Introdução: O câncer de orofaringe representa 10 a 12 % entre todos os tumores malignos do trato aero digestivo superior com incidência crescente nos Estados Unidos e Europa. O Papillomavírus humano (HPV) está associado aos tumores de orofaringe em até 63%, promovendo uma evolução e prognóstico melhor. Objetivo: Descrever a prevalência do HPV em carcinomas de células escamosas de orofaringe tratados por cirurgia. Analisar a associação entre a presença do HPV e as características demográficas, clínicas, patológicas e terapêuticas. Avaliar a importância da presença do HPV na sobrevida livre de doença e sobrevida global. Método: Pesquisamos a presença do Papillomavirus humano, por PCR, no anátomo patológico. A descrição da amostra foi realizada através de média, frequência absoluta e relativa. Foi estimada a prevalência do HPV e seu respectivo intervalo de 95% de confiança. A análise da associação entre a presença de HPV e as características demográficas, clínicas e patológicas, foi feita pelo teste de associação pelo quiquadrado. A análise da sobrevida livre de doença e sobrevida global foi feita pelo estimador produto limite de Kaplan-Meier e modelos de risco proporcionais de Cox. Resultados: Os pacientes apresentavam idade variando de 34 a 78 anos, com uma média de 56,9 anos. Apenas 10 mulheres no estudo, totalizando com 76 homens. A maioria dos pacientes eram brancos (83,7%). Até 6 meses foi o tempo que a maioria dos pacientes apresentaram como início dos sintomas (69,0%). O sintoma mais comum foi a odinofagia (38,4%). A amígadala foi a localização mais frequente (69,8%). Quanto ao estádio clínico, o III e o IV apresentavam a maior frequência (71,4%). Forma realizadas cirurgias amplas como as bucofaringectomias em 76 pacientes (88,4%). O esvaziamento cervical ipsilateral foi realizado em 81 pacientes (94,2%) e no contralateral em apenas 21 (24,4%). A prevalência do HPV foi de 57%, e o tipo mais comum foi o 16, em 83,6%. A única associação estatisticamente significativa entre as variáveis do estudo com o HPV, foi o tabagismo, onde todos os não fumantes apresentavam HPV. As taxas de sobrevida livre de doença foram 73,9%, 65,9 e 57,9% respectivamente para 12, 24 e 60 meses. Houve diferença estatisticamente significativa com piores taxas, para idade menor que 55 anos e margens comprometidas. A presença do HPV não influenciou a sobrevida livre de doença, nem a sobrevida global. As taxas de sobrevida global foram 75,6%, 54,7% e 43,0%, respectivamente aos 12, 24 e 60 meses. Houveram piores taxas para o paciente etilista e com recidiva.Conclusão:A presença do HPV não se mostrou importante, como fator prognóstico, nessa série cirúrgica se o paciente for etilista e ou tabagista / Introduction:Oropharynx cancer is considered to enact approximately 10 to 12% of the cases among all malignant tumors from the upper aero digestive tract showing significant growth in its frequency rate in The United States and Europe. Human papillomavirus (HPV) is associated to oropharynx cancer in up to 63% of the cases, promoting better evolution and prognostic.Objective:Describe the prevalence of the HPV in oropharynx squamous cells carcinoma submitted to surgery. Investigate the association between HPV presence and the demographic, clinical, pathologic and therapeutic features. Estimate the importance of the HPV existence on the diseasefree survival and overall survival. Material andMethods: The existence of Human papillomavirus was studied through the use of PCR. The sample account was conducted through average, absolute and relative frequency. It has been estimated the prevalence of HPV and its corresponding 95% confidence interval. The association analysis between the presence of HPV and the demographic, clinical and pathological features was completed by the Qui-square association test. The disease-free survival timeline and the overall survival were estimated using the product limit estimator Kaplan-Meier and Cox proportional hazards model. Results: The studied patients were aged between 34 and 78, showing an average of 56.9 years of age. There were only 10 women in the study, thus presenting 76 men. Most of the patients were white (83.7%). It