Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus : studies in the pig model of influenza

Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs

A review of modelling methodologies for flood source area (FSA) identification

Flooding is an important global hazard that causes an average annual loss of over 40 billion USD and affects a population of over 250 million globally. The complex process of flooding depends on spatial and temporal factors such as weather patterns, topography, and geomorphology. In urban environments where the landscape is ever-changing, spatial factors such as ground cover, green spaces, and drainage systems have a significant impact. Understanding source areas that have a major impact on flooding is, therefore, crucial for strategic flood risk management (FRM). Although flood source area (FSA) identification is not a new concept, its application is only recently being applied in flood modelling research. Continuous improvements in the technology and methodology related to flood models have enabled this research to move beyond traditional methods, such that, in recent years, modelling projects have looked beyond affected areas and recognised the need to address flooding at its source, to study its influence on overall flood risk. These modelling approaches are emerging in the field of FRM and propose innovative methodologies for flood risk mitigation and design implementation; however, they are relatively under-examined. In this paper, we present a review of the modelling approaches currently used to identify FSAs, i.e. unit flood response (UFR) and adaptation-driven approaches (ADA). We highlight their potential for use in adaptive decision making and outline the key challenges for the adoption of such approaches in FRM practises

A refined guinea pig model of foot-and-mouth disease virus infection for assessing the efficacy of antiviral compounds

An antiviral containment strategy for foot-and-mouth disease (FMD) outbreaks could support or replace current contingency plans in case of an outbreak in Europe and could spare many healthy animals from being pre-emptively culled. Recently, substantial progress has been made towards the development of small molecule drugs that inhibit FMD virus (FMDV) replication in vitro. For the initial in vivo evaluation of antiviral lead molecules, a refined FMDV-infection model in guinea pigs (GP) is herewith described. This GP model was validated by demonstrating the antiviral effect of T-1105 (an influenza virus inhibitor with reported activity against FMDV). Sixteen animals were orally administered with T-1105 twice daily (400 mg/kg/day) for five consecutive days and inoculated intraplantarly with 100 GPID50 of the GP-adapted FMDV strain O1 Manisa 1 h after the first administration. The efficacy of T-1105 was compared with that of prophylactic vaccination with a highly potent double-oil emulsion-inactivated O1 Manisa vaccine. Ten animals received a single, full (2 ml) cattle vaccine dose and were inoculated 3 weeks later. Fourteen T-1105-treated and all vaccinated GP were completely protected from generalization of vesicular lesions. At 2 dpi, viral RNA was detected in serum of 9/16 T-1105-treated and of 6/10 vaccinated animals. At 4 dpi, viral RNA was detected in serum, organs and oral swabs of half of the T-1105-treated animals and only in the serum of 1/10 of the vaccinated animals. Mean viral RNA levels in serum and organs of T-1105-treated and vaccinated animals were reduced compared to untreated controls (P < 0.01). T-1105 conferred a substantial clinical and virological protection against infection with O1 Manisa, similar to the protection afforded by vaccination. These results validate the suitability of the enhanced GP model for the purpose of initial evaluation of inhibitors of FMDV replication and illustrate the potential of selective inhibitors of viral replication to control FMD outbreaks.status: publishe

Conservation agriculture in Sub-Saharan Africa

Specific practices of conservation agriculture (CA) in sub-Saharan Africa are diverse and vary according to local farming conditions. However, despite more than two decades of investment in its development and dissemination, adoption of CA is low. Crop responses to CA are highly variable, and not always positive, which is an important hindrance for adoption, especially for resource-poor farmers who need immediate returns with their investments in CA in order to be able to feed their families. In contrast with commercial farms such as in Brazil, reduced costs with CA on smallholder farms in sub-Saharan Africa are not always observed. Another major challenge with the practice of CA is the use of crop residues for mulching since crop residues are a major source of feed for livestock, especially in semiarid regions, where biomass production is limited and livestock plays a crucial role in farming systems. Studies indicate that the three principles of CA, including mulching, are needed to increase crop yields compared with conventional tillage (CT)-based practices. Among the three principles of CA, mulching is certainly the one that is least observed in past and current cropping practices in Africa. CA has a potential to improve the soil water balance and increase soil fertility, and it is undoubtedly a cropping practice that can result in substantial benefits for certain farmers in Africa. The question is when and how it is the best approach for smallholder farmers in sub-Saharan Africa. In general, CA is more likely to be attractive for farmers with a strategy of intensification than for farmers who struggle to produce food for their family. The latter too often face multiple constraints that limit the possibilities to engage in technological innovations. Some farmers may not be interested in new technologies because they earn their income from off-farm activities. Good markets of input supply and sale of extra produce are a prerequisite condition for adoption of CA as they are for any other new agricultural technology that aims at intensification. In sub-Saharan Africa, there is certainly a need to better target CA to potential end users and adapt the CA practices to their local circumstances and specific farming contexts. (Résumé d'auteur

Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism.

BACKGROUND: Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear. METHODS: In a randomized, double-blind, noninferiority study, we randomly assigned patients with acute venous thromboembolism, who had initially received heparin, to receive edoxaban at a dose of 60 mg once daily, or 30 mg once daily (e.g., in the case of patients with creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg), or to receive warfarin. Patients received the study drug for 3 to 12 months. The primary efficacy outcome was recurrent symptomatic venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. RESULTS: A total of 4921 patients presented with deep-vein thrombosis, and 3319 with a pulmonary embolism. Among patients receiving warfarin, the time in the therapeutic range was 63.5%. Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome, which occurred in 130 patients in the edoxaban group (3.2%) and 146 patients in the warfarin group (3.5%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.70 to 1.13; P&lt;0.001 for noninferiority). The safety outcome occurred in 349 patients (8.5%) in the edoxaban group and 423 patients (10.3%) in the warfarin group (hazard ratio, 0.81; 95% CI, 0.71 to 0.94; P=0.004 for superiority). The rates of other adverse events were similar in the two groups. A total of 938 patients with pulmonary embolism had right ventricular dysfunction, as assessed by measurement of N-terminal pro-brain natriuretic peptide levels; the rate of recurrent venous thromboembolism in this subgroup was 3.3% in the edoxaban group and 6.2% in the warfarin group (hazard ratio, 0.52; 95% CI, 0.28 to 0.98). CONCLUSIONS: Edoxaban administered once daily after initial treatment with heparin was noninferior to high-quality standard therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism, including those with severe pulmonary embolism. (Funded by Daiichi-Sankyo; Hokusai-VTE ClinicalTrials.gov number, NCT00986154.)