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Nwi-Mozu, Isaac. "Robustness of Semi-Parametric Survival Model: Simulation Studies and Application to Clinical Data." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etd/3618.
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An efficient way of analyzing survival clinical data such as cancer data is a great concern to health experts. In this study, we investigate and propose an efficient way of handling survival clinical data. Simulation studies were conducted to compare performances of various forms of survival model techniques using an R package ``survsim". Models performance was conducted with varying sample sizes as small ($n5000$). For small and mild samples, the performance of the semi-parametric outperform or approximate the performance of the parametric model. However, for large samples, the parametric model outperforms the semi-parametric model. We compared the effectiveness and reliability of our proposed techniques using a real clinical data of mild sample size. Finally, systematic steps on how to model and explain the proposed techniques on real survival clinical data was provided.
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Pecková, Monika. "Efficiency based adaptive tests for censored survival data /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/9599.
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Ekman, Mattias. "Studies in health economics : modelling and data analysis of costs and survival." Doctoral thesis, Stockholm : Economic Research Institute, Stockholm School of Economics [Ekonomiska forskningsinstitutet vid Handelshögsk.] (EFI), 2002. http://www.hhs.se/efi/summary/598.htm.
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Nan, Bin. "Information bounds and efficient estimates for two-phase designs with lifetime data /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/9587.
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Molinares, Carlos A. "Parametric and Bayesian Modeling of Reliability and Survival Analysis." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3252.
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The objective of this study is to compare Bayesian and parametric approaches to determine the best for estimating reliability in complex systems. Determining reliability is particularly important in business and medical contexts. As expected, the Bayesian method showed the best results in assessing the reliability of systems.
In the first study, the Bayesian reliability function under the Higgins-Tsokos loss function using Jeffreys as its prior performs similarly as when the Bayesian reliability function is based on the squared-error loss. In addition, the Higgins-Tsokos loss function was found to be as robust as the squared-error loss function and slightly more efficient.
In the second study, we illustrated that--through the power law intensity function--Bayesian analysis is applicable in the power law process. The power law intensity function is the key entity of the power law process (also called the Weibull process or the non-homogeneous Poisson process). It gives the rate of change of a system's reliability as a function of time. First, using real data, we demonstrated that one of our two parameters behaves as a random variable. With the generated estimates, we obtained a probability density function that characterizes the behavior of this random variable. Using this information, under the commonly used squared-error loss function and with a proposed adjusted estimate for the second parameter, we obtained a Bayesian reliability estimate of the failure probability distribution that is characterized by the power law process. Then, using a Monte Carlo simulation, we showed the superiority of the Bayesian estimate compared with the maximum likelihood estimate and also the better performance of the proposed estimate compared with its maximum likelihood counterpart.
In the next study, a Bayesian sensitivity analysis was performed via Monte Carlo simulation, using the same parameter as in the previous study and under the commonly used squared-error loss function, using mean square error comparison. The analysis was extended to the second parameter as a function of the first, based on the relationship between their maximum likelihood estimates. The simulation procedure demonstrated that the Bayesian estimates are superior to the maximum likelihood estimates and that the selection of the prior distribution was sensitive. Secondly, we found that the proposed adjusted estimate for the second parameter has better performance under a noninformative prior.
In the fourth study, a Bayesian approach was applied to real data from breast cancer research. The purpose of the study was to investigate the applicability of a Bayesian analysis to survival time of breast cancer data and to justify the applicability of the Bayesian approach to this domain. The estimation of one parameter, the survival function, and hazard function were analyzed. The simulation analysis showed that the Bayesian estimate of the parameter performed better compared with the estimated value under the Wheeler procedure. The excellent performance of the Bayesian estimate is reflected even for small sample sizes. The Bayesian survival function was also found to be more efficient than its parametric counterpart.
In the last study, a Bayesian analysis was carried out to investigate the sensitivity to the choice of the loss function. One of the parameters of the distribution that characterized the survival times for breast cancer data was estimated applying a Bayesian approach and under two different loss functions. Also, the estimates of the survival function were determined under the same setting. The simulation analysis showed that the choice of the squared-error loss function is robust in estimating the parameter and the survival function.
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McNeil, Alexander John. "Statistical methods in AIDS progression studies with an analysis of the Edinburgh City Hospital Cohort." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307053.
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Moayyeri, Alireza. "Risk assessment for osteoporotic fractures among men and women from a prospective population study : the EPIC-Norfolk study." Thesis, University of Cambridge, 2012. https://www.repository.cam.ac.uk/handle/1810/243860.
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Osteoporotic fractures are a major and increasing clinical and public health concern internationally. Identification of individuals at high risk for fragility fractures may enable us to target preventive interventions more effectively. In this thesis, I aimed to evaluate novel risk factors for osteoporosis and develop a fracture risk assessment model among the middle-aged and older people. I used data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, which is a large population-based prospective study started in 1993. About 25,000 men and women were assessed at baseline and about 15,000 of them returned for a second examination 4 years later. All participants are followed up to the present for clinical events including fractures. My work is in two parts. For the first part, I examined the risk of fracture associated with some novel or less well studied risk factors. These risk factors included change in height over time, respiratory function, physical activity and body fat mass. We found that men and women with annual height loss >0.5 cm are at increased risk of hip and any fracture (relative risk=1.9 (95% CI 1.3-2.7) per cm/year height loss). One litre lower forced expiratory volume in 1 second (FEV1) was associated with a 2-fold risk of hip fracture in men and women. We also observed a non-linear association, independent of body mass index, between increasing body fat mass and lower fracture risk in women but not in men. I performed a systematic review and meta-analysis of studies evaluating the association between physical activity and hip fractures. Using a new validated questionnaire in EPIC-Norfolk, we observed varying relationships between physical activity in different domains of life and fracture risk in men and women. For the second part of the thesis, I developed a biostatistical model to calculate 10-year risk of developing a fracture among EPIC-Norfolk study participants. This model incorporates clinical and radiological assessments known to be associated with fractures and can be extended to other risk factors assessed in other prospective cohorts. This helps clinicians to achieve a better estimate of the prospective risk of fracture in their patients. I applied this model to compare the predictive value of two different clinical assessment methods for osteoporosis, namely dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS). We found that that the predictive power of QUS is comparable to, and independent of, predictive power of DXA. In summary, my studies have added to our knowledge about some novel and easy-to-use risk factors of osteoporosis and proposed a practical method to merge and utilise data from different risk factors for estimation of fracture risk in individuals.
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Vizcain, Dorian Charles. "Investigating the Hispanic/Latino Male Dropout Phenomenon: Using Logistic Regression and Survival Analysis." [Tampa, Fla] : University of South Florida, 2005. http://purl.fcla.edu/usf/dc/et/SFE0001322.
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Näpänkangas, R. (Ritva). "Fixed metal ceramic prostheses:treatment need, complications and survival of conventional fixed prosthodontics." Doctoral thesis, University of Oulu, 2001. http://urn.fi/urn:isbn:9514265408.
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Abstract
The aims of this study were to evaluate the treatment need of fixed
bridges according to the distribution of pontics in dentition in different
age groups, and to investigate the primary and late complications and
survival of the conventional fixed metal ceramic prostheses, as well as
patients' satisfaction with the prosthetic treatment.
The whole material consisted of the patients treated with fixed metal
ceramic prostheses by undergraduate students at the Institute of Dentistry
during the years 1984 - 1996. There were altogether 772 patients, 460
women (60 %) and 312 men (40 %). Their mean age was 47 years (23 - 81
years). Altogether 944 single metal ceramic crowns and 543 fixed bridges
(1374 abutments and 807 pontics) were prepared.
It can be concluded that the fixed bridges are most often prepared to
replace upper first premolars and lower first molars also in the future.
The most usual primary complications related to fixed bridges occurred
during preprosthetic endodontic treatment of abutment teeth and during the
preparation of the root canals. Previous restoration of the prepared tooth
does not have any marked effect on the prognosis of single crowns with
dowels, although anatomically complicated upper lateral incisors and upper
first premolars need special attention in the treatment planning. Patients
were satisfied with aesthetics and function of the fixed metal ceramic
prostheses. Late complications found in clinical examinations were few,
and the survival rate for the fixed metal ceramic bridge prostheses was
calculated to be 84 % after 10 years, long fixed bridges having a lower
survival than the shorter ones.
The treatment need for conventional fixed bridges seems to be highest
among patients over 50 years of age in the future. Age does not influence
the longevity of the fixed prostheses, but basic circumstances of the
mouth, especially low secretion of saliva affected by diseases and/or
medications and high scores of lactobacilli and streptococcus mutans of
the saliva seem to decrease the survival.
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Kelly, Jodie. "Topics in the statistical analysis of positive and survival data." Thesis, Queensland University of Technology, 1998.
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Bedair, Khaled Farag Emam. "Statistical Methods for Multi-type Recurrent Event Data Based on Monte Carlo EM Algorithms and Copula Frailties." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/64981.
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In this dissertation, we are interested in studying processes which generate events repeatedly over the follow-up time of a given subject. Such processes are called recurrent event processes and the data they provide are referred to as recurrent event data. Examples include the cancer recurrences, recurrent infections or disease episodes, hospital readmissions, the filing of warranty claims, and insurance claims for policy holders. In particular, we focus on the multi-type recurrent event times which usually arise when two or more different kinds of events may occur repeatedly over a period of observation. Our main objectives are to describe features of each marginal process simultaneously and study the dependence among different types of events. We present applications to a real dataset collected from the Nutritional Prevention of Cancer Trial. The objective of the clinical trial was to evaluate the efficacy of Selenium in preventing the recurrence of several types of skin cancer among 1312 residents of the Eastern United States.
Four chapters are involved in this dissertation. Chapter 1 introduces a brief background to the statistical techniques used to develop the proposed methodology. We cover some concepts and useful functions related to survival data analysis and present a short introduction to frailty distributions. The Monte Carlo expectation maximization (MCEM) algorithm and copula functions for the multivariate variables are also presented in this chapter.
Chapter 2 develops a multi-type recurrent events model with multivariate Gaussian random effects (frailties) for the intensity functions. In this chapter, we present nonparametric baseline intensity functions and a multivariate Gaussian distribution for the multivariate correlated random effects. An MCEM algorithm with MCMC routines in the E-step is adopted for the partial likelihood to estimate model parameters. Equations for the variances of the estimates are derived and variances of estimates are computed by Louis' formula. Predictions of the individual random effects are obtained because in some applications the magnitude of the random effects is of interest for a better understanding and interpretation of the variability in the data. The performance of the proposed methodology is evaluated by simulation studies, and the developed model is applied to the skin cancer dataset.
Chapter 3 presents copula-based semiparametric multivariate frailty models for multi-type recurrent event data with applications to the skin cancer data. In this chapter, we generalize the multivariate Gaussian assumption of the frailty terms and allow the frailty distributions to have more features than the symmetric, unimodal properties of the Gaussian density. More flexible approaches to modeling the correlated frailty, referred to as copula functions, are introduced. Copula functions provide tremendous flexibility especially in allowing taking the advantages of a variety of choices for the marginal distributions and correlation structures. Semiparametric intensity models for multi-type recurrent events based on a combination of the MCEM with MCMC sampling methods and copula functions are introduced. The combination of the MCEM approach and copula function is flexible and is a generally applicable approach for obtaining inferences of the unknown parameters for high dimension frailty models. Estimation procedures for fixed effects, nonparametric baseline intensity functions, copula parameters, and predictions for the subject-specific multivariate frailties and random effects are obtained. Louis' formula for variance estimates are derived and calculated. We investigate the impact of the specification of the frailty and random effect models on the inference of covariate effects, cumulative baseline intensity functions, prediction of random effects and frailties, and the estimation of the variance-covariance components. Performances of proposed models are evaluated by simulation studies. Applications are illustrated through the dataset collected from the clinical trial of patients with skin cancer. Conclusions and some remarks for future work are presented in Chapter 4.Ph. D.
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Ukale, Valiant. "Pleurodesis in chronic effusions : studies on inflammatory mediators, respiratory function, predictability of treatment outcome, drug efficiency and survival after treatment /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-031-1/.
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Kamath, Vidya P. "Enhancing Gene Expression Signatures in Cancer Prediction Models: Understanding and Managing Classification Complexity." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3653.
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Cancer can develop through a series of genetic events in combination with
external influential factors that alter the progression of the disease. Gene expression
studies are designed to provide an enhanced understanding of the progression of cancer
and to develop clinically relevant biomarkers of disease, prognosis and response to
treatment. One of the main aims of microarray gene expression analyses is to develop
signatures that are highly predictive of specific biological states, such as the molecular
stage of cancer. This dissertation analyzes the classification complexity inherent in gene
expression studies, proposing both techniques for measuring complexity and algorithms
for reducing this complexity.
Classifier algorithms that generate predictive signatures of cancer models must
generalize to independent datasets for successful translation to clinical practice. The
predictive performance of classifier models is shown to be dependent on the inherent
complexity of the gene expression data. Three specific quantitative measures of
classification complexity are proposed and one measure ( f) is shown to correlate highly
(R 2=0.82) with classifier accuracy in experimental data.
