Critérios para avaliar a validade dos resultados apresentados em análises de subgrupo em ensaios clínicos

In observational studies, identification of associations within particular subgroups is the usual method of investigation. As an exploratory method, it is the bread and butter of epidemiological research. Nearly everything that has been learned in epidemiology has been derived from the analysis of subgroups. In a randomized clinical trial, the entire purpose is the comparison of the test subjects and the controls, and when there is particular interest in the results of treatment in a certain section of trial participants, a subgroup analysis is performed. These subgroups are examined to see if they are liable to a greater benefit or risk from treatment. Thus, analyzing patient subsets is a natural part of the process of improving therapeutic knowledge through clinical trials. Nevertheless, the reliability of subgroup analysis can often be poor because of problems of multiplicity and limitations in the numbers of patients studied. The naive interpretation of the results of such examinations is a cause of great confusion in the therapeutic literature. We emphasize the need for readers to be aware that inferences based on comparisons between subgroups in randomized clinical trials should be approached more cautiously than those based on the main comparison. That is, subgroup analysis results derived from a sound clinical trial are not necessarily valid; one must not jump to conclusions and accept the validity of subgroup analysis results without an appropriate judgment.Em estudos de observação, a identificação de associações dentro de subgrupos particulares é o método habitual de investigação. Como um método exploratório, faz parte do dia-a-dia da pesquisa epidemiológica. Quase tudo o que se sabe hoje em Epidemiologia foi derivado da análise de subgrupo. Em ensaios clínicos randomizados, o propósito principal é a comparação dos indivíduos sob experimentação e os controles, e quando nós estamos particularmente interessados nos resultados do tratamento em uma certa seção de participantes do ensaio, uma análise de subgrupo é executada. Estes subgrupos são examinados para verificar se eles foram objeto de um maior benefício ou malefício secundário ao tratamento. Assim, analisar subconjuntos de pacientes é uma parte natural do processo de melhorar o conhecimento terapêutico através de ensaios clínicos randomizados. Não obstante, a confiança na análise de subgrupo pode ser pobre devido a problemas de multiplicidade de comparações e limitações em números de pacientes estudados. A interpretação simplista dos resultados de tal técnica é uma causa de grande confusão na literatura terapêutica. Nós enfatizamos a necessidade de chamar a atenção dos leitores que as conclusões baseadas em comparações entre subgrupos em ensaios clínicos randomizados sejam examinadas com mais cautela do que aquelas baseadas na comparação principal. Ou seja, resultados de análise de subgrupo provenientes de ensaios clínicos corretamente desenhados não são necessariamente válidos, portanto, não devemos tirar conclusões precipitadas e aceitar a validade dos resultados sem um julgamento judicioso

Sex differences and correlates of poor glycaemic control in type 2 diabetes: a cross-sectional study in Brazil and Venezuela.

OBJECTIVE: Examine whether glycaemic control varies according to sex and whether the latter plays a role in modifying factors associated with inadequate glycaemic control in patients with type 2 diabetes (T2D) in Brazil and Venezuela. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, nationwide survey conducted in Brazil and Venezuela from February 2006 to June 2007 to obtain information about glycaemic control and its determinants in patients with diabetes mellitus attending outpatient clinics. MAIN OUTCOME MEASURES: Haemoglobin A1c (HbA1c) level was measured by liquid chromatography, and patients with HbA1c ≥7.0% (53 mmol/mol) were considered to have inadequate glycaemic control. The association of selected variables with glycaemic control was analysed by multivariate linear regression, using HbA1c as the dependent variable. RESULTS: A total of 9418 patients with T2D were enrolled in Brazil (n=5692) and in Venezuela (n=3726). They included 6214 (66%) women and 3204 (34%) men. On average, HbA1c levels in women were 0.13 (95% CI 0.03 to 0.24; p=0.015) higher than in men, after adjusting for age, marital status, education, race, country, body mass index, duration of disease, complications, type of healthcare, adherence to diet, adherence to treatment and previous measurement of HbA1c. Sex modified the effect of some factors associated with glycaemic control in patients with T2D in our study, but had no noteworthy effect in others. CONCLUSIONS: Women with T2D had worse glycaemic control than men. Possible causes for poorer glycaemic control in women compared with men include differences in glucose homeostasis, treatment response and psychological factors. In addition, sex modified factors associated with glycaemic control, suggesting the need to develop specific treatment guidelines for men and women

