Distribution of ABCB1 polymorphisms among Brazilians: impact of population admixture

Introduction: Interethnic admixture is a source of cryptic population structure that may lead to spurious genotype-phenotype associations in pharmacogenomic studies. We studied the impact of population stratification on the distribution of ABCB1 polymorphisms (1236C > T, 2677G > T/A and 3435C > T) among Brazilians, a highly admixed population with Amerindian, European and African ancestral roots. Methods: Individual DNA from 320 healthy adults was genotyped with a panel of ancestry informative markers, and the proportions of African component of ancestry (ACA) were estimated. ABCB1 genotypes were determined by the single base extension/termination method. We describe the association between ABCB1 polymorphisms and ACA by fitting a linear proportional odds logistic regression model to the data. Results: The distribution of the ABCB1 2677G > T/A and 3435C > T, but not the 1236C > T, SNPs displayed a significant trend for decreasing frequency of the T alleles and TT genotypes from White to Intermediate to Black individuals. The same trend was observed in the frequency of the T/nonG/T haplotype at the 1236, 2677 and 3435 loci. When the population sample was proportioned in quartiles, according to the individual ACA estimates, the frequency of the T allele and TT genotype at each locus declined progressively from the lowest (< 0.25 ACA) to the highest (> 0.75 ACA) quartile. Linear proportional odds logistic regression analysis confirmed that the odds of having the T allele at each locus decreases in a continuous manner with the increase of the ACA, throughout the ACA range (0.13-0.94) observed in the overall population sample. A significant association was also detected between the individual ACA estimates and the presence of the T/nonG/T haplotype in the overall population. Conclusion: Self-identification according to the racial/color categories proposed by the Brazilian Census is insufficient to properly control for population stratification in pharmacogenomic studies of ABCB1.

Pharmacogenetics of Warfarin: Development of a Dosing Algorithm for Brazilian Patients

A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital. The VKORC1 3673G>A genotype was the most important predictor of warfarin dose, with a partial R(2) value of 23.9%. Replacing the VKORC1 3673G>A genotype with VKORC1 diplotype did not increase the algorithm`s predictive power. We suggest that three other single-nucleotide polymorphisms (SNPs) (5808T>G, 6853G>C, and 9041G>A) that are in strong linkage disequilibrium (LD) with 3673G>A would be equally good predictors of the warfarin dose requirement. The algorithm`s predictive power was similar across the self-identified ""race/color"" subsets. ""Race/color"" was not associated with stable warfarin dose in the multiple regression model, although the required warfarin dose was significantly lower (P = 0.006) in white (29 +/- 13 mg/week, n = 196) than in black patients (35 +/- 15 mg/week, n = 76).

Is there wage premium to computer use in Sweden

This paper examines the wage premium to computer use in Sweden in the early 1990’s. I use simple regression model and interaction terms in my paper to examine the effect of computer use at work. Although the data is only one-year cross-section data, my results clearly show a wage premium to computer use in Sweden. There are also interesting findings in my paper by using Swedish data. From the results, I find wage premium to be related to intensity of computer use at work.

Design/Evaluation of A Methodology For Performance Optimization Of Indexable Carbide Inserts

In this project, two broad facets in the design of a methodology for performance optimization of indexable carbide inserts were examined. They were physical destructive testing and software simulation.For the physical testing, statistical research techniques were used for the design of the methodology. A five step method which began with Problem definition, through System identification, Statistical model formation, Data collection and Statistical analyses and results was indepthly elaborated upon. Set-up and execution of an experiment with a compression machine together with roadblocks and possible solution to curb road blocks to quality data collection were examined. 2k factorial design was illustrated and recommended for process improvement. Instances of first-order and second-order response surface analyses were encountered. In the case of curvature, test for curvature significance with center point analysis was recommended. Process optimization with method of steepest ascent and central composite design or process robustness studies of response surface analyses were also recommended.For the simulation test, AdvantEdge program was identified as the most used software for tool development. Challenges to the efficient application of this software were identified and possible solutions proposed. In conclusion, software simulation and physical testing were recommended to meet the objective of the project.