Three quantization methods are proposed to enhance contrast in gene expression
data and reduce classification complexity. The accuracy for cancer prognosis prediction
is shown to improve using quantization in two datasets studied: from 67% to 90% in lung
cancer and from 56% to 68% in colorectal cancer. A corresponding reduction in
classification complexity is also observed.
A random subspace based multivariable feature selection approach using costsensitive
analysis is proposed to model the underlying heterogeneous cancer biology and
address complexity due to multiple molecular pathways and unbalanced distribution of
samples into classes. The technique is shown to be more accurate than the univariate ttest
method. The classifier accuracy improves from 56% to 68% for colorectal cancer
prognosis prediction.
A published gene expression signature to predict radiosensitivity of tumor cells is
augmented with clinical indicators to enhance modeling of the data and represent the
underlying biology more closely. Statistical tests and experiments indicate that the
improvement in the model fit is a result of modeling the underlying biology rather than
statistical over-fitting of the data, thereby accommodating classification complexity
through the use of additional variables.
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Wao, Hesborn Otieno. "A mixed methods approach to examining factors related to time to attainment of the doctorate in education." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002554.
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Cong, Chunling. "Statistical Analysis and Modeling of Breast Cancer and Lung Cancer." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3563.
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The objective of the present study is to investigate various problems associate with breast cancer and lung cancer patients. In this study, we compare the effectiveness of breast cancer treatments using decision tree analysis and come to the conclusion that although certain treatment shows overall effectiveness over the others, physicians or doctors should discretionally give different treatment to breast cancer patients based on their characteristics. Reoccurrence time of breast caner patients who receive different treatments are compared in an overall sense, histology type is also taken into consideration. To further understand the relation between relapse time and other variables, statistical models are applied to identify the attribute variables and predict the relapse time. Of equal importance, the transition between different breast cancer stages are analyzed through Markov Chain which not only gives the transition probability between stages for specific treatment but also provide guidance on breast cancer treatment based on stating information.
Sensitivity analysis is conducted on breast cancer doubling time which involves two commonly used assumptions: spherical tumor and exponential growth of tumor and the analysis reveals that variation from those assumptions could cause very different statistical behavior of breast cancer doubling time.
In lung cancer study, we investigate the mortality time of lung cancer patients from several different perspectives: gender, cigarettes per day and duration of smoking. Statistical model is also used to predict the mortality time of lung cancer patients.
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de, Rossiter Cher. "Quality-of-Life Indicators for African American and European American Long-term Survivors of Early-stage Breast Cancer." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/31.
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This meta-analysis investigated the difference in perceptions of health-related quality of life (HRQOL) among long-term early-stage breast cancer survivors (BCS). The comparison was between African American and European American women. Initial pilot searches suggested that enough studies existed for a meaningful meta-analysis of a BCS population at least 5 years post diagnosis. Only studies using the outcome measure HRQOL were included in the study; this yielded an initial sample of 212 study reports, with 56 reports entering the coding phase of the process. African American women were grossly underrepresented in this set of studies in comparison to the overall breast cancer population. Separate analyses of Medical Outcomes Study 36- Item Short- Form Health Survey, Quality of Life-Cancer Survivor and Quality of Life Index - Cancer Version III instruments were executed. However, no stringent comparison across instruments of the difference between the HRQOL of African American and European American women was possible. When African American women were included in the populations, researchers often did not report their data separately but rather included their data in an overall population and thus differences were masked. The data that were available, including qualitative studies for African American women, suggested that there was a lower perception of the quality of survival in some areas for African American women. These differences suggest the need for greater attention to the physical components of African American BCS. The results point to a need to improve African American participant recruitment in research and to use online databases as a results repository to improve data availability for analysis.
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Martel, Guillaume. "Evaluating Surgical Outcomes: A Systematic Comparison of Evidence from Randomized Trials and Observational Studies in Laparoscopic Colorectal Cancer Surgery." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/20534.
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Background: Laparoscopic surgery for colorectal cancer is a novel healthcare technology, for which much research evidence has been published. The objectives of this work were to compare the oncologic outcomes of this technology across different study types, and to define patterns of adoption on the basis of the literature.
Methods: A comprehensive systematic review of the literature was conducted using 1) existing systematic reviews, 2) randomized controlled trials (RCTs), and 3) observational studies. Outcomes of interest were overall survival, and total lymph node harvest. Outcomes were compared for congruence. Adoption was evaluated by means of summary expert opinions in the literature.
Results: 1) Existing systematic reviews were of low to moderate quality and displayed evidence of overlap and duplication. 2) Laparoscopy was not inferior to open surgery in terms of oncologic outcomes in any study type. 3) Oncologic outcomes from RCTs and observational studies were congruent. 4) Expert opinion in the literature has been supportive of this technology, paralleling the publication of large RCTs.
Conclusions: The evaluation of laparoscopic surgery for colorectal cancer in RCTs and observational studies suggests that it is not inferior to open surgery. Adoption of this technology has paralleled RCT evidence.
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Dreilich, Martin, Michael Bergqvist, Martin Moberg, Daniel Brattström, Inger Gustavsson, Stefan Bergström, Alkwin Wanders, Patrik Hesselius, Gunnar Wagenius, and Ulf Gyllensten. "High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma : a pilot study." Uppsala universitet, Institutionen för onkologi, radiologi och klinisk immunologi, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-94408.
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BACKGROUND: Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. METHODS: We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. RESULTS: HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). CONCLUSION: Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma.De två första författarna delar förstaförfattarskapet.
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Sjöberg, Niklas B. "Eel migration - results from tagging studies with relevance to management." Doctoral thesis, Stockholms universitet, Institutionen för ekologi, miljö och botanik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-113829.
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In response to the drastic decline of the European eel (Anguilla anguilla (L.)) fisheries have been reduced and elvers are stocked in areas where natural abundances are low. Are these measures adequate? To answer different aspects of this question, we have analysed more than a century of eel tagging, using both traditional and more novel capture – recapture analyses. Based on these long-term data, we have evaluated the impact of the Swedish eel coastal fisheries using Survival analysis. Our analysis indicates that the fishing mortality just prior the 2009 fishing restrictions were in the order of 10%. More recent tagging programs have focused on issues related to the fate of stocked fish. If and how they migrate out of the Baltic Sea and further on towards the Atlantic Ocean. Both earlier and our new studies reveal that all eels recaptured on the Swedish East Coast, no matter of their origin, migrate at a reasonable speed and direction towards the outlets of the Baltic Sea. Even though it is sometimes difficult to determine their origin, our analyses indicate that stocked fish were scarce among the recaptures. In an experiment on the Swedish West Coast, we knew the individuals’ origin (stocked or wild) and they had similar migration patterns. In contrast, silver eel in Lake Mälaren – assumed to have been stocked as elvers or bootlace eels – seemed to have difficulties in finding the outlets. Instead they overwintered and lost weight. However, weight losses are also significant among non-stocked individuals in the Baltic Sea, both if they overwinter and if they appear to be on their way out from the area. It remains an open question whether eels from the Baltic region in general, and whether the overwintered fish in particular, manage to reach the spawning area in the Atlantic Ocean. Based on current knowledge, I advocate invoking the precautionary approach and to concentrate Swedish eel stockings to the West Coast and allow the young fish to spread out on their own.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.
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Begum, Mubeena. "Gene expression profiles and clinical parameters for survival prediction in stage II and III colorectal cancer." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001554.
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Moral, Rafael de Andrade. "Statistical modelling of data from insect studies." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/11/11134/tde-06042018-153400/.
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Data from insect studies may present different features. Univariate responses may be analyzed using generalized linear models (continuous and discrete data), survival models (time until event data), mixed effects models (longitudinal data), among other methods. These models may be used to analyse data from experiments which assess complex ecological processes, such as competition and predation. In that sense, computational tools are useful for researchers in several fields, e.g., insect biology and physiology, applied ecology and biological control. Using different datasets from entomology as motivation, as well as other types of datasets for illustration purposes, this work intended to develop new modelling frameworks and goodness-of-fit assessment tools. We propose accelerated failure rate mixed models with simultaneous location and scale modelling with regressors to analyse time-until-attack data from a choice test experiment. We use the exponential, Weibull and exponentiated-Weibull models, and assess goodness-of-fit using half-normal plots with simulation envelopes. These plots are the subject of an entire Chapter on an R package, called hnp, developed to implement them. We use datasets from different types of experiments to illustrate the use of these plots and the package. A bivariate extension to the N-mixture modelling framework is proposed to analyse longitudinal count data for two species from the same food web that may interact directly or indirectly, and example datasets from ecological studies are used. An advantage of this modelling framework is the computation of an asymmetric correlation coefficient, which may be used by ecologists to study the degree of association between species. The jointNmix R package was also developed to implement the estimation process for these models. Finally, we propose a goodness-of-fit assessment tool for bivariate models, analogous to the half-normal plot with a simulation envelope, and illustrate the approach with simulated data and insect competition data. This tool is also implemented in an R package, called bivrp. All software developed in this thesis is made available freely on the Comprehensive R Archive Network.Dados provenientes de estudos com insetos podem apresentar características diferentes. Respostas univariadas podem ser analisadas utilizando-se modelos lineares generalizados (dados contínuos e discretos), modelos de análise de sobrevivência (dados de tempo até ocorrência de um evento), modelos de efeitos mistos (dados longitudinais), dentre outros métodos. Esses modelos podem ser usados para analisar dados provenientes de experimentos que avaliam processos ecológicos complexos, como competição e predação. Nesse sentido, ferramentas computacionais são úteis para pesquisadores em diversos campos, por exemplo, biologia e fisiologia de insetos, ecologia aplicada e controle biológico. Utilizando diferentes conjuntos de dados entomológicos como motivação, assim como outros tipos de dados para ilustrar os métodos, este trabalho teve como objetivos desenvolver novos modelos e ferramentas para avaliar a qualidade do ajuste. Foram propostos modelos de tempo de vida acelerado mistos, com modelagem simultânea dos parâmetros de locação e de escala com regressores, para analisar dados de tempo até ataque de um experimento que avaliou escolha de predadores. Foram utilizados modelos exponencial, Weibull e Weibull-exponenciado, e a qualidade do ajuste foi avaliada utilizando gráficos meio-normais com envelope de simulação. Esses gráficos são o assunto de um Capítulo inteiro sobre um pacote para o software R, chamado hnp, desenvolvido para implementá-los. Foram utilizados conjuntos de dados de diferentes tipos de experimentos para ilustrar o uso desses gráficos e do pacote. Uma extensão bivariada para os modelos chamados \"N-mixture\" foi proposta para analisar dados longitudinais de contagem para duas espécies pertencentes à mesma teia trófica, que podem interagir direta e indiretamente, e conjuntos de dados provenientes de estudos ecológicos são usados para ilustrar a abordagem. Uma vantagem dessa estratégica de modelagem é a obtenção de um coeficiente de correlação assimétrico, que pode ser utilizado por ecologistas para inferir acerca do grau de associação entre espécies. O pacote jointNmix foi desenvolvido para implemetar o processo de estimação para esses modelos. Finalmente, foi proposta uma ferramenta de avaliação de qualidade do ajuste para modelos bivariados, análoga ao gráfico meio-normal com envelope de simulação, e a metodologia _e ilustrada com dados simulados e dados de competição de insetos. Essa ferramenta está também implementada em um pacote para o R, chamado bivrp. Todo o software desenvolvido nesta tese está disponível, gratuitamente, na Comprehensive R Archive Network (CRAN).
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Josefsson, Andreas. "Prognostic markers in prostate cancer : studies of a watchful waiting cohort with long follow up." Doctoral thesis, Umeå universitet, Patologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-50722.
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Background: Prostate Cancer (PC) is a common and highly variable disease. Using current diagnostic methods, the prostate specific antigen (PSA) blood test and histological grading of prostate tissue needle biopsies, it is often difficult to evaluate whether the patient has a PC that requires active treatment or not. The absolute majority of all 10,000 cases of PCs diagnosed annually in Sweden have tumours graded as Gleason score (GS) 6-7 and a PSA value in blood below 10. Many of these are harmless and can be left without active treatment and hence spared problematic post-therapy side-effects, others are highly malignant and require early diagnosis and treatment. Better prognostic markers are needed and the aim of this study was to evaluate prognostic markers and to test if these markers could identify patients with indolent tumours. Methods: We have studied tumour material from 419 men consecutively diagnosed with PC at transurethral resection (1975-1990). The majority of these patients (295) had no metastasis at diagnosis and was not given any curative treatment and only hormonal treatment upon symptoms from metastatic progression. Standard histological sections and tissue microarrays (TMA) from these tumours and surrounding normal prostate tissue were stained and evaluated for cell proliferation (Ki67), blood vessels (endoglin and von Willebrand factor, vWf) and the extracellular matrix component hyaluronan (HA). An orthotopic rat PC model was used to explore hyaluronan staining, hyaluronic acid synthase (HAS)-1 mRNA levels and the effect of local HA treatment on tumour growth. Results: Tumour cell proliferation (Ki67) and the density of intra-tumoural endoglin stained blood vessels were independent prognostic markers (i.e. they added prognostic information to the conventional prognostic markers; clinical stage and GS). None of the GS 6 patients with low staining for both Ki67 and endoglin died of PC within 15 years of follow-up. High HA staining in the tumour epithelium and stroma was a negative prognostic marker of cancer specific survival but they were not independent of GS. High HA staining and high vascular density in the stroma of the surrounding morphologically normal prostate were prognostic for short cancer specific survival. Implantation of tumour cells in the normal rat prostate resulted in an increase in HA and HAS-1 mRNA levels in the prostate tissue surrounding prostate tumours. Concurrently intra-prostatic injection of HA also stimulated tumour growth. Conclusions: By evaluating both tumour cell proliferation (Ki67) and vascular density, it is possible to identify patients with very low risk of cancer specific death in the absence of active treatment. Prostate tumours influence the surrounding non-malignant prostate tissue, for example they cause an increased angiogenesis and synthesis of hyaluronan. Such responses can possibly be used to diagnose PC and to evaluate PC aggressiveness.
