@misc{price_windbichler_unckless_sutter_runge_ross_pomiankowski_nuckolls_montchamp-moreau_mideo_et al._2020, title={Resistance to natural and synthetic gene drive systems}, volume={33}, ISSN={["1420-9101"]}, DOI={10.1111/jeb.13693}, abstractNote={Abstract}, number={10}, journal={JOURNAL OF EVOLUTIONARY BIOLOGY}, author={Price, Tom A. R. and Windbichler, Nikolai and Unckless, Robert L. and Sutter, Andreas and Runge, Jan-Niklas and Ross, Perran A. and Pomiankowski, Andrew and Nuckolls, Nicole L. and Montchamp-Moreau, Catherine and Mideo, Nicole and et al.}, year={2020}, month={Oct}, pages={1345–1360} }
 @article{legros_otero_romeo aznar_solari_gould_lloyd_2016, title={Comparison of two detailed models of Aedes aegypti
 population dynamics}, volume={7}, ISSN={2150-8925}, url={http://dx.doi.org/10.1002/ecs2.1515}, DOI={10.1002/ecs2.1515}, abstractNote={Abstract}, number={10}, journal={Ecosphere}, publisher={Wiley}, author={Legros, Mathieu and Otero, Marcelo and Romeo Aznar, Victoria and Solari, Hernan and Gould, Fred and Lloyd, Alun L.}, year={2016}, month={Oct}, pages={e01515} }
 @article{legros_xu_morrison_scott_lloyd_gould_2013, title={Modeling the Dynamics of a Non-Limited and a Self-Limited Gene Drive System in Structured Aedes aegypti Populations}, volume={8}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0083354}, DOI={10.1371/journal.pone.0083354}, abstractNote={Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local vector populations. Because of the potential of these selfish elements to spread through populations, control approaches based on these strategies must be carefully evaluated to ensure a balance between the desirable spread of the refractoriness-conferring genetic cargo and the avoidance of potentially unwanted outcomes such as spread to non-target populations. There is also a need to develop better estimates of the economics of such releases. We present here an evaluation of two such strategies using a biologically realistic mathematical model that simulates the resident Aedes aegypti mosquito population of Iquitos, Peru. One strategy uses the selfish element Medea, a non-limited element that could permanently spread over a large geographic area; the other strategy relies on Killer-Rescue genetic constructs, and has been predicted to have limited spatial and temporal spread. We simulate various operational approaches for deploying these genetic strategies, and quantify the optimal number of released transgenic mosquitoes needed to achieve definitive spread of Medea-linked genes and/or high frequencies of Killer-Rescue-associated elements. We show that for both strategies the most efficient approach for achieving spread of anti-pathogen genes within three years is generally to release adults of both sexes in multiple releases over time. Even though females in these releases should not transmit disease, there could be public concern over such releases, making the less efficient male-only release more practical. This study provides guidelines for operational approaches to population replacement genetic strategies, as well as illustrates the use of detailed spatial models to assist in safe and efficient implementation of such novel genetic strategies.}, number={12}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Legros, Mathieu and Xu, Chonggang and Morrison, Amy and Scott, Thomas W. and Lloyd, Alun L. and Gould, Fred}, editor={Adelman, Zach NEditor}, year={2013}, month={Dec}, pages={e83354} }
 @article{legros_xu_okamoto_scott_morrison_lloyd_gould_2012, title={Assessing the Feasibility of Controlling Aedes aegypti with Transgenic Methods: A Model-Based Evaluation}, volume={7}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0052235}, DOI={10.1371/journal.pone.0052235}, abstractNote={Suppression of dengue and malaria through releases of genetically engineered mosquitoes might soon become feasible. Aedes aegypti mosquitoes carrying a conditionally lethal transgene have recently been used to suppress local vector populations in small-scale field releases. Prior to releases of transgenic insects on a wider scale, however, most regulatory authorities will require additional evidence that suppression will be effective in natural heterogeneous habitats. We use a spatially explicit stochastic model of an Ae. aegypti population in Iquitos, Peru, along with an uncertainty analysis of its predictions, to quantitatively assess the outcome of varied operational approaches for releases of transgenic strains with conditional death of females. We show that population elimination might be an unrealistic objective in heterogeneous populations. We demonstrate that substantial suppression can nonetheless be achieved if releases are deployed in a uniform spatial pattern using strains combining multiple lethal elements, illustrating the importance of detailed spatial models for guiding genetic mosquito control strategies.}, number={12}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Legros, Mathieu and Xu, Chonggang and Okamoto, Kenichi and Scott, Thomas W. and Morrison, Amy C. and Lloyd, Alun L. and Gould, Fred}, editor={Vasilakis, NikosEditor}, year={2012}, month={Dec}, pages={e52235} }
