22 research outputs found

    Financial Evaluation of Different Vaccination Strategies for Controlling the Bluetongue Virus Serotype 8 Epidemic in the Netherlands in 2008

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    Background: Bluetongue (BT) is a vector-borne disease of ruminants caused by bluetongue virus that is transmitted by biting midges (Culicoides spp.). In 2006, the introduction of BTV serotype 8 (BTV-8) caused a severe epidemic in Western and Central Europe. The principal effective veterinary measure in response to BT was believed to be vaccination accompanied by other measures such as movement restrictions and surveillance. As the number of vaccine doses available at the start of the vaccination campaign was rather uncertain, the Dutch Ministry of Agriculture, Nature and Food Quality and the Dutch agricultural industry wanted to evaluate several different vaccination strategies. This study aimed to rank eight vaccination strategies based on their efficiency (i.e. net costs in relation to prevented losses or benefits) for controlling the bluetongue virus serotype 8 epidemic in 2008 Methodology/Principal Findings: An economic model was developed that included the Dutch professional cattle, sheep and goat sectors together with the hobby farms. Strategies were evaluated based on the least cost - highest benefit frontier, the benefit-cost ratio and the total net returns. Strategy F, where all adult sheep at professional farms in the Netherlands would be vaccinated was very efficient at lowest costs, whereas strategy D, where additional to all adult sheep at professional farms also all adult cattle in the four Northern provinces would be vaccinated, was also very efficient but at a little higher costs. Strategy C, where all adult sheep and cattle at professional farms in the whole of the Netherlands would be vaccinated was also efficient but again at higher costs. Conclusions/Significance: This study demonstrates that a financial analysis differentiates between vaccination strategies and indicates important decision rules based on efficienc

    Pathophysiology of Cardiopulmonary Bypass

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    Pathophysiology of Cardiopulmonary Bypass

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    The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses

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    The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with a conserved genome architecture. ExoN, a homolog of canonical DNA proof-reading enzymes, is exclusively encoded by nidoviruses with genomes larger than 20 kb. All other known non-segmented RNA viruses have smaller genomes. Here we use evolutionary analyses to show that the two- to three-fold expansion of the nidovirus genome was accompanied by a large number of replacements in conserved proteins at a scale comparable to that in the Tree of Life. To unravel common evolutionary patterns in such genetically diverse viruses, we established the relation between genomic regions in nidoviruses in a sequence alignment-free manner. We exploited the conservation of the genome architecture to partition each genome into five non-overlapping regions: 5′ untranslated region (UTR), open reading frame (ORF) 1a, ORF1b, 3′ORFs (encompassing the 3′-proximal ORFs), and 3′ UTR. Each region was analyzed for its contribution to genome size change under different models. The non-linear model statistically outperformed the linear one and captured >92% of data variation. Accordingly, nidovirus genomes were concluded to have reached different points on an expansion trajectory dominated by consecutive increases of ORF1b, ORF1a, and 3′ORFs. Our findings indicate a unidirectional hierarchical relation between these genome regions, which are distinguished by their expression mechanism. In contrast, these regions cooperate bi-directionally on a functional level in the virus life cycle, in which they predominantly control genome replication, genome expression, and virus dissemination, respectively. Collectively, our findings suggest that genome architecture and the associated region-specific division of labor leave a footprint on genome expansion and may limit RNA genome size
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