EFSA's OpenFoodTox: An open source toxicological database on chemicals in food and feed and its future developments.

Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances in >2000 Scientific Opinions, Statements and Conclusions through the work of its Scientific Panels, Units and Scientific Committee. OpenFoodTox is an open source toxicological database, available both for download and data visualisation which provides data for all substances evaluated by EFSA including substance characterisation, links to EFSA's outputs, applicable legislations regulations, and a summary of hazard identification and hazard characterisation data for human health, animal health and ecological assessments. The database has been structured using OECD harmonised templates for reporting chemical test summaries (OHTs) to facilitate data sharing with stakeholders with an interest in chemical risk assessment, such as sister agencies, international scientific advisory bodies, and others. This manuscript provides a description of OpenFoodTox including data model, content and tools to download and search the database. Examples of applications of OpenFoodTox in chemical risk assessment are discussed including new quantitative structure-activity relationship (QSAR) models, integration into tools (OECD QSAR Toolbox and AMBIT-2.0), assessment of environmental footprints and testing of threshold of toxicological concern (TTC) values for food related compounds. Finally, future developments for OpenFoodTox 2.0 include the integration of new properties, such as physico-chemical properties, exposure data, toxicokinetic information; and the future integration within in silico modelling platforms such as QSAR models and physiologically-based kinetic models. Such structured in vivo, in vitro and in silico hazard data provide different lines of evidence which can be assembled, weighed and integrated using harmonised Weight of Evidence approaches to support the use of New Approach Methodologies (NAMs) in chemical risk assessment and the reduction of animal testing.

Short communication: Identifying key parameters for modelling the impacts of livestock health conditions on greenhouse gas emissions.

Improved animal health can reduce greenhouse gas (GHG) emissions intensity in livestock systems while increasing productivity. Integrated modelling of disease impacts on farm-scale emissions is important in identifying effective health strategies to reduce emissions. However, it requires that modellers understand the pathways linking animal health to emissions and how these might be incorporated into models. A key barrier to meeting this need has been the lack of a framework to facilitate effective exchange of knowledge and data between animal health experts and emissions modellers. Here, these two communities engaged in workshops, online exchanges and a survey to i) identify a comprehensive list of disease-related model parameters and ii) test its application to evaluating models. Fifty-six parameters were identified and proved effective in assessing the potential of farm-scale models to characterise livestock disease impacts on GHG emissions. Easy wins for the emissions models surveyed include characterising disease impacts related to feeding.

Early intensification of backyard poultry systems in the tropics: a case study.

Poultry production is an important way of enhancing the livelihoods of rural populations, especially in low- and middle-income countries (LMICs). As poultry production in LMICs remains dominated by backyard systems with low inputs and low outputs, considerable yield gaps exist. Intensification can increase poultry productivity, production and income. This process is relatively recent in LMICs compared to high-income countries. The management practices and the constraints faced by smallholders trying to scale-up their production, in the early stages of intensification, are poorly understood and described. We thus investigated the features of the small-scale commercial chicken sector in a rural area distant from major production centres. We surveyed 111 commercial chicken farms in Kenya in 2016. We targeted farms that sell the majority of their production, owning at least 50 chickens, partly or wholly confined and provided with feeds. We developed a typology of semi-intensive farms. Farms were found mainly to raise dual-purpose chickens of local and improved breeds, in association with crops and were not specialized in any single product or market. We identified four types of semi-intensive farms that were characterized based on two groups of variables related to intensification and accessibility: (i) remote, small-scale old farms, with small flocks, growing a lot of their own feed; (ii) medium-scale, old farms with a larger flock and well located in relation to markets and (iii) large-scale recently established farms, with large flocks, (iii-a) well located and buying chicks from third-party providers and (iii-b) remotely located and hatching their own chicks. The semi-intensive farms we surveyed were highly heterogeneous in terms of size, age, accessibility, management, opportunities and challenges. Farm location affects market access and influences the opportunities available to farmers, resulting in further diversity in farm profiles. The future of these semi-intensive farms could be compromised by several factors, including the competition with large-scale intensive farmers and with importations. Our study suggests that intensification trajectories in rural areas of LMICs are potentially complex, diverse and non-linear. A better understanding of intensification trajectories should, however, be based on longitudinal data. This could, in turn, help designing interventions to support small-scale farmers.

