Personalized mechanistic models for exercise, meal and insulin interventions in children and adolescents with type 1 diabetes.

Personalized mechanistic models involving exercise, meal and insulin interventions for type 1 diabetic children and adolescents are not commonly seen in the literature. Patient specific variations in blood glucose homeostasis and adverse effects of exercise-induced hypoglycemia emphasize the need for personalized models. Hence, a modified mechanistic model for exercise, meal and insulin interventions is proposed and tailored as personalized models for 34 type 1 diabetic children and adolescents. This is achieved via a 3-stage methodology comprising of modification, a priori identifiability analysis, and personalized parameter estimation and validation using the clinical data. Rate of perceived exertion is introduced as a marker quantifying exercise intensity. Six out of 16 parameters in the modified model are identified to be estimable and are estimated for each subject as personalized parameters. The R(2) values for both fitness and validation vary between 0.7 and 0.96 in 97% of the patients, indicating the goodness of the proposed model in explaining the glucose dynamics. For most of the estimated parameters, values of personalized point estimates and their confidence intervals are found to be within physiological ranges reported in the modeling literature. Personalized values of appearance rate of exercise effect on glucose uptake in 34 subjects are 54-250% higher than the nominal values of adults. This is expected for children and adolescents as the literature shows that they exhibit higher fat and exogenous carbohydrate oxidation rates during exercise when compared to adults.

Comparison of toxin removal outcomes in online hemodiafiltration and intra-dialytic exercise in high-flux hemodialysis: a prospective randomized open-label clinical study protocol.

BACKGROUND: Maintenance hemodialysis (HD) patients universally suffer from excess toxin load. Hemodiafiltration (HDF) has shown its potential in better removal of small as well as large sized toxins, but its efficacy is restricted by inter-compartmental clearance. Intra-dialytic exercise on the other hand is also found to be effective for removal of toxins; the augmented removal is apparently obtained by better perfusion of skeletal muscles and decreased inter-compartmental resistance. The aim of this trial is to compare the toxin removal outcome associated with intra-dialytic exercise in HD and with post-dilution HDF. METHODS/DESIGN: The main hypothesis of this study is that intra-dialytic exercise enhances toxin removal by decreasing the inter-compartmental resistance, a major impediment for toxin removal. To compare the HDF and HD with exercise, the toxin rebound for urea, creatinine, phosphate, and ß2-microglobulin will be calculated after 2 hours of dialysis. Spent dialysate will also be collected to calculate the removed toxin mass. To quantify the decrease in inter-compartmental resistance, the recently developed regional blood flow model will be employed. The study will be single center, randomized, self-control, open-label prospective clinical research where 15 study subjects will undergo three dialysis protocols (a) high flux HD, (b) post-dilution HDF, (c) high flux HD with exercise. Multiple blood samples during each study session will be collected to estimate the unknown model parameters. DISCUSSION: This will be the first study to investigate the exercise induced physiological change(s) responsible for enhanced toxin removal, and compare the toxin removal outcome both for small and middle sized toxins in HD with exercise and HDF. Successful completion of this clinical research will give important insights into exercise effect on factors responsible for enhanced toxin removal. The knowledge will give confidence for implementing, sustaining, and optimizing the exercise in routine dialysis care. We anticipate that toxin removal outcomes from intra-dialytic exercise session will be comparable to that obtained by standalone HDF. These results will encourage clinicians to combine HDF with intra-dialytic exercise for significantly enhanced toxin removal. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01674153.

Multi-objective optimization of an industrial penicillin V bioreactor train using non-dominated sorting genetic algorithm.

Bulk of the penicillin produced is used as raw material for semi-synthetic penicillin (such as amoxicillin and ampicillin) and semi-synthetic cephalosporins (such as cephalexin and cefadroxil). In the present paper, an industrial penicillin V bioreactor train is optimized for multiple objectives simultaneously. An industrial train, comprising a bank of identical bioreactors, is run semi-continuously in a synchronous fashion. The fermentation taking place in a bioreactor is modeled using a morphologically structured mechanism. For multi-objective optimization for two and three objectives, the elitist non-dominated sorting genetic algorithm (NSGA-II) is chosen. Instead of a single optimum as in the traditional optimization, a wide range of optimal design and operating conditions depicting trade-offs of key performance indicators such as batch cycle time, yield, profit and penicillin concentration, is successfully obtained. The effects of design and operating variables on the optimal solutions are discussed in detail.