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As infected and vaccinated population increases, some countries decided not to impose non-pharmaceutical intervention measures anymore and to coexist with COVID-19. However, we do not have a comprehensive understanding of its consequence, especially for China where most population has not been infected and most Omicron transmissions are silent. This paper aims to reveal the complete silent transmission dynamics of COVID-19 by agent-based simulations overlaying a big data of more than 0.7 million real individual mobility tracks without any intervention measures throughout a week in a Chinese city, with an extent of completeness and realism not attained in existing studies. Together with the empirically inferred transmission rate of COVID-19, we find surprisingly that with only 70 citizens to be infected initially, 0.33 million becomes infected silently at last. We also reveal a characteristic daily periodic pattern of the transmission dynamics, with peaks in mornings and afternoons. In addition, by inferring individual professions, visited locations and age group, we found that retailing, catering and hotel staff are more likely to get infected than other professions, and elderly and retirees are more likely to get infected at home than outside home. Author summary: Since 2019, we have witnessed the worldwide battle against COVID-19. As infected and vaccinated population increases, some countries chose not to impose any non-pharmaceutical measures and to live with COVID-19. In the literature, an extensive effort has been made to understand the effectiveness of intervention measures against COVID-19 and to predict its prevalence, but much less is known about the risk of choosing to coexist with COVID-19. Here, we conduct agent-based simulations overlaying a high-frequency mobility big data which records individual mobility tracks up to every second in a large-scale city in northern China, revealing the comprehensive transmission dynamics from a few initial infected individuals to city-wise infections. Such comprehensive understanding will provide useful insights into our battle against COVID-19. [ABSTRACT FROM AUTHOR]

Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of appropriate data. However, mathematical and computational tools can be used to extract part of this information from the available data, like some hidden age-related characteristics. In this paper, we present a method to investigate age-specific differences in transmission parameters related to susceptibility to and infectiousness upon contracting SARS-CoV-2 infection. More specifically, we use panel-based social contact data from diary-based surveys conducted in Belgium combined with the next generation principle to infer the relative incidence and we compare this to real-life incidence data. Comparing these two allows for the estimation of age-specific transmission parameters. Our analysis implies the susceptibility in children to be around half of the susceptibility in adults, and even lower for very young children (preschooler). However, the probability of adults and the elderly to contract the infection is decreasing throughout the vaccination campaign, thereby modifying the picture over time. Author summary: Basic transmission dynamic characteristics of SARS-CoV-2, such as the probability of acquiring infection when exposed ("susceptibility"), and the probability of transmitting infection when infected ("infectiousness") may be age-dependent. We present a computational method to estimate these age-specific characteristics using Belgian social contact and surveillance data. We found that children are less susceptible to infection than adults, with the former experiencing 20% to 50% of the susceptibility in adults, while the infectiousness is more difficult to discern. The force of infection (probability of acquiring infection per unit time) decreases over time for the oldest age groups first, following the roll-out of the vaccination campaign which targeted the elderly first. [ABSTRACT FROM AUTHOR]

Surprise is a key component of many learning experiences, and yet its precise computational role, and how it changes with age, remain debated. One major challenge is that surprise often occurs jointly with other variables, such as uncertainty and outcome probability. To assess how humans learn from surprising events, and whether aging affects this process, we studied choices while participants learned from bandits with either Gaussian or bi-modal outcome distributions, which decoupled outcome probability, uncertainty, and surprise. A total of 102 participants (51 older, aged 50—73; 51 younger, 19–30 years) chose between three bandits, one of which had a bimodal outcome distribution. Behavioral analyses showed that both age-groups learned the average of the bimodal bandit less well. A trial-by-trial analysis indicated that participants performed choice reversals immediately following large absolute prediction errors, consistent with heightened sensitivity to surprise. This effect was stronger in older adults. Computational models indicated that learning rates in younger as well as older adults were influenced by surprise, rather than uncertainty, but also suggested large interindividual variability in the process underlying learning in our task. Our work bridges between behavioral economics research that has focused on how outcomes with low probability affect choice in older adults, and reinforcement learning work that has investigated age differences in the effects of uncertainty and suggests that older adults overly adapt to surprising events, even when accounting for probability and uncertainty effects. Author summary: Learning is a skill that requires a finely adjusted process of extracting just the right information from past experiences to benefit future choices. As we age, this process begins to alter, changing how we react to ambiguity, risk or uncertainty. One challenging aspect of learning is that sometimes we will encounter very surprising consequences of our actions, raising the question whether we should assign more or less weight to these events. We know relatively little about how humans react to these surprises and how age affects learning from surprising outcomes. To learn more about this question, we asked 51 older and 51 younger adults to play a reinforcement learning task that confronted them with surprising outcomes and analyzed their choices. We found that both age groups showed heightened sensitivity to surprising outcomes that resulted in distinctive behavioral adjustments. Notably, older adults weighted these surprising events more than younger adults. Comparing the choices of participants with computational models that incorporated surprises in different ways, we found a model that modulated its learning with the amount of surprise to mimic participants' choices best. The results help to better understand the role of past surprising events during learning in older and younger adults. [ABSTRACT FROM AUTHOR]