Study of the magnification effect on self-organizing maps

Self-Organizing Maps (SOM), are a type of neuronal network (Kohonen, 1982b) that has been used mainly in data clustering problems, using unsupervised learning. Among the multiple areas of application, SOM has been used in various problems of direct interest to the Navy (V. J. Lobo, 2009), including route planning and the location of critical infrastructures. The SOM has also been used to sample large databases. In this sort of application, they have a behaviour called the magnification effect (Bauer & Der, 1996), which causes areas of the attribute space of data with less density to be overrepresented or magnified. This dissertation uses an experimental approach to mitigate the lack of theoretical explanation for this effect except for one-dimensional and quite simple cases. From experimental evidence obtained for carefully designed problems we infer a relationship between input data densities and output neuron densities that can be applied universally, or at least in a broad set of situations. A large number of experiments were conducted using one-dimensional to one-dimensional mappings followed by 2D to 2D, 3D to 1, 2 and 3D. We derived an empirical relationship whereby the density in the output space is equal to a constant times the density of the input space raised to the power of (alpha) which although depending on a number of factors can be approximated by the root index n of 2/3 where n is the input space dimension. The correlation that we found in our experiments, for both the well-known 1- dimensional case and for more general 2 to 3-dimensional cases is a useful guide to predict the magnification effect in practical situations.Therefore, in chapter 4 we produce a populational cartogram of Angola and we prove that our relation can be used to correct the magnification effect on 2-dimensional cases.Os mapas auto-organizados ou SOM (Self Organizing Maps), são um tipo de rede neuronal (Kohonen, 1982) que tem sido utilizada sobretudo em problemas agrupamento de dados (clustering), usando aprendizagem não supervisionada. Entre as múltiplas áreas de aplicação, os SOM têm sido usados em vários problemas com interesse direto para a Marinha (Lobo, 2009), incluindo o planeamento de rotas e a localização de infraestruturas críticas. Os SOM também têm sido usados para fazer amostragem de grandes bases de dados, e nesse tipo de aplicações têm um comportamento, denominado efeito de magnificação (Bauer & R. Der, 1996), que faz com que zonas do espaço de atributos dos dados com menor densidade sejam sobre representadas, ou seja magnificadas. Esta dissertação traz uma abordagem experimental para mitigar a falta de explicação teórica para este efeito, com exceção de casos unidimensionais e bastante simples. A partir de provas experimentais obtidas para problemas cuidadosamente concebidos, inferimos uma relação entre densidades de dados de entrada e densidades de neuronios à saída que podem ser aplicadas universalmente, ou pelo menos num conjunto alargado de situações. Foram realizadas um grande numero de experiências usando mapeamentos unidimensionais para mapeamentos unidimensionais seguidos por 2D para 2D, 3D para 1, 2 e 3D. Derivamos uma relação empírica em que a densidade no espaço de saída é igual a uma constante vezes a densidade do espaço de entrada elevada a (alpha) que, embora dependendo de uma série de fatores, pode ser aproximado pela raiz de índice n de 2/3 onde n é a dimensão do espaço de entrada. A correlação que encontramos nas nossas experiências, tanto para o caso unidimensional bem como para casos mais gerais de 2 a 3 dimensões é um guia útil para prever o efeito de magnificação em situações práticas. No capítulo 4 produzimos um cartograma populacional de Angola e provamos que a nossa relação pode ser usada para corrigir o efeito de magnificação em casos bidimensionais

Invariant measures for Cherry flows

We investigate the invariant probability measures for Cherry flows, i.e. flows on the two-torus which have a saddle, a source, and no other fixed points, closed orbits or homoclinic orbits. In the case when the saddle is dissipative or conservative we show that the only invariant probability measures are the Dirac measures at the two fixed points, and the Dirac measure at the saddle is the physical measure. In the other case we prove that there exists also an invariant probability measure supported on the quasi-minimal set, we discuss some situations when this other invariant measure is the physical measure, and conjecture that this is always the case. The main techniques used are the study of the integrability of the return time with respect to the invariant measure of the return map to a closed transversal to the flow, and the study of the close returns near the saddle.Comment: 12 pages; updated versio

Importancia do tamanho do cálculo quanto a eficiencia e complicaçőes no tratamento ureteroscópico de cálculo no ureter distal /

Orientador: Renato Tambara FilhoDissertaçăo (mestrado) - Universidade Federal do Paraná, Setor de Cięncias da Saúde, Programa de Pós-Graduaçăo em Clínica Cirúrgica. Defesa: Curitiba, 2000.Inclui bibliografi

Experiments for analysis of video transmission via ATM

A large quantity of data of different types and priorities pass through on high-speed networks. A relevant part of these data, like continuous media (audio, video, and so), need a control of its Quality of Service (QoS). This paper describes experiments on the characteristics of the ATM network technology that provide support to quality video streaming transmission. The experiments were realized considering QoS, connection admission control, network congestion, transmission priorities and bandwidth demand associated to applications and network configuration. Three basic kinds of videos were analyzed-movies (smooth movies), sports (action movies) and talking head movies. Data about video transmission were collected from an ATM switch, showing results that can be used in the future on ATM channel mapping to multimedia data distribution (in applications like Interactive TV and Video-on-Demand, for example).Facultad de Informátic

Newton's problem : the essentially inert matter versus the evident activity in nature

Orientador: Fatima Regina Rodrigues EvoraDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Filosofia e Ciencias HumanasResumo: Essa dissertação analisa o chamado "problema de Newton", isto é, o problema de conciliar conceitualmente a inatividade essencial da matéria com a evidente atividade na natureza representada pela força de gravitação universal. Num primeiro momento, temos por objetivo examinar a gênese desse problema e, num segundo momento, os argumentos que Newton desenvolve procurando rebatê-loAbstract: This thesis analyses the so-called "Newton's problem", that is, the problem of conceptually conciliating the essential inactivity of matter with the evident activity in nature represented by the universal gravitation force. In a first moment, we are intended to examine the origin of this problem and, in a second moment, the arguments Newton develop in order to solve itMestradoFilosofiaMestre em Filosofi