Com o objetivo de avaliar o atendimento dos pacientes submetidos à intervenção cirúrgica cardiovascular no protocolo de atendimento na via rápida (fast track recovery) em relação ao protocolo convencional, foi comparada a movimentação dos pacientes atendidos em ambos os protocolos nas diferentes unidades hospitalares. O estudo foi realizado em hospital público universitário especializado em cardiologia de 400 leitos, de referência terciária para o Sistema Único de Saúde. Foram estudados 175 pacientes, 107 (61%) homens e 68 (39%) mulheres, de idades entre 2 meses a 81 anos, dos quais 107 operados no protocolo da via rápida e 68 no protocolo convencional. Foram avaliadas variáveis demográficas, clínicas e, para avaliar a movimentação dos pacientes nas diferentes unidades hospitalares, as taxas de alta por unidade de tempo em cada unidade. A análise estatística foi feita por meio de análise exploratória, método de Kaplan Meier e modelo de riscos proporcionais de Cox. A análise de variância foi empregada para comparar o faturamento das despesas. A taxa de alta das diferentes unidades hospitalares por unidade de tempo dos portadores de cardiopatia congênita atendidos no protocolo da via rápida em relação ao protocolo da via convencional foi: a) 11,3 vezes a taxa de alta quando assistidos no protocolo na via convencional quanto ao tempo de permanência no centro cirúrgico; b) 6,3 vezes quanto à duração da intervenção cirúrgica; c) 6,8 vezes quanto à duração da anestesia; d) 1,5 vezes quanto à duração da perfusão; e) 2,8 vezes quanto à permanência na unidade de recuperação pós-operatória I; f) 6,7 vezes quanto à duração da hospitalização; g) 2,8 vezes quanto à permanência na unidade de internação pré-operatória; h) 2,1 vezes quanto à permanência na unidade de internação após a alta da unidade de terapia intensiva de recuperação pós-operatória. Para os portadores de cardiopatia isquêmica, as taxas de alta das unidades hospitalares para os protocolos de atendimento no protocolo da via rápida e no protocolo convencional não demonstraram diferença estatisticamente significante. Os valores de faturamento das despesas de internação dos portadores de cardiopatia congênita decorrentes de exames e procedimentos realizados nas fases pré- e pós-operatória e dos exames da fase trans-operatória foram menores quando os pacientes foram assistidos no protocolo da via rápida. Portanto, os portadores de cardiopatias congênita apresentaram menor permanência hospitalar nos recursos médicos hospitalares instalados, quando assistidos no protocolo de atendimento na via rápida, bem como menores despesas nas fases pré- e pós- operatória da internação. / Objective - To evaluate patient assistance in pre, per and postoperative phases of cardiac surgical intervention under fast track recovering protocol compared to the conventional way. Patients - 175 patients were studied, 107 (61%) men and 68 (39%) women. Ages 2 months to 81 years old. Patients included: first surgical intervention, congenital and ischemic cardiopathy without complexity, normal ventricular function and with at least 2 preoperative ambulatory consultations. Patients submitted to emergency surgeries were excluded. Interventions - assistance submitted by fast track and conventional protocol. Statistical analysis (measures) - exploratory, uni-varied (Kaplan Meier) and multi-varied (Cox) of the time in each admission unit. Hospital installations were classified in ambulatory, preoperative admission unit, surgical center, postoperative recovery unit and postoperative admission unit; the expression of this use was the discharge rate by unit of time from the significant interaction observed between assistance protocol and the kind of cardiopathy for the stay in the surgical center, surgical intervention time, stay in postoperative recovery unit, anesthesia time and time between admission and surgery dates. Results - the patients of congenital cardiopathy who underwent the protocol of conventional way recovery in relation to the fast track protocol, in the reliability range of 95% allows one to state that discharge rate by unit of time of the congenital cardiopathy patients assisted by the fast track protocol was: 11.3 times the discharge rate when assisted by the conventional way protocol as to the time of staying in the surgical center; 6.3 times as to the duration of the surgical intervention; 6.8 times as to duration of the anesthesia; 1.5 times as to the duration of the perfusion; 2.8 times as to the stay in the postoperative recovery unit; 6.7 times as to the stay in the hospital (period of time between the admission and the discharge date); 2.8 times as to the stay in the preoperative admission unit ( period of time between the admission date and the surgery date); 2.1 times as to the stay in the postoperative unit (period of time between the date of leaving the postoperative recovery unit and the date of discharge from the hospital). For the ischemia cardiopathy patients the risks concerning the protocols of recovery by the traditional way and the fast track were the same. CONCLUSIONS - The data concerning this study allows one to suggest that the assistance can be more efficient if one takes into consideration some variables studied in the protocol of fast track recovery. The congenital and ischemic cardiopathy patients presented shorter interval of time (concerning hospital stay in doctor-hospital installed facilities) when assisted in the fast track recovery protocol as well as fewer expenses with medical and hospital assistance.

