933 resultados para Modelo de risco proporcional de cox.


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Uma vez que existe uma grande necessidade de se obter um maior conhecimento das comunidades imigrantes residentes no Distrito, este trabalho tem como principal objectivo caracterizar a população de imigrantes comunitários residentes no distrito de Évora. Em particular, procuramos analisar os casamentos realizados não só entre os não nacionais e portugueses, bem como entre os nãos nacionais entre si. Consideramos os 354 imigrantes que constituem os imigrantes comunitários inscritos legalmente nos Serviços Estrangeiros e Fronteiras de Évora entre 2006 a 2009. Por outro lado, analisamos, para o mesmo período, os casamentos dos imigrantes que casaram com os portugueses num total de 165 indivíduos. Começamos por levar a efeito uma investigação básica de tipo descritivo para uma caracterização dos imigrantes relativamente a diferentes variáveis e investigamos algumas associações entre elas via tabelas de contingência. Refira-se que a maioria dos imigrantes é do sexo feminino, sendo a nacionalidade mais representativa a brasileira. Com base no modelo de regressão de Cox identificamos factores de risco e diferentes perfis associados à rotura do casamento. Mostramos que há evidência estatística para considerar que um menor nível de escolaridade, o pertencer a um país da União Europeia e o ter entrado à procura de trabalho são níveis de factores que aumentam o risco de rotura do casamento. Analisam-se, ainda, de uma forma crítica, a abordagem paramétrica, procurando modelar os dados através dos modelos Exponencial, Weibull, Lognormal e Log-logístico. ABSTRACT: There is a need to obtain a greater understanding of immigrant communities in the district; this work has as main objective to characterize the population of immigrant community residing in the district of Évora. ln particular, we analyze not only marriages between Portuguese and non-nationals, as well as among non-nationals among themselves. We consider the 354 immigrants who are legally registered immigrants in the Community Service of Foreigners and Frontiers of Évora, from 2006 to 2009. Moreover, we analyze, for the same period, the marriages of immigrants who intermarried with the Portuguese for a total of 165 individuals. We start by carrying out a basic descriptive research in order to characterize the immigrants in relation to several variables and investigated some associations between them by contingency tables. It should be noted that most immigrants are women, and the more representative the Brazilian nationality. Based on the Cox regression model, were possible to identify risk factors and identify profiles of high and low risk associated with the rupture of the marriage. We show that there is statistical evidence to conclude that a less educated levels, belonging to a country inside the European Union and have gone looking for work are factors that increase the risk of rupture of the marriage. The parametric approach is analyzed also, in a critical way, seeking to model the data using exponential, Weibull, Lognormal and Log-logistic.

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A "Mentoria", relação pessoal de desenvolvimento, em que uma das pessoas - a mais experiente - promove a evolução e desenvolvimento da pessoa menos experiente. O objectivo principal é motivar e inspirar o "mentorado", aumentar o seu potencial e também transmitir algum saber-fazer. O termo Mentoring tem a sua origem na mitologia grega, mais concretamente na obra "Odisseia" de Homero.  Quando o personagem Ulisses vai em viagem, pede a um sábio grego chamado Mentor que se ocupe da educação do seu filho. para simbolizar a pessoa estimada e culta que guia e aconselha uma pessoa jovem e menos experiente. O princípio do Mentoring existiu de forma bastante presente nas corporações de artes e profissões nos tempos medievais. Os artesãos frequentemente aceitavam jovens aprendizes que viviam e trabalhavam na sua oficina (muitas vezes na própria casa sem o risco de perder "segredos do negócio" para a concorrência.

