The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge

Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P ≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P ≤0.05). In addition, lactoferrin (P ≤0.002), transferrin receptor (P ≤0.05) and solute carrier family 11A1 (P ≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria.

The determinants of a cross market arbitrage opportunity: theory and evidence for the European bond market

This paper examines the determinants of cross-platform arbitrage profits. We develop a structural model that enables us to decompose the likelihood of an arbitrage opportunity into three distinct factors: the fixed cost to trade the opportunity, the level at which one of the platforms delays a price update and the impact of the order flow on the quoted prices (inventory and asymmetric information effects). We then investigate the predictions from the theoretical model for the European Bond market with the estimation of a probit model. Our main finding is that the results found in the empirical part corroborate strongly the predictions from the structural model. The event of a cross market arbitrage opportunity has a certain degree of predictability where an optimal ex ante scenario is represented by a low level of spreads on both platforms, a time of the day close to the end of trading hours and a high volume of trade.

An evaluation of the theoretical potential and practical opportunity for using greywater for domestic purposes in Ghana

Assessments concerning the effects of climate change, water resource availability and water deprivation in West Africa have not frequently considered the positive contribution to be derived from collecting and reusing water for domestic purposes. Where the originating water is taken from a clean water source and has been used the first time for washing or bathing, this water is commonly called “greywater”. Greywater is a prolific resource that is generated wherever people live. Treated greywater can be used for domestic cleaning, for flushing toilets where appropriate, for washing cars, sometimes for watering kitchen gardens, and for clothes washing prior to rinsing. Therefore, a large theoretical potential exists to increase total water resource availability if greywater were to be widely reused. Locally treated greywater reduces the distribution network requirement, lower construction effort and cost and, wherever possible, minimising the associated carbon footprint. Such locally treated greywater offers significant practical opportunities for increasing the total available water resources at a local level. The reuse of treated greywater is one important action that will help to mitigate the reducing availability of clean water supplies in some areas, and the expected mitigation required in future aligns well with WHO/UNICEF (2012) aspirations. The evaluation of potential opportunities for prioritising greywater systems to support water reuse takes into account the availability of water resources, water use indicators and published estimates in order to understand typical patterns of water demand. The approach supports knowledge acquisition regarding local conditions for enabling capacity building for greywater reuse, the understanding of systems that are most likely to encourage greywater reuse, and practices and future actions to stimulate greywater infrastructure planning, design and implementation. Although reuse might be considered to increase the uncertainty of achieving a specified quality of the water supply, robust methods and technologies are available for local treatment. Resource strategies for greywater reuse have the potential to consistently improve water efficiency and availability in water impoverished and water stressed regions of Ghana and West Africa. Untreated greywater is referred to as “greywater”; treated greywater is referred to as “treated greywater” in this paper.

Tracking the uncertainty in flood alerts driven by grand ensemble weather predictions

The incorporation of numerical weather predictions (NWP) into a flood warning system can increase forecast lead times from a few hours to a few days. A single NWP forecast from a single forecast centre, however, is insufficient as it involves considerable non-predictable uncertainties and can lead to a high number of false or missed warnings. Weather forecasts using multiple NWPs from various weather centres implemented on catchment hydrology can provide significantly improved early flood warning. The availability of global ensemble weather prediction systems through the ‘THORPEX Interactive Grand Global Ensemble’ (TIGGE) offers a new opportunity for the development of state-of-the-art early flood forecasting systems. This paper presents a case study using the TIGGE database for flood warning on a meso-scale catchment (4062 km2) located in the Midlands region of England. For the first time, a research attempt is made to set up a coupled atmospheric-hydrologic-hydraulic cascade system driven by the TIGGE ensemble forecasts. A probabilistic discharge and flood inundation forecast is provided as the end product to study the potential benefits of using the TIGGE database. The study shows that precipitation input uncertainties dominate and propagate through the cascade chain. The current NWPs fall short of representing the spatial precipitation variability on such a comparatively small catchment, which indicates need to improve NWPs resolution and/or disaggregating techniques to narrow down the spatial gap between meteorology and hydrology. The spread of discharge forecasts varies from centre to centre, but it is generally large and implies a significant level of uncertainties. Nevertheless, the results show the TIGGE database is a promising tool to forecast flood inundation, comparable with that driven by raingauge observation.

Washington's growth and opportunity act or Beijing's 'Overarching Brilliance': will African governments choose neither?

