Estimation of the mean quality-adjusted survival using a multistate model for the sojourn times

In clinical trials, it may be of interest taking into account physical and emotional well-being in addition to survival when comparing treatments. Quality-adjusted survival time has the advantage of incorporating information about both survival time and quality-of-life. In this paper, we discuss the estimation of the expected value of the quality-adjusted survival, based on multistate models for the sojourn times in health states. Semiparametric and parametric (with exponential distribution) approaches are considered. A simulation study is presented to evaluate the performance of the proposed estimator and the jackknife resampling method is used to compute bias and variance of the estimator. (C) 2007 Elsevier B.V. All rights reserved.

Expression, purification and kinetic characterization of His-tagged glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi

Trypanosomes are flagellated protozoa responsible for serious parasitic diseases that have been classified by the World Health Organization as tropical sicknesses of major importance. One important drug target receiving considerable attention is the enzyme glyceraldehyde-3-phosphate dehydrogenase from the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (T. cruzi Glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH); EC 1.2.1.12). TcGAPDH is a key enzyme in the glycolytic pathway of T. cruzi and catalyzes the oxidative phosphorylation of D-glyceraldehyde-3-phosphate (G3P) to 1,3-bisphosphoglycerate (1,3-BPG) coupled to the reduction of oxidized nicotinamide adenine dinucleotide, (NAD(+)) to NADH, the reduced form. Herein, we describe the cloning of the T. cruzi gene for TcGAPDH into the pET-28a(+) vector, its expression as a tagged protein in Escherichia coli, purification and kinetic characterization. The His(6)-tagged TcGAPDH was purified by affinity chromatography. Enzyme activity assays for the recombinant His(6)-TcGAPDH were carried out spectrophotometrically to determine the kinetic parameters. The apparent Michaelis-Menten constant (K(M)(app)) determined for D-glyceraldehyde-3-phosphate and NAD(+) were 352 +/- 21 and 272 +/- 25 mu M, respectively, which were consistent with the values for the untagged enzyme reported in the literature. We have demonstrated by the use of Isothermal Titration Calorimetry (ITC) that this vector modification resulted in activity preserved for a higher period. We also report here the use of response surface methodology (RSM) to determine the region of optimal conditions for enzyme activity. A quadratic model was developed by RSM to describe the enzyme activity in terms of pH and temperature as independent variables. According to the RMS contour plots and variance analysis, the maximum enzyme activity was at 29.1 degrees C and pH 8.6. Above 37 degrees C, the enzyme activity starts to fall, which may be related to previous reports that the quaternary structure begins a process of disassembly. (C) 2010 Elsevier Inc. All rights reserved.

Genetic Control of Residual Variance for Teat Number in Pigs

The genetic improvement in litter size in pigs has been substantial during the last 10-15 years. The number of teats on the sow must increase as well to meet the needs of the piglets, because each piglet needs access to its own teat. We applied a genetic heterogeneity model on teat numberin sows, and estimated medium-high heritability for teat number (0.5), but low heritability for residual variance (0.05), indicating that selection for reduced variance might have very limited effect. A numerically positive correlation (0.8) between additive genetic breeding values for mean and for variance was found, but because of the low heritability for residual variance, the variance will increase very slowly with the mean.

Genetic heterogeneity of residual variance : estimation of variance components using double hierarchical generalized linear models

Background: The sensitivity to microenvironmental changes varies among animals and may be under genetic control. It is essential to take this element into account when aiming at breeding robust farm animals. Here, linear mixed models with genetic effects in the residual variance part of the model can be used. Such models have previously been fitted using EM and MCMC algorithms. Results: We propose the use of double hierarchical generalized linear models (DHGLM), where the squared residuals are assumed to be gamma distributed and the residual variance is fitted using a generalized linear model. The algorithm iterates between two sets of mixed model equations, one on the level of observations and one on the level of variances. The method was validated using simulations and also by re-analyzing a data set on pig litter size that was previously analyzed using a Bayesian approach. The pig litter size data contained 10,060 records from 4,149 sows. The DHGLM was implemented using the ASReml software and the algorithm converged within three minutes on a Linux server. The estimates were similar to those previously obtained using Bayesian methodology, especially the variance components in the residual variance part of the model. Conclusions: We have shown that variance components in the residual variance part of a linear mixed model can be estimated using a DHGLM approach. The method enables analyses of animal models with large numbers of observations. An important future development of the DHGLM methodology is to include the genetic correlation between the random effects in the mean and residual variance parts of the model as a parameter of the DHGLM.

Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease

The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.

The trade-off between incentives and endogenous risk

Standard models of moral hazard predict a negative relationship between risk and incentives, but the empirical work has not confirmed this prediction. In this paper, we propose a model with adverse selection followed by moral hazard, where effort and the degree of risk aversion are private information of an agent who can control the mean and the variance of profits. For a given contract, more risk-averse agents suppIy more effort in risk reduction. If the marginal utility of incentives decreases with risk aversion, more risk-averse agents prefer lower-incentive contractsj thus, in the optimal contract, incentives are positively correlated with endogenous risk. In contrast, if risk aversion is high enough, the possibility of reduction in risk makes the marginal utility of incentives increasing in risk aversion and, in this case, risk and incentives are negatively related.

Cyanobacteria and Cyanotoxin in the Billings Reservoir (São Paulo, SP, Brazil)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dehydration of dedo de moça pepper: kinetics and phytochemical concentration

A pimenta vermelha é rica em vitamina C e outros fitoquímicos e pode ser consumida como produto desidratado. A avaliação das melhores condições de secagem pode garantir melhor qualidade do produto. Assim, o objetivo deste trabalho foi estudar o efeito da temperatura do ar de secagem (55, 65, 75 ºC) sobre a cinética de secagem, conteúdos de vitamina C e fenólicos totais e cor do produto desidratado, comparando-os à pimenta in natura. A desidratação foi feita por convecção forçada em estufa. A cinética de secagem foi determinada por pesagens periódicas até peso constante. A umidade da pimenta in natura foi de aproximadamente 86%. As curvas de secagem foram ajustadas por três modelos diferentes, avaliados na literatura. O modelo de Page apresentou o melhor ajuste para este processo. A análise de variância mostrou que a temperatura de secagem influenciou significativamente (p < 0,05) os parâmetros de qualidade (conteúdo de vitamina C, conteúdo de fenólicos totais, cor) da pimenta desidratada quando comparados aos da pimenta in natura. Após a secagem, a retenção de vitamina C aumentou com a redução da temperatura de secagem. de maneira geral, a qualidade do produto foi favorecida na secagem com menor temperatura, devido à redução nas perdas de compostos bioativos.

Variable parameter and double sampling (X)over-bar charts in the presence of correlation: The Markov chain approach

The general assumption under which the (X) over bar chart is designed is that the process mean has a constant in-control value. However, there are situations in which the process mean wanders. When it wanders according to a first-order autoregressive (AR (1)) model, a complex approach involving Markov chains and integral equation methods is used to evaluate the properties of the (X) over bar chart. In this paper, we propose the use of a pure Markov chain approach to study the performance of the (X) over bar chart. The performance of the chat (X) over bar with variable parameters and the (X) over bar with double sampling are compared. (C) 2011 Elsevier B.V. All rights reserved.

The double sampling and the EWMA charts based on the sample variances

We propose a new statistic to control the covariance matrix of bivariate processes. This new statistic is based on the sample variances of the two quality characteristics, in short VMAX statistic. The points plotted on the chart correspond to the maximum of the values of these two variances. The reasons to consider the VMAX statistic instead of the generalized variance vertical bar S vertical bar is its faster detection of process changes and its better diagnostic feature; that is, with the VMAX statistic it is easier to identify the out-of-control variable. We study the double sampling (DS) and the exponentially weighted moving average (EWMA) charts based on the VMAX statistic. (C) 2008 Elsevier B.V. All rights reserved.

Discoloration process modeling by neural network

The photo-oxidation of acid orange 52 dye was performed in the presence of H2O2, utilizing UV light, aiming the discoloration process modeling and the process variable influence characterization. The discoloration process was modeled by the use of feedforward neural network. Each sample was characterized by five independent variables (dye concentration, pH, hydrogen peroxide volume, temperature and time of operation) and a dependent variable (absorbance). The neural model has also provided, through Garson Partition coefficients and the Pertubation method, the independent variable influence order determination. The results indicated that the time of operation was the predominant variable and reaction mean temperature was the lesser influent variable. The neural model obtained presented coefficients of correlation on the order 0.98, for sets of trainability, validation and testing, indicating the power of prediction of the model and its character of generalization. (c) 2007 Elsevier B.V. All rights reserved.

