We model Covid-19 vaccine uptake as a reinforcement learning dynamic between two populations: the vaccine adopters, and the vaccine hesitant. Using data available from the Center for Disease Control ...(CDC), we estimate the payoff matrix governing the interaction between these two groups over time and show they are playing a Hawk–Dove evolutionary game with an internal evolutionarily stable Nash equilibrium (the asymptotic percentage of vaccinated in the population). We then ask whether vaccine adoption can be improved by implementing dynamic incentive schedules that reward/punish the vaccine hesitant, and if so, what schedules are optimal and how effective are they likely to be? When is the optimal time to start an incentive program, how large should the incentives be, and is there a point of diminishing returns? By using a tailored replicator dynamic reinforcement learning model together with optimal control theory, we show that well designed and timed incentive programs can improve vaccine uptake by shifting the Nash equilibrium upward in large populations, but only so much, and incentive sizes above a certain threshold show diminishing returns.
•Covid-19 vaccine uptake is modeled as a Hawk–Dove evolutionary game.•Two populations of players compete: vaccine adopters and vaccine hesitant.•Optimal control is used to test different dynamic incentive strategies.•Dynamic incentives can increase vaccine uptake, but only so much.•Larger incentives do not necessary produce better responses.
The prisoner's dilemma (PD) game offers a simple paradigm of competition between two players who can either cooperate or defect. Since defection is a strict Nash equilibrium, it is an asymptotically ...stable state of the replicator dynamical system that uses the PD payoff matrix to define the fitness landscape of two interacting evolving populations. The dilemma arises from the fact that the average payoff of this asymptotically stable state is suboptimal. Coaxing the players to cooperate would result in a higher payoff for both. Here we develop an optimal control theory for the prisoner's dilemma evolutionary game in order to maximize cooperation (minimize the defector population) over a given cycle time T, subject to constraints. Our two time-dependent controllers are applied to the off-diagonal elements of the payoff matrix in a bang-bang sequence that dynamically changes the game being played by dynamically adjusting the payoffs, with optimal timing that depends on the initial population distributions. Over multiple cycles nT (n>1), the method is adaptive as it uses the defector population at the end of the nth cycle to calculate the optimal schedule over the n+1st cycle. The control method, based on Pontryagin's maximum principle, can be viewed as determining the optimal way to dynamically alter incentives and penalties in order to maximize the probability of cooperation in settings that track dynamic changes in the frequency of strategists, with potential applications in evolutionary biology, economics, theoretical ecology, social sciences, reinforcement learning, and other fields where the replicator system is used.
Summary
Background
Screening overweight and obese children for non‐alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies ...have called for more data before making a formal recommendation.
Aim
To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD.
Methods
Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed.
Results
Non‐alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%.
Conclusions
Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner.
Objectives: To provide a revised version of earlier guidelines published in 2006.
Background: Primary dystonias are chronic and often disabling conditions with a widespread spectrum mainly in young ...people.
Diagnosis: Primary dystonias are classified as pure dystonia, dystonia plus or paroxysmal dystonia syndromes. Assessment should be performed using a validated rating scale for dystonia. Genetic testing may be performed after establishing the clinical diagnosis. DYT1 testing is recommended for patients with primary dystonia with limb onset before age 30, and in those with an affected relative with early‐onset dystonia. DYT6 testing is recommended in early‐onset or familial cases with cranio‐cervical dystonia or after exclusion of DYT1. Individuals with early‐onset myoclonus should be tested for mutations in the DYT11 gene. If direct sequencing of the DYT11 gene is negative, additional gene dosage is required to improve the proportion of mutations detected. A levodopa trial is warranted in every patient with early‐onset primary dystonia without an alternative diagnosis. In patients with idiopathic dystonia, neurophysiological tests can help with describing the pathophysiological mechanisms underlying the disorder.
Treatment: Botulinum toxin (BoNT) type A is the first‐line treatment for primary cranial (excluding oromandibular) or cervical dystonia; it is also effective on writing dystonia. BoNT/B is not inferior to BoNT/A in cervical dystonia. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for primary generalized or cervical dystonia, after medication or BoNT have failed. DBS is less effective in secondary dystonia. This treatment requires a specialized expertise and a multidisciplinary team.
Description of the NIF Laser Spaeth, M. L.; Manes, K. R.; Kalantar, D. H. ...
Fusion science and technology,
02/2016, Volume:
69, Issue:
1
Journal Article
Peer reviewed
Open access
The possibility of imploding small capsules to produce mini-fusion explosions was explored soon after the first thermonuclear explosions in the early 1950s. Various technologies have been pursued to ...achieve the focused power and energy required for laboratory-scale fusion. Each technology has its own challenges. For example, electron and ion beams can deliver the large amounts of energy but must contend with Coulomb repulsion forces that make focusing these beams a daunting challenge. The demonstration of the first laser in 1960 provided a new option. Energy from laser beams can be focused and deposited within a small volume; the challenge became whether a practical laser system can be constructed that delivers the power and energy required while meeting all other demands for achieving a high-density, symmetric implosion. The National Ignition Facility (NIF) is the laser designed and built to meet the challenges for study of high-energy-density physics and inertial confinement fusion (ICF) implosions. This paper describes the architecture, systems, and subsystems of NIF. It describes how they partner with each other to meet these new, complex demands and describes how laser science and technology were woven together to bring NIF into reality.
