Evolution, Medicine, and Public Health

Parasitism is one of the key, structural, interspecific interactions in ecology. One remarkable parasitic strategy that has been documented in multiple systems is the behavioral manipulation of hosts to increase parasite fitness. While not yet documented in humans, we propose that a ubiquitous zoonotic parasite - Toxoplasma gondii - may change human behavior to favor the parasite by increasing the fitness of the parasites definitive host - cats. Specifically, we assess the possibility that human behavioral changes resulting from chronic, latent T. gondii infection lead to measurable changes in attitudes, actions and dopaminergic responses towards cats that function to increase domestic cat fitness. We assessed the potential role of humans in the T. gondii lifecycle by identifying and testing behavioral changes in humans that benefit the parasite; specifically, human affection for cats. We assessed T. gondii infection status in 68 participants using T. gondii serum antibody testing, and assessed their attitudes towards cats in three ways: i) surveys, ii) participant behavior in the presence of domestic cats, and iii) participant oxytocin levels before and after interactions with cats to assess dopaminergic changes. Only 2 of 68 participants were positive for T. gondii antibodies, limiting statistical power. However, our results indicated that T. gondii-positive participants both reported a greater affection for cats in surveys, and spent more time engaged with cats during behavioral trials than T. gondii-negative participants (87% of study time engaging with cats vs 75%). Oxytocin results were inconclusive.

Parental rejection of apparently healthy newborns is widely classified as a behavioural abnormality in captive primate colonies, yet its biological significance remains unclear. In owl monkeys (Aotus nancymaae), parental rejection, defined here as cessation of nursing leading to rescue nursery rearing, is typically lethal for offspring and is transmitted across generations despite reducing offspring survival. Here, we tested whether parental rejection is associated with lifespan and reproductive differences in parents and their surviving offspring. We analysed long-term demographic records from a captive colony of 962 individuals and compared survival and reproductive outcomes between rejector and non-rejector parents using survival analyses and regression-based models. Parents who rejected offspring lived significantly longer than non-rejectors, with an average lifespan advantage of approximately 4-4.5 years in both males and females. This survival difference was concentrated during the prime reproductive period (6-20 years). Well-reared offspring of rejector parents also lived longer than offspring of non-rejectors, with a mean lifespan difference of 1.26 years. Rejector parents produced more offspring overall, but this difference was explained by extended lifespan rather than higher reproductive output per year. Analyses stratified by rejection timing showed no longevity advantage in first-birth rejectors, whereas parents rejecting later-born offspring exhibited longer survival. Together, these findings show that parental rejection is associated with longer lifespan in parents and in their well-reared offspring under captive conditions. These patterns are consistent with altered allocation of parental investment under energetic or environmental stress.

Evolution of drug resistance to one drug can alter the minimum inhibitory concentration to another drug. This phenomenon, known as a collateral effect, can manifest as either cross-resistance or collateral sensitivity. Various patterns of collateral effects have been observed experimentally. Repeated adaptation from the same parental strain may result in variable collateral effects; this is non-repeatability. Additionally, adaptation of a pathogen to one drug may produce a specific collateral effect to a second drug, while altering the order of drug exposure can result in a different, or even absent, collateral effect. This phenomenon is termed unidirectionality. The genetic and evolutionary mechanisms underlying these patterns remain incompletely characterised. Here, we propose a frame-work that integrates pharmacodynamics and population genetics and provide minimal examples to explain these patterns and their combinations. Furthermore, we demonstrate that drug concentration and selection regime strongly influence patterns of collateral effects, including repeatability, directionality, and their temporal dynamics.

Influenza infection results from tightly coupled interactions between viral replication, host immune responses, and the emergence of clinical symptoms. While mathematical models have extensively characterized viral and immune dynamics, the mechanistic link between immune activity and disease severity remains poorly understood. Here, we develop an integrative within-host modeling framework that explicitly connects infection dynamics, immune responses, and symptom manifestation through a unified dynamical system. Using murine influenza data, we incorporate key immune components alongside a mechanistic representation of symptom progression, quantified via host weight loss. Our analysis identifies inflammatory signaling, particularly TNF--mediated pathways, as a central driver linking immune activity to symptom severity. Importantly, we demonstrate that age-dependent alterations in immune regulation reshape this coupling: aged hosts exhibit prolonged inflammatory responses that amplify and sustain symptom burden despite comparable viral kinetics. These results highlight that disease severity cannot be inferred from viral load alone, but instead emerges from the dynamical interplay between immune regulation and host physiology. This framework provides a quantitative basis for understanding age-specific morbidity and offers a foundation for designing interventions that target immune-mediated pathology rather than viral replication alone.