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Bette, Miriam. "Political tourism? : A critical social analysis on ecotourism and the indigenous struggle in the Ecuadorian Amazons." Thesis, Stockholms universitet, Romanska och klassiska institutionen, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-168891.
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Enabled by a Minor Field Study scholarship from SIDA, this thesis examines indigenous involvement in ecotourism in the Ecuadorian Amazons. Indigenous people are the most marginalized social group world-wide, and coincidingly often live in resource rich pristine land. The oil-rich lands of the Amazons is called a resource frontier and is now increasingly important for the tourism sector, which comes to entail conflict of interests between the State and indigenous communities living in this area. Both the global call for sustainable development and national policies of “Buen Vivir” promotes ecotourism as an ecologically, socio-economically, and culturally sustainable activity. Scholarly opinion suggest that ecotourism generates potential tools of empowerment for the involved indigenous communities. With this backdrop and with the theoretical framework of the postcolonial debate, main opportunities and challenges are examined with the correlation of tourism ventures and socio-political implications in the local reality of indigenous organizations in Tena, Napo. Complex impediments are uncovered and analysed within the social field of indigenous ecotourism. The conviction of the study holds the call for attentive cross-cultural communication in order to continue the seemingly inevitable path of globalization in a more sustainable and non-discriminatory manner.
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Silva, Franciane Figueiredo da. "Epidemiologia das Leucemias Infantis de 1997 a 2013, São Paulo, Brasil." Universidade de São Paulo, 2019. http://www.teses.usp.br/teses/disponiveis/6/6141/tde-27022019-160813/.
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Introdução: A leucemia é o tipo mais comum de câncer em crianças de 0 a 14 anos. Estudos apontam que, em diversos países do mundo, as taxas de incidência estão aumentando, ou se mantêm estáveis, e que, por outro lado, as taxas de mortalidade estão caindo. Em países desenvolvidos, a leucemia é considerada uma doença curável, possuindo taxas de sobrevida superiores a 80%. Objetivos: Descrever a epidemiologia da leucemia na infância no município de São Paulo, no período de 1997 a 2013, analisando as tendências de incidência e mortalidade, e as taxas de sobrevida, segundo sexo, faixa etária, tipo de leucemia e região administrativa. Métodos: As taxas brutas e ajustadas de incidência e mortalidade foram calculadas segundo sexo e idade. Foram estimados modelos de regressão polinomial e calculados os percentuais anuais de mudança (Annual Percentual Change, APC) das taxas de incidência e mortalidade. Foi calculado o estimador não paramétrico produto limite de Kaplan-Meier e utilizado o teste de logrank para comparação das curvas de sobrevida. Foi construído o modelo de riscos proporcionais de Cox para estimar as hazard ratios de cada variável de estudo. Resultados: Foram contabilizados 2028 casos novos e 660 óbitos por leucemias, em crianças de 0 a 14 anos, no município de São Paulo, no período estudado. A taxa de incidência foi de 49,8 casos por 1 milhão de crianças e a taxa de mortalidade foi de 15,7 óbitos por 1 milhão de crianças, sendo mais frequente o subtipo leucemia linfoide aguda, entre o sexo masculino, na faixa etária de 0 a 4 anos. No período de 1997 a 2013, a taxa de incidência por leucemia em crianças no município de São Paulo foi decrescente (APC= -2,7%). Já a taxa de mortalidade, no geral, se manteve estável, mas foi decrescente para algumas características específicas, tais como, para sexo masculino (APC= -1,9%) e para o subtipo das leucemias mieloides agudas (APC= -1,8%). As taxas de sobrevida foram de 86%, 73% e 68%, respectivamente, após 12, 36 e 60 meses, bem abaixo do que se observa nos países desenvolvidos. Conclusão: Os percentuais e taxas de mortalidade e incidência da leucemia em crianças no município de São Paulo se assemelham aos valores encontrados na América Latina. O comportamento da tendência das taxas de incidência se difere ao encontrado na maioria dos países e o comportamento da tendência das taxas de mortalidade acompanha o padrão mundial. A leucemia em crianças é considerada uma doença curável, porém as taxas de sobrevida encontradas estão bem abaixo do esperado. Esta análise com dados do registro de câncer de base populacional mostra o panorama da leucemia em crianças no município de São Paulo. Estes resultados poderão ser utilizados desde a gestão dos serviços de saúde, a dar suporte a pesquisas futuras, sobre etiologia da doença.Introduction: Leukemia is the most common type of cancer in children 0-14 years old. Studies show that, in several countries around the world, incidence rates are increasing, or remain stable, and that, on the other hand, mortality rates are decreasing. In developed countries, leukemia is considered a curable disease, with survival rates above 80%. Objectives: To describe the epidemiology of childhood leukemia in the city of São Paulo from 1997 to 2013, analyzing trends in incidence and mortality, and survival rates, according to sex, age group, type of leukemia and administrative region. Methods: Crude and adjusted rates of incidence and mortality were calculated according to sex and age. Polynomial regression models were estimated and the Annual Percentual Change (APC) of the incidence and mortality rates were calculated. It was estimated the non-parametric Kaplan-Meier limit product estimator and the logrank test was used to compare the survival curves. The Cox proportional hazards model was constructed to estimate the hazard ratios of each study variable. Results: A total of 2028 new cases and 660 deaths by leukemias were recorded in children aged 0 to 14 years, in the city of São Paulo, during the period studied. The incidence rate was 49.8 cases per 1 million children and the mortality rate was 15.7 deaths per 1 million children, which most frequent being the acute lymphoid leukemia subtype among males in the age group of 0 to 4 years old, living in the Southeast region of the city of São Paulo. In the period from 1997 to 2013, the incidence rate by leukemia in children in the city of São Paulo decreased (APC = -2.7%). The overall mortality rate remained stable, and decreased to some specific characteristics, such as for males (APC = -1.9%) and for the acute myeloid leukemia subtype (APC = -1.8% ). Survival rates were 86%, 73% and 68%, respectively, after 12, 36 and 60 months, below of those observed in developed countries. Conclusion: The percentages and mortality and incidence rates by leukemia in children in the city of São Paulo are similar to those found in Latin America. The trends of incidence rates differs from that found in most countries and the trends of mortality rates follows the world standard. Leukemia in children is considered a curable disease, but the survival rates found are below of the developed countries. This analysis with data from the population-based cancer registry shows the picture of leukemia in children in the city of São Paulo. These results can be used since the management of the health services, to support future research on the etiology of the disease.
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Hultman, Bo. "Clinical and Experimental Studies in Peritoneal Metastases from Gastric Cancer." Doctoral thesis, Uppsala universitet, Kolorektalkirurgi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-197776.
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Gastric cancer (GC) is one of leading causes of death in the world, and peritoneal metastases (PM) are a major site of recurrence. PM from GC implies a poor prognosis, with median overall survival (mOS) approximately 3 months and no survival at five years. The aims of this thesis were to explore the incidence and evaluate prognostic factors for mOS of PM from GC in a defined population; to investigate the outcome of a new multimodal treatment; to analyse the treatment costs, and to investigate differences in drug sensitivity between individual patient samples and between various tumours. The incidence of loco-regional advanced GC was 3.8 per 100,000 person-years. Synchronous loco-regional GC in combination with synchronous distant metastasis was a negative prognostic factor while chemotherapy and good performance status, and radiotherapy plus chemotherapy were positive prognostic factors . There were no significant differences in mOS for the group of patients included during the period 2000-2004 versus 2005-2009, and this lack of improvement in mOS during the past decade justifies new treatment approaches. In a Phase II study of patients treated with neoadjuvant systemic chemotherapy followed by cytoreductive surgery + hyperthermic intraperitoneal chemotherapy, mOS was 14.3 months and for patients with macroscopically radical surgery mOS was 19.1 months. The mean overall cost of the loco-regional treatment was $145,700 compared to $59,300 with systemic chemotherapy treatment. In an ex vivo chemo-sensitivity test, it was determined that GC samples were equivalent to colorectal cancer in chemo-sensitivity to standard drugs and targeted drugs, whereas ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the drugs, arguing for individualized drug selection. The incidence of loco-regional advanced GC was more common than previously reported and there were no improvements in mOS over the past decade. The mOS for patients with neoadjuvant systemic chemotherapy followed by macroscopically radical cytoreductive surgery + hyperthermic intraperitoneal chemotherapy was better than in recent reports on treatment with systemic chemotherapy. Treatment of advanced GC patients is costly irrespective of treatment modality. The GC samples varied considerably between individuals in terms of sensitivity to increasing concentrations of the drugs and were comparable to colorectal cancer in chemo-sensitivity.
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Strock, Cynthia Lynn. "The impact of electronic clinical reminders on medication trends and six-month survival after coronary artery bypass graft surgery in the Veterans Healthcare Administration /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
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Thesis (Ph.D. in Clinical Science) -- University of Colorado Denver, 2007.Typescript. Includes bibliographical references (leaves 86-91). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Ahlsson, Anders. "Atrial fibrillation in cardiac surgery." Doctoral thesis, Örebro universitet, Hälsoakademin, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-2442.
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Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice. In cardiac surgery, one-third of the patients experience episodes of AF during the first postoperative days (postoperative AF), and patients with preoperative AF (concomitant AF) can be offered ablation procedures in conjunction with surgery, in order to restore ordinary sinus rhythm (SR). The aim of this work was to study the relation between postoperative AF and inflammation; the long-term consequences of postoperative AF on mortality and late arrhythmia; and atrial function after concomitant surgical ablation for AF. In 524 open-heart surgery patients, C-reactive protein (CRP) serum concentrations were measured before and on the third day after surgery. There was no correlation between levels of CRP and the development of postoperative AF. All 1,419 patients with no history of AF, undergoing primary aortocoronary bypass surgery (CABG) in the years 1997–2000 were followed up after 8.0 years. The mortality rate was 191 deaths/1,000 patients (19.1%) in patients with no AF and 140 deaths/419 patients (33.4%) in patients with postoperative AF. Postoperative AF was an age-independent risk factor for late mortality, with a hazard ratio (HR) of 1.56 (95% CI 1.23–1.98). Postoperative AF patients had a more than doubled risk of death due to cerebral ischaemia, myocardial infarction, sudden death, and heart failure compared with patients without AF. All 571 consecutive patients undergoing primary CABG during the years 1999–2000 were followed-up after 6 years. Questionnaires were obtained from 91.6% of surviving patients and an electrocardiogram (ECG) from 88.3% of all patients. In postoperative AF patients, 14.1% had AF at follow-up, compared with 2.8% of patients with no AF at surgery (p<.001). An episode of postoperative AF was found to be an independent risk factor for development of late AF, with an adjusted risk ratio (RR) of 3.11 (95% CI 1.41–6.87). Epicardial microwave ablation was performed in 20 open-heart surgery patients with concomitant AF. Transthoracic echocardiography was performed preoperatively and at 6 months postoperatively. At 12 months postoperatively 14/19 patients (74%) were in SR with no anti-arrhythmic drugs. All patients in SR had preserved left and right atrial filling waves (A-waves) and Tissue velocity echocardiography (TVE) showed preserved atrial wall velocities and atrial strain. In conclusion, postoperative AF is an independent risk factor for late mortality and later development of AF. There is no correlation between the inflammatory marker CRP and postoperative AF. Epicardial microwave ablation of concomitant AF results in SR in the majority of patients and seems to preserve atrial mechanical function.
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Rezende, Marina Aleixo Diniz. "A fragilidade e sua relação com a mortalidade em idosos de uma comunidade brasileira." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/22/22132/tde-30092016-162423/.