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O gerenciamento de riscos climáticos requer informação sobre estados futuros de variáveis climáticas, geralmente representada por funções de distribuição de probabilidade acumulada (FDPA, P(Y?y) ou por sua funções complementares (P(Y>y)), ditas funções probabilidade de exceder (FPE). Uma variedade de métodos estatísticos tem sido utilizada para estimação de FPE, incluindo, modelos de regressão linear múltipla, regressão logística e métodos não paramétricos (MAIA et al, 2007; LO et al, 2008). Apesar de parecer intuitivo que a incerteza associada às estimativas das FPE é fundamental para os tomadores de decisão, esse tipo de informação raramente é fornecido. Modelos estatísticos de previsão baseados em séries históricas da variável de interesse (chuva, temperatura) e de preditores derivados de estados do oceano e da atmosfera (índices climáticos tais como: temperaturas da superfície do mar ? TSM, índice de oscilação sul, IOS, El Nino/Oscilação Sul - ENSO) se constituem em alternativas promissoras para auxílio às tomada de decisão, em escalas locais e regionais. O uso de tais indicadores permite incorporar mudanças de padrão derivadas de mudanças climáticas em modelos estatísticos que utilizam informação histórica. Neste trabalho, mostramos como o Modelo de Regressão de Cox (MRC; COX, 1972), tradicionalmente utilizado para modelagem de tempos de falha, em investigações na área médica e em ciências sociais, pode ser de grande utilidade para avaliação probabilística de riscos climáticos, mesmo para variáveis que não representam tempos de falha tais como chuva, produtividade de culturas, lucros, entre outras. O MRC pode ser utilizado para avaliar a influência de preditores (índices climáticos) sobre riscos de interesse (representados pelas FPE), estimar FPE para combinações específicas de preditores e incertezas associadas além de fornecer informação sobre riscos relativos, de grande valor para tomadores de decisão. Apresentamos dois estudos de caso nos quais o Modelo de Cox foi usado para investigar: a) o efeito do IOS e de um índice derivado de TSM do Pacífico sobre o início da estação chuvosa em Cairns (Austrália) e b) a influência o índice Nino 3.4, derivado de estados da TSM no Pacífico Equatorial sobre o chuva acumulada no período de Março a Junho em Limoeiro do Norte (Ceará, Brasil). O objetivo da apresentação desses estudos é meramente didático, para demonstrar o potencial do método proposto como ferramenta de auxílio à tomada de decisão.

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O objetivo desse trabalho foi simular o risco de lixiviação de trinta e oito poluentes orgânicos presentes em lodos de esgotos provenientes de estações de tratamentos. Para tanto, foi assumido um cultivo hipotético de milho em um solo Latossolo vermelho distrófico, característico de solos de regiões produtoras de milho, no qual foi aplicada uma dose de lodo de esgoto como fertilizante. Lodos de esgotos são ricos em matéria orgânica e micronutrientes úteis na fertilização de solos para a produção de plantas, mas também podem conter poluentes de importância ambiental. A lixiviação dos poluentes foi simulada utilizando-se o modelo CMLS94 e os dados climáticos de mil anos independentes e igualmente prováveis gerados pelo simulador de clima WGEN, a partir de uma seqüência de quatorze anos consecutivos observados e registrados pela Estação Experimental do Instituto Agronômico de Campinas. A análise de risco de lixiviação indicou que os poluentes benzidina > n-nitrosodi-n-propilamina > fenol > 2,4-dinitrofenol > isoforano > nitrobenzeno > p-cresol > o-cresol > m-cresol > 2-clorofenol, nessa ordem, devem ser monitorados em águas subterrâneas de regiões de solos nos quais foram aplicados doses de lodo.

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Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE 2, which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA 2 in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD 2 and its metabolite 15d-PGJ2, PGF 1α and PGI 2. Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity.A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. © 2011 Elsevier B.V.

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An important aspect of decision support systems involves applying sophisticated and flexible statistical models to real datasets and communicating these results to decision makers in interpretable ways. An important class of problem is the modelling of incidence such as fire, disease etc. Models of incidence known as point processes or Cox processes are particularly challenging as they are ‘doubly stochastic’ i.e. obtaining the probability mass function of incidents requires two integrals to be evaluated. Existing approaches to the problem either use simple models that obtain predictions using plug-in point estimates and do not distinguish between Cox processes and density estimation but do use sophisticated 3D visualization for interpretation. Alternatively other work employs sophisticated non-parametric Bayesian Cox process models, but do not use visualization to render interpretable complex spatial temporal forecasts. The contribution here is to fill this gap by inferring predictive distributions of Gaussian-log Cox processes and rendering them using state of the art 3D visualization techniques. This requires performing inference on an approximation of the model on a discretized grid of large scale and adapting an existing spatial-diurnal kernel to the log Gaussian Cox process context.