has been ascertained that 69.0% of the patients presented the symptoms onset up to the sixth month of the disease. The most common symptom among 38.4% of the cases was odinophagy. In regards to the tumor location 69.8% were found in the amygdala.Clinical stagings III and IV were found to be the ones with greater representation among patients (71.4%). Extensive surgeries such as bucopharyngectomy were performed in 76 patients (88.4%). In order to treat ipsilateral neck 81 patients underwent neck dissection (94.2%). Contralateral neck dissection was applied in 21 patients (24.4%). The prevalence of HPV was of 57%, and the most common type was 16, present in 83.6% of the cases. It was possible to notice smoking as the only statistically significant association, which showed all nonsmoking having HPV. The disease-free survival rates were of 73.9%, 65.9% and 57.9% to 12, 24 and 60 months respectively. The study has shown significant statistical difference with worse rates, to the ones under 55 years of age and presenting compromised margins. HPV presence did not influence the disease-free survival timeline, or the overall survival. The overall survival rates were of 75.6%, 54.7% and 43.0% to 12, 24 and 60 months respectively. Worse rates were found in alcoholic patients as well as in relapse cases. Conclusion: In these surgical series, HPV existence was not identified as an important prognosis factor when considering smokers and/or alcoholic patients

Many breast cancer diagnoses and second cancers are associated with BRCA gene mutations. Early detection of cancer is necessary to improve health outcomes, particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading to the development of cancer. Composite endpoint was used to define second primary cancer occurrences, and Kaplan-Meier survival curves were used to compare the median time-to-event among comparison groups and BRCA gene mutation status. Cox proportional hazards was used to examine the relationships between age at diagnosis, ethnicity, BRCA gene mutation status, and diagnosis of a second primary cancer. The overall median time to event for diagnosis of second primary cancers was 14 years. The hazard ratios for BRCA2 = 1.47, 95% CI [1.03 - 2.11], White = 1.511, 95% CI [1.18 - 1.94], and American Indian/Hawaiian = 1.424, 95% CI [1.12 -1.81] showing positive significant associations between BRCA2 mutation status and risk of diagnosis of second primary colorectal, endometrial, cervical, kidney, thyroid, and bladder cancers. Data on risk factors for development of second cancers would allow for identification of appropriate and timely screening procedures, determining the best course of action for prevention and treatment, and improving quality of life among breast cancer survivors.

成比例危險迴歸模式常被用於分析存活資料，Weibull模式更是其中惟一兼具加速失敗特性者。本論文將利用兩種分析方法，以研究任意設限及截斷資料的Weibull迴歸模式。第一種方法是利用最大概似估計法求算設限及截斷資料下的參數估計值（MLE），第二種方法則是對左設限及區間設限分別以所在區間之中點代入，稱其為中點估計法，再求算模式中的參數估計值（MDE）。並對此兩種估計方法進行比較。模擬結果顯示，相當地大樣本之下，最大概似估計法在許多情況均優於中點估計法；而在樣本少、危險率為平穩或接近平穩且區間設限比率約為0.5時，中點估計法是可被推薦的。而且，本論文亦提出對設限及截斷資料的Weibull模式之適合度檢驗程序。 / The proportional hazards regression model is most commonly used model for lifetime data. The Weibull model is the only parametric model which has both a proportional hazards representation and an accelerated failure-time representation. This paper studies the use of a Weibull-based proportional hazards regression model when any censored and truncated data are observed. Two alternative methods of analysis are considered. First, the maximum likelihood estimates（MLEs） of parameters are computed for the observed censoring and truncation pattern. Second, the estimates where midpoints are substituted for left- and interval-censored data（midpoint estimation, MDE）are computed. Then, MLEs are compared with MDEs. Simulation studies indicate that for relative large samples there are many instances when the MLE is superior to the MDE. For small samples where the hazard rate is flat or nearly so, and the percentage of interval-censored data is nearly half of samples, the MDE is adequate. Also, an evaluation of the adequacy of the Weibull model for any censored and truncated data is proposed.