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A fragilidade é uma síndrome geriátrica de causa multifatorial e está associada ao declínio funcional, à dependência, a quedas recorrentes, a fraturas, à institucionalização, hospitalização e morte. O objetivo deste estudo foi analisar a evolução da fragilidade e sua relação com a mortalidade em idosos que vivem em uma comunidade brasileira, em um período médio de seguimento de 2055,5 (dp=86,4) dias. Trata-se de uma coorte, realizada em duas avaliações na cidade de Ribeirão Preto-SP, com uma amostra na primeira etapa em 2007/2008 de 515 idosos e na segunda com 262 idosos que viviam na comunidade de ambos os sexos e idade igual ou superior a 65 anos. Os dados foram coletados por meio de visitas domiciliares, utilizando-se os instrumentos de informação pessoal, perfil social, morbidades autorreferidas, Edmonton Frail Scale (EFS) e mortalidade. Os dados foram analisados por meio do Programa SPSS, onde foram realizadas as análises estatísticas. Utilizou-se análise univariada dos dados e para as variáveis qualitativas a distribuição de frequências absolutas(n) e relativas(%). Para as variáveis quantitativas, foram usados medidas de tendência central (média e mediana), dispersão (desvio-padrão); Teste t pareado, teste de qui-quadrado, teste de McNemar, teste de Wilcoxon, Coeficiente de correlação de Pearson, Exato de Fisher, Risco Relativo, análise de sobrevivência de Kaplan-Meier e Regressão de Cox. O projeto foi aprovado pelo Comitê de Ética da Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo. Na primeira avaliação, em 2007/2008, participaram da pesquisa 515 idosos, sendo 67,4% do sexo feminino, média de idade de 75,37, sendo maior proporção de casados e média de 5,56 doenças. Em 2013, foram reavaliados 262 participantes, sendo maioria de mulheres com a média de idade de 79,31, maior proporção de viúvos e com média de doenças de 5,16. Quanto à evolução da fragilidade, houve um aumento significativo, durante o período de seguimento, com uma prevalência de fragilidade de 17,6%, em 2007/2008, e 50,4%, em 2013. Na análise dos itens da escala, percebeu-se uma diferença significativa entre as duas avaliações na função cognitiva, internação dos últimos 12 meses, descrição do estado de saúde, capacidade funcional, polifarmácia, incontinência urinária e desempenho funcional. Observou-se, ainda, uma correlação entre a escolaridade e o número de doenças e fragilidade, em que quanto menor a escolaridade, maior o escore de fragilidade. E quanto maior a evolução do número de doenças, maior o escore de fragilidade. Entre os idosos que faleceram, a maioria era do sexo feminino, com uma média de idade de 79,18 anos, maior percentagem de viúvos e 45,7% frágeis. O risco relativo de óbito foi significativamente maior entre os idosos mais velhos e entre aqueles que não tinham companheiro. Ao verificar a análise de sobrevivência, constatou-se ainda que a proporção de sobreviventes foi significativamente maior entre os idosos que tinham companheiro e entre aqueles não frágeis. E considerando o modelo de regressão de Cox, verificou-se que o grupo etário e a fragilidade foram preditores para o óbito. Portanto, reconhecer os fatores que contribuem para a evolução da fragilidade pode contribuir para a melhoria da qualidade de vida e, consequentemente, para uma maior sobrevidaFrailty is a geriatric syndrome of multifactorial cause and is associated with functional decline, dependency, recurrent falls, fractures, institutionalization, hospitalization and death. The objective of this study was to analyze the evolution of frailty and its association with mortality in older people who live in a Brazilian community in a mean follow-up period of 2055.5 (sd=86.4) days. This is a cohort study conducted in two assessments in the city of Ribeirão Preto, in the state of São Paulo, Brazil, with a first stage sample of 515 older people in 2007 and 2008, and the second with 262 older people of both genders, aged 65 years and older, who lived in the community. Data were collected by means of home visits, with the use of the following tools: personal information, social profile, self-reported morbidities, Edmonton Frail Scale (EFS) and mortality. The data were analyzed by means of the SPSS software, where statistical analyses were conducted. Univariate analysis of the data, and absolute(n) and relative(%) frequencies for qualitative variables were used. Measures of central tendency (mean and median), dispersion (standard deviation); paired t-test, chi- squared test, McNemar\'s test, Wilcoxon signed-rank test, Pearson\'s correlation coefficient, Fisher\'s exact test, relative risk, Kaplan-Meier survival analysis and Cox regression were used for quantitative variables. The research project was approved by the Ribeirão Preto College of Nursing Ethics Committee, at University of São Paulo. In the first assessment in 2007 and 2008, 515 older people participated in the study, being 67.4% women, with a mean age of 75.37 years, a higher proportion of married individuals and who had a mean of 5.56 diseases. In 2013, 262 participants were re-evaluated, being most women with a mean age of 79.3 years, with a higher proportion of widowers and a mean of 5.16 diseases. Regarding the evolution of frailty, a significant increase was observed during the follow-up period, with frailty prevalence of 17.6% in 2007 and 2008, and 50.4% in 2013. In the analysis of the scale items, a significant difference was observed between the two assessments as for the cognitive function, hospitalization in the last 12 months, description of the health condition, functional capacity, polypharmacy, urinary incontinence and functional performance. A correlation between education and number of diseases with frailty was also observed, in which, the lower the education level, the higher the frailty score, and the higher the evolution of the number of diseases, the higher the frailty score. Among the older people who died, most were women, with a mean age of 79.18 years, with a higher proportion of widowers and 45.7% frail individuals. The relative risk of death was significantly higher among the oldest individuals and those who did not have partners. When verifying the survival analysis, it was also noted that the proportion of survivors was significantly higher among the older people who did not have partners and those who were not frail. Moreover, considering the Cox regression model, it was verified that age group and frailty were predictors for death. Therefore, recognizing factors that contribute to the evolution of frailty can contribute to improving quality of life, and consequently having a longer life
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Soares, Felipe Fagundes. "Desigualdades sociais na sobrevida de câncer de boca e orofaringe em São Paulo." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/6/6132/tde-23042018-091300/.
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Introdução. Há evidências de que a desigualdade social pode influenciar o prognóstico do câncer quando foram comparadas as taxas de sobrevida segundo o status socioeconômico, entretanto isso ainda não foi estudado no Brasil. Objetivo. Analisar a desigualdade social na determinação da sobrevida específica em um, três e cinco anos, de pacientes diagnosticados com câncer de boca e orofaringe em São Paulo. Metodologia. Utilizou-se a coorte de base hospitalar do grupo de pesquisa Genoma Clínico do Câncer de Cabeça e Pescoço (GENCAPO), à qual foram aplicados novos critérios de exclusão. Assim, foram analisados dados demográficos, socioeconômicos, comportamentais, sintomas autorreferidos e de condições clínicas de 1.154 pacientes, com diagnóstico de malignidade nas regiões de boca (C00.3-C06) e orofaringe (C09-C10), arrolados de 2001 a 2009 e acompanhados por cinco anos. A desigualdade social foi aferida pela escolaridade e a ocupação. As probabilidades acumuladas de sobrevida específica em um, três e cinco anos foram calculadas pelo método de Kaplan-Meier e as diferenças entre as curvas de sobrevida, pelo teste de Log-rank. A regressão de Cox univariada e múltipla possibilitou a análise dos fatores associados à sobrevida - Hazard Ratio (HR) com IC95%. Resultados. As probabilidades acumuladas de sobrevida específica em um, três e cinco anos para câncer de boca e orofaringe, foram de 74,72%, 49,86 e 42,46%, respectivamente. Baixa escolaridade (HR=1,25; IC95%=1,03-1,51) e realização de trabalhos manuais (HR=1,37; IC95%=1,05-1,78) foram associados à menor probabilidade de sobrevivência em cinco anos na análise não ajustada. A cor da pele preta/parda, tumor de tamanho T3 ou T4 e comprometimento de linfonodos foram fatores independentemente associados à menor sobrevida específica por câncer de boca e orofaringe em um, três e cinco anos. Disfagia e dificuldade respiratória foram associados à menor sobrevida específica em um ano. Em três anos, observou-se também a otalgia e em cinco anos, a dificuldade de deglutição. Conclusões. Foi identificada associação entre a desigualdade social, menor escolaridade e trabalho manual, à menor sobrevida em 5 anos. Esses fatores, na análise ajustada pelas características demográficas, tiveram sua associação potencialmente explicada pela cor da pele preta/parda.Introduction. There is evidence that social inequality may influence the prognosis of cancer when comparing survival rates according to socioeconomic status, but this has not been studied in Brazil. Aim. To evaluate social inequality in the determination of one, three and five years specific survival of patients diagnosed with oral and oropharyngeal cancer in São Paulo. Methodology. A hospital-based cohort of the research group \"Clinical Genome of Head and Neck Cancer\" (GENCAPO) was used, applying new exclusion criteria. Demographic, socioeconomic, behavioral, selfreported symptoms and clinical conditions characteristics of 1,154 patients, diagnosed with malignancy in the mouth (C00.3-C06) and oropharynx (C09-C10) regions, included from 2001 to 2009 and followed up for five years, were analyzed. Social inequality was measured by schooling and occupation. The cumulative probabilities of one, three, and five years specific survival were calculated by the Kaplan-Meier method and differences between the survival curves by the log-rank test. Univariate and Multiple Cox Regression allowed to analyze the factors associated with survival - Hazard Ratio (HR) with 95% CI. Results. The accumulated probabilities of one, three and five years specific survival for oral and oropharyngeal cancer were 74.72%, 49.86 and 42.46%, respectively. Low schooling (HR = 1.25, 95% CI = 1.03-1.51) and manual work (HR = 1.37, 95% CI = 1.05-1.78) were associated with a lower survival probability at five years in the unadjusted analysis. Dysphagia and breathing difficulties were associated with lower one year specific survival. At three years, it was also observed earache, and at five years, swallowing difficulty. Conclusions. An association among social inequality, lower schooling and manual labor, with the lowest survival at 5 years, was identified. These results were potentially explained by black/brown skin color in the adjusted analysis for demographic characteristics.
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Sanders, Carolyn L. "Clinical antecedents of a medical emergency team response as predictors of ICU transfer /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008.
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Thesis (Ph.D. in Nursing) -- University of Colorado Denver, 2008.Typescript. Includes bibliographical references (leaves 100-107). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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Aliberti, Márlon Juliano Romero. "Avaliação geriátrica compacta de 10 minutos: desenvolvimento e validação de um instrumento de rastreio multidimensional breve para idosos." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5169/tde-28022019-085029/.
