the use of activity meter detecting estrous after the voluntary waiting period (VWP), the second assessed the efficiency of use of activity meter in the detection of the return estrous after use of a fixed-time artificial insemination (TAI) protocol, the third assessed the cost-benefit of acquisition of the system. In the first estrous after the VWP, the activity meter presented higher estrous detection rate, compared with the visual observation. The system has special vantage in the detection of multiparous high producing cows, if compared with visual observation. In the experiment of detecting return estrous after use of TAI, the activity meter detected greater number of animals in less time, however, changes in the pattern of animal behavior caused by hormones during the synchronization, decreased the accuracy of the automated system. On the other hand, the number of animals detected in real estrous of the automated system was superior than in visual observation. In the cost-benefit analysis, the internal rate of return obtained, showed that the activity meter is a profitable investment. Referent to the false positives generated by the system, it is suggested to integrate the indications made by the automated system with the experience of the functionaries of the dairy farms.

Grandes avanços tem sido feitos para melhorar a produção de leite, mas estes avanços têm resultado numa queda geral da eficiência reprodutiva. Para se combater esta queda, tem sido seguidos principalmente três caminhos: um relacionado com a vaca, outro com as gametas e outro com o ambiente. Os problemas associados à vaca compreendem os problemas relacionados com a detecção de cio e os problemas hormonais que resultam em baixas taxas de concepção e aumento das mortes embrionárias precoces. Alternativas para melhorar a detecção de cio tem sido procuradas, dentre estas, os medidores de atividade são uma alternativa promissória, porém ainda em desenvolvimento. Com o fim de avaliar a eficiência do uso de medidor de atividade na detecção de cio de vacas leiteiras de alta produção, foram desenvolvidos três experimentos. O primeiro avaliou a eficiência do uso de medidor de atividade na detecção de cio após o período de espera voluntario (PEV), o segundo avaliou a eficiência do uso de medidor de atividade na detecção do cio de retorno após o uso de um protocolo de inseminação artificial a tempo fixo (IATF), o terceiro avaliou a relação custo-benefício da aquisição do aparelho. Na detecção do primeiro cio efetivo após o PEV o medidor de atividade apresentou maior taxa de detecção de cio, comparado com a observação visual de cio. O aparelho mostrou especial avantaja sobre a observação visual de cio na detecção de vacas multíparas de alta produção. No experimento de detecção de cio de retorno após o uso de IATF, o medidor de atividade detectou maior número de animais em menor tempo, porém, as mudanças no padrão de comportamento animal causadas pelos hormônios próprios da sincronização de cio, diminuíram a confiabilidade do sistema automatizado de detecção, ainda assim o numero de animais detectados em cio verdadeiro do sistema automatizado foi superior. Na análise de custo-benefício, a taxa interna de retorno obtida, demonstrou que o medidor de atividade é um investimento rentável o que possibilita sua aquisição. Enquanto aos falsos positivos gerados pelo sistema, sugere-se integrar as indicações feitas pelo sistema automatizado com a experiência dos funcionários das fazendas. / Huge progress has been made to improve the milk yield, but these advances have resulted in a general decrease of reproductive efficiency. Three main ways have been taken to combat this decrease: one related to the cow, another with the gametes and the lasts related with the environment. The problems associated with cow comprehend the estrous detection problems and the hormonal disorders that results in low conception rates and increases the early embryonic deaths. Alternatives to improve the heat detection has been developed. Among them, the activity meters are a promissory alternative, but still in development. Three experiments were developed in order to assess the efficiency of use of an activity meter in the estrous detection of high producing dairy cows. The first assessed the efficiency of the use of activity meter detecting estrous after the voluntary waiting period (VWP), the second assessed the efficiency of use of activity meter in the detection of the return estrous after use of a fixed-time artificial insemination (TAI) protocol, the third assessed the cost-benefit of acquisition of the system. In the first estrous after the VWP, the activity meter presented higher estrous detection rate, compared with the visual observation. The system has special vantage in the detection of multiparous high producing cows, if compared with visual observation. In the experiment of detecting return estrous after use of TAI, the activity meter detected greater number of animals in less time, however, changes in the pattern of animal behavior caused by hormones during the synchronization, decreased the accuracy of the automated system. On the other hand, the number of animals detected in real estrous of the automated system was superior than in visual observation. In the cost-benefit analysis, the internal rate of return obtained, showed that the activity meter is a profitable investment. Referent to the false positives generated by the system, it is suggested to integrate the indications made by the automated system with the experience of the functionaries of the dairy farms.

A new nanodosimetry-based cell survival model for mixed high- and low-LET radiations has been developed. The new model employs three dosimetry quantities and three biological quantities. The three dosimetry quantities are related to energy depositions at two nanometer scales, 5nm and 25nm. The three biological quantities are related to lesion production and interaction probabilities, and lesion repair rate. The model assumes that the lesions created at the two nanometer scales are directly or indirectly responsible for cell death depending on the lesions interaction and repair rate. The cell survival fraction derived from the new model can be expressed by the familiar dose-dependent linear quadratic formula. The coefficients alpha and beta are based on the three nanodosimetry quantities and the three biological quantities. Validation of the new model has been performed both by using published data and by the experimental data obtained. Published cell survival curves for V-79 Chinese hamster cells irradiated with various LET of radiations were used for validation. The new model was applied to radiation therapy by irradiating V-79 cells with mixed fission neutron and gamma-rays. The results show that the new model has been successfully used in a mixed n+g field to predict the synergistic effect between neutron and gamma-ray lesions and the RBE for fission neutrons.

