Luís Miguel Cunha

Optimal experimental design for estimating the kinetic parameters of processes described by the Weibull probability distribution function

Abstract The optimum experimental design for determining the kinetic parameters of the model resulting from the Weibull probability density function was studied, by defining the sampling conditions that lead to a minimum confidence region of the estimates, for a number of observations equal to the number of parameters. It was found that for one single isothermal experiment the optimum sampling times corresponded always to fractional concentrations that are irrational numbers (approximately 0.70 and 0.19) whose product is exactly 1 e 2 . The experimental determination of the equilibrium conversion (for growth kinetics) is very important, but in some situations this is not possible, e.g. due to product degradation over the length of time required. Sampling times leading to a maximum precision were determined as a function of the maximum conversion (or yield) attainable. For studies of kinetic parameters over a range of temperatures, performed with a minimum of three isothermal experiments, it was proved that the optimum design consists of two experiments at one limit temperature with two sampling times (those corresponding to fractional concentrations of approximately 0.70 and 0.19) and another at the other limit temperature for a sampling time such that the fractional concentration is 1 e . Case studies are included for clarification of the concepts and procedures.

Empirical model building based on Weibull distribution to describe the joint effect of pH and temperature on the thermal resistance of Bacillus cereus in vegetable substrate

A mathematical model based on Weibull parameters was built to describe the joint effect of temperature and pH on thermal inactivation of Bacillus cereus spores (strain INRA TZ415). The effect of these factors on Weibull model parameters (beta, 1/alpha) was also studied. Heat inactivation tests were carried out in acidified carrot broth as vegetable substrate, following a full factorial design at four levels for temperature (80, 85, 90 and 95 degrees C) and pH (6.2, 5.8, 5.2 and 4.7). The Weibull distribution model provided good individual fits for the different combinations of temperature-pH tested, with discrepancy factors, Df, coming close to 25% for most cases. The temperature and pH did not have a significant effect on the shape parameter (beta), which yielded a mean value of 0.88. The scale parameter (alpha) decreased with pH, and its inverse (1/alpha) followed an Arrhenius-type relationship with temperature. A global model was built, including the dependence of the alpha parameter on temperature and pH, and the model parameters were estimated by using a one-step nonlinear least-squares regression to improve the precision of the estimates. Results indicated that the global model provides a satisfactory description of the thermal inactivation of B. cereus spores, with R2 equal to 0.983.

Optimal experimental design for estimating the kinetic parameters of the Bigelow model

Abstract The optimum experimental design for systems following the Bigelow model was studied by determining the sampling conditions that lead to a minimum confidence region for a number of observations equal to the number of parameters. For isothermal conditions, it was found that this corresponds to the sampling times when the fractional concentration of the decaying factor ( η i ) is equal to e −1 and that the experiments should be performed in the limit range of temperatures chosen. These results are identical to those described in the literature for a first-order Arrhenius model. For non-isothermal experiments with linearly increasing temperature, the optimal experimental design is obtained with a maximum heating rate, a minimum initial temperature and sampling times when the product of the fractional concentrations is e −2 (with η 1 ≅ 0.70 and η 2 ≅ 0.19). The influence of the heating rate on the precision of the estimates is more significant for high z values and the influence of the initial temperature is more significant for low values of the heating rate.

Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source: Design of the NAVIGATE ESUS randomized trial

Background Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. Main hypothesis In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. Design Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. Summary The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.