The COVID-19 pandemic saw successive emergence and global spread of novel viral variants, exhibiting enhanced transmissibility or evasion of immunity. While the genotypic and phenotypic basis of SARS-CoV-2 variants have been extensively characterized, the evolutionary factors governing their patterns of emergence are less well understood. In this study we systematically investigated how the invasion dynamics of viral variants depend on variant phenotype (increased transmissibility or immune evasion), source (local evolution vs importation), the timing of introduction, the distribution of population susceptibility, and the contact network structure. Using a stochastic multi-strain epidemic model, we find that strains with only a transmission advantage are more likely to emerge earlier in the epidemic, and rapidly and predictably dominate the viral population. In contrast, immune-escape variants tend to linger at low prevalence for extended time periods after emergence, avoiding detection, until a critical amount of immunity has built up in the population and they begin to rapidly outcompete existing strains. We find that two common features of realistic human contact networks---heterogeneity in contacts (overdispersion) and clustering---lead to more punctuated evolutionary dynamics. This work provides insight into past dynamics of SARS-CoV-2 variants and can help define planning scenarios for future epidemic modeling efforts.

Object play - seemingly non-functional interactions with objects - can promote the development of foraging skills, tool use, and behavioral innovation. Among Catarrhine monkeys, it was described in macaques and baboons. Wild geladas, although closely related to baboons, have been described as lacking object play (observed only in captivity) linked to their specialized grazing ecology. Here, we provide the first evidence of both social and solitary object play in a wild gelada population (NOMUs=13) at Debre Libanos (Ethiopia) and compare it with object play in sympatric olive baboons (Nindividuals=42). Notably, immature geladas engaged in object play both socially and solitarily, but the latter case was most frequent also with novel objects introduced by researchers. Solitary object play occurred at levels comparable to those of baboons, challenging previous reports of limited object interest in geladas. This finding aligns with the occurrence of object play in phylogenetically related species and with the retention in wild geladas of arboreal behavior and fruit consumption and hand morphology enhancing fine manipulation. Hence, object play in geladas under certain environmental conditions may reflect a biologically rooted capacity and underscores the importance of ecological variability, as distinct behavioral ecotypes can emerge across different populations of the same species.

Interactions among co-circulating parasite species influence infection risk and disease progression. Such interactions can occur within hosts, for example altering susceptibility, or indirectly through host demography or movement, potentially affecting landscape-scale transmission. Despite their ubiquity, the spatial implications of these interactions have received limited attention. We combine spatially-explicit modelling with laboratory experiments to investigate how different parasite-parasite interactions influence disease spread. We model within-host, demographic, and dispersal-related interactions across a linear landscape, showing that within-host interactions modifying host susceptibility have the strongest effects on parasite prevalence, spatial heterogeneity, and rate of spread. Furthermore, these effects are amplified when parasites invade sequentially, generating pronounced patch-level spatial priority effects. We tested these predictions experimentally using a protist host (Paramecium caudatum) and two bacterial parasites (Holospora undulata and H. obtusa). Consistent with model predictions, we found that H. obtusa reduces prevalence and spatial spread of H. undulata through reductions in host susceptibility, and found evidence for spatial priority effects, observing reduced H. undulata prevalence when introduced after H. obtusa. Our theoretical and experimental results highlight that parasite-parasite interactions can have important implications for parasite spatial epidemiology, but the magnitude of those effects depend on the interaction type and the timing of invasion.

