Cost of resistance: an unreasonably expensive concept

The concept of “cost of resistance” has been very important for decades, for fundamental reasons (theory of adaptation), with a wide range of applications for the genetics and genomics of resistance: resistance to antibiotics, insecticide, herbicide, fungicides; resistance to chemotherapy in cancer research; coevolution between all kinds of parasites and their hosts. This paper reviews this history, including latest developments, shows the interest of the idea but also challenges the usefulness and limits of this widely used concept, based on the most recent development of adaptation theory. It explains how the concept can be flawed and how this can impede research efforts in the field of resistance at large, including all applied aspects. In particular, it would be clearer to simply measure the fitness effects of mutations across environments and to better distinguish those effects from ‘pleiotropic effects’ of those mutations. Overall, we show how to correct the concept, and how this correction helps to better understand the wealth of data that has accumulated in recent years. The main points are: 1. The concept of «cost of resistance» needs to be carefully used, to avoid misconceptions, false paradox and flawed applications. The recent developments in adaptation theory are useful to clarify this. 2. “Cost of resistance” and pleiotropy have to be distinguished. More than one trait is required to discuss pleiotropy. Resistance evolution must at least involve the modification of one trait. If there is an irreducible trade-off on that trait between environments with and without drug, it creates a fitness effect that is not due to pleiotropy. Pleiotropic effects can, but need not, occur in addition. 3. “Cost of resistance” must depend on the pair of environments considered with and without drug. Hence, there are as many measures of cost as there are environments without drug. If the focal genotype is not well adapted to one focal environment, it is relatively easy to observe “negative” costs of resistance. There is nothing surprising about this, and it does not indicate an absence of trade-off. 4. Environments with drug can differ according to the dose. It may be more informative to measure the possible trade-offs among all doses than to focus exclusively on the fitness contrast between the presence and the absence of drug.

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Robust estimation of vertical symmetry axis models via joint migration inversion: Including multiples in anisotropic parameter estimation

Geophysics ◽

10.1190/geo2017-0856.1 ◽

2019 ◽

Vol 84 (1) ◽

pp. C57-C74 ◽

Cited By ~ 4

Author(s):

Abdulrahman A. Alshuhail ◽

Dirk J. Verschuur

Keyword(s):

Symmetry Axis ◽

Transverse Isotropy ◽

Half Cycle ◽

Anisotropic Parameter ◽

Data Set ◽

Trade Off ◽

Trade Offs ◽

Highly Nonlinear ◽

Wide Range ◽

Internal Multiples

Because the earth is predominately anisotropic, the anisotropy of the medium needs to be included in seismic imaging to avoid mispositioning of reflectors and unfocused images. Deriving accurate anisotropic velocities from the seismic reflection measurements is a highly nonlinear and ambiguous process. To mitigate the nonlinearity and trade-offs between parameters, we have included anisotropy in the so-called joint migration inversion (JMI) method, in which we limit ourselves to the case of transverse isotropy with a vertical symmetry axis. The JMI method is based on strictly separating the scattering effects in the data from the propagation effects. The scattering information is encoded in the reflectivity operators, whereas the phase information is encoded in the propagation operators. This strict separation enables the method to be more robust, in that it can appropriately handle a wide range of starting models, even when the differences in traveltimes are more than a half cycle away. The method also uses internal multiples in estimating reflectivities and anisotropic velocities. Including internal multiples in inversion not only reduces the crosstalk in the final image, but it can also reduce the trade-off between the anisotropic parameters because internal multiples usually have more of an imprint of the subsurface parameters compared with primaries. The inverse problem is parameterized in terms of a reflectivity, vertical velocity, horizontal velocity, and a fixed [Formula: see text] value. The method is demonstrated on several synthetic models and a marine data set from the North Sea. Our results indicate that using JMI for anisotropic inversion makes the inversion robust in terms of using highly erroneous initial models. Moreover, internal multiples can contain valuable information on the subsurface parameters, which can help to reduce the trade-off between anisotropic parameters in inversion.

