scholarly journals Vaccination strategies when vaccines are scarce: On conflicts between reducing the burden and avoiding the evolution of escape mutants

2021 ◽  
Author(s):  
Félix Geoffroy ◽  
Arne Traulsen ◽  
Hildegard Uecker
Keyword(s):  
Booster Dose ◽  
Large Fraction ◽  
Population Level ◽  
Type Model ◽  
Time Interval ◽  
Trade Off ◽  
Vaccination Strategies ◽  
Escape Mutants ◽  
Set Up ◽  
Dose Vaccine

When vaccine supply is limited but population immunisation urgent, the allocation of the available doses needs to be carefully considered. One aspect of dose allocation is the time interval between the primer and the booster injections in two-dose vaccines. By stretching this interval, more individuals can be vaccinated with the first dose more quickly. Even if the level of immunity of these 'half-vaccinated' individuals is lower than that of those who have received both shots, delaying the second injection can be beneficial in reducing case numbers, provided a single dose is sufficiently effective. On the other hand, there has been concern that intermediate levels of immunity in partially vaccinated individuals may favour the evolution of vaccine escape mutants. In that case, a large fraction of half-vaccinated individuals would pose a risk – but only if they encounter the virus. This raises the question whether there is a conflict between reducing the burden and the risk of vaccine escape evolution or not. We develop a minimal model to assess the population-level effects of the timing of the booster dose. We set up an SIR-type model, in which more and more individuals become vaccinated with a two-dose vaccine over the course of a pandemic. As expected, there is no trade-off when vaccine escape evolves at equal probabilities in unvaccinated and half-vaccinated patients. If vaccine escape evolves more easily in half-vaccinated patients, the presence or absence of a trade-off depends on the reductions in susceptibility and transmissibility elicited by the primer dose.

scholarly journals Investigating hot-Jupiter inflated radii with hierarchical Bayesian modelling

2018 ◽  
Vol 616 ◽  
pp. A76 ◽  
Author(s):  
Marko Sestovic ◽  
Brice-Olivier Demory ◽  
Didier Queloz
Keyword(s):  
Large Fraction ◽  
Population Level ◽  
Mass Range ◽  
Hierarchical Bayesian ◽  
Incident Flux ◽  
Hot Jupiters ◽  
Probabilistic Relation ◽  
Relationship Of ◽  
The Relationship ◽  
Level Analysis

Context. As of today, hundreds of hot Jupiters have been found, yet the inflated radii of a large fraction of them remain unexplained. A number of mechanisms have been proposed to explain these anomalous radii, however most of these can only work under certain conditions and may not be sufficient to explain the most extreme cases. It is still unclear whether a single mechanism can sufficiently explain the entire distribution of radii, or whether a combination of these mechanisms is needed. Aims. We seek to understand the relationship of radius with stellar irradiation and mass and to find the range of masses over which hot Jupiters are inflated. We also aim to find the intrinsic physical scatter in their radii, caused by unobservable parameters, and to constrain the fraction of hot Jupiters that exhibit inflation. Methods. By constructing a hierarchical Bayesian model, we inferred the probabilistic relation between planet radius, mass, and incident flux for a sample of 286 gas giants. We separately incorporated the observational uncertainties of the data and the intrinsic physical scatter in the population. This allowed us to treat the intrinsic physical scatter in radii, due to latent parameters such as the heavy element fraction, as a parameter to be inferred. Results. We find that the planetary mass plays a key role in the inflation extent and that planets in the range ~0.37−0.98  MJ show the most inflated radii. At higher masses, the radius response to incident flux begins to decrease. Below a threshold of 0.37 ± 0.03  MJ we find that giant exoplanets as a population are unable to maintain inflated radii ≿1.4  RJ but instead exhibit smaller sizes as the incident flux is increased beyond 106 W m−2. We also find that below 1  MJ, there is a cut-off point at high incident flux beyond which we find no more inflated planets, and that this cut-off point decreases as the mass decreases. At incident fluxes higher than ~1.6 × 106 W m−2 and in a mass range 0.37−0.98  MJ, we find no evidence for a population of non-inflated hot Jupiters. Our study sheds a fresh light on one of the key questions in the field and demonstrates the importance of population-level analysis to grasp the underlying properties of exoplanets.

