Weibull ß value for the discernment of drug release mechanism of PLGA particles.

Mathematical models are used to characterize and optimize drug release in drug delivery systems (DDS). One of the most widely used DDS is the poly(lactic-co-glycolic acid) (PLGA)-based polymeric matrix owing to its biodegradability, biocompatibility, and easy manipulation of its properties through the manipulation of synthesis processes. Over the years, the Korsmeyer-Peppas model has been the most widely used model for characterizing the release profiles of PLGA DDS. However, owing to the limitations of the Korsmeyer-Peppas model, the Weibull model has emerged as an alternative for the characterization of the release profiles of PLGA polymeric matrices. The purpose of this study was to establish a correlation between the n and ß parameters of the Korsmeyer-Peppas and Weibull models and to use the Weibull model to discern the drug release mechanism. A total of 451 datasets describing the overtime drug release of PLGA-based formulations from 173 scientific articles were fitted to both models. The Korsmeyer-Peppas model had a mean Akaike Information Criteria (AIC) value of 54.52 and an n value of 0.42, while the Weibull model had a mean AIC of 51.99 and a ß value of 0.55, and by using reduced major axis regression values, a high correlation was found between the n and ß values. These results demonstrate the ability of the Weibull model to characterize the release profiles of PLGA-based matrices and the usefulness of the ß parameter for determining the drug release mechanism.

High-pressure pulses for Aspergillus niger spore inactivation in a model pharmaceutical lipid emulsion.

High hydrostatic pressure (HHP) is a non-thermal process widely used in the food industry to reduce microbial populations. However, rarely its effect has been assessed in products with high oil content. This study evaluated the efficacy of HHP (200, 250, and 300 MPa) at different temperatures (25, 35, and 45 °C) by cycles (1, 2, or 3) of 10 min in the inactivation of Aspergillus niger spores in a lipid emulsion. After treatments at 300 MPa for 1 cycle at 35 or 45 °C, no surviving spores were recovered. All treatments were modeled by the linear and Weibull models. The presence of shoulders and tails in the treatments at 300 MPa at 35 or 45 °C resulted in sigmoidal curves which cannot be described by the linear model, hence the Weibull + Tail, Shoulder + Log-lin + Tail, and double Weibull models were evaluated to elucidate the inactivation kinetics. The tailing formation could be related to the presence of resistance subpopulations. The double Weibull model showed better goodness of fit (RMSE <0.2) to describe the inactivation kinetics of the treatments with the higher spore reductions. HHP at 200-300 MPa and 25 °C did not reduce the Aspergillus niger spores. The combined HHP and mild temperatures (35-45 °C) favored fungal spore inactivation. Spore inactivation in lipid emulsions by HHP did not follow a linear inactivation. HHP at mild temperatures is an alternative to the thermal process in lipid emulsions.

Weibull Regression and Machine Learning Survival Models: Methodology, Comparison, and Application to Biomedical Data Related to Cardiac Surgery.

In this article, we propose a comparative study between two models that can be used by researchers for the analysis of survival data: (i) the Weibull regression model and (ii) the random survival forest (RSF) model. The models are compared considering the error rate, the performance of the model through the Harrell C-index, and the identification of the relevant variables for survival prediction. A statistical analysis of a data set from the Heart Institute of the University of São Paulo, Brazil, has been carried out. In the study, the length of stay of patients undergoing cardiac surgery, within the operating room, was used as the response variable. The obtained results show that the RSF model has less error rate for the training and testing data sets, at 23.55% and 20.31%, respectively, than the Weibull model, which has an error rate of 23.82%. Regarding the Harrell C-index, we obtain the values 0.76, 0.79, and 0.76, for the RSF and Weibull models, respectively. After the selection procedure, the Weibull model contains variables associated with the type of protocol and type of patient being statistically significant at 5%. The RSF model chooses age, type of patient, and type of protocol as relevant variables for prediction. We employ the randomForestSRC package of the R software to perform our data analysis and computational experiments. The proposal that we present has many applications in biology and medicine, which are discussed in the conclusions of this work.

Modeling Salmonella spp. inactivation in chicken meat subjected to isothermal and non-isothermal temperature profiles.