Fine-scale species distribution modelling and genotyping by sequencing to examine hybridisation between two narrow endemic plant species.

Hybridization has an important and often positive role in plant evolution. However, it can also have negative consequences for species. Two closely related species of Ornduffia are endemic to the Porongurup Range in the South West Australian Global Biodiversity Hotspot. The rare Ornduffia calthifolia is found exclusively on the summits, while O. marchantii is more widely dispersed across a greater range of elevation and is not considered threatened. Hybridisation in suitable overlapping habitat has been suspected between them for decades. Here we combine genotyping by sequencing to verify hybridisation genetically, and fine scale (2 m resolution) species distribution modelling (SDM) to test if hybrids occur in suitable intersecting habitat. From a study area of c. 4700 ha, SDM identified c. 275 ha and c. 322 ha of suitable habitat for O. calthifolia and O. marchantii, respectively. We identified range overlap between species of c. 59 ha), which enveloped 32 individuals confirmed to be hybrids. While the hybrids were at the margin of suitable habitat for O. marchantii, their preference for elevated habitat was closer to the more narrowly distributed O. calthifolia. The combination of genetic data and fine scale spatial modelling approaches enabled a better understanding of hybridisation among taxa of conservation significance. However, the level to which hybrid proliferation and competition for habitat presents as a threat to O. calthifolia is currently unknown and requires priority in conservation management given the threats from global warming and disturbance by tourism.

Deterministic processes structure bacterial genetic communities across an urban landscape.

Land-use change is predicted to act as a driver of zoonotic disease emergence through human exposure to novel microbial diversity, but evidence for the effects of environmental change on microbial communities in vertebrates is lacking. We sample wild birds at 99 wildlife-livestock-human interfaces across Nairobi, Kenya, and use whole genome sequencing to characterise bacterial genes known to be carried on mobile genetic elements (MGEs) within avian-borne Escherichia coli (n = 241). By modelling the diversity of bacterial genes encoding virulence and antimicrobial resistance (AMR) against ecological and anthropogenic forms of urban environmental change, we demonstrate that communities of avian-borne bacterial genes are shaped by the assemblage of co-existing avian, livestock and human communities, and the habitat within which they exist. In showing that non-random processes structure bacterial genetic communities in urban wildlife, these findings suggest that it should be possible to forecast the effects of urban land-use change on microbial diversity.

Review: Animal health and sustainable global livestock systems.

This paper discusses the sustainability of livestock systems, emphasising bidirectional relations with animal health. We review conventional and contrarian thinking on sustainability and argue that in the most common approaches to understanding sustainability, health aspects have been under-examined. Literature review reveals deep concerns over the sustainability of livestock systems; we recognise that interventions are required to shift to more sustainable trajectories, and explore approaches to prioritising in different systems, focusing on interventions that lead to better health. A previously proposed three-tiered categorisation of 'hot spots', 'cold spots' and 'worried well' animal health trajectories provides a mental model that, by taking into consideration the different animal health status, animal health risks, service response needs and key drivers in each system, can help identify and implement interventions. Combining sustainability concepts with animal health trajectories allows for a richer analysis, and we apply this to three case studies drawn from North Africa and the Middle East; Bangladesh; and the Eastern Cape of South Africa. We conclude that the quest for sustainability of livestock production systems from the perspective of human and animal health is elusive and difficult to reconcile with the massive anticipated growth in demand for livestock products, mainly in low- and middle-income countries, as well as the aspirations of poor livestock keepers for better lives. Nevertheless, improving the health of livestock can contribute to health sustainability both through reducing negative health impacts of livestock and increasing efficiency of production. However, the choice of the most appropriate options must be under-pinned by an understanding of agro-ecology, economy and values. We argue that a new pillar of One Health should be added to the three traditional sustainability pillars of economics, society and environment when addressing livestock systems.

