Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population

Background Lifestyle factors such as diet and physical activity have been shown to modify the association between fat mass and obesity–associated (FTO) gene variants and metabolic traits in several populations; however, there are no gene-lifestyle interaction studies, to date, among Asian Indians living in India. In this study, we examined whether dietary factors and physical activity modified the association between two FTO single nucleotide polymorphisms (rs8050136 and rs11076023) (SNPs) and obesity traits and type 2 diabetes (T2D). Methods The study included 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the urban component of the Chennai Urban Rural Epidemiology Study (CURES). Dietary intakes were assessed using a validated interviewer administered semi-quantitative food frequency questionnaire (FFQ). Physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the linear/logistic regression model. Results There was a significant interaction between SNP rs8050136 and carbohydrate intake (% energy) (Pinteraction = 0.04), where the ‘A’ allele carriers had 2.46 times increased risk of obesity than those with ‘CC’ genotype (P = 3.0 × 10−5) among individuals in the highest tertile of carbohydrate intake (% energy, 71 %). A significant interaction was also observed between SNP rs11076023 and dietary fibre intake (Pinteraction = 0.0008), where individuals with AA genotype who are in the 3rd tertile of dietary fibre intake had 1.62 cm lower waist circumference than those with ‘T’ allele carriers (P = 0.02). Furthermore, among those who were physically inactive, the ‘A’ allele carriers of the SNP rs8050136 had 1.89 times increased risk of obesity than those with ‘CC’ genotype (P = 4.0 × 10−5). Conclusions This is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. Our findings suggest that the association between FTO SNPs and obesity might be influenced by carbohydrate and dietary fibre intake and physical inactivity. Further understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions is warranted to advance the development of behavioral intervention and personalised lifestyle strategies, which could reduce the risk of metabolic diseases in this Asian Indian population.

Assessment of inbreeding depression in a Guzerat dairy herd: Effects of individual increase in inbreeding coefficients on production and reproduction

Influences of inbreeding on daily milk yield (DMY), age at first calving (AFC), and calving intervals (CI) were determined on a highly inbred zebu dairy subpopulation of the Guzerat breed. Variance components were estimated using animal models in single-trait analyses. Two approaches were employed to estimate inbreeding depression: using individual increase in inbreeding coefficients or using inbreeding coefficients as possible covariates included in the statistical models. The pedigree file included 9,915 animals, of which 9,055 were inbred, with an average inbreeding coefficient of 15.2%. The maximum inbreeding coefficient observed was 49.45%, and the average inbreeding for the females still in the herd during the analysis was 26.42%. Heritability estimates were 0.27 for DMY and 0.38 for AFC. The genetic variance ratio estimated with the random regression model for CI ranged around 0.10. Increased inbreeding caused poorer performance in DMY, AFC, and CI. However, some of the cows with the highest milk yield were among the highly inbred animals in this subpopulation. Individual increase in inbreeding used as a covariate in the statistical models accounted for inbreeding depression while avoiding overestimation that may result when fitting inbreeding coefficients.

Non-stationary frequency analysis of extreme daily rainfall in Sao Paulo, Brazil

This work is an assessment of frequency of extreme values (EVs) of daily rainfall in the city of Sao Paulo. Brazil, over the period 1933-2005, based on the peaks-over-threshold (POT) and Generalized Pareto Distribution (GPD) approach. Usually. a GPD model is fitted to a sample of POT Values Selected With a constant threshold. However. in this work we use time-dependent thresholds, composed of relatively large p quantities (for example p of 0.97) of daily rainfall amounts computed from all available data. Samples of POT values were extracted with several Values of p. Four different GPD models (GPD-1, GPD-2, GPD-3. and GDP-4) were fitted to each one of these samples by the maximum likelihood (ML) method. The shape parameter was assumed constant for the four models, but time-varying covariates were incorporated into scale parameter of GPD-2. GPD-3, and GPD-4, describing annual cycle in GPD-2. linear trend in GPD-3, and both annual cycle and linear trend in GPD-4. The GPD-1 with constant scale and shape parameters is the simplest model. For identification of the best model among the four models WC used rescaled Akaike Information Criterion (AIC) with second-order bias correction. This criterion isolates GPD-3 as the best model, i.e. the one with positive linear trend in the scale parameter. The slope of this trend is significant compared to the null hypothesis of no trend, for about 98% confidence level. The non-parametric Mann-Kendall test also showed presence of positive trend in the annual frequency of excess over high thresholds. with p-value being virtually zero. Therefore. there is strong evidence that high quantiles of daily rainfall in the city of Sao Paulo have been increasing in magnitude and frequency over time. For example. 0.99 quantiles of daily rainfall amount have increased by about 40 mm between 1933 and 2005. Copyright (C) 2008 Royal Meteorological Society

Factors associated with health-related quality of life after successful kidney transplantation: a population-based study

