Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-01-21T18:23:30Z No. of bitstreams: 1 robertawolpdiniz.pdf: 1863742 bytes, checksum: 6c164077a0182789343f2f09aa65af87 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-01-25T18:48:13Z (GMT) No. of bitstreams: 1 robertawolpdiniz.pdf: 1863742 bytes, checksum: 6c164077a0182789343f2f09aa65af87 (MD5) / Made available in DSpace on 2016-01-25T18:48:13Z (GMT). No. of bitstreams: 1 robertawolpdiniz.pdf: 1863742 bytes, checksum: 6c164077a0182789343f2f09aa65af87 (MD5) Previous issue date: 2014-09-12 / O câncer de mama é um problema de saúde pública, sendo o segundo mais frequente no mundo e o de maior incidência na população feminina, além de ser uma das principais causas de óbito por câncer em mulheres. O objetivo deste estudo foi analisar a sobrevida livre de doença (SLD) em cinco anos e fatores prognósticos em mulheres com câncer de mama invasivo não metastático diagnosticadas entre 2003 e 2005 e tratadas em centro de assistência oncológica de referência de cidade de porte médio do Sudeste do país. As pacientes foram identificadas através do registro hospitalar de câncer da instituição. O seguimento dos casos foi realizado através de consulta aos prontuários, complementado por busca no banco do Sistema de Informação sobre Mortalidade (SIM) e contato telefônico. As variáveis analisadas foram distribuídas nos seguintes blocos: sociodemográficas (idade ao diagnóstico, cor da pele, grau de escolaridade, história familiar de câncer de mama, etc.), características relativas ao tumor (tamanho tumoral, comprometimento linfonodal, estadiamento, invasão neurovascular, grau tumoral, perfil imunohistoquímico, etc.), características relativas ao tratamento (tipo de cirurgia, realização de quimioterapia, radioterapia e hormonioterapia, completude do tratamento quimioterápico, tempo entre a cirurgia e terapia complementar, etc.). As funções de sobrevida foram calculadas por meio do método de Kaplan-Meier e o modelo de riscos proporcionais de Cox foi utilizado para avaliação dos fatores prognósticos. O estudo mostrou uma sobrevida livre de doença em cinco anos de 72% (IC95%: 67,6 – 75,9). As principais variáveis associadas à SLD, de forma independente, foram o comprometimento linfonodal, a realização de hormonioterapia e nível de escolaridade. Esse estudo mostrou a importância do diagnóstico precoce na SLD. Reforça-se ainda a relevância dessa pesquisa no país haja vista a escassez de estudos a respeito de SLD na população brasileira. / Breast cancer is a public health problem, being the second most common in the world and the highest incidence in the female population, in addition to being a major cause of death from cancer in this population overall. The aim of this study was to analyze the disease-free survival (DFS) at five years and prognostic factors in women with non metastatic invasive breast cancer diagnosed between 2003 and 2005 and treated at a referencial center of cancer care on a medium sized town of Southeast. Patients were identified using the medical records and data from the cancer registries of the institution. The follow up of the cases were performed using hospital records, supplemented by searching the database of the Mortality Information System (SIM) and telephone contact. The variables analyzed were: sociodemographic (age at diagnosis, race, education level, family history of breast cancer and presence of diagnostic mammography), related to tumor characteristics (size, lymph node involvement, stage, neurovascular invasion, tumor grade, immunohistochemical profile), characteristics related to treatment (type of surgery, use of chemotherapy, radiotherapy and hormone therapy, completion of chemotherapy, time between surgery and adjunctive therapy). Survival functions were calculated using the Kaplan-Meier model while the Cox proportional hazards method was used to evaluate prognostic factors. The study showed a disease-free survival at 60 months 72% (95% CI 67.6 to 75.9). The main variables associated with SLD, independently, were lymph node involvement, use of hormone therapy and degree of schooling. This study showed the importance of early diagnosis in DFS. This research is relevant due the lack of studies regarding the DFS at the Brazilian population.