 @article{legros_magori_morrison_xu_scott_lloyd_gould_2011, title={Evaluation of Location-Specific Predictions by a Detailed Simulation Model of Aedes aegypti Populations}, volume={6}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0022701}, DOI={10.1371/journal.pone.0022701}, abstractNote={Background Skeeter Buster is a stochastic, spatially explicit simulation model of Aedes aegypti populations, designed to predict the outcome of vector population control methods. In this study, we apply the model to two specific locations, the cities of Iquitos, Peru, and Buenos Aires, Argentina. These two sites differ in the amount of field data that is available for location-specific customization. By comparing output from Skeeter Buster to field observations in these two cases we evaluate population dynamics predictions by Skeeter Buster with varying degrees of customization. Methodology/Principal Findings Skeeter Buster was customized to the Iquitos location by simulating the layout of houses and the associated distribution of water-holding containers, based on extensive surveys of Ae. aegypti populations and larval habitats that have been conducted in Iquitos for over 10 years. The model is calibrated by adjusting the food input into various types of containers to match their observed pupal productivity in the field. We contrast the output of this customized model to the data collected from the natural population, comparing pupal numbers and spatial distribution of pupae in the population. Our results show that Skeeter Buster replicates specific population dynamics and spatial structure of Ae. aegypti in Iquitos. We then show how Skeeter Buster can be customized for Buenos Aires, where we only had Ae. aegypti abundance data that was averaged across all locations. In the Argentina case Skeeter Buster provides a satisfactory simulation of temporal population dynamics across seasons. Conclusions This model can provide a faithful description of Ae. aegypti populations, through a process of location-specific customization that is contingent on the amount of data available from field collections. We discuss limitations presented by some specific components of the model such as the description of food dynamics and challenges that these limitations bring to model evaluation.}, number={7}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Legros, Mathieu and Magori, Krisztian and Morrison, Amy C. and Xu, Chonggang and Scott, Thomas W. and Lloyd, Alun L. and Gould, Fred}, editor={Ooi, Eng EongEditor}, year={2011}, month={Jul}, pages={e22701} }
 @article{legros_koella_2010, title={Experimental evolution of specialization by a microsporidian parasite}, volume={10}, journal={BMC Evolutionary Biology}, author={Legros, M. and Koella, J. C.}, year={2010} }
 @article{huang_lloyd_legros_gould_2010, title={Gene-drive into insect populations with age and spatial structure: a theoretical assessment}, volume={4}, ISSN={1752-4571}, url={http://dx.doi.org/10.1111/j.1752-4571.2010.00153.x}, DOI={10.1111/j.1752-4571.2010.00153.x}, abstractNote={Abstract}, number={3}, journal={Evolutionary Applications}, publisher={Wiley}, author={Huang, Yunxin and Lloyd, Alun L. and Legros, Mathieu and Gould, Fred}, year={2010}, month={Sep}, pages={415–428} }
 @article{jongsma_gould_legros_yang_loon_dicke_2010, title={Insect oviposition behavior affects the evolution of adaptation to Bt crops: consequences for refuge policies}, volume={24}, ISSN={["0269-7653"]}, DOI={10.1007/s10682-010-9368-3}, abstractNote={The major lepidopteran insect pests of cotton and maize harbor intra-specific variation for behavior determining the selection of host plants for oviposition. Yet, the consequences of behavioral adaptation for fitness have neither been modeled nor monitored for Bt cotton and maize crops, the most widely grown transgenic herbivore-resistant plants. Here, we present a general two-locus heuristic model to examine potential outcomes