investments to support countries with greatest burden of viral hepatitis All heavily burdened countries to have fully funded elimination plans by 2019 Recognition of need to focus on high burden countries and support for national policy development (All) Funding for national elimination plans Creation of fiscal space for new programmes with costed investment programmes Adopt domestic innovative finance tools where appropriate Support national policy makers in their activity (WHO, UNITAID, NGOs) Provide international support for financing measures (UNITAID, GFATM, bilaterial donors) Prevention Ensure all WHO elimination targets addressed in plans Address operational challenges in delivery of birth dose HBV vaccine Ensure provision of harm reduction services and engage with marginalised group (e.g. prisoners, PWIDs). Ensure clear public health messages to encourage testing and treatment Support countries to decriminalise injecting drug use and ensure equitable access to services for all (NGOs, WHO, civil society) Ensure appropriate funding for HBV vaccine, including birth dose (GAVI, WHO) Support R&D into HCV vaccine development (Research funders and pharma) Testing and Models of Care Focus on substantially scaling up testing for HBV and HCV Create and evaluate simplified care pathways relevant to local setting, integrating with existing services. Promote task sharing and decentralisation of care through capacity building, training and removal of Support operational research into simplified pathways (Research funders, UNITAID) requirements for specialised prescribing Diagnostics Ensure testing is integrated into the wider healthcare system, rather than centralised facilties Ensure access to quality diagnostics through Essential Diagnostic List and prequalification (WHO, funders) Support implementation science for models of care and R&D into novel diagnostics suitable for decentralised settings. (Research funders, FIND, industry) Access to treatment Ensure all Essential Medicines for viral hepatitis are included in national programmes, with an emphasis on pan-genotypic regimens Apply comprehensive policy approach to promoting access, including compulsory licensing Ensure all essential medicines are pre-qualified and either available through voluntary licensing or Medicines Patent Pool (WHO, NGOs, civil society, funders) Support shared procurement mechanisms for treatment (PAHO) Monitor Progress National plans need clearly defined, measurable objectives Develop new indices of national progress Progress of individual countries needs to be closely monitored towards elimination goals (Polaris, WHO, Creation of Elimination Index) Develop greater capacity for advocacy in high burden regions (all) Viral hepatitis is one of the leading causes of death in the world. 96% of those deaths are due to hepatitis B and C, which are the focus of this commission. Unlike many other major diseases, the tools exist to eliminate viral hepatitis. A highly effective vaccine is available to prevent hepatitis B, and a revolution in HCV treat...

A combined scanning electrochemical-atomic force microscope (SECM-AFM) has been used to probe the diffusional transport of target electroactive solutes in isolated nanopores of a track-etched membrane. A polycarbonate membrane (100-nm-diam pore size) hydrated with an electrolyte solution, containing a redox-active probe molecule, such as IrCl6(3-) or Fe(phen)3(2+), functions as the model membrane system. The use of a mobile Pt-coated AFM probe enables individual solution-filled pores to be topographically identified. Analysis of the corresponding current images for the diffusion-limited oxidation of the redox mediator indicates that solution is largely confined to pores in the membrane. Moreover, the tip collector current response provides information on diffusion of the mediator through the pore. Force-distance tip approach and retract measurements allow the radius of contact between the electrochemical-AFM tip and solution confined within a pore at the point of pull-off to be estimated.

Alphaviruses are arthropod-borne viruses that represent a significant threat to public health at a global level. While the formation of alphaviral nucleocapsid cores, consisting of cargo nucleic acid and the viral capsid protein, is an essential molecular process of infection, the precise interactions between the two partners are ill-defined. A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus. The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence. Mutational analyses of the cytoplasmic viral RNA-capsid interaction sites revealed a functional role for capsid binding early in infection. Interaction site mutants exhibited decreased viral growth kinetics; however, this defect was not a function of decreased particle production. Rather mutation of the cytoplasmic capsid-RNA interaction sites negatively affected the functional capacity of the incoming viral genomic RNAs leading to decreased infectivity. Furthermore, cytoplasmic capsid interaction site mutants are attenuated in a murine model of neurotropic alphavirus infection. Collectively, the findings of this study indicate that the identified cytoplasmic interactions of the viral capsid protein and genomic RNA, while not essential for particle formation, are necessary for genomic RNA function early during infection. This previously unappreciated role of capsid protein during the alphaviral replication cycle also constitutes a novel virulence determinant.

The surface processes accompanying dissolution from the (010) surface of potassium ferrocyanide trihydrate in aqueous solution have been determined using an integrated electrochemical-atomic force microscope (IE-AFM). This instrument employs a Pt-coated AFM tip that functions as an electrode, as well as a conventional topographical imaging device. The dissolution process was induced by oxidizing ferrocyanide at the tip, from an initially saturated solution, thereby creating a local undersaturation at the crystal-solution interface. The subsequent dissolution behavior was imaged in real time as a function of the diffusional driving force. At low driving force, the dissolution process proceeds mainly by the retreat of preexisiting steps aligned in the dominant [102] direction. With increasing driving force, dissolution occurs via the unwinding of steps from screw dislocation sites, leading to the formation of macroscopic etch pits, with an outline morphology determined by the [102] and [201] directions. At the highest driving forces the density of etch pits corresponds closely with the observed density of growth hillocks on the crystal surface, prior to dissolution. The surface dynamics observed under diffusion-controlled conditions are consistent with earlier scanning electrochemical microscopy kinetic studies (Macpherson,

The surface processes involved in the initial stages of the proton-assisted dissolution of the calcite single crystal cleavage plane (1014) have been identified using a combined scanning electro-chemical-atomic force microscope (SECM-AFM). This instrument employs a platinum-coated AFM probe, which functions as an electrode as well as a high-resolution topographical sensor. Dissolution in this arrangement is effected by the local electrogeneration of protons, produced by oxidation of water at the probe electrode. By careful control of the applied potential, it is possible to vary the magnitude of the electrogenerated flux of protons from the probe towards the calcite surface. Crucially, by generating a small proton flux for short time periods (0.5 s) it is possible to observe and monitor the initial sites in the dissolution process. Topographical images were recorded in the same area of the surface both prior to and after inducing dissolution, as a function of the proton flux. At low proton fluxes, of the order of 1 nmol cm-2s-1 or less, the surface was observed to dissolve by the nucleation of monolayer deep pits, with densities of about 10(8) cm-2. These pits are likely to be formed at point vacancies or atomic (impurity, for example) defects in the crystal lattice. As the proton flux was increased (over two orders of magnitude), these same etch pits were found to open into wider macro-pits, with an outline morphology that reflected the crystallographic orientation of the surface. At the highest proton fluxes, dissolution from macroscopic step edges became significant.