Early warning systems in biosecurity; translating risk into action in predictive systems for invasive alien species.

Invasive alien species (IAS) are one of the most severe threats to biodiversity and are the subject of varying degrees of surveillance activity. Predictive early warning systems (EWS), incorporating automated surveillance of relevant dataflows, warning generation and dissemination to decision makers are a key target for developing effective management around IAS, alongside more conventional early detection and horizon scanning technologies. Sophisticated modelling frameworks including the definition of the 'risky' species pool, and pathway analysis at the macro and micro-scale are increasingly available to support decision making and to help prioritise risks from different regions and/or taxa. The main challenges in constructing such frameworks, to be applied to border inspections, are (i) the lack of standardisation and integration of the associated complex digital data environments and (ii) effective integration into the decision making process, ensuring that risk information is disseminated in an actionable way to frontline surveillance staff and other decision makers. To truly achieve early warning in biosecurity requires close collaboration between developers and end-users to ensure that generated warnings are duly considered by decision makers, reflect best practice, scientific understanding and the working environment facing frontline actors. Progress towards this goal will rely on openness and mutual understanding of the role of EWS in IAS risk management, as much as on developments in the underlying technologies for surveillance and modelling procedures.

Quantifying the hidden costs of imperfect detection for early detection surveillance.

The global spread of pathogens poses an increasing threat to health, ecosystems and agriculture worldwide. As early detection of new incursions is key to effective control, new diagnostic tests that can detect pathogen presence shortly after initial infection hold great potential for detection of infection in individual hosts. However, these tests may be too expensive to be implemented at the sampling intensities required for early detection of a new epidemic at the population level. To evaluate the trade-off between earlier and/or more reliable detection and higher deployment costs, we need to consider the impacts of test performance, test cost and pathogen epidemiology. Regarding test performance, the period before new infections can be first detected and the probability of detecting them are of particular importance. We propose a generic framework that can be easily used to evaluate a variety of different detection methods and identify important characteristics of the pathogen and the detection method to consider when planning early detection surveillance. We demonstrate the application of our method using the plant pathogen Phytophthora ramorum in the UK, and find that visual inspec-tion for this pathogen is a more cost-effective strategy for early detection surveillance than an early detection diagnostic test. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'. This theme issue is linked with the earlier issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'.

Extending the durability of cultivar resistance by limiting epidemic growth rates.

Cultivar resistance is an essential part of disease control programmes in many agricultural systems. The use of resistant cultivars applies a selection pressure on pathogen populations for the evolution of virulence, resulting in loss of disease control. Various techniques for the deployment of host resistance genes have been proposed to reduce the selection for virulence, but these are often difficult to apply in practice. We present a general technique to maintain the effectiveness of cultivar resistance. Derived from classical population genetics theory; any factor that reduces the population growth rates of both the virulent and avirulent strains will reduce selection. We model the specific example of fungicide application to reduce the growth rates of virulent and avirulent strains of a pathogen, demonstrating that appropriate use of fungicides reduces selection for virulence, prolonging cultivar resistance. This specific example of chemical control illustrates a general principle for the development of techniques to manage the evolution of virulence by slowing epidemic growth rates.

The Evolution of Fungicide Resistance Resulting from Combinations of Foliar-Acting Systemic Seed Treatments and Foliar-Applied Fungicides: A Modeling Analysis.

For the treatment of foliar diseases of cereals, fungicides may be applied as foliar sprays or systemic seed treatments which are translocated to leaves. Little research has been done to assess the resistance risks associated with foliar-acting systemic seed treatments when used alone or in combination with foliar sprays, even though both types of treatment may share the same mode of action. It is therefore unknown to what extent adding a systemic seed treatment to a foliar spray programme poses an additional resistance risk and whether in the presence of a seed treatment additional resistance management strategies (such as limiting the total number of treatments) are necessary to limit the evolution of fungicide-resistance. A mathematical model was developed to simulate an epidemic and the resistance evolution of Zymoseptoria tritici on winter wheat, which was used to compare different combinations of seed and foliar treatments by calculating the fungicide effective life, i.e. the number of years before effective disease control is lost to resistance. A range of parameterizations for the seed treatment fungicide and different fungicide uptake models were compared. Despite the different parameterizations, the model consistently predicted the same trends in that i) similar levels of efficacy delivered either by a foliar-acting seed treatment, or a foliar application, resulted in broadly similar resistance selection, ii) adding a foliar-acting seed treatment to a foliar spray programme increased resistance selection and usually decreased effective life, and iii) splitting a given total dose-by adding a seed treatment to foliar treatments, but decreasing dose per treatment-gave effective lives that were the same as, or shorter than those given by the spray programme alone. For our chosen plant-pathogen-fungicide system, the model results suggest that to effectively manage selection for fungicide-resistance, foliar acting systemic seed treatments should be included as one of the maximum number of permitted fungicide applications.

