The role of population PK-PD modelling in paediatric clinical research

Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK-PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK-PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK-PD parameters with the highest precision. Once a population PK-PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child

Habitat manipulation to mitigate the impacts of invasive arthropod pests

Exotic invaders are some of the most serious insect pests of agricultural crops around the globe. Increasingly, the structure of landscape and habitat is recognized as having a major influence on both insect pests and their natural enemies. Habitat manipulation that aims at conserving natural enemies can potentially contribute to safer and more effective control of invasive pests. In this paper, we review habitat management experiments, published during the last 10 years, which have aimed to improve biological control of invasive pests. We then discuss during what conditions habitat management to conserve natural enemies is likely to be effective and how the likelihood of success of such methods can be improved. We finally suggest an ecologically driven research agenda for habitat management programmes.We acknowledge the following funding sources: the Tertiary Education Commission, New Zealand, through the Bio-Protection Research Centre, Lincoln University, New Zealand (Mattias Jonsson and Steve Wratten), the New Zealand Foundation for Research, Science and Technology (FRST); project LINX0303 (Steve Wratten, Ross Cullen, Jean Tompkins), Lincoln University, New Zealand, for a Post-graduate Scholarship to Jean Tompkins, USDA CSREES Risk Avoidance and Mitigation Program (2004-51101-02210), USDA NC SARE Project (LCN 04-249), USDA CSREES Arthropod and Nematode Biology (2004-35302-14811), North Central Regional IPM, NSF-LTER at Kellogg Biological Station (NSF DEB 0423627), and the Michigan Agricultural Experiment Station (Doug Landis)

Abundance, population structure and claw morphology of the semi-terrestrial crab Pachygrapsus marmoratus (Fabricius, 1787) on shores of differing wave exposure

Wave action is known to influence the abundance and distribution of intertidal organisms. Wave action will also determine the duration and suitability of various foraging windows (high-tide and low-tide, day and night)for predation and can also affect predator behaviour, both directly by impeding prey handling and indirectly by influencing prey abundance. It remains uncertain whether semiterrestrial mobile predators such as crabs which can access intertidal prey during emersion when the effects of wave action are minimal, are influenced by exposure. Here, we assessed the effect of wave action on the abundance andpopulation structure (size and gender) of the semi-terrestrial intertidal crab Pachygrapsus marmoratus on rocky shores in Portugal. The activity of P. marmoratus with the tidal cycle on sheltered and exposed shores was established using baited pots at high-tide to examine whether there was activity during intertidal immersion and by low-tide searches. Because prey abundance varies along a wave exposure gradient on most Portuguese shores and because morphology of crab chelipeds are known to be related to diet composition, we further tested the hypothesis that predator stomach contents reflected differences in prey abundance along the horizontal gradient in wave exposure and that this would be correlated with the crab cheliped morphology. Thus, we examined phenotypic variation in P. marmoratus chelipeds across shores of differing exposure to wave action. P. marmoratus was only active during lowtide. Patterns of abundance and population structure of crabs did not vary with exposure to wave action. Stomach contents, however, varied significantly between shores of differing exposure with a higher consumption of hardshelled prey (mussels) on exposed locations, where this type of prey is more abundant, and a higher consumption of barnacles on sheltered shores. Multivariate geometric analysis of crab claws showed that claws were signifocantly larger on exposed shores. There was a significant correlation between animals with larger claws and the abundance of mussels in their stomach. Variation in cheliped size may have resulted from differing food availability on shelteredand exposed shores