In survival analysis interest often lies in the relationship between the survival function and a certain number of covariates. It usually happens that for some individuals we cannot observe the event of interest, due to the presence of right censoring and/or left truncation. A typical example is given by a retrospective medical study, in which one is interested in the time interval between birth and death due to a certain disease. Patients who die of the disease at early age will rarely have entered the study before death and are therefore left truncated. On the other hand, for patients who are alive at the end of the study, only a lower bound of the true survival time is known and these patients are hence right censored. In the case of censored and/or truncated responses, lots of models exist in the literature that describe the relationship between the survival function and the covariates (proportional hazards model or Cox model, log-logistic model, accelerated failure time model, additive risks model, etc.). In these models, the regression coefficients are usually supposed to be constant over time. In practice, the structure of the data might however be more complex, and it might therefore be better to consider coefficients that can vary over time. In the previous examples, certain covariates (e.g. age at diagnosis, type of surgery, extension of tumor, etc.) can have a relatively high impact on early age survival, but a lower influence at higher age. This motivated a number of authors to extend the Cox model to allow for time-dependent coefficients or consider other type of time-dependent coefficients models like the additive hazards model. In practice it is of great use to have at hand a method to check the validity of the above mentioned models. First we consider a very general model, which includes as special cases the above mentioned models (Cox model, additive model, log-logistic model, linear transformation models, etc.) with time-dependent coefficients and study the parameter estimation by means of a least squares approach. The response is allowed to be subject to right censoring and/or left truncation. Secondly we propose an omnibus goodness-of-fit test that will test if the general time-dependent model considered above fits the data. A bootstrap version, to approximate the critical values of the test is also proposed. In this dissertation, for each proposed method, the finite sample performance is evaluated in a simulation study and then applied to a real data set.

The focus of this thesis was the development of failure prognosis methods (prognostics) in rotating machinery with use of multiple sensors digital signal processing and machine learning techniques. The motivation stems from the void in literature concerning prognostics in meshing gearboxes. Moreover, there are several but inconclusive works regarding bearing prognosis. Few research groups have studied multi-hour fatigue gear experiments and this was one of the contributions of this thesis. Moreover, the study expanded beyond the sheer application of vibration monitoring with the addition of an Oil Debris Monitoring probe (ODM) as well as Acoustic emission (AE). The method of AE monitoring is, once again, proposed as a robust technique for failure prognosis being better correlated with gear pitting level compared to the classic vibration monitoring technique. Moreover, judging from ODM recordings the gear pitting comprises of two phases i) a linear phase, with an almost constant pitting rate and ii) a very short non linear phase where the pitting rate increases exponentially, an explicit indication of a critical failure. Multi-hour gear experiments that are close to real scale applications are very demanding in time as well as in invested capital. To bypass this shortfall a gear failure like simulation is proposed. The simulation framework is based on real life