Denise Duarte

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations

Significance The EPIGEN Brazil Project is the largest Latin-American initiative to study the genomic diversity of admixed populations and its effect on phenotypes. We studied 6,487 Brazilians from three population-based cohorts with different geographic and demographic backgrounds. We identified ancestry components of these populations at a previously unmatched geographic resolution. We broadened our understanding of the African diaspora, the principal destination of which was Brazil, by revealing an African ancestry component that likely derives from the slave trade from Bantu/eastern African populations. In the context of the current debate about how the pattern of deleterious mutations varies between Africans and Europeans, we use whole-genome data to show that continental admixture is the main and complex determinant of the amount of deleterious genotypes in admixed individuals. While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6–8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

Surgical site infection in patients submitted to orthopedic surgery: the NNIS risk index and risk prediction

UNLABELLED The applicability of the risk index for surgical site infection of the National Nosocomial Infection Surveillance (NNIS) has been evaluated for its performance in different surgeries. In some procedures, it is necessary to include other variables to predict. OBJECTIVE to evaluate the applicability of the NNIS index for prediction of surgical site infection in orthopedic surgeries and to propose an alternative index. The study involved a historical cohort of 8236 patients who had been submitted to orthopaedic surgery. Statistical analysis was performed using multivariate logistic regression to fit the model. The incidence of infection was 1.41%. Prediction models were evaluated and compared to the NNIS index. The proposed model was not considered a good predictor of infection, despite moderately stratified orthopedic surgical patients in at least three of the four scores. The alternative model scored higher than the NNIS models in the prediction of infection.La aplicabilidad del Indice de Riesgo de Infeccion Quirurgica del National Nosocomial Infection Surveillance-NNIS ha sido evaluada en cuanto a su desempeno en diferentes cirugias. En algunos procedimientos es necesaria la inclusion de otras variables de prediccion. El objetivo de este estudio fue evaluar la aplicabilidad del Indice NNIS para la prediccion de la Infeccion de Sitio Quirurgico en cirugias ortopedicas y proponer un indice alternativo. Se realizo un estudio de cohorte historica en 8.236 pacientes sometidos a cirugias ortopedicas. Se utilizo el modelo logistico multivariado para ajustar el modelo. La incidencia de infeccion fue 1,41%. Modelos de prediccion fueron evaluados y comparados al Indice NNIS. El modelo propuesto fue aquel que presento mayor precision en clasificar pacientes con y sin infeccion. El Indice NNIS no fue considerado un buen factor de prediccion de la infeccion, a pesar de haber estratificado moderadamente a los pacientes quirurgicos ortopedicos en por el menos tres de los cuatro puntajes. El modelo alternativo fue superior al modelo NNIS en la prediccion de infeccion.

Population genetics of immune-related multilocus copy number variation in Native Americans

While multiallelic copy number variation (mCNV) loci are a major component of genomic variation, quantifying the individual copy number of a locus and defining genotypes is challenging. Few methods exist to study how mCNV genetic diversity is apportioned within and between populations (i.e. to define the population genetic structure of mCNV). These inferences are critical in populations with a small effective size, such as Amerindians, that may not fit the Hardy–Weinberg model due to inbreeding, assortative mating, population subdivision, natural selection or a combination of these evolutionary factors. We propose a likelihood-based method that simultaneously infers mCNV allele frequencies and the population structure parameter f, which quantifies the departure of homozygosity from the Hardy–Weinberg expectation. This method is implemented in the freely available software CNVice, which also infers individual genotypes using information from both the population and from trios, if available. We studied the population genetics of five immune-related mCNV loci associated with complex diseases (beta-defensins, CCL3L1/CCL4L1, FCGR3A, FCGR3B and FCGR2C) in 12 traditional Native American populations and found that the population structure parameters inferred for these mCNVs are comparable to but lower than those for single nucleotide polymorphisms studied in the same populations.

Use of jump process to model mobility in massive multiplayer on-line games

ABSTRACT This paper proposes a methodology to model the mobility of characters in Massively Multiplayer On-line (MMO) Games. We propose to model the mobility of characters in the map of an MMO game as a jump process using two approaches to model the times spent in the states of the process: parametric and non-parametric. Furthermore, a simulator for the mobility is presented. We analyze geographic position data of the characters in the map of the game World of Warcraft and compare the observed and simulated data. The proposed methodology and the simulator can be used to optimize computing load allocation of servers, which is extremely important for game performance, service quality and cost.

