Estimation of entrainment response using electrograms from remote sites: validation in animal and computer models of reentrant tachycardia

INTRODUCTION: Studies suggest that entrainment response (ER) of reentrant tachycardia to overdrive pacing can be estimated using signals from sites other than the paced site. METHODS AND RESULTS: A formula for estimation of ER using remote sites against the difference between the postpacing interval (PPI) and tachycardia cycle length (TCL) determined solely from the paced site signal was validated in experimental data and using a simple two-dimensional cellular automata model of reentry. The model also was used to study the behavior and features of entrained surfaces, including the resetting of tachycardia phase by single premature paced stimuli. Experimental results from 1,484 remote sites in 115 pacing sequences showed the average of the median ER estimate error at each pacing site was -2 +/- 5 msec, and the median ER estimate was within 10 msec of PPI-TCL for 94% of pacing sites. From simulation results, ER at the paced site was accurately estimated from >99.8% of 20,764 remote sites during pacing at 24 sites and three paced cycle lengths. Intervals measured from remote electrograms revealed whether the site was activated orthodromically or nonorthodromically during pacing, and results of simulations illustrated that the portion of the surface activated nonorthodromically during pacing increased with distance from the pacing site to the circuit. The phenomenon of nonorthodromic activation of reentrant circuits predicted by modeling was discernible in measurements taken from the animal model of reentrant tachycardia. Results also showed that, for single premature stimuli that penetrated the tachycardia circuit, phase reset of the tachycardia was linearly related to distance between the central obstacle and the paced site. CONCLUSION: The ER is a complex but predictable perturbation of the global activation sequence of reentrant tachycardias. This predictability allows calculations of the response from anywhere on the perturbed surface. These findings suggest new techniques for measurement of the ER, which may lend themselves to computer-based methods for accurate and rapid mapping of reentrant circuits.     

A C-Peptide-Based Model of Pancreatic Insulin Secretion in Extremely Preterm Neonates in Intensive Care

Background:

Model-based glycemic control relies on sufficiency of underlying models to describe underlying patient physiology. In particular, very preterm infant glucose-insulin metabolism can differ significantly from adults, and is relatively unstudied. In this study, C-peptide concentrations are used to develop insulin-secretion models for the purposes of glycemic control in neonatal intensive care.

Methods:

Plasma C-peptide, insulin, and blood glucose concentrations (BGC) were retrospectively analyzed from a cohort of 41 hyperglycemic very preterm (median age 27.2 [26.2-28.7] weeks) and very low birth-weight infants (median birth weight 839 [735-1000] g). A 2-compartment model of C-peptide kinetics was used to estimate insulin secretion. Insulin secretion was examined with respect to nutritional intake, exogenous and plasma insulin concentration, and BGC.

Results:

Insulin secretion was found to be highly variable between patients and over time, and could not be modeled with respect to age, weight, or protein or dextrose intake. In 13 of 54 samples exogenous insulin was being administered, and insulin secretion was lower. However, low data numbers make this result inconclusive. Insulin secretion was found to increase with BG, with a stronger association in female infants than males (R² = .51 vs R² = .13, and R² = .26 for the combined cohort).

Conclusions:

A sex-based insulin secretion model was created and incorporated into a model-based glycemic control framework. Nutritional intake did not predict insulin secretion, indicating that insulin secretion is a complex function of a number of metabolic factors.     

Role of N-vinyl-2-pyrrolidinone on the thermoresponsive behavior of PNIPAm hydrogel and its release kinetics using dye and vitamin-B12 as model drug

Temperature-sensitive hydrogels hold great promise in biological applications as they can respond to changes in physiological temperature to produce a desired effect like controlled drug delivery. In this study, a series of poly(N-isopropylacrylamide-co-N-vinyl-2-pyrrolidinone) thermosensitive hydrogels were synthesized by radical copolymerization of NIPAm with 1-vinyl-2-pyrrolidinone (NVP). By altering the initial NIPAm/NVP mole ratios, copolymers were synthesized to have their own distinctive lower critical solution temperature which was established using differential scanning calorimetry. The swelling behavior of the hydrogel was analyzed gravimetrically and it was observed that reswelling rate increases with increasing NVP mole ratio. Further characterizations of the hydrogels were performed using Fourier transform infrared spectroscopy and scanning electron microscopy. Release kinetics with respect to temperature was studied using methylene blue dye solution and vitamin B12. Kinetic modeling of the release profile revealed that the release mechanism is a non-Fickian diffusion mechanism. These results suggested that this material has potential application as intelligent drug carriers. The quantities of residual monomers in the PIV4 hydrogel were determined by HPLC method, and the results show almost complete conversion.     

Persistence and uncertainty in the academic career

Understanding how institutional changes within academia may affect the overall potential of science requires a better quantitative representation of how careers evolve over time. Because knowledge spillovers, cumulative advantage, competition, and collaboration are distinctive features of the academic profession, both the employment relationship and the procedures for assigning recognition and allocating funding should be designed to account for these factors. We study the annual production n(i)(t) of a given scientist i by analyzing longitudinal career data for 200 leading scientists and 100 assistant professors from the physics community. Our empirical analysis of individual productivity dynamics shows that (i) there are increasing returns for the top individuals within the competitive cohort, and that (ii) the distribution of production growth is a leptokurtic "tent-shaped" distribution that is remarkably symmetric. Our methodology is general, and we speculate that similar features appear in other disciplines where academic publication is essential and collaboration is a key feature. We introduce a model of proportional growth which reproduces these two observations, and additionally accounts for the significantly right-skewed distributions of career longevity and achievement in science. Using this theoretical model, we show that short-term contracts can amplify the effects of competition and uncertainty making careers more vulnerable to early termination, not necessarily due to lack of individual talent and persistence, but because of random negative production shocks. We show that fluctuations in scientific production are quantitatively related to a scientist's collaboration radius and team efficiency.