experiments and is applied to assess a number of data-driven Remaining Useful Life (RUL) estimation techniques namely i) Proportional Hazards Μodel (PHM), ii) ε- Support Vector Regression ε-SVR and iii) Exponential extrapolation based on bootstrap sampling. In the current thesis a feature extraction scheme for prognosis is proposed and assessed based on time domain, frequency domain statistical features and Wavelet Packet (WP) energy derived from AE and vibration recordings. ICA is proposed as a preferable fusion technique for gear failure prognostics. Application of ICA for feature fusion provided a clear improvement regarding the earlier presented bootstrap extrapolation technique. Bearings are also taken into account since they are closely connected to gearboxes. In the current thesis a wavelet denoising method is proposed for bearing vibration recordings aiming to the improvement of the diagnostic and prognostic potential of vibration. Finally the importance of data fusion is highlighted in the case of bearings. It is observed that a feature extraction scheme can generalize the application of prognostics, even in cases where RMS may yield no important degradation trend. / Η παρούσα εργασία εστιάζεται στην ανάπτυξη μεθοδολογιών πρόβλεψης τελικής αστοχίας σε περιστρεφόμενα συστήματα με χρήση πολλαπλών αισθητήρων και μεθόδων μηχανικής μάθησης και επεξεργασίας σήματος. Το κίνητρο προήλθε από το κενό που υπάρχει στη βιβλιογραφία όσον αφορά την προγνωστική σε κιβώτια ταχυτήτων. Η προγνωστική σε έδρανα έχει μεν μελετηθεί αλλά σε μικρό βαθμό και η παρούσα εργασία έρχεται να συμβάλλει και σε αυτό τον τομέα. Στα πλαίσια αυτής της εργασίας εκπονήθηκε ένας αριθμός πειραμάτων κόπωσης κιβωτίων ταχυτήτων. Η μελέτη επεκτάθηκε πέραν της παρακολούθησης κατάστασης με τη μέθοδο των κραδασμών και συγκεκριμένα μελετήθηκαν καταγραφές σωματιδίων σιδήρου στο λιπαντικό (ODM) καθώς και Ακουστική Εκπομπής (AE). Η μέθοδος ΑΕ ευρέθη πιο στενά συσχετισμένη με τη σταδιακή υποβάθμιση της ακεραιότητας του κιβωτίου ταχυτήτων σε σχέση με τις καταγραφές κραδασμών. Επίσης με βάση τις καταγραφές του αισθητήρα σωματιδίων σιδήρου διακρίθηκαν δύο στάδια  υποβάθμισης i) μια γραμμική περιοχή με σχεδόν σταθερό ρυθμό απελευθέρωσης υλικού από την επιφάνεια των δοντιών και ii) μια σύντομη αλλά έντονα μη γραμμική αύξηση στο ρυθμό αυτό πολύ κοντά στο τέλος της λειτουργίας του κιβωτίου. Tα πολύωρα πειράματα κόπωσης σε γρανάζια είναι πολύ απαιτητικά. Για να παρακαμφθεί αυτή η δυσκολία αναπτύχθηκε ένα φαινομενολογικό μοντέλο για αναπαραγωγή χρονοσειρών που ομοιάζουν σε καταγραφές γραναζιών σε κόπωση. Το μοντέλο αυτό στηρίχθηκε σε πραγματικά πειράματα κόπωσης. Έτσι έγινε δυνατό να εξεταστούν και να συγκριθούν ένας αριθμός μεθοδολογιών εκτίμησης εναπομένουσας ζωής και συγκεκριμένα i) Proportional Hazards Model (PHM), ii) ε- Support Vector Regression ε-SVR και iii) Exponential extrapolation βασισμένο σε μια διαδικασία bootstrap sampling. Στην παρούσα μελέτη προτείνεται ένα σύνολο παραμέτρων προερχόμενο από το πεδίο της συχνότητας, του χρόνου και κυματοπακέτων. Αυτό, συνδυαζόμενο με μια διαδικασία σύμπτυξης δεδομένων (ανάλυση σε πρωταρχικές και ανεξάρτητες συνιστώσες) αξιοποιείται για πρόγνωση σε γρανάζια σε κόπωση. Η τεχνική ανεξάρτητων συνιστωσών προτείνεται σαν προτιμότερη από τη σκοπιά της προγνωστικής καθώς βελτιώνει την εκτίμηση της εναπομένουσας ζωής. Η εργασία επεκτάθηκε και σε έδρανα κύλισης. Προτάθηκε μια διαδικασία wavelet denoising η οποία ενισχύει τόσο τη διαγνωστική όσο και την προγνωστική δυνατότητα του αισθητήρα κραδασμών. Τέλος, η σημασία της εξαγωγής παραμέτρων υπογραμμίζεται και στην περίπτωση της προγνωστικής σε έδρανα. Συνδυάζοντας πολλαπλές παραμέτρους και αισθητήρες κραδασμών μαζί με ένα μοντέλο ε-SVR παρέχεται ένα ολοκληρωμένο μοντέλο πιθανοτικής εκτίμησης εναπομένουσας ζωής σε έδρανα κύλισης ακόμα και σε περιπτώσεις που η τιμή RMS των κραδασμών δεν παρέχει πληροφορία.