scholarly journals Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants

2011 ◽  
Vol 208 (13) ◽  
pp. 2599-2606 ◽  
Author(s):  
Whitney E. Purtha ◽  
Thomas F. Tedder ◽  
Syd Johnson ◽  
Deepta Bhattacharya ◽  
Michael S. Diamond
Keyword(s):  
B Cells ◽  
Plasma Cells ◽  
Large Fraction ◽  
West Nile Virus Infection ◽  
Immune Serum ◽  
Memory B Cells ◽  
Viral Escape ◽  
Variant Virus ◽  
Escape Mutants

Memory B cells (MBCs) and long-lived plasma cells (LLPCs) persist after clearance of infection, yet the specific and nonredundant role MBCs play in subsequent protection is unclear. After resolution of West Nile virus infection in mice, we demonstrate that LLPCs were specific for a single dominant neutralizing epitope, such that immune serum poorly inhibited a variant virus that encoded a mutation at this critical epitope. In contrast, a large fraction of MBC produced antibody that recognized both wild-type (WT) and mutant viral epitopes. Accordingly, antibody produced by the polyclonal pool of MBC neutralized WT and variant viruses equivalently. Remarkably, we also identified MBC clones that recognized the mutant epitope better than the WT protein, despite never having been exposed to the variant virus. The ability of MBCs to respond to variant viruses in vivo was confirmed by experiments in which MBCs were adoptively transferred or depleted before secondary challenge. Our data demonstrate that class-switched MBC can respond to variants of the original pathogen that escape neutralization of antibody produced by LLPC without a requirement for accumulating additional somatic mutations.

scholarly journals Experimental assessment of harmonic contributions using a ternary pulse sequence

2021 ◽  
Vol 18 (3) ◽  
pp. 271-289
Author(s):  
Evgeniia Bulycheva ◽  
Sergey Yanchenko
Keyword(s):  
Real Time ◽  
Pulse Sequence ◽  
Wide Band ◽  
Voltage Source ◽  
Time Interval ◽  
Time Frequency ◽  
Grid Impedance ◽  
Set Up ◽  
Grid Voltage Distortion ◽  
Operational Modes

Harmonic contributions of utility and customer may feature significant variations due to network switchings and changing operational modes. In order to correctly define the impacts on the grid voltage distortion the frequency dependent impedance characteristic of the studied network should be accurately measured in the real-time mode. This condition can be fulfilled by designing a stimuli generator measuring the grid impedance as a response to injected interference and producing time-frequency plots of harmonic contributions during considered time interval. In this paper a prototype of a stimuli generator based on programmable voltage source inverter is developed and tested. The use of ternary pulse sequence allows fast wide-band impedance measurements that meet the requirements of real-time assessment of harmonic contributions. The accuracy of respective analysis involving impedance determination and calculation of harmonic contributions is validated experimentally using reference characteristics of laboratory test set-up with varying grid impedance.

scholarly journals Five-Year Experience of Liver Transplant at Kerman University of Medical Sciences: Afzalipoor Hospital

2020 ◽  
Author(s):  
Masood Dehghani
Keyword(s):  
Liver Transplantation ◽  
Liver Transplant ◽  
Cross Sectional Study ◽  
Outcome Data ◽  
Time Interval ◽  
Cross Sectional ◽  
The Past ◽  
Transplantation Center ◽  
Set Up ◽  
End Stage