Preterm birth or low birth weight is the single largest cause of death in newborns, however this mortality can be reduced through newborn care interventions, including Kangaroo Mother Care (KMC). ...Previously, a multi-country randomized controlled trial, coordinated by the World Health Organization (WHO), reported a significant survival advantage with initiation of continuous KMC immediately after birth compared with initiation of continuous KMC a few days after birth when the baby is considered clinically stable. Whether the survival advantage would lead to higher rates of neurodevelopmental morbidities, or the immediate KMC will also have a beneficial effect on cognitive development also, has not been investigated. We therefore propose to test the hypothesis that low-birth-weight infants exposed to immediate KMC will have lower rates of neurodevelopmental impairment in comparison to traditional KMC-treated infants, by prospectively following up infants already enrolled in the immediate KMC trial for the first 2 years of life, and assessing their growth and neurodevelopment.
This prospective cohort study will enroll surviving neonates from the main WHO immediate KMC trial. The main trial as well as this follow-up study are being conducted in five low- and middle-income countries in South Asia and sub-Saharan Africa. The estimated sample size for comparison of the risk of neurodevelopmental impairment is a total of 2200 children. The primary outcome will include rates of cerebral palsy, hearing impairment, vision impairment, mental and motor development, and epilepsy and will be assessed by the age of 3 years. The analysis will be by intention to treat.
Immediate KMC can potentially reduce low-birth-weight-associated complications such as respiratory disease, hypothermia, hypoglycemia, and infection that can result in impaired neurocognitive development. Neuroprotection may also be mediated by improved physiological stabilization that may lead to better maturation of neural pathways, reduced risk of hypoxia, positive parental impact, improved sleep cycles, and improved stress responses. The present study will help in evaluating the overall impact of KMC by investigating the long-term effect on neurodevelopmental impairment in the survivors.
Clinical Trials Registry-India CTRI/2019/11/021899. Registered on 06 November 2019. Trials registration of parent trial: ACTRN12618001880235; Clinical Trials Registry-India: CTRI/2018/08/015369.
Chemotherapeutic resistance via the mechanism of competitive release of resistant tumor cell subpopulations is a major problem associated with cancer treatments and one of the main causes of tumor ...recurrence. Often, chemoresistance is mitigated by using multidrug schedules (two or more combination therapies) that can act synergistically, additively, or antagonistically on the heterogeneous population of cells as they evolve. In this paper, we develop a three-component evolutionary game theory model to design two-drug adaptive schedules that mitigate chemoresistance and delay tumor recurrence in an evolving collection of tumor cells with two resistant subpopulations and one chemosensitive population that has a higher baseline fitness but is not resistant to either drug. Using the nonlinear replicator dynamical system with a payoff matrix of Prisoner's Dilemma (PD) type (enforcing a cost to resistance), we investigate the nonlinear dynamics of this three-component system along with an additional tumor growth model whose growth rate is a function of the fitness landscape of the tumor cell populations. A key parameter determines whether the two drugs interact synergistically, additively, or antagonistically. We show that antagonistic drug interactions generally result in slower rates of adaptation of the resistant cells than synergistic ones, making them more effective in combating the evolution of resistance. We then design evolutionary cycles (closed loops) in the three-component phase space by shaping the fitness landscape of the cell populations (i.e., altering the evolutionary stable states of the game) using appropriately designed time-dependent schedules (adaptive therapy), altering the dosages and timing of the two drugs. We describe two key bifurcations associated with our drug interaction parameter which help explain why antagonistic interactions are more effective at controlling competitive release of the resistant population than synergistic interactions in the context of an evolving tumor.
REASONS FOR PERFORMING THE STUDY: Few data are available on the prevalence of obesity in the general equine population of Great Britain (GB), and its associated risk factors. OBJECTIVES: To estimate ...the prevalence of owner‐reported obesity in veterinary‐registered horses and ponies in GB, and identify factors associated with obesity. STUDY DESIGN: A cross‐sectional survey of horse/pony owners in GB was undertaken using a postal questionnaire. METHODS: Thirty veterinary practices randomly selected horse/pony owners to complete a self‐administered postal questionnaire. Owners estimated body condition score using a modified Carroll and Huntington method (1–6 scale), and animals were classified as obese if they were scored as either 5 (fat) or 6 (very fat). Factors associated with obesity were assessed using logistic regression analysis. RESULTS: Prevalence of obesity was 31.2% (n = 247/792; 95% confidence interval CI 27.9–34.2%). Factors associated with increased odds of obesity were breed (P<0.001), ease of maintaining weight (P<0.001) and primary use (P = 0.002). Compared to Thoroughbreds, draught‐type (odds ratio OR 7.3; 95% CI 3.1–17.1), cob‐type (OR 5.6; 95% CI 2.5–12.5), native (OR 3.2; 95% CI 1.8–5.78) and Welsh breeds (OR 3.5; 95% CI 1.9–6.2) were more likely to be obese. Animals described as ‘good doers’ were more likely to be obese than those described as readily maintaining normal weight (OR 3.7; 95% CI 2.6–5.3). Compared to competition animals, animals used for pleasure riding (OR 2.5; 95% CI 1.4–4.4) and nonridden animals (OR 2.9; 95% CI 1.5–5.5) were more likely to be obese. CONCLUSIONS: Identification of at‐risk breeds and other horse‐ and management‐level risk factors for obesity will enable optimal targeting of owner education regarding management strategies to reduce the frequency of equine obesity.
PDF