The greenhouse gas abatement potential of productivity improving measures applied to cattle systems in a developing region.

Developing countries are experiencing an increase in total demand for livestock commodities, as populations and per capita demands increase. Increased production is therefore required to meet this demand and maintain food security. Production increases will lead to proportionate increases in greenhouse gas (GHG) emissions unless offset by reductions in the emissions intensity (Ei) (i.e. the amount of GHG emitted per kg of commodity produced) of livestock production. It is therefore important to identify measures that can increase production whilst reducing Ei cost-effectively. This paper seeks to do this for smallholder agro-pastoral cattle systems in Senegal; ranging from low input to semi-intensified, they are representative of a large proportion of the national cattle production. Specifically, it identifies a shortlist of mitigation measures with potential for application to the various herd systems and estimates their GHG emissions abatement potential (using the Global Livestock Environmental Assessment Model) and cost-effectiveness. Limitations and future requirements are identified and discussed. This paper demonstrates that the Ei of meat and milk from livestock systems in a developing region can be reduced through measures that would also benefit food security, many of which are likely to be cost-beneficial. The ability to make such quantification can assist future sustainable development efforts.

A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based chemical sensor.

Selective, robust and cost-effective chemical sensors for detecting small volatile-organic compounds (VOCs) have widespread applications in industry, healthcare and environmental monitoring. Here we design a Pt(II) pincer-type material with selective absorptive and emissive responses to methanol and water. The yellow anhydrous form converts reversibly on a subsecond timescale to a red hydrate in the presence of parts-per-thousand levels of atmospheric water vapour. Exposure to methanol induces a similarly-rapid and reversible colour change to a blue methanol solvate. Stable smart coatings on glass demonstrate robust switching over 104 cycles, and flexible microporous polymer membranes incorporating microcrystals of the complex show identical vapochromic behaviour. The rapid vapochromic response can be rationalised from the crystal structure, and in combination with quantum-chemical modelling, we provide a complete microscopic picture of the switching mechanism. We discuss how this multiscale design approach can be used to obtain new compounds with tailored VOC selectivity and spectral responses.

Mapping the benefit-cost ratios of interventions against bovine trypanosomosis in Eastern Africa.

This study builds upon earlier work mapping the potential benefits from bovine trypanosomosis control and analysing the costs of different approaches. Updated costs were derived for five intervention techniques: trypanocides, targets, insecticide-treated cattle, aerial spraying and the release of sterile males. Two strategies were considered: continuous control and elimination. For mapping the costs, cattle densities, environmental constraints, and the presence of savannah or riverine tsetse species were taken into account. These were combined with maps of potential benefits to produce maps of benefit-cost ratios. The results illustrate a diverse picture, and they clearly indicate that no single technique or strategy is universally profitable. For control using trypanocide prophylaxis, returns are modest, even without accounting for the risk of drug resistance but, in areas of low cattle densities, this is the only approach that yields a positive return. Where cattle densities are sufficient to support it, the use of insecticide-treated cattle stands out as the most consistently profitable technique, widely achieving benefit-cost ratios above 5. In parts of the high-potential areas such as the mixed farming, high-oxen-use zones of western Ethiopia, the fertile crescent north of Lake Victoria and the dairy production areas in western and central Kenya, all tsetse control strategies achieve benefit-cost ratios from 2 to over 15, and for elimination strategies, ratios from 5 to over 20. By contrast, in some areas, notably where cattle densities are below 20per km(2), the costs of interventions against tsetse match or even outweigh the benefits, especially for control scenarios using aerial spraying or the deployment of targets where both savannah and riverine flies are present. If the burden of human African trypanosomosis were factored in, the benefit-cost ratios of some of the low-return areas would be considerably increased. Comparatively, elimination strategies give rise to higher benefit-cost ratios than do those for continuous control. However, the costs calculated for elimination assume problem-free, large scale operations, and they rest on the outputs of entomological models that are difficult to validate in the field. Experience indicates that the conditions underlying successful and sustained elimination campaigns are seldom met. By choosing the most appropriate thresholds for benefit-cost ratios, decision-makers and planners can use the maps to define strategies, assist in prioritising areas for intervention, and help choose among intervention techniques and approaches. The methodology would have wider applicability in analysing other disease constraints with a strong spatial component.