Global populations are ageing at an unprecedented rate. For many diseases, age is a strong indicator of susceptibility, morbidity, or mortality. Principles of evolutionary biology can be leveraged to understand how pathogens may optimally exploit new populations, and the impact of this on the global burden of infectious-disease-induced mortality. We parameterised an age-specific R0 model with 2017 epidemiological data on Measles, Tuberculosis, Meningitis, and Ebola, and age-specific demographic estimates for 2017 and 2050, for the seven Global Burden of Disease super-regions. We explored the theoretical trade-offs between pathogen virulence & transmission, and virulence & host recovery, parameterising trade-off parameters using Latin Hypercube Sampling. Population ageing between 2017-2050 saw an increase in virulence induced mortality in four settings: 1) Ebola in sub-Saharan Africa, 2) Measles in central/eastern Europe & central Asia region, 3) Measles in North Africa & the Middle East and 4) Tuberculosis in the central/eastern Europe & central Asia region. The decrease in infection duration due to an increase of elderly people drives pathogen virulence down for diseases in the remaining settings. Understanding the mechanisms that shape pathogen dynamics and leveraging this to predict future challenges is key to endemic disease management in a rapidly changing world. Author SummaryKey aspects of disease transmission including susceptibility to infection, the severity of infection, and the probability of dying from that infection, are affected by host age. Global populations are rapidly ageing, so that the mean age of most populations is generally higher than it used to be and is set to continue on this trajectory. This suggests that the dynamics of infectious diseases are also likely to change, although infectious disease dynamics tend to be non-linear as these key parameters interact. We have developed a dynamic modelling framework to explore how changes in population age structure might impact the optimal level of pathogen virulence in a population. We have chosen four infectious diseases as case studies, that differentially impact certain age classes to illustrate these dynamics. We have parameterised this framework with open access data for each of the seven Global Burden of Disease super-regions and show that population ageing can increase virulence for several diseases in differing global regions, whilst increased background rates of mortality can drive virulence down in others.

Female genital cutting (FGC) is identified within global health and human rights discourse as aligned with gender inequality and female disempowerment. The persistence of FGC in high-prevalence societies is assumed to reflect womens limited influence over decisions concerning their daughters. Yet anthropological research has questioned whether this interpretation adequately reflects how FGC is organized within practicing communities. Across two studies with 176,728 participants from 15 African and Asian countries, we examine whether mothers attitudes toward FGC predict daughters circumcision status and whether this relationship varies with regional FGC prevalence. Multilevel logistic regression models show that maternal attitudes strongly predict daughter circumcision status across both datasets. Contrary to expectations derived from disempowerment frameworks, the association between maternal attitudes and daughter outcomes is not weaker in high-prevalence contexts, it is stronger. These findings suggest that interpretations of FGC as reflecting female disempowerment may mischaracterize the social dynamics of societies in which FGC is common. Policy implications of the findings are discussed.

Our bodies have evolved to maintain homeostasis through regulatory systems that continuously adapt to keep physiological processes within a normal range. From this perspective, complex chronic disease can be understood as a breakdown of compensatory mechanisms, resulting in loss of homeostasis. Here we propose that adaptive receptor expression dynamics may serve as one such compensatory mechanism, increasing receptor surface expression when external ligand is insufficient, and clearing it when signaling is excessive. To explore this, we adapt a previously published agent-based model and simulate it under a range of scenarios. We find that the system of adaptive receptor expression is robust to oscillatory perturbations but not to chronic stress. We propose that receptor turnover dynamics may be better understood as an adaptive, environmentally responsive process rather than a fixed biological property, and that in some cases, disease manifests only after compensatory mechanisms have been pushed past their limits. We conclude with a discussion of implications for understanding complex chronic diseases, for thinking about epigenetic and mutational change as escalating layers of adaptation, and for how we model receptor dynamics in the context of receptor-mediated drug activity.

