TCF7L2 variant genotypes and type 2 diabetes risk in Brazil: significant association, but not a significant tool for risk stratification in the general population

Background: Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population. Methods: We genotyped the single nucleotide polymorphisms (SNP) rs7903146 of the TCF7L2 gene in 560 patients with known coronary disease enrolled in the MASS II (Medicine, Angioplasty, or Surgery Study) Trial and in 1,449 residents of Vitoria, in Southeast Brazil. The associations of this gene variant to diabetes risk and metabolic characteristics in these two different populations were analyzed. To access the potential benefit of using this marker for diabetes risk prediction in the general population we analyzed the impact of this genetic variant on a validated diabetes risk prediction tool based on clinical characteristics developed for the Brazilian general population. Results: SNP rs7903146 of the TCF7L2 gene was significantly associated with type 2 diabetes in the MASS-II population (OR = 1.57 per T allele, p = 0.0032), confirming, in the Brazilian population, previous reports of the literature. Addition of this polymorphism to an established clinical risk prediction score did not increased model accuracy (both area under ROC curve equal to 0.776). Conclusion: TCF7L2 rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease. However, the inclusion of this polymorphism in a risk prediction tool developed for the general population resulted in no improvement of performance. This is the first study, to our knowledge, that has confirmed this recent association in a South American population and adds to the great consistency of this finding in studies around the world. Finally, confirming the biological association of a genetic marker does not guarantee improvement on already established screening tools based solely on demographic variables.

CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Background: Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population. Methods: One hundred and eighty-three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the ABCB1c.C3435T (rs1045642), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*4 (rs28399504), CYP2C19*5 (rs56337013), and CYP2C19*17 (rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The CYP2C19*3, CYP2C19*4 and CYP2C19*5 variants were genotyped in a subsample of subjects (300 samples randomly selected). Results: The CYP2C19*3 and CYP2C19*5 variant alleles were not detected and the CYP2C19*4 variant allele presented a frequency of 0.3%. The allelic frequencies for the ABCB1c.C3435T, CYP2C19*2 and CYP2C19*17 polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population. Conclusion: Our findings indicate the existence of inter-ethnic differences in the ABCB1 and CYP2C19 variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more cost-effective programs towards individualization of clopidogrel therapy.

Contralateral cortical response of a subpopulation of interneurons and the glial glutamate transporter GLT1 to an ischemic core

Introduction: Cerebral ischemia is an important cause of brain lesion in humans. The target in research has been the ischemic core or the penumbra zones; little attention has been given to areas outside the core or the penumbra but connected with the primary site of injury. Objective: Evaluate the laminar response of a subpopulation of gabaergic cells, those that are parvalbumin (PV) positive and the astrocytes through the expression of the glial transporter GLT1 on the contralateral cortex to an ischemic core. Methodology: For this purpose we used the medial cerebral artery occlusion model in rats. The artery was occluded for 90 minutes and the animals were sacrificed at 24 and 72 hours post-ischemia. The brains were removed, cut in a vibratome at 50 microns and incubated with the primary antibodies against PV or GLT1. Sections were developed using the vectastain Kit. In control tissue the primary antibody was omitted. Results: When compared with control animals, treated ones show a decrease in the expression of GLT1, especially in layers III and IV of the contralateral cortex to the ischemic core. PV positive cells increases in layers II and V. Conclusion: Increases in the expression of PV cells could correspond to an adaptation associated with glutamate increases in the synaptic compartment. These increases may be due to decreases in the expression of GLT1 transporter, that could not remove the glutamate present in the synaptic cleft, generating hyperactivity in the contralateral cortex. These changes could represent an example of neuronal and glial plasticity in remote areas to an ischemic core but connected to the primary site of injury.

POLLING SYSTEMS WITH PARAMETER REGENERATION, THE GENERAL CASE

We consider a polling model with multiple stations, each with Poisson arrivals and a queue of infinite capacity. The service regime is exhaustive and there is Jacksonian feedback of served customers. What is new here is that when the server comes to a station it chooses the service rate and the feedback parameters at random; these remain valid during the whole stay of the server at that station. We give criteria for recurrence, transience and existence of the sth moment of the return time to the empty state for this model. This paper generalizes the model, when only two stations accept arriving jobs, which was considered in [Ann. Appl. Probab. 17 (2007) 1447-1473]. Our results are stated in terms of Lyapunov exponents for random matrices. From the recurrence criteria it can be seen that the polling model with parameter regeneration can exhibit the unusual phenomenon of null recurrence over a thick region of parameter space.