[EN] The global objective of the present thesis was to study the functional longevity defined as length of productive life (LPL) in five Spanish specialized lines of rabbit (A, V, H and LP). Chapter 3, aimed to check the genetic heterogeneity for longevity between the five lines estimating the additive variance and the corresponding effective heritabilities. As well as to test the genetic importance of time-dependent factors such as positive palpation order (OPP), physiological status (PS) and number of kits born alive (NBA) on the genetics of longevity. This point has been assessed using four different Cox proportional hazard models; the first one (Model 1) included all the previous factors in addition to the year-season effect, the inbreeding coefficient effect and finally the animal effect as random factor. The remaining three models were the same as Model 1 but excluding OPP (Model 2), or PS (Model 3), or NBA (Model 4). The complete data set comprised 15,670 does with records 35.6 % having censoring data, and the full pedigree file involved 19,405 animals. The heritability estimates for longevity in the five lines were low and ranged from 0.02±0.01 to 0.14±0.09, and consequently, it is not recommended to include this trait as selection criteria in rabbit breeding programs. Despite of the large variation of the heritability estimates, the corresponding HPD95% always overlapped and consequently the hypothesis of all lines having the same heritability cannot be discarded. Comparing the additive variance estimates of the four models, it was observed that by correcting for PS 51, 39, 38, 83 and 75% of the additive variance in lines A, V, H, LP and R, respectively, was removed. The risk of death or culling decreases as OPP advanced. Non-pregnant-non-lactating females are those under the higher risk. The does which had zero NBA had the highest risk, apart for this special figure (zero NBA) the risk decreased as NBA increased. Chapter 4 intended to estimate the genetic and environmental correlations between longevity and two prolificacy traits (number of kits born alive (NBA) and number of kits alive at weaning (NW)). Furthermore, to estimate the genetic and environmental correlations between longevity and the percentage of days that the doe spent in the different physiological statuses with respect to its entire productive life. The complete pedigree file comprised 19,405 animals. The datasets included records on 15,670 does which had 58,329 kindlings and 57,927 weanings. In general the genetic correlations between NBA and NW, and the hazard were low to very low, and the only line for which it can be said these genetic correlation to be different from zero was the LP line. Regarding the correlations between longevity and the percentage of days the doe spent in each physiological status, there were evidences of non-negligible genetic correlations between the two traits. Chapter 5 purposed to compare the five lines at their foundation and at fixed time periods during their selection programs. The first comparison was done at the origin of the lines, involving the complete data set, and using a genetic model (CM) including the additive values of the animals, so the effect of selection was considered. For the second comparison the same model as the first comparison was used, but excluding the additive effects from the model of analysis (IM), and involving only the data corresponding to each period, so the differences between the lines included the additive values of the animals. The lines V, H and LP showed at foundation a substantial superiority over line A. The line R had higher risk of death or culling with relevant differences when compared to V, H and LP lines. The maximum relative risks were observed between the lines LP and R (0.239), and between LP and A (0.317). For the comparisons at fixed times, the pattern of the differences between the A line and the others was similar to those observed at foundation. / [ES] El objetivo global de la presente tesis fue estudiar la longevidad funcional en cinco líneas españolas de conejos (A, V, H y LP), el carácter se definió como la longitud de la vida productiva. En el Capítulo 