Darbo metu buvo išnagrinėta įvairių faktorių (kovariančių) įtaka reumatoidiniu artritu sergančio 531 ligonio mirtingumui. Buvo taikomas vienas iš regresinių išgyvenamumo modelių – Cox’o modelis. Iš minėtos 531 ligonio imties mirę buvo 32 ligoniai. Iš pradžių buvo tiriama ligonių imtis laiko nuo ligos pradžios aspektu. Šiuo atveju prognozuojantys veiksniai buvo amžius, kada liga buvo diagnozuota (AMZDGN), lytis (LYTKOD), gydymas Metotreksatu (GYD_MTX) ir gydymas Azatriopinu/Imuranu (AZA_IMUR). Vėliau, tiriant ligonių mirtingumą kaip amžiaus funkciją, nustatyti svarbiausi lemiantys veiksniai buvo šie: ligonių lytis (LYTKOD) ir gydymas Azatriopinu/Imuranu (AZA_IMUR). Gauti rezultatai, t.y. ligonių išgyvenamumą lemiančios kovariantės (veiksniai), beveik visiškai sutampa su gydytojų nurodytais. Tai dar kartą patvirtina matematinių statistinių modelių, šiuo atveju nagrinėjamo Cox‘o modelio, taikymo realiame gyvenime, svarbą. Kitai duomenų imčiai, t.y. vėžiu sergančių ligonių duomenų aibei, buvo taikomas Persikertančių mirimų intensyvumų (SCE) modelis, t.y. tikrinama Cox‘o modelio adekvatumo duomenims hipotezė. Hipotezė buvo atmesta, nes minėtiems duomenims Cox‘o modelis negalioja. Pagrindinis darbo rezultatas yra šis: gautas kriterijus Cox‘o modelio adekvatumui tikrinti, naudojant nupjautus iš kairės ir cenzūruotus iš dešinės duomenis, sudarytos programos kriterijui realizuoti. Reumatoidinio artrito ligonių duomenų aibei, t.y. nupjautiems iš kairės ir cenzūruotiems iš dešinės... [toliau žr. visą tekstą] / In this work the Cox proportional hazards model was applied to investigate the influence of various factors (covariates) to mortality of rheumatoid arthritis patients of Vilnius. In the first case, the sample of 531 patients was analysed. Analysing survival of patients of the sample as function of time from the beginnig of the disease, the prognostic factors were LYTKOD (the sex of patients), AMZDGN (patients‘ age, when the rheumatoid arthritis was diagnosed), GYD_MTX (treatment with metotrexat) and AZA_IMUR (treatment with Azatriopin/Imuran). When survival was analysed as function of age then the prognostic factor were LYTKOD (the sex of patients) and AZA_IMUR (treatment with Azatriopin/Imuran). The results are almost identical to those, which doctors suggested. This fact confirms the importance of using mathematical statistical models to solve the problems of the real life. In this case, the importance of using the Cox model. On the other hand, Simple cross-effects (SCE) model was aplied for the sample of canser patients. In the case of this model the hypothesis of Cox model fiting for canser patients‘ data was rejected. The most important result of this work is that the criterion of Cox model fitting to left truncated and right censored data was constructed. Also a program of SAS for the criterion was created. The the hypothesis of Cox model fiting for the rheumatoid arthritis patients wasn‘t rejected, because Cox model fit for these data.

Made available in DSpace on 2016-06-02T20:06:01Z (GMT). No. of bitstreams: 1 1988.pdf: 463519 bytes, checksum: ca45424706e2fdb08c40f42f1f560364 (MD5) Previous issue date: 2008-06-13 / Financiadora de Estudos e Projetos / In survival analysis some studies show a meaningful cure rate after treatment followup, so considering standard survival models can not be appropriate. In this work is extended the long-term survival model proposed by Chen, Ibrahim and Sinha (1999) via generating function of a real sequence introduced by Feller (1967). This new formulation is the uni_cation of the long-term survival models proposed by Rodrigues el al. (2008). Also, as in Rodrigues el al. (2008) it is shown that the long-term survival generating function satis_es the proportional hazard property if only if the number of competing causes related to the occurence of a event of interest follows a Poisson distribution. A real data set is considered to illustrate this approach. / Em análise de sobrevivência, determinados estudos caracterizam-se por apresentar uma fração significativa de sobreviventes, ou seja, pacientes em tratamento que não apresentaram o evento de interesse, mesmo após um longo período de acompanhamento. Assim considerar modelos de sobrevivência usuais, que assumem que a função de sobrevivência converge para zero quando a variável tempo tende a infinito, pode não ser adequado. Nesse trabalho é apresentado uma extensão do modelo proposto por Chen, Ibrahim e Sinha (1999), usando a função geradora de uma sequência de números reais introduzida por Feller (1967). Essa extensão possibilitou o desenvolvimento de uma teoria unificada para os modelos de sobrevivência de longa-duração, Rodrigues et al. (2008). Mostra-se que modelos já existentes na literatura são considerados casos particulares da teoria unificada, por exemplo, o modelo de Berkson & Gage (1952). Também tem-se em Rodrigues et al. (2008), que a função geradora de longa-duração satisfaz a propriedade de risco proporcional se, e somente se, o número de causas competitivas relacionadas a ocorrência do evento de interesse segue uma distribuição de Poisson. Como ilutração utiliza-se um conjunto de dados reais.