Defining Relevant Product Markets for Pharmaceuticals

To identify the relevant product markets for Swedish pharmaceuticals, a spatial econometrics approach is employed. First, we calculate Moran’s Is for different market definitions and then we use a spatial Durbin model to determine the effect of price changes on quantity sold off own and competing products. As expected, the results show that competition is strongest between close substitutes; however, the relevant product markets for Swedish pharmaceuticals extend beyond close substitutes down to products included in the same class on the four-digit level of the Anatomic Therapeutic Chemical system as defined by the World Health Organization. The spatial regression model further indicates that increases in the price of a product significantly lower the quantity sold of that product and in the same time increase the quantity sold of competing products. For close substitutes (products belonging to the same class on the seven-digit level of the Anatomic Therapeutic Chemical system), as well as for products that, without being close substitutes, belong to the same therapeutic/pharmacological/chemical subgroup (the same class on the five-digit level of the Anatomic Therapeutic Chemical system), a significant change towards increased competition is also visible after 1 July 2009 when the latest policy changes with regards to pharmaceuticals have been implemented in Sweden.

Modelling dominance in a flexible intercross analysis

The aim of this paper is to develop a flexible model for analysis of quantitative trait loci (QTL) in outbred line crosses, which includes both additive and dominance effects. Our flexible intercross analysis (FIA) model accounts for QTL that are not fixed within founder lines and is based on the variance component framework. Genome scans with FIA are performed using a score statistic, which does not require variance component estimation. RESULTS: Simulations of a pedigree with 800 F2 individuals showed that the power of FIA including both additive and dominance effects was almost 50% for a QTL with equal allele frequencies in both lines with complete dominance and a moderate effect, whereas the power of a traditional regression model was equal to the chosen significance value of 5%. The power of FIA without dominance effects included in the model was close to those obtained for FIA with dominance for all simulated cases except for QTL with overdominant effects. A genome-wide linkage analysis of experimental data from an F2 intercross between Red Jungle Fowl and White Leghorn was performed with both additive and dominance effects included in FIA. The score values for chicken body weight at 200 days of age were similar to those obtained in FIA analysis without dominance. CONCLUSION: We have extended FIA to include QTL dominance effects. The power of FIA was superior, or similar, to standard regression methods for QTL effects with dominance. The difference in power for FIA with or without dominance is expected to be small as long as the QTL effects are not overdominant. We suggest that FIA with only additive effects should be the standard model to be used, especially since it is more computationally efficient.

Parameter estimation of Poisson generalized linear mixed models based on three different statistical principles : a simulation study

Generalized linear mixed models are flexible tools for modeling non-normal data and are useful for accommodating overdispersion in Poisson regression models with random effects. Their main difficulty resides in the parameter estimation because there is no analytic solution for the maximization of the marginal likelihood. Many methods have been proposed for this purpose and many of them are implemented in software packages. The purpose of this study is to compare the performance of three different statistical principles - marginal likelihood, extended likelihood, Bayesian analysis-via simulation studies. Real data on contact wrestling are used for illustration.

Nurses' research utilization two years after graduation : a national survey ofassociated individual, organizational, and educational factors

Background. Nurses' research utilization (RU) as part of evidence-based practice is strongly emphasized in today's nursing education and clinical practice. The primary aim of RU is to provide high-quality nursing care to patients. Data on newly graduated nurses' RU are scarce, but a predominance of low use has been reported in recent studies. Factors associated with nurses' RU have previously been identified among individual and organizational/contextual factors, but there is a lack of knowledge about how these factors, including educational ones, interact with each other and with RU, particularly in nurses during the first years after graduation. The purpose of this study was therefore to identify factors that predict the probability for low RU among registered nurses two years after graduation. Methods. Data were collected as part of the LANE study (Longitudinal Analysis of Nursing Education), a Swedish national survey of nursing students and registered nurses. Data on nurses' instrumental, conceptual, and persuasive RU were collected two years after graduation (2007, n = 845), together with data on work contextual factors. Data on individual and educational factors were collected in the first year (2002) and last term of education (2004). Guided by an analytic schedule, bivariate analyses, followed by logistic regression modeling, were applied. Results. Of the variables associated with RU in the bivariate analyses, six were found to be significantly related to low RU in the final logistic regression model: work in the psychiatric setting, role ambiguity, sufficient staffing, low work challenge, being male, and low student activity. Conclusions. A number of factors associated with nurses' low extent of RU two years postgraduation were found, most of them potentially modifiable. These findings illustrate the multitude of factors related to low RU extent and take their interrelationships into account. This knowledge might serve as useful input in planning future studies aiming to improve nurses', specifically newly graduated nurses', RU.