Younger and older adults often differ in their risky choices. Theoretical frameworks on human aging point to various cognitive and motivational factors that might underlie these differences. Using a novel computational model based on the framework of resource rationality, we find that the two age groups rely on different strategies. Importantly, older adults did not use simpler strategies than younger adults, they did not select among fewer strategies, they did not make more errors, and they did not put more weight on cognitive costs. Instead, older adults selected strategies that had different risk propensities than those selected by younger adults. Our modeling approach suggests that age differences in risky choice are not necessarily a consequence of cognitive decline; instead, they may reflect motivational differences between age groups. Author summary: What are the psychological mechanisms underlying adult age differences in economic decision making? We investigated this question with a model based on the framework of resource rationality, which posits that people adaptively use the cognitive resources available to them. Unlike commonly used economic models of decision making, this model can shed light on the cognitive processes that drive age differences in choice. Our findings show that younger and older adults use different decision strategies and that the age differences are not necessarily the result of cognitive decline; instead, they may be a result of age differences in motivational factors. By providing novel insights into the psychological mechanisms of age differences in decision making, our modeling approach can inform interventions and choice architectures supporting older adults' decision making. [ABSTRACT FROM AUTHOR]

Human populations show rich cultural diversity. Underpinning this diversity of tools, rituals, and cultural norms are complex interactions between cultural evolutionary and demographic processes. Most models of cultural change assume that individuals use the same learning modes and methods throughout their lives. However, empirical data on ‘learning life histories’—the balance of dominant modes of learning (for example, learning from parents, peers, or unrelated elders) throughout an individual’s lifetime—suggest that age structure may play a crucial role in determining learning modes and cultural evolutionary trajectories. Thus, studied in isolation, demographic and cultural evolutionary models show only part of the picture. This paper describes a mathematical and computational framework that combines demographic and cultural evolutionary methods. Using this general framework, we examine interactions between the ways in which culture is spread throughout an individual’s lifetime and cultural change across generations. We show that including demographic structure alongside cultural dynamics can help to explain domain-specific patterns of cultural evolution that are a persistent feature of cultural data, and can shed new light on rare but significant demographic events. [ABSTRACT FROM AUTHOR]

This paper presents a data analysis framework to uncover relationships between health conditions, age and sex for a large population of patients. We study a massive heterogeneous sample of 1.7 million patients in Brazil, containing 47 million of health records with detailed medical conditions for visits to medical facilities for a period of 17 months. The findings suggest that medical conditions can be grouped into clusters that share very distinctive densities in the ages of the patients. For each cluster, we further present the ICD-10 chapters within it. Finally, we relate the findings to comorbidity networks, uncovering the relation of the discovered clusters of age densities to comorbidity networks literature. [ABSTRACT FROM AUTHOR]

Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic. Author summary: We utilized two geographic-age-structured models (an individual-based model and a meta-population model) to conduct a scenario-based analysis aimed at evaluating strategies for geographic prioritization of COVID-19 vaccines in Norway. By reconstructing the dynamics of COVID-19 transmission from January to July of 2021, we compared various alternative vaccination strategies through model simulations, given the limited number of vaccine doses. We found that prioritization of vaccines based on geographic location, alongside considering age, was preferable to a baseline strategy without geographic prioritization. We assessed the selection of which municipalities to prioritize and the degree of prioritization they should receive. Our findings indicated that optimal strategies depended on whether the aim was to minimize infections, hospitalizations, ICU admissions, or deaths. Trade-offs in infection growth between municipalities and subsequent risk-class allocations (such as age groups) were the primary factors influencing optimal vaccine allocation. Furthermore, we found that earlier implementation of most geographic prioritization strategies was advantageous in reducing the overall burden of COVID-19. [ABSTRACT FROM AUTHOR]