of natural selection when pest populations initially have low frequencies of alleles for both physiological and behavioral adaptation to Bt crops. We demonstrate that certain ecological conditions allow for the evolution of behavioral choices favoring alternative oviposition hosts that limit the increase in resistance alleles, even when they are phenotypically dominant. These results have implications for current refuge policies, which should be adapted to promote the evolution of certain behavioral choices for alternative oviposition hosts in addition to dilution of physiological resistance alleles. Collection of data on oviposition host preference as a component of monitoring schemes will provide important insights into mechanisms underlying the durability of Bt-transgenic host-plant resistance.}, number={5}, journal={EVOLUTIONARY ECOLOGY}, author={Jongsma, Maarten A. and Gould, Fred and Legros, Mathieu and Yang, Limei and Loon, Joop J. A. and Dicke, Marcel}, year={2010}, month={Sep}, pages={1017–1030} }
 @article{xu_legros_gould_lloyd_2010, title={Understanding Uncertainties in Model-Based Predictions of Aedes aegypti Population Dynamics}, volume={4}, ISSN={1935-2735}, url={http://dx.doi.org/10.1371/journal.pntd.0000830}, DOI={10.1371/journal.pntd.0000830}, abstractNote={Background Aedes aegypti is one of the most important mosquito vectors of human disease. The development of spatial models for Ae. aegypti provides a promising start toward model-guided vector control and risk assessment, but this will only be possible if models make reliable predictions. The reliability of model predictions is affected by specific sources of uncertainty in the model. Methodology/Principal Findings This study quantifies uncertainties in the predicted mosquito population dynamics at the community level (a cluster of 612 houses) and the individual-house level based on Skeeter Buster, a spatial model of Ae. aegypti, for the city of Iquitos, Peru. The study considers two types of uncertainty: 1) uncertainty in the estimates of 67 parameters that describe mosquito biology and life history, and 2) uncertainty due to environmental and demographic stochasticity. Our results show that for pupal density and for female adult density at the community level, respectively, the 95% prediction confidence interval ranges from 1000 to 3000 and from 700 to 5,000 individuals. The two parameters contributing most to the uncertainties in predicted population densities at both individual-house and community levels are the female adult survival rate and a coefficient determining weight loss due to energy used in metabolism at the larval stage (i.e. metabolic weight loss). Compared to parametric uncertainty, stochastic uncertainty is relatively low for population density predictions at the community level (less than 5% of the overall uncertainty) but is substantially higher for predictions at the individual-house level (larger than 40% of the overall uncertainty). Uncertainty in mosquito spatial dispersal has little effect on population density predictions at the community level but is important for the prediction of spatial clustering at the individual-house level. Conclusion/Significance This is the first systematic uncertainty analysis of a detailed Ae. aegypti population dynamics model and provides an approach for identifying those parameters for which more accurate estimates would improve model predictions.}, number={9}, journal={PLoS Neglected Tropical Diseases}, publisher={Public Library of Science (PLoS)}, author={Xu, Chonggang and Legros, Mathieu and Gould, Fred and Lloyd, Alun L.}, editor={O'Neill, ScottEditor}, year={2010}, month={Sep}, pages={e830} }
 @article{legros_lloyd_huang_gould_2009, title={Density-Dependent Intraspecific Competition in the Larval Stage of Aedes aegypti (Diptera: Culicidae): Revisiting the Current Paradigm}, volume={46}, ISSN={["0022-2585"]}, DOI={10.1603/033.046.0301}, abstractNote={ABSTRACT Density-dependent intraspecific competition has been considered an important determinant of the dynamics of larval stages of Aedes aegypti. A model was published in 1984 providing a mathematical description of this density dependence, based on field data, that has since been widely used. This description, however, is based on the strong assumption that all mortality is density-dependent. We re-examine the data without this premise and find a reduced importance of density dependence, as well as a different functional form. Based on these discrepancies, we emphasize that the characterization of density dependence in the larval stages of Ae. aegypti should be based on a more complete dataset, and we use artificially generated data to explore how such additional information could help developing a better description of this density dependence. We review other empirical studies on larval competition, discuss the need for further dedicated studies, and provide a few simple guidelines for the design of such studies.}, number={3}, journal={JOURNAL OF MEDICAL ENTOMOLOGY}, author={Legros, Mathieu and Lloyd, Alun L. and Huang, Yunxin and Gould, Fred}, year={2009}, month={May}, pages={409–419} }