Infección de sitio quirúrgico en pacientes sometidos a cirugías ortopédicas: el índice de riesgo NNIS y la predicción de riesgo

UNLABELLED The applicability of the risk index for surgical site infection of the National Nosocomial Infection Surveillance (NNIS) has been evaluated for its performance in different surgeries. In some procedures, it is necessary to include other variables to predict. OBJECTIVE to evaluate the applicability of the NNIS index for prediction of surgical site infection in orthopedic surgeries and to propose an alternative index. The study involved a historical cohort of 8236 patients who had been submitted to orthopaedic surgery. Statistical analysis was performed using multivariate logistic regression to fit the model. The incidence of infection was 1.41%. Prediction models were evaluated and compared to the NNIS index. The proposed model was not considered a good predictor of infection, despite moderately stratified orthopedic surgical patients in at least three of the four scores. The alternative model scored higher than the NNIS models in the prediction of infection.La aplicabilidad del Indice de Riesgo de Infeccion Quirurgica del National Nosocomial Infection Surveillance-NNIS ha sido evaluada en cuanto a su desempeno en diferentes cirugias. En algunos procedimientos es necesaria la inclusion de otras variables de prediccion. El objetivo de este estudio fue evaluar la aplicabilidad del Indice NNIS para la prediccion de la Infeccion de Sitio Quirurgico en cirugias ortopedicas y proponer un indice alternativo. Se realizo un estudio de cohorte historica en 8.236 pacientes sometidos a cirugias ortopedicas. Se utilizo el modelo logistico multivariado para ajustar el modelo. La incidencia de infeccion fue 1,41%. Modelos de prediccion fueron evaluados y comparados al Indice NNIS. El modelo propuesto fue aquel que presento mayor precision en clasificar pacientes con y sin infeccion. El Indice NNIS no fue considerado un buen factor de prediccion de la infeccion, a pesar de haber estratificado moderadamente a los pacientes quirurgicos ortopedicos en por el menos tres de los cuatro puntajes. El modelo alternativo fue superior al modelo NNIS en la prediccion de infeccion.

Infecção de sítio cirúrgico em pacientes submetidos a cirurgias ortopédicas: o índice de risco NNIS e predição de risco

UNLABELLED The applicability of the risk index for surgical site infection of the National Nosocomial Infection Surveillance (NNIS) has been evaluated for its performance in different surgeries. In some procedures, it is necessary to include other variables to predict. OBJECTIVE to evaluate the applicability of the NNIS index for prediction of surgical site infection in orthopedic surgeries and to propose an alternative index. The study involved a historical cohort of 8236 patients who had been submitted to orthopaedic surgery. Statistical analysis was performed using multivariate logistic regression to fit the model. The incidence of infection was 1.41%. Prediction models were evaluated and compared to the NNIS index. The proposed model was not considered a good predictor of infection, despite moderately stratified orthopedic surgical patients in at least three of the four scores. The alternative model scored higher than the NNIS models in the prediction of infection.La aplicabilidad del Indice de Riesgo de Infeccion Quirurgica del National Nosocomial Infection Surveillance-NNIS ha sido evaluada en cuanto a su desempeno en diferentes cirugias. En algunos procedimientos es necesaria la inclusion de otras variables de prediccion. El objetivo de este estudio fue evaluar la aplicabilidad del Indice NNIS para la prediccion de la Infeccion de Sitio Quirurgico en cirugias ortopedicas y proponer un indice alternativo. Se realizo un estudio de cohorte historica en 8.236 pacientes sometidos a cirugias ortopedicas. Se utilizo el modelo logistico multivariado para ajustar el modelo. La incidencia de infeccion fue 1,41%. Modelos de prediccion fueron evaluados y comparados al Indice NNIS. El modelo propuesto fue aquel que presento mayor precision en clasificar pacientes con y sin infeccion. El Indice NNIS no fue considerado un buen factor de prediccion de la infeccion, a pesar de haber estratificado moderadamente a los pacientes quirurgicos ortopedicos en por el menos tres de los cuatro puntajes. El modelo alternativo fue superior al modelo NNIS en la prediccion de infeccion.