The role of angiogenic and antiangiogenic factors in the second trimester in the prediction of preeclampsia in pregnant women with type 1 diabetes

OBJECTIVE To assess the association between circulating angiogenic and antiangiogenic factors in the second trimester and risk of preeclampsia in women with type 1 diabetes.

RESEARCH DESIGN AND METHODS Maternal plasma concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) were available at 26 weeks of gestation in 540 women with type 1 diabetes enrolled in the Diabetes and Preeclampsia Intervention Trial.

RESULTS Preeclampsia developed in 17% of pregnancies (n = 94). At 26 weeks of gestation, women in whom preeclampsia developed later had significantly lower PlGF (median [interquartile range]: 231 pg/mL [120–423] vs. 365 pg/mL [237–582]; P < 0.001), higher sFlt-1 (1,522 pg/mL [1,108–3,393] vs. 1,193 pg/mL [844–1,630] P < 0.001), and higher sEng (6.2 ng/mL [4.9–7.9] vs. 5.1 ng/mL[(4.3–6.2]; P < 0.001) compared with women who did not have preeclampsia. In addition, the ratio of PlGF to sEng was significantly lower (40 [17–71] vs. 71 [44–114]; P < 0.001) and the ratio of sFlt-1 to PlGF was significantly higher (6.3 [3.4–15.7] vs. 3.1 [1.8–5.8]; P < 0.001) in women who later developed preeclampsia. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to a logistic model containing established risk factors (area under the curve [AUC], 0.813) significantly improved the predictive value (AUC, 0.850 and 0.846, respectively; P < 0.01) and significantly improved reclassification according to the integrated discrimination improvement index (IDI) (IDI scores 0.086 and 0.065, respectively; P < 0.001).

CONCLUSIONS These data suggest that angiogenic and antiangiogenic factors measured during the second trimester are predictive of preeclampsia in women with type 1 diabetes. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to established clinical risk factors significantly improves the prediction of preeclampsia in women with type 1 diabetes.

Preeclampsia is characterized by the development of hypertension and new-onset proteinuria during the second half of pregnancy (1,2), leading to increased maternal morbidity and mortality (3). Women with type 1 diabetes are at increased risk for development of preeclampsia during pregnancy, with rates being two-times to four-times higher than that of the background maternity population (4,5). Small advances have come from preventive measures, such as low-dose aspirin in women at high risk (6); however, delivery remains the only effective intervention, and preeclampsia is responsible for up to 15% of preterm births and a consequent increase in infant mortality and morbidity (7).

Although the etiology of preeclampsia remains unclear, abnormal placental vascular remodeling and placental ischemia, together with maternal endothelial dysfunction, hemodynamic changes, and renal pathology, contribute to its pathogenesis (8). In addition, over the past decade accumulating evidence has suggested that an imbalance between angiogenic factors, such as placental growth factor (PlGF), and antiangiogenic factors, such as soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng), plays a key role in the pathogenesis of preeclampsia (8,9). In women at low risk (10–13) and women at high risk (14,15), concentrations of angiogenic and antiangiogenic factors are significantly different between women who later develop preeclampsia (lower PlGF, higher sFlt-1, and higher sEng levels) compared with women who do not.

Few studies have specifically focused on circulating angiogenic factors and risk of preeclampsia in women with diabetes, and the results have been conflicting. In a small study, higher sFlt-1 and lower PlGF were reported at the time of delivery in women with diabetes who developed preeclampsia (16). In a longitudinal prospective cohort of pregnant women with diabetes, Yu et al. (17) reported increased sFlt-1 and reduced PlGF in the early third trimester as potential predictors of preeclampsia in women with type 1 diabetes, but they did not show any difference in sEng levels in women with preeclampsia compared with women without preeclampsia. By contrast, Powers et al. (18) reported only increased sEng in the second trimester in women with pregestational diabetes who developed preeclampsia.

The aim of this study, which was significantly larger than the previous studies highlighted, was to assess the association between circulating angiogenic (PlGF) and antiangiogenic (sFlt-1 and sEng) factors and the risk of preeclampsia in women with type 1 diabetes. A further aim was to evaluate the added predictive ability and clinical usefulness of angiogenic factors and established risk factors for preeclampsia risk prediction in women with type 1 diabetes.

