[PLoS Computational Biology, 14 August 2023]

The use of an antibiotic may lead to the emergence and spread of bacterial strains resistant to this antibiotic. Experimental and theoretical studies have investigated the drug dose that minimizes the risk of resistance evolution over the course of treatment of an individual, showing that the optimal dose will either be the highest or the lowest drug concentration possible to administer; however, no analytical results exist that help decide between these two extremes. To address this gap, we develop a stochastic mathematical model of bacterial dynamics under antibiotic treatment. We explore various scenarios of density regulation (bacterial density affects cell birth or death rates), and antibiotic modes of action (biostatic or biocidal). We derive analytical results for the survival probability of the resistant subpopulation until the end of treatment, the size of the resistant subpopulation at the end of treatment, the carriage time of the resistant subpopulation until it is replaced by a sensitive one after treatment, and we verify these results with stochastic simulations. We find that the scenario of density regulation and the drug mode of action are important determinants of the survival of a resistant subpopulation. Resistant cells survive best when bacterial competition reduces cell birth and under biocidal antibiotics. Compared to an analogous deterministic model, the population size reached by the resistant type is larger and carriage time is slightly reduced by stochastic loss of resistant cells. Moreover, we obtain an analytical prediction of the antibiotic concentration that maximizes the survival of resistant cells, which may help to decide which drug dosage (not) to administer. Our results are amenable to experimental tests and help link the within and between host scales in epidemiological models.

[PNAS, 30 May 2023]

The distribution of fitness effects (DFE) of new mutations is key to our understanding of many evolutionary processes. Theoreticians have developed several models to help understand the patterns seen in empirical DFEs. Many such models reproduce the broad patterns seen in empirical DFEs but these models often rely on structural assumptions that cannot be tested empirically. Here, we investigate how much of the underlying “microscopic” biological processes involved in the mapping of new mutations to fitness can be inferred from “macroscopic” observations of the DFE. We develop a null model by generating random genotype-to-fitness maps and show that the null DFE is that with the largest possible information entropy. We further show that, subject to one simple constraint, this null DFE is a Gompertz distribution. Finally, we illustrate how the predictions of this null DFE match empirically measured DFEs from several datasets, as well as DFEs simulated from Fisher’s geometric model. This suggests that a match between models and empirical data is often not a very strong indication of the mechanisms underlying the mapping of mutation to fitness.

[PLoS Biology, 25 May 2023]

Within many species, and particularly fish, fecundity does not scale with mass linearly; instead, it scales disproportionately. Disproportionate intraspecific size–reproduction relationships contradict most theories of biological growth and present challenges for the management of biological systems. Yet the drivers of reproductive scaling remain obscure and systematic predictors of how and why reproduction scaling varies are lacking. Here, we parameterise life history optimisation model to predict global patterns in the life histories of marine fishes. Our model predict latitudinal trends in life histories: Polar fish should reproduce at a later age and show steeper reproductive scaling than tropical fish. We tested and confirmed these predictions using a new, global dataset of marine fish life histories, demonstrating that the risks of mortality shape maturation and reproductive scaling. Our model also predicts that global warming will profoundly reshape fish life histories, favouring earlier reproduction, smaller body sizes, and lower mass-specific reproductive outputs, with worrying consequences for population persistence.