3, dirigido a comprobar la heterogeneidad genética de la longevidad entre las 5 líneas, se estimaron las varianzas aditivas y sus correspondientes heredabilidades efectivas. Y además se evaluó la importancia del orden de la palpación positiva (OPP), el estado fisiológico (PS) y el número de gazapos nacidos vivos (NBA) sobre el determinismo genético de la longevidad. Para ello se utilizaron 4 modelos de Cox de riesgos proporcionales; el primer modelo (Modelo 1) incluyó todos los factores anteriores, además del efecto del año-estación, el efecto de la consanguinidad y, finalmente, el valor aditivo de los animales como efecto aleatorio. Los otros tres modelos fueron igual que el Modelo 1 pero excluyendo OPP (Modelo 2), o PS (Modelo 3), o NBA (Modelo 4). Los datos de longevidad estaban referidos a 15,670 conejas y tuvieron una tasa de censura de 35.6%. La genealogía completa involucró a 19,405 animales. Las estimas de heredabilidad efectiva para la longevidad en las 5 líneas fueron bajas y variaron de 0.02±0.01 a 0.14±0.09. A pesar de la gran variación de las estimas puntuales de heredabilidad, los correspondientes intervalos HPD95% siempre se solaparon y por lo tanto la hipótesis de que todas las líneas tengan la misma heredabilidad no pudo descartase. Se observó que la exclusión de PS incrementó la varianza aditiva aproximadamente, en un 51, 39, 38, 83 y 75% en las líneas A, V, H, LP y R, respectivamente. El riesgo de muerte o eliminación disminuía a medida que avanzaba el OPP, observándose el riesgo más alto durante los primeros dos partos, partos en los que las conejas todavía están creciendo lo que sería un factor de riesgo importante. El nivel No-Gestante-No-Lactante de PS tuvo el mayor riesgo. Este nivel se interpreta como indicador de baja fertilidad y/o problemas de salud de la coneja. Las conejas que tenían cero NBA tuvieron el mayor riesgo de muerte o eliminación, aunque para el resto de niveles de NBA se apreció una disminución del riesgo a medida que aumenta la prolificidad. En el capítulo 4, se estimaron las correlaciones genéticas y ambientales entre la longevidad y dos caracteres de prolificidad [número de gazapos nacidos vivos (NBA) y el número de destetados (NW)]. El fichero de datos incluyó 58,329 partos y 57,927 destetes. También se estimaron las correlaciones entre longevidad y el porcentaje de días que la coneja pasó en los diferentes estados fisiológicos con respecto a la totalidad de su vida productiva. La única línea para la que se puede decir que la correlación genética entre NBA o NW y el riesgo fue significativamente diferente de cero fue la línea LP. Hubo evidencias de correlaciones genéticas no despreciables entre la longevidad y el porcentaje de días que la hembra pasó en cada estado fisiológico los dos caracteres. En el capítulo 5 se compararon las longevidades medias de las 5 líneas en su fundación y en períodos de tiempo determinados. La comparación de las líneas en el origen, utilizó todos los datos y un modelo genético (CM) que incluía los valores aditivos de los animales. Para la comparación en tiempos fijos se utilizó el mismo modelo, pero excluyendo los efectos aditivos del modelo de análisis (IM), utilizando sólo los datos correspondientes a cada período, por lo que las diferencias entre las líneas incluían los cambios debidos a la selección. Las líneas V, H y LP mostraron una superioridad sustancial sobre las líneas A y R. Los riesgos relativos máximos se observaron entre las líneas LP y R (0.239), y entre LP y A (0.317). Con respecto a las comparaciones en tiempos fijos, el patrón de las diferencias entre la línea de A y las otras líneas fue similar a los observados en la fundación. / [CAT] L'objectiu global de la present tesi va ser estudiar la longevitat funcional en cinc línies espanyoles de conills (A, V, H i LP), el caràcter es va definir com la longitud de la vida productiva. Al Capítol 3, dirigit a comprovar l'heterogeneïtat genètica de la longevitat entre les 5 línies, es van estimar les variàncies additives i les seues corresponents heretabilitats efectives. A més a més, es va avaluar la importància de factors dependents del temps, com l'orde de la palpació positiva (OPP) , l'estat