Salmonella genus has foodborne pathogen species commonly involved in many outbreaks related to the consumption of chicken meat. Many studies have aimed to model bacterial inactivation as a function of the temperature. Due to the large heterogeneity of the results, a unified description of Salmonella spp. inactivation behavior is hard to establish. In the current study, by evaluating the root mean square errors, mean absolute deviation, and Akaike and Bayesian information criteria, the double Weibull model was considered the most accurate primary model to fit 61 datasets of Salmonella inactivation in chicken meat. Results can be interpreted as if the bacterial population is divided into two subpopulations consisting of one more resistant (2.3% of the total population) and one more sensitive to thermal stress (97.7% of the total population). The thermal sensitivity of the bacteria depends on the fat content of the chicken meat. From an adapted version of the Bigelow secondary model including both temperature and fat content, 90% of the Salmonella population can be inactivated after heating at 60 °C of chicken breast, thigh muscles, wings, and skin during approximately 2.5, 5.0, 9.5, and 57.4 min, respectively. The resulting model was applied to four different non-isothermal temperature profiles regarding Salmonella growth in chicken meat. Model performance for the non-isothermal profiles was evaluated by the acceptable prediction zone concept. Results showed that >80% of the predictions fell in the acceptable prediction zone when the temperature changes smoothly at temperature rates lower than 20 °C/min. Results obtained can be used in risk assessment models regarding contamination with Salmonella spp. in chicken parts with different fat contents.

Ohmic heating increases inactivation and morphological changes of Salmonella sp. and the formation of bioactive compounds in infant formula.

The effect of ohmic heating (OH) (50, 55, and 60 °C, 6 V/cm) on the inactivation kinetics (Weibull model) and morphological changes (scanning electron microscopy and flow cytometry) of Salmonella spp. in infant formula (IF) was evaluated. In addition, thermal load indicators (hydroxymethylfurfural and whey protein nitrogen index, HMF, and WPNI) and bioactive compounds (DPPH, total phenolics, ACE, α-amylase, and α-glucosidase inhibitory activities) were also studied. OH presented a more intense inactivation rate than conventional heating, resulting in a reduction of about 5 log CFU per mL at 60 °C in only 2.91 min, being also noted a greater cell membrane deformation, higher formation of bioactive compounds, and lower values for the thermal load parameters. Overall, OH contributed to retaining the nutritional value and improve food safety in IF processing.

Firth adjusted score function for monotone likelihood in the mixture cure fraction model.

Models for situations where some individuals are long-term survivors, immune or non-susceptible to the event of interest, are extensively studied in biomedical research. Fitting a regression can be problematic in situations involving small sample sizes with high censoring rate, since the maximum likelihood estimates of some coefficients may be infinity. This phenomenon is called monotone likelihood, and it occurs in the presence of many categorical covariates, especially when one covariate level is not associated with any failure (in survival analysis) or when a categorical covariate perfectly predicts a binary response (in the logistic regression). A well known solution is an adaptation of the Firth method, originally created to reduce the estimation bias. The method provides a finite estimate by penalizing the likelihood function. Bias correction in the mixture cure model is a topic rarely discussed in the literature and it configures a central contribution of this work. In order to handle this point in such context, we propose to derive the adjusted score function based on the Firth method. An extensive Monte Carlo simulation study indicates good inference performance for the penalized maximum likelihood estimates. The analysis is illustrated through a real application involving patients with melanoma assisted at the Hospital das Clínicas/UFMG in Brazil. This is a relatively novel data set affected by the monotone likelihood issue and containing cured individuals.

Modeling Salmonella Typhimurium Inactivation in Dry-Fermented Sausages: Previous Habituation in the Food Matrix Undermines UV-C Decontamination Efficacy.