Mixtures as a fungicide resistance management tactic.

We have reviewed the experimental and modeling evidence on the use of mixtures of fungicides of differing modes of action as a resistance management tactic. The evidence supports the following conclusions. 1. Adding a mixing partner to a fungicide that is at-risk of resistance (without lowering the dose of the at-risk fungicide) reduces the rate of selection for fungicide resistance. This holds for the use of mixing partner fungicides that have either multi-site or single-site modes of action. The resulting predicted increase in the effective life of the at-risk fungicide can be large enough to be of practical relevance. The more effective the mixing partner (due to inherent activity and/or dose), the larger the reduction in selection and the larger the increase in effective life of the at-risk fungicide. 2. Adding a mixing partner while lowering the dose of the at-risk fungicide reduces the selection for fungicide resistance, without compromising effective disease control. The very few studies existing suggest that the reduction in selection is more sensitive to lowering the dose of the at-risk fungicide than to increasing the dose of the mixing partner. 3. Although there are very few studies, the existing evidence suggests that mixing two at-risk fungicides is also a useful resistance management tactic. The aspects that have received too little attention to draw generic conclusions about the effectiveness of fungicide mixtures as resistance management strategies are as follows: (i) the relative effect of the dose of the two mixing partners on selection for fungicide resistance, (ii) the effect of mixing on the effective life of a fungicide (the time from introduction of the fungicide mode of action to the time point where the fungicide can no longer maintain effective disease control), (iii) polygenically determined resistance, (iv) mixtures of two at-risk fungicides, (v) the emergence phase of resistance evolution and the effects of mixtures during this phase, and (vi) monocyclic diseases and nonfoliar diseases. The lack of studies on these aspects of mixture use of fungicides should be a warning against overinterpreting the findings in this review.

Governing principles can guide fungicide-resistance management tactics.

Fungicide-resistance management would be more effective if principles governing the selection of resistant strains could be determined and validated. Such principles could then be used to predict whether a proposed change to a fungicide application program would decrease selection for resistant strains. In this review, we assess a governing principle that appears to have good predictive power. The principle states that reducing the product of the selection coefficient (defined as the difference between the per capita rate of increase of the sensitive and resistant strains) and the exposure time of the pathogen to the fungicide reduces the selection for resistance. We show that observations as well as modeling studies agree with the predicted effect (i.e., that a specific change to a fungicide program increased or decreased selection or was broadly neutral in its effect on selection) in 84% of the cases and that only 5% of the experimental results contradict predictions. We argue that the selection coefficient and exposure time principle can guide the development of resistance management tactics.

Quantitative resistance can lead to evolutionary changes in traits not targeted by the resistance QTLs.

This paper addresses the general concern in plant pathology that the introduction of quantitative resistance in the landscape can lead to increased pathogenicity. Hereto, we study the hypothetical case of a quantitative trait loci (QTL) acting on pathogen spore production per unit lesion area. To regain its original fitness, the pathogen can break the QTL, restoring its spore production capacity leading to an increased spore production per lesion. Or alternatively, it can increase its lesion size, also leading to an increased spore production per lesion. A data analysis shows that spore production per lesion (affected by the resistance QTL) and lesion size (not targeted by the QTL) are positively correlated traits, suggesting that a change in magnitude of a trait not targeted by the QTL (lesion size) might indirectly affect the targeted trait (spore production per lesion). Secondly, we model the effect of pathogen adaptation towards increased lesion size and analyse its consequences for spore production per lesion. The model calculations show that when the pathogen is unable to overcome the resistance associated QTL, it may compensate for its reduced fitness by indirect selection for increased pathogenicity on both the resistant and susceptible cultivar, but whereby the QTLs remain effective.