Mathematical and statistical models can be used to make predictions of how epidemics may progress in the near future and form a central part of outbreak mitigation and control. Renewal equation based models allow inference of epidemiological parameters from historical data and forecast future epidemic dynamics without requiring complex mechanistic assumptions. However, these models typically ignore interaction between age groups, partly due to challenges in parameterising a time varying interaction matrix. Social contact data collected regularly during the COVID-19 epidemic provide a means to inform interaction between age groups in real-time. We developed an age-specific forecasting framework and applied it to two age-stratified time-series: incidence of SARS-CoV-2 infection, estimated from a national infection and antibody prevalence survey; and, reported cases according to the UK national COVID-19 dashboard. Jointly fitting our model to social contact data from the CoMix study, we inferred a time-varying next generation matrix which we used to project infections and cases in the four weeks following each of 29 forecast dates between October 2020 and November 2021. We evaluated the forecasts using proper scoring rules and compared performance with three other models with alternative data and specifications alongside two naive baseline models. Overall, incorporating age interaction improved forecasts of infections and the CoMix-data-informed model was the best performing model at time horizons between two and four weeks. However, this was not true when forecasting cases. We found that age group interaction was most important for predicting cases in children and older adults. The contact-data-informed models performed best during the winter months of 2020–2021, but performed comparatively poorly in other periods. We highlight challenges regarding the incorporation of contact data in forecasting and offer proposals as to how to extend and adapt our approach, which may lead to more successful forecasts in future. Author summary: Short term epidemic forecasts help policy makers to plan and implement response activities. It can be useful to have such forecasts separately for different age groups, in order to reflect potential differences in transmission and incidence of infection between age groups as well as differences in risk of severe disease or death. A key challenge in developing age-specific models is understanding how different age-groups interact. We used data collected during a large-scale weekly survey of social contacts in the UK to inform this interaction in a model for short-term forecasts of COVID-19. To assess whether allowing interaction between age-groups and the use of contact data improved forecasts, we compared our forecasts to those from a set of models that either didn't use current contact data or treated each age group as a separate population. We found that including timely contact data improved predictions when forecasting two to four weeks into the future, but this improvement was not consistent throughout the epidemic. The best improvement was measured during a long national "lockdown". We also found that inclusion of age-group interaction and use of contact data were most important when forecasting infections in older adults and young children. [ABSTRACT FROM AUTHOR]

COVID-19 has disproportionately impacted individuals depending on where they live and work, and based on their race, ethnicity, and socioeconomic status. Studies have documented catastrophic disparities at critical points throughout the pandemic, but have not yet systematically tracked their severity through time. Using anonymized hospitalization data from March 11, 2020 to June 1, 2021 and fine-grain infection hospitalization rates, we estimate the time-varying burden of COVID-19 by age group and ZIP code in Austin, Texas. During this 15-month period, we estimate an overall 23.7% (95% CrI: 22.5–24.8%) infection rate and 29.4% (95% CrI: 28.0–31.0%) case reporting rate. Individuals over 65 were less likely to be infected than younger age groups (11.2% [95% CrI: 10.3–12.0%] vs 25.1% [95% CrI: 23.7–26.4%]), but more likely to be hospitalized (1,965 per 100,000 vs 376 per 100,000) and have their infections reported (53% [95% CrI: 49–57%] vs 28% [95% CrI: 27–30%]). We used a mixed effect poisson regression model to estimate disparities in infection and reporting rates as a function of social vulnerability. We compared ZIP codes ranking in the 75th percentile of vulnerability to those in the 25th percentile, and found that the more vulnerable communities had 2.5 (95% CrI: 2.0–3.0) times the infection rate and only 70% (95% CrI: 60%-82%) the reporting rate compared to the less vulnerable communities. Inequality persisted but declined significantly over the 15-month study period. Our results suggest that further public health efforts are needed to mitigate local COVID-19 disparities and that the CDC's social vulnerability index may serve as a reliable predictor of risk on a local scale when surveillance data are limited. Author summary: COVID-19 disproportionately impacted communities based on their socioeconomic and racial composition. Studies have documented catastrophic disparities at multiple geographic scales, but have not yet tracked how they evolved over time. Here, we use fine-grain epidemiological data to estimate the time-varying disparate burden of COVID-19 by age group and ZIP code in Austin, Texas. During this 15-month period, we estimate that 23.7% (95% CrI: 22.5–24.8%) of the population was infected and 29.4% (95% CrI: 28.0–31.0%) of those infections were reported. Infections were not spread evenly across the region. Individuals over 65 were significantly less likely to be infected than younger age groups (11.2% [95% CrI: 10.3–12.0%] vs 25.1% [95% CrI: 23.7–26.4%]), suggesting that efforts to protect those populations may have been effective. We found that the most vulnerable ZIP codes in the region faced 2.5 times the infection risks compared with the least vulnerable ZIP codes, and that infections were only 70% as likely to be reported in vulnerable communities. Inequality persisted but declined significantly over the 15-month study period. Further public health efforts are needed to address local COVID-19 disparities. [ABSTRACT FROM AUTHOR]

