Hepatitis B virus (HBV) infection constitutes a global public health problem. In order to establish how HBV was disseminated across different geographic regions, we estimated the levels of regional clustering for genotypes D and A. We used 916 HBV-D and 493 HBV-A full-length sequences to reconstruct their global phylogeny. Phylogeographic analysis was conducted by the reconstruction of ancestral states using the criterion of parsimony. The putative origin of genotype D was in North Africa/Middle East. HBV-D sequences form low levels of regional clustering for the Middle East and Southern Europe. In contrast, HBV-A sequences form two major clusters, the first including sequences mostly from sub-Saharan Africa, and the second including sequences mostly from Western and Central Europe. Conclusion: We observed considerable differences in the global dissemination patterns of HBV-D and HBV-A and different levels of monophyletic clustering in relation to the regions of prevalence of each genotype.

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Conclusions: Given that an efficient uniform price is dependent on the uptake in each indication, there are additional challenges to implement the optimal price in a market, compared to indication-specific pricing. The difference in the drug acquisition incurred for the payer under different strategies will lead to the profits for the manufacturer varying under the different pricing strategies. For an estimated efficient uniform price there may be reduced patient access and inefficient pricing if the indications reaching final approval are different to those used to set this price.

Early numeracy is related to preschoolers' acquisition of skills such as understanding and operating with quantities. Consequently, early numeracy has substantial impact on first Graders' attainments in typical mathematics. Meta-analysis was conducted to address the extent in which early numeracy interventions are effective. Twenty studies were analyzed, including 3.080 young low-performing children (Ncontrol = 1.815, Ntreatment = 1.265). The overall best estimate for programs based on Early Numeracy Interventions odds ratio was moderately effective g = 0.61. Heterogeneity was large. Results of the final meta-regression model predicted larger treatment effects for short-term interventions including 1 to 9 sessions. On average, the interventions included instructional strategies such as explicit instruction, corrective feedback, CRA, concrete manipulatives, and visual representation, and one-to-one instructional arrangement are moderately effective for children aged 5-8. Results of the study are discussed with respect to implications for designing early numeracy interventions.

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