The diversification of biodiversity progresses as newly evolving species adapt to occupy available niche space - including the temporal dimension. Throughout the history of life, animal species adapted to occupy specific regions, or all regions (cathemerality), of the day-night temporal spectrum. While adaptive radiation theory is predicted to drive much of the global proliferation of biodiversity, the role that the day-night temporal dimension plays in offering ecological opportunity for lineages to diversify remains fundamentally neglected. Using a dataset spanning 19,940 species from across all four main tetrapod lineages (amphibians, squamates (restricted to lizards), mammals and archosaurs), we perform the very first evolutionarily standardised temporal niche diversification analysis and the first to include substantial number of ectotherms. We examine temporal niche as a source of ecological opportunity for adaptive radiation and contrast how lineages have leveraged ecological opportunity spread across 24h time. Findings revealed that tetrapods most frequently transitioned towards diurnality, suggesting a general opening of ecological opportunity in diurnal niche space since the K-Pg mass extinction. Moreover, amphibians are faster and more flexible than amniotes in temporal niche evolution, supported by a relatively higher speed of temporal niche transition and by spending relatively more in time cathemerality, potentially compensating for limitations in geographic dispersal. This interpretation suggests the day-night temporal niche dimension interacts with the geographic dimension, as it exhibits processes which unfold in parallel to (independent of) the geographic dimension as well as processes which unfold in response to what occurs in the geographic dimension.

Collective behavior in animal societies can buffer individual costs and confer resilience to environmental challenges. However, the mechanisms by which groups sustain function when members are compromised remain poorly understood. In the presented study, we investigate how social context shapes collective fanning, a thermoregulatory behavior critical for colony function, in Western honeybees (Apis mellifera). Using oxytetracycline (OTC), a known physiologically disruptive antibiotic to honeybees, to selectively impair certain group members, we tested our hypothesis that the presence of untreated bees would rescue the fanning response in mixed-composition groups. We show that groups containing untreated individuals fan at levels comparable to fully untreated groups, despite the presence of OTC-impaired bees. This preservation of collective thermoregulatory function was correlated with both treated and untreated individuals in mixed groups shifting their interaction dynamics and social network positions. These findings reveal a decentralized mechanism of collective resilience, whereby behavioral compensation by individuals sustains group-level thermoregulation under partial disruption. Our results provide a framework for understanding how social insect colonies maintain function in the face of individual-level perturbations, with broader implications for predicting the limits of collective resilience in animal societies experiencing increasing environmental pressures.

A populations social structure, often represented as a social network, shapes fundamental biological processes including the spread of disease, information, and behaviour. The Friendship Paradox is a network phenomenon whereby the average individual has fewer friends than their friends do. This effect can be quantified as relationship disparity (the difference between an individuals connectedness and those they are connected to) which captures the local social environment. Previous work has shown that such relationship disparity can be exploited in effective outbreak monitoring, targeted health interventions and optimized contact tracing. Yet, how its magnitude varies across real-world social networks remains poorly understood. Here, we analyse relationship disparity across 391 empirical animal social networks to test how intrinsic network properties and biological attributes predict its extent. We find that smaller and sparser networks exhibit stronger relationship disparity, and that mammalian and avian social systems generally showed stronger relationship disparity than reptilian systems. After controlling for variation in individual sociability, mammalian and reptilian social networks displayed weaker relationship disparity than expected based on network structure alone. Together, these findings demonstrate that both network structure and biological attributes shape relationship disparity in natural social systems, providing a foundation for predicting how higher-order network architecture influences social processes such as contagion. Significance StatementIn natural populations, social connections are unevenly distributed, often resulting in a small subset of individuals that are highly connected while many are relatively peripheral. The Friendship Paradox is a measure of relationship disparity between individuals and their local social environment. Understanding how features of the social network and biological system are associated with relationship disparity can contribute to understanding what shapes social behaviour. Relationship disparity may not just be an emergent network property but could reflect a higher level of social structuring, and therefore shape processes that depend on social contacts. Our findings demonstrate the value of comparative network analysis for generating insights into fundamental principles structuring real-world societies.