We evaluate the efficiency of various heuristic strategies for allocating vaccines against COVID-19 and compare them to strategies found using optimal control theory. Our approach is based on a mathematical model which tracks the spread of disease among different age groups and across different geographical regions, and we introduce a method to combine age-specific contact data to geographical movement data. As a case study, we model the epidemic in the population of mainland Finland utilizing mobility data from a major telecom operator. Our approach allows to determine which geographical regions and age groups should be targeted first in order to minimize the number of deaths. In the scenarios that we test, we find that distributing vaccines demographically and in an age-descending order is not optimal for minimizing deaths and the burden of disease. Instead, more lives could be saved by using strategies which emphasize high-incidence regions and distribute vaccines in parallel to multiple age groups. The level of emphasis that high-incidence regions should be given depends on the overall transmission rate in the population. This observation highlights the importance of updating the vaccination strategy when the effective reproduction number changes due to the general contact patterns changing and new virus variants entering. Author summary: The COVID-19 vaccines are now available worldwide and many countries follow the practice of distributing them heuristically e.g. in age-descending order and demographically. Here we evaluate the effectiveness of such strategies by comparing them with optimized ones from an age and spatially-structured mathematical model of COVID-19 transmission. We find that vaccinating multiple age groups simultaneously and targeting regions with the the highest incidence can save more lives than heuristic strategies. Our work also reveals the importance of assessing the vaccination strategy at different stages of the epidemic. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines have been approved for children of age five and older in many countries. However, there is an ongoing debate as to whether children should be vaccinated and at what priority. In this work, we use mathematical modeling and optimization to study how vaccine allocations to different age groups effect epidemic outcomes. In particular, we consider the effect of extending vaccination campaigns to include the vaccination of children. When vaccine availability is limited, we consider Pareto-optimal allocations with respect to competing measures of the number of infections and mortality and systematically study the trade-offs among them. In the scenarios considered, when some weight is given to the number of infections, we find that it is optimal to allocate vaccines to adolescents in the age group 10-19, even when they are assumed to be less susceptible than adults. We further find that age group 0-9 is included in the optimal allocation for sufficiently high values of the basic reproduction number. Author summary: The management of a vaccination campaign requires constant evaluation, and, as conditions change, redesign of the campaign for the future. One example of a change that leads to a decision point is the extension of vaccine eligibility to broader segments of the population. Indeed, one of the questions public health experts and policymakers confront is whether children of age 5 and older should be vaccinated against COVID-19 and at what priority. In this work, we use mathematical and computational methods to study this question in a systematic, quantitative way, by considering optimal outcomes, under different criteria for optimality, that can be achieved with and without vaccination of children, under conditions of limited vaccine availability. To explore tradeoffs among different goals, such as reducing the number of infections and reducing mortality, we use the the idea of Pareto optimization. Our results show that, under a broad range of conditions, optimal vaccine allocations include vaccination of age group 10–19, while the population-level benefits of vaccination of age group 0–9 depends on the reproductive number and vaccine availability. [ABSTRACT FROM AUTHOR]