 @article{huang_lloyd_legros_gould_2009, title={Gene-drive in age-structured insect populations}, volume={2}, ISSN={1752-4571 1752-4571}, url={http://dx.doi.org/10.1111/j.1752-4571.2008.00049.x}, DOI={10.1111/j.1752-4571.2008.00049.x}, abstractNote={Abstract}, number={2}, journal={Evolutionary Applications}, publisher={Wiley}, author={Huang, Yunxin and Lloyd, Alun L. and Legros, Mathieu and Gould, Fred}, year={2009}, month={May}, pages={143–159} }
 @article{magori_legros_puente_focks_scott_lloyd_gould_2009, title={Skeeter Buster: A Stochastic, Spatially Explicit Modeling Tool for Studying Aedes aegypti Population Replacement and Population Suppression Strategies}, volume={3}, ISSN={1935-2735}, url={http://dx.doi.org/10.1371/journal.pntd.0000508}, DOI={10.1371/journal.pntd.0000508}, abstractNote={Background Dengue is the most important mosquito-borne viral disease affecting humans. The only prevention measure currently available is the control of its vectors, primarily Aedes aegypti. Recent advances in genetic engineering have opened the possibility for a new range of control strategies based on genetically modified mosquitoes. Assessing the potential efficacy of genetic (and conventional) strategies requires the availability of modeling tools that accurately describe the dynamics and genetics of Ae. aegypti populations. Methodology/Principal findings We describe in this paper a new modeling tool of Ae. aegypti population dynamics and genetics named Skeeter Buster. This model operates at the scale of individual water-filled containers for immature stages and individual properties (houses) for adults. The biology of cohorts of mosquitoes is modeled based on the algorithms used in the non-spatial Container Inhabiting Mosquitoes Simulation Model (CIMSiM). Additional features incorporated into Skeeter Buster include stochasticity, spatial structure and detailed population genetics. We observe that the stochastic modeling of individual containers in Skeeter Buster is associated with a strongly reduced temporal variation in stage-specific population densities. We show that heterogeneity in container composition of individual properties has a major impact on spatial heterogeneity in population density between properties. We detail how adult dispersal reduces this spatial heterogeneity. Finally, we present the predicted genetic structure of the population by calculating FST values and isolation by distance patterns, and examine the effects of adult dispersal and container movement between properties. Conclusions/Significance We demonstrate that the incorporated stochasticity and level of spatial detail have major impacts on the simulated population dynamics, which could potentially impact predictions in terms of control measures. The capacity to describe population genetics confers the ability to model the outcome of genetic control methods. Skeeter Buster is therefore an important tool to model Ae. aegypti populations and the outcome of vector control measures.}, number={9}, journal={PLoS Neglected Tropical Diseases}, publisher={Public Library of Science (PLoS)}, author={Magori, Krisztian and Legros, Mathieu and Puente, Molly E. and Focks, Dana A. and Scott, Thomas W. and Lloyd, Alun L. and Gould, Fred}, editor={Kittayapong, PattamapornEditor}, year={2009}, month={Sep}, pages={e508} }
 @article{gould_huang_legros_lloyd_2008, title={A Killer-Rescue system for self-limiting gene drive of anti-pathogen constructs}, volume={275}, ISSN={["0962-8452"]}, url={https://publons.com/publon/8709314/}, DOI={10.1098/rspb.2008.0846}, abstractNote={A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2 : 1 release (engineered : wild) or after four 1 : 2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.}, number={1653}, journal={PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES}, publisher={The Royal Society}, author={Gould, Fred and Huang, Yunxin and Legros, Mathieu and Lloyd, Alun L.}, year={2008}, month={Dec}, pages={2823–2829} }