LIMIT THEOREMS FOR A GENERAL STOCHASTIC RUMOUR MODEL

We study a general stochastic rumour model in which an ignorant individual has a certain probability of becoming a stifler immediately upon hearing the rumour. We refer to this special kind of stifler as an uninterested individual. Our model also includes distinct rates for meetings between two spreaders in which both become stiflers or only one does, so that particular cases are the classical Daley-Kendall and Maki-Thompson models. We prove a Law of Large Numbers and a Central Limit Theorem for the proportions of those who ultimately remain ignorant and those who have heard the rumour but become uninterested in it.

Recursive linear estimation for general discrete-time descriptor systems

This paper considers the optimal linear estimates recursion problem for discrete-time linear systems in its more general formulation. The system is allowed to be in descriptor form, rectangular, time-variant, and with the dynamical and measurement noises correlated. We propose a new expression for the filter recursive equations which presents an interesting simple and symmetric structure. Convergence of the associated Riccati recursion and stability properties of the steady-state filter are provided. (C) 2010 Elsevier Ltd. All rights reserved.

New prediction methods for CO2 evaporation inside tubes: Part II - An updated general flow boiling heat transfer model based on flow patterns

Corresponding to the updated flow pattern map presented in Part I of this study, an updated general flow pattern based flow boiling heat transfer model was developed for CO2 using the Cheng-Ribatski-Wojtan-Thome [L. Cheng, G. Ribatski, L. Wojtan, J.R. Thome, New flow boiling heat transfer model and flow pattern map for carbon dioxide evaporating inside horizontal tubes, Int. J. Heat Mass Transfer 49 (2006) 4082-4094; L. Cheng, G. Ribatski, L. Wojtan, J.R. Thome, Erratum to: ""New flow boiling heat transfer model and flow pattern map for carbon dioxide evaporating inside tubes"" [Heat Mass Transfer 49 (21-22) (2006) 4082-4094], Int. J. Heat Mass Transfer 50 (2007) 391] flow boiling heat transfer model as the starting basis. The flow boiling heat transfer correlation in the dryout region was updated. In addition, a new mist flow heat transfer correlation for CO2 was developed based on the CO2 data and a heat transfer method for bubbly flow was proposed for completeness sake. The updated general flow boiling heat transfer model for CO2 covers all flow regimes and is applicable to a wider range of conditions for horizontal tubes: tube diameters from 0.6 to 10 mm, mass velocities from 50 to 1500 kg/m(2) s, heat fluxes from 1.8 to 46 kW/m(2) and saturation temperatures from -28 to 25 degrees C (reduced pressures from 0.21 to 0.87). The updated general flow boiling heat transfer model was compared to a new experimental database which contains 1124 data points (790 more than that in the previous model [Cheng et al., 2006, 2007]) in this study. Good agreement between the predicted and experimental data was found in general with 71.4% of the entire database and 83.2% of the database without the dryout and mist flow data predicted within +/-30%. However, the predictions for the dryout and mist flow regions were less satisfactory due to the limited number of data points, the higher inaccuracy in such data, scatter in some data sets ranging up to 40%, significant discrepancies from one experimental study to another and the difficulties associated with predicting the inception and completion of dryout around the perimeter of the horizontal tubes. (C) 2007 Elsevier Ltd. All rights reserved.

An exact conserving algorithm for nonlinear dynamics with rotational DOFs and general hyperelasticity. Part 2: shells

Following the approach developed for rods in Part 1 of this paper (Pimenta et al. in Comput. Mech. 42:715-732, 2008), this work presents a fully conserving algorithm for the integration of the equations of motion in nonlinear shell dynamics. We begin with a re-parameterization of the rotation field in terms of the so-called Rodrigues rotation vector, allowing for an extremely simple update of the rotational variables within the scheme. The weak form is constructed via non-orthogonal projection, the time-collocation of which ensures exact conservation of momentum and total energy in the absence of external forces. Appealing is the fact that general hyperelastic materials (and not only materials with quadratic potentials) are permitted in a totally consistent way. Spatial discretization is performed using the finite element method and the robust performance of the scheme is demonstrated by means of numerical examples.