fisiològic (PS) i el nombre de llorigons nascuts vius (NBA) sobre el determinisme genètic de la longevitat. Per a això es van utilitzar 4 models de Cox de riscos proporcionals; el primer model (Model 1) va incloure tots els factors anteriorment assenyalats, a més de l'efecte de l'any-estació, l'efecte de la consanguinitat i, finalment, el valor additiu dels animals com a efecte aleatori. Els altres tres models van ser igual que el Model 1 però excloent l'OPP (Model 2) , o PS (Model 3) , o NBA (Model 4) . Les dades de longevitat estaven referides a 15,670 conilles i van tindre una taxa de censura de 35.6%. La genealogia completa va involucrar a 19,405 animals. Les estimes d'heretabilitat efectiva (Model 1) per a la longevitat en les 5 línies van ser baixes i van variar de 0.02±0.01 a 0.14±0.09. A pesar de la gran variació de les estimes puntuals d'heretabilitat, els corresponents intervals HPD95% sempre es van solapar i per tant la hipòtesi que totes les línies tinguen la mateixa heretabilitat no va poder descartar-se. Es va observar que l'exclusió de PS va incrementar la variància additiva, aproximadament, en un 51, 39, 38, 83 i 75% en les línies A, V, H, LP i R, respectivament. El risc de mort o eliminació disminuïa a mesura que avançava l'OPP, observant-se el risc més alt durant els primers dos parts, en què les conilles encara estan creixent el que seria un factor de risc important. El nivell No-Gestant-No-Lactant de PS va tindre el major risc en comparació amb els altres nivells. Les conilles que tenien zero NBA van tindre el major risc de mort o eliminació, encara que per a la resta de nivells de NBA es va apreciar una disminució del risc a mesura que augmentà la prolificitat. Al Capítol 4, es van estimar les correlacions genètiques i ambientals entre la longevitat i dos caràcters de prolificitat [nombre de llorigons nascuts vius (NBA) i el nombre de deslletats (NW)]. El fitxer de dades va incloure 58,329 parts i 57,927 deslletaments. L'única línia per a la que es pot dir que la correlació genètica entre NBA o NW i el risc va ser significativament diferent de zero va ser la línia LP. Evidències de correlacions genètiques no menyspreables entre longevitat i els percentatge de dies que la femella va passar en cada estat fisiològic. Al Capítol 5 es compararen les longevitats mitges de les 5 línies en la seua fundació i en períodes de temps determinats. Per a la comparació de les línies a l'origen, es van utilitzar totes les dades i un model genètic (CM) que incloïa els valors additius dels animals, per la qual cosa es va considerar l'efecte de la selecció a partir de la fundació. En la comparació en temps fixos se va utilitzar el mateix model que en l'anterior, però excloent els efectes additius del model d'anàlisi (IM), utilitzant només les dades corresponents a cada període, per la qual cosa les diferències entre les línies incloïen els canvis deguts a la selecció. Les línies V, H i LP van mostrar una superioritat substancial sobre les línies A i R. Els riscos relatius màxims es van observar entre les línies LP i R (0.239), i entre LP i A (0.317). Respecte a les comparacions en temps fixos, el patró de les diferències entre la línia de A i les altres línies va ser semblant als observats en la fundació. / El Nagar, AGF. (2015). Genetic analysis of longevity in specialized lines of rabbits [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/52390 / TESIS

Millions of people in the United States alone suffer from undiagnosed or late-diagnosed chronic diseases such as Chronic Kidney Disease and Type II Diabetes. Catching these diseases earlier facilitates preventive healthcare interventions, which in turn can lead to tremendous cost savings and improved health outcomes. We develop algorithms for predicting disease occurrence by drawing from ideas and techniques in the field of machine learning. We explore standard classification methods such as logistic regression and random forest, as well as more sophisticated sequence models, including recurrent neural networks. We focus especially on the use of medical code data for disease prediction, and explore different ways for representing such data in our prediction algorithms.