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In a multifaceted immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX-2) by Mycobacterium bovis bacillus Calmette-Guerin (BCG) may act as an important influencing factor for the effective host immunity. We here demonstrate that M. bovis BCG-triggered TLR2-dependent signaling leads to COX-2 and PGE2 expression in vitro in macrophages and in vivo in mice. Further, the presence of PGE2 could be demonstrated in sera or cerebrospinal fluid of tuberculosis patients. The induced COX-2 expression in macrophages is dependent on NF-kappa B activation, which is mediated by inducible NO synthase (iNOS)/NO-dependent participation of the members of Notch1-PI-3K signaling cascades as well as iNOS-independent activation of ERK1/2 and p38 MAPKs. Inhibition of iNOS activity abrogated the M. bovis BCG ability to trigger the generation of Notch1 intracellular domain (NICD), a marker for Notch1 signaling activation, as well as activation of the PI-3K signaling cascade. On the contrary, treatment of macrophages with 3-morpholinosydnonimine, a NO donor, resulted in a rapid increase in generation of NICD, activation of PI-3K pathway, as well as the expression of COX-2. Stable expression of NICD in RAW 264.7 macrophages resulted in augmented expression of COX-2. Further, signaling perturbations suggested the involvement of the cross-talk of Notch1 with members with the PI-3K signaling cascade. These results implicate the dichotomous nature of TLR2 signaling during M. bovis BCG-triggered expression of COX-2. In this perspective, we propose the involvement of iNOS/NO as one of the obligatory, early, proximal signaling events during M. bovis BCG-induced COX-2 expression in macrophages.

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Activation of inflammatory immune responses during granuloma formation by the host upon infection of mycobacteria is one of the crucial steps that is often associated with tissue remodeling and breakdown of the extracellular matrix. In these complex processes, cyclooxygenase-2 (COX-2) plays a major role in chronic inflammation and matrix metalloproteinase-9 (MMP-9) significantly in tissue remodeling. In this study, we investigated the molecular mechanisms underlying Phosphatidyl-myo-inositol dimannosides (PIM2), an integral component of the mycobacterial envelope, triggered COX-2 and MMP-9 expression in macrophages. PIM2 triggers the activation of Phosphoinositide-3 Kinase (PI3K) and Notch1 signaling leading to COX-2 and MMP-9 expression in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Notch1 signaling perturbations data demonstrate the involvement of the cross-talk with members of PI3K and Mitogen activated protein kinase pathway. Enforced expression of the cleaved Notch1 in macrophages induces the expression of COX-2 and MMP-9. PIM2 triggered significant p65 nuclear factor-kappa B (NF-kappa B) nuclear translocation that was dependent on activation of PI3K or Notch1 signaling. Furthermore, COX-2 and MMP-9 expression requires Notch1 mediated recruitment of uppressor of Hairless (CSL) and NF-kappa B to respective promoters. Inhibition of PIM2 induced COX-2 resulted in marked reduction in MMP-9 expression clearly implicating the role of COX-2 dependent signaling events in driving the MMP-9 expression. Taken together, these data implicate PI3K and Notch1 signaling as obligatory early proximal signaling events during PIM2 induced COX-2 and MMP-9 expression in macrophages.