Is motor learning mediated by tDCS intensity?

Although tDCS has been shown to improve motor learning, previous studies reported rather small effects. Since physiological effects of tDCS depend on intensity, the present study evaluated this parameter in order to enhance the effect of tDCS on skill acquisition. The effect of different stimulation intensities of anodal tDCS (atDCS) was investigated in a double blind, sham controlled crossover design. In each condition, thirteen healthy subjects were instructed to perform a unimanual motor (sequence) learning task. Our results showed (1) a significant increase in the slope of the learning curve and (2) a significant improvement in motor performance at retention for 1.5 mA atDCS as compared to sham tDCS. No significant differences were reported between 1 mA atDCS and sham tDCS; and between 1.5 mA atDCS and 1 mA atDCS.

Controlling annual weeds in cereals by deploying crop rotation at the landscape scale: Avena sterilis as an example.

Weed control through crop rotation has mainly been studied in a nonspatial context. However, weed seeds are often spread beyond the crop field by a variety of vectors. For weed control to be successful, weed management should thus be evaluated at the landscape level. In this paper we assess how seed dispersal affects the interactions between crop rotation and landscape heterogeneity schemes with regard to weed control. A spatially explicit landscape model was developed to study both short- and long-term weed population dynamics under different management scenarios. We allowed for both two- and three-crop species rotations and three levels of between-field weed seed dispersal. All rotation scenarios and seed dispersal fractions were analyzed for both completely homogeneous landscapes and heterogeneous landscapes in which more than one crop was present. The potential of implementing new weed control methods was also analyzed. The model results suggest that, like crop rotation at the field level, crop rotation implemented at the landscape level has great potential to control weeds, whereby both the number of crop species and the cropping sequence within the crop rotation have significant effects on both the short- and long-term weed population densities. In the absence of seed dispersal, weed populations became extinct when the fraction of each crop in the landscape was randomized. In general, weed seed densities increased in landscapes with increasing similarity in crop proportions, but in these landscapes the level of seed dispersal affected which three-crop species rotation sequence was most efficient at controlling the weed densities. We show that ignoring seed dispersal between fields might lead to the selection of suboptimal tactics and that homogeneous crop field patches that follow a specific crop rotation sequence might be the most sustainable method of weed control. Effective weed control through crop rotation thus requires coordination between farmers with regard to cropping sequences, crop allocation across the landscape, and/ or the fraction of each crop across the landscape.

Involvement of the primary motor cortex in controlling movements executed with the ipsilateral hand differs between left- and right-handers.

Unimanual motor tasks, specifically movements that are complex or require high forces, activate not only the contralateral primary motor cortex (M1) but evoke also ipsilateral M1 activity. This involvement of ipsilateral M1 is asymmetric, such that the left M1 is more involved in motor control with the left hand than the right M1 in movements with the right hand. This suggests that the left hemisphere is specialized for movement control of either hand, although previous experiments tested mostly right-handed participants. In contrast, research on hemispheric asymmetries of ipsilateral M1 involvement in left-handed participants is relatively scarce. In the present study, left- and right-handed participants performed complex unimanual movements, whereas TMS was used to disrupt the activity of ipsilateral M1 in accordance with a "virtual lesion" approach. For right-handed participants, more disruptions were induced when TMS was applied over the dominant (left) M1. For left-handed participants, two subgroups could be distinguished, such that one group showed more disruptions when TMS was applied over the nondominant (left) M1, whereas the other subgroup showed more disruptions when the dominant (right) M1 was stimulated. This indicates that functional asymmetries of M1 involvement during ipsilateral movements are influenced by both hand dominance as well as left hemisphere specialization. We propose that the functional asymmetries in ipsilateral M1 involvement during unimanual movements are primarily attributable to asymmetries in the higher-order areas, although the contribution of transcallosal pathways and ipsilateral projections cannot be completely ruled out.

Excitability of the motor cortex ipsilateral to the moving body side depends on spatio-temporal task complexity and hemispheric specialization.