Kidney transplantation improves the quality of life of end-stage renal disease patients. The quality of life benefits, however, pertain to patients on average, not to all transplant recipients. The aim of this study was to identify factors associated with health-related quality of life after kidney transplantation. Population-based study with a cross-sectional design was carried out and quality of life was assessed by SF-36 Health Survey Version 1. A multivariate linear regression model was constructed with sociodemographic, clinical and laboratory data as independent variables. Two hundred and seventy-two kidney recipients with a functioning graft were analyzed. Hypertension, diabetes, higher serum creatinine and lower hematocrit were independently and significantly associated with lower scores for the SF-36 oblique physical component summary (PCSc). The final regression model explained 11% of the PCSc variance. The scores of oblique mental component summary (MCSc) were worse for females, patients with a lower income, unemployed and patients with a higher serum creatinine. The regression model explained 9% of the MCSc variance. Among the studied variables, comorbidity and graft function were the main factors associated with the PCSc, and sociodemographic variables and graft function were the main determinants of MCSc. Despite comprehensive, the final regression models explained only a little part of the heath-related quality of life variance. Additional factors, such as personal, environmental and clinical ones might influence quality of life perceived by the patients after kidney transplantation.

Small-Sample Corrections for Score Tests in Birnbaum-Saunders Regressions

In this article, we deal with the issue of performing accurate small-sample inference in the Birnbaum-Saunders regression model, which can be useful for modeling lifetime or reliability data. We derive a Bartlett-type correction for the score test and numerically compare the corrected test with the usual score test and some other competitors.

Improved likelihood inference in Birnbaum-Saunders regressions

The Birnbaum-Saunders regression model is commonly used in reliability studies. We address the issue of performing inference in this class of models when the number of observations is small. Our simulation results suggest that the likelihood ratio test tends to be liberal when the sample size is small. We obtain a correction factor which reduces the size distortion of the test. Also, we consider a parametric bootstrap scheme to obtain improved critical values and improved p-values for the likelihood ratio test. The numerical results show that the modified tests are more reliable in finite samples than the usual likelihood ratio test. We also present an empirical application. (C) 2009 Elsevier B.V. All rights reserved.

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.

Computerized identification of motor complications in Parkinson's disease

Objective: To investigate whether spirography-based objective measures are able to effectively characterize the severity of unwanted symptom states (Off and dyskinesia) and discriminate them from motor state of healthy elderly subjects. Background: Sixty-five patients with advanced Parkinson’s disease (PD) and 10 healthy elderly (HE) subjects performed repeated assessments of spirography, using a touch screen telemetry device in their home environments. On inclusion, the patients were either treated with levodopa-carbidopa intestinal gel or were candidates for switching to this treatment. On each test occasion, the subjects were asked trace a pre-drawn Archimedes spiral shown on the screen, using an ergonomic pen stylus. The test was repeated three times and was performed using dominant hand. A clinician used a web interface which animated the spiral drawings, allowing him to observe different kinematic features, like accelerations and spatial changes, during the drawing process and to rate different motor impairments. Initially, the motor impairments of drawing speed, irregularity and hesitation were rated on a 0 (normal) to 4 (extremely severe) scales followed by marking the momentary motor state of the patient into 2 categories that is Off and Dyskinesia. A sample of spirals drawn by HE subjects was randomly selected and used in subsequent analysis. Methods: The raw spiral data, consisting of stylus position and timestamp, were processed using time series analysis techniques like discrete wavelet transform, approximate entropy and dynamic time warping in order to extract 13 quantitative measures for representing meaningful motor impairment information. A principal component analysis (PCA) was used to reduce the dimensions of the quantitative measures into 4 principal components (PC). In order to classify the motor states into 3 categories that is Off, HE and dyskinesia, a logistic regression model was used as a classifier to map the 4 PCs to the corresponding clinically assigned motor state categories. A stratified 10-fold cross-validation (also known as rotation estimation) was applied to assess the generalization ability of the logistic regression classifier to future independent data sets. To investigate mean differences of the 4 PCs across the three categories, a one-way ANOVA test followed by Tukey multiple comparisons was used. Results: The agreements between computed and clinician ratings were very good with a weighted area under the receiver operating characteristic curve (AUC) coefficient of 0.91. The mean PC scores were different across the three motor state categories, only at different levels. The first 2 PCs were good at discriminating between the motor states whereas the PC3 was good at discriminating between HE subjects and PD patients. The mean scores of PC4 showed a trend across the three states but without significant differences. The Spearman’s rank correlations between the first 2 PCs and clinically assessed motor impairments were as follows: drawing speed (PC1, 0.34; PC2, 0.83), irregularity (PC1, 0.17; PC2, 0.17), and hesitation (PC1, 0.27; PC2, 0.77). Conclusions: These findings suggest that spirography-based objective measures are valid measures of spatial- and time-dependent deficits and can be used to distinguish drug-related motor dysfunctions between Off and dyskinesia in PD. These measures can be potentially useful during clinical evaluation of individualized drug-related complications such as over- and under-medications thus maximizing the amount of time the patients spend in the On state.

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.

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.