Biomonitoring of a population of Portuguese workers exposed to lead

Lead is a heavy metal that has been used for many centuries and it is still used for various industrial purposes thanks to its physical and chemical characteristics. Human exposure to lead can result in a wide range of biological effects depending upon the level and duration of exposure. Despite the fact that lead has been found capable of eliciting genotoxic responses in a wide range of tests, not all studies have been conclusive. Although several experimental studies have shown that lead may modulate immune responses, data in exposed humans are still preliminary. The purpose of our study was to evaluate the genotoxic and immunotoxic effects of lead exposure in a group of 70 male workers from two Portuguese factories. The control group comprised 38 healthy males. The exposed individuals showed significantly higher levels of lead in blood and zinc protoporphyrin, and significantly lower δ-aminolevulinic acid dehydratase activity than the controls, suggesting a relatively high lead exposure. Nevertheless, the limit of 70 μg/dl for lead in blood established by the Portuguese regulation was never reached. Results of the comet assay were not modified by the exposure, but a significant increase in the mutation frequency in the exposed workers was obtained in the T-cell receptor mutation assay. Furthermore, data obtained in the analysis of the different lymphocyte subsets showed a significant decrease in %CD8+ cells and a significant increase in the %CD4+/%CD8+ ratio in exposed individuals with regard to the controls. No clear effect was observed for vitamin D receptor genetic polymorphism on the parameters evaluated. In view of our results showing mutagenic and immunotoxic effects related to lead exposure in occupational settings, it seems that the Portuguese biological exposure limit for lead needs to be revised in order to increase the safety of exposed workers.

Effect of Minimal Processing Conditions on Respiration Rate of Carrots

Measurement, analysis, and modeling of respiration rate (RR) of fresh produce are fundamental for the engineering design of MAP. This study investigates the effect of type of cutting (sliced in circular shape, batons in rectangular shape, and shredded into thin strips) on the respiration rate of carrots at different temperatures (4, 8, 12, 16, and 20 degrees C) with ambient atmosphere. The higher respiration rates were found for shredded carrots and the lowest for whole carrots at all the temperatures tested. The RR increased from 9 +/- 1 to 26 +/- 3, 10 +/- 1 to 53 +/- 2, 11 +/- 1 to 55 +/- 2, and 18 +/- 1 to 75 +/- 3 mL of O(2) per kilogram hour for whole, sliced, baton, and shredded carrots, respectively, as the temperature increased from 4 to 20 degrees C. On an average, RO2 and RCO2 were increased by 85% and 64%, 100% and 72%, and 151% and 124% for sliced, baton, and shredded carrots, respectively, compared to the RR values of whole carrots. The temperature dependence of RR followed an Arrhenius-type relationship for all types of carrots, with activation energies in the range of 35 +/- 3 to 62 +/- 2 kJ/mol. Type of cut was the major factor for both RO2 and RCO2, with shredded carrots having the highest rates and whole carrots the lowest. RR of whole carrots did not vary during storage, whereas it increased for cut carrots and especially for shredded carrots. The respiratory quotient (RQ) increased with temperature and did not vary during storage in all types of carrots, except the RQ of whole carrots decreased significantly over time.

Determination of plate waste in primary school lunches by weighing and visual estimation methods: A validation study

The aim of this study was to validate the visual estimation method for aggregated plate waste of main dish at Portuguese primary school canteens. For this purpose plate waste at school lunch was measured for 505 individual servings, using weighing individual servings and plate waste and visual estimation method by a 6-point scale, as developed by Comstock et al. (1981). A high variability of initial serving weights was found with serving sizes ranging from 88.9 to 283.3g and with a coefficient of variation ranging from 5.5% to 24.7%. Mean plate waste was 27.5% according to the weighing method. There was a significant bias in the conversion of the visual waste estimations to actual waste, being overestimated by an average of 8.0 g (ranging from -12.9 g to 41.4 g). According to Bland and Altman plot, the mean difference between methods was of 8.0 g and the amplitude interval was 102.6g. The study showed that the visual estimation method is not as accurate as the weighing method in assessing nonselective aggregated plate waste at primary school canteens. Our findings are thus very important on considering plate waste assessment, since the wide variation on initial servings introduces a relevant bias when considering standard portions or a random sample of initial servings. Although, greater convenience, time-saving and the possibility to monitor plate waste of large groups, make the visual estimation method an important method to assess plate waste at school canteens, these results highlighted the need of portions standardization and control of initial servings to allow for its use.