Enteric coated magnetic HPMC capsules evaluated in human gastrointestinal tract by AC biosusceptometry

Purpose. To employ the AC Biosusceptometry (ACB) technique to evaluate in vitro and in vivo characteristics of enteric coated magnetic hydroxypropyl methylcellulose (HPMC) capsules and to image the disintegration process.Materials and Methods. HPMC capsules filled with ferrite (MnFe2O4) and coated with Eudragit (R) were evaluated using USP XXII method and administered to fasted volunteers. Single and multisensor ACB systems were used to characterize the gastrointestinal (GI) motility and to determine gastric residence time (GRT), small intestinal transit time (SITT) and orocaecal transit time (OCTT). Mean disintegration time (t (50)) was quantified from 50% increase of pixels in the imaging area.Results. In vitro and in vivo performance of the magnetic HPMC capsules as well as the disintegration process were monitored using ACB systems. The mean disintegration time (t (50)) calculated for in vitro was 25 +/- 5 min and for in vivo was 13 +/- 5 min. In vivo also were determined mean values for GRT (55 +/- 19 min), SITT (185 +/- 82 min) and OCTT (240 +/- 88 min).Conclusions. AC Biosusceptometry is a non-invasive technique originally proposed to monitoring pharmaceutical dosage forms orally administered and to image the disintegration process.

Caroticoclinoid foramen in human skulls: incidence, morphometry and its clinical implications

The caroticoclinoid foramen is an inconstant structure, formed by the union of the anterior and middle clinoid processes. The aim of this study was to perform an incidence and morphometry of the caroticoclinoid foramen in Brazilian human skulls and discuss its clinical implications. Eighty dry human skulls with sex distinction were used, and 3 groups of incidence were determined: General, sex, and sides. The morphometry was performed using a manual caliper and the major diameter of the foramina was measured; the values were also divided in general, according to sex and sides. The incidence of skulls with at least one foramen was 8.5%. According to the sides, 8.5% of the skulls showed foramen on the right side and 2.5% on the left. We found 2.5% of the skulls with bilateral foramen and 6.25% with unilateral foramen. In relation to sex, the foramens were found in 5% of male skulls and 12.5% of female skulls. The major diameter of this structure presented on mean, values of 5.23 mm on general, 5.18 mm on the right side and 5.35 mm on the left, 5.30 mm in male skulls and 5.18 mm in female skulls. The anatomical characteristics of this foramen should be considered in view of its clinical implications associated with neurosurgery as clinoid process removal, and symptoms as headache due to internal carotid artery alterations in this region. In conclusion knowledge of this structure supports the diagnosis and treatment of clinical complications related to this variation.

The Efficacy of Laser Fluorescence to Detect in Vitro Demineralization and Remineralization of Smooth Enamel Surfaces

Objective: The purpose of this study was to evaluate the efficacy of the laser fluorescence (LF) device in detecting in vitro demineralization and remineralization of smooth surface caries-like lesions. Background Data: The early detection of smooth surface caries-like lesions is important to provide proper management of carious lesions, and allows monitoring of them over time. Also, some authors suggest that LF could be useful in monitoring the caries pathological process. Materials and Methods: Seventy-eight blocks of bovine teeth were obtained, and then submitted to artificial caries lesion induction and to a pH-cycling process. Superficial microhardness (SMH) and laser fluorescence analysis were performed at baseline, after induction of caries-like lesions, and after the pH-cycling regimen to promote remineralization. Results: Friedman's and multiple comparison tests were performed for all variables. SMH analysis showed significant differences (p < 0.05) between baseline (286.77 +/- 1.49 Vickers hardness number [VHN] units), before (38.48 +/- 0.85 VHN), and after remineralization (131.93 +/- 2.63 VHN). Baseline values for LF were extremely low (2.71 +/- 0.05), and a statistically significant difference was observed only after remineralization (3.61 +/- 0.08), as demonstrated by the increase in LF values. Conclusion: The LF device did not show efficacy for monitoring in vitro demineralization and remineralization of smooth enamel surfaces.

Tree population and community dynamics in a Brazilian tropical semideciduous forest

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)