Root Cause Analysis by a Combined Sparse Classification and Monte Carlo Approach

Classification methods with embedded feature selection capability are very appealing for the analysis of complex processes since they allow the analysis of root causes even when the number of input variables is high. In this work, we investigate the performance of three techniques for classification within a Monte Carlo strategy with the aim of root cause analysis. We consider the naive bayes classifier and the logistic regression model with two different implementations for controlling model complexity, namely, a LASSO-like implementation with a L1 norm regularization and a fully Bayesian implementation of the logistic model, the so called relevance vector machine. Several challenges can arise when estimating such models mainly linked to the characteristics of the data: a large number of input variables, high correlation among subsets of variables, the situation where the number of variables is higher than the number of available data points and the case of unbalanced datasets. Using an ecological and a semiconductor manufacturing dataset, we show advantages and drawbacks of each method, highlighting the superior performance in term of classification accuracy for the relevance vector machine with respect to the other classifiers. Moreover, we show how the combination of the proposed techniques and the Monte Carlo approach can be used to get more robust insights into the problem under analysis when faced with challenging modelling conditions.

Predictors of place of death for those in receipt of home-based palliative care services in Ontario, Canada

Many cancer patients die in institutional settings despite their preference to die at home. A longitudinal, prospective cohort study was conducted to comprehensively assess the determinants of home death for patients receiving home-based palliative care. Data collected from biweekly telephone interviews with caregivers (n=302) and program databases were entered into a multivariate logistic model. Patients with high nursing costs (odds ratio [OR]: 4.3; confidence interval [CI]: 1.8-10.2) and patients with high personal support worker costs (OR: 2.3; CI: 1.1-4.5) were more likely to die at home than those with low costs. Patients who lived alone were less likely to die at home than those who cohabitated (OR: 0.4; CI: 0.2-0.8), and those with a high propensity for a home-death preference were more likely to die at home than those with a low propensity (OR: 5.8; CI: 1.1-31.3). An understanding of the predictors of place of death may contribute to the development of effective interventions that support home death.

The Development and Testing of a New Version of the Cognitive Reflection Test Applying Item Response Theory (IRT)

The cognitive reflection test (CRT) is a short measure of a person's ability to resist intuitive response tendencies and to produce a normatively correct response, which is based on effortful reasoning. Although the CRT is a very popular measure, its psychometric properties have not been extensively investigated. A major limitation of the CRT is the difficulty of the items, which can lead to floor effects in populations other than highly educated adults. The present study aimed at investigating the psychometric properties of the CRT applying item response theory analyses (a two-parameter logistic model) and at developing a new version of the scale (the CRT-long), which is appropriate for participants with both lower and higher levels of cognitive reflection. The results demonstrated the good psychometric properties of the original, as well as the new scale. The validity of the new scale was also assessed by measuring correlations with various indicators of intelligence, numeracy, reasoning and decision-making skills, and thinking dispositions. Moreover, we present evidence for the suitability of the new scale to be used with developmental samples. Finally, by comparing the performance of adolescents and young adults on the CRT and CRT-long, we report the first investigation into the development of cognitive reflection.

A Retrospective Claims Analysis of Medication Adherence and Persistence Among Patients Taking Antidepressants for the Treatment of Major Depressive Disorder (MDD)

Thesis (Master's)--University of Washington, 2015

Sélection de modèle d'imputation à partir de modèles bayésiens hiérarchiques linéaires multivariés

Les logiciels utilisés sont Splus et R.

Facteurs contextuels influençant l’implantation d’un modèle de hiérarchisation des soins en santé mentale : une étude de cas en milieu montréalais

Cette étude de cas vise à comparer le modèle de soins implanté sur le territoire d’un centre de santé et des services sociaux (CSSS) de la région de Montréal aux modèles de soins en étapes et à examiner l’influence de facteurs contextuels sur l’implantation de ce modèle. Au total, 13 cliniciens et gestionnaires travaillant à l’interface entre la première et la deuxième ligne ont participé à une entrevue semi-structurée. Les résultats montrent que le modèle de soins hiérarchisés implanté se compare en plusieurs points aux modèles de soins en étapes. Cependant, certains éléments de ces derniers sont à intégrer afin d’améliorer l’efficience et la qualité des soins, notamment l’introduction de critères d’évaluation objectifs et la spécification des interventions démontrées efficaces à privilégier. Aussi, plusieurs facteurs influençant l’implantation d’un modèle de soins hiérarchisés sont dégagés. Parmi ceux-ci, la présence de concertation et de lieux d’apprentissage représente un élément clé. Néanmoins, certains éléments sont à considérer pour favoriser sa réussite dont l’uniformisation des critères et des mécanismes de référence, la clarification des rôles du guichet d’accès en santé mentale et l’adhésion des omnipraticiens au modèle de soins hiérarchisés. En somme, l’utilisation des cadres de référence et d’analyse peut guider les gestionnaires sur les enjeux à considérer pour favoriser l’implantation d’un modèle de soins basé sur les données probantes, ce qui, à long terme, devrait améliorer l’efficience des services offerts et leur adéquation avec les besoins populationnels.

