Improving antibiotic prescribing for children in the resource-poor setting.

Antibiotics are a critically important part of paediatric medical care in low- and middle-income countries (LMICs), where infectious diseases are the leading cause of child mortality. The World Health Organization estimates that >50% of all medicines are prescribed, dispensed or sold inappropriately and that half of all patients do not take their medicines correctly. Given the rising prevalence of antimicrobial resistance globally, inappropriate antibiotic use is of international concern, and countries struggle to implement basic policies promoting rational antibiotic use. Many barriers to rational paediatric prescribing in LMICs persist. The World Health Organization initiatives, such as 'Make medicines child size', the Model List of Essential Medicines for Children and the Model Formulary for Children, have been significant steps forward. Continued strategies to improve access to appropriate drugs and formulations, in conjunction with improved evidence-based clinical guidelines and dosing recommendations, are essential to the success of such initiatives on both a national and an international level. This paper provides an overview of these issues and considers future developments that may improve LMIC antibiotic prescribing

Inertial wave turbulence driven by elliptical instability

The combination of elliptical deformation of streamlines and vorticity can lead to the destabilisation of any rotating flow via the elliptical instability. Such a mechanism has been invoked as a possible source of turbulence in planetary cores subject to tidal deformations. The saturation of the elliptical instability has been shown to generate turbulence composed of non-linearly interacting waves and strong columnar vortices with varying respective amplitudes, depending on the control parameters and geometry. In this paper, we present a suite of numerical simulations to investigate the saturation and the transition from vortex-dominated to wave-dominated regimes. This is achieved by simulating the growth and saturation of the elliptical instability in an idealised triply periodic domain, adding a frictional damping to the geostrophic component only, to mimic its interaction with boundaries. We reproduce several experimental observations within one idealised local model and complement them by reaching more extreme flow parameters. In particular, a wave-dominated regime that exhibits many signatures of inertial wave turbulence is characterised for the first time. This regime is expected in planetary interiors

Canine tick-borne pathogens in Cyprus and a unique canine case of multiple co-infections

Canine tick-borne pathogens such as Ehrlichia canis and Hepatozoon canis are widespread in the Mediterranean basin but have never been reported or investigated in Cyprus. We describe herein the presence of canine tick-borne pathogens in three dogs with clinical signs compatible with vector-borne diseases from Paphos area of Cyprus. Molecular and phylogenetic analysis revealed the presence of E. canis, Anaplasma platys, H. canis, Babesia vogeli and Mycoplasma haemocanis in Cyprus. One dog co-infected with E. canis, H. canis, B. vogeli and M. haemocanis is, to the best of our knowledge, the first report of this multiple co-infection in dogs. The tick-borne pathogens reported in the current study should be considered in the differential diagnoses in dogs exposed to ticks in Cyprus

Effects of Temperature on Emergence and Seasonality of West Nile Virus in California

Temperature has played a critical role in the spatiotemporal dynamics of West Nile virus transmission throughout California from its introduction in 2003 through establishment by 2009. We compared two novel mechanistic measures of transmission risk, the temperature-dependent ratio of virus extrinsic incubation period to the mosquito gonotrophic period (BT), and the fundamental reproductive ratio (R0) based on a mathematical model, to analyze spatiotemporal patterns of receptivity to viral amplification. Maps of BT and R0 were created at 20-km scale and compared throughout California to seroconversions in sentinel chicken flocks at half-month intervals. Overall, estimates of BT and R0 agreed with intensity of transmission measured by the frequency of sentinel chicken seroconversions. Mechanistic measures such as these are important for understanding how temperature affects the spatiotemporal dynamics of West Nile virus transmission and for delineating risk estimates useful to inform vector control agency intervention decisions and communicate outbreak potential

Pharmacokinetic studies in children: recommendations for practice and research.

Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose-concentration-effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight

FCNC Processes from D-brane Instantons

Low string scale models might be tested at the LHC directly by their Regge resonances. For such models it is important to investigate the constraints of Standard Model precision measurements on the string scale. It is shown that highly suppressed FCNC processes like K0- bar K^0 oscillations or leptonic decays of the D0-meson provide non-negligible lower bounds on both the perturbatively and surprisingly also non-perturbatively induced string theory couplings. We present both the D-brane instanton formalism to compute such amplitudes and discuss various possible scenarios and their constraints on the string scale for (softly broken) supersymmetric intersecting D-brane models.Comment: 28 pages, 13 figures, reference added, 1 typo corrected, style file adde

On parton distributions beyond the leading order

The importance of properly taking into account the factorization scheme dependence of parton distribution functions is emphasized. A serious error in the usual handling of this topic is pointed out and the correct procedure for transforming parton distribution functions from one factorisation scheme to another recalled. It is shown that the conventional $\overline{\rm {MS}}$ and DIS definitions thereof are ill-defined due to the lack of distinction between the factorisation scheme dependence of parton distribution functions and renormalisation scheme dependence of the strong coupling constant $\alpha_s$. A novel definition of parton distribution functions is suggested and its role in the construction of consistent next-to-leading order event generators briefly outlined.Comment: PRA-HEP-93/05, Latex, 10 pages and 2 Postscript figures appended at the end of this fil

Transport properties of dense fluid argon

We calculate using molecular dynamics simulations the transport properties of realistically modeled fluid argon at pressures up to $\simeq 50GPa$ and temperatures up to $3000K$. In this context we provide a critique of some newer theoretical predictions for the diffusion coefficients of liquids and a discussion of the Enskog theory relevance under two different adaptations: modified Enskog theory (MET) and effective diameter Enskog theory. We also analyze a number of experimental data for the thermal conductivity of monoatomic and small diatomic dense fluids.Comment: 8 pages, 6 figure

Formation and destruction of polycyclic aromatic hydrocarbon clusters in the interstellar medium

The competition between the formation and destruction of coronene clusters under interstellar conditions is investigated theoretically. The unimolecular nucleation of neutral clusters is simulated with an atomic model combining an explicit classical force field and a quantum tight-binding approach. Evaporation rates are calculated in the framework of the phase space theory and are inserted in an infrared emission model and compared with the growth rate constants. It is found that, in interstellar conditions, most collisions lead to cluster growth. The time evolution of small clusters (containing up to 312 carbon atoms) was specifically investigated under the physical conditions of the northern photodissociation region of NGC 7023. These clusters are found to be thermally photoevaporated much faster than they are reformed, thus providing an interpretation for the lowest limit of the interstellar cluster size distribution inferred from observations. The effects of ionizing the clusters and density heterogeneities are also considered. Based on our results, the possibility that PAH clusters could be formed in PDRs is critically discussed.Comment: 14 pages, 14 figures. Astronomy & Astrophysics, accepted for publicatio