An exact conserving algorithm for nonlinear dynamics with rotational DOFs and general hyperelasticity. Part 1: Rods

A fully conserving algorithm is developed in this paper for the integration of the equations of motion in nonlinear rod dynamics. The starting point is a re-parameterization of the rotation field in terms of the so-called Rodrigues rotation vector, which results in an extremely simple update of the rotational variables. The weak form is constructed with a non-orthogonal projection corresponding to the application of the virtual power theorem. Together with an appropriate time-collocation, it ensures exact conservation of momentum and total energy in the absence of external forces. Appealing is the fact that nonlinear hyperelastic materials (and not only materials with quadratic potentials) are permitted without any prejudice on the conservation properties. Spatial discretization is performed via the finite element method and the performance of the scheme is assessed by means of several numerical simulations.

General results for the beta-modified Weibull distribution

We study in detail the so-called beta-modified Weibull distribution, motivated by the wide use of the Weibull distribution in practice, and also for the fact that the generalization provides a continuous crossover towards cases with different shapes. The new distribution is important since it contains as special sub-models some widely-known distributions, such as the generalized modified Weibull, beta Weibull, exponentiated Weibull, beta exponential, modified Weibull and Weibull distributions, among several others. It also provides more flexibility to analyse complex real data. Various mathematical properties of this distribution are derived, including its moments and moment generating function. We examine the asymptotic distributions of the extreme values. Explicit expressions are also derived for the chf, mean deviations, Bonferroni and Lorenz curves, reliability and entropies. The estimation of parameters is approached by two methods: moments and maximum likelihood. We compare by simulation the performances of the estimates from these methods. We obtain the expected information matrix. Two applications are presented to illustrate the proposed distribution.

Alternative Analytical Expressions for the General van Genuchten-Mualem and van Genuchten-Burdine Hydraulic Conductivity Models

The van Genuchten expressions for the unsaturated soil hydraulic properties, first published in 1980, are used frequently in various vadose zone flow and transport applications assuming a specific relationship between the m and n soil hydraulic parameters. By comparison, probably because of the complexity of the hydraulic conductivity equations, the more general solutions with independent m and n values are rarely used. We expressed the general van Genuchten-Mualem and van Genuchten-Burdine hydraulic conductivity equations in terms of hypergeometric functions, which can be approximated by infinite series that converge rapidly for relatively large values of the van Genuchten-Mualem parameter n but only very slowly when n is close to one. Alternative equations were derived that provide very close approximations of the analytical results. The newly proposed equations allow the use of independent values of the parameters m and n in the soil water retention model of van Genuchten for subsequent prediction of the van Genuchten-Mualem and van Genuchten-Burdine hydraulic conductivity models, thus providing more flexibility in fitting experimental pressure-head-dependent water content, theta(h), and hydraulic conductivity, K(h), or K(theta) data.

Consumer`s evaluation of the effects of gamma irradiation and natural antioxidants on general acceptance of frozen beef burger

The effect of addition of rosemary and oregano extracts on the sensory quality of irradiated beef burger was investigated. Batches of beef burgers were prepared with 400 ppm of rosemary or oregano extract and a group prepared with 200 ppm of synthetic butyl-hydroxytoluene (BHT)/butyl-hydroxy-anisol (BHA) was used as a control. Half of each formulation was irradiated at the maximum dose allowed for frozen meat (7 kGy). Samples were kept under frozen conditions (-20 degrees C) during the whole storage period, including during irradiation. Two analyses were performed after 20 and 90 days to verify the influence of the addition of the different types of antioxidants and the effect of irradiation and storage time on the acceptance of the product. Thirty-three and thirty-four untrained panelists were invited to participate in the first and second test, respectively. A structured hedonic scale ranging from 1 to 9 points was used in both analyses. BHT/BHA formulation obtained the highest score (6.73) and regarding the natural antioxidants, oregano received better acceptance (6.36). Irradiated samples formulated with oregano received a lower score, 6.03 in the first test and 5.06 in the second one, compared to the non-irradiated sample (6.36 and 5.79). In the second test (90 days), the sample formulated with BHT/BHA and which was irradiated received a higher score (6.59) when compared to the non-irradiated one (5.85). In both tests, the irradiated samples formulated with rosemary extract obtained a better score compared to the non-irradiated one, the scores being 5.00-3.82 and 5.00-3.76 in the first and second test, respectively. Our results allowed us to conclude that the natural antioxidants, rosemary and oregano extracts, present a good alternative for replacing synthetic additives in food industries, and that the irradiation process, in some cases, may help to enhance the sensory quality of food. (C) 2008 Elsevier Ltd. All rights reserved.

Northern wing, General Purpose North 3, University of Queensland, St Lucia

As seen from Blair Road.

Northern wing, General Purpose North 3, University of Queensland, St Lucia

As seen from Balir Road.