Made available in DSpace on 2014-12-17T15:34:49Z (GMT). No. of bitstreams: 1 DeborahGPG_DISSERT.pdf: 1421770 bytes, checksum: da1c0ade32fb8610306243b0cf52f13d (MD5) Previous issue date: 2014-02-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Among the traits of economic importance to dairy cattle livestock those related to sexual precocity and longevity of the herd are essential to the success of the activity, because the stayability time of a cow in a herd is determined by their productive and reproductive lives. In Brazil, there are few studies about the reproductive efficiency of Swiss-Brown cows and no study was found using the methodology of survival analysis applied to this breed. Thus, in the first chapter of this study, the age at first calving from Swiss-Brown heifers was analyzed as the time until the event by the nonparametric method of Kaplan-Meier and the gamma shared frailty model, under the survival analysis methodology. Survival and hazard rate curves associated with this event were estimated and identified the influence of covariates on such time. The mean and median times at the first calving were 987.77 and 1,003 days, respectively, and significant covariates by the Log-Rank test, through Kaplan-Meier analysis, were birth season, calving year, sire (cow s father) and calving season. In the analysis by frailty model, the breeding values and the frailties of the sires (fathers) for the calving were predicted modeling the risk function of each cow as a function of the birth season as fixed covariate and sire as random covariate. The frailty followed the gamma distribution. Sires with high and positive breeding values possess high frailties, what means shorter survival time of their daughters to the event, i.e., reduction in the age at first calving of them. The second chapter aimed to evaluate the longevity of dairy cows using the nonparametric Kaplan-Meier and the Cox and Weibull proportional hazards models. It were simulated 10,000 records of the longevity trait from Brown-Swiss cows involving their respective times until the occurrence of five consecutive calvings (event), considered here as typical of a long-lived cow. The covariates considered in the database were age at first calving, herd and sire (cow s father). All covariates had influence on the longevity of cows by Log-Rank and Wilcoxon tests. The mean and median times to the occurrence of the event were 2,436.285 and 2,437 days, respectively. Sires that have higher breeding values also have a greater risk of that their daughters reach the five consecutive calvings until 84 months / Dentre as caracter?sticas de import?ncia econ?mica para a pecu?ria leiteira aquelas relacionadas com a precocidade sexual e a longevidade do rebanho s?o determinantes para o sucesso da atividade, uma vez que o tempo de perman?ncia de uma vaca num rebanho ? determinado por suas vidas produtiva e reprodutiva. No Brasil, existem poucos estudos sobre a efici?ncia reprodutiva de vacas Pardo-Su??as e n?o foi encontrado nenhum estudo abordando o uso da metodologia de an?lise de sobreviv?ncia aplicada a esta ra?a. Assim, no primeiro cap?tulo deste trabalho, a idade ao primeiro parto de novilhas Pardo-Su??as foi analisada como o tempo at? o evento por meio do m?todo n?o-param?trico de Kaplan-Meier e do modelo de fragilidade compartilhado gama, sob a metodologia de an?lise de sobreviv?ncia. Foram estimadas curvas de sobreviv?ncia e de taxa de risco associadas com este evento e verificada a influ?ncia das covari?veis consideradas sobre o tempo. Os tempos m?dio e mediano ao primeiro parto foram 987,77 e 1.003 dias, respectivamente; e as covari?veis significativas pelo teste de Log-Rank, na an?lise por Kaplan-Meier, foram esta??o de nascimento, ano de parto, touro (pai da vaca) e esta??o de parto. Na an?lise pelo modelo de fragilidade, foram preditos os valores gen?ticos e as fragilidades dos touros (pais) para o parto, modelando-se a fun??o de risco de cada vaca em fun??o da covari?vel fixa esta??o de nascimento e da covari?vel aleat?ria