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Chronic rejection in the form of obliterative bronchiolitis (OB) is the major cause of death 5 years after lung transplantation. The exact mechanism of OB remains unclear. This study focused on the role of cyclo-oxygenase (COX) -2, tenascin, and C-reactive protein (CRP) expression, and the occurrence of ingraft chimerism (= cells from two genetically distinct individuals in a same individual) in post-transplant OB development. In our porcine model, OB developed invariably in allografts, while autografts stayed patent. The histological changes were similar to those seen in human OB. In order to delay or prevent obliteration, animals were medicated according to certain protocol. In the beginning of the bronchial allograft reaction, COX-2 induction occurred in airway epithelial cells prior to luminal obliteration. COX-2 expression in macrophages and fibroblasts paralleled the onset of inflammation and fibroblast proliferation. This study demonstrated for the first time, that COX-2 expression is associated with the early stage of post- transplant obliterative airway disease. Tenascin expression in the respiratory epithelium appeared to be predictive of histologic features observed in human OB, and influx of immune cells. Expression in the bronchial wall and in the early obliterative lesions coincided with the onset of onset of fibroblast and inflammatory cell proliferation in the early stage of OB and was predictive of further influx of inflammatory and immune cells. CRP expression in the bronchial wall coincided with the remodelling process. High grade of bronchial wall CRP staining intensity predicted inflammation, accelerated fibroproliferation, and luminal obliteration, which are all features of OB. In the early obliterative plaque, majority of cells expressed CRP, but in mature, collagen-rich plaque, expression declined. Local CRP expression might be a response to inflammation and it might promote the development of OB. Early appearance of chimeric (= recipient-derived) cells in the graft airway epithelium predicted epithelial cell injury and obliteration of the bronchial lumen, which both are features of OB. Chimeric cells appeared in the airway epithelium after repair following transplantation-induced ischemic injury. Ingraft chimerism might be a mechanism to repair alloimmune-mediated tissue injury and to protect allografts from rejection after transplantation. The results of this study indicate, that COX-2, tenascin, CRP, and ingraft chimerism have a role in OB development. These findings increase the understanding of the mechanisms of OB, which may be beneficial in further development of diagnostic options.

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Macrophages, as sentinels of robust host immunity, are key regulators of innate immune responses against invading mycobacteria; however, pathogenic mycobacteria survive in the infected host by subverting host innate immunity. Infection dependent expression of early secreted antigenic target protein 6 (ESAT-6) by Mycobacterium tuberculosis is strongly correlated with subversion of innate immune responses against invading mycobacteria. As a part of multifaceted immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX-2) may act as an important influencing factor towards effective host immunity. In the current investigation, we demonstrate that ESAT-6 triggers COX-2 expression both in vitro and in vivo in a TLR2 dependent manner. Signaling perturbation data suggest that signaling dynamics of PI3K and p38 and JNK1/2 MAPK assume critical importance in ESAT-6 triggered expression of COX-2 in macrophages. Interestingly, ESAT-6 triggered PI3K-MAPK signaling axis holds the capacity to regulate coordinated activation of NF-kappa B and AP-1. Overall, current investigation provides mechanistic insights into ESAT-6 induced COX-2 expression and unravels TLR2 mediated interplay of PI3K and MAPK signaling axis as a rate-determining step during intricate host immune responses. These findings would serve as a paradigm to understand pathogenesis of mycobacterial infection and clearly pave a way towards development of novel therapeutics. (C) 2011 Elsevier Ltd. All rights reserved.

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The crystal structures of two polymorphs and two polymorphic hemihydrates of Etoricoxib are reported. Etoricoxib is a non-steroidal anti-inflammatory drug (NSAID) that is a selective inhibitor of COX-2. It is used in the treatment of various types of inflammation, pain and fever. Clas et al. have reported four polymorphs (labeled I through IV) and two solvates (hemi-and sesquihydrate) of the API in US patent 6,441,002 (Clas et al, US patent 6,441,002, 2002). However, no crystal structures have been reported for any of these forms. A comparison was made between the PXRD patterns reported in patent `002 and the powder spectra simulated from single crystal data. The two polymorphs characterized here correspond to form I and form IV of the patent. Form II of the patent could not be obtained by us with a variety of experimental conditions. Form III of the patent corresponds to hemihydrate II of this study. Form III is therefore not a polymorph of form I and form IV. What we have termed hemihydrate I in this study is obtained under a wide variety of conditions and it is also the only hemihydrate reported as such in the patent. Because the Etoricoxib molecule contains no conventional hydrogen bond donors, there cannot be any strong hydrogen bonds in the crystal structures of forms I and IV. The packing is accordingly characterized by weak hydrogen bonds of the C-H center dot center dot center dot O=S and C-H center dot center dot center dot N type. Thermal data were collected for form I, form IV and hemihydrate I to shed some light on relative stabilities. PXRD diffractograms show the transformation of form IV to form I at elevated temperature, indicating that form I is more stable than form IV. However, this transformation occurs only in samples of form IV that contain some form I; it does not occur in pure form IV. The formation of the two hemihydrates could follow from the known tendency of an acceptor-rich molecule to crystallize as a hydrate.