Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml-1 and is causal, attributable to drug activity against liver stage parasites. Parasites that appear after subtherapeutic doses remain atovaquone-sensitive. Pharmacokinetic–pharmacodynamic analysis indicates protection can translate to humans at clinically achievable and safe drug concentrations, potentially offering protection for at least 1 month after a single administration. These findings support the use of long-acting injectable formulations as a new approach for malaria prophylaxis in travellers and for malaria control in the field.

No abstract

Water soluble gold nanoparticles are coated with peptides bearing a dithiol surface active group for studies of lanthanide binding; characteristic red luminescence is observed upon europium binding to the nanoparticles.

This paper describes a proposed framework for linking soft systems methodology (SSM), a problem structuring technique for use in messy, ill-defined problem situations, with Jackson System Development (JSD), an information system development methodology which has object-oriented characteristics. The approach taken has been to embed the modelling phase of JSD within SSM after the conceptual modelling stage, but before the debate on desirable and feasible change. The JSD modelling phase is carried out at a conceptual rather than a real world level. The framework comprises of a series of steps which enable JSD entity structure diagrams to be derived to a large extent from the activities in an SSM conceptual model. A data model may then be built up by exploding the activities in the conceptual model or by using 'conceptual hows' to identify more entities and actions. One of the main benefits expected to arise from the use of such a framework is an improved user requirement definition, which is important to successful systems implementation. The difficulties in actually achieving a link relate to the methodological and philosophical differences between SSM and JSD.

Botulinum neurotoxin is one of the deadliest biological toxins known to mankind and is able to cause the debilitating disease botulism. The rapid detection of the different serotypes of botulinum neurotoxin is essential for both diagnosis of botulism and identifying the presence of toxin in potential cases of terrorism and food contamination. The modes of action of botulinum neurotoxins are well-established in literature and differ for each serotype. The toxins are known to specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an interaction that can be monitored by electrochemical impedance spectroscopy. This study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five botulinum neurotoxin serotypes (A–E) using electrochemical impedance spectroscopy. The biosensors are able to detect concentrations of toxins as low as 25 fg/mL, in a short time-frame compared with the current standard methods of detection. Both biosensors show greater specificity for their compatible serotypes compared with incompatible serotypes and denatured toxins.

No abstract

Luminescence and imaging studies of 500 nm diameter colloidal silica stained with the transition metal complex [Ru(bpy)3Cl2], [Ru(bpy)3⊂SiNP], have been detailed and suggest that such particles are ideal for particle tracking velocimetry (PTV) or particle imaging velocimetry (PIV) for analysis of fluid flow in microchannels. Silica particles were synthesized using a modification to the Stöber synthesis to cage the transition metal complex within the core of the nanoscale particles. The particles [Ru(bpy)3⊂SiNP] exhibit luminescence at 620 nm, characteristic of the caged [Ru(bpy)3]2+ species with a lifetime of 790 ns upon excitation at 450 nm. A collection of the luminescence spectra from the images of the particles in a microchannel have the same profile as the spectra collected from solutions of [Ru(bpy)3⊂SiNP], confirming that the luminescence images are attributed to [Ru(bpy)3]2+ luminescence. PIV and PTV measurements from image sequences give flow velocities that match well with the theoretical velocity profile for a rectangular-sided microchannel of 100 µm depth.

The control of COVID-19 across the world requires the formation of a range of interventions including vaccines to elicit an immune response and immunomodulatory or antiviral therapeutics. Here, we demonstrate...