O diabetes mellitus (DM) é a principal causa de doença renal crônica (DRC) em vários países do mundo. Para pacientes diabéticos com DRC estágio 5 e indicação da terapia renal substitutiva, o transplante (Tx) renal representa uma modalidade terapêutica com técnica bem estabelecida e com excelentes resultados. O transplante simultâneo de rim-pâncreas (TSRP), uma alternativa mais recente praticada em um número mais restrito de centros, apresenta resultados positivos adicionais no controle metabólico, na qualidade de vida e nas complicações crônicas do diabetes. Entretanto, está associado a um risco maior de complicações pós-operatórias e maior número de internações. Tanto o transplante renal quanto o TSRP estão associados a melhor sobrevida do paciente em relação à diálise. A escolha da melhor modalidade de transplante para o paciente diabético com DRC ainda não está clara. O objetivo deste estudo foi analisar os resultados de diferentes modalidades de transplante em pacientes diabéticos com DRC estágio 5, realizados em 3 Centros Brasileiros de Transplante. Assim, analisar a sobrevida do paciente e do enxerto renal após 1, 5 e 8 anos em pacientes DM tipo 1 submetidos a TSRP comparados com transplante renal isolado com doador vivo (DM1-DV) ou transplante de renal isolado com doador falecido (DM1-DF) (Estudo de 3 modalidades de Tx em DM tipo1). Além disso, avaliar em pacientes DM tipo 2, os resultados do transplante renal realizado com doador vivo (DM2-DV) ou doador falecido (DM2-DF) comparados com pacientes DM tipo 1 submetidos ao transplante renal com doador vivo (DM1-DV) ou doador falecido (DM1-DF) (Estudo do Tx em DM tipo 2 vs DM tipo1). Os transplantes foram realizados em 3 Centros de Transplante (Hospital Beneficência Portuguesa, Hospital do Rim e Santa Casa de Porto Alegre). No \"Estudo de 3 modalidades de Tx em DM tipo 1\", foram incluídos 372 transplantes, sendo 262 TSRP, 78 DM1-DV e 32 DM1-DF. No \"Estudo do Tx em DM tipo 2 vs DM tipo 1\", foram incluídos 254 transplantes, sendo 78 DM1-DV, 32 DM1-DF, 61 DM2-DV, 83 DM2-DF. As curvas de sobrevida do paciente e do enxerto renal (Kaplan-Meyer) foram calculadas 1, 5 e 8 anos após o transplante. No \"Estudo de 3 modalidades de Tx em DM tipo 1\", a sobrevida do paciente de receptores de DM1-DV foi significativamente superior comparada com a sobrevida dos receptores de DM1-DF e TSRP no 1º ano (98,7%, 87,5% e 83,2%, respectivamente; p < 0,05) e no 5º ano pós-Tx (90,5%, 70% e 77%, respectivamente; p < 0,05). Não foi observada diferença entre a sobrevida dos pacientes do grupo DM1-DV e TSRP em 8 anos. A sobrevida do enxerto renal foi superior nos receptores DM1-DV no 1º ano pós-Tx, quando comparada com a sobrevida dos receptores DM1-DF e TSRP (96,1%, 84,4% e 80,2%, respectivamente; p < 0,05). Após 5 e 8 anos, a sobrevida do enxerto renal foi semelhante entre os grupos. Ocorreram 90 óbitos durante o período de estudo sendo as principais causas, a infecção (50%) e doença cardiovascular (22%). Óbito com enxerto funcionante e nefropatia crônica do enxerto foram as principais causas de perda do enxerto renal. No \"Estudo do Tx em DM tipo 2 vs DM tipo 1\", como esperado, os pacientes DM tipo 1 eram mais jovens em relação aos pacientes DM tipo 2 (mediana 37,5 e 55 anos, respectivamente; p < 0,0001). Os pacientes transplantados com doador falecido permaneceram maior tempo em tratamento dialítico pré-transplante (mediana 36 meses em DM1-DF e 36 meses em DM2-DF) comparados com pacientes transplantados com doador vivo (mediana 14 meses em DM1-DV e 18 meses em DM2-DV; p < 0,0001). Em pacientes com DM tipo 2, a sobrevida do paciente em 1, 5 e 8 anos nos pacientes DM2-DV foi 95,1%, 87,9% e 81,8%, respectivamente, significativamente maior do que nos pacientes DM2-DF (74,7%, 59,4% e 48,5%, respectivamente; p < 0,01). Em pacientes com DM tipo 1, a sobrevida do paciente em 1, 5 e 8 anos foi 98,7%, 90,5% e 82,1%, respectivamente, significativamente maior do que nos pacientes DM1-DV que nos pacientes DM1-DF (87,5%, 70% e 66,3%, respectivamente; p < 0,01). Comparando-se a sobrevida dos pacientes DM tipo 2 em relação aos DM tipo 1 submetidos a transplante com um mesmo tipo de doador, não foi observado diferença estatisticamente significante. Pacientes do grupo DM2-DV e pacientes DM1-DV apresentaram sobrevidas semelhantes. A sobrevida dos pacientes DM2-DF encontrada foi inferior em relação aos pacientes DM1-DF, porém sem diferença estatística. Em pacientes com DM tipo 2, a sobrevida do enxerto renal em 1, 5 e 8 anos nos pacientes DM2-DV foi 91,8%, 81,2% e 75,3%, respectivamente, significativamente maior do que nos pacientes DM2-DF (73,5%, 54,9% e 44.3%, respectivamente; p < 0,01). Em pacientes com DM tipo 1, a sobrevida do enxerto renal em 1, 5 e 8 anos nos pacientes DM1-DV foi 96,1%, 80,8% e 72,3%, respectivamente, significativamente maior do que nos pacientes DM1-DF (84,4%, 66,8% e 59,3%, respectivamente; p < 0,01) apenas no primeiro ano. Ocorreram 52 óbitos em pacientes DM tipo 2 sendo a infecção principal causa de óbito nos pacientes DM2-DF e a doença cardiovascular a principal causa de óbito nos DM2-DV. Ocorreram 23 óbitos no grupo de pacientes DM tipo 1 e a principal causa foi infecção nos pacientes DM1-DF e a doença cardiovascular nos DM1-DV. A principal causa de perda do enxerto renal foi óbito com enxerto funcionante (74%), seguido pela nefropatia crônica do enxerto (15%). Conclusão: Os resultados do \"Estudo de 3 modalidades de Tx em DM tipo1\" mostraram que em pacientes