Life history traits are often correlated, creating trade-offs that may impede the response to natural selection and be responsible for the evolution of senescence. These trade-offs may arise through pleiotropic effects, which can affect the response to selection in ways that resemble intra-locus sexual antagonism. Despite these hypothesized relationships, we lack clear connections between pleiotropy, sexual antagonism, and the evolution of life histories. Empirical tests for inter-sexual differences in life-history traits, including sex-specific aging, can be used to evaluate hypotheses about how pleiotropy and sexual conflict affect evolutionary trade-offs. To those ends, we measured lifespan, development time, and body size in Drosophila pseudoobscura males and females, each of which carried one of six third chromosome inversion genotypes. Temperature affected lifespan and development more than any other factor; higher temperatures increased mortality rate, decreased lifespan, and accelerated development. However, we also observed sex differences in mortality rates and development times that depended on genotype and temperature. Notably, temperature elevated the initial mortality rate across all flies, yet increasing temperatures reduced the rate of aging in some genotype-sex combinations. Similarly, direct effects of genotype on mortality rate and development time depended greatly on sex and temperature, but there was no genotype effect on body size. Despite these context-dependent genotype effects on life history traits, we failed to identify any correlations that would serve as clear evidence for sexual conflict or trade-offs. Our results therefore suggest that either historical conflicts have been resolved or any conflicts that may exist do not result in the correlations predicted by existing models.

Predator-prey interactions are key drivers of behavioural and life-history evolution, yet their mechanisms remain difficult to study in natural contexts. The nematode Pristionchus pacificus is a model predator, but most studies exploring its behaviours use Caenorhabditis elegans as prey, a species that it likely only rarely encountered in nature. Here, we examine predation within nematode communities associated with beetle carcasses, the native necromenic habitat of P. pacificus. We identify Oscheius myriophilus as a cohabiting species, likely representing natural prey. Using predatory assays, automated tracking, and machine-learning-based behavioural analysis, we show that P. pacificus actively kills and consumes O. myriophilus. Strikingly, predation rates are lower than those observed for C. elegans, suggesting partial resistance or reciprocal adaptation in O. myriophilus. Consistent with this, O. myriophilus exhibits a mixed reproductive strategy, with early oviposition followed by ovoviviparity and matricide. As later developmental stages are more resistant to predation, internal hatching may protect offspring while providing maternal resources for development. These findings establish these nematodes as a tractable model for investigating predator-prey interactions and their evolutionary consequences, highlighting how behavioural strategies and life-history traits can co-evolve in natural communities.

Early-life trauma in humans, including maternal loss, is strongly associated with increased risk of chronic diseases, reduced life expectancy, and accelerated biological aging, as measured through epigenetic modifications, such as DNA methylation. Whether similar patterns occur in other long-lived, socially complex non-primate species, however, remains unknown. Elephants share key life-history traits with humans, including longevity, strong social bonds, and advanced cognitive abilities. Yet wild elephant populations face significant anthropogenic and environmental pressures, including poaching, habitat loss, and human-wildlife conflict that can result in maternal mortality and subsequent calf orphaning. We examined whether orphaning of elephant calves was associated with accelerated DNA methylation age and distinct epigenetic signatures. Contrary to our hypothesis and patterns observed in other species, orphaned African savanna elephants exhibited a younger DNA methylation age than non-orphans, no accelerated aging, and only limited differential methylation at CpG sites. At the genome-wide level, chronological age was not associated with differential CpG methylation after correcting for multiple testing. One interpretation of these findings is that elephants may have evolved mechanisms that buffer against epigenetic instability following stressful events. Investigating these protective mechanisms in elephants could inform strategies to mitigate the long-term health impacts of early-life trauma in humans. Significance StatementIn most mammals, early-life adversity, including maternal loss is associated with shorter lifespans and widespread epigenetic alterations. In contrast, we found that orphaned African savanna elephants exhibited a younger epigenetic age compared to non-orphans and showed only a weak distinct epigenetic signature. This unexpected pattern may reflect environmental influences, such as living under human care, or evolutionary adaptations that buffer against epigenetic instability. If the latter is confirmed, such mechanisms could confer resilience to the epigenetic consequences of early-life adversity.

