We thank Vonk (1) for her interest in our paper (2) in PNAS. We appreciate her concerns; however, several comments in her Letter are already discussed and supported by data in our paper. We thus respectfully disagree with her claims about the limitations of our study and theoretical interpretation.
by
Angela R Garcia;
Caleb Finch;
Margaret Gatz;
Thomas Kraft;
Daniel Eid Rodriguez;
Daniel Cummings;
Mia Charifson;
Kenneth Buetow;
Bret A Beheim;
Hooman Allayee;
Gregory S Thomas;
Jonathan Stieglitz;
Michael D Gurven;
Hilard Kaplan;
Benjamin C Trumble
In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypoth-esize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N = 1266, 50 % female), APOE4 is associated with 30 % lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be bene-ficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.
Purpose: Pre-exposure prophylaxis (PrEP) has been proven safe and effective in preventing HIV among adolescent sexual minority males (ASMM), but the cost-effectiveness of PrEP in ASMM remains unknown. Building on a recent epidemiological network modeling study of PrEP among ASMM, we estimated the cost-effectiveness of PrEP use in a high prevalence U.S. setting with significant disparities in HIV between black and white ASMM. Methods: Based on the estimated number of infections averted and the number of ASMM on PrEP from the previous model and published estimates of PrEP costs, HIV treatment costs, and quality-adjusted life years (QALYs) gained per infection prevented, we estimated the cost-effectiveness of PrEP use in black and white ASMM over 10 years using a societal perspective and lifetime horizon. Effectiveness was measured as lifetime QALYs gained. Cost estimates included 10-year PrEP costs and lifetime HIV treatment costs saved. Cost-effectiveness was measured as cost/QALY gained. Multiple sensitivity analyses were performed on key model input parameters and assumptions used. Results: Under base-case assumptions, PrEP use yielded an incremental cost-effectiveness ratio of $33,064 per QALY in black ASMM and $427,788 per QALY in white ASMM. In all sensitivity analyses, the cost-effectiveness ratio of PrEP use remained <$100,000 per QALY in black ASMM and >$100,000 per QALY in white ASMM. Conclusions: We found favorable cost-effectiveness ratios for PrEP use among black ASMM or other ASMM in communities with high HIV burden at current PrEP costs. Clinicians providing services in high-prevalence communities, and particularly those serving high-prevalence communities of color, should consider including PrEP services.
The South American continent is remarkably diverse in its ecological zones, spanning the Amazon rainforest, the high-altitude Andes, and Tierra del Fuego. Yet the original human populations of the continent successfully inhabited all these zones, well before the buffering effects of modern technology. Therefore, it is likely that the various cultures were successful, in part, due to positive natural selection that allowed them to successfully establish populations for thousands of years. Detecting positive selection in these populations is still in its infancy, as the ongoing effects of European contact have decimated many of these populations and introduced gene flow from outside of the continent. In this review, we explore hypotheses of possible human biological adaptation, methods to identify positive selection, the utilization of ancient DNA, and the integration of modern genomes through the identification of genomic tracts that reflect the ancestry of the first populations of the Americas.
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Maria Elisa Mancuso;
Johnny Mahlangu;
Robert Sidonio Jr;
Peter Trask;
Marianne Uguen;
Tiffany Chang;
Midori Shima;
Guy Young;
Johannes Oldenburg;
Sylvia von Mackensen
Introduction
Persons with haemophilia A (PwHA) with factor (F)VIII inhibitors, including children, have impaired health‐related quality of life (HRQoL). The HAVEN 2 study (NCT027955767) of paediatric PwHA with FVIII inhibitors demonstrated that subcutaneous emicizumab prophylaxis resulted in low annualizedbleed rates.
Aim
We assessed the impact of emicizumab prophylaxis on the HRQoL of children and their caregivers participating in HAVEN 2.
Methods
Children aged 8‐11 years self‐reported HRQoL using the Haemophilia‐Specific Quality of Life Assessment Instrument for Children and Adolescents Short Form (Haemo‐QoL SF II). Caregivers of children aged 0‐11 years completed the Adapted Inhibitor‐Specific Quality of Life Assessment with Aspects of Caregiver Burden. All scores were transformed to a 0‐100 scale, where lower scores reflect a better HRQoL. The number of missed days from school/day care and hospitalizations was also recorded.