Cette thèse porte sur les déterminants de la migration des compétences au Liban, dont l'objet principal est l'identification des facteurs et des risques associés à la migration chez les individus hautement qualifiés. La problématique se résume par la question suivante : À formation universitaire égale, quel diplômé devient-il migrant ? Afin de combler le manque de données sur le sujet, nous avons réalisé une enquête (en ligne) auprès des diplômés de la Lebanese American University et de l'Université Saint-Esprit de Kaslik, au Liban. Ces diplômés forment une pluralité et une mixité culturelle, linguistique et socio-économique représentatives des étudiants du Liban. L'objectif de l'enquête était de comparer les similarités et de contraster les différences entre des diplômés migrants et non-migrants, afin de comprendre les logiques différenciées de leurs comportements migratoires. Au début, nous avons effectué une segmentation des diplômés pour les répartir en sous-groupes en fonction de leur statut migratoire, ce qui nous a permis d'identifier et de comprendre les logiques différenciées de leurs comportements migratoires. L'analyse descriptive des résultats de l'enquête révèle des différences en termes de caractéristiques démographiques, économiques et familiales entre diplômés migrants et non-migrants, mais un peu moins de divergences en ce qui concerne leurs parcours universitaires et le domaine des études. À partir de la modélisation, nous avons démontré comment le risque de migrer à l'étranger peut être déterminé par certains facteurs individuels et familiaux, mais surtout en fonction du temps, c'est-à-dire en fonction de la durée depuis l'obtention du diplôme universitaire le plus élevé. Nous démontrons ainsi que, même à formation universitaire égale, le capital humain et le capital social peuvent engendrer des migrations internationales parmi des diplômés ayant effectué un même parcours universitaire et ayant vécu les mêmes conditions socio-économiques au Liban. Nous examinons également des obstacles qui freinent la migration des compétences, pour finalement analyser brièvement les facteurs qui déterminent la migration de retour au Liban. Sur la base de ces conclusions, nous confirmons que nous avons vérifié nos hypothèses par les faits qui se basent sur les résultats de notre enquête. Malgré la difficulté relative à l'étude des migrations internationales en générale et à l'utilisation de la technique de l'enquête en ligne, nous avons réussi à obtenir des résultats très intéressants, que nous avons comparés à des données disponibles sur la migration des compétences au Liban et à l'échelle globale. / This thesis focuses on the determinants of the highly skilled migration in Lebanon whose main purpose is to identify factors and risks associated with migration among highly skilled graduates. The research problem is summarized in the following main question: Given equal level of education, which graduate becomes a migrant? To address the lack of data on this particular topic, we conducted a (online) survey on graduates from the Lebanese American University and the Holy Spirit University of Kaslik in Lebanon. Graduates from both universities form diverse cultural, linguistic and socioeconomic characteristics that are representative of Lebanese graduates in general. The aim of the survey was to compare similarities and contrast differences between migrant and non-migrant graduates in order to understand their diverse behavior with regard to migration. Based on survey results, we carried out a segmentation of graduates and divided them into sub-groups based on their migration status allowing us to understand their behavior with regard to migration. The descriptive analysis of the survey results reveals differences in demographic, economic and family characteristics between migrant and non-migrant graduates, but little divergence were found regarding their university studies and the field of education. We also modeled a number of risks associated with migration and we demonstrated that the risk of migrating could be determined by a number of individual and family factors, but mainly over time, i.e. the time since graduation with the highest university degree. We also demonstrate that even at equal level of education, human capital and social capital can determine international migration among graduates who have obtained the same level of education and experienced the same socio-economic conditions in Lebanon. We have also explored barriers that hinder migration among skilled graduates and briefly analyzed the main factors determining their return migration to Lebanon. Based on these findings we confirm that we have validated our assumptions by facts based on survey results. Despite the relative difficulty in the study of international migration in general and the implementation of online surveys, we managed to obtain very interesting results which we also compared to available data on skilled migration in Lebanon and at the global level.

Health technology assessment: case study on breast carcinoma treatment in the Czech Republic Bc. Lenka Šlegerová January 4, 2019 Abstract This thesis proposes an original method for assessing total costs of med- ical treatment. It defines the semi-Markov model with four states that are associated with specific costs of the treatment, and not with patients' health statuses. This method is applied to individuals' treatment data drawn from the Czech clinical practice in the treatment of the metastatic HER2+ breast cancer. The aim is to assess the cost-effectiveness of adding medication per- tuzumab to the combination of trastuzumab+docetaxel within first-line therapy and to examine whether using individual data on Czech patients and the economic conditions leads to different results from foreign stud- ies. Furthermore, employing censored data from the clinical practice in the thesis complicates the estimation of patients' overall survival in compari- son to clinical-trials data that form random samples. Therefore, survival functions were not only estimated by the Kaplan-Meier estimator but also using the Cox proportional hazard model and the Accelerated failure time model that both control for the effects of included covariates. The addition of pertuzumab does not result in significantly longer pa- tients'...