Introduction: The only option for treatment of end stage liver diseases is liver transplantation. Afzalipour Hospital in Kerman, Iran is the third largest liver transplantation center in Iran. In this study, the outcomes of this center have been studied during the past 5 years. Methods: In this cross-sectional study, the pre and post transplantation’s clinical, demographic and outcome data of all patients who received liver transplant at Afzalipour Hospital during the past 5 years have been collected and reviewed. SPSS software ver. 16 was used to analyze the data. Results: Forty-three patients have received liver transplantation during this time interval. The 3-year survival rate of patients was 77%. The most common cause of death was primary nonfunction graft after transplantation. The most common complication was acute rejection (15%), all of which were successfully treated with corticosteroids. Conclusion:  Due to increment of cases of acute and chronic liver failure in the community and since the final treatment of these cases is liver transplantation, so there is need to develop liver transplant centers in the future. Quantitative and qualitative study of the activity of centers based liver transplant in Iran is necessary to set up successful centers.

scholarly journals Evaluation of COVID-19 vaccination strategies with a delayed second dose

PLoS Biology ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. e3001211
Author(s):  
Seyed M. Moghadas ◽  
Thomas N. Vilches ◽  
Kevin Zhang ◽  
Shokoofeh Nourbakhsh ◽  
Pratha Sah ◽  
...  
Keyword(s):  
Program Effectiveness ◽  
Credible Interval ◽  
The United States ◽  
Optimal Time ◽  
Time Interval ◽  
Policy Debate ◽  
Agent Based ◽  
Vaccination Strategies ◽  
Supply And Distribution ◽  
The Impact

Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8–29.7) infections, 0.69 (95% CrI: 0.52–0.97) hospitalizations, and 0.34 (95% CrI: 0.25–0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37–0.89) hospitalizations and 0.32 (95% CrI: 0.23–0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.

Guidance for Using State-and Prediction-Based Theory

2020 ◽  
pp. 93-122
Keyword(s):  
Population Level ◽  
Population Models ◽  
Dynamic State ◽  
Trade Off ◽  
State Variable

This chapter outlines the guidance on using state- and prediction-based theory (SPT) to build models of populations and communities of adaptive individuals, detailing five steps unique to SPT. The most important aspect of SPT to remember is that one is not trying to build optimal, or even necessarily accurate, models of how an organism's behavior affects its future fitness. Instead, one is trying to find simplistic models that produce realistic behavior in contexts where optimization is impossible. While SPT can be used like dynamic state variable modeling (DSVM), as a framework for thinking about and modeling how an individual makes a particular decision, its main purpose is to model adaptive trade-off decisions in individual-based population models. Thus, using SPT is part of the larger process of developing, analyzing, and applying an IBM to address population-level questions, and the five steps therefore include that process.

scholarly journals Human Papillomavirus Genotype Replacement: Still Too Early to Tell?

2020 ◽  
Author(s):  
Irene Man ◽  
Simopekka Vänskä ◽  
Matti Lehtinen ◽  
Johannes A Bogaards
Keyword(s):  
Human Papillomavirus ◽  
Hpv Vaccination ◽  
Population Level ◽  
Cross Protection ◽  
Transmission Model ◽  
Trade Off ◽  
Long Run ◽  
Vaccine Type ◽  
Cross Immunity ◽  
Different Levels

Abstract Background Although human papillomavirus (HPV) vaccines are highly efficacious in protecting against HPV infections and related diseases, vaccination may trigger replacement by nontargeted genotypes if these compete with the vaccine-targeted types. HPV genotype replacement has been deemed unlikely, based on the lack of systematic increases in the prevalence of nonvaccine-type (NVT) infection in the first decade after vaccination, and on the presence of cross-protection for some NVTs. Methods To investigate whether type replacement can be inferred from early postvaccination surveillance, we constructed a transmission model in which a vaccine type and an NVT compete through infection-induced cross-immunity. We simulated scenarios of different levels of cross-immunity and vaccine-induced cross-protection to the NVT. We validated whether commonly used measures correctly indicate type replacement in the long run. Results Type replacement is a trade-off between cross-immunity and cross-protection; cross-immunity leads to type replacement unless cross-protection is strong enough. With weak cross-protection, NVT prevalence may initially decrease before rebounding into type replacement, exhibiting a honeymoon period. Importantly, vaccine effectiveness for NVTs is inadequate for indicating type replacement. Conclusions Although postvaccination surveillance thus far is reassuring, it is still too early to preclude type replacement. Monitoring of NVTs remains pivotal in gauging population-level impacts of HPV vaccination.