Growing criticism of Chinese engagement in Africa centres on the risk to African development posed by China's aggressive export policies and the threat to the Washington Consensus and African governance posed by China's 'non-interference' approach to engagement. This article challenges both these assumptions. The growth of Chinese trade has a wide range of impacts, depending on the sector in question, and the current terms of trade Washington extends to Africa under the auspices of the AGOA do not result in uniformly beneficial effects. With regard to African governance, it is argued that the 'Washington Consensus' has been based on competing and often muddled perceptions of US national interest. This fact tempers the regret felt at Washington's loss of influence over the good governance agenda. Evidence is provided to show that China can work within properly regulated countries and industries, if the African governments in question can provide fair, efficient and transparent environments in which to operate.

Environmental SLAPPs in the UK: threat or opportunity?

Strategic lawsuits against public participation (SLAPPs) brought against the environmental movement in the UK since the 1990s are examined. SLAPPs, a form of Green backlash, have been mobilised across a wide range of policy areas that have seen vigorous campaigning and protest by the movement, including roads, GMOs and, more recently, climate change. SLAPPs are typically regarded as a threat, designed to close down democratic free speech and protest. However, in the UK, there are some notable cases where the environmental movement has been able to use agency to convert what may appear as a legal threat into a positive legal or media opportunity.

Margin squeeze: an above cost predatory pricing approach

We provide a new legal perspective for the antitrust analysis of margin squeeze conducts. Building on recent economic analysis, we explain why margin squeeze conducts should solely be evaluated under adjusted predatory pricing standards. The adjustment corresponds to an increase in the cost benchmark used in the predatory pricing test by including opportunity costs due to missed upstream sales. This can reduce both the risks of false-positives and false-negatives in margin squeeze cases. We justify this approach by explaining why classic arguments against above-cost predatory pricing typically do not hold in vertical structures where margin squeezes take place and by presenting case law evidence supporting this adjustment. Our approach can help to reconcile the divergent US and EU antitrust stances on margin squeeze.

Opportunity agriculture. The next decade: towards a sustainably competitive industry

Report provided and presented at the Oxford Farming Conference

Missed, not missing: phylogenomic evidence for the existence of Avian FoxP3

The Forkhead box transcription factor FoxP3 is pivotal to the development and function of regulatory T cells (Tregs), which make a major contribution to peripheral tolerance. FoxP3 is believed to perform a regulatory role in all the vertebrate species in which it has been detected. The prevailing view is that FoxP3 is absent in birds and that avian Tregs rely on alternative developmental and suppressive pathways. Prompted by the automated annotation of foxp3 in the ground tit (Parus humilis) genome, we have questioned this assumption. Our analysis of all available avian genomes has revealed that the foxp3 locus is missing, incomplete or of poor quality in the relevant genomic assemblies for nearly all avian species. Nevertheless, in two species, the peregrine falcon (Falco peregrinus) and the saker falcon (F. cherrug), there is compelling evidence for the existence of exons showing synteny with foxp3 in the ground tit. A broader phylogenomic analysis has shown that FoxP3 sequences from these three species are similar to crocodilian sequences, the closest living relatives of birds. In both birds and crocodilians, we have also identified a highly proline-enriched region at the N terminus of FoxP3, a region previously identified only in mammals.

Surveillance for adverse events after DTwP/Hib vaccination in Brazil: Sensitivity and factors associated with reporting

We estimated the sensitivity, i.e., the proportion of all cases of adverse events following immunization (AEFIs) reported to the Brazilian passive surveillance for adverse events following immunization (PSAEFI) with the diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b (DTwP/Hib) vaccine, as well as investigating factors associated with AEFIs reporting. During 2003-2004, 8303 AEFIs associated with DTwP-Hib were reported; hypotonic-hyporesponsive episodes (HHEs), fever and convulsions being the most common. Cure without sequel was achieved in 98.4% of the cases. The mean sensitivity of the PSAEFI was 22.3% and 31.6%, respectively, for HHE and convulsions, varying widely among states. Reporting rates correlated positively with the Human Development Index and coverage of adequate prenatal care, correlating negatively with infant mortality rates. Quality of life indicators and the degree of organization of health services are associated with greater PSAEFI sensitivity. In addition to consistently describing the principal AEFIs, PSAEFI showed the DTwP/Hib vaccine to be safe and allayed public fears related to its use. (C) 2010 Elsevier Ltd. All rights reserved.