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Cost–benefit and water resources policy: a survey

Water Policy ◽

10.2166/wp.2011.021 ◽

2011 ◽

Vol 14 (2) ◽

pp. 250-280 ◽

Cited By ~ 17

Author(s):

Frank A. Ward

Keyword(s):

Water Policy ◽

Cost Benefit Analysis ◽

Cost Benefit ◽

Benefit Analysis ◽

Trade Offs ◽

Wide Range ◽

Recent Developments ◽

The Difference ◽

Policy Cost ◽

The Right

This paper reviews recent developments in cost–benefit analysis for water policy researchers who wish to understand the applications of economic principles to inform emerging water policy debates. The cost–benefit framework can provide a comparison of total economic gains and losses resulting from a proposed water policy. Cost–benefit analysis can provide decision-makers with a comparison of the impacts of two or more water policy options using methods that are grounded in time-tested economic principles. Economic efficiency, measured as the difference between added benefits and added costs, can inform water managers and the public of the economic impacts of water programs to address peace, development, health, the environment, climate and poverty. Faced by limited resources, cost–benefit analysis can inform policy choices by summarizing trade-offs involved in designing, applying, or reviewing a wide range of water programs. The data required to conduct a cost–benefit analysis are often poor but the steps needed to carry out that analysis require posing the right questions.

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Heterotrophic eukaryotes show a slow-fast continuum, not a gleaner–exploiter trade-off

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2008370117 ◽

2020 ◽

Vol 117 (40) ◽

pp. 24893-24899

Author(s):

Thomas Kiørboe ◽

Mridul K. Thomas

Keyword(s):

Positive Relationship ◽

Ingestion Rate ◽

Negative Relationship ◽

Large Mammals ◽

Ecological Processes ◽

Trade Off ◽

Trade Offs ◽

Wide Range ◽

Fast Gradient ◽

Using Data

Gleaners and exploiters (opportunists) are organisms adapted to feeding in nutritionally poor and rich environments, respectively. A trade-off between these two strategies—a negative relationship between the rate at which organisms can acquire food and ingest it—is a critical assumption in many ecological models. Here, we evaluate evidence for this trade-off across a wide range of heterotrophic eukaryotes from unicellular nanoflagellates to large mammals belonging to both aquatic and terrestrial realms. Using data on the resource acquisition and ingestion rates in >500 species, we find no evidence of a trade-off across species. Instead, there is a positive relationship between maximum clearance rate and maximum ingestion rate. The positive relationship is not a result of lumping together diverse taxa; it holds within all subgroups of organisms we examined as well. Correcting for differences in body mass weakens but does not reverse the positive relationship, so this is not an artifact of size scaling either. Instead, this positive relationship represents a slow–fast gradient in the “pace of life” that overrides the expected gleaner–exploiter trade-off. Other trade-offs must therefore shape ecological processes, and investigating them may provide deeper insights into coexistence, competitive dynamics, and biodiversity patterns in nature. A plausible target for study is the well-documented trade-off between growth rate and predation avoidance, which can also drive the slow–fast gradient we observe here.

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An integrated methodology to assess the operational and environmental performance of a conceptual regenerative helicopter

The Aeronautical Journal ◽

10.1017/s0001924000010253 ◽

2015 ◽

Vol 119 (1211) ◽

pp. 67-90 ◽

Cited By ~ 1

Author(s):

F. Ali ◽

I. Goulos ◽

V. Pachidis

Keyword(s):