Results
In HAVEN 2 (n = 88), the median age was 6.5 years (range: 1‐15 years); 85 participants were aged < 12 years and included in this analysis, and 34 participants were aged 8‐11 years, thereby eligible to complete the Haemo‐QoL SF II questionnaire. The mean (standard deviation, n) baseline Haemo‐QoL SF II ‘Total’ score was 30.2 (14.9, 30), indicating moderate impairment; with emicizumab, mean score decreased by −9.62 (7.73, 17) points to 23.0 (13.93, 20) by Week 49. The most improved domains were ‘Sports & School’ and ‘Physical Health’. Caregivers reported similar improvements.
Conclusion
Prophylactic emicizumab is accompanied by substantial and sustained improvements in HRQoL of paediatric PwHA with FVIII inhibitors and their caregivers.
Purpose: Pre-exposure prophylaxis (PrEP)—an effective and safe intervention to prevent HIV transmission—was recently approved by the Food and Drug Administration for use by adolescents. Informed by studies of sexual behavior and PrEP adherence, retention, and promotion, we model the potential impact of PrEP use among at-risk adolescent sexual minority males. Methods: We simulate an HIV epidemic among men who have sex with men (MSM) aged 13–39. We assume adult MSM ages 19–39 have had PrEP available for 3 years with 20% coverage among eligible MSM based on the Centers for Disease Control and Prevention guidelines. PrEP interventions for ages 16–18 are then simulated using adherence and retention profiles drawn from the ATN113 and Enhancing Preexposure Prophylaxis in Community studies across a range of uptake parameters (10%–100%). Partnerships across age groups were modeled using parameterizations from the RADAR study. We compare the percent of incident infections averted (impact), person-years on PrEP per infection averted (efficiency), and changes in prevalence over 10 years. Results: As compared to no PrEP use, baseline PrEP adherence and retention among adolescent sexual minority males drawn from the ATN113 and Enhancing Preexposure Prophylaxis in Community studies averted from 2.8% to 41.0% of HIV infections depending on the fraction of eligible adolescent sexual minority males that initiated PrEP at their annual health-care visit. Improved adherence and retention achieved with an array of focused interventions from real-world settings increased the percent of infections averted by as much as 26%–70%. Conclusions: Empirically demonstrated improvements in the PrEP continuum of care in response to existing interventions can substantially reduce incident HIV infections among adolescent sexual minority males.
Humans often experience striking performance deficits when their outcomes are determined by their own performance, colloquially referred to as “choking under pressure.” Physiological stress responses that have been linked to both choking and thriving are well-conserved in primates, but it is unknown whether other primates experience similar effects of pressure. Understanding whether this occurs and, if so, its physiological correlates, will help clarify the evolution and proximate causes of choking in humans. To address this, we trained capuchin monkeys on a computer game that had clearly denoted high- and low-pressure trials, then tested them on trials with the same signals of high pressure, but no difference in task difficulty. Monkeys significantly varied in whether they performed worse or better on high-pressure testing trials and performance improved as monkeys gained experience with performing under pressure. Baseline levels of cortisol were significantly negatively related to performance on high-pressure trials as compared to low-pressure trials. Taken together, this indicates that less experience with pressure may interact with long-term stress to produce choking behavior in early sessions of a task. Our results suggest that performance deficits (or improvements) under pressure are not solely due to human specific factors but are rooted in evolutionarily conserved biological factors.