touro. A fragilidade seguiu a distribui??o gama. Touros com valores gen?ticos positivos e altos possuem fragilidades altas, o que significa menor tempo de sobreviv?ncia de suas filhas ao evento, ou seja, redu??o na idade ao primeiro parto delas. O segundo cap?tulo teve como objetivo avaliar a longevidade de vacas leiteiras utilizando o estimador n?o-param?trico de Kaplan-Meier e os modelos de riscos proporcionais de Weibull e de Cox. Foram simulados 10.000 registros da caracter?stica longevidade de f?meas Pardo-Su??as denotando seus respectivos tempos at? a ocorr?ncia de cinco partos consecutivos (evento), considerados aqui como t?picos de uma vaca longeva. As covari?veis consideradas no banco de dados foram a idade da vaca ao primeiro parto, o rebanho e o pai da vaca. Todas as covari?veis exerceram influ?ncia sobre a longevidade das vacas de acordo com os testes de Log-Rank e Wilcoxon. Os tempos m?dio e mediano para a ocorr?ncia do evento foram de 2.436,285 e 2.437 dias. Touros com maior valor gen?tico tamb?m possuem um maior risco de que as suas filhas alcancem os cinco partos aos 84 meses

Diversos modelos têm sido propostos na literatura com o objetivo de analisar dados de sobrevivência em que a população sob estudo é assumida ser uma mistura de indivíduos suscetíveis (em risco) e não suscetíveis a um específico evento de interesse. Tais modelos são usualmente denominados modelos com sobreviventes de longa duração ou modelos com fração de cura. Neste trabalho, diversos desses modelos (nos contextos paramétrico e semi-paramétrico) foram considerados para analisar os dados de um ensaio clínico aleatorizado conduzido com o objetivo de comparar três estratégias terapêuticas (cirurgia, angioplastia e medicamentoso) utilizadas no tratamento de pacientes com doença coronariana multiarterial. Em todos os modelos, as funções de ligação logito e complemento log-log foram utilizadas para modelar a proporção de sobreviventes de longa duração (indivíduos não suscetíveis). Quanto à função de sobrevivência dos indivíduos suscetíveis, foram utilizados os modelos de Weibull e de Cox. Covariáveis foram consideradas tanto na proporção de sobreviventes de longa duração quanto na função de sobrevivência dos indivíduos suscetíveis. De modo geral, os modelos considerados se mostraram adequados para analisar os dados do ensaio clínico aleatorizado, indicando a cirurgia como a estratégia terapêutica mais eficiente. Indicaram também, que as covariáveis idade, hipertensão e diabetes mellitus exercem influência na ocorrência do óbito cardíaco, mas não no tempo até a ocorrência deste óbito nos pacientes suscetíveis. / Several models have been proposed in the literature with the aim of analyzing survival data when the population under study is assumed to be a mixture of susceptible (at risk) and not susceptible individuals to a specific event of interest. Such models are usually called long-term survivors models or cure rate models. In this work, several of these models (under both parametric and semi-parametric approaches) were considered to analyze the data from a randomized clinical trial conducted in order to compare three therapeutic strategies (surgery, angioplasty and medicine) used in the treatment of patients with multivessel coronary artery disease. For all models the logit and complementary log-log link functions were used to model the proportion of long-term survivors (not susceptible individuals). In regards to the survival function of the susceptible individuals, the Weibull and Cox models were used. Covariates were considered both in the proportion of longterm survivors and in the survival function of the susceptible individuals. Overall, the models considered were suitable for analyzing the data from the randomized clinical trial indicating surgery as the most effective therapeutic strategy. They also indicated that the covariates age, hypertension and diabetes mellitus exhibit influence on the occurrence of cardiac death, but not on the time to the occurrence of this death in susceptible patients.