Agribusiness Opportunity Costs and Environmental Legal Protection: Investigating Trade-Off on Hotspot Preservation in the State of So Paulo, Brazil

Prior to deforestation, So Paulo State had 79,000 km(2) covered by Cerrado (Brazilian savanna) physiognomies, but today less than 8.5% of this biodiversity hotspot remains, mostly in private lands. The global demand for agricultural goods has imposed strong pressure on natural areas, and the economic decisions of agribusiness managers are crucial to the fate of Cerrado domain remaining areas (CDRA) in Brazil. Our aim was to investigate the effectiveness of Brazilian private protected areas policy, and to propose a feasible alternative to promote CDRA protection. This article assessed the main agribusiness opportunity costs for natural areas preservation: the land use profitability and the arable land price. The CDRA percentage and the opportunity costs were estimated for 349 municipal districts of So Paulo State through secondary spatial data and profitability values of 38 main agricultural products. We found that Brazilian private protected areas policy fails to preserve CDRA, although the values of non-compliance fines were higher than average opportunity costs. The scenario with very restrictive laws on private protected areas and historical high interest rates allowed us to conceive a feasible cross compliance proposal to improve environmental and agricultural policies.

Hospital-based Surveillance to Evaluate the Impact of Rotavirus Vaccination in Sao Paulo, Brazil

Background: Brazil implemented routine immunization with the human rotavirus vaccine, Rotarix, in 2006 and vaccination coverage reached 81% in 2008 in Sao Paulo. Our aim was to assess the impact of immunization on the incidence of severe rotavirus acute gastroenteritis (AGE). Methods: We performed a 5-year (2004-2008) prospective surveillance at a sentinel hospital in Sao Paulo, with routine testing for rotavirus in all children less than 5 years of age hospitalized with AGE. Genotypes of positive samples were determined by reverse transcription polymerase chain reaction. Results: During the study, 655 children hospitalized with AGE were enrolled; of whom 169 (25.8%) were positive for rotavirus. In the post-vaccine period, a 59% reduction in the number of hospitalizations of rotavirus AGE and a 42.2% (95% confidence interval [CI], 18.6%-59.0%; P = 0.001) reduction in the proportion of rotavirus-positive results among children younger than 5 years were observed, with the greatest decline among infants (69.2%; 95% CI, 24.7%-87.4%; P = 0.004). Furthermore, the number of all-cause hospitalizations for AGE was reduced by 29% among children aged <5 years. The onset and peak incidences of rotavirus AGE occurred 3 months later in the 2007 and 2008 seasons compared with previous years. Genotype G2 accounted for 15%, 70%, and 100% of all cases identified, respectively, in 2006, 2007, and 2008. Conclusions: After vaccine implementation, a marked decline in rotavirus AGE hospitalizations was demonstrated among children younger than 5 years of age, with the greatest reduction in the age groups targeted for vaccination. The predominance of genotype G2P[4] highlights the need of continued postlicensure surveillance studies.

Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs

Introduction: This study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (MMF). Side effects were investigated. Methods: Sixty-nine patients received one dose of inactivated trivalent influenza vaccine. Antihemagglutinin (HI) antibody response against each strain was measured before and one to six months after vaccination. Results: Geometric mean HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to 13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and 36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively. There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2 protection rates and the seroconversion rate for the H1N1 strain when compared with the use of azathioprine, and subjects transplanted less than 87 months also had inferior antibody response. Adverse events were mild and there were no change on renal function post-vaccination. Conclusion: Renal transplant patients vaccinated against influenza responded with antibody production for in. uenza A virus strains, but not for in. uenza B. Use of MMF and shorter time from transplantation decreased the immune response to the vaccine.

Yellow fever vaccination coverage among children in Brazilian capitals

Brazil recommends universal yellow fever (YF) vaccination for children who reside in or travel to endemic areas. We conducted a household survey to calculate YF vaccine coverage among children 18-30 months of age in 27 capital cities. A total of 9285 children were surveyed in the 15 cities with YF fever universal vaccination; 7290(79%) had documented evidence of YF vaccination by 12 months of age, 7996 (86%) by 18 months of age, and 8479 (91%) prior to the survey. In 12 cities with selective YF vaccination coverage was only 1% by 18 months of age. YF fever vaccination can be improved to reach all children where vaccine is recommended. (C) 2010 Elsevier Ltd. All rights reserved.