Environmental Impact ◽

Environmental Performance ◽

Engine Performance ◽

Comprehensive Assessment ◽

Operational Performance ◽

Reactor Model ◽

Trade Off ◽

Emissions Inventory ◽

Trade Offs ◽

Wide Range

AbstractThis paper aims to present an integrated multidisciplinary simulation framework, deployed for the comprehensive assessment of combined helicopter–powerplant systems at mission level. Analytical evaluations of existing and conceptual regenerative engine designs are carried out in terms of operational performance and environmental impact. The proposed methodology comprises a wide-range of individual modeling theories applicable to helicopter flight dynamics, gas turbine engine performance as well as a novel, physics-based, stirred reactor model for the rapid estimation of various helicopter emissions species. The overall methodology has been deployed to conduct a preliminary trade-off study for a reference simple cycle and conceptual regenerative twin-engine light helicopter, modeled after the Airbus Helicopters Bo105 configuration, simulated under the representative mission scenarios. Extensive comparisons are carried out and presented for the aforementioned helicopters at both engine and mission level, along with general flight performance charts including the payload-range diagram. The acquired results from the design trade-off study suggest that the conceptual regenerative helicopter can offer significant improvement in the payload-range capability, while simultaneously maintaining the required airworthiness requirements. Furthermore, it has been quantified through the implementation of a representative case study that, while the regenerative configuration can enhance the mission range and payload capabilities of the helicopter, it may have a detrimental effect on the mission emissions inventory, specifically for NOx(Nitrogen Oxides). This may impose a trade-off between the fuel economy and environmental performance of the helicopter. The proposed methodology can effectively be regarded as an enabling technology for the comprehensive assessment of conventional and conceptual helicopter-powerplant systems, in terms of operational performance and environmental impact as well as towards the quantification of their associated trade-offs at mission level.

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Anomalous invasion dynamics due to dispersal polymorphism and dispersal-reproduction trade-offs

10.1101/2020.02.19.956425 ◽

2020 ◽

Author(s):

Vincent A. Keenan ◽

Stephen J. Cornell

Keyword(s):

Life History Theory ◽

Invasion Speed ◽

Complex Behaviour ◽

Trade Off ◽

Invasion Dynamics ◽

Population Growth Rates ◽

Trade Offs ◽

Invasion Fronts ◽

Wide Range ◽

Dispersal Polymorphism

AbstractDispersal polymorphism and mutation play significant roles during biological invasions, potentially leading to evolution and complex behaviour such as accelerating or decelerating invasion fronts. However, life history theory predicts that reproductive fitness — another key determinant of invasion dynamics – may be lower for more dispersive strains. Here, we use a mathematical model to show that unexpected invasion dynamics emerge from the combination of heritable dispersal polymorphism, dispersal-fitness trade-offs, and mutation between strains. We show that the invasion dynamics are determined by the trade-off relationship between dispersal and population growth rates of the constituent strains. We find that invasion dynamics can be “anomalous” (i.e. faster than any of the strains in isolation), but that the ultimate invasion speed is determined by the traits of at most two strains. The model is simple but generic, so we expect the predictions to apply to a wide range of ecological, evolutionary or epidemiological invasions.

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Under what circumstances could vaccination offset the harm from a more transmissible variant of SARS-COV-2 in NYC? Trade-offs regarding prioritization and speed of vaccination

10.1101/2021.01.29.21250710 ◽

2021 ◽

Author(s):

Hae-Young Kim ◽

Anna Bershteyn ◽

Jessica B. McGillen ◽

R. Scott Braithwaite

Keyword(s):