The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries. Author summary: Over 100 countries have reported laboratory-confirmed cases of atypical pneumonia caused by 2019 novel coronavirus (COVID-19). Cases are largely reported in older age groups, suggesting a strong age-dependent component to either transmission or the probability of developing symptoms and thus being detected. We introduce a mathematical model for COVID-19 transmission in which contact behaviour, susceptibility, detection probability, and transmission from undetected cases all vary with age. We fit our model to epidemiological data from the outbreak in China for the special case where asymptomatic transmission is negligible, and compare it to a null model where only contact behaviour varies with age. Our fitted model suggests that contacts involving older individuals are particularly likely to generate new detected cases, intensifying the spread of infection in countries with older populations. We estimate the basic reproductive ratio (a measure of a pathogen's capacity for spread) of COVID-19 in 152 countries under both models, and find that estimates of the basic reproductive ratio are highly dependent on the assumed underlying transmission structure; our more complex model predicts higher values in Japan and much of Europe and lower values in much of Africa, in comparison to the contact frequency-based model where this pattern is reversed. [ABSTRACT FROM AUTHOR]

Given the highly dynamic and complex nature of the human gut microbial community, the ability to identify and predict time-dependent compositional patterns of microbes is crucial to our understanding of the structure and functions of this ecosystem. One factor that could affect such time-dependent patterns is microbial interactions, wherein community composition at a given time point affects the microbial composition at a later time point. However, the field has not yet settled on the degree of this effect. Specifically, it has been recently suggested that only a minority of taxa depend on the microbial composition in earlier times. To address the issue of identifying and predicting temporal microbial patterns we developed a new model, MTV-LMM (Microbial Temporal Variability Linear Mixed Model), a linear mixed model for the prediction of microbial community temporal dynamics. MTV-LMM can identify time-dependent microbes (i.e., microbes whose abundance can be predicted based on the previous microbial composition) in longitudinal studies, which can then be used to analyze the trajectory of the microbiome over time. We evaluated the performance of MTV-LMM on real and synthetic time series datasets, and found that MTV-LMM outperforms commonly used methods for microbiome time series modeling. Particularly, we demonstrate that the effect of the microbial composition in previous time points on the abundance of taxa at later time points is underestimated by a factor of at least 10 when applying previous approaches. Using MTV-LMM, we demonstrate that a considerable portion of the human gut microbiome, both in infants and adults, has a significant time-dependent component that can be predicted based on microbiome composition in earlier time points. This suggests that microbiome composition at a given time point is a major factor in defining future microbiome composition and that this phenomenon is considerably more common than previously reported for the human gut microbiome. [ABSTRACT FROM AUTHOR]

For encapsulated bacteria such as Streptococcus pneumoniae, asymptomatic carriage is more common and longer in duration than disease, and hence is often a more convenient endpoint for clinical trials of vaccines against these bacteria. However, using a carriage endpoint entails specific challenges. Carriage is almost always measured as prevalence, whereas the vaccine may act by reducing incidence or duration. Thus, to determine sample size requirements, its impact on prevalence must first be estimated. The relationship between incidence and prevalence (or duration and prevalence) is convex, saturating at 100% prevalence. For this reason, the proportional effect of a vaccine on prevalence is typically less than its proportional effect on incidence or duration. This relationship is further complicated in the presence of multiple pathogen strains. In addition, host immunity to carriage accumulates rapidly with frequent exposures in early years of life, creating potentially complex interactions with the vaccine’s effect. We conducted a simulation study to predict the impact of an inactivated whole cell pneumococcal vaccine—believed to reduce carriage duration—on carriage prevalence in different age groups and trial settings. We used an individual-based model of pneumococcal carriage that incorporates relevant immunological processes, both vaccine-induced and naturally acquired. Our simulations showed that for a wide range of vaccine efficacies, sampling time and age at vaccination are important determinants of sample size. There is a window of favorable sampling times during which the required sample size is relatively low, and this window is prolonged with a younger age at vaccination, and in a trial setting with lower transmission intensity. These results illustrate the ability of simulation studies to inform the planning of vaccine trials with carriage endpoints, and the methods we present here can be applied to trials evaluating other pneumococcal vaccine candidates or comparing alternative dosing schedules for the existing conjugate vaccines. [ABSTRACT FROM AUTHOR]

Annual incidence rates of varicella infection in the general population in France have been rather stable since 1991 when clinical surveillance started. Rates however show a statistically significant increase over time in children aged 0–3 years, and a decline in older individuals. A significant increase in day-care enrolment and structures’ capacity in France was also observed in the last decade. In this work we investigate the potential interplay between an increase of contacts of young children possibly caused by earlier socialization in the community and varicella transmission dynamics. To this aim, we develop an age-structured mathematical model, informed with historical demographic data and contact matrix estimates in the country, accounting for longitudinal linear increase of early childhood contacts. While the reported overall varicella incidence is well reproduced independently of mixing variations, age-specific empirical trends are better captured by accounting for an increase in contacts among pre-school children in the last decades. We found that the varicella data are consistent with a 30% increase in the number of contacts at day-care facilities, which would imply a 50% growth in the contribution of 0-3y old children to overall yearly infections in 1991–2015. Our findings suggest that an earlier exposure to pathogens due to changes in day-care contact patterns, represents a plausible explanation for the epidemiological patterns observed in France. Obtained results suggest that considering temporal changes in social factors in addition to demographic ones is critical to correctly interpret varicella transmission dynamics. [ABSTRACT FROM AUTHOR]