Mapping the economic benefits to livestock keepers from intervening against bovine trypanosomosis in Eastern Africa.

Endemic animal diseases such as tsetse-transmitted trypanosomosis are a constant drain on the financial resources of African livestock keepers and on the productivity of their livestock. Knowing where the potential benefits of removing animal trypanosomosis are distributed geographically would provide crucial evidence for prioritising and targeting cost-effective interventions as well as a powerful tool for advocacy. To this end, a study was conducted on six tsetse-infested countries in Eastern Africa: Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda. First, a map of cattle production systems was generated, with particular attention to the presence of draught and dairy animals. Second, herd models for each production system were developed for two scenarios: with or without trypanosomosis. The herd models were based on publications and reports on cattle productivity (fertility, mortality, yields, sales), from which the income from, and growth of cattle populations were estimated over a twenty-year period. Third, a step-wise spatial expansion model was used to estimate how cattle populations might migrate to new areas when maximum stocking rates are exceeded. Last, differences in income between the two scenarios were mapped, thus providing a measure of the maximum benefits that could be obtained from intervening against tsetse and trypanosomosis. For this information to be readily mappable, benefits were calculated per bovine and converted to US$ per square kilometre. Results indicate that the potential benefits from dealing with trypanosomosis in Eastern Africa are both very high and geographically highly variable. The estimated total maximum benefit to livestock keepers for the whole of the study area amounts to nearly US$ 2.5 billion, discounted at 10% over twenty years--an average of approximately US$ 3300 per square kilometre of tsetse-infested area--but with great regional variation from less than US$ 500 per square kilometre to well over US$ 10,000. The greatest potential benefits accrue to Ethiopia, because of its very high livestock densities and the importance of animal traction, but also to parts of Kenya and Uganda. In general, the highest benefit levels occur on the fringes of the tsetse infestations. The implications of the models' assumptions and generalisations are discussed.

Estimating the costs of tsetse control options: an example for Uganda.

Decision-making and financial planning for tsetse control is complex, with a particularly wide range of choices to be made on location, timing, strategy and methods. This paper presents full cost estimates for eliminating or continuously controlling tsetse in a hypothetical area of 10,000km(2) located in south-eastern Uganda. Four tsetse control techniques were analysed: (i) artificial baits (insecticide-treated traps/targets), (ii) insecticide-treated cattle (ITC), (iii) aerial spraying using the sequential aerosol technique (SAT) and (iv) the addition of the sterile insect technique (SIT) to the insecticide-based methods (i-iii). For the creation of fly-free zones and using a 10% discount rate, the field costs per km(2) came to US$283 for traps (4 traps per km(2)), US$30 for ITC (5 treated cattle per km(2) using restricted application), US$380 for SAT and US$758 for adding SIT. The inclusion of entomological and other preliminary studies plus administrative overheads adds substantially to the overall cost, so that the total costs become US$482 for traps, US$220 for ITC, US$552 for SAT and US$993 - 1365 if SIT is added following suppression using another method. These basic costs would apply to trouble-free operations dealing with isolated tsetse populations. Estimates were also made for non-isolated populations, allowing for a barrier covering 10% of the intervention area, maintained for 3 years. Where traps were used as a barrier, the total cost of elimination increased by between 29% and 57% and for ITC barriers the increase was between 12% and 30%. In the case of continuous tsetse control operations, costs were estimated over a 20-year period and discounted at 10%. Total costs per km(2) came to US$368 for ITC, US$2114 for traps, all deployed continuously, and US$2442 for SAT applied at 3-year intervals. The lower costs compared favourably with the regular treatment of cattle with prophylactic trypanocides (US$3862 per km(2) assuming four doses per annum at 45 cattle per km(2)). Throughout the study, sensitivity analyses were conducted to explore the impact on cost estimates of different densities of ITC and traps, costs of baseline studies and discount rates. The present analysis highlights the cost differentials between the different intervention techniques, whilst attesting to the significant progress made over the years in reducing field costs. Results indicate that continuous control activities can be cost-effective in reducing tsetse populations, especially where the creation of fly-free zones is challenging and reinvasion pressure high.

