Requirements for global elimination of hepatitis B: a modelling study

Background Despite the existence of effective prevention and treatment interventions, hepatitis B virus (HBV) infection continues to cause nearly 1 million deaths each year. WHO aspires to global control and elimination of HBV infection. We aimed to evaluate the potential impact of public health interventions against HBV, propose targets for reducing incidence and mortality, and identify the key developments required to achieve them. Methods We developed a simulation model of the global HBV epidemic, incorporating data on the natural history of HBV, prevalence, mortality, vaccine coverage, treatment dynamics, and demographics. We estimate the impact of current interventions and scaling up of existing interventions for prevention of infection and introducing wide-scale population screening and treatment interventions on the worldwide epidemic. Findings Vaccination of infants and neonates is already driving a large decrease in new infections; vaccination has already prevented 210 million new chronic infections by 2015 and will have averted 1·1 million deaths by 2030. However, without scale-up of existing interventions, our model showed that there will be a cumulative 63 million new cases of chronic infection and 17 million HBV-related deaths between 2015 and 2030 because of ongoing transmission in some regions and poor access to treatment for people already infected. A target of a 90% reduction in new chronic infections and 65% reduction in mortality could be achieved by scaling up the coverage of infant vaccination (to 90% of infants), birth-dose vaccination (to 80% of neonates), use of peripartum antivirals (to 80% of hepatitis B e antigen-positive mothers), and population-wide testing and treatment (to 80% of eligible people). These interventions would avert 7·3 million deaths between 2015 and 2030, including 1·5 million cases of cancer deaths. An elimination threshold for incidence of new chronic infections would be reached by 2090 worldwide. The annual cost would peak at US$7·5 billion worldwide ($3·4 billion in low-income and lower-middle-income countries), but decrease rapidly and this would be accelerated if a cure is developed. Interpretation Scale-up of vaccination coverage, innovations in scalable options for prevention of mother-to-child transmission, and ambitious population-wide testing and treatment are needed to eliminate HBV as a major public health threat. Achievement of these targets could make a major contribution to one of the Sustainable Development Goals of combating hepatitis

Telepresence and the Role of the Senses

The telepresence experience can be evoked in a number of ways. A well-known example is a player of videogames who reports about a telepresence experience, a subjective experience of being in one place or environment, even when physically situated in another place. In this paper we set the phenomenon of telepresence into a theoretical framework. As people react subjectively to stimuli from telepresence, empirical studies can give more evidence about the phenomenon. Thus, our contribution is to bridge the theoretical with the empirical. We discuss theories of perception with an emphasis on Heidegger, Merleau-Ponty and Gibson, the role of the senses and the Spinozian belief procedure. The aim is to contribute to our understanding of this phenomenon. A telepresence-study that included the affordance concept is used to empirically study how players report sense-reactions to virtual sightseeing in two cities. We investigate and explore the interplay of the philosophical and the empirical. The findings indicate that it is not only the visual sense that plays a role in this experience, but all senses

A Surprising Prevention Success: Why Did the HIV Epidemic Decline in Zimbabwe?

Daniel Halperin and colleagues examine reasons for the remarkable decline in HIV in Zimbabwe, in the context of severe social, political, and economic disruption

Errors in ‘BED’-Derived Estimates of HIV Incidence Will Vary by Place, Time and Age

The BED Capture Enzyme Immunoassay, believed to distinguish recent HIV infections, is being used to estimate HIV incidence, although an important property of the test--how specificity changes with time since infection--has not been not measured.We construct hypothetical scenarios for the performance of BED test, consistent with current knowledge, and explore how this could influence errors in BED estimates of incidence using a mathematical model of six African countries. The model is also used to determine the conditions and the sample sizes required for the BED test to reliably detect trends in HIV incidence.If the chance of misclassification by BED increases with time since infection, the overall proportion of individuals misclassified could vary widely between countries, over time, and across age-groups, in a manner determined by the historic course of the epidemic and the age-pattern of incidence. Under some circumstances, changes in BED estimates over time can approximately track actual changes in incidence, but large sample sizes (50,000+) will be required for recorded changes to be statistically significant.The relationship between BED test specificity and time since infection has not been fully measured, but, if it decreases, errors in estimates of incidence could vary by place, time and age-group. This means that post-assay adjustment procedures using parameters from different populations or at different times may not be valid. Further research is urgently needed into the properties of the BED test, and the rate of misclassification in a wide range of populations

Orbital interactions and chemical reactivity of metal particles and metal surfaces

A review is presented with 101 refs. on chem. bonding to metal surfaces and small metal particles demonstrating the power of symmetry concepts to predict changes in chem. bonding. Ab-initio calcns. of chemisorption to small particles, as well as semiempirical extended Hueckel calcns. applied to the study of the reactivity of metal slabs are reviewed. On small metal particles, classical notions of electron promotion and hybridization are found to apply. The surroundings of a metal atom (ligands in complexes, other metal atoms at surfaces), affect bonding and reactivity through the prehybridization they induce. A factor specific for large particles and surfaces is the required localization of electrons on the atoms involved in the metal surface bond. At the surface, the bond energy is found to relate to the grou8p orbital local d. of states at the Fermi level. The use of this concept is extensively discussed and illustrated for chemisorption of CO and dissocn. of NO on metal surfaces. A discussion is given of the current decompn. schemes of bond energies and related concepts (exchange (Pauli)-repulsion, polarization, charge transfer). The role of non-orthogonality of fragment orbitals and of kinetic and potential energy for Pauli repulsion and (orbital) polarization is analyzed. Numerous examples are discussed to demonstrate the impact of those concepts on chem. bonding theor

Drosophila selenophosphate synthetase 1 regulates vitamin B6 metabolism: prediction and confirmation

<p>Abstract</p> <p>Background</p> <p>There are two selenophosphate synthetases (SPSs) in higher eukaryotes, SPS1 and SPS2. Of these two isotypes, only SPS2 catalyzes selenophosphate synthesis. Although SPS1 does not contain selenophosphate synthesis activity, it was found to be essential for cell growth and embryogenesis in <it>Drosophila</it>. The function of SPS1, however, has not been elucidated.</p> <p>Results</p> <p>Differentially expressed genes in <it>Drosophila </it>SL2 cells were identified using two-way analysis of variance methods and clustered according to their temporal expression pattern. Gene ontology analysis was performed against differentially expressed genes and gene ontology terms related to vitamin B6 biosynthesis were found to be significantly affected at the early stage at which megamitochondria were not formed (day 3) after <it>SPS1 </it>knockdown. Interestingly, genes related to defense and amino acid metabolism were affected at a later stage (day 5) following knockdown. Levels of pyridoxal phosphate, an active form of vitamin B6, were decreased by <it>SPS1 </it>knockdown. Treatment of SL2 cells with an inhibitor of pyridoxal phosphate synthesis resulted in both a similar pattern of expression as that found by <it>SPS1 </it>knockdown and the formation of megamitochondria, the major phenotypic change observed by <it>SPS1 </it>knockdown.</p> <p>Conclusions</p> <p>These results indicate that SPS1 regulates vitamin B6 synthesis, which in turn impacts various cellular systems such as amino acid metabolism, defense and other important metabolic activities.</p

Investigation of the biomechanical effect of variable stiffness shoe on external knee adduction moment in various dynamic exercises

10.1186/1757-1146-6-39Journal of Foot and Ankle Research61