The effects of previous Salmonella Typhimurium habituation to an Italian-style salami concerning pathogen resistance against ultraviolet-C light (UV-C) treatment were modeled in order to establish treatment feasibility for the decontamination of dry-fermented sausage. S. Typhimurium following 24 h habituation in fermented sausage (habituated cells) or non-habituation (non-habituated cells) were exposed to increasing UV-C radiation treatment times. The Weibull model was the best fit for describing S. Typhimurium UV-C inactivation. Heterogeneity in UV-C treatment susceptibilities within the S. Typhimurium population was observed, revealing intrinsic persistence in a sub-population. UV-C radiation up to 1.50 J/cm2 was a feasible treatment for dry-fermented sausage decontamination, as the matrices retained instrumental color and lipid oxidation physiochemical characteristics. However, habituation in the sausage matrix led to a 14-fold increase in the UV-C dose required to achieve the first logarithm reduction (δ value) in S. Typhimurium population. The results indicate that, although UV-C radiation might be considered an efficient method for dry-fermented sausage decontamination, effective doses should be reconsidered in order to reach desirable food safety parameters while preserving matrix quality.

High-Intensity Light Pulses To Inactivate Salmonella Typhimurium on Mexican Chia (Salvia hispanica L.) Seeds.

Chia seeds provide a suitable environment for microorganisms. However, it is difficult to disinfect these seeds with water and/or chemical disinfectant solutions because the mucilage in the seeds can absorb water and consequently form gels. High-intensity light pulses (HILP) is one of the most promising emerging technologies for inactivating microorganisms on surfaces, in clear liquids and beverages, and on solid foods. The aim of this work was to evaluate the effect of HILP on Salmonella Typhimurium in culture medium (in vitro tests) and inoculated onto chia seeds (in vivo tests). HILP was effective against Salmonella Typhimurium under both conditions: 8 s of treatment (10.32 J/cm2) resulted in a 9-log reduction during in vitro tests, and 15 s of treatment (19.35 J/cm2) resulted in a 4-log reduction on the inoculated chia seeds. Salmonella Typhimurium inactivation kinetics were accurately described using the Weibull model (R2 > 0.939). These results indicate that the use of HILP for microbial inactivation on seeds could generate products suitable for human consumption.

Oven drying and hot water cooking processes decrease HCN contents of cassava leaves.

The aim of this work was to study the effects of temperature and time of oven drying and hot water cooking processes on HCN (hydrocyanic acid) degradation of cassava leaves as a contribution for obtaining a safe product for human consumption. Nine varieties of cassava leaves collected in the Amazonian region of Brazil (Pará State) were characterized regarding moisture, pH, total acidity, ashes, total lipids, total protein, water activity, carbohydrates, total energetic value and HCN contents. The leaves of the three cassava varieties, which presented the highest HCN contents, were submitted to the thermal degradation of HCN, under drying and boiling conditions. All the leaves presented similar physicochemical characteristics and the HCN contents varied from 90.6 to 560.9 mg HCN/kg fresh leaves (total HCN) and from 16.6 to 59.2 mg HCN/kg fresh leaves (free HCN). Thermal degradation studies on HCN showed that the drying and boiling processes were effective on total HCN removal after 180 min. Furthermore, a remarkable decrease in HCN contents was observed after 20 min of boiling. Regarding free HCN, the drying method was more effective than boiling, showing high degradation percentages: 74.1%-92.2% to 1.1%-72.4%, respectively.

Effect of soluble solids concentration on Neosartorya fischeri inactivation using UV-C light.

Ascospores of Neosartorya fischeri are heat-resistant and can survive thermal commercial treatments normally applied to the juices, as apple juice. Non-thermal processing of food such as exposure to ultraviolet light (UV-C) is reported to induce minimal quality changes while reduces microbial load. The main objective of this study was to determine the effect at different soluble solids concentration (12, 25, 30, 40, 50, 60 and 70 °Brix) on N. fischeri ascospores inactivation in apple juice, using UV-C light intensity (38 W/m2). Weibull model was fitted to experimental data. Then, a secondary model was used to describe how the inactivation kinetic parameters varied with the changes in soluble solids concentration. Results showed that the UV-C light had influence on N. fischeri ascospores inactivation in apple juice even at the highest soluble solids concentrations used, reaching approximately 4 log reductions at all concentrations used. The inactivation parameters, obtained by Weibull model, were δ (dose for the first decimal reduction) and p (the shape factor). Exponential model was chosen to describe the influence of soluble solids concentration on δ and p parameters. It can be concluded that UV-C light is a promising treatment with a drastic impact on the loads of N. fischeri, especially when low soluble solids concentration is used and a model was obtained to describe Brix effect.