Public health related decisions often have to balance the cost of intervention strategies with the benefit of the reduction in disease burden. While the cost can often be inferred, forward modelling of the effect of different intervention options is complicated and disease specific. Here we introduce a package that is aimed to simplify this process. The package allows one to infer parameters using a Bayesian approach, perform forward modelling of the likely results of the proposed intervention and finally perform cost effectiveness analysis of the results. The package is based on a method previously used in the UK to inform vaccination strategies for influenza, with extensions to make it easily adaptable to other diseases and data sources. [ABSTRACT FROM AUTHOR]

Heterogeneities in contact networks have a major effect in determining whether a pathogen can become epidemic or persist at endemic levels. Epidemic models that determine which interventions can successfully prevent an outbreak need to account for social structure and mixing patterns. Contact patterns vary across age and locations (e.g. home, work, and school), and including them as predictors in transmission dynamic models of pathogens that spread socially will improve the models’ realism. Data from population-based contact diaries in eight European countries from the POLYMOD study were projected to 144 other countries using a Bayesian hierarchical model that estimated the proclivity of age-and-location-specific contact patterns for the countries, using Markov chain Monte Carlo simulation. Household level data from the Demographic and Health Surveys for nine lower-income countries and socio-demographic factors from several on-line databases for 152 countries were used to quantify similarity of countries to estimate contact patterns in the home, work, school and other locations for countries for which no contact data are available, accounting for demographic structure, household structure where known, and a variety of metrics including workforce participation and school enrolment. Contacts are highly assortative with age across all countries considered, but pronounced regional differences in the age-specific contacts at home were noticeable, with more inter-generational contacts in Asian countries than in other settings. Moreover, there were variations in contact patterns by location, with work-place contacts being least assortative. These variations led to differences in the effect of social distancing measures in an age structured epidemic model. Contacts have an important role in transmission dynamic models that use contact rates to characterize the spread of contact-transmissible diseases. This study provides estimates of mixing patterns for societies for which contact data such as POLYMOD are not yet available. [ABSTRACT FROM AUTHOR]

The study objective is to estimate the epidemiological and economic impact of vaccine interventions during influenza pandemics in Chicago, and assist in vaccine intervention priorities. Scenarios of delay in vaccine introduction with limited vaccine efficacy and limited supplies are not unlikely in future influenza pandemics, as in the 2009 H1N1 influenza pandemic. We simulated influenza pandemics in Chicago using agent-based transmission dynamic modeling. Population was distributed among high-risk and non-high risk among 0–19, 20–64 and 65+ years subpopulations. Different attack rate scenarios for catastrophic (30.15%), strong (21.96%), and moderate (11.73%) influenza pandemics were compared against vaccine intervention scenarios, at 40% coverage, 40% efficacy, and unit cost of $28.62. Sensitivity analysis for vaccine compliance, vaccine efficacy and vaccine start date was also conducted. Vaccine prioritization criteria include risk of death, total deaths, net benefits, and return on investment. The risk of death is the highest among the high-risk 65+ years subpopulation in the catastrophic influenza pandemic, and highest among the high-risk 0–19 years subpopulation in the strong and moderate influenza pandemics. The proportion of total deaths and net benefits are the highest among the high-risk 20–64 years subpopulation in the catastrophic, strong and moderate influenza pandemics. The return on investment is the highest in the high-risk 0–19 years subpopulation in the catastrophic, strong and moderate influenza pandemics. Based on risk of death and return on investment, high-risk groups of the three age group subpopulations can be prioritized for vaccination, and the vaccine interventions are cost saving for all age and risk groups. The attack rates among the children are higher than among the adults and seniors in the catastrophic, strong, and moderate influenza pandemic scenarios, due to their larger social contact network and homophilous interactions in school. Based on return on investment and higher attack rates among children, we recommend prioritizing children (0–19 years) and seniors (65+ years) after high-risk groups for influenza vaccination during times of limited vaccine supplies. Based on risk of death, we recommend prioritizing seniors (65+ years) after high-risk groups for influenza vaccination during times of limited vaccine supplies. [ABSTRACT FROM AUTHOR]

