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.
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.
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