New York ◽

Healthcare Workers ◽

High Speed ◽

Hospital Admissions ◽

Herd Immunity ◽

Vaccine Delivery ◽

Vaccine Dose ◽

Trade Off ◽

Trade Offs ◽

Wide Range

AbstractIntroductionNew York City (NYC) was a global epicenter of COVID-19. Vaccines against COVID-19 became available in December 2020 with limited supply, resulting in the need for policies regarding prioritization. The next month, SARS-CoV-2 variants were detected that were more transmissible but still vaccine-susceptible, raising scrutiny of these policies. In particular, prioritization of higher-risk people could prevent more deaths per dose of vaccine administered but could also delay herd immunity if the prioritization introduced bottlenecks that lowered vaccination speed (the number of doses that could be delivered per day). We used mathematical modeling to examine the trade-off between prioritization and the vaccination speed.MethodsA stochastic, discrete-time susceptible-exposed-infected-recovered (SEIR) model with age- and comorbidity-adjusted COVID-19 outcomes (infections, hospitalizations, and deaths by July 1, 2021) was used to examine the trade-off between vaccination speed and whether or not vaccination was prioritized to individuals age 65+ and “essential workers,” defined as including first responders and healthcare, transit, education, and public safety workers. The model was calibrated to COVID-19 hospital admissions, hospital census, ICU census, and deaths in NYC. Vaccination speed was assumed to be 10,000 doses per day starting December 15th, 2020 targeting healthcare workers and nursing home populations, and to subsequently expand at alternative starting times and speeds. We compared COVID-outcomes across alternative expansion starting times (January 15th, January 21st, or February 1st) and speeds (20,000, 30,000, 50,000, 100,000, 150,000, or 200,000 doses per day for the first dose), as well as alternative prioritization options (“yes” versus “no” prioritization of essential workers and people age 65+). Model projections were produced with and without considering the emergence of a SARS-COV-2 variant with 56% greater transmissibility over January and February, 2021.ResultsIn the absence of a COVID-19 vaccine, the emergence of the more transmissible variant would triple the peak in infections, hospitalizations, and deaths and more than double cumulative infections, hospitalizations, and deaths. To offset the harm from the more transmissible variant would require reaching a vaccination speed of at least 100,000 doses per day by January 15th or 150,000 per day by January 21st. Prioritizing people ages 65+ and essential workers increased the number of lives saved per vaccine dose delivered: with the emergence of a more transmissible variant, 8,000 deaths could be averted by delivering 115,000 doses per day without prioritization or 71,000 doses per day with prioritization. If prioritization were to cause a bottleneck in vaccination speed, more lives would be saved with prioritization only if the bottleneck reduced vaccination speed by less than one-third of the maximum vaccine delivery capacity. These trade-offs between vaccination speed and prioritization were robust over a wide range of delivery capacity.ConclusionsThe emergence of a more transmissible variant of SARS-CoV-2 has the potential to triple the 2021 epidemic peak and more than double the 2021 COVID-19 burden in NYC. Vaccination could only offset the harm of the more transmissible variant if high speed were achieved in mid-to late January. Prioritization of COVID-19 vaccines to higher-risk populations saves more lives only if it does not create an excessive vaccine delivery bottleneck.

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Meta-Analysis Identifies Pleiotropic Loci Controlling Phenotypic Trade-offs in Sorghum

Genetics ◽

10.1093/genetics/iyab087 ◽

2021 ◽

Author(s):

Ravi V Mural ◽

Marcin Grzybowski ◽

Chenyong Miao ◽

Alyssa Damke ◽

Sirjan Sapkota ◽

...

Keyword(s):

Genetic Marker ◽

Genetic Basis ◽

Association Studies ◽

Meta Analysis ◽

Pleiotropic Effects ◽

Genome Wide Association Studies ◽

Trade Offs ◽

Genome Wide ◽

Wide Range ◽

Sorghum Genotypes

Abstract Community association populations are composed of phenotypically and genetically diverse accessions. Once these populations are genotyped, the resulting marker data can be reused by different groups investigating the genetic basis of different traits. Because the same genotypes are observed and scored for a wide range of traits in different environments, these populations represent a unique resource to investigate pleiotropy. Here we assembled a set of 234 separate trait datasets for the Sorghum Association Panel, a group of 406 sorghum genotypes widely employed by the sorghum genetics community. Comparison of genome wide association studies conducted with two independently generated marker sets for this population demonstrate that existing genetic marker sets do not saturate the genome and likely capture only 35-43% of potentially detectable loci controlling variation for traits scored in this population. While limited evidence for pleiotropy was apparent in cross-GWAS comparisons, a multivariate adaptive shrinkage approach recovered both known pleiotropic effects of existing loci and new pleiotropic effects, particularly significant impacts of known dwarfing genes on root architecture. In addition, we identified new loci with pleiotropic effects consistent with known trade-offs in sorghum development. These results demonstrate the potential for mining existing trait datasets from widely used community association populations to enable new discoveries from existing trait datasets as new, denser genetic marker datasets are generated for existing community association populations.