Unilateral movements are mainly controlled by the contralateral hemisphere, even though the primary motor cortex ipsilateral (M1(ipsi)) to the moving body side can undergo task-related changes of activity as well. Here we used transcranial magnetic stimulation (TMS) to investigate whether representations of the wrist flexor (FCR) and extensor (ECR) in M1(ipsi) would be modulated when unilateral rhythmical wrist movements were executed in isolation or in the context of a simple or difficult hand-foot coordination pattern, and whether this modulation would differ for the left versus right hemisphere. We found that M1(ipsi) facilitation of the resting ECR and FCR mirrored the activation of the moving wrist such that facilitation was higher when the homologous muscle was activated during the cyclical movement. We showed that this ipsilateral facilitation increased significantly when the wrist movements were performed in the context of demanding hand-foot coordination tasks whereas foot movements alone influenced the hand representation of M1(ipsi) only slightly. Our data revealed a clear hemispheric asymmetry such that MEP responses were significantly larger when elicited in the left M1(ipsi) than in the right. In experiment 2, we tested whether the modulations of M1(ipsi) facilitation, caused by performing different coordination tasks with the left versus right body sides, could be explained by changes in short intracortical inhibition (SICI). We found that SICI was increasingly reduced for a complex coordination pattern as compared to rest, but only in the right M1(ipsi). We argue that our results might reflect the stronger involvement of the left versus right hemisphere in performing demanding motor tasks.

Hemispheric asymmetries of the premotor cortex are task specific as revealed by disruptive TMS during bimanual versus unimanual movements.

The premotor cortex (PMC) is functionally lateralized, such that the left PMC is activated for unimanual movements of either hand, whereas the right PMC is particularly active during complex bimanual movements. Here we ask the question whether the high activation of right PMC in the bimanual context reflects either hemispheric specialization or handedness. Left- and right-handed subjects performed a bimanual antiphase tapping task at different frequencies while transcranial magnetic stimulation (TMS) was used to temporarily disrupt left versus right PMC during complex bimanual movements. For both handedness groups, more disruptions were induced when TMS was applied over the motor nondominant PMC than over the motor dominant PMC or when sham-TMS was used. In a second experiment, right-handers performed complex unimanual tapping with either hand, while TMS was applied to the PMC in both hemispheres. The novel result was that the high susceptibility of the motor nondominant PMC was specific to the bimanual context, indicating that hemispheric asymmetries of the PMC depend on the bimanual versus unimanual nature of the motor task. We hypothesize that asymmetries of PMC involvement in bimanual control reflect interhemispheric interactions, whereby the motor nondominant PMC appears to prevent motor cross talk arising from the dominant hemisphere.

The presence of generalist plant pathogens might not explain the long-term coexistence of plant species.

Pathogens have been shown to contribute to the possibility of coexistence of competing plant species by creating ecological distinction between the coexisting species. This coexistence promoting mechanism resembles intra-specific density dependence as found in Lotka-Volterra models. However, plant species adapt in their level of resistance against pathogen infection and this adaptation has been shown to be traded-off by a reduction in growth rate. A model is developed to show that taking into account the possible adaptation of plant species to increase their resistance against pathogen infection by generalist pathogens has consequences for the coexistence of the plant species. The results show that in systems where plants adapt to the pathogen infection, coexistence becomes impossible. The implication of this finding is that plant pathogens might contribute less to the coexistence of plant species than is commonly thought.

Use of the local lymph node assay in assessment of immune function.

The murine local lymph node assay (LLNA) was originally developed as a predictive test method for the identification of chemicals with sensitizing potential. In this study we demonstrated that an adapted LLNA can also be used as an immune function assay by studying the effects of orally administered immunomodulating compounds on the T-cell-dependent immune response induced by the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). C57Bl/6 mice were treated with the immunotoxic compounds cyclosporin A (CsA), bis(tri-n-butyltin)oxide (TBTO) or benzo[a]pyrene, (B[a]P). Subsequently, cell proliferation and interferon-gamma (IFN-gamma) and interleukin (IL)-4 release were determined in the auricular lymph nodes (LNs) after DNCB application on both ears. Immunosuppression induced by CsA, TBTO and B[a]P was clearly detectable in this application of the LLNA. Cytokine release measurements proved valuable to confirm the results of the cell proliferation assay and to obtain an indication of the effect on Th1/Th2 balance. We believe to have demonstrated the applicability of an adapted LLNA as an immune function assay in the mouse.