Normative models of human cognition often appeal to Bayesian filtering, which provides optimal online estimates of unknown or hidden states of the world, based on previous observations. However, in many cases it is necessary to optimise beliefs about sequences of states rather than just the current state. Importantly, Bayesian filtering and sequential inference strategies make different predictions about beliefs and subsequent choices, rendering them behaviourally dissociable. Taking data from a probabilistic reversal task we show that subjects’ choices provide strong evidence that they are representing short sequences of states. Between-subject measures of this implicit sequential inference strategy had a neurobiological underpinning and correlated with grey matter density in prefrontal and parietal cortex, as well as the hippocampus. Our findings provide, to our knowledge, the first evidence for sequential inference in human cognition, and by exploiting between subject variation in this measure we provide pointers to its neuronal substrates. [ABSTRACT FROM AUTHOR]

De novo creation of protein coding genes involves the formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the populationThese orphan proteins need to, at the bare minimum, not cause serious harm to the organism, meaning that they should for instance not aggregate. Therefore, although the creation of short ORFs could be truly random, the fixation should be subjected to some selective pressure. The selective forces acting on orphan proteins have been elusive, and contradictory results have been reported. In Drosophila young proteins are more disordered than ancient ones, while the opposite trend is present in yeast. To the best of our knowledge no valid explanation for this difference has been proposed. To solve this riddle we studied structural properties and age of proteins in 187 eukaryotic organisms. We find that, with the exception of length, there are only small differences in the properties between proteins of different ages. However, when we take the GC content into account we noted that it could explain the opposite trends observed for orphans in yeast (low GC) and Drosophila (high GC). GC content is correlated with codons coding for disorder promoting amino acids. This leads us to propose that intrinsic disorder is not a strong determining factor for fixation of orphan proteins. Instead these proteins largely resemble random proteins given a particular GC level. During evolution the properties of a protein change faster than the GC level causing the relationship between disorder and GC to gradually weaken. [ABSTRACT FROM AUTHOR]

During language processing, humans form complex embedded representations from sequential inputs. Here, we ask whether a “geometrical language” with recursive embedding also underlies the human ability to encode sequences of spatial locations. We introduce a novel paradigm in which subjects are exposed to a sequence of spatial locations on an octagon, and are asked to predict future locations. The sequences vary in complexity according to a well-defined language comprising elementary primitives and recursive rules. A detailed analysis of error patterns indicates that primitives of symmetry and rotation are spontaneously detected and used by adults, preschoolers, and adult members of an indigene group in the Amazon, the Munduruku, who have a restricted numerical and geometrical lexicon and limited access to schooling. Furthermore, subjects readily combine these geometrical primitives into hierarchically organized expressions. By evaluating a large set of such combinations, we obtained a first view of the language needed to account for the representation of visuospatial sequences in humans, and conclude that they encode visuospatial sequences by minimizing the complexity of the structured expressions that capture them. [ABSTRACT FROM AUTHOR]

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. [ABSTRACT FROM AUTHOR]

Adolescence is a period of life characterised by changes in learning and decision-making. Learning and decision-making do not rely on a unitary system, but instead require the coordination of different cognitive processes that can be mathematically formalised as dissociable computational modules. Here, we aimed to trace the developmental time-course of the computational modules responsible for learning from reward or punishment, and learning from counterfactual feedback. Adolescents and adults carried out a novel reinforcement learning paradigm in which participants learned the association between cues and probabilistic outcomes, where the outcomes differed in valence (reward versus punishment) and feedback was either partial or complete (either the outcome of the chosen option only, or the outcomes of both the chosen and unchosen option, were displayed). Computational strategies changed during development: whereas adolescents’ behaviour was better explained by a basic reinforcement learning algorithm, adults’ behaviour integrated increasingly complex computational features, namely a counterfactual learning module (enabling enhanced performance in the presence of complete feedback) and a value contextualisation module (enabling symmetrical reward and punishment learning). Unlike adults, adolescent performance did not benefit from counterfactual (complete) feedback. In addition, while adults learned symmetrically from both reward and punishment, adolescents learned from reward but were less likely to learn from punishment. This tendency to rely on rewards and not to consider alternative consequences of actions might contribute to our understanding of decision-making in adolescence. [ABSTRACT FROM AUTHOR]

