Bistability versus Bimodal Distributions in Gene Regulatory Processes from Population Balance

In recent times, stochastic treatments of gene regulatory processes have appeared in the literature in which a cell exposed to a signaling molecule in its environment triggers the synthesis of a specific protein through a network of intracellular reactions. The stochastic nature of this process leads to a distribution of protein levels in a population of cells as determined by a Fokker-Planck equation. Often instability occurs as a consequence of two (stable) steady state protein levels, one at the low end representing the “off” state, and the other at the high end representing the “on” state for a given concentration of the signaling molecule within a suitable range. A consequence of such bistability has been the appearance of bimodal distributions indicating two different populations, one in the “off” state and the other in the “on” state. The bimodal distribution can come about from stochastic analysis of a single cell. However, the concerted action of the population altering the extracellular concentration in the environment of individual cells and hence their behavior can only be accomplished by an appropriate population balance model which accounts for the reciprocal effects of interaction between the population and its environment. In this study, we show how to formulate a population balance model in which stochastic gene expression in individual cells is incorporated. Interestingly, the simulation of the model shows that bistability is neither sufficient nor necessary for bimodal distributions in a population. The original notion of linking bistability with bimodal distribution from single cell stochastic model is therefore only a special consequence of a population balance model

Infection in total hip replacement: meta-analysis

While total hip arthroplasty has progressed to become one of the most successful surgical procedures ever developed, infection remains a serious complication. We have conducted a review of the literature pertaining to management of deep infection in total hip arthroplasty, specifically focusing on clinically relevant articles published in the last five years. A search was conducted using MEDLINE and PubMed, as well as a review of the Cochrane database, using the terms “total hip arthroplasty”, “total hip replacement” and “infection”. References for all selected articles were cross-checked. While the so-called two-stage revision is generally considered to be the gold standard for management, numerous studies now report outcomes for implant retention and reassessing one-stage revision strategies. There are encouraging reports for complex reconstruction options in patients with associated severe bone stock loss. The duration of antibiotic therapy remains controversial. There is concern about increasing bacterial resistance especially with the widespread use of vancomycin and ertapenem (carbapenem)