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INTRODUÇÃO: A avaliação geriátrica ampla promove uma triagem programada das síndromes e alterações mais comuns nos idosos. Este instrumento multidimensional apresenta excelente desempenho na identificação precoce de pacientes em risco para desfechos adversos. No entanto, tempo e recursos limitados impedem o seu uso em serviços de saúde concorridos, em especial aqueles que oferecem cuidados agudos. OBJETIVOS: Desenvolver e investigar as propriedades psicométricas de uma avaliação geriátrica compacta de 10 minutos (AGC-10) para idosos em serviços de saúde ocupados. MÉTODOS: Na primeira etapa, um consenso de especialistas (técnica Delphi) composto por 62 geriatras de todas as regiões do Brasil desenvolveu o instrumento. Na segunda etapa, as propriedades psicométricas da AGC-10 foram investigadas em uma coorte prospectiva envolvendo 534 idosos com doenças agudas ou crônicas descompensadas (média de 79,5 ± 8,4 anos de idade; 63% mulheres) consecutivamente admitidos em um hospital dia de um centro médico acadêmico, em São Paulo, Brasil. A AGC-10 foi administrada na admissão. O Frailty Index e o fenótipo de fragilidade foram usados para explorar a validade da AGC-10. Houve seguimento de um ano por contato telefônico mensal para aferição dos desfechos perda funcional para atividades básicas de vida diária (ABVD), hospitalização e morte. Modelos de riscos proporcionais, que consideraram morte como um evento competitivo, associaram a AGC-10 com os desfechos adversos após ajuste para fatores sociodemográficos (idade, sexo, raça e renda) e índice de comorbidades de Charlson. A confiabilidade interexaminadores e o tempo para administrar o instrumento foram examinados em uma subamostra representativa de 53 participantes. RESULTADOS: Em três rodadas de opinião, os especialistas de 32 instituições diferentes estabeleceram consenso de que a AGC-10 deveria incluir 10 domínios (suporte social, hospitalizações recentes, quedas, número de medicamentos, ABVD, cognição, autoavaliação da saúde, sintomas depressivos, estado nutricional e velocidade de marcha). Houve acordo sobre os instrumentos específicos para avaliar cada domínio. Um índice total de 0 a 1 expressou a média dos déficits encontrados nos 10 domínios e classificou os pacientes em três níveis: baixo (0-0,29), médio (0,3-0,39) e alto (0,4-1) risco. O índice AGC-10 correlacionou-se fortemente com o Frailty Index (coeficiente de Spearman=0,79; IC95%=0,76-0,82) e apresentou acurácia excelente para identificar indivíduos frágeis (área sob a curva ROC=0,84 IC95%=0,81-0,87). Em comparação aos de baixo risco, pacientes classificados como médio e alto risco na AGC-10 tiveram maior incidência de perda funcional (33% vs. 13%, sub-HR=2,3 IC95%=1,3-4,0; 51% vs. 13%, sub-HR=4,1 IC95%=2,4-6,9, respectivamente), hospitalização (44% vs. 22%, sub-HR=2,4 IC95%=1,5-3,9; 51% vs. 22%, sub-HR=3,2 IC95%=2,0-4,9, respectivamente) e morte (18% vs. 5%, HR=2,9 IC95%=1,2-7,3; 24% vs. 5%, HR=3,9 IC95%=1,7-9,3, respectivamente) em um ano. O índice AGC-10 mostrou excelente confiabilidade interexaminadores (coeficiente de correlação intraclasse=0,92 IC95%=0,87-0,95). O tempo médio de administração do novo instrumento foi de 9,5 ± 2,2 minutos. CONCLUSÕES: O estudo apresenta evidências robustas que sustentam a validade e confiabilidade da AGC-10. Este instrumento de rastreio multidimensional breve pode ser uma opção prática e eficiente para identificar condições geriátricas, prever desfechos adversos e guiar os cuidados dos idosos em serviços de saúde em que os profissionais tenham limitação de tempo e recursosBACKGROUND: Comprehensive geriatric assessment promotes a systematic screening of the geriatric syndromes and other health problems that commonly affect older adults. This multidimensional instrument has excellent performance to identify high-risk older patients for adverse outcomes. However, limited time and resources hinder its use in busy healthcare settings. OBJECTIVES: To develop and investigate the psychometric properties of a 10-minute targeted geriatric assessment (10-TaGA) designed for older adults in fast-paced healthcare settings. METHODS: A consensus of experts (Delphi technique) comprising 62 geriatrics from all regions of Brazil developed the instrument. We investigated the psychometric properties of 10-TaGA in a prospective cohort study involving 534 acutely ill older outpatients (mean age 79,5 ± 8,4 years; 63% female) consecutively admitted to a day hospital at an academic medical center, in Sao Paulo, Brazil. The 10-TaGA was administered on admission. The Frailty index and Physical Frailty Phenotype were used to explore 10-TaGA\'s validity. We conducted 1-year follow-up by monthly phone contacts to assess the outcomes, which included new dependence in basic activities of daily living (ADL), hospitalization, and death. Hazard models, considering death as a competing event, were used to associate 10-TaGA with the adverse outcomes after adjusting for sociodemographic factors (age, sex, race, and income) and Charlson comorbidity index. The interrater reliability and time to complete the instrument were evaluated in a 53-person representative subsample. RESULTS: In three rounds of opinion, experts from 32 institutions achieved consensus that the 10-TaGA should include 10 domains (social support, recent hospitalizations, falls, number of medications, ADL, cognition, self-rated health, depressive symptoms, nutritional status, and gait speed). They arrived at sufficient agreement on specific tools to evaluate each domain. A single numerical score from 0 to 1 expressed the cumulative deficits across the 10 domains and classified participants into three levels: low (0-0.29), medium (0.3-0.39), and high (0.4-1) risk. The 10-TaGA score was highly correlated with the Frailty Index (Spearman coefficient=0.79, 95CI%=0.76-0.82) and had an excellent accuracy to identify frail older adults (area under the ROC curve=0.84, 95%CI=0.81-0.87). Compared to low-risk patients, those classified as medium-risk and high-risk according to 10-TaGA presented a higher incidence of new ADL dependence (33% vs. 13%, sub- HR=2.3, 95%CI=1.3-4.0; 51% vs. 13%, sub-HR=4.1, 95%CI=2.4-6.9, respectively), hospitalization (44% vs. 22%, sub-HR=2.4, 95%CI=1.5-3.9; 51% vs. 22%, sub-HR=3.2, 95%CI=2.0-4.9, respectively) e death (18% vs. 5%, HR=2.9, 95%CI=1.2-7.3; 24% vs. 5%, HR=3.9, 95%CI=1.7-9.3, respectively) during the 1-year follow-up period. The 10-TaGA score had excellent interrater reliability (intraclass correlation coefficient=0.92, 95%CI=0.87-0.95). Mean time to administer the instrument was 9.5 ± 2.2 minutes. CONCLUSIONS: The study presents robust evidence supporting 10-TaGA\'s validity and reliability. This brief multidomain screener tool may be a practical and efficient approach to identify geriatric syndromes, predict adverse outcomes, and guide the care of older adults in healthcare settings where providers have limited time and resources
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Lamarca, Casado Rosa. "Gender diferences in the association between disability and mortality in the elderly." Doctoral thesis, Universitat Pompeu Fabra, 2006. http://hdl.handle.net/10803/7097.
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Aquesta tesi avalua l'existència de diferencies per gènere en la relació entre discapacitat i mortalitat, i aspectes metodològics en l'anàlisi de supervivènciad'estudis de gent gran. Es van utilitzar les dades provinents d'una cohort de 1.315 subjectes amb edats superiors o iguals a 65 anys que van ser seguits durant un periode de 8 anys. La discapacitat es va mesurar mitjançant la capacitat que declarava l'individu per dur a terme activitats de la vida diària bàsiques. La discapacitat va evolucionar al llarg del temps empitjorant amb l'edat, però una proporció no menyspreable va ser capaç de recuperar-se. Es van observar diferències per gènere en l'evolució de la discapacitat: les dones tenien més dificultats en recuperar la seva capacitat funcional un cop esdevenien discapacitades. La força de l'associació entre la discapacitat i la mortalitat disminuia a edats avançades. Es van trobar diferencies per sexe: les dones depenents mostraven un risc de morir més alt que el homes depenents.
Polítiques de salut dirigides a dones discapacitades haurien de ser implementades degut a la proporció més elevada de dones discapacitades, la probabilitat menor que tenen de recuperar la capacitat funcional, i el risc de morir més elevat que presenten comparat amb homes dicapacitats.
This thesis evaluates the existence of gender differences in the relationship between disability and mortality, as well as methodological aspects of the survival analysis for elderly studies. Data from a cohort of 1,315 subjects aged 65 years and older followed-up 8 years was used. Disability was assessed by self-reported difficulty to perform basic activities of daily living.
Disability evolved over time worsening with age, but a non-negligible proportion was able to recover. There were gender differences in the evolution of disability: women were less able to regain functional capacity once they become disabled. The strength of the association between disability and mortality decreased in the older ages. But differences by gender were found: dependent elderly women showed a higher risk of dying compared to dependent men.
Health policies focusing on disabled women should be implemented, due to the higher proportion of disabled women, the lower probability of regaining functional capacity, and their higher risk of dying compared to disabled men.
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Furuya, Tatiane Katsue. "Associação entre polimorfismos em genes relacionados à resposta inflamatória e a suscetibilidade, progressão e prognóstico do câncer gástrico." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-11052017-083936/.
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INTRODUÇÃO: A persistência de um microambiente cronicamente inflamado no estômago tem sido descrita como um componente crítico tanto para a iniciação, quanto para a progressão tumoral. Além disso, variações genéticas tem demonstrado influenciar na variabilidade interindividual da resposta inflamatória. Desta forma, esse estudo teve como objetivo investigar a associação de polimorfismos em genes relacionados à resposta inflamatória com o risco para o desenvolvimento do câncer gástrico, com suas variáveis anatomopatológicas e com a sobrevida global e livre de doença em uma amostra da população Brasileira. MÉTODOS: Dezesseis variantes genéticas selecionadas em onze genes (COX-2, OGG1, TNFB, TNFA, HSPA1L, HSPA1B, VEGFA, IL17F, LGALS3, PHB e TP53) foram genotipadas em 262 indivíduos controles e 178 pacientes diagnosticados com câncer gástrico. As análises de associações genéticas foram realizadas em diferentes modelos (Genótipos, Alelos, Dominante e Recessivo) considerando a amostra total de casos (N=178) e estratificada somente para os casos com o subtipo histológico difuso de Lauren (N=112). Também foi investigado o desequilíbrio de ligação entre os polimorfismos e as análises de associação com os haplótipos formados foram realizadas por meio dos softwares Haploview e PLINK. RESULTADOS: No estudo caso-controle, indivíduos portadores do alelo Pro do polimorfismo rs1042522 (TP53) apresentaram risco cerca de duas vezes maior em desenvolver o câncer gástrico em análise multivariada, sendo esse risco ainda maior quando considerado somente os casos com o subtipo difuso. Por outro lado, a presença do alelo A do polimorfismo rs699947 (VEGFA) foi associada com uma proteção para o câncer gástrico. Em relação às variáveis anatomopatológicas, os polimorfismos rs689466 (COX-2); rs1052133 (OGG1); rs699947, rs833061 e rs2010963 (VEGFA); rs4644 (LGALS3) e rs1042522 (TP53) foram significativamente associados com características de pior progressão da doença, enquanto que rs5275 (COX-2); rs2227956 (HSPA1L) e rs3025039 (VEGFA) foram associados às variáveis de melhor progressão da doença, na amostra total de casos. Também foi observado que o polimorfismo rs909253 (TNFB) foi capaz de predizer uma melhor progressão da doença quando considerado somente os casos com subtipo difuso. Além disso, em relação ao impacto sobre a sobrevida, rs909253 (TNFB) foi associado a um melhor prognóstico quando analisadas ambas as curvas de sobrevida global e livre de doença, enquanto que portadores do alelo His do polimorfismo rs4644 (LGALS3) apresentaram um pior prognóstico com menor tempo de sobrevida livre de doença. Por fim, nas análises de associação com os haplótipos, identificamos que o haplótipo CTC (formado por rs699947, rs833061 e rs2010963 do gene VEGFA), demonstrou ser um fator de maior suscetibilidade ao câncer gástrico. Também foram observadas associações entre o haplótipo GG (TNFB/TNFA) e invasão perineural; haplótipo ACG (VEGFA) e invasão sanguínea; haplótipo CTC (VEGFA) e invasão para outros órgãos; haplótipo GT (rs689466 e rs5275 do gene COX-2) e subtipo histológico intestinal. CONCLUSÕES: Os resultados desse estudo nos ajudaram a esclarecer o potencial papel desses polimorfismos em genes envolvidos com a modulação da resposta inflamatória na patogênese do câncer gástrico, indicando que variantes genéticas do hospedeiro atuam conjuntamente com outros fatores, influenciando na suscetibilidade, progressão e prognóstico dessa doençaINTRODUCTION: The chronic inflammatory microenvironment in the stomach has been described as a critical component for both tumor initiation and progression. Furthermore, genetic variants have shown to influence the interindividual variations in the inflammatory response. Therefore, we aimed to investigate whether polymorphisms in inflammatory response related-genes were associated with risk for gastric tumor development, clinical outcomes, overall and disease free survival of this disease in a Brazilian population sample. METHODS: Sixteen selected genetic variants in eleven genes (COX-2, OGG1, TNFB, TNFA, HSPA1L, HSPA1B, VEGFA, IL17F, LGALS3, PHB and TP53) were genotyped in 262 control individuals and 178 gastric cancer patients. Genetic association analyses were investigated in different models (Genotype, Allele, Dominant and Recessive) in both total sample (N=178) and stratified for the diffuse histological subtype based on Lauren´s classification (N=112). We also calculated the linkage disequilibrium among the polymorphisms and the haplotype associations were carried out using Haploview and PLINK softwares. RESULTS: In the case-control study, rs1042522 (TP53) Pro allele carriers presented about 2-fold higher risk for developing gastric cancer in a multivariate analysis and this association was even stronger when analyzing only cases with the diffuse subtype. On the other hand, the presence of A allele of rs699947 (VEGFA) was associated with a protection for developing gastric cancer. About the significant associations detected with the clinicopathological features, we found that rs689466 (COX-2); rs1052133 (OGG1); rs699947, rs833061 and rs2010963 (VEGFA); rs4644 (LGALS3) and rs1042522 (TP53) were able to predict outcomes associated with a worse progression of the disease while rs5275 (COX-2); rs2227956 (HSPA1L) and rs3025039 (VEGFA) were associated with better outcomes in the total sample. We also observed that the polymorphism rs909253 (TNFB) was able to predict a better outcome only for the individuals diagnosed with the diffuse subtype. Additionally, regarding the impact on the survival curves, rs909253 (TNFB) was associated with a better prognosis when analyzing both the overall and disease-free survivals while rs4644 (LGALS3) His allele carriers presented a worse prognosis with shorter disease-free survival. Finally, concerning the haplotype associations, we found that CTC haplotype (composed by rs699947, rs833061 and rs2010963 of VEGFA) showed an association with gastric malignancy. We also observed associations between GG haplotype (TNFB/TNFA) and perineural invasion; ACG haplotype (VEGFA) and venous vascular invasion; CTC haplotype (VEGFA) and invasion to other organs and GT haplotype (rs689466 and rs5275 of COX-2 gene) and the intestinal histologic subtype. CONCLUSIONS: These results helped us to clarify the potential role of these polymorphisms in genes involved in the modulation of the inflammatory response in the pathogenesis of gastric malignancy, highlighting that the host genetic variants act together with other factors to influence in the susceptibility, progression and prognosis of gastric cancer
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Etzel, Arnaldo. "Estudo das infecções pelo HTLV-I e pelo HTLV-II como fatores prognósticos em uma coorte de portadores do HIV acompanhados em Santos-SP." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/5/5134/tde-07102014-091147/.