Adults combine information from different sensory modalities to estimate object properties such as size or location. This process is optimal in that (i) sensory information is weighted according to relative reliability: more reliable estimates have more influence on the combined estimate and (ii) the combined estimate is more reliable than the component uni-modal estimates. Previous studies suggest that optimal sensory integration does not emerge until around 10 years of age. Younger children rely on a single modality or combine information using inappropriate sensory weights. Children aged 4–11 and adults completed a simple audio-visual task in which they reported either the number of beeps or the number of flashes in uni-modal and bi-modal conditions. In bi-modal trials, beeps and flashes differed in number by 0, 1 or 2. Mutual interactions between the sensory signals were evident at all ages: the reported number of flashes was influenced by the number of simultaneously presented beeps and vice versa. Furthermore, for all ages, the relative strength of these interactions was predicted by the relative reliabilities of the two modalities, in other words, all observers weighted the signals appropriately. The degree of cross-modal interaction decreased with age: the youngest observers could not ignore the task-irrelevant modality—they fully combined vision and audition such that they perceived equal numbers of flashes and beeps for bi-modal stimuli. Older observers showed much smaller effects of the task-irrelevant modality. Do these interactions reflect optimal integration? Full or partial cross-modal integration predicts improved reliability in bi-modal conditions. In contrast, switching between modalities reduces reliability. Model comparison suggests that older observers employed partial integration, whereas younger observers (up to around 8 years) did not integrate, but followed a sub-optimal switching strategy, responding according to either visual or auditory information on each trial. [ABSTRACT FROM AUTHOR]

The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 – 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 – 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic. [ABSTRACT FROM AUTHOR]

What factors determine a protein's rate of evolution are actively debated. Especially unclear is the relative role of intrinsic factors of present-day proteins versus historical factors such as protein age. Here we study the interplay of structural properties and evolutionary age, as determinants of protein evolutionary rate. We use a large set of one-to-one orthologs between human and mouse proteins, with mapped PDB structures. We report that previously observed structural correlations also hold within each age group - including relationships between solvent accessibility, designabililty, and evolutionary rates. However, age also plays a crucial role: age modulates the relationship between solvent accessibility and rate. Additionally, younger proteins, despite being less designable, tend to evolve faster than older proteins. We show that previously reported relationships between age and rate cannot be explained by structural biases among age groups. Finally, we introduce a knowledge-based potential function to study the stability of proteins through large-scale computation. We find that older proteins are more stable for their native structure, and more robust to mutations, than younger ones. Our results underscore that several determinants, both intrinsic and historical, can interact to determine rates of protein evolution. [ABSTRACT FROM AUTHOR]

Urogenital schistosomiasis is a tropical disease infecting more than 100 million people in sub-Saharan Africa. Individuals in endemic areas endure repeated infections with long-lived schistosome worms, and also encounter larval and egg stages of the life cycle. Protective immunity against infection develops slowly with age. Distinctive age-related patterns of infection and specific antibody responses are seen in endemic areas, including an infection 'peak shift' and a switch in the antibody types produced. Deterministic models describing changing levels of infection and antibody with age in homogeneously exposed populations were developed to identify the key mechanisms underlying the antibody switch, and to test two theories for the slow development of protective immunity: that (i) exposure to dying (long-lived) worms, or (ii) experience of a threshold level of antigen, is necessary to stimulate protective antibody. Different model structures were explored, including alternative stages of the life cycle as the main antigenic source and the principal target of protective antibody, different worm survival distributions, antigen thresholds and immune cross-regulation. Models were identified which could reproduce patterns of infection and antibody consistent with field data. Models with dying worms as the main source of protective antigen could reproduce all of these patterns, but so could some models with other continually-encountered life stages acting as the principal antigen source. An antigen threshold enhanced the ability of the model to replicate these patterns, but was not essential for it to do so. Models including either non-exponential worm survival or cross-regulation were more likely to be able to reproduce field patterns, but neither of these was absolutely required. The combination of life cycle stage stimulating, and targeted by, antibody was found to be critical in determining whether models could successfully reproduce patterns in the data, and a number of combinations were excluded as being inconsistent with field data. INSET: Author Summary. [ABSTRACT FROM AUTHOR]