Inactivation of Alicyclobacillus acidoterrestris ATCC 49025 spores in apple juice by pulsed light: Influence of initial contamination and required reduction levels / Inactivación de esporas de Alicyclobacillus acidoterrestris ATCC 49025 por luz pulsada en jugo de manzana: Influencia de la contaminación inicial y de las reducciones requeridas

The purpose of this study was to analyze the response of different initial contamination levels of Alicydobadllus acidoterrestris ATCC 49025 spores in apple juice as affected by pulsed light treatment (PL, batch mode, xenon lamp, 3pulses/s, 0-71.6 J/cm²). Biphasic and Weibull frequency distribution models were used to characterize the relationship between inoculum size and treatment time with the reductions achieved after PL exposure. Additionally, a second order polynomial model was computed to relate required PL processing time to inoculum size and requested log reductions. PL treatment caused up to 3.0-3.5 log reductions, depending on the initial inoculum size. Inactivation curves corresponding to PL-treated samples were adequately characterized by both Weibull and biphasic models (R²d j 94-96%), and revealed that lower initial inoculum sizes were associated with higher inactivation rates. According to the polynomial model, the predicted time for PL treatment increased exponentially with inoculum size.

El objetivo del presente trabajo fue evaluar la influencia de la concentración de esporas de Alicyclobacillus acidoterrestris ATCC 49025 en la respuesta de inactivación por acción de la luz pulsada (modo estanco, lámpara de xenón, 3 pulsos/s, 0-71,6 J/cm²) en jugo de manzana comercial. Para caracterizar la relación existente entre la concentración de esporas y el tiempo de tratamiento con las reducciones logarítmicas alcanzadas luego de la exposición a la luz pulsada (LP), se aplicaron 2 modelos: el de Weibull y el bifásico. Adicionalmente, se estimó la relación entre el tiempo de tratamiento con LP y la concentración inicial de inoculo en el jugo con las reducciones logarítmicas logradas mediante regresión múltiple y la metodología de superficie de respuesta (MSR). La inactivación por LP provocó entre 3 y 3,5 reducciones logarítmicas, según la concentración inicial de esporas. Las curvas de inactivación fueron adecuadamente caracterizadas por los modelos matemáticos propuestos (Restado = 94-96%). El análisis por MSR permitió predecir un aumento exponencial del tiempo de tratamiento requerido conforme se incrementa el nivel de contaminación inicial.

Inactivation of Alicyclobacillus acidoterrestris ATCC 49025 spores in apple juice by pulsed light. Influence of initial contamination and required reduction levels.

The purpose of this study was to analyze the response of different initial contamination levels of Alicyclobacillus acidoterrestris ATCC 49025 spores in apple juice as affected by pulsed light treatment (PL, batch mode, xenon lamp, 3pulses/s, 0-71.6J/cm2). Biphasic and Weibull frequency distribution models were used to characterize the relationship between inoculum size and treatment time with the reductions achieved after PL exposure. Additionally, a second order polynomial model was computed to relate required PL processing time to inoculum size and requested log reductions. PL treatment caused up to 3.0-3.5 log reductions, depending on the initial inoculum size. Inactivation curves corresponding to PL-treated samples were adequately characterized by both Weibull and biphasic models (Radj2 94-96%), and revealed that lower initial inoculum sizes were associated with higher inactivation rates. According to the polynomial model, the predicted time for PL treatment increased exponentially with inoculum size.

Evaluation of longevity modeling censored records in Nellore.