Utilidade do exame fundoscópico realizado por não-oftalmologistas na avaliação de pacientes hipertensos

O objetivo deste estudo foi avaliar a utilidade da oftalmoscopia direta realizada por não-oftalmologistas em 400 pacientes hipertensos não diabéticos. Em um estudo transversal, analisou-se a associação entre exame fundoscópico, categorizado em normal e anormal e de acordo com uma classificação de Keith, Wagener e Barker (KW) modificada, com pressão arterial, duração da hipertensão e anormalidades eletrocardiográficas. Associações entre pressão arterial e anormalidades eletrocardiográficas também foram realizadas. As anormalidades de fundo-de-olho foram mais freqüentes em pacientes com pressão arterial diastólica maior que 105 mmHg (P = 0,001), pressão sistólica maior que 180 mmHg (P < 0,001) e com duração da hipertensão maior que 3 anos (P = 0.003). Também houve maior freqüência de anormalidades à fundoscopia em pacientes com estágios mais graves de hipertensão segundo a classificação do V Joint National Committee (V-JNC). Não houve associação entre gravidade da hipertensão e as classes KW 1 e KW 2: 34,5% dos pacientes classificados como KW 1 tinham pressão diastólica acima de 105 mmHg, contra somente 25,3% daqueles classificados como KW 2. Esta categoria também foi mais freqüente em todos os estágios de hipertensão segundo o V-JNC. As anormalidades da classe 3 de KW foram pouco freqüentes, ocorrendo em somente 2,5% dos pacientes da coorte. Em um modelo de regressão logística, o estreitamento arteriolar difuso foi associado com maior pressão diastólica (P = 0,002) e maior idade (P < 0,001). Anormalidades de cruzamentos arteriovenosos foram associados com maior pressão sangüínea sistólica (P = 0,003) e duração da hipertensão maior do que 3 anos (P = 0,024). O valor preditivo positivo de qualquer anormalidade fundoscópica estimar a gravidade da hipertensão foi de 75,20% e o valor preditivo negativo, 41,75%. Observou-se maior proporção de eletrocardiograma anormal (qualquer anormalidade) e de sobrecarga ventricular esquerda em pacientes com pressão diastólica maior que 105 mmHg (P = 0,039 e P = 0,032 respectivamente) e com sistólica maior que 180 mmHg (P = 0,034 e P = 0,001 respectivamente). Anormalidades entre oftalmoscopia e eletrocardiograma não mostraramse associadas. Os resultados deste estudo demostraram que, apesar das anormalidades fundoscópicas terem sido mais freqüentes em hipertensos mais graves, o exame de fundode- olho não proporcionou uma idéia acurada da gravidade da hipertensão na maioria dos pacientes examinados por internistas e cardiologistas e, que a classificação de Keith, Wagener e Barker teve uma aplicação limitada. A observação de um cruzamento arteriovenoso alterado sugere que a pressão sistólica seja elevada. A presença de estreitamento arteriolar difuso é mais freqüente em pacientes mais velhos e naqueles com pressão diastólica elevada.

Avaliação do papel da ultra-sonografia obstétrica de rotina, no rastreamento pré-natal das anormalidades cardíacas