portadores de DM tipo 1 o transplante renal isolado realizado com doador vivo apresentou resultados superiores em relação às outras modalidades de transplante. Entretanto, em longo prazo, a sobrevida dos pacientes submetidos ao transplante renal com doador vivo não foi estatisticamente diferente do TSRP. Os resultados do \"Estudo do Tx em DM tipo 2 vs DM tipo1\" mostraram que o transplante renal com doador vivo é uma boa opção de terapia renal substitutiva para pacientes com DM tipo 2. Entretanto, os resultados observados nesta análise desencorajam a indicação de transplante renal com doador falecido para pacientes portadores de DM tipo 2, devendo ser indicado apenas em casos selecionados / Diabetes mellitus is the leading cause of chronic kidney disease (CKD) in several countries around the world. For diabetic patients with stage 5 CKD with an indication of renal replacement therapy, renal transplantation is a therapeutic modality with well-established technique and with excellent results. The simultaneous kidney-pancreas transplantation (SPK), a more recent modality of treatment, performed in a limited number of centers, presents additional positive results in metabolic control, quality of life, and chronic complications of diabetes mellitus (DM). However, it is associated with an increased risk of postoperative complications and a higher number of hospitalizations. Both renal and SPK transplantation are associated with better patient survival outcomes compared to dialysis. The choice of the best modality of transplantation for diabetic patients with CKD is not yet clear. The aim of this study was to analyze the results of different modalities of transplant for diabetic patients with CKD stage 5, performed in 3 Brazilian Transplant Centers. More specifically, the aim of this study was to analyze the patient and graft survival after 1, 5, and 8 years post-transplantation in type 1 DM patients submitted to SPK compared with diabetic patients submitted to isolated kidney transplant with living donor (DM1-LD) or deceased donor (DM1-DD) (Study of 3 Tx (transplant) modalities in type 1 DM). In addition, the aim of this study was also to evaluate the results of renal transplantation in type 2 DM performed with living donor (DM2-LD) or deceased donor (DM2-DD) compared with kidney transplantation in type 1 DM performed with living donor (DM2-LD) or deceased donor (DM2-DD) (Study of Tx in type 2 DM vs. type 1 DM). The transplants were performed in 3 Transplant Centers (Hospital Beneficência Portuguesa, Hospital do Rim, and Santa Casa de Porto Alegre). In the \"Study of 3 transplant modalities in type 1 DM\", 372 recipients were included, (262 SPK, 78 DM1-LD, and 32 DM1-DD). In the \"Study of Tx in type 2 DM vs. type 1 DM\", 254 transplants were included, 78 DM1-LD, 32 DM1-DD, 61 DM2-LD, 83 DM2-DD. Patient and graft survival distribution estimates were calculated using the Kaplan-Meier method in the 1, 5 and 8 years post-transplantation. In the \"Study of 3 transplant Tx modalities in type 1 DM\", the patient survival of DM1-LD recipients was significantly higher compared with the survival of DM1-DD and SPK at 1 year (98.7%, 87.5% and 83.2%, respectively; p < 0.05), and at 5 years post-transplantation (90.5%, 70% and 77%, respectively; p < 0.05). After 8 years, there was no significant difference between the survival of patients in group DM1-LD and SPK. The kidney graft survival was higher in DM1-LD, at 1 year, compared with survival of DM1-DD and SPK (96.2%, 84.4% and 80.8%, respectively; p < 0.05). After 5 and 8 years, the kidney graft survival was similar between the groups. There were 90 deaths during the study period and infection (50%) and cardiovascular disease (22%) were the major causes. Death with a functioning graft and chronic allograft nephropathy were the main causes of kidney graft loss. In the \"Study of Tx in type 2 DM vs. type 1 DM\", type 1 DM patients were younger compared to type 2 DM patients (median 37.5 and 55 years, respectively; p < 0.0001). Recipients of deceased donor remained longer time on dialysis before transplantation (median 36 months in DM1-DD, and 36 in DM2-DD) compared with patients transplanted with living donor (median 14 months in DM1-LD and 18 months in DM2-LD, p < 0.0001). In type 2 DM, patient survival at 1, 5 and 8 years in the group DM2-LD was 95.1%, 87.9%, and 81.8, respectively, significantly higher than patient survival in DM2-DD recipients (74.7, 59,4, and 48.5; respectively, p < 0.01). In type 1 DM, patient survival at 1, 5 and 8 years in the group DM1-LD was 98.7%, 90.5% and 82.1%, respectively, significantly higher than patient survival in DM1-DD recipients ( 87.5%, 70%, and 48.5%; respectively, p < 0.01). The comparison between patient survival with type 2 DM and type 1 DM undergoing kidney transplantation with the same type of donor, was not statistically different between the groups. Patient survival in group DM2-LD and DM1-LD was not different. Patient survival in the group DM2-DD was inferior to the group DM1-DD but without significant differences. In type 2 DM, kidney survival at 1, 5 and 8 years in the group DM2-LD was 91.8%, 81 2%, and 75.3%, respectively, significantly higher than patient survival in DM2-DD recipients (73.5%, 54.9%, and 44.3%, respectively, p < 0.01). In type 1 DM, kidney survival at 1, 5 and 8 years in the group DM1-LD was 96.1%, 80.8%, and 72.3%,, respectively, significantly higher than patient survival in DM1-DD recipients (84.4%, 66.8%, and 59.3%, respectively, p < 0.01) only in the first year. In these patients the kidney graft survival was superior in the group DM2-LD compared with DM2-DD. In type 1 DM patients kidney graft survival was 96.1%, 80.8% and 72.3% in patients DM1-LD; 84.4%, 66.8% and 59.3% in patients DM1-DD (p < 0.01); respectively. There were 52 deaths in the group of type 2 DM patients. Infection was the main cause of death in the group DM2-DD, and cardiovascular disease was the main cause in DM2-LD. There were 23 deaths in the group of type 1 DM patients and the main cause was infection in the group DM1-DD and cardiovascular disease in the group DM1-LD. The main cause of kidney graft loss was death with a functioning graft (74%), followed by chronic allograft nephropathy (15%). Patients in group DM2-LD showed good survival rates, particularly in the first year. Conclusion: The \"Study of 3 transplant modalities in type 1 DM\" showed better patient and graft survival with isolated kidney transplantation with living donor compared with others transplant modalities. However, at longer follow up (8 years), survival of patients undergoing living donor kidney transplantation was not statistically different to SPK. In the \"Study of Tx in type 2 DM vs. type 1 DM\", renal transplantation performed with living donor is a good option of renal replacement therapy for type 2 DM. The results observed in this analysis discourage the indication of kidney transplantation with deceased donor for patients with type 2 DM, which should be indicated in selected cases

O câncer de mama é a principal causa de mortalidade por câncer entre as mulheres. Alguns biomarcadores e características clínicas são utilizados para avaliar o prognóstico e prever a resposta a uma série de abordagens terapêuticas. A Homocisteína é conhecida como um fator de risco para doença vascular aterosclerótica, mas sua participação na biologia do câncer ainda é incerta. Cisteína é o aminoácido sulfurado derivado da Homocisteína no ciclo da Metionina. Este ciclo metabólico origina as bases nitrogenadas e também determina o nível de metilação da molécula de DNA. É atualmente reconhecido que a hipometilação global do genoma é um evento chave na transformação maligna das células. O objetivo deste estudo foi avaliar os níveis séricos de homocisteína e cisteína como biomarcadores de sobrevida e de progressão da doença em câncer de mama. Também foi avaliado o efeito de um curso de curta duração (um mês) de tratamento hormonal sobre os níveis de Homocisteína, Cisteína e metilação do DNA. Amostras de sangue foram obtidos por ocasião da biópsia inicial (pré-tratamento) em todas as pacientes e, de tumor e de tecido normal adjacente, ao diagnóstico eem um mês após, para as pacientes que receberam o regime hormonal neo-adjuvante (pré-operatório). Todas as pacientes eram mulheres na pós-menopausa, com tumores de mama ressecáveis, acompanhadas em dois hospitais públicos, que consentiram em participar de outros dois protocolos de pesquisa prévios. Homocisteína e Cisteína foram analisadas por HPLC e a metilação global do DNA do tecido foi determinada por meio da técnica de MSRE (Methylation-Sensitive Restriction Enzyme). Foi observada uma diferença significativa entre os níveis pré e póstratamento de Homocisteína e Cisteína em tumores avançados, sugerindo um papel prognóstico em pacientes com características clínicas reservadas. As variações nos níveis de Homocisteína se mostraram significativamente correlacionadas com a sobrevida livre de doença. O modelo de risco proporcional de Cox demonstrou que os níveis de homocisteína e o status dos linfonodos representaram fatores prognósticos independentes em termos de sobrevida livre de doença. Embora mais estudos sejam necessários para confirmar estes resultados, nossa pesquisa sugere que a Homocisteína pode ser usada como um biomarcador de prognóstico para câncer de mama / Breast cancer is the leading cause of cancer mortality among women. Some biomarkers and clinical features are used to evaluate prognosis and to predict response to a range of therapeutic approaches. Homocysteine is well known as a risk factor in atherosclerotic vascular diseases, but its participation in cancer biology is still unclear. Cysteine is a sulfur amino acid derived from Homocysteine in the Methionine cycle. This metabolic cycle originates the nitrogenous bases and determines the methylation level of the DNA molecule as well. It is currently recognized that the global hipomethylation of the genome is a key event in the malign transformation of cells. The aim of this study was to evaluate serum Homocysteine and Cysteine as biomarkers of survival and disease progression in breast tumor, as well as the methylation status of tumor and normal tissues. The effect of a short course (one month) of hormonal treatment on Homocysteine, Cysteine and DNA methylation levels was also evaluated. Blood samples were collected during the initial biopsy (pretreatment) in all patients and, tumor samples and normal adjacent tissue, at diagnosis and one month after, for the patients that received neo-adjuvant hormonal regimen (pre-treatment). All patients were post-menopausal women, with resectable breast tumors, followed at two public hospitals, and that had consented to participate in two previous research protocols related to their disease. Serum Homocysteine and Cysteine were analyzed by HPLC and tissue global DNA methylation was determined by the MSRE (Methylation- Sensitive Restriction Enzyme) technique. A significant difference was observed between pre- and post-treatment levels of Homocysteine and Cysteine in advanced tumors, suggesting a prognostic role in patients with poor clinical characteristics. Variations in Homocysteine levels were significantly correlated with disease free survival. Cox proportional risk model demonstrated that nodal status and Homocysteine levels were independent prognostic factors for Disease Free Survival. Although more studies are needed to confirm these results, our research suggests that Homocysteine might be used as a prognostic biomarker for breast cancer

