Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future

Optimizing DNA Nanotechnology through Coarse-Grained Modeling: A Two-Footed DNA Walker

DNA has enormous potential as a programmable material for creating artificial nanoscale structures and devices. For more complex systems, however, rational design and optimization can become difficult. We have recently proposed a coarse-grained model of DNA that captures the basic thermodynamic, structural, and mechanical changes associated with the fundamental process in much of DNA nanotechnology, the formation of duplexes from single strands. In this article, we demonstrate that the model can provide powerful insight into the operation of complex nanotechnological systems through a detailed investigation of a two-footed DNA walker that is designed to step along a reusable track, thereby offering the possibility of optimizing the design of such systems. We find that applying moderate tension to the track can have a large influence on the operation of the walker, providing a bias for stepping forward and helping the walker to recover from undesirable overstepped states. Further, we show that the process by which spent fuel detaches from the walker can have a significant impact on the rebinding of the walker to the track, strongly influencing walker efficiency and speed. Finally, using the results of the simulations, we propose a number of modifications to the walker to improve its operation