The cold European winter of 2005-2006 assisted the spread and persistence of H5N1 influenza virus in wild birds.

In January 2006, a major cold spell affected Europe, coinciding with an increase of H5N1 influenza virus detected in wild birds, mostly dead mute swans, starting along the River Danube and the Mediterranean coast line. Subsequently H5N1 detections in wild birds were concentrated in central and western parts of Europe, reaching a peak in mid February. We tested the hypothesis that the geographic distribution of these H5N1 infections was modulated by the long-term wintering line, the 0 °C isotherm marking the limit beyond which areas are largely unsuitable for wintering waterfowl. Given the particularly cold 2005-2006 European winter, we also considered the satellite-derived contemporary frost conditions. This brought us to select the long-term maximum rather than the mean January 0 °C isotherm as the best approximation for the 2005-2006 wintering line. Our analysis shows that H5N1 detection sites were closer to the wintering line than would be expected by chance, even when the geographic distribution of water bird wintering sites was accounted for. We argue that partial frost conditions in water bodies are conducive to bird congregation, and this may have enhanced H5N1 transmission and local spread. Because the environmental virus load also would build up in these hot spots, H5N1 virus may have readily persisted during the spring, at least in cooler areas. We conclude that H5N1 introduction, spread, and persistence in Europe may have been enhanced by the cold 2005-2006 winter.

Antiangiogenic agents: studies on fumagillin and curcumin analogs.

Cancer is a general term used to describe many disease states, each of which are characterized by abnormal cell proliferation. The causes which bring about this abnormal cellular behavior are specific to each type of cancer. The success of tumor-targeted therapy is limited by this diversity. One common denominator for all types of cancer is the requirement of a suitable blood supply. Therefore, tumor vasculature has emerged as a potential target for therapeutic intervention. New blood vessel growth from preexisting vasculature stimulated by biochemical signals is termed angiogenesis. Tumor masses require a constant supply of oxygen and nutrients, and a means of efficient waste removal to ensure sustained development. Diffusion from nearby capillaries can supply adequate nutrition for tumors less than 2 mm in size, but for continued growth the tumors must develop their own blood supply. Alteration of the delicate balance of angiogenic stimulating factors and angiogenic inhibitors results in the phenotypic change from quiescence to active endothelial proliferation. To date, this angiogenic switch is not completely understood. The goal of antiangiogenic therapy is to interfere with these mechanisms and prevent tumor cells from developing a viable blood supply. Fumagillin is a naturally occurring antifungal agent. Curcumin is a natural product isolated from the spice turmeric. Both compounds have been shown to have antiangiogenic properties in vitro and in vivo. This paper describes efforts to design and prepare fumagillin and curcumin analogs and evaluate their corresponding antiangiogenic activities.

The effect of inoculum size and sublethal injury on the ability of Listeria monocytogenes to initiate growth under suboptimal conditions.

