A Stochastic Optimization approach for the design of Individualized Dosage Regimens

Quantitative methods for individualizing and optimizing the dosage regimen and clinically monitoring each patient are desirable to insure that each patient can obtain effective therapeutic benefit while minimizing undesirable side effects. This is of special concern for medicines that are expensive or whose toxic side effects are severe (e.g., oncological agents). The optimal dosage regimen for an individual is a combination of dose amount and/or dosing interval (i.e., time between doses) which minimizes the risk that the drug exposure deviates from the desired therapeutic window. The therapeutic window is defined as the range of drug exposure (e.g., blood concentration, area under the curve concentration‐time) which is below a threshold defining an acceptable toxic side effect and above a threshold defining a minimum acceptable level of therapeutic efficacy. In this work, the dosage regimen optimization problem defined in terms of general pharmacometric models (i.e., described by differential‐algebraic equations) is presented and a solution approach outlined which uses a scenario‐based stochastic optimization formulation that minimizes a risk metric. The scenarios are derived from the posterior joint probability distribution of the individual's pharmacometric parameters which is obtained following an approximate Bayesian inference approach. A Smolyak rule is used for the selection of the scenarios (i.e., combination of pharmacometric parameters) to be considered and for computing the approximation to the risk metric. Two case studies, gabapentin and cyclophosphamide, are presented to elucidate the advantages and limitations of the proposed approach. The numerical results demonstrate that low risk optimal solutions can be generated via the proposed stochastic optimization; while significantly reducing the computational burden in comparison with the conventional Markov chain Monte Carlo—grid search approach. This partially alleviates implementation issues preventing the deployment of dosage regimen individualization in clinical practice. Since stochastic optimization has been extensively used in other domains, the approach for uncertainty characterization proposed in this work may have general relevance beyond the pharmacometrics domain. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3296–3307, 2013     

Fundamental thermo‐mechanical property modeling of triglyceride‐based thermosetting resins

The glass transition temperature (T_g) of acrylated triglycerides was clearly a function of the level of acrylation of triglyceride‐based polymers and was modeled using simple empirical relationships. We began by calculating the distribution of unsaturation sites in plant oils. We assumed a binomial distribution of chemical functionality that was added to these unsaturation sites to calculate the distribution of epoxides, acrylates, and reacted acrylates to predict the crosslink density, thermal softening, and dynamic mechanical behavior. The glass transition temperatures of n‐acrylated triglycerides were used as the relaxation temperatures of acrylated oils with a broad distribution of functionality for prediction of the modulus as a function of temperature. Essentially, the percent drop in the elastic modulus is equal to the percentage of n‐acrylated triglycerides in the acrylated oil with T_g less than that of the ambient temperature. The tan (δ) was also accurately predicted based on the percentage change of n‐functional triglycerides as the temperature changes from one relaxation temperature to the next. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Indirect Determination of Hydroxyl Radicals in Fine Particle Mist Generated from an Odor Control Technology via HPLC

Size distribution analysis of microsized water particle mist generated from an odor control technology showed the majority of particles to be in the low micron range. The indirect detection and determination of hydroxyl radicals generated by their reaction with benzene to produce phenol was performed through UV-Vis spectrophotometry (UV-Vis) and high performance liquid chromatography (HPLC). These techniques gave verification of the presence of hydroxyl radical species in the water samples collected via this odor control technology. This technology is currently being utilized at various wastewater treatment plants.     

Iron concentration and acceptation of yoghurt prepared in casting iron pots (iron migration and acceptation of yogurt)

Food fortification is an interesting strategy to treat and prevent iron anemia. This study aims to quantify the iron in yoghurt, with gelatin and sugar and without, prepared in iron and glass containers. Sensorial test was use to evaluate the acceptance and preference of the both products. The yoghurt was prepared in containers of iron and glass with UHT milk, powder milk and natural industrialized yoghurt. After fermentation, half of the product received addition of sugar and strawberry flavor gelatin. The collected samples get the total iron quantified by ICP OES. Sensorial analysis involving 105 consumers was use to determine the acceptance and preference of the products. 0,018 and 0,882mg of iron per 100g added in the natural yoghurt prepared in the glass and in the iron pots, respectively. The yoghurt with gelatin presented 0,037 and 1,302mg of iron per 100g when prepared in the glass and in the iron pots, respectively. The preference was low for the yoghurt prepared in the iron pot (29,5%), but when added strawberry gelatin it was about 51,5%. The yoghurt prepared in iron pots, is easily home made and adds important amount of iron. Add gelatin and sugar can favored its consumption.     

H2S retention with Ca-based sorbents in a pressurized fixed-bed reactor: application to moving-bed design

The H₂S retention with Ca-based sorbents in a pressurized fixed-bed reactor (1 MPa) has been analyzed, obtaining the breakthrough curves with a dolomite and two different limestones, different particle size (+0.8-1.0, +1.25-1.6, and +1.6-2.0 mm), and both at calcining (1173 K) and non-calcining conditions (1123 K). The effect of the stoichiometric time in the breakthrough curves has been analyzed varying the bed length, the gas velocity and the sorbent fraction in the bed. From these results, the conversion and H₂S concentration profiles in the transition zone and the length of unused bed (LUB) have been determined. H₂S retention in fixed-bed until concentration close to the given by the thermodynamic equilibrium was obtained using dolomite or limestone at calcining conditions, and dolomite at non-calcining conditions. The results of H₂S retention in a fixed-bed reactor has been applied to the calculus of the minimum height of a countercurrent moving-bed reactor to obtain the maximum H₂S retention with the minimum amount of sorbent. A mathematical model was developed to predict the experimental results obtained in the fixed-bed reactor, which was also valid for the design of countercurrent moving-bed reactors for gas desulphurization.     

Obesity: Prevalence,Theories, Medical Consequences,Management, and Research Directions

Obesity and its associated disorders are a growing epidemic across the world. Many genetic, physiological, and behavioral factors play a role in the etiology of obesity. Diet and exercise are known to play a valuable role in the treatment and prevention of obesity and associated disorders such as hypertension, heart disease, and diabetes. Therefore, the purpose of this review is to examine the prevalence, etiology, consequences, and treatment of obesity.