La question démographique, occupant une place centrale au coeur du conflit qui sévit en Israël et en Palestine, a fait couler beaucoup d’encre. De nombreux chercheurs issus de disciplines telles que la sociologie, la science politique ou même la philosophie ont contribué à la compréhension des origines de ce conflit et de ses conséquences sur les populations humaines. Il va sans dire que les enjeux qui y sont associés sont nombreux et que, pour les comprendre de manière exhaustive, l’interaction de nombreuses disciplines est requise. Puisqu’il s’agit ici d’une thèse en démographie, nous nous limitons aux aspects démographiques du conflit israélo-palestinien. De nombreux ouvrages rigoureux dans d’autres disciplines sont disponibles pour une approche plus holistique. La fécondité exceptionnelle observée dans la région est souvent associée à une “guerre des berceaux” visant ultimement à obtenir la majorité sur le territoire. Plusieurs théories visant à lier fécondité et contexte politique ont émergé dans la littérature démographique mais aucune d’entre elles n’a été vérifiée empiriquement à la fois auprès des populations palestiniennes et juives (en Israël et dans les territoires palestiniens de la Cisjordanie et Gaza). Ainsi, dans la poursuite de cette thèse, nous souhaitons explorer des avenues qui nous permettraient d’enrichir la connaissance des dynamiques de fécondité dans la région et contribuer à l’effort collectif visant à mieux évaluer les conséquences d’un conflit endémique sur les comportements reproductifs. Le premier objectif de cette thèse par articles consiste à dresser un bilan de l’état de la fécondité chez les Juives et les Palestiniennes demeurant en Israël et dans les territoires palestiniens en accordant un intérêt particulier à certains déterminants de la fécondité tels que : la contraception, l’âge au mariage, l’origine ethnique et la religiosité. Tout en prenant en considération l’importante hétérogénéité des groupes d’intérêt, nous cherchons à établir certaines similitudes entre Palestiniennes et Juives d’Israël et des territoires palestiniens, qui sont exposées, à des niveaux variables, aux conséquences du conflit. Il s’agit d’une première tentative afin de regrouper ces individus dans une même étude à l’aide de données d’enquêtes. En second lieu, nous visons à faire la lumière sur les différents comportements de fécondité des Juives en Israël et dans les colonies des territoires palestiniens afin de départager les effets des principaux déterminants de la fécondité israélienne (nationalisme, religiosité et statut socioéconomique) dans les deux régions et leurs évolutions temporelles grâce à des données de recensement. Bien que de nombreuses études se soient penchées sur la fécondité israélienne au niveau national, peu se sont attardées à étudier la sous-population constituée par les colons juifs qui demeure, par conséquent, largement méconnue. Finalement, nous nous intéressons à l’influence exercée par des facteurs individuels et contextuels sur la fécondité des Palestiniennes en Cisjordanie et à Gaza. Nous tentons de quantifier les effets du contexte et du nationalisme sur la fécondité. L’objectif consiste principalement à analyser les facteurs liés à la fécondité palestinienne en mettant l’accent sur le rôle des variables contextuelles tout en prenant en compte les divers facteurs socioéconomiques et démographiques. Bien que le conflit soit régulièrement invoqué dans l’explication de la fécondité palestinienne, aucune étude n’a encore démontré empiriquement son rôle. Les conclusions de cette thèse apportent un éclairage important à la recherche sur la fécondité dans cette région. En effet, il en ressort que les déterminants habituels de la fécondité ne semblent pas avoir un impact majeur sur la fécondité. Cette relative inefficacité des déterminants “classiques” de la fécondité s’expliquerait en partie par des conséquences du conflit. Il en découle une religiosité accrue dans de nombreuses tranches de la population, un fort sentiment nationaliste et des institutions qui veillent à éliminer les obstacles à la fécondité grâce à de nombreux incitatifs fiscaux. Dans un climat social et politique incertain, les valeurs traditionnelles familiales procurent une certaine stabilité. / Demography is central to the Israeli-Palestinian conflict and the consequences of high Palestinian and Israeli fertility have interested many scientists, as population balance is a key determinant in a potential peace settlement. Many researchers from various disciplines such as sociology, political science, or even philosophy contributed to the general understanding of the origins of the conflict and of its consequences on human populations. It goes without saying that to fully understand the issues and consequences of the conflict, a multidisciplinary approach is