AIMS: To investigate the effect of inoculum size and physiological state on the ability of Listeria monocytogenes cells to initiate growth under suboptimal conditions of salt concentration and pH. METHODS AND RESULTS: Cell suspensions were serially diluted in media of different salt concentration or pH and replicate inocula distributed into 96-well microplates. The proportion of wells showing growth at each dilution level was determined after incubation for 6 weeks for each set of conditions. Growth occurred from single cells up to a concentration of 1.2 mol l-1 NaCl; above this threshold, the inoculum size needed to initiate growth became progressively larger. A similar effect was seen with decreasing pH but only very close to the growth/no growth boundary. The threshold for inoculum-dependent growth was lower in exponential phase cells than in stationary phase ones and sublethal injury greatly decreased the probability of growth from small inocula. CONCLUSIONS: The growth/no growth boundary for L. monocytogenes is not an absolute cut-off point but represents a region where the probability of growth rapidly decreases as conditions become more extreme. We interpret the requirement for a critical inoculum size for growth as being due to death of a proportion of cells in the inoculum rather than to co-operative population effects. SIGNIFICANCE AND IMPACT OF THE STUDY: Physiological heterogeneity within the cell population and inoculum size will affect the risk of L. monocytogenes growing in food.

A cardinal model to describe the effect of water activity on the growth of moulds.

A simple model was proposed to describe the effect of water activity (Aw) on the radial growth rate of moulds. This model is deduced from the cardinal model family proposed by Rosso in 1995, which is only defined from cardinal values of environmental factors (minimum, optimum and maximum values), the growth rate observed at the optimal value of the environmental factors, and n, a shape parameter. For Aw, a simple form of cardinal model is proposed. This form is obtained for n = 2 and Aw(max) = 1.0 (pure water). The final model is so defined from only three parameters: Aw(min), Aw(opt), and optimal radial growth rate (RGR(opt)). This model was successfully fitted on a data set of Aspergillus flavus, Aspergillus nomius, Aspergillus oryzae, Aspergillus parasiticus, Aspergillus candidus, Aspergillus sydowii, Eurotium amstelodami, Eurotium chevalieri, and Xeromyces bisporus. The same quality of fit was obtained for different solutes used to control the Aw (NaCl, glucose/fructose mixture, glycerol), and at different pH values. From this model and using cardinal values extracted from the literature, theoretical evolutions of the RGR of enicillium roqueforti, and Paecilomyces variotii, were proposed and superimposed on data published in the literature. The results showed a good concordance between the predicted and the observed values for these species. The use of this model in Predictive Microbiology is discussed.

The effect of inoculum size on the lag phase of Listeria monocytogenes.

The effect of inoculum size on population lag times of Listeria monocytogenes was investigated using the Bioscreen automated microtitre plate incubator and reader. Under optimum conditions, lag times were little affected by inoculum size and there was little variation between replicate inocula even at very low cell numbers. However, in media containing inhibitory concentrations of NaCl, both the mean lag time and variation between replicate inocula increased as the inoculum size became smaller. The variation in lag time of cells within a population was investigated in more detail by measuring the distribution of detection times from 64 replicate inocula containing only one or two cells capable of initiating growth. The variance of the lag time distribution increased with increasing salt concentration and was greater in exponential than in stationary phase inocula. The number of cells required to initiate growth increased from one cell under optimum conditions to 10(5) cells in medium with 1.8 M NaCl. The addition of spent medium from a stationary phase culture reduced the variance and decreased lag times. The ability to initiate growth under severe salt stress appears to depend on the presence of a resistant sub-fraction of the population, although high cell densities assist adaptation of those resistant cells to the unfavourable growth conditions by some unspecified medium conditioning effect. These results are relevant to the prediction of lag times and probability of growth from low numbers of stressed cells in food.

Spatial statistics and geographical information systems in epidemiology and public health.

This chapter surveys the principles behind spatial statistics and geographic information systems (GIS), and their application to epidemiology and public health. Like the other introductory chapters, it is aimed mainly to facilitate understanding in the chapters specific to certain diseases that follow, and to provide a short introduction to the field. A brief overview of spatial statistics and GIS is provided in the introduction. The sections that follow explore the ways in which we can map the distribution of disease, ways in which we can look for spatial patterns in the distribution of disease, and ways in which we can apply spatial statistics and GIS to the problem of identifying the causal factors of observed patterns. In the last section I discuss some of the ways in which these techniques have been applied to assist decision making for disease intervention, and conclude by discussing future developments in the field, and some of the issues surrounding the integration of spatial statistics and GIS.