@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{xu_gertner_2011, title={Reliability of global sensitivity indices}, volume={81}, number={12}, journal={Journal of Statistical Computation and Simulation}, author={Xu, C. G. and Gertner, G. Z.}, year={2011}, pages={1939–1969} }
 @article{xu_gertner_2011, title={Understanding and comparisons of different sampling approaches for the Fourier Amplitudes Sensitivity Test (FAST)}, volume={55}, number={1}, journal={Computational Statistics & Data Analysis}, author={Xu, C. G. and Gertner, G.}, year={2011}, pages={184–198} }
 @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} }