scholarly journals Evolutionary stability of collateral sensitivity to antibiotics in the model pathogenPseudomonas aeruginosa

2019 ◽  
Author(s):  
Camilo Barbosa ◽  
Roderich Roemhild ◽  
Philip Rosenstiel ◽  
Hinrich Schulenburg
Keyword(s):  
Clinical Utility ◽  
Evolutionary Stability ◽  
Order Effects ◽  
Fitness Costs ◽  
Adaptive Potential ◽  
Trade Off ◽  
Adaptive Mutations ◽  
Collateral Sensitivity ◽  
Trade Offs ◽  
Drug Order

AbstractEvolution is at the core of the impending antibiotic crisis. Sustainable therapy must thus account for the adaptive potential of pathogens. One option is to exploit evolutionary trade-offs, like collateral sensitivity, where evolved resistance to one antibiotic causes hypersensitivity to another one. To date, the evolutionary stability and thus clinical utility of this trade-off is unclear. We performed a critical experimental test on this key requirement, using evolution experiments withPseudomonas aeruginosacombined with genomic and genetic analyses, and identified three main outcomes: (i) bacteria commonly failed to counter hypersensitivity and went extinct; (ii) hypersensitivity sometimes converted into multidrug resistance; and (iii) resistance gains occasionally caused re-sensitization to the previous drug, thereby maintaining the trade-off. Drug order affected the evolutionary outcome, most likely due to variation in fitness costs and epistasis among adaptive mutations. Our finding of robust genetic trade-offs and drug-order effects can guide design of evolution-informed antibiotic therapy.

scholarly journals Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Camilo Barbosa ◽  
Roderich Römhild ◽  
Philip Rosenstiel ◽  
Hinrich Schulenburg
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Evolutionary Stability ◽  
Order Effects ◽  
Fitness Costs ◽  
Adaptive Potential ◽  
Trade Off ◽  
Adaptive Mutations ◽  
Collateral Sensitivity ◽  
Trade Offs ◽  
Drug Order

Evolution is at the core of the impending antibiotic crisis. Sustainable therapy must thus account for the adaptive potential of pathogens. One option is to exploit evolutionary trade-offs, like collateral sensitivity, where evolved resistance to one antibiotic causes hypersensitivity to another one. To date, the evolutionary stability and thus clinical utility of this trade-off is unclear. We performed a critical experimental test on this key requirement, using evolution experiments with Pseudomonas aeruginosa, and identified three main outcomes: (i) bacteria commonly failed to counter hypersensitivity and went extinct; (ii) hypersensitivity sometimes converted into multidrug resistance; and (iii) resistance gains frequently caused re-sensitization to the previous drug, thereby maintaining the trade-off. Drug order affected the evolutionary outcome, most likely due to variation in the effect size of collateral sensitivity, epistasis among adaptive mutations, and fitness costs. Our finding of robust genetic trade-offs and drug-order effects can guide design of evolution-informed antibiotic therapy.

scholarly journals Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses

2014 ◽  
Vol 281 (1794) ◽  
pp. 20141679 ◽  
Author(s):  
Mato Lagator ◽  
Nick Colegrave ◽  
Paul Neve
Keyword(s):  
Multiple Drug ◽  
Driving Mechanism ◽  
Fitness Costs ◽  
Epistatic Interactions ◽  
Adaptive Mutations ◽  
Changing Environments ◽  
Modes Of Action ◽  
Selection History ◽  
Trade Offs ◽  
Novel Environments

In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii . Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments.

scholarly journals The evolution of juvenile susceptibility to infectious disease

2018 ◽  
Vol 285 (1881) ◽  
pp. 20180844 ◽  
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.

scholarly journals Rapid and robust evolution of collateral sensitivity in Pseudomonas aeruginosa antibiotic-resistant mutants

2020 ◽  
Vol 6 (32) ◽  
pp. eaba5493
Author(s):  
Sara Hernando-Amado ◽  
Fernando Sanz-García ◽  
José Luis Martínez
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Rational Design ◽  
Antibiotic Resistant ◽  
Trade Off ◽  
Collateral Sensitivity ◽  
Trade Offs ◽  
Resistant Mutants ◽  
Antibiotic Resistant Mutants

The analysis of trade-offs, as collateral sensitivity, associated with the acquisition of antibiotic resistance, is mainly based on the use of model strains. However, the possibility of exploiting these trade-offs for fighting already resistant isolates has not been addressed in depth, despite the fact that bacterial pathogens are frequently antibiotic-resistant, forming either homogeneous or heterogeneous populations. Using a set of Pseudomonas aeruginosa-resistant mutants, we found that ceftazidime selects pyomelanogenic tobramycin-hypersusceptible mutants presenting chromosomal deletions in the analyzed genetic backgrounds. Since pyomelanogenic resistant mutants frequently coexist with other morphotypes in patients with cystic fibrosis, we analyzed the exploitation of this trade-off to drive extinction of heterogeneous resistant populations by using tobramycin/ceftazidime alternation. Our work shows that this approach is feasible because phenotypic trade-offs associated with the use of ceftazidime are robust. The identification of conserved collateral sensitivity networks may guide the rational design of evolution-based antibiotic therapies in P. aeruginosa infections.

