Paediatric medicines research in the UK: How to move forward?

There have been numerous studies to show that many of the medicines used in children are used off-label or are unlicensed for use in children. When children are prescribed unlicensed and off-label medications, some people may see them as unknowing participants in informal and uncontrolled experiments. However, the licensing status of a drug can be seen as a by-product of the real issues: the safety, efficacy and quality of these medicines in the current licensing system. It is important to conduct research in order to provide high quality data regarding safety and efficacy to support evidence-based paediatric prescribing. Clinical trials will always be an invaluable means of acquiring vital information about a drug; but when it comes to children, we may find that these trials are not always practical for technical, ethical and financial reasons; therefore, it is important to explore other methodologies in paediatric medicines research. Pharmacoepidemiological and prospective cohort studies could provide vital safety and efficacy data on paediatric medicines; however, resources need to be invested in the methodological research. Paediatric drug formulation research is under-resourced and under-valued, and, unfortunately, fatal and serious adverse reactions due to inappropriate formulations have been reported in many instances. Paediatric medication is a complex problem; we need to use all available tools for research on safety, efficacy and formulation. The reason for lack of progress in paediatric drug research is most likely due to lack of resources and research capacity. The industry and government should work together and invest more money in paediatric drug research. Finally, regulatory authorities, healthcare professionals and academics need to rethink the research strategy in order to provide better medicines for children.link_to_subscribed_fulltex

Lateral Dispersal and Foraging Behavior of Entomopathogenic Nematodes in the Absence and Presence of Mobile and Non-Mobile Hosts

Entomopathogenic nematodes have been classified into cruisers (active searchers) and ambushers (sit and wait foragers). However, little is known about their dispersal and foraging behavior at population level in soil. We studied lateral dispersal of the ambush foraging Steinernema carpocapsae (ALL strain) and cruise foraging Heterorhabditis bacteriophora (GPS11 strain) from infected host cadavers in microcosms (0.05 m2) containing Wooster silt-loam soil (Oxyaquic fragiudalf) and vegetation in the presence or absence of non-mobile and mobile hosts. Results showed that the presence of a non-mobile host (Galleria mellonella larva in a wire mesh cage) enhanced H. bacteriophora dispersal for up to 24 hr compared with no-host treatment, but had no impact on S. carpocapsae dispersal. In contrast, presence of a mobile host (G. mellonella larvae) increased dispersal of S. carpocapsae compared with no host treatment, but had no effect on H. bacteriophora dispersal. Also H. bacteriophora was better at infecting non-mobile than mobile hosts released into the microcosms and S. carpocapsae was better at infecting mobile than non-mobile hosts, thus affirming the established cruiser-ambusher theory. However, results also revealed that a large proportion of infective juveniles (IJs) of both species stayed near (≤ 3.8 cm) the source cadaver (88-96% S. carpocapsae; 67-79% H. bacteriophora), and the proportion of IJs reaching the farthest distance (11.4 cm) was significantly higher for S. carpocapsae (1.4%) than H. bacteriophora (0.4%) in the presence of mobile hosts. S. carpocapsae also had higher average population displacement than H. bacteriophora in the presence of both the non-mobile (5.07 vs. 3.6 cm/day) and mobile (8.06 vs. 5.3 cm/day) hosts. We conclude that the two species differ in their dispersal and foraging behavior at the population level and this behavior is affected by both the presence and absence of hosts and by their mobility

Nonequilibrium thermodynamics and maximum entropy production in the Earth system

The Earth system is maintained in a unique state far from thermodynamic equilibrium, as, for instance, reflected in the high concentration of reactive oxygen in the atmosphere. The myriad of processes that transform energy, that result in the motion of mass in the atmosphere, in oceans, and on land, processes that drive the global water, carbon, and other biogeochemical cycles, all have in common that they are irreversible in their nature. Entropy production is a general consequence of these processes and measures their degree of irreversibility. The proposed principle of maximum entropy production (MEP) states that systems are driven to steady states in which they produce entropy at the maximum possible rate given the prevailing constraints. In this review, the basics of nonequilibrium thermodynamics are described, as well as how these apply to Earth system processes. Applications of the MEP principle are discussed, ranging from the strength of the atmospheric circulation, the hydrological cycle, and biogeochemical cycles to the role that life plays in these processes. Nonequilibrium thermodynamics and the MEP principle have potentially wide-ranging implications for our understanding of Earth system functioning, how it has evolved in the past, and why it is habitable. Entropy production allows us to quantify an objective direction of Earth system change (closer to vs further away from thermodynamic equilibrium, or, equivalently, towards a state of MEP). When a maximum in entropy production is reached, MEP implies that the Earth system reacts to perturbations primarily with negative feedbacks. In conclusion, this nonequilibrium thermodynamic view of the Earth system shows great promise to establish a holistic description of the Earth as one system. This perspective is likely to allow us to better understand and predict its function as one entity, how it has evolved in the past, and how it is modified by human activities in the future