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s retrovírus humanos incluem o vírus da imunodeficiência humana (HIV), agente causal da síndrome da imunodeficiência adquirida (AIDS), e os vírus linfotrópicos de células T humanas do tipo I (HTLV-I) e do tipo II (HTLV-II), estes associados etiologicamente a doenças de natureza linfoproliferativa e/ou neurodegenerativa. Apresentam as mesmas formas de transmissão, resultando em fatores comuns de risco e em sobreposição de populações expostas. Embora os três vírus sejam linfotrópicos, o HIV se apresenta com altas taxas de replicação e proporciona a morte celular em todos os estágios da infecção, enquanto o HTLV-I e o HTLV-II podem causar proliferação e eventualmente transformação celular. O efeito do HTLV-I e do HTLV-II sobre o sistema imunológico como um dos fatores que interferem na evolução da AIDS envolve um grande interesse e ainda é motivo de controvérsia. Pesquisas in vitro sugerem que o HTLV-I e o HTLV-II podem aumentar a replicação e a expressão do HIV. Alguns estudos clínico-epidemiológicos apontam na direção de que exista efeito da concomitância das infecções pelo HIV e pelo HTLV-I ou pelo HTLV-II sobre a evolução da progressão da AIDS. Em um estudo anterior, desenvolvido entre portadores do HIV atendidos no Centro de Referência em AIDS de Santos-SP, observou-se uma soroprevalência de 6,0% da infecção pelo HTLV-I e de 7,4% pelo HTLV-II, o que poderia justificar a investigação de possível modificação na evolução da história natural da infecção pelo HIV nesses pacientes co-infectados. O presente trabalho foi desenvolvido, como um estudo de coorte retrospectiva, visando a avaliar o tempo de sobrevida dos portadores do HIV na população estudada e sua associação com as infecções pelo HTLV-I e pelo HTLV-II, bem como com outros fatores prognósticos e marcadores de progressão. Dos 495 portadores do HIV acompanhados entre 1997 e 2002, em um número total de 23.031,5 pacientes-mês, foi observado que 145 pacientes evoluíram para o óbito em decorrência da AIDS. A análise multivariada pelo modelo dos riscos proporcionais de Cox indicou que o tempo de evolução para o óbito por AIDS na população estudada foi associado de forma independente à raça negra (HR ajustado 1,50 - IC 95% 1,03-2,17), com menos de três anos de escolaridade formal (HR ajustado 1,90 - IC 95% 1,12-3,25), com os linfócitos CD4+ em número inferior a 200 células/mm³ no início do estudo (HR ajustado 4,44 - IC 95% 2,70-7,31), com a classificação CDC em categoria B ou C no início do estudo (HR ajustado 3,63 - IC 95% 1,54-8,56), com a soropositividade anti-HTLV-I (HR ajustado 1,95 - IC 95% 1,08-3,52), com a soropositividade anti-HCV (HR ajustado 1,76 - IC 95% 1,20-2,60) e com o uso de esquemas terapêuticos altamente ativos (HAART) em menos de 50% do tempo de seguimento (HR ajustado 2,36 - IC 95% 1,61-3,45). Não houve associação significativa com a soropositividade anti-HTLV-II. O estudo reforça as evidências de que a infecção pelo HTLV-I constitui um fator prognóstico de menor sobrevida em portadores do HIVHuman retroviruses include the human immunodeficiency virus (HIV), etiologic agent of the acquired immunodeficiency syndrome (AIDS), and also the human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II), which can cause lymphoproliferative and/or neurodegenerative diseases. The three retroviruses present similar transmission patterns and share common risk factors resulting in overlap of exposed populations. Although these retroviruses are all lymphotropic, HIV has a high replication rate and induces cell death throughout the course of infection, whereas HTLV-I and HTLV-II can cause cell proliferation and occasionally cell transformation. HTLV-I and HTLV-II effects on the immune system and their interference in the progression of AIDS is a matter of great interest and still controversial. In vitro studies suggest that HTLV-I and HTLV-II may increase the replication and expression of HIV. Clinical epidemiologic studies indicate possible effects of simultaneous infections by HIV and HTLV-I or HTLV-II on the progression of AIDS. In a previous study, carried out among HIV-positive patients treated at an AIDS center in Santos - SP (Centro de Referência em AIDS de Santos), a seroprevalence of 6.0% for HTLV-I and of 7.4% for HTLV-II infections was observed, what enables further investigation on a possible modification in the progression of HIV disease in co-infected patients. This study was carried out with a retrospective cohort design, aimed at evaluating the survival time of HIV-positive patients in the studied group and its association with HTLV-I and HTLV-II infections, as well as with other prognostic factors and progression markers. Four hundred and ninety-five patients were monitored between 1997 and 2002. In this period, in a total of 23,031.5 patients/month, 145 AIDS related deaths were reported. Multivariate analysis using Cox proportional hazards model showed AIDS to be associated in the studied group with the following variables: black race (adjusted HR 1.50 - 95% CI 1.03-2.17), less than three-year education (adjusted HR 1.90 - 95% CI 1.12-3.25), less than 200 CD4+ baseline cells/mm3 (adjusted HR 4.44 - 95% CI 2.70-7.31), CDC classification B or C at study onset (adjusted HR 3.63 - 95% CI 1.54-8.56), anti-HTLV-I seropositivity (adjusted HR 1.95 - 95% CI 1.08-3.52), anti-HCV seropositivity (adjusted HR 1.76 - 95% CI 1.20-2.60), use of Highly Active Antiretroviral Therapy (HAART) in less than 50% of follow-up (adjusted HR 2.36 - 95% CI 1.61-3.45). There was no significant association with anti-HTLV-II seropositivity. This study provides further evidence that HTLV-I infection is a prognostic factor leading to reduced survival time of HIV-infected individuals
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Salomonsson, Lovisa. "Like an Oak Tree He Survived : An Analysis of Masculinity Norms in Post-War Namibia." Thesis, Uppsala universitet, Statsvetenskapliga institutionen, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-402760.
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During the last decades, international organisations have worked hard to implement a gender awareness in their peace- and development programs. Many organizations, however, fail to include an awareness of masculinity construction, and gender has become synonymous with women. This is despite the fact that throughout history, key actors in armed conflicts have been men. Understanding how masculinity is constructed in relation to armed-conflicts can therefore be beneficial to achieve a lasting peace. Thus, the aim of this thesis is to examine how masculinity norms are expressed among Namibians after the Namibian war of independence, and how these norms have developed during the post-war era. By conducting a mixed-method of content and discourse analysis, this study investigates how the hegemonic masculinity is constructed by the citizens of Namibia through the “letters to the editor”-section in the national newspaper The Namibian. All letters published during 1991, 1992, 2002 and 2003 were analysed to achieve an understanding of how the masculinity norms had developed. The study found that the hegemonic masculinity in the earlier years consisted of a strong and honourable man, with a high education and the possibility to independently take care of his family. The hegemonic masculinity had in the later years developed into a more caring and compassionate man, who supported his working wife. The study also found that some aspects of the hegemonic masculinity had remained the same, such as heterosexuality and monogamy. The study encourages further research on the development of masculinity norms in a post-conflict setting, and how these norms may hinder or encourage a lasting peace.
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Ohlsson, Catharina. "Den ansiktslösa rösten : Analyser av Jenny Holzers verk och en studie i den konsthistoriska bilden av henne." Thesis, Halmstad University, School of Humanities (HUM), 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-1238.
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Denna uppsats tittar närmare på fyra verk av Jenny Holzer. Hennes konstnärskap jämförs även med Guerilla Girls. Huvudmetoden utgörs av bildanalyser och jag presenterar också tolkningsmöjligheter utifrån ett genusperspektiv. Utöver detta har jag med en konsthistoriografisk undersökning fått fram hur den generella bilden av Holzer ser ut.
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Mesquita, Pablo Girardelli Mendonça. "Análise da sobrevida do paciente e do enxerto de diabéticos submetidos a diferentes modalidades de transplante." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5148/tde-20022014-110532/.
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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 selecionadosDiabetes 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
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Stacey, Bibi. "Can minority languages survive around English? : An investigation into family language policy in the UK." Thesis, Stockholms universitet, Engelska institutionen, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-144461.
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Family language policy (FLP) focusses on how languages are dealt with within the home; typically how languages are used and how they are maintained or promoted by family members. The present study investigates families living in the UK, where one parent is a native English speaker, and the other a native speaker of another language, the minority language. By use of a mixed-methods design, utilising questionnaires, interviews and logs, this paper answers the questions: what are the reported language practices of children and parents in bi- or multilingual families, what ideologies about FLP do parents in these families possess and what strategies do families reportedly employ in their homes. Through a nexus analysis approach, the paper establishes connections between the historical bodies, the interaction orders and the DIP of the families in order to account for their language behaviours in the home. The nexus analysis suggests that although parents show positive attitudes towards minority language use, it is the macro-level societal factors that are most powerful in determining language use within the home. That is, space plays an important role in choice of language practices. This finding suggests that children need more minority language exposure outside the home, therefore this paper suggests that the UK government could promote and encourage minority language maintenance through the implementation of language policy.
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Granberg, Hannes, and Linn Johansson. "”Men tydligast minns jag den hand som räddade mig” : En studie om journalistikens Estoniahjältar." Thesis, Linnéuniversitetet, Institutionen för medier och journalistik (MJ), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-70117.
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This thesis examines how the Swedish newspapers Aftonbladet and Expressen portrays heroes in the aftermath of the sinking of the M/S Estonia in September of 1994. Our research questions are 1) How is heroism portrayed in the news reports about the Estonia disaster in the newspapers Expressen and Aftonbladet? 2) Are there similarities and distinctions between female and male heroes? We have approached our material from a qualitative perspective analyzing 12 articles using critical discourse analysis. Upon completion of our research we found that both men and women can be heroes, but regardless of gender heroes are all portrayed with traditionally male attributes, such as being aggressive, rational and courageous. To find and understand the hero in news context, the victim plays a periphery but important role. Our result also shows that the victim is needed in order for the hero to perform his or her actions. The victim can be both male or female, but are all described with female attributes as being weak, dependent and fragile. The results of our study may be of use to understand how the journalistic practice actively uses stories about heroes to 1. personify a disaster, 2. summarize a fragmented chain of events and 3. project a distinction between the contemporary aspect of male and female.
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Persson, Daniel, and Johannes Ahlström. "Går det att prediktera konkurs i svenska aktiebolag? : En kvantitativ studie om hur finansiella nyckeltal kan användas vid konkursprediktion." Thesis, Linköpings universitet, Företagsekonomi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-119867.
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Från 1900-talets början har banker och låneinstitut använt nyckeltal som hjälpmedel vid bedömning och kvantifiering av kreditrisk. För dagens investerare är den ekonomiska miljön mer komplicerad än för bara 40 år sedan då teknologin och datoriseringen öppnade upp världens marknader mot varandra. Bedömning av kreditrisk idag kräver effektiv analys av kvantitativa data och modeller som med god träffsäkerhet kan förutse risker. Under 1900-talets andra hälft skedde en snabb utveckling av de verktyg som används för konkursprediktion, från enkla univariata modeller till komplexa data mining-modeller med tusentals observationer. Denna studie undersöker om det är möjligt att prediktera att svenska företag kommer att gå i konkurs och vilka variabler som innehåller relevant information för detta. Metoderna som används är diskriminantanalys, logistisk regression och överlevnadsanalys på 50 aktiva och 50 företag försatta i konkurs. Resultaten visar på en träffsäkerhet mellan 67,5 % och 75 % beroende på vald statistisk metod. Oavsett vald statistisk metod är det möjligt att klassificera företag som konkursmässiga två år innan konkursens inträffande med hjälp av finansiella nyckeltal av typerna lönsamhetsmått och solvensmått. Samhällskostnader reduceras av bättre konkursprediktion med hjälp av finansiella nyckeltal vilka bidrar till ökad förmåga för företag att tillämpa ekonomistyrning med relevanta nyckeltal i form av lager, balanserad vinst, nettoresultat och rörelseresultat.From the early 1900s, banks and lending institutions have used financial ratios as an aid in the assessment and quantification of credit risk. For today's investors the economic environment is far more complicated than 40 years ago when the technology and computerization opened up the world's markets. Credit risk assessment today requires effective analysis of quantitative data and models that can predict risks with good accuracy. During the second half of the 20th century there was a rapid development of the tools used for bankruptcy prediction. We moved from simple univariate models to complex data mining models with thousands of observations. This study investigates if it’s possible to predict bankruptcy in Swedish limited companies and which variables contain information relevant for this cause. The methods used in the study are discriminant analysis, logistic regression and survival analysis on 50 active and 50 failed companies. The results indicate accuracy between 67.5 % and 75 % depending on the choice of statistical method. Regardless of the selected statistical method used, it’s possible to classify companies as bankrupt two years before the bankruptcy occurs using financial ratios which measures profitability and solvency. Societal costs are reduced by better bankruptcy prediction using financial ratios which contribute to increasing the ability of companies to apply financial management with relevant key ratios in the form of stock , retained earnings , net income and operating income.