Dual Goals for Speed and Accuracy on the Same Performance Task

2012 ◽  
Vol 11 (3) ◽  
pp. 118-126 ◽  
Author(s):  
Olive Emil Wetter ◽  
Jürgen Wegge ◽  
Klaus Jonas ◽  
Klaus-Helmut Schmidt
Keyword(s):  
Memory Scanning ◽  
Performance Task ◽  
Performance Tasks ◽  
Trade Off ◽  
Test Experiment ◽  
Trade Offs ◽  
New Finding ◽  
Sternberg Paradigm ◽  
Speed Accuracy ◽  
Speed And Accuracy

In most work contexts, several performance goals coexist, and conflicts between them and trade-offs can occur. Our paper is the first to contrast a dual goal for speed and accuracy with a single goal for speed on the same task. The Sternberg paradigm (Experiment 1, n = 57) and the d2 test (Experiment 2, n = 19) were used as performance tasks. Speed measures and errors revealed in both experiments that dual as well as single goals increase performance by enhancing memory scanning. However, the single speed goal triggered a speed-accuracy trade-off, favoring speed over accuracy, whereas this was not the case with the dual goal. In difficult trials, dual goals slowed down scanning processes again so that errors could be prevented. This new finding is particularly relevant for security domains, where both aspects have to be managed simultaneously.

The Effects of Decision Time on Perceptions of Decisions and Decision Makers in (Moral) Trade-Off Scenarios

2019 ◽  
Author(s):  
Anna Katharina Spälti ◽  
Mark John Brandt ◽  
Marcel Zeelenberg
Keyword(s):  
Decision Process ◽  
Decision Time ◽  
Decision Makers ◽  
Process Information ◽  
Total N ◽  
Trade Off ◽  
Financial Gain ◽  
Trade Offs ◽  
Sacred Values ◽  
Moral Context

People often have to make trade-offs. We study three types of trade-offs: 1) "secular trade-offs" where no moral or sacred values are at stake, 2) "taboo trade-offs" where sacred values are pitted against financial gain, and 3) "tragic trade-offs" where sacred values are pitted against other sacred values. Previous research (Critcher et al., 2011; Tetlock et al., 2000) demonstrated that tragic and taboo trade-offs are not only evaluated by their outcomes, but are also evaluated based on the time it took to make the choice. We investigate two outstanding questions: 1) whether the effect of decision time differs for evaluations of decisions compared to decision makers and 2) whether moral contexts are unique in their ability to influence character evaluations through decision process information. In two experiments (total N = 1434) we find that decision time affects character evaluations, but not evaluations of the decision itself. There were no significant differences between tragic trade-offs and secular trade-offs, suggesting that the decisions structure may be more important in evaluations than moral context. Additionally, the magnitude of the effect of decision time shows us that decision time, may be of less practical use than expected. We thus urge, to take a closer examination of the processes underlying decision time and its perception.

Predicting Undesired Treatment Outcome in Mental Healthcare: Machine Learning Study (Preprint)

2019 ◽  
Author(s):  
Kasper Van Mens ◽  
Joran Lokkerbol ◽  
Richard Janssen ◽  
Robert de Lange ◽  
Bea Tiemens
Keyword(s):  
Machine Learning ◽  
Treatment Outcome ◽  
Mental Health Treatment ◽  
Mental Healthcare ◽  
Machine Learning Algorithms ◽  
Gradient Boosting ◽  
Trade Off ◽  
Trade Offs ◽  
Outcome Monitoring ◽  
Extreme Gradient Boosting

BACKGROUND It remains a challenge to predict which treatment will work for which patient in mental healthcare. OBJECTIVE In this study we compare machine algorithms to predict during treatment which patients will not benefit from brief mental health treatment and present trade-offs that must be considered before an algorithm can be used in clinical practice. METHODS Using an anonymized dataset containing routine outcome monitoring data from a mental healthcare organization in the Netherlands (n = 2,655), we applied three machine learning algorithms to predict treatment outcome. The algorithms were internally validated with cross-validation on a training sample (n = 1,860) and externally validated on an unseen test sample (n = 795). RESULTS The performance of the three algorithms did not significantly differ on the test set. With a default classification cut-off at 0.5 predicted probability, the extreme gradient boosting algorithm showed the highest positive predictive value (ppv) of 0.71(0.61 – 0.77) with a sensitivity of 0.35 (0.29 – 0.41) and area under the curve of 0.78. A trade-off can be made between ppv and sensitivity by choosing different cut-off probabilities. With a cut-off at 0.63, the ppv increased to 0.87 and the sensitivity dropped to 0.17. With a cut-off of at 0.38, the ppv decreased to 0.61 and the sensitivity increased to 0.57. CONCLUSIONS Machine learning can be used to predict treatment outcomes based on routine monitoring data.This allows practitioners to choose their own trade-off between being selective and more certain versus inclusive and less certain.