required. However, because this is a thesis in demography, we limit ourselves to the demographic aspects of the Israeli-Palestinian conflict. For a more holistic approach, many important works are available. The exceptionally high fertility in the region is often described as a “war of the cradles” ultimately aimed at gaining majority over the land. Such theories implying a political fertility have never been tested empirically simultaneously on both Palestinian Arabs and Jews (in Israel and the settlements in the Palestinian territories). The objective of this thesis is thus to explore different avenues allowing to expand knowledge on fertility dynamics in the region and to contribute to the existing literature on the demography of conflict and more precisely, on the consequences of an endemic conflict on fertility behaviour. In the first of three articles, we are producing a descriptive portrait of fertility among Israelis and Palestinians living in Israel and the Palestinian territories of the West Bank and Gaza Strip with a particular interest for a number of fertility determinants such as contraception, age at marriage, immigration, and religiosity among others. Despite a clear heterogeneity between the subgroups, we aim at finding some resemblances among them, all exposed at different intensities to the consequences of the Israeli-Palestinian conflict. This represents the first attempt to analyze all groups in the same project using survey data. The aim of the second article is to highlight the differences in fertility behaviour of the Jewish population living in Israel and to that of the Jewish population living in the settlements of the West Bank and Gaza Strip and to distinguish the effects of various determinants of Israeli fertility (nationalism, religiosity, and socioeconomic status) in both regions and over time using data from the 1995 and 2008 censuses. Even though many articles have studied the impact of such determinants of fertility in Israel, none yet has put the emphasis on the largely unknown settler population that has a significantly higher fertility than their counterparts in Israel. In the last article, we are interested in quantifying the impact of individual and contextual factors on Palestinian fertility in the West Bank and Gaza Strip. We thus specifically evaluate the impact of contextual variables (number of checkpoints and year of violent uprising) and nationalism (proportion of Jewish settlers living in the same district) associated with the conflict while controlling for various socioeconomic and demographic variables often used in fertility studies. Even though the consequences of the conflict are often brought up as an explanation for the high Palestinian fertility, no research has tried to empirically test the validity of such hypotheses using survey data. This thesis brings important contributions to the literature on fertility in this region. Indeed, it appears a though the usual determinants of fertility change do not seem to have an important effect on these populations. The inefficiency of such determinants can be partly explained by the consequences of the conflict. They led to an increased religiosity among many population groups, to a strong nationalist sentiment, and to institutions trying to alleviate most of the obstacles to fertility by generous fiscal incentives. In an uncertain social and political climate, traditional values such as family provide stability.

Dans cette thèse, nous étudions des modèles définis par des équations de moments conditionnels. Une grande partie de modèles statistiques (régressions, régressions quantiles, modèles de transformations, modèles à variables instrumentales, etc.) peuvent se définir sous cette forme. Nous nous intéressons au cas des modèles avec un paramètre à estimer de dimension finie, ainsi qu’au cas des modèles semi paramétriques nécessitant l’estimation d’un paramètre de dimension finie et d’un paramètre de dimension infinie. Dans la classe des modèles semi paramétriques étudiés, nous nous concentrons sur les modèles à direction révélatrice unique qui réalisent un compromis entre une modélisation paramétrique simple et précise, mais trop rigide et donc exposée à une erreur de modèle, et l’estimation non paramétrique, très flexible mais souffrant du fléau de la dimension. En particulier, nous étudions ces modèles semi paramétriques en présence de censure aléatoire. Le fil conducteur de notre étude est un contraste sous la forme d’une U-statistique, qui permet d’estimer les paramètres inconnus dans des modèles généraux. / In this dissertation we study statistical models defined by condition estimating equations. Many statistical models could be stated under this form (mean regression, quantile regression, transformation models, instrumental variable models, etc.). We consider models with finite dimensional unknown parameter, as well as semiparametric models involving an additional infinite dimensional parameter. In the latter case, we focus on single-index models that realize an appealing compromise between parametric specifications, simple and leading to accurate estimates, but too restrictive and likely misspecified, and the nonparametric approaches, flexible but suffering from the curse of dimensionality. In particular, we study the single-index models in the presence of random censoring. The guiding line of our study is a U-statistics which allows to estimate the unknown parameters in a wide spectrum of models.