Introdução: O câncer de orofaringe representa 10 a 12 % entre todos os tumores malignos do trato aero digestivo superior com incidência crescente nos Estados Unidos e Europa. O Papillomavírus humano (HPV) está associado aos tumores de orofaringe em até 63%, promovendo uma evolução e prognóstico melhor. Objetivo: Descrever a prevalência do HPV em carcinomas de células escamosas de orofaringe tratados por cirurgia. Analisar a associação entre a presença do HPV e as características demográficas, clínicas, patológicas e terapêuticas. Avaliar a importância da presença do HPV na sobrevida livre de doença e sobrevida global. Método: Pesquisamos a presença do Papillomavirus humano, por PCR, no anátomo patológico. A descrição da amostra foi realizada através de média, frequência absoluta e relativa. Foi estimada a prevalência do HPV e seu respectivo intervalo de 95% de confiança. A análise da associação entre a presença de HPV e as características demográficas, clínicas e patológicas, foi feita pelo teste de associação pelo quiquadrado. A análise da sobrevida livre de doença e sobrevida global foi feita pelo estimador produto limite de Kaplan-Meier e modelos de risco proporcionais de Cox. Resultados: Os pacientes apresentavam idade variando de 34 a 78 anos, com uma média de 56,9 anos. Apenas 10 mulheres no estudo, totalizando com 76 homens. A maioria dos pacientes eram brancos (83,7%). Até 6 meses foi o tempo que a maioria dos pacientes apresentaram como início dos sintomas (69,0%). O sintoma mais comum foi a odinofagia (38,4%). A amígadala foi a localização mais frequente (69,8%). Quanto ao estádio clínico, o III e o IV apresentavam a maior frequência (71,4%). Forma realizadas cirurgias amplas como as bucofaringectomias em 76 pacientes (88,4%). O esvaziamento cervical ipsilateral foi realizado em 81 pacientes (94,2%) e no contralateral em apenas 21 (24,4%). A prevalência do HPV foi de 57%, e o tipo mais comum foi o 16, em 83,6%. A única associação estatisticamente significativa entre as variáveis do estudo com o HPV, foi o tabagismo, onde todos os não fumantes apresentavam HPV. As taxas de sobrevida livre de doença foram 73,9%, 65,9 e 57,9% respectivamente para 12, 24 e 60 meses. Houve diferença estatisticamente significativa com piores taxas, para idade menor que 55 anos e margens comprometidas. A presença do HPV não influenciou a sobrevida livre de doença, nem a sobrevida global. As taxas de sobrevida global foram 75,6%, 54,7% e 43,0%, respectivamente aos 12, 24 e 60 meses. Houveram piores taxas para o paciente etilista e com recidiva.Conclusão:A presença do HPV não se mostrou importante, como fator prognóstico, nessa série cirúrgica se o paciente for etilista e ou tabagista / Introduction:Oropharynx cancer is considered to enact approximately 10 to 12% of the cases among all malignant tumors from the upper aero digestive tract showing significant growth in its frequency rate in The United States and Europe. Human papillomavirus (HPV) is associated to oropharynx cancer in up to 63% of the cases, promoting better evolution and prognostic.Objective:Describe the prevalence of the HPV in oropharynx squamous cells carcinoma submitted to surgery. Investigate the association between HPV presence and the demographic, clinical, pathologic and therapeutic features. Estimate the importance of the HPV existence on the diseasefree survival and overall survival. Material andMethods: The existence of Human papillomavirus was studied through the use of PCR. The sample account was conducted through average, absolute and relative frequency. It has been estimated the prevalence of HPV and its corresponding 95% confidence interval. The association analysis between the presence of HPV and the demographic, clinical and pathological features was completed by the Qui-square association test. The disease-free survival timeline and the overall survival were estimated using the product limit estimator Kaplan-Meier and Cox proportional hazards model. Results: The studied patients were aged between 34 and 78, showing an average of 56.9 years of age. There were only 10 women in the study, thus presenting 76 men. Most of the patients were white (83.7%). It has been ascertained that 69.0% of the patients presented the symptoms onset up to the sixth month of the disease. The most common symptom among 38.4% of the cases was odinophagy. In regards to the tumor location 69.8% were found in the amygdala.Clinical stagings III and IV were found to be the ones with greater representation among patients (71.4%). Extensive surgeries such as bucopharyngectomy were performed in 76 patients (88.4%). In order to treat ipsilateral neck 81 patients underwent neck dissection (94.2%). Contralateral neck dissection was applied in 21 patients (24.4%). The prevalence of HPV was of 57%, and the most common type was 16, present in 83.6% of the cases. It was possible to notice smoking as the only statistically significant association, which showed all nonsmoking having HPV. The disease-free survival rates were of 73.9%, 65.9% and 57.9% to 12, 24 and 60 months respectively. The study has shown significant statistical difference with worse rates, to the ones under 55 years of age and presenting compromised margins. HPV presence did not influence the disease-free survival timeline, or the overall survival. The overall survival rates were of 75.6%, 54.7% and 43.0% to 12, 24 and 60 months respectively. Worse rates were found in alcoholic patients as well as in relapse cases. Conclusion: In these surgical series, HPV existence was not identified as an important prognosis factor when considering smokers and/or alcoholic patients