Développement des dimensions du capital culturel dans l'étude des inégalités sociales liées au tabagisme chez les jeunes adultes

La théorie du capital culturel est de plus en plus utilisée en santé publique et pourrait être utile à l’étude des inégalités sociales liées au tabagisme chez les jeunes adultes. Ceux-ci véhiculent une haute prévalence du tabagisme et plusieurs particularités qui font d’eux un groupe cible qui mérite davantage d’attention. Cependant, le développement du capital culturel porte encore peu de consensus quant à sa définition et son opérationnalisation. Nous proposons un nouveau cadre de référence autour de trois dimensions – champs, générations et états – et établissons une application empirique de celui-ci en étudiant l’association entre certains indicateurs du capital culturel et le tabagisme des jeunes adultes. Nous utilisons les données du projet Interdisciplinary Study of Inequalities in Smoking qui a recruté 2 093 jeunes adultes à Montréal, Canada en 2011-2012. Nos variables dépendantes sont le statut tabagique courant et le nombre de cigarettes fumées dans une journée. Nous examinons les corrélations entre les indicateurs de capital culturel et leur association avec le tabagisme au travers de modèles de régression hiérarchique logistique et linéaire. Nous observons de faibles associations entre les indicateurs retenus. Nous observons aussi que les indicateurs du capital culturel liés aux champs de la santé et de l’éducation, chez les participants et leurs parents, étaient tous associés au comportement tabagique. A la lumière de notre cadre de référence, une approche multidimensionnelle à l’utilisation du capital culturel peut nous permettre de mieux comprendre les inégalités sociales liées au tabagisme chez les jeunes adultes.

Modelo de internacionalización del sector de reciclaje en Colombia

El presente documento se realiza un análisis de tres empresas del sector del reciclaje: Smurfit Kappa Cartón de Colombia S.A., Ecoeficiencia S.A.S y Fibras Nacionales S.A.S, para conocer la aplicación de las teorías de internacionalización y observar cómo se desarrollan en la realidad Colombiana. El sector de reciclaje actualmente es poco explorado y explotado en Colombia, principalmente por el bajo interés del sector público y privado en alcanzar las innumerables ventajas económicas y sociales que éste ofrece, toda vez que, es considerado un sector no formal dentro de la economía colombiana. Más adelante se describe la situación actual de las tres empresas basado en una revisión bibliográfica de las teorías de internacionalización y posteriormente se aplican los conceptos a cada una de las empresas. Finalmente, se propone la ruta de internacionalización del sector del reciclaje en Colombia y un modelo logístico general para que las empresas de este sector lo apliquen y así mejoren sus procesos. Se plantea como estrategia el desarrollo de un Cluster para lograr la efectividad de la ruta de internacionalización del sector del reciclaje. Es necesaria la conformación de una red de empresas, agentes e instituciones públicas y privadas dentro del entorno del reciclaje y el manejo de residuos, para la consolidación del sector. El objetivo es que este documento sirva como medio de consulta para empresarios y empresas interesadas en mejorar el nivel de vida de los recicladores, contribuir con el medio ambiente y mejorar la competitividad y productividad del reciclaje en Colombia, logrando convertirse en un sector de talla mundial. Es importante mencionar que en la medida es que el sector se formalice, los recicladores se verán beneficiados y harán parte importante de una cadena de valor que permitirá mejorar las condiciones actuales del sector y podrán participar activamente en la economía, generando un impacto positivo y global.

Curva de aprendizaje para ventana ecográfica de la vena cava inferior, en residentes de medicina de emergencias