Acesso a atendimento médico continuado : uma estratégia para reduzir a utilização de consultas não urgentes em serviços de emergência

A utilização de uma emergência por pacientes com problemas médicos eletivos contribui para a demanda excessiva e impede de acesso a pacientes com emergência verdadeira. O presente estudo se propôs: (1) investigar as características do usuário da emergência em relação a aspectos demográficos, local de moradia e tempo que apresenta os sintomas que o levaram a consultar; (2) identificar as diferenças da demanda entre o final de semana e durante a semana; (3) investigar a prevalência de saúde mental, alcoolismo, doença coronariana e hipertensão; (4) avaliar como é a utilização e o acesso a serviços de saúde para pacientes que referem ter um médico definido em comparação com quem refere não ter; (5) avaliar a satisfação dos pacientes com o atendimento na emergência e (6) verificar se o atendimento através de um médico definido ou em serviço de atenção primária em saúde diminui o afluxo de casos não urgentes aos serviços de emergência. Foi realizado um estudo transversal na Emergência do Hospital N.S. da Conceição de Porto Alegre (RS) no período de 6 de janeiro a 25 de junho de 1996, tendo sido incluídos 20 dias escolhidos entre o meio-dia de sábado e o meio-dia de domingo, para caracterizar a demanda do final de semana, e o meio-dia de segunda-feira e meio-dia de terça-feira, para a dos outros dias. Fizeram parte da amostra 553 pacientes selecionados através de amostragem aleatória sistemática, com uma taxa de resposta de 88%. A coleta de dados consistiu de questionário de 156 questões aplicado aos pacientes. O registro e análise dos dados foram realizados utilizando-se os programas Epi-Info, EGRET e SPSS. As análises incluíram tabulações simples para determinação de prevalência das condições investigadas e regressão logística para avaliar o efeito conjunto das variáveis independentes sobre cada uma das variáveis dependentes. A população que freqüenta a emergência do HNSC é composta de jovens, predominantemente do sexo feminino, mora em Porto Alegre (especialmente, no bairro Sarandi) e na Grande Porto Alegre (especialmente, Alvorada), desloca-se preferencialmente de ônibus até o serviço de emergência, vem acompanhada, na maioria das vezes, de algum familiar, e a maioria decide consultar por iniciativa própria ou por indicação de algum familiar. Os homens internam com maior freqüência. Os serviços de atenção primária representaram 23% do atendimento habitual dos pacientes. As consultas foram definidas pelos emergencistas como de emergência em 15% dos casos, de urgência em 46%, e programáveis em 39% poderiam ser programadas. A prevalência de hipertensão foi 19%; de angina, 13%; de alcoolismo, 16%; de problema psiquiátrico menor, 32% entre os homens e 51% entre as mulheres (p< 0,0001). Como desfecho da consulta, 73% dos pacientes foram encaminhados para o domicílio ou para um serviço especializado, 10% foram para sala de observação e para apenas 5% foi indicada a internação. A maioria dos pacientes referiram estar satisfeitos com o atendimento. Os que consultaram no final de semana apresentaram, em média, um tempo menor de sintomas até decidir consultar, um menor tempo de deslocamento até o serviço de emergência, maior satisfação, média de idade maior, maior proporção de moradores de Porto Alegre e foram levados de carro até a emergência mais do que aqueles que consultaram durante a semana. O modelo de regressão logística identificou as variáveis independentes determinantes de ter um médico definido: consulta habitual em atenção primária em saúde (RC=3,22 IC95%=2,04-5,09), consulta definida como emergência ou urgência (RC=2,46 IC95%=1,55-3,92) e afastamento do trabalho (RC=1,59 IC95%= 1,03-2,45). Este resultado demonstra que o paciente que habitualmente consulta em serviços de atenção primária tem mais probabilidade para ter a continuidade no atendimento. A consulta ser de emergência ou de urgência apresentou associação significativa com as seguintes variáveis independentes, após ser colocada num modelo de regressão logística: pacientes internados ou em observação (RC=5,80 IC95%=3,33-10,17), costume de consultar com o mesmo médico (RC=2,98 IC95%=1,84-4,80) e ida de carro até a emergência (RC=2,67 IC95%=1,75-4,05). A variável hábito de consultar em serviço de atenção primária deixou de ficar estatisticamente significativa ao ser colocada no modelo de regressão logística. Este resultado revela que pacientes com médico definido têm três vezes mais chances de consultar por um problema de emergência no serviço de emergência do que aqueles que não têm um médico definido. Assim, uma estratégia para reduzir a ocorrência de consultas não urgentes em serviços de emergência é o paciente ter tal vínculo. No entanto, aqueles pacientes que referiram o posto de saúde como local onde habitualmente consultam não evitam, necessariamente, a utilização de um serviço de emergência por motivo considerado como programável. É necessário otimizar o atendimento de pacientes com problemas não urgentes que chegam à emergência através de estratégias no nível de atenção primária – especialmente possibilitando o atendimento médico continuado -, onde uma abordagem integral com ênfase na prevenção garanta um atendimento de melhor qualidade e custo menor.