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Hamy, Anne-Sophie. "Identification of Factors Predicting Sensitivity or Resistance to Neoadjuvant Chemotherapy in Breast Cancer Neoadjuvant treatment : the future of patients with breast cancer Neoadjuvant treatment for intermediate/high-risk HER2-positive and triple-negative breast cancers: no longer an “option” but an ethical obligation Long-term outcome of the REMAGUS 02 trial, a multicenter randomised phase II trial in locally advanced breast cancer patients treated with neoadjuvant chemotherapy with or without celecoxib or trastuzumab according to HER2 status BIRC5 (survivin) : a pejorative prognostic marker in stage II/III breast cancer with no response to neoadjuvant chemotherapy Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort The presence of an in situ component on pre-treatment biopsy is not associated with response to neoadjuvant chemotherapy for breast cancer Chemosensitivity, tumor infiltrating lymphocytes (TILs), and survival of postpartum PABC patients treated by neoadjuvant chemotherapy Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma New insight for pharmacogenomics studies from the transcriptional analysis of two large-scale cancer cell line panels Biological network-driven gene selection identifies a stromal immune module as a key determinant of triple-negative breast carcinoma prognosis A Stromal Immune Module Correlated with the Response to Neoadjuvant Chemotherapy, Prognosis and Lymphocyte Infiltration in HER2-Positive Breast Carcinoma Is Inversely Correlated with Hormonal Pathways Stromal lymphocyte infiltration after neoadjuvant chemotherapy is associated with aggressive residual disease and lower disease-free survival in HER2-positive breast cancer Interaction between molecular subtypes, stromal immune infiltration before and after treatment in breast cancer patients treated with neoadjuvant chemotherapy COX2/PTGS2 Expression Is Predictive of Response to Neoadjuvant Celecoxib in HER2-negative Breast Cancer Patients Celecoxib With Neoadjuvant Chemotherapy for Breast Cancer Might Worsen Outcomes Differentially by COX-2 Expression and ER Status: Exploratory Analysis of the REMAGUS02 Trial Comedications influence immune infiltration and pathological response to neoadjuvant chemotherapy in breast cancer." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS129.
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La chimiothérapie néoadjuvante (CNA) est utilisée dans les cancers du sein agressifs ou localement avancés (CS). Au delà des bénéfices cliniques, elle représente une opportunité pour monitorer in vivo la sensibilité d’une tumeur à un traitement.A partir de l’analyse de sets de données de patients traités par CNA, nous souhaitons identifier des mécanismes associes à la résistance ou sensibilité au traitement. Dans la première partie, nous avons évalué des paramètres, cliniques, anatomopathologiques et transcriptomiques. Nous avons démontré que des éléments non explorés comme la présence d’embols après CNA revêtaient une information pronostique importante. Dans une 2ème partie, nous avons analysé l’impact de l’infiltrat immunitaire dans le cancer du sein, et avons décrit les changements observés entre des échantillons avant et après CNA. Nous avons montré que l’impact pronostique des TILs était différent avant et après CNA, et était opposé dans les CS triple négatif ou HER2-positif. Finalement, nous avons analysé l’impact des comédications pendant la CNA. Nous avons trouvé des effets positifs – via l’augmentation de l’infiltrat immunitaire et la réponse au traitement – et des effets négatifs avec des effets délétères dans certains sous groupes de patients. En conclusion, la situation néoadjuvante représente une plateforme pour générer et potentiellement valider des hypothèses de recherche. La mise à disposition de jeux de données de patients traités par chimiothérapie néoadjuvante constituerait une ressource majeure pour accélérer la recherche contre le cancer du seinNeoadjuvant chemotherapy (NAC i.e. chemotherapy before surgery) is increasingly being used for aggressive or locally advanced breast cancer (BCs). Beyond clinical benefits, it represents an opportunity to monitor in vivo sensitivity to treatment. Based on the analysis of datasets of BCs patients treated with NAC, we aimed at identifying mechanisms associated with resistance or sensitivity to treatment.In the first part, we evaluated biological, clinical, pathological and transcriptomic patterns. We demonstrated that unexplored pathological features such as post-NAC lymphovascular invasion may carried an important prognostic information.In a second part, we analyzed impact of imune infiltration in BC and we described extensively the changes of tumor infiltrating lymphocytes (TILs) between pre and post-NAC samples. We showed that the prognostic impact of TILs was different before and after NAC, and was opposite in TNBC and HER2-positive BCs. Finally, we investigated the impact of comedications use during NAC. We found both positive effects - while enhancing immune infiltration and response to treatment - and negative effects with deleterisous oncologic outcomes in specific patients subgroups. In conclusion, the neoadjuvant setting represents a platform to both generate and potentially validate research hypotheses aiming at increasing the efficacy of treatment. The public release of real-life datasets of BC patients treated with NAC would represent a major resource to accelerate BC research
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Tavares, Lucas Alves. "O envolvimento da proteína adaptadora 1 (AP-1) no mecanismo de regulação negativa do receptor CD4 por Nef de HIV-1." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17136/tde-06012017-113215/.
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O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal.The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.
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Tsai, Chin-Chih, and 蔡金池. "Stability Analysis Of Broccoli And Black Rot Survival Studies By PCR Detection." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/67634090832552718266.
Full textAbstract:
碩士國立臺灣大學
園藝暨景觀學系
103
Broccoli, an important domestic vegetable crop adapts to cool climate. Heat stress will affect its appearance, yield and quality. Due to the summer high temperature broccoli can not be produced in domestic. In recent years, many breeders bred domestic heat tolerant varieties, which have good stability in high-temperature environment. Those varieties maintain crop traits better at high temperature. The purpose of this study is to analyze the stability of heat-tolerant broccoli varieties with traits or not, through the collection of six heat-resistant varieties with an existing commercial varieties of broccoli, field trials in three different seasons. Including a tip bud microscopic observation experiments . Trials were RCB designed, plots area is divided into four blocks, each block 12 samples, the line spacing is 60cm * 60cm. Head traits were recorded, including head weight, head diameter, stem diameter, bracteal leaf, projecting leaf, head shape, flatness, Days from transplant to harvest.In Summer trials ''excellent'' stagnanted, no head production, late curd initiation, decrease of yield and quality occurred in other varieties. In the yield of summer, ''Tsinghua III'', ''AV515'', ''AV530'' are significantly more. And the effects of seasonal and variety have a certain interaction, choosing seasonal varieties gets high yield. The resistant for decrease in quality of ''AV515'', ''AV530'' is not as good as ''B35'', ''B45'' and ''Tsinghua III''. Gene effect in head shape and flatness is much more than climate effect and their interaction. To pursue good head shape and flatness must choose varieties with good genes. Xanthomonas campestris pv. Campestris cause black rot of cruciferous vegetables is a worldwide disease. Bacteria survival in seeds. Produce healthy seed is the key strategies to prevent and control black rot, also to maintain the quality of broccoli production. So the detection of this pathogen can ensure the maintenance of healthy seed . Trials testing different annual production of broccoli seeds, obtained electrophoresis graph by PCR, using the specificity primer. And use the dish to observe the appearance of colonies. The results showed that the annual production of 2011 contaminated seed and consistent with the observation of the colony appearance. And there is no specific relationship between black rot with the annual detection rate and soaking temperature, because PCR detection of nucleic acid fragments, whether the object is whether the survival of bacteria will be detected, but the temperature can affect the degree of adhesion of the bacteria surviving rate.
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Hsu, Wei-Chih, and 許維志. "Prevalence、Incidence and Survival Analysis of Somatic andAutonomic Diabetic Neuropathy in Community-Based Studies." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/05677998460029469851.
Full textAbstract:
博士國立臺灣大學
預防醫學研究所
97
Background： Because the prevalence of diabetes is increasing, the diabetes-related complications, including macrovascular and microvascular complications, lead to significant medical and economic burdens to patients, their families and whole society. Therefore, early detection and identification of complications among diabetic patients in community and intervention for modification of risk factors are important. Regarding to microvascular complications, the epidemiological studies of neuropathy have been rarely addressed in the literature. Purpose： This thesis aimed to conduct a series of community- based epidemiological studies for diabetic neuropathies, including somatic sensorimotor and autonomic neuropathy. These studies encompassed prevalence rate, incidence rate, important correlates affecting the occurrence of neuropathies and the sequel to mortality, survival analysis and computer simulation of diabetic neuropathies in the community setting. Materials and Methods： Patients enrolled in this thesis were from two community-based integrated screening programs in Keelung and Matsu. The Keelung cohort included a large numbers of participants, so a two-stage design was performed for identifying subjects with diabetic neuropathy. The first step in the two-stage study design used the Neurological Symptom Score (NSS) questionnaire to identify positive cases. These positive cases were further confirmed by nerve conduction tests in the second stage. A validation study was conducted for detecting the sensitivity, specificity of questionnaire. Another 587 diabetics were selected for main study. Subjects who screened positive in the first stage were referred to nerve conduction test for confirmation. Potential risk factors were assessed, including fasting plasma glucose, HbA1c, body mass index, retinopathy, age, sex, diabetic duration, total cholesterol, triglyceride, hemoglobin and life styles. The second cohort, Matsu, is a small community. Therefore, all potential subjects with somatic sensorimotor and autonomic neuropathy were investigated. The somatic neuropathy was diagnosed by nerve conduction tests and the autonomic neuropathy was confirmed by 5-min resting electrocardiograph for heart rate variability. This thesis consists of ：（1）investigating prevalence of somatic and autonomic neuropathy at Matsu cohort; besides, Bayesian analysis, using validation data and publications data as prior, was employed to estimate the prevalence rate; （2）incidence rate of diabetic neuropathy was estimated from those who were found to be free of diabetic neuropathy at screening programs in 2001. Information about the time and diagnosis of peripheral nerve disorders at outpatient clinics after screen activity was obtained till the end of 2004 from National Health Insurance;（3）correlates of somatic and autonomic neuropathy were investigated;（4）survival analysis was performed on 708 diabetic patients and 326 diabetic patients who accepted nerve conduction study in 2001. Those patients were linked to National Health Insurance till the end of 2006, information of date and cause of death can be gathered for deceased. Kaplan-Meier test was done by the presence of somatic neuropathy or not. Important correlates and life styles for predicting all-cause and diabetes-related mortality were also studied;（5）Monte-Carlo simulation was used to predict the disease burden. The disease course of the 1000 patients in 10 years was randomly assigned. Results： （1）A number of 143 persons was found to have high fasting plasma glucose (>110 mg/dl) or with past history of type 2 diabetes in Matsu cohort. For 133 subjects who accepted NCS, 12 subjects (12/133=9.0%) were categorized into definite somatic neuropathy, 27 subjects 27/133=20.3%) were probable somatic neuropathy and 94 subjects (94/133=70.7%) were classified as no somatic neuropathy. Among 118 subjects who completed validated heart rate variability test, results of SDNN consist of : 17（17/118=14.4%）diabetics was categorized into low SDNN level, 64 （54.2%） patients were middle SDNN and 37（31.4%）patients were high SDNN level. （2） Among of the 326 diabetic patients who accepted nerve conduction study, 218 patients were classified as no somatic neuropathy in 2001. After linking to outpatient clinics dataset of National Health Insurance, 28 subjects were diagnosed as having peripheral nerve disorders till the end of 2004. Three of these 218 patients died, and 160 patients remained asymptomatic for peripheral neuropathy. Besides, a number of 27 had diagnosis of peripheral nerve lesion already before the screening date. The incidence rate of diabetic neuropathy was 4.8 per hundred person years. After adjusted for the 27 already existed cases before screening among 218 cases, the incidence rate was 5.5 per hundred person years. Because prevalence rate of diabetic neuropathy was 28.46~36.30%, the duration of developing symptomatic diabetic neuropathy was 7.2-10.3 years.（3）Correlates associated with somatic sensorimotor and autonomic neuropathies in pre-diabetic and diabetic subjects are different. In multivariate analysis, systolic blood pressure (OR=1.07 ; 95% CI=1.00-1.14) and fasting blood glucose (OR=1.07; 95% CI=1.03-1.11) accounted for somatic sensorimotor neuropathies where as no significant factors were found in autonomic neuropathy group. A total of 93 subjects died among 708 diabetic patients after 5-year follow up. Among these 708 diabetic patients, 326 patients who accepted nerve conduction study for screening somatic neuropathy, a total of 44 patients died. The statistically significant correlates for all-cause mortality in 93 deceased were: age（HR=1.06），male sex（HR=0.38），BMI（HR=0.90），BUN （HR=0.92），creatinine（HR=6.92），prior cardio-and cerebrovascular diseases（HR=2.25）in multivariate analysis. For diabetes-related death, the statistically significant correlates were: age（HR=1.06），creatinine level（HR=7.97），prior cardio- and cerebrovascular diseases （HR=2.99）. Targeting the 326 subjects with nerve conduction tests, diabetic neuropathy is the strongest predictor for all cause mortality and the second strongest predictor for diabetes-related mortality, next to prior cardio-/cerebrovascular disease in univariate analysis. In selected model, presence of diabetic neuropathy （HR=4.38）, fasting glucose（HR=1.01） and creatinine level （HR=13.23）and serum cholesterol（HR=0.99） remained statistically significant for all-cause mortality. For disease-related mortality, presence of neuropathy（HR=5.69）, fasting glucose（HR=1.01）, hemoglobin（HR=0.70）, serum BUN （HR=0.84）and creatinine（HR=26.99） levels are statistically significant. （4）Kaplan-Meier curves during the 5 years of follow up showed that diabetic neuropathy was a statistically significant factor for all-cause （p<0.001）and diabetes-related mortality（p<0.001）by log-rank test. （5）By simulated cohort, 59.7% of diabetic patients will progress to somatic neuropathy after 10-year follow up. For patients with somatic neuropathy, 14.7% of diabetic patient will die of diabetes-related causes and 9.2% of these will die of non-diabetes related causes. For patients without somatic neuropathy, 3% of these will die of diabetes-related causes and also 3% will die of non-diabetes related causes. . Conclusion: The present thesis provided an insight into estimating the prevalence rates, incidence rate, survival analysis, important correlates and medical burdens of diabetic neuropathy, including both types of somatic sensorimotor and autonomic neuropathies, by using a population-based screening program. We finds that the prevalence rates of somatic neuropathy in type 2 diabetes were approximate 30% in Keeling and Matsu community and autonomic neuropathy even doubled this figure. The incidence rate of developing diabetic neuropathy was 4.8-5.5 per hundred-person years. Correlates of both types of neuropathy and for predicting mortality were different. Somatic neuropathy is an independent risk factor for all-cause and diabetes-related mortality. After 10-years’ time in simulation study, prevalence rate of somatic neuropathy will be doubled among diabetic patients. The high prevalence rate will cause great medical and economic burdens on patient, family and whole society. Prevention of diabetic complications, and diabetic neuropathy in particular, were dependent on early detection, monitor and control blood sugar strictly and modification of life style in these vulnerable subjects. Screening programs for diabetic neuropathy, including cost-effective and cost-benefit analysis, should be carried out in the future for identifying the benefits in public health.