A ultra-sonografia obstétrica é um método diagnóstico tradicionalmente utilizado na rotina do atendimento pré-natal, tendo sido estudados de forma ampla suas vantagens e limitações. O advento do diagnóstico intra-uterino de cardiopatias congênitas e de arritmias através da ecocardiografia fetal modificou completamente o prognóstico perinatal dessas afecções, por permitir planejar o adequado manejo cardiológico no período neonatal imediato e, em algumas situações, o tratamento e sua resolução in utero. Sendo muito elevada a prevalência de cardiopatias congênitas durante a vida fetal, sua detecção torna-se fundamental. Considerando a inviabilidade operacional de realizar rotineiramente ecocardiografia fetal em todas as gestações, levando-se em conta as condições locais do sistema de saúde, o encaminhamento para exame por especialista passa a ser otimizado com a possibilidade da suspeita de alterações estruturais ou funcionais do coração e do sistema circulatório durante o exame ultra-sonográfico obstétrico de rotina. Não são conhecidos, em nosso meio, dados que avaliem de forma sistemática a acurácia da ultra-sonografia obstétrica no que se refere à suspeita pré-natal de cardiopatias. A partir deste questionamento, este trabalho foi delineado com o objetivo de avaliar o papel da ultra-sonografia obstétrica de rotina na suspeita pré-natal de cardiopatias congênitas ou arritmias graves e os fatores envolvidos na sua efetividade. A amostra foi constituída de 77 neonatos ou lactentes internados no Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia (IC/FUC) no período de maio a outubro de 2000, com diagnóstico pós-natal confirmado de cardiopatia estrutural ou arritmia grave, que tenham sido submetidos, durante a vida fetal, a pelo menos uma ultra-sonografia obstétrica após a 18a semana de gestação. Para a coleta de dados, foi utilizado um questionário padronizado, respondido pelos pais ou responsáveis, após consentimento informado. As variáveis categóricas foram comparadas pelo teste do qui-quadrado ou pelo teste de Fisher, com um alfa crítico de 0,05. Um modelo de regressão logística foi utilizado para determinar variáveis independentes eventualmente envolvidas na suspeita pré-natal de cardiopatia. Em 19 pacientes (24,7%), a ultra-sonografia obstétrica foi capaz de levantar suspeita de anormalidades estruturais ou de arritmias. Ao serem consideradas apenas as cardiopatias congênitas, esta prevalência foi de 19,2% (14/73). Em 73,7% destes, as cardiopatias suspeitadas eram acessíveis ao corte de 4-câmaras isolado. Observou-se que 26,3% das crianças com suspeita pré-natal de cardiopatia apresentaram arritmias durante o estudo ecográfico, enquanto apenas 3,4% dos pacientes sem suspeita pré-natal apresentaram alterações do ritmo (P=0,009). Constituiram-se em fatores comparativos significantes entre o grupo com suspeita pré-natal e o sem suspeita a paridade (P=0,029), o parto cesáreo (P=0,006), a internação em unidade de tratamento intensivo (P=0,046) e a escolaridade paterna (P=0,014). Não se mostraram significativos o número de gestações, a história de abortos prévios, o estado civil, o sexo dos pacientes, o tipo de serviço e a localidade em que foram realizados o pré-natal e a ultra-sonografia obstétrica, a indicação da ecografia, o número de ultra-sonografias realizadas, a renda familiar e a escolaridade materna. À análise multivariada, apenas a presença de alteração do ritmo cardíaco durante a ultra-sonografia obstétrica mostrou-se como variável independente associada à suspeita pré-natal de anormalidade cardíaca. Este trabalho demonstra que a ultra-sonografia obstétrica de rotina ainda tem sido subutilizada no rastreamento pré-natal de cardiopatias congênitas, levantando a suspeita de anormalidades estruturais em apenas um quinto dos casos. Considerando a importância prognóstica do diagnóstico intra-uterino de cardiopatias congênitas e arritmias graves, todos os esforços devem ser mobilizados no sentido de aumentar a eficácia da ecografia obstétrica de rotina para a suspeita de anormalidades cardíacas fetais. O treinamento dirigido dos ultra-sonografistas e a conscientização do meio obstétrico e da própria população são instrumentos para esta ação.

Predictability of equity models

In this study, we verify the existence of predictability in the Brazilian equity market. Unlike other studies in the same sense, which evaluate original series for each stock, we evaluate synthetic series created on the basis of linear models of stocks. Following Burgess (1999), we use the “stepwise regression” model for the formation of models of each stock. We then use the variance ratio profile together with a Monte Carlo simulation for the selection of models with potential predictability. Unlike Burgess (1999), we carry out White’s Reality Check (2000) in order to verify the existence of positive returns for the period outside the sample. We use the strategies proposed by Sullivan, Timmermann & White (1999) and Hsu & Kuan (2005) amounting to 26,410 simulated strategies. Finally, using the bootstrap methodology, with 1,000 simulations, we find strong evidence of predictability in the models, including transaction costs.