Residents of retirements homes in region of Zlín in point of demographic view Abstract Presented work introduces the law no. 108/2006 on social services that determines retirements homes as one of the facilities providing social services. The capacity of these facilities in the Zlín region is evaluated with the help of availability indices and facility normatives. More detailed attention was drawn to an analysis of age, gender, former permanent address and dependence degree of residents in selected retirement homes. This part of the research is based on data provided by five retirement homes in Zlín region. Obtained data was evaluated with the Kaplan-Meier method in order to estimate surviving function for these clients. The resemblance was tested employing the determination of the null hypothesis by log-rank test or Wilcoxon test. Keywords: ageing, residents of retirements homes, law on social services, survival analysis

Cette thèse s'intéresse à l'analyse des données longitudinales, potentiellement grandes selon les trois axes suivants : nombre d'individus, fréquence d'observation et nombre de covariables. A partir de ces données, éventuellement censurées, nous considérons comme facteur d'étude le temps d'apparition d'un ou plusieurs évènements. Nous cherchons dans des classes de modèles à coefficients dépendant du temps à estimer l’intensité d’apparition des événements. Or les estimateurs actuels, ne permettent pas de traiter efficacement un grand nombre d’observations et/ou un grand nombre de covariables. Nous proposons un nouvel estimateur défini via la vraisemblance complète de Cox et une pénalisation permettant à la fois la sélection de variables et de forcer, quand c’est possible, les coefficients à être constants. Nous introduisons des algorithmes d'optimisation proximaux, permettant d'estimer les coefficients du modèle de manière efficace. L'implémentation de ces méthodes en C++ et dans le package R coxtv permet d'analyser des jeux de données de taille supérieure à la mémoire vive; via un streaming du flux de données et des méthodes d'apprentissage en ligne, telles que la descente de gradient stochastique proximale aux pas adaptatifs. Nous illustrons les performances du modèle sur des simulations en nous comparant aux méthodes existantes. Enfin, nous nous intéressons à la problématique du design des jeux vidéo. Nous montrons que l'application directe de ce modèle, sur les grands jeux de données dont dispose l'industrie du jeu vidéo, permet de mettre en évidence des leviers d'amélioration du design des jeux étudiés. Nous nous intéressons d'abord à l'analyse des composantes bas niveau, telles que les choix d'équipement fait par les joueurs au fils du temps et montrons que le modèle permet de quantifier l'effet de chacun de ces éléments de jeu, offrant ainsi aux designers des leviers d'amélioration direct du design. Enfin, nous montrons que le modèle permet de dégager des enseignements plus généraux sur le design tels que l'influence de la difficulté sur la motivation des joueurs. / This thesis focuses on longitudinal time to event data possibly large along the following tree axes : number of individuals, observation frequency and number of covariates. We introduce a penalised estimator based on Cox complete likelihood with data driven weights. We introduce proximal optimization algorithms to efficiently fit models coefficients. We have implemented thoses methods in C++ and in the R package coxtv to allow everyone to analyse data sets bigger than RAM; using data streaming and online learning algorithms such that proximal stochastic gradient descent with adaptive learning rates. We illustrate performances on simulations and benchmark with existing models. Finally, we investigate the issue of video game design. We show that using our model on large datasets available in video game industry allows us to bring to light ways of improving the design of studied games. First we have a look at low level covariates, such as equipment choices through time and show that this model allows us to quantify the effect of each game elements, giving to designers ways to improve the game design. Finally, we show that the model can be used to extract more general design recommendations such as dificulty influence on player motivations.

This master thesis investigates the use of machine learning for predicting and assessing the risk of railway vehicle component failures. Data used for failure prediction often comes with limitations due to the complex nature of maintenance or sometimes requires investments for the extraction of information. Instead of real-time data, historical data and failure timestamps, easily accessed by organisations, are examined to see if they have the potential to contribute to a more effective maintenance strategy. Datasets used in maintenance often contain censored data and to overcome this problem survival machine learning models were also examined. Therefore both traditional machine learning models and survival machine learning models were evaluated and compared based on their C-index value. The results demonstrate that the survival machine learning models, which incorporate the risk and time-to-event aspects of the data, performed better than the traditional ones regarding the risk ranking of components. Random survival forest had the best result, and a ranking of important features. These findings indicate that there is a potential for survival machine learning, applied to existing historical data used for risk assessment for components failure.

No description available.