L’esclavage des Autochtones et des Noirs au Canada français est peu connu dans l’historiographie. Ce mémoire comble les lacunes de la littérature démographique existante sur cette population marginalisée en estimant la mortalité des esclaves avec les techniques de l’analyse des transitions. Au travers de ces analyses, ce mémoire répond à la question suivante : quelle est l’intersection du genre et de l’ethnie dans le risque de mortalité des esclaves du Québec ancien entre 1632 et 1834 ? Pour y parvenir, j’ai créé la BDPEQA (Base de données de la population esclave du Québec ancien) à partir des données qualitatives compilées dans le Dictionnaire des esclaves et leurs propriétaires par Marcel Trudel (1990). Une analyse descriptive des données de la BDPEQA montre que la population esclave du Québec ancien de 1632 à 1834 est composée à 65% d’esclaves autochtones et 35% d’esclaves noirs. Ces esclaves vivent surtout à Montréal et la moitié d’entre eux vivent sous le régime français. Ensuite, un calcul des médianes au décès et une analyse de survie est effectuée à l’aide des courbes de survie de Kaplan Meier et des régressions multivariées effectuées avec la méthode de Cox, pour évaluer l’association entre le risque de décès avant 40 ans et l’ethnie, le genre, la zone de résidence, les épidémies ainsi que les périodes. On découvre alors que les Autochtones décèdent à un âge médian de 17 ans et les Noirs à un âge médian de 40 ans. Cette étude démontre aussi que les hommes autochtones sont les esclaves les plus à risque de décéder jeunes, peu importe le milieu de vie, la période ou les épidémies. / The enslavement of Indigenous peoples and persons of African origin by French Canadians is seldom addressed in the historical demography of Québec. Even less is known of the mortality patterns of these two groups. This master’s mémoire fills the gaps in the existing demographic literature on this marginalized population, by estimating slaves’ mortality risk with event history analysis. Through these analyses, this master’s mémoire answers the following question: what was the role of gender and ethnicity in determining slaves’ mortality risk? To achieve this objective, I compiled biographical information about the enslaved population of Québec in the BDPEQA (Database of the slaves in ancient Quebec) from qualitative data in the Dictionnaire des esclaves et leurs propriétaires by Marcel Trudel in 1990. A descriptive analysis of the BDPEQA data shows that the enslaved population of Québec from 1632 to 1834 is composed of 65% Indigenous peoples and 35% Blacks, lived mainly in Montréal, and during the French regime. Descriptive analyses of biographical data from the BDPEQA (with Kaplan-Meier survival curves and median ages at death) as well as Cox regression models of slaves’ risk of death before age 40 indicate that Black slaves had better survival chances than their Indigenous counterparts. Indeed, Indigenous slaves had a median age at death of 17 years compared to 40 years for Black slaves. In addition, Indigenous men have the highest risk of dying, regardless of living environment, period or observation or exposure to epidemics.

Indiana University-Purdue University Indianapolis (IUPUI) / Joint models of longitudinal and survival outcomes have been used with increasing frequency in clinical investigations. Correct specification of fixed and random effects, as well as their functional forms is essential for practical data analysis. However, no existing methods have been developed to meet this need in a joint model setting. In this dissertation, I describe a penalized likelihood-based method with adaptive least absolute shrinkage and selection operator (ALASSO) penalty functions for model selection. By reparameterizing variance components through a Cholesky decomposition, I introduce a penalty function of group shrinkage; the penalized likelihood is approximated by Gaussian quadrature and optimized by an EM algorithm. The functional forms of the independent effects are determined through a procedure for structural discovery. Specifically, I first construct the model by penalized cubic B-spline and then decompose the B-spline to linear and nonlinear elements by spectral decomposition. The decomposition represents the model in a mixed-effects model format, and I then use the mixed-effects variable selection method to perform structural discovery. Simulation studies show excellent performance. A clinical application is described to illustrate the use of the proposed methods, and the analytical results demonstrate the usefulness of the methods.

Survival analysis is a subfield of statistics where the goal is to analyse and model the data where the outcome is the time until the occurrence of an event of interest. Because of the intrinsic temporal nature of the analysis, the employment of more recently developed sequential models (Recurrent Neural Network (RNN) and Long Short Term Memory (LSTM)) has been paired with the use of dynamic temporal features, in contrast with the past reliance on static ones. Such an abrupt shift of policy has left open the challenge of understanding how those two kinds of features influence the predictive capabilities of models. This thesis aims at assessing the effect of combining static and dynamic features on the most commonly used models in survival analysis. In doing so, we compare the error measurements of such models with dataset composed of purely dynamic features or a combination of static and dynamic ones. Empirical measurements have shown that models respond differently to the addition of static features to the analysis, with more complex, sequential models like the LSTM struggling to deal with the added data complexity (with a 12% increase in error), while non sequential models see reductions of up to 14.7% in error. The thesis also includes a clusterization task aimed at aiding the interpretation of survival analysis outcomes. / Överlevnadsanalys är ett delområde inom statistiken där målet är att analysera och modellera data där utfallet är tiden fram till dess att en händelse av intresse inträffar. På grund av analysens inneboende tidsmässiga karaktär har användningen av mer nyligen utvecklade sekventiella modeller (RNN och LSTM) kombinerats med användningen av dynamiska tidsmässiga egenskaper, i motsats till den tidigare förlitningen på statiska