Um estudo dos supermercados no Brasil: uma investigação sobre a demanda de mercado, a fatia de mercado e a área de influência

Esse trabalho dá continuidade a estudos anteriores e visa contribuir para o avanço da ainda embrionária teoria varejista. Conseguimos desenvolver e operacionalizar os conceitos de área de influência, demanda de mercado e fatia de mercado, e analisar os resultados desses indicadores para os 27 supermercados de São Paulo, que participaram de nossa extensa pesquisa empírica. Um processo de modelagem econométrica foi conduzido, resultando em um modelo de regressão múltipla que satisfatoriamente explica e prevê área de influência como função de três variáveis: tamanho da loja, densidade populacional e disponibilidade de transporte coletivo. Apoiado em rigorosa metodologia de previsão de mercado, o estudo também revela estimativas de mercado que substancialmente diferem dos valores que vem sendo publicados na mídia especializada do setor. Nossa estimativa da demanda de mercado para o setor 'supermercados' no Brasil, em 2002, chega a superar R$ 100 bilhões, enquanto que nossa projeção da concentração das 5 maiores empresas no setor é de apenas 25%.

The influence of materialism on consumption indebtedness in the context of low income consumers from the city of São Paulo

This research is in the domains of materialism, consumer vulnerability and consumption indebtedness, concepts frequently approached in the literature on consumer behavior, macro-marketing and economic psychology. The influence of materialism on consumer indebtedness is investigated within a context that is characterized by poverty and by factors that cause vulnerability, such as high interest rates, limited access to credit and to quality affordable goods. The objectives of this research are: to produce a materialism scale that is well adapted to its environment, characterizing materialism adequately for the population studied; to compare results obtained with results of other studies; and to measure the relationship between materialism, socio-demographic variables, attitude to debt and consumption indebtedness. The primary data used in the analyses were collected from field research carried out in August, 2005 that relied on a probabilistic household sample of 450 low income individuals who live in poor regions of the city of Sao Paulo. The materialism scale, adapted and translated into Portuguese from Richins (2004), proved to be very successful and encourages new work in the area. It was noted that younger adults tend to be more materialistic than older ones; that illiterate adults tend to be less materialistic than those who did literacy courses when they were already adults; and that gender, income and race are not associated with the materialism construct. Among the other results, a logistic regression model was developed in order to distinguish those individuals who have an installment plan payment booklet from those who do not, based on materialism, socio-demographic variables and purchasing and consumer habits. The proposed model confirms materialism as a behavioral variable useful for forecasting the probability of an individual getting into debt in order to consume, in some cases almost doubling the chance of occurrence of this event. Findings confirm the thesis that it is not only adverse economic factors that lead people to get into debt; and that the study of demand for credit for consumption purposes must, of necessity, include variables of a psychological nature. It is suggested that the low income materialistic consumer experiences feelings of powerlessness and exclusion because of the gap that exists between their possessions and their desires. Lines of conduct to combat this marginalization from the consumer society are drawn targeting marketing professionals, public policy makers and vulnerability researchers. Finally, the possibility of new studies involving the materialism construct, which is central to literature on consumer behavior, albeit little used in empirical studies in Brazil, are discussed.

Um modelo de mudança Markoviana para a função de reação do banco central brasileiro

O objetivo desta dissertação é analisar a política de juros do Banco Central durante o período entre os anos de 1995 a 2002, procurando verificar se houve mudança nesta política, isto é se houve mudanças de regimes na condução da política monetária, principalmente com a mudança do regime cambial. Para tanto o modelo estimado mais adequado para a análise foi um switching regression model que determina endogenamente se há mudança de regimes.

Fundos de investimento: uma análise da dinâmica entre tamanho, captação e rentabilidade

O presente trabalho tem como objetivo avaliar a relação existente entre o retorno de um fundo, o seu tamanho, o total de recursos sob gestão da instituição gestora, entre outros fatores. Para a realização dos testes propostos, utilizamos o modelo de regressão com dados em painel. Consideramos para a análise os últimos cinco anos de informações disponíveis (maio de 2005 a abril de 2010) para duas categorias de fundos: Multimercados e Renda Variável. Outro ponto que buscamos investigar neste trabalho são os fatores que explicam a captação dos fundos. Neste caso, como possíveis variáveis explicativas, utilizamos, por exemplo, o retorno do fundo e seu Índice de Sharpe nos últimos 6 meses.