INTRODUCCIÓN. El ultrasonido es fundamental en la medicina de emergencias, no se conoce cual debería ser la curva de aprendizaje para obtener las competencias técnicas y operativas; ACEP recomienda por cada ventana ecográfica realizar 25 repeticiones. No existe una curva de aprendizaje para ventana de VCI en la población de residentes colombianos. OBJETIVO: Determinar la curva de aprendizaje necesaria para obtener una proporción mayor al 80% de éxitos en la toma de la ventana ecográfica de la VCI, usando la escala de calificación para el aseguramiento de la calidad sugerida por ACEP, en residentes de I a III año de medicina de emergencias. METODOLOGÍA: Estudio experimental no comparativo, que evaluó la proporción de éxito en función del las tomas repetidas de la VCI por ultrasonido, mediciones que se tomaron luego de participar en una capacitación teórica y demostrativa de la técnica propuesta; se calificaron los videos según la escala publicada por ACEP. El análisis estadístico se realizó con un modelo logístico multinivel para la proporción del éxito, agrupado por repetición y agrupado por sujeto. RESULTADOS: Se obtuvo información de 8 residentes, cada uno realizo 25 repeticiones a 3 modelos sanos con asignación aleatoria. Se realizó la curva de aprendizaje obteniendo en 11 repeticiones una proporción de 0.80 (rango 0.54 a 0.92) y en 21 repeticiones una proporción de 0.9 (rango 0.75 a 0.96), datos ajustados por numero de repetición y residente. CONCLUSIÓN: La curva de aprendizaje para la ventana ecográfica de la VCI es de 11 y 21 repeticiones para obtener el 80% y 90% de éxito en residentes de medicina de emergencias de I a III año de la universidad del rosario.

A Bayesian approach for dose-escalation in a phase I clinical trial incorporating pharmacodynamic endpoints

Bayesian decision procedures have already been proposed for and implemented in Phase I dose-escalation studies in healthy volunteers. The procedures have been based on pharmacokinetic responses reflecting the concentration of the drug in blood plasma and are conducted to learn about the dose-response relationship while avoiding excessive concentrations. However, in many dose-escalation studies, pharmacodynamic endpoints such as heart rate or blood pressure are observed, and it is these that should be used to control dose-escalation. These endpoints introduce additional complexity into the modeling of the problem relative to pharmacokinetic responses. Firstly, there are responses available following placebo administrations. Secondly, the pharmacodynamic responses are related directly to measurable plasma concentrations, which in turn are related to dose. Motivated by experience of data from a real study conducted in a conventional manner, this paper presents and evaluates a Bayesian procedure devised for the simultaneous monitoring of pharmacodynamic and pharmacokinetic responses. Account is also taken of the incidence of adverse events. Following logarithmic transformations, a linear model is used to relate dose to the pharmacokinetic endpoint and a quadratic model to relate the latter to the pharmacodynamic endpoint. A logistic model is used to relate the pharmacokinetic endpoint to the risk of an adverse event.

Bricks vs clicks: entrepreneurial online banking behaviour and relationship banking

Purpose – Little research has been conducted on the effects of information technology on financing entrepreneurial businesses or small and medium sized enterprises (SMEs). The purpose of this paper is to examine the impacts of entrepreneurial online banking and relationship banking on the severity of financial problems perceived by entrepreneurs and their interactive effect. It also investigates how characteristics of individual businesses and entrepreneurial demographics influence SMEs’ financial situation. Design/methodology/approach – An ordered logistic model is used on a UK dataset to empirically test the hypotheses derived in this paper. The empirical evidence is drawn from the 2004 UK survey of SME finances, which contains a sample of 2,500 firms. Findings – This paper finds that both entrepreneurial online banking behaviour and relationship banking alleviates the severity of financial problems perceived by entrepreneurs. The relationship affect is less evident for entrepreneurs who most frequently use an online approach to communicate with their banks than for those using traditional methods. Business and entrepreneur characteristics also have a strong impact on the severity of the financial problems suffered by SMEs. Originality/value – This paper provides evidence supporting the favourable impacts of the application of information technology on entrepreneurial finance from the perspective of entrepreneur/business. It also identifies a substitute relationship between entrepreneurial online banking behaviour and relationship banking, a relationship which contradicts existing evidence.

Semiparametric Bayesian measurement error modeling

This work presents a Bayesian semiparametric approach for dealing with regression models where the covariate is measured with error. Given that (1) the error normality assumption is very restrictive, and (2) assuming a specific elliptical distribution for errors (Student-t for example), may be somewhat presumptuous; there is need for more flexible methods, in terms of assuming only symmetry of errors (admitting unknown kurtosis). In this sense, the main advantage of this extended Bayesian approach is the possibility of considering generalizations of the elliptical family of models by using Dirichlet process priors in dependent and independent situations. Conditional posterior distributions are implemented, allowing the use of Markov Chain Monte Carlo (MCMC), to generate the posterior distributions. An interesting result shown is that the Dirichlet process prior is not updated in the case of the dependent elliptical model. Furthermore, an analysis of a real data set is reported to illustrate the usefulness of our approach, in dealing with outliers. Finally, semiparametric proposed models and parametric normal model are compared, graphically with the posterior distribution density of the coefficients. (C) 2009 Elsevier Inc. All rights reserved.