The aim of the present study was to evaluate the prediction ability of models that cope with longevity phenotypic expression as uncensored and censored in Nellore cattle. Longevity was defined as the difference between the dates of last weaned calf and cow birth. There were information of 77 353 females, being 61 097 cows with uncensored phenotypic information and 16 256 cows with censored records. These data were analyzed considering three different models: (1) Gaussian linear model (LM), in which only uncensored records were considered; and two models that consider both uncensored and censored records: (2) Censored Gaussian linear model (CLM); and (3) Weibull frailty hazard model (WM). For the model prediction ability comparisons, the data set was randomly divided into training and validation sets, containing 80% and 20% of the records, respectively. There were considered 10 repetitions applying the following restrictions: (a) at least three animals per contemporary group in the training set; and (b) sires with more than 10 progenies with uncensored records (352 sires) should have daughters in the training and validation sets. The variance components estimated using the whole data set in each model were used as true values in the prediction of breeding values of the animals in the training set. The WM model showed the best prediction ability, providing the lowest χ 2 average and the highest number of sets in which a model had the smallest value of χ 2 statistics. The CLM and LM models showed prediction abilities 2.6% and 3.7% less efficient than WM, respectively. In addition, the accuracies of sire breeding values for LM and CLM were lower than those obtained for WM. The percentages of bulls in common, considering only 10% of sires with the highest breeding values, were around 75% and 54%, respectively, between LM-CLM and LM-WM models, considering all sires, and 75% between LM-CLM and LM-WM, when only sires with more than 10 progenies with uncensored records were taken into account. These results are indicative of reranking of animals in terms of genetic merit between LM, CLM and WM. The model in which censored records of longevity were excluded from the analysis showed the lowest prediction ability. The WM provides the best predictive performance, therefore this model would be recommended to perform genetic evaluation of longevity in this population.

Estimation of genetic parameters for longevity considering the cow's age at last calving.

The aim of this study was to estimate heritability and predict breeding values for longevity among cows in herds of Nellore breed, considering the trait cow's age at last calving (ALC), by means of survival analysis methodology. The records of 11,791 animals from 22 farms were used. The variable ALC has been used by a criterion that made it possible to include cows not only at their first calving but also at their ninth calving. The criterion used was the difference between the date of each cow's last calving and the date of the last calving on each farm. If this difference was greater than 36 months, the cow was considered to have failed and uncensored. If not, this cow was censored, thus indicating that future calving remained possible for this cow. The survival model used for the analyses was the proportional hazards model, and the base risk was given by a Weibull distribution. The heritability estimate obtained was equal to 0.25. It was found that the ALC variable had the capacity to respond to selection for the purpose of increasing the longevity of the cows in the herds.

Aplicación del modelo de weibull normalizado en la deshidratación osmótica de láminas de sardina / Application of Normalized Weibull Model in the Osmotic Dehydration of Sardine Sheets

Conocer la cinética de deshidratación osmótica de un alimento y los factores que la afectan son aspectos importantes para diseñar un adecuado proceso. En este trabajo se investigó la aplicación del modelo de Weibull normalizado para describir la deshidratación osmótica de láminas finitas de sardina y determinar el coeficiente de difusión efectivo del agua. La deshidratación osmótica se realizó durante 4 horas utilizando salmueras de diferentes concentraciones (0,15-0,27 g NaCl/g) y temperaturas (30-38°C). Durante el proceso se midió el contenido de agua en las láminas y estos valores se ajustaron al modelo de Weibull normalizado. Los altos valores del coeficiente de regresión (R² > 0,99), la alta significancia (α < 0,001) para el coeficiente de difusión (D) y el parámetro β, y los bajos valores del ji-cuadrado reducido, indicaron la aceptabilidad del modelo para describir el proceso y determinar el coeficiente de difusión efectivo De del agua. Los valores de D variaron entre 1,01 x 10-11 m²/s y 4, 30 x 10-11 m²/s.

Knowledge of kinetics of osmotic dehydration of a food and factors that cause effects are aspects import for the appropriate design of process. In this work the application of normalized Weibull model was investigated for describing the osmotic dehydration (OD) of sardine finite sheets and determining the effective diffusion coefficient for water. The OD was carried out during 4 hours using brine at different concentrations (0.15-0.27 g NaCl/g) and temperatures (30-38°C). During process the water content of shhets was measured and these values were fitted to normalized Weibull model. The high values of regression coefficients (R² > 0.99), high significance (α < 0.001) of diffusion coefficient (D), parameter β, and low values of chi-square indicated the acceptability of Weibull model for describing the process and determining the effective diffusion coefficient De for water. The values of D ranged from 1.01 x 10-11 m²/s to 4.30 x 10-11 m²/s.