Citerank: (22) 679703EIDM?The Emerging Infectious Diseases Modelling Initiative (EIDM) – by the Public Health Agency of Canada and NSERC – aims to establish multi-disciplinary network(s) of specialists across the country in modelling infectious diseases to be applied to public needs associated with emerging infectious diseases and pandemics such as COVID-19. [1]7F1CEB7, 679761Caroline ColijnDr. Caroline Colijn works at the interface of mathematics, evolution, infection and public health, and leads the MAGPIE research group. She joined SFU's Mathematics Department in 2018 as a Canada 150 Research Chair in Mathematics for Infection, Evolution and Public Health. She has broad interests in applications of mathematics to questions in evolution and public health, and was a founding member of Imperial College London's Centre for the Mathematics of Precision Healthcare.10019D3ABAB, 679769Christopher CottonChristopher Cotton is a Professor of Economics at Queen’s University where he holds the Jarislowsky-Deutsch Chair in Economic & Financial Policy.10019D3ABAB, 679776David EarnProfessor of Mathematics and Faculty of Science Research Chair in Mathematical Epidemiology at McMaster University.10019D3ABAB, 679797Huaiping ZhuProfessor of mathematics at the Department of Mathematics and Statistics at York University, a York Research Chair (YRC Tier I) in Applied Mathematics, the Director of the Laboratory of Mathematical Parallel Systems at the York University (LAMPS), the Director of the Canadian Centre for Diseases Modelling (CCDM) and the Director of the One Health Modelling Network for Emerging Infections (OMNI-RÉUNIS). 10019D3ABAB, 679806Jane HeffernanJane Heffernan is a professor of infectious disease modelling in the Mathematics & Statistics Department at York University. She is a co-director of the Canadian Centre for Disease Modelling, and she leads national and international networks in mathematical immunology and the modelling of waning and boosting immunity.10019D3ABAB, 679812Jianhong WuProfessor Jianhong Wu is a University Distinguished Research Professor and Senior Canada Research Chair in industrial and applied mathematics at York University. He is also the NSERC Industrial Research Chair in vaccine mathematics, modelling, and manufacturing. 10019D3ABAB, 679826Laura CowenAssociate Professor in the Department of Mathematics and Statistics at the University of Victoria.10019D3ABAB, 679842Mark LewisProfessor Mark Lewis, Kennedy Chair in Mathematical Biology at the University of Victoria and Emeritus Professor at the University of Alberta.10019D3ABAB, 679858Patrick BrownAssociate Professor in the Centre for Global Health Research at St. Michael’s Hospital, and in the Department of Statistical Sciences at the University of Toronto.10019D3ABAB, 679859Patrick LeightonPatrick Leighton is a Professor of Epidemiology and Public Health at the Faculty of Veterinary Medicine, University of Montreal, and an active member of the Epidemiology of Zoonoses and Public Health Research Group (GREZOSP) and the Centre for Public Health Research (CReSP). 10019D3ABAB, 679869Rob DeardonAssociate Professor in the Department of Production Animal Health in the Faculty of Veterinary Medicine and the Department of Mathematics and Statistics in the Faculty of Science at the University of Calgary.10019D3ABAB, 679875Sarah OttoProfessor in Zoology. Theoretical biologist, Canada Research Chair in Theoretical and Experimental Evolution, and Killam Professor at the University of British Columbia.10019D3ABAB, 679893Kumar MurtyProfessor Kumar Murty is in the Department of Mathematics at the University of Toronto. His research fields are Analytic Number Theory, Algebraic Number Theory, Arithmetic Algebraic Geometry and Information Security. He is the founder of the GANITA lab, co-founder of Prata Technologies and PerfectCloud. His interest in mathematics ranges from the pure study of the subject to its applications in data and information security.10019D3ABAB, 686724Ellen RaffertyDr. Ellen Rafferty has a Master of Public Health and a PhD in epidemiology and health economics from the University of Saskatchewan. Dr. Rafferty’s research focuses on the epidemiologic and economic impact of public health policies, such as estimating the cost-effectiveness of immunization programs. She is interested in the incorporation of economics into immunization decision-making, and to that aim has worked with a variety of provincial and national organizations.10019D3ABAB, 701020CANMOD – PublicationsPublications by CANMOD Members144B5ACA0, 701037MfPH – Publications144B5ACA0, 701071OSN – Publications144B5ACA0, 701222OMNI – Publications144B5ACA0, 704045Covid-19859FDEF6, 714608Charting a FutureCharting a Future for Emerging Infectious Disease Modelling in Canada – April 2023 [1] 2794CAE1, 715387SMMEID – Publications144B5ACA0

We propose an independent institute of emerging infectious disease modellers and policy experts, with an academic core, capable of renewing itself as needed. This institute will combine science and knowledge translation to inform decision-makers at all levels of government and ensure the highest level of preparedness (and readiness) for the next public health emergency. The Public Health Modelling Institute will provide cost-effective, science-based modelling for public policymakers in an easily visualizable, integrated framework, which can respond in an agile manner to changing needs, questions, and data. To be effective, the Institute must link to modelling groups within government, who are best able to pose questions and convey results for use by public policymakers.