Separation and Execution of graphical engine on a cross platform IDE to enhance performance

“Biosim” is a simulation software which works to simulate the harvesting system.This system is able to design a model for any logistic problem with the combination of several objects so that the artificial system can show the performance of an individual model. The system will also describe the efficiency, possibility to be chosen for real life application of that particular model. So, when any one wish to setup a logistic model like- harvesting system, in real life he/she may be noticed about the suitable prostitution for his plants and factories as well as he/she may get information about the least number of objects, total time to complete the task, total investment required for his model, total amount of noise produced for his establishment in advance. It will produce an advance over view for his model. But “Biosim” is quite slow .As it is an object based system, it takes long time to make its decision. Here the main task is to modify the system so that it can work faster than the previous. So, the main objective of this thesis is to reduce the load of “Biosim” by making some modification of the original system as well as to increase its efficiency. So that the whole system will be faster than the previous one and performs more efficiently when it will be applied in real life. Theconcept is to separate the execution part of ”Biosim” form its graphical engine and run this separated portion in a third generation language platform. C++ is chosenhere as this external platform. After completing the proposed system, results with different models have been observed. The results show that, for any type of plants of fields, for any number of trucks, the proposed system is faster than the original system. The proposed system takes at least 15% less time “Biosim”. The efficiency increase with the complexity of than the original the model. More complex the model, more efficient the proposed system is than original “Biosim”.Depending on the complexity of a model, the proposed system can be 56.53 % faster than the original “Biosim”.

Equidade educacional no Brasil: análise das oportunidades educacionais em 2001 e 2011

Esta tese tem por objetivo analisar a equidade educacional no Brasil, em 2001 e 2011. Para tanto, avaliarei as oportunidades dos alunos de terem professores mais qualificados, verificando a evolução por gênero, cor/raça e nível socioeconômico. O referencial teórico da tese divide-se em duas partes: o debate sobre equidade e a discussão sobre a importância da escola e de seus recursos e processos internos. Na primeira parte, apresento diversas perspectivas sobre equidade e proponho a divisão do campo em três linhas, além de inserir o debate num contexto mais amplo sobre justiça social. Utilizarei, nesta pesquisa, a abordagem pluralista, que entende equidade como um termo que engloba recursos, processos e resultados. Na segunda parte, trato da importância da escola para o desempenho dos alunos a partir da apresentação de pesquisas que comprovam que as escolas são peças fundamentais para o desempenho dos alunos, principalmente em países desiguais. Dentre os recursos e processos escolares, verifica-se que os professores têm o maior impacto sobre as notas – e, portanto, são capazes de trazer maior contribuição para políticas educacionais equitativas. O debate sobre a importância da escola e dos professores para o desempenho dos alunos é particularmente relevante no Brasil, onde a literatura demonstra um grande impacto das escolas e dos professores sobre os resultados escolares, atrelado a uma enorme desigualdade na distribuição dos recursos. Feita a discussão teórica, apresento o modelo elaborado para analisar a equidade no Brasil, em 2001 e 2011. Desenvolvi um modelo logístico para determinar as oportunidades de um aluno ter professores mais qualificados – classificados, neste trabalho, a partir de quatro características: diploma de ensino superior, pós-graduação, experiência em sala de aula e que faça a cobertura do currículo. São apresentadas duas especificações do modelo: simples, que contém apenas características dos alunos como variáveis independentes; e completa, que, além das características dos alunos, inclui informações sobre os estados, sobre o tipo de rede (privada ou pública) e sobre a localidade (rural ou urbana). As análises são conduzidas para o 5º e 9º ano, em 2001 e 2011, utilizando os dados do SAEB de Língua Portuguesa e Matemática. Os resultados apontam para quatro conclusões importantes: em primeiro lugar, o nível socioeconômico mostrou-se mais relevante na determinação das oportunidades educacionais em comparação à cor/raça ou gênero dos alunos; em segundo lugar, há semelhança nas tendências de desempenho do 5º e 9º anos, com a identificação de três padrões de evolução das oportunidades educacionais; em terceiro lugar, verifica-se que o impacto das características observáveis dos professores sobre a proficiência dos alunos mudou de 2001 a 2011, em decorrência das políticas de incentivo à escolarização docente; por fim, verifica-se grande heterogeneidade dentre os estados brasileiros, com os estados das regiões Sul e Sudeste garantindo maior oportunidade educacional aos alunos. Com base nestes resultados, aponto, nas considerações finais, para três pilares presentes em países mais equitativos: a definição de padrões mínimos de recursos e processos; a adoção de políticas compensatórias e a discriminação positiva na distribuição dos recursos; e, por fim, o investimento nos professores.