We present the first radiographic ageing framework for common dolphins (Delphinus delphis), based on ossification and epiphyseal fusion patterns in the pectoral flipper, demonstrating higher reliability for chronological age estimation than currently available epigenetic approaches for this species. Using individuals of known dental age, we calibrated two modelling approaches to predict dental age from radiographic bone scores: 1) a univariate polynomial regression using a total bone score (sum of 16 scores across all assessed flipper bones), and 2) a multivariate canonical analysis of principal coordinates (CAP) incorporating 16 individual bone-score variables. Both approaches successfully predicted dental age from skeletal ossification patterns. For an age range of 0 to 24 years, polynomial regression demonstrated high predictive accuracy with median absolute errors (MAEs) of 1.25 years in females (Spearmans {rho} = 0.93, R{superscript 2} = 0.90) and 1.08 years in males ({rho} = 0.95, R{superscript 2} = 0.86). The CAP model yielded MAEs of 1.35 years in females ({rho} = 0.90, R{superscript 2} = 0.85) and 1.80 years in males ({rho} = 0.94, R{superscript 2} = 0.84). Notably, both radiographic bone ageing models achieved equal or lower median absolute errors and higher coefficients of determination than a recently developed epigenetic clock for common dolphins derived from the same population (MAE = 1.80, Pearsons correlation (r) = 0.91, R{superscript 2} = 0.82). When applying the bone ageing models to individuals of unknown dental age, both models produced age estimates consistent with expected life-history stages (foetus, neonate, juvenile, subadult, adult), although accuracy declined in dolphins above 20 years, likely as a consequence of subtle age-related variation in skeletal changes in this species. Radiographic ageing provides an accurate non-invasive tool for demographic assessment to support conservation management of common dolphins.

PurposeAntibiotic use (ABU) is a major driver of antimicrobial resistance (AMR), but ABU patterns are poorly understood in low-income countries where the burden of AMR is great and ABU is insufficiently regulated. Here, we report ABU from ten sites ranging from rural villages to small cities in Madagascar, a country with high AMR levels, and present results from modeling to identify factors that may be associated with ABU in this setting. MethodsWe conducted surveys of 290 individuals from ten sites in the SAVA Region of northeast Madagascar to gather data on sociodemographic characteristics, agricultural and animal husbandry practices, recent antibiotic use, the antibiotics that participants recalled using in their lifetimes, and the sources of their antibiotics. Using these data, we conducted statistical analyses with a mixed-effects logistic model to determine which characteristics were associated with recent antibiotic use. ResultsNearly all respondents (N=283, 97.6%) reported ABU in their lifetimes, with amoxicillin being the most widely reported antibiotic (N=255, 90.1% of those reporting ABU). All recalled antibiotics were classified as frontline drugs except for ciprofloxacin. Most respondents who reported antibiotic use also reported obtaining antibiotics without prescriptions from local stores (N=273, 96.5%), while only 52.3% (N=148) reported obtaining antibiotics through a prescriptive route, such as from a health clinic or private doctor. Of the 127 individuals (44.9%) who reported recent ABU, men were found to be significantly less likely to have recently taken antibiotics than women. ConclusionsOur findings provide new insights into ABU in agricultural settings in low-income countries, which have historically been understudied in AMR and pharmacoepidemiologic research. Knowledge of ABU patterns supports understanding of AMR dynamics and AMR control efforts in these contexts, such as interventions on inappropriate antibiotic dispensing. Key pointsO_LIAntibiotic use (ABU) in Madagascar is largely unstudied despite its role in antimicrobial resistance (AMR), which Madagascar faces a high burden of. C_LIO_LIABU was widespread among livestock owners in northeast Madagascar, with the majority of study participants reporting ABU in their lifetimes and most people reporting ABU also having taken antibiotics in the previous three months. C_LIO_LIMost respondents reported obtaining their antibiotics from non-pharmaceutical stores, indicating high levels of unregulated ABU, though more than half also reported sourcing their antibiotics through prescriptive means (like doctors and health clinics). C_LIO_LIMen were less likely than women to have taken antibiotics in the previous three months. C_LIO_LIThese findings support the development of interventions to mitigate the burden of AMR in Madagascar and similar contexts while underscoring the need for more comprehensive research on the drivers and patterns of ABU. C_LI Plain language summaryIn this study, we provide basic information on antibiotic use (ABU) patterns in Madagascar, a country that experiences high levels of resistance but has been particularly understudied in AMR and pharmacological research. We surveyed 290 farmers with livestock from ten sites across northeast Madagascar about their ABU and found that nearly all study participants (N=283, 97.6%) have used antibiotics in their lifetimes, while a little under half of those who reported ABU also reported using antibiotics in the previous three months (N=127, 44.9%). The most used antibiotic was amoxicillin (N=255, 90.1%). Most people obtained their antibiotics from sources that do not require prescriptions, like general stores, indicating that most ABU is unregulated. Through modeling, we also found that men were less likely than women to have taken antibiotics in the previous three months (OR=0.50, CI 0.30-0.82). These findings help us better understand the dynamics of ABU in low-income countries, which have historically been understudied in AMR and pharmacological research. They also support efforts to mitigate the burden of AMR by revealing ABU dynamics that may contribute to the emergence and spread of AMR, as well as identifying targets for intervention to curb inappropriate ABU.