Thesis (Ph.D. (Statistics)) -- University of Limpopo, 2022 / This thesis is based on application of frailty and copula models to under five child mortality data set in South Africa. The main purpose of the study was to apply sample splitting techniques in a survival analysis setting and compare clustered survival models considering left truncation to the under five child mortality data set in South Africa. The major contributions of this thesis is in the application of the shared frailty model and a class of Archimedean copulas in particular, Clayton-Oakes copula with completely monotone generator, and introduction of sample splitting techniques in a survival analysis setting. The findings based on shared frailty model show that clustering effect was sig nificant for modelling the determinants of time to death of under five children, and revealed the importance of accounting for clustering effect. The conclusion based on Clayton-Oakes model showed association between survival times of children from the same mother. It was found that the parameter estimates for the shared frailty and the Clayton-Oakes models were quite different and that the two models cannot be comparable. Gender, province, year, birth order and whether a child is part of twin or not were found to be significant factors affect ing under five child mortality in South Africa. / NRF-TDG Flemish Interuniversity Council Institutional corporation (VLIR-IUC) VLIR-IUC Programme of the University of Limpopo

Thesis (M.Sc. (Statistics)) -- University of Limpopo, 2020 / Peritoneal Dialysis (PD) is a process of replacing kidney function which cleans waste from the blood and remove extra fluid from the body. In most cases, the process of PD is slowed down by a peritoneal membrane infection called peritonitis. Despite recent advancements in treatments and prevention, peritonitis still remains the leading complication which results in high morbidity and technique failure among PD patients. Using a prospective peritonitis dataset of 159 kidney patients who were on PD from 2008 to 2015 in Pietersburg Provincial Hospital, the aim of this study was to identify potential social, demographic and biological risk factors that contribute to the first episode of peritonitis. Both semi-parametric (Cox PH) and parametric (Accelerated Failure Time: Weibull, exponential, loglogistic, and gamma) survival models were fitted to the peritonitis dataset. Akaike Information Criterion (AIC) was applied to select models which best fit to the peritonitis data. Accordingly, log-logistic Accelerated Failure Time (AFT) model was found to be a working model that best fit to the data. A total of 96 (60.38%) peritonitis cases were recorded over the follow-up period with majority of peritonitis infection coming from females (65.4%) and rural dwellers (65.7%) with (62.6%) of black Africans showing higher risk of developing peritonitis. The multivariate log-logistic AFT model revealed that availability of water (p-value=0.018), electricity (p-value=0.018), dwelling (p-value=0.008), haemoglobin status (p-value=0.002) and duration on PD (p-value=0.001) are significant risk factors for the development of peritonitis. Therefore, patients with no water and electricity, coming from rural background with low level of haemoglobin and shorter duration on PD are associii ated with high risk or hazard of developing peritonitis for the first time.

Alzheimer's disease (AD), the most common form of dementia, is a chronic neurodegenerative disease. The HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene is expressed in human brain and may play a role in the pathogenesis of neurodegenerative disorders. Till now, no previous study has reported the association of the HACE1 gene with the risk and age at onset (AAO) of AD; while few studies have checked the proportional hazards assumption in the survival analysis of AAO of AD using Cox proportional hazards model. In this study, we examined the associations of 14 single nucleotide polymorphisms (SNPs) in the HACE1 gene with the risk and the AAO of AD using 791 AD patients and 782 controls. Multiple logistic regression model identified one SNP (rs9499937 with p = 1.8×10) to be associated with the risk of AD. For survival analysis of AAO, both classic Cox regression model and Bayesian survival analysis using the Cox proportional hazards model were applied to examine the association of each SNP with the AAO. The hazards ratio (HR) with its 95% confidence interval (CI) was estimated. Survival analysis using the classic Cox regression model showed that 4 SNPs were significantly associated with the AAO (top SNP rs9499937 with HR=1.33, 95%CI=1.13-1.57, p=5.0×10). Bayesian Cox regression model showed similar but a slightly stronger associations (top SNP rs9499937 with HR=1.34, 95%CI=1.11-1.55) compared with the classic Cox regression model. Using an independent family-based sample, one SNP rs9486018 was associated with the risk of AD (p=0.0323) and the T-T-G haplotype from rs9786015, rs9486018 and rs4079063 showed associations with both the risk and AAO of AD (p=2.27×10 and 0.0487, respectively). The findings of this study provide first evidence that several genetic variants in the HACE1 gene were associated with the risk and AAO of AD.