sådana. En sådan drastisk förändring av ansatsen har lämnat öppet för utmaningen att förstå hur dessa två typer av egenskaper påverkar modellernas förutsägande förmåga. Syftet med denna uppsats är att bedöma effekten av att kombinera statiska och dynamiska egenskaper på de vanligaste modellerna för överlevnadsanalys. I detta syfte jämför vi felmätningar av sådana modeller med dataset som består av rent dynamiska egenskaper eller en kombination av statiska och dynamiska egenskaper. Empiriska mätningar har visat att modellerna reagerar olika på tillägget av statiska egenskaper till analysen, där mer komplexa, sekventiella modeller som LSTM kämpar för att hantera den ökade datakomplexiteten (med en ökning av felet med 12 %), medan icke-sekventiella modeller ser en minskning av felet med upp till 14,7 %. Uppsatsen innehåller också en klusteruppgift som syftar till att underlätta tolkningen av resultaten av överlevnadsanalyser. / L’analisi della sopravvivenza è una branca della statistica il cui obiettivo è l’analisi e la modellazione di dati il cui risultato è il tempo che intercorre fino al verificarsi di un evento di interesse. A causa dell’intrinseca natura temporale dell’analisi, l’impiego di modelli sequenziali di più recente sviluppo (RNN e LSTM) è stato abbinato all’uso di attributi temporali dinamici, a differenza dell’uso più diffuso in passato di attributi statici. Questo brusco cambiamento ha lasciato aperta la sfida di capire come questi due tipi di attributi influenzino le capacità predittive dei modelli. Questa tesi si propone di valutare l’effetto della combinazione di attributi statici e dinamici sui modelli più comunemente utilizzati nell’analisi della sopravvivenza. A tal fine, confrontiamo le misure di errore di tali modelli con set di dati composti da attributi puramente dinamici o da una combinazione di statici e dinamici. I risultati empirici hanno mostrato che i modelli rispondono in modo diverso all’aggiunta di attrbiuti statici, con i modelli sequenziali più complessi, come l’LSTM, che faticano a gestire la complessità dei dati aggiunti (con un aumento dell’errore del 12%), mentre i modelli non sequenziali registrano riduzioni dell’errore fino al 14,7%. La tesi comprende anche una clusterizzazione volta a facilitare l’interpretazione dei risultati dell’analisi di sopravvivenza.

Breast cancer, as the most prevalent cancer in women, is responsible for more than 15% of new cancer cases and about 6.9% of all cancer-related death in the US. A major cause of therapeutic failure in breast cancer is the development of resistance to chemotherapy, especially for triple-negative breast cancer (TNBC). Therefore, how to overcome chemoresistance is the major challenge to improve the life expectancy of breast cancer patients. Our studies demonstrate that TNBC cells surviving the chronic treatment of chemotherapeutic drugs show significantly higher expression of the dual serine/threonine and tyrosine protein kinase (DSTYK) than non-treated parental cells. In our in vitro cellular models, DSTYK knockout via the CRISPR/Cas9-mediated technique results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, DSTYK knockout promotes chemotherapeutic drug-induced tumor cell death in an orthotopic mouse model. These findings suggest that DSTYK exerts an important and previously unknown role in promoting chemoresistance. Our studies provide fundamental insight into the role of DSTYK in chemoresistance in TNBC cells and lay the foundation for the development of new strategies targeting DSTYK for improving TNBC therapy.

Today there exists two types of preventive surgical treatment procedures for Abdominal Aortic Aneurysm. In order to make an informed choice of treatment, the clinician needs to have a clear picture of how the choice will affect the patients chances of survival. In this master thesis, machine learning techniques are used to predict survival probabilities after respective treatment procedure and the performance is compared to the more conventional Kaplan-Meier estimator.  Using Danish patient data, different machine learning models for survival predictions were trained and evaluated by their performance. Administrative Brier Score was used as performance metric as the data was administratively censored. An Ensemble model consisting of one Random Survival Forest and one Neural Multi Task Logistic Regression model was shown to achieve the best performance and significantly outperformed the conventional Kaplan-Meier model. Furthermore, an approach to investigate the predicted effects of choice of treatment was introduced. It showed that on average the Ensemble model predicted the choice of treatment to have less effect on the long term survival than what the corresponding prediction using the Kaplan-Meier estimator suggested. This applies to the full patient group as well as for patients of age between 70 and 79 years. In the latter case this prediction was also shown to be more accurate. / Idag finns det två typer av förebyggande kirurgiska behandlingsmetoder för abdominal aortaaneurysm. För att göra ett välgrundat val av behandlingsmetod måste läkaren ha en tydlig bild av hur valet kommer att påverka patienternas överlevadschanser. I detta examensarbete används maskininlärningstekniker för att förutsäga överlevnadssannolikheten efter respektive behandlingsmetod och prestandan jämförs mot den mer konventionella Kaplan-Meier-estimatorn. Med hjälp av dansk patientdata tränades olika maskininlärningsmodeller avsedda för överlevnadanalys och utvärderades utifrån deras prestanda. Administrativt Brier Score användes som mätvärde då censureringen i datan skett administrativt. En Ensemble-modell bestående av en Random Survival Forest- och en Neural Multi-Task Logistic Regression-modell visade sig uppnå bäst prestanda och överträffade signifikant den konventionella Kaplan-Meier-estimatorn.  Dessutom introducerades ett tillvägagångssätt för att undersöka de predikterade effekterna av valet av behandling. Resultaten visade att Ensemble-modellen i genomsnitt förutspådde valet av behandling att ha mindre effekt på den långsiktiga överlevnaden än vad motsvarande förutsägelse med Kaplan-Meier-estimatorn föreslog. Detta både för alla patienter såväl som för patienter i åldern mellan 70 och 79 år. I det senare fallet visade sig denna förutsägelse också vara mer träffsäker.