scholarly journals Cultural selection shapes network structure

2019 ◽  
Vol 5 (8) ◽  
pp. eaaw0609 ◽  
Author(s):  
Marco Smolla ◽  
Erol Akçay
Keyword(s):  
Social Networks ◽  
Network Structure ◽  
Cultural Evolution ◽  
Level Structure ◽  
Population Level ◽  
Trade Off ◽  
Skill Sets ◽  
Individual Level ◽  
Dense Networks ◽  
The Social

Cultural evolution relies on the social transmission of cultural traits along a population’s social network. Research indicates that network structure affects information spread and thus the capacity for cumulative culture. However, how network structure itself is driven by population-culture co-evolution remains largely unclear. We use a simple model to investigate how populations negotiate the trade-off between acquiring new skills and getting better at existing skills and how this trade-off shapes social networks. We find unexpected eco-evolutionary feedbacks from culture onto social networks and vice versa. We show that selecting for skill generalists results in sparse networks with diverse skill sets, whereas selecting for skill specialists results in dense networks and a population that specializes on the same few skills on which everyone is an expert. Our model advances our understanding of the complex feedbacks in cultural evolution and demonstrates how individual-level behavior can lead to the emergence of population-level structure.

Phase Type Viewpoint Spectrum Sensing for Cognitive Radios

Frequenz ◽  
2015 ◽  
Vol 69 (9-10) ◽  
Author(s):  
Mohammadreza Amini ◽  
Asra Mirzavandi
Keyword(s):  
Spectrum Sensing ◽  
Cognitive Radios ◽  
Type Model ◽  
Computationally Efficient ◽  
Channel State ◽  
Secondary Users ◽  
Trade Off ◽  
Phase Type ◽  
Error Probabilities ◽  
Sensing Time

AbstractSpectrum sensing is one of the main functionalities of cognitive radios to find transmission opportunities without interfering primary users’ transmission. The more accurate and efficient the spectrum sensing is, the higher the throughput of secondary and primary networks is achieved. This paper presents adaptive spectrum sensing method based on phase type modelling that is computationally efficient for secondary users to conclude about the channel state (idle or busy) under collision constraint. The parameters of phase type model can be adjusted based on the desired operating point of the receiver sensor in its ROC curve. The presented approach can run a simple trade off between sensing time and the two error probabilities of the receiver sensor i.e. False alarm and Miss-detection, the trade off that cannot be easily achieved in other sensing method.

Waiting for the Payday? The Market for Startups and the Timing of Entrepreneurial Exit

2020 ◽  
Author(s):  
Ashish Arora ◽  
Andrea Fosfuri ◽  
Thomas Rønde
Keyword(s):  
Analytical Model ◽  
Business Strategy ◽  
Exit Strategy ◽  
Trade Off ◽  
Early Exit ◽  
Early Acquisition ◽  
Set Up ◽  
Exclusive Choice ◽  
Early Market ◽  
Technology Startups

Most technology startups are set up for exit through acquisition by large corporations. In choosing when to sell, startups face a trade-off. Early acquisition reduces execution errors, but later acquisition both improves the likelihood of finding a better match and benefits from increased buyer competition. Startups’ exit strategies vary considerably: Some startups aim to sell early; others remain in stealth mode by developing the invention for a late sale. We develop an analytical model to study the timing of the exit strategy. We find that startups with more capable founding teams commit to a late exit, whereas those with less capable founding teams commit to an early exit. Finally, startups with founding teams of intermediate capabilities remain flexible: They seek early offers but eventually sell late. If trying the early market is so costly that startups have to make a mutually exclusive choice between an early and late sale, startups sell inefficiently late. Instead, if they can collect early offers at no cost before deciding on the timing of sale, there are too many early acquisitions. This paper was accepted by David Simchi-Levi, business strategy.

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