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Reynaldo Martorell;
Shane Norris;
Jithin S Varghese;
Linda S Adair;
Shivani Patel;
Sonny Agustin Bechayda;
Santosh K Bhargava;
Delia B Carba;
Bernardo L Horta;
Natalia P Lima;
Ana MB Menezes;
Linda M Richter;
Manuel Ramirez-Zea;
Harshpal Singh Sachdev;
Fernando C Wehrmeister;
Aryeh Stein
Background: Temporally-harmonized asset-based measures of wealth can be used to study the association of life-course wealth exposures in the same scale with health outcomes in low- and middle-income countries (LMICs). The within-individual longitudinal stability of asset-based indices of wealth in LMICs is poorly understood. Methods: Using data from five birth cohorts from three continents, we developed temporally-harmonized asset indices over the life course through polychoric principal component analysis of a common set of assets collected consistently over time (18 years in Brazil to 50 years in Guatemala). For each cohort, we compared the harmonized index to cross-sectional indices created using more comprehensive asset measures using rank correlations. We evaluated the rank correlation of the harmonized index in early life and adulthood with maternal schooling and own attained schooling, respectively. Results: Temporally-harmonized asset indices developed from a consistently-collected set of assets (range: 10 in South Africa to 30 in Philippines) suggested that mean wealth improved over time for all birth cohorts. Cross-sectional indices created separately for each study wave were correlated with the harmonized index for all cohorts (Brazil: r = 0.78 to 0.96; Guatemala: r = 0.81 to 0.95; India: 0.75 to 0.93; Philippines: r = 0.92 to 0.99; South Africa: r = 0.84 to 0.96). Maternal schooling (r = 0.15 to 0.56) and attained schooling (r = 0.23 to 0.53) were positively correlated with the harmonized asset index in childhood and adulthood respectively. Conclusions: Temporally-harmonized asset indices displayed coherence with cross-sectional indices as well as construct validity with schooling.
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Jessica R Deere;
Kathryn L Schaber;
Steffen Foerster;
Ian C Gilby;
Joseph T Feldblum;
Kimberly VanderWaal;
Tiffany M Wolf;
Dominic A Travis;
Jane Raphael;
Iddi Lipende;
Deus Mjungu;
Anne E Pusey;
Elizabeth Lonsdorf;
Thomas Gillespie
Abstract: Increased risk of pathogen transmission through proximity and contact is a well-documented cost of sociality. Affiliative social contact, however, is an integral part of primate group life and can benefit health. Despite its importance to the evolution and maintenance of sociality, the tradeoff between costs and benefits of social contact for group-living primate species remains poorly understood. To improve our understanding of this interplay, we used social network analysis to investigate whether contact via association in the same space and/or physical contact measured through grooming were associated with helminth parasite species richness in a community of wild chimpanzees (Pan troglodytes schweinfurthii). We identified parasite taxa in 381 fecal samples from 36 individuals from the Kasekela community of chimpanzees in Gombe National Park, Tanzania, from November 1, 2006, to October 31, 2012. Over the study period, eight environmentally transmitted helminth taxa were identified. We quantified three network metrics for association and grooming contact, including degree strength, betweenness, and closeness. Our findings suggest that more gregarious individuals—those who spent more time with more individuals in the same space—had higher parasite richness, while the connections in the grooming network were not related to parasite richness. The expected parasite richness in individuals increased by 1.13 taxa (CI: 1.04, 1.22; p = 0.02) per one standard deviation increase in degree strength of association contact. The results of this study add to the understanding of the role that different types of social contact play in the parasite richness of group-living social primates. Significance statement: Parasite infections reveal costs of group living among wild animal populations. We studied the relationship between sociality and parasite transmission by assessing whether variation in social behavior among wild chimpanzees is associated with the number of unique helminth parasites detected in individual fecal samples. Our findings revealed that associating in the same shared space, but not grooming contact, is related to higher parasite richness. These findings improve our understanding of the complex interplay of parasitism and sociality with important implications for parasite transmission patterns in host species with flexible grouping patterns.
Our species’ long childhood is hypothesized to have evolved as a period for learning complex foraging skills. Researchers studying the development of foraging proficiency have focused on assessing this hypothesis, yet studies present inconsistent conclusions regarding the connection between foraging skill development and niche complexity. Here, we leverage published records of child and adolescent foragers from 28 societies to (i) quantify how skill-intensive different resources are and (ii) assess whether children’s proficiency increases more slowly for more skill-intensive resources. We find that foraging returns increase slowly for more skill-intensive, difficult-to-extract resources (tubers and game), consistent with peak productivity attained in adulthood. Foraging returns for easier-to-extract resources (fruit and fish/shellfish) increase rapidly during childhood, with adult levels of productivity reached by adolescence. Our findings support the view that long childhoods evolved as an extended period for learning to extract complex resources characteristic of the human foraging niche.