Improved model based on the Weibull distribution to describe the combined effect of pH and temperature on the heat resistance of Bacillus cereus in carrot juice

The effect of pH and temperature on the thermal inactivation of different strains of Bacillus cereus was modeled. Inactivation tests were carried out in carrot broth, following a full factorial design at four levels for temperature (from 90 to 105 degrees C, depending on the strain) and pH (6.2, 5.8, 5.2, and 4.7). Individual inactivation curves were analyzed by applying the Weibull model function (with percent discrepancy close to 20% for most cases), and the effects of pH and temperature on the scale parameter (designated D(beta)) and the shape parameter (beta) were also studied. Temperature and pH did not have a significant effect on the shape parameter (beta). The effect of temperature on the scale parameter was modeled by the zeta concept. The scale parameter decreased with pH, although the behavior of the strains was not homogeneous. Two global models with a small number of parameters were developed, providing a satisfactory description of the thermal inactivation of B. cereus, with percent discrepancy ranging from 18 to 25%.

Effect of storage time and heat processing on the volatile profile of Senegalese sole (Solea senegalensis Kaup, 1858) muscle

The effect of heat treatment and the presence or absence of fish skin on the volatile composition of Senegalese sole muscle was studied. The volatile profile of Senegalese sole at different storage periods was also evaluated. All samples were analysed by HS-SPME-GC-IT/MS and subjected to sensory evaluation. As expected, cooking enhanced the production/liberation of volatile compounds. Fish with the skin present, after cooking, had higher levels of sulphur compounds, 2-nonanone, ethyl octanoate and lower contents of hexanol and heptanol than skinned fish; moreover, the samples with the skin had a better overall sensory acceptability. During storage, changes on the volatile composition of Senegalese sole samples were found. The major differences were obtained after 2 weeks of storage. Compounds such as hexanal, heptanal, octanal, decanal, (E)-2-hexenal, (E)-2-decen-1-al, (E,Z)-2,6-nonadienal, benzaldehyde, 4-ethyl-benzaldehyde, 1-penten-3-ol, heptanol and (E)-2-octen-1-ol decreased after 2 weeks of storage, and other compounds, such as 3-methyl-1-butanal, 2-methyl-1-butanal, 2-heptanone, dimethyl trisulphide, dimethyl tetrasulphide and 2-methyltetrahydrothiophen-3-one increased. These differences were confirmed by sensory evaluation. Principal component analysis was applied to the chemical data.

Recanalization Modulates Association Between Blood Pressure and Functional Outcome in Acute Ischemic Stroke

Background and Purpose— Historical stroke cohorts reported a U- or J-shaped relationship between blood pressure (BP) and clinical outcome. However, these studies predated current revascularization strategies, disregarding the recanalization state of the affected arterial territory. We aimed to investigate the relationship between BP in the first 24 hours after ischemic stroke and clinical outcome in patients submitted to intravenous or intra-arterial recanalization treatments. Methods— Consecutive patients with acute stroke treated with intravenous thrombolysis or intra-arterial therapies were enrolled in a retrospective cohort study. BP was measured on regular intervals throughout day and night during the first 24 hours after stroke onset. The mean systolic BP and diastolic BP during the first 24 hours post stroke were calculated. Recanalization was assessed at 6 hours by transcranial color-coded Doppler, angiography, or angio–computed tomography. Functional outcome was assessed at 3 months by modified Rankin Scale. Linear and quadratic multivariate regression models were performed to determine associations between BP and functional outcome for the whole population and recanalyzed and nonrecanalyzed patients. Results— We included 674 patients; mean age was 73.28 (SD, 11.50) years. Arterial recanalization was documented in 355 (52.70%) patients. In multivariate analyses, systolic BP and diastolic BP in the first 24 hours post stroke show a J-shaped relationship with functional outcome in the total population and in the nonrecanalyzed patients. Recanalyzed patients show a linear association with functional outcome (systolic BP: odds ratio, 1.015; 95% confidence interval, 1.007–1.024; P=0.001; R2 change=0.001; P=0.412 and diastolic BP: odds ratio, 1.019; 95% confidence interval, 1.004–1.033; P=0.012; R2 change<0.001; P=0.635). Conclusions— Systemic BP in the first 24 hours after ischemic stroke influences 3-month clinical outcome. This association is dependent on the revascularization status.