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The opportunity cost of information: an economic framework for understanding the balance between assessment and control in sea lamprey (Petromyzon marinus) management

Canadian Journal of Fisheries and Aquatic Sciences ◽

10.1139/f09-163 ◽

2010 ◽

Vol 67 (1) ◽

pp. 209-216 ◽

Cited By ~ 8

Author(s):

Eli P. Fenichel ◽

Gretchen J.A. Hansen

Keyword(s):

Optimal Allocation ◽

Petromyzon Marinus ◽

Empirical Work ◽

Sea Lamprey ◽

Allocation Of Resources ◽

Trade Off ◽

Management Actions ◽

Trade Offs ◽

Wide Range ◽

And Control

Fisheries managers must make trade-offs between competing management actions; however, the inherent trade-offs associated with information gathering are seldom explicitly considered. Incorporating economics into management decisions at the outset can aid managers in explicitly considering the trade-off between collecting more information to guide management and taking management actions. We use control of the invasive sea lamprey ( Petromyzon marinus ) in the Laurentian Great Lakes to illustrate how budget constraints shape this trade-off. Economic theory is used to frame previous empirical work showing that reducing the allocation of resources to conducting assessment, and thereby freeing resources for treatment, would result in a greater reduction of sea lamprey populations — the overarching management objective. The optimal allocation of resources between assessment and control depends on the total budget, the relative cost of each management activity, the marginal reduction in uncertainty associated with increased assessment, and the marginal effectiveness of increased treatment. Formal incorporation of prior information can change the optimal allocation of resources. The approach presented here is generally applicable to a wide range of fishery management and research questions.

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The evolution of juvenile susceptibility to infectious disease

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2018.0844 ◽

2018 ◽

Vol 285 (1881) ◽

pp. 20180844 ◽

Cited By ~ 12

Author(s):

Ben Ashby ◽

Emily Bruns

Keyword(s):

Life History Traits ◽

Adult Stage ◽

Wide Spectrum ◽

Immune Defence ◽

Demographic Structure ◽

Fitness Costs ◽

Trade Off ◽

Physiological Constraints ◽

Trade Offs ◽

Wide Range

Infection prior to reproduction usually carries greater fitness costs for hosts than infection later in life, suggesting selection should tend to favour juvenile resistance. Yet, juveniles are generally more susceptible than adults across a wide spectrum of host taxa. While physiological constraints and a lack of prior exposure can explain some of this pattern, studies in plants and insects suggest that hosts may trade off juvenile susceptibility against other life-history traits. However, it is unclear precisely how trade-offs shape the evolution of juvenile susceptibility. Here, we theoretically explore the evolution of juvenile susceptibility subject to trade-offs with maturation or reproduction, which could realistically occur due to resource allocation during development (e.g. prioritizing growth over immune defence). We show how host lifespan, the probability of maturation (i.e. of reaching the adult stage) and transmission mode affect the results. Our key finding is that elevated juvenile susceptibility is expected to evolve over a wide range of conditions, but should be lowest when hosts have moderate lifespans and an intermediate probability of reaching the adult stage. Our results elucidate how interactions between trade-offs and the epidemiological-demographic structure of the population can lead to the evolution of elevated juvenile susceptibility.

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Anomalous invasion dynamics due to dispersal polymorphism and dispersal–reproduction trade-offs

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2020.2825 ◽

2021 ◽

Vol 288 (1942) ◽

pp. 20202825

Author(s):

Vincent A. Keenan ◽

Stephen J. Cornell

Keyword(s):

Life History Theory ◽

Invasion Speed ◽

Complex Behaviour ◽

Trade Off ◽

Invasion Dynamics ◽

Population Growth Rates ◽

Trade Offs ◽

Invasion Fronts ◽

Wide Range ◽

Dispersal Polymorphism

Dispersal polymorphism and mutation play significant roles during biological invasions, potentially leading to evolution and complex behaviour such as accelerating or decelerating invasion fronts. However, life-history theory predicts that reproductive fitness—another key determinant of invasion dynamics—may be lower for more dispersive strains. Here, we use a mathematical model to show that unexpected invasion dynamics emerge from the combination of heritable dispersal polymorphism, dispersal-fitness trade-offs, and mutation between strains. We show that the invasion dynamics are determined by the trade-off relationship between dispersal and population growth rates of the constituent strains. We find that invasion dynamics can be ‘anomalous’ (i.e. faster than any of the strains in isolation), but that the ultimate invasion speed is determined by the traits of, at most, two strains. The model is simple but generic, so we expect the predictions to apply to a wide range of ecological, evolutionary, or epidemiological invasions.

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