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Borges, Higor. "Marginal bone loss and survival rate of clinical studies with zirconia dental implants : systematic review and meta-analysis." Master's thesis, 2019. http://hdl.handle.net/10400.14/28471.
Full textAbstract:
Objetivo: Avaliar a taxa de sobrevivência cumulativa e a perda óssea marginal peri
implantar de implantes dentários de zircónia submetidos a um acompanhamento de
pelo menos 12 meses após a reabilitação protética. Materiais e Métodos: A procura
sistemática eletrónica através dos bancos de dados PubMed (MEDLINE) e EMBASE
foi realizada independentemente por dois revisores a fim de identificar estudos clínicos
publicados entre janeiro de 2005 e abril de 2019 com no mínimo 10 pacientes e 12
meses de acompanhamento após carga funcional. As referências dos artigos
selecionados foram revisadas manualmente à procura de estudos adicionais.
Resultados: A remodelação marginal óssea apresentou perdas médias de 0.80 mm
(95% CI 0.60-1.00 mm) e 1.01 mm (95% CI 0.72-1.29 mm) em 1 ano e após 2 anos
de funcionalização respetivamente. Não foi possível realizar a meta-análise para a
taxa de sobrevivência uma vez que a maioria dos estudos não forneceram valores de
intervalo de confiança ou desvio padrão. A taxa de falha foi reportada para um período
de 2.75 anos de acompanhamento, onde a prevalência de falha precoce, falha tardia
e fratura foi de 3.4%, 1.7% e 1.7% respetivamente. Conclusão: Os implantes de
zircónia apresentaram resultados comparáveis aos dos implantes de titânio no que diz
respeito à perda óssea marginal em períodos de observação de curto prazo após a
restauração protética. No entanto, mais estudos clínicos a longo prazo bem
planejados são necessários antes seja dada recomendação para adoção de implantes
de zircónia na prática diária.Purpose: To evaluate cumulative survival rate and peri-implant marginal bone loss of zirconia dental implants subjected to a follow-up of at least 12 months after prosthetic rehabilitation. Materials and Methods: A systematic electronic search through the databases PubMed (MEDLINE) and EMBASE was performed by two independent reviewers to identify clinical studies published between January 2005 and April 2019 with a minimum of 10 patients and 12 months of follow-up after functional loading. References from the selected articles were manually reviewed for further studies. Results: From the initial 1225 articles retrieved, only 19 met all the inclusion criteria. The marginal bone remodelling accounted mean losses of 0.8 mm (95% CI 0.60-1.00 mm) and 1.01 mm (95% CI 0.72-1.29 mm) at 1-year and after 2-year post-loading respectively. Failure rate of 6.8% was calculated for a mean follow-up period of 2.75 years, where the prevalence of early failure, late failure and implant fracture was 3.4%, 1.7% and 1.7% respectively. The meta-analysis regarding the survival rate of one- and two-piece zirconia dental implants was not possible due to the lack of information about confidential interval or standard deviation on most of the included articles. Conclusion: Zirconia implants presented values comparable to titanium implants with respect to marginal bone loss at short-term observation periods following prosthetic delivery. However, more long-term well-designed clinical studies are required before giving the recommendation on the adoption of zirconia implants in daily practice.
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Himali, Jayandra Jung. "Effect of selection of censoring times on survival analysis estimation of disease incidence and association with risk factors." Thesis, 2013. https://hdl.handle.net/2144/13660.
Full textAbstract:
In longitudinal cohort studies, potential risk factors are measured at baseline, subjects are followed over time, and disease endpoints are ascertained via extensive surveillance. Individual follow-up time is from baseline to the event, if one is observed during the study period. Follow-up time is censored for subjects who are not observed to have the event during the study period, at the end of the study period for subjects who remain event-free, but during the study period for subjects who leave the study early by choice or by mortality, or whose last evaluation was before the end of the study. Survival analytic techniques are unique in that the unit of analysis is not the individual but the person-time contributed by the individual.
Surveillance in longitudinal studies is generally quite rigorous. Subjects are examined in waves and their event status is ascertained. Surveillance continues between waves, and events come to the attention of the investigator. If there is a long time between waves,
analyses can be conducted on all available data, with non-events censored early at the last examination and events followed beyond the general examination to the incident event.
Motivated by analyses using the Framingham Heart Study (FHS) with cardiovascular endpoints, we consider four censoring methods for non-events and evaluate their impact on estimates of incidence, and on tests of association between risk factors and incidence. We further investigate the impact of early censoring of non-events (as compared to events) under various scenarios with respect to incidence estimation, robustness, and power using a simulation study of Weibull survival models over a range of sample sizes and distribution parameters.
Our FHS and simulation investigations show early censoring of non-events causes over estimation of incidence, particularly when the baseline incidence is low. Early censoring of non-events did not affect the robustness of the Wald test [Ho: Hazard Ratio (HR) =1]. However, in both the FHS and over the range of simulation scenarios, under early censoring of non-events, estimates of HR were closer to the null (1.0), and the power to detect associations with risk factors was markedly reduced.
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"Bootstrap distribution for testing a change in the cox proportional hazard model." 2000. http://library.cuhk.edu.hk/record=b5890302.
Full textAbstract:
Lam Yuk Fai.Thesis (M.Phil.)--Chinese University of Hong Kong, 2000.
Includes bibliographical references (leaves 41-43).
Abstracts in English and Chinese.
Chapter 1 --- Basic Concepts --- p.9
Chapter 1.1 --- Survival data --- p.9
Chapter 1.1.1 --- An example --- p.9
Chapter 1.2 --- Some important functions --- p.11
Chapter 1.2.1 --- Survival function --- p.12
Chapter 1.2.2 --- Hazard function --- p.12
Chapter 1.3 --- Cox Proportional Hazards Model --- p.13
Chapter 1.3.1 --- A special case --- p.14
Chapter 1.3.2 --- An example (continued) --- p.15
Chapter 1.4 --- Extension of the Cox Proportional Hazards Model --- p.16
Chapter 1.5 --- Bootstrap --- p.17
Chapter 2 --- A New Method --- p.19
Chapter 2.1 --- Introduction --- p.19
Chapter 2.2 --- Definition of the test --- p.20
Chapter 2.2.1 --- Our test statistic --- p.20
Chapter 2.2.2 --- The alternative test statistic I --- p.22
Chapter 2.2.3 --- The alternative test statistic II --- p.23
Chapter 2.3 --- Variations of the test --- p.24
Chapter 2.3.1 --- Restricted test --- p.24
Chapter 2.3.2 --- Adjusting for other covariates --- p.26
Chapter 2.4 --- Apply with bootstrap --- p.28
Chapter 2.5 --- Examples --- p.29
Chapter 2.5.1 --- Male mice data --- p.34
Chapter 2.5.2 --- Stanford heart transplant data --- p.34
Chapter 2.5.3 --- CGD data --- p.34
Chapter 3 --- Large Sample Properties and Discussions --- p.35
Chapter 3.1 --- Large sample properties and relationship to goodness of fit test --- p.35
Chapter 3.1.1 --- Large sample properties of A and Ap --- p.35
Chapter 3.1.2 --- Large sample properties of Ac and A --- p.36
Chapter 3.2 --- Discussions --- p.37
48
Foley, Christine Marie. "Comparison And Application Of Methods To Address Confounding By Indication In Non-Randomized Clinical Studies." 2013. https://scholarworks.umass.edu/theses/1121.
Full textAbstract:
Objective: The project aimed to compare marginal structural models, and propensity score adjusted models with Cox Proportional Hazards models to address confounding by indication due to time-dependent confounders. These methods were applied to data from approximately 120,000 women in the Women’s Health Initiative to evaluate the causal effect of antidepressant medication with respect to diabetes risk.
Methods: Four approaches were compared. Three Cox Models were used. The first used baseline covariates. The second used time-varying antidepressant medication use, BMI and presence of elevated depressive symptoms and adjusted for other baseline covariates. The third used time-varying antidepressant medication use, BMI and presence of elevated depressive symptoms and adjusted for other baseline covariates and propensity to taking antidepressants at baseline. Our fourth method used a Marginal Structural Cox Model with Inverse Probability of Treatment Weighting that included time-varying antidepressant medication, BMI and presence of elevated depressive symptoms and adjusted for other baseline covariates.
Results: All approaches showed an increase in diabetes risk for those taking antidepressants. Diabetes risk increased with adjustment for time-dependent confounding and results for these three approaches were similar. All models were statistically significant. Ninety-five percent confidence intervals overlapped for all approaches showing they were not different from one another.
Conclusions: Our analyses did not find a difference between Cox Proportional Hazards Models and Marginal Structural Cox Models in the WHI cohorts. Estimates of the Inverse Probability of Treatment Weights were very close to 1 which explains why we observed similar results.
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Austin, Elizabeth. "Regression Analysis for Ordinal Outcomes in Matched Study Design: Applications to Alzheimer's Disease Studies." 2018. https://scholarworks.umass.edu/masters_theses_2/628.
Full textAbstract:
Alzheimer's Disease (AD) affects nearly 5.4 million Americans as of 2016 and is the most common form of dementia. The disease is characterized by the presence of neurofibrillary tangles and amyloid plaques [1]. The amount of plaques are measured by Braak stage, post-mortem. It is known that AD is positively associated with hypercholesterolemia [16]. As statins are the most widely used cholesterol-lowering drug, there may be associations between statin use and AD. We hypothesize that those who use statins, specifically lipophilic statins, are more likely to have a low Braak stage in post-mortem analysis.
In order to address this hypothesis, we wished to fit a regression model for ordinal outcomes (e.g., high, moderate, or low Braak stage) using data collected from the National Alzheimer's Coordinating Center (NACC) autopsy cohort. As the outcomes were matched on the length of follow-up, a conditional likelihood-based method is often used to estimate the regression coefficients. However, it can be challenging to solve the conditional-likelihood based estimating equation numerically, especially when there are many matching strata. Given that the likelihood of a conditional logistic regression model is equivalent to the partial likelihood from a stratified Cox proportional hazard model, the existing R function for a Cox model, coxph( ), can be used for estimation of a conditional logistic regression model. We would like to investigate whether this strategy could be extended to a regression model for ordinal outcomes.
More specifically, our aims are to (1) demonstrate the equivalence between the exact partial likelihood of a stratified discrete time Cox proportional hazards model and the likelihood of a conditional logistic regression model, (2) prove equivalence, or lack there-of, between the exact partial likelihood of a stratified discrete time Cox proportional hazards model and the conditional likelihood of models appropriate for multiple ordinal outcomes: an adjacent categories model, a continuation-ratio model, and a cumulative logit model, and (3) clarify how to set up stratified discrete time Cox proportional hazards model for multiple ordinal outcomes with matching using the existing coxph( ) R function and interpret the regression coefficient estimates that result. We verified this theoretical proof through simulation studies. We simulated data from the three models of interest: an adjacent categories model, a continuation-ratio model, and a cumulative logit model. We fit a Cox model using the existing coxph( ) R function to the simulated data produced by each model. We then compared the coefficient estimates obtained. Lastly, we fit a Cox model to the NACC dataset. We used Braak stage as the outcome variables, having three ordinal categories. We included predictors for age at death, sex, genotype, education, comorbidities, number of days having taken lipophilic statins, number of days having taken hydrophilic statins, and time to death. We matched cases to controls on the length of follow up. We have discussed all findings and their implications in detail.
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He, Zangdong. "Variable selection and structural discovery in joint models of longitudinal and survival data." Thesis, 2014. http://hdl.handle.net/1805/6365.
Full textAbstract:
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.