Research on stochastic phenotypic variation (i.e., variation arising despite the apparent absence of genetic and environmental differences) has recently emerged as a rapidly growing area in biological research. But despite growing recognition of both its existence and fitness relevance, it remains unknown whether and to what extent such stochastically induced variation is transmitted across generations, potentially making it an unrecognized contributor to evolutionary processes and the adaptive potential of populations. In order to address this knowledge gap, we here performed a two-generation behavioral screening with a naturally clonal fish: 34 genetically identical mothers and their 232 offspring were separated directly after birth into near-identical environments and tracked continuously at high resolution, constituting a total of [~]19,000 observation hours. We find that consistent among-individual differences in behavioral profiles (i.e., activity and feeding patterns) of both mothers and offspring emerged despite the absence of apparent genetic and environmental differences. Mother feeding behavior - but not mother activity - was positively associated with offspring activity: mothers that spent more time feeding produced more active offspring, explaining [~] 33 % of the total variation in offspring activity. This link between mother and offspring behavior was not mediated by mother size or offspring size at parturition. Our study provides first evidence for the non-genetic transmission of among-individual phenotypic differences that arise despite the apparent lack of genetic or environmental variation, highlighting the potential importance of this variation for evolutionary processes and the adaptability of populations.

Introduction: Despite global progress in tuberculosis (TB) control, treatment outcomes remain suboptimal, particularly in high-burden settings and among people with HIV or drug-resistant TB. Identifying predictors of unsuccessful treatment is essential to improve TB care and policy. Methods: We evaluated TB treatment outcomes and patient characteristics associated with unsuccessful outcomes in five cohorts of the International epidemiology database to evaluate AIDS (IeDEA); Center for Infectious Disease Research, Zambia; Chiure health center, Mozambique; Martin Preuss Center, Lighthouse clinic, Malawi; Masvingo health center Zimbabwe; and Themba Lethu clinic, Hellen Joseph hospital, South Africa. We included all patients with TB aged 15 years starting TB treatment and assessed their treatment outcomes in association with sociodemographic and clinical characteristics using multivariable mixed-effects models. Unsuccessful outcomes were defined as death, loss to follow-up and treatment failure. Results: Among 1438 people with TB, median age was 39 years, 67% males, 40% with HIV, and 4% with MDR-TB; 1151 (80%) treatment outcomes were successful (606 cured and 545 completed treatment), 221 (15%) unsuccessful (89 deaths, 129 loss to follow-up and 3 treatment failures), and 66 (5%) other (49 unknown and 17 transfer-outs). Unsuccessful outcomes were more probable among people with multidrug-resistant TB (MDR-TB) and among participants without formal education. Risk of death was lower for people with bacteriologically confirmed TB (adjusted odds ratio (aOR) 0.5, 95%-credible interval [CI] 0.25-0.80), those with a secondary or higher education (aOR 0.3, 95%-CI 0.13-0.69) and BMI 318 kg/m{superscript 2} (aOR 0.6, 95%-CI 0.36-0.99). MDR-TB was associated with an increase (aOR 2.4 95%-CI 1.17-4.97) and primary and secondary or higher education with a decrease in loss to follow-up (aOR 0.3, 95%-CI 0.14-0.89 and aOR 0.3, 95%-CI 0.11-0.67, respectively). Conclusions: TB treatment outcomes fell short of the targets set by the World Health Organization of <10% unsuccessful outcomes, indicating a critical need for enhanced management strategies. Tackling loss to follow-up is crucial, especially among MDR-TB patients, including stronger retention activities and improved diagnostic capacities.