Challenges in the Empirical Study of Global Governance Legitimacy

2018 ◽  
Author(s):  
Steven Bernstein
Keyword(s):  
Empirical Study ◽  
Global Governance ◽  
Research Agenda ◽  
Cultural Factors ◽  
Theory Building ◽  
Trade Off ◽  
Trade Offs ◽  
Different Types ◽  
Political Communities

This commentary discusses three challenges for the promising and ambitious research agenda outlined in the volume. First, it interrogates the volume’s attempts to differentiate political communities of legitimation, which may vary widely in composition, power, and relevance across institutions and geographies, with important implications not only for who matters, but also for what gets legitimated, and with what consequences. Second, it examines avenues to overcome possible trade-offs from gains in empirical tractability achieved through the volume’s focus on actor beliefs and strategies. One such trade-off is less attention to evolving norms and cultural factors that may underpin actors’ expectations about what legitimacy requires. Third, it addresses the challenge of theory building that can link legitimacy sources, (de)legitimation practices, audiences, and consequences of legitimacy across different types of institutions.

scholarly journals Toward Inclusive Landscape Governance in Contested Landscapes: Exploring the Contribution of Participatory Tools in the Upper Suriname River Basin

2021 ◽  
Author(s):  
Lisa Best ◽  
Kimberley Fung-Loy ◽  
Nafiesa Ilahibaks ◽  
Sara O. I. Ramirez-Gomez ◽  
Erika N. Speelman
Keyword(s):  
Land Use ◽  
River Basin ◽  
Scenario Planning ◽  
Community Members ◽  
Trade Off ◽  
3 Dimensional ◽  
Landscape Governance ◽  
Information Tools ◽  
Tribal Communities ◽  
Trade Offs

AbstractNowadays, tropical forest landscapes are commonly characterized by a multitude of interacting institutions and actors with competing land-use interests. In these settings, indigenous and tribal communities are often marginalized in landscape-level decision making. Inclusive landscape governance inherently integrates diverse knowledge systems, including those of indigenous and tribal communities. Increasingly, geo-information tools are recognized as appropriate tools to integrate diverse interests and legitimize the voices, values, and knowledge of indigenous and tribal communities in landscape governance. In this paper, we present the contribution of the integrated application of three participatory geo-information tools to inclusive landscape governance in the Upper Suriname River Basin in Suriname: (i) Participatory 3-Dimensional Modelling, (ii) the Trade-off! game, and (iii) participatory scenario planning. The participatory 3-dimensional modelling enabled easy participation of community members, documentation of traditional, tacit knowledge and social learning. The Trade-off! game stimulated capacity building and understanding of land-use trade-offs. The participatory scenario planning exercise helped landscape actors to reflect on their own and others’ desired futures while building consensus. Our results emphasize the importance of systematically considering tool attributes and key factors, such as facilitation, for participatory geo-information tools to be optimally used and fit with local contexts. The results also show how combining the tools helped to build momentum and led to diverse yet complementary insights, thereby demonstrating the benefits of integrating multiple tools to address inclusive landscape governance issues.

scholarly journals On the effectiveness of tracking and testing in SEIR models for improving health vs. economy trade-offs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoav Kolumbus ◽  
Noam Nisan
Keyword(s):  
Additional Parameter ◽  
Patient Privacy ◽  
Economic Costs ◽  
Trade Off ◽  
Seir Model ◽  
Social Question ◽  
Social Distancing ◽  
Trade Offs ◽  
Asymptomatic Individuals ◽  
Testing Policies

AbstractWe study the effectiveness of tracking and testing policies for suppressing epidemic outbreaks. We evaluate the performance of tracking-based intervention methods on a network SEIR model, which we augment with an additional parameter to model pre-symptomatic and asymptomatic individuals, and study the effectiveness of these methods in combination with or as an alternative to quarantine and global lockdown policies. Our focus is on the basic trade-off between human-lives lost and economic costs, and on how this trade-off changes under different quarantine, lockdown, tracking, and testing policies. Our main findings are as follows: (1) Tests combined with patient quarantines reduce both economic costs and mortality, however, an extensive-scale testing capacity is required to achieve a significant improvement. (2) Tracking significantly reduces both economic costs and mortality. (3) Tracking combined with a moderate testing capacity can achieve containment without lockdowns. (4) In the presence of a flow of new incoming infections, dynamic “On–Off” lockdowns are more efficient than fixed lockdowns. In this setting as well, tracking strictly improves efficiency. The results show the extreme usefulness of policies that combine tracking and testing for reducing mortality and economic costs, and their potential to contain outbreaks without imposing any social distancing restrictions. This highlights the difficult social question of trading-off these gains against patient privacy, which is inevitably infringed by tracking.

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