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Avian influenza A virus (IAV) surveillance in Northern California, USA, revealed unique IAV hemagglutinin (HA) genome sequences in cloacal swabs from lesser scaups. We found two closely related HA sequences in the same duck species in 2010 and 2013. Phylogenetic analyses suggest that both sequences belong to the recently discovered H19 subtype, which thus far has remained uncharacterized. We demonstrate that H19 does not bind the canonical IAV receptor sialic acid (Sia). Instead, H19 binds to the major histocompatibility complex class II (MHC class II), which facilitates viral entry. Unlike the broad MHC class II specificity of H17 and H18 from bat IAV, H19 exhibits a species-specific MHC class II usage that suggests a limited host range and zoonotic potential. Using cell lines overexpressing MHC class II, we rescued recombinant H19 IAV. We solved the H19 crystal structure and identified residues within the putative Sia receptor binding site (RBS) that impede Sia-dependent entry., Competing Interests: Declaration of interests The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories, and Merck outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer, and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. A.G.-S. is an inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines, influenza virus vaccines, and influenza virus therapeutics, which list F.K. as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2 and another company, Castlevax, to develop SARS-CoV-2 vaccines. F.K. is a co-founder and scientific advisory board member of Castlevax. F.K. has consulted for Merck, Curevac, Seqirus, and Pfizer and is currently consulting for 3rd Rock Ventures, GSK, Gritstone, and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Contextual modulation occurs for many aspects of high-level vision but is relatively unexplored for the perception of walking direction. In a recent study, we observed an effect of the temporal context on perceived walking direction. Here, we examined the spatial contextual modulation by measuring the perceived direction of a target point-light walker in the presence of two flanker walkers, one on each side. Experiment 1 followed a within-subjects design. Participants (n = 30) completed a spatial context task by judging the walking direction of the target in 13 different conditions: a walker alone in the center or with two flanking walkers either intact or scrambled at a flanker deviation of ±15°, ±30°, or ±45°. For comparison, participants completed an adaptation task where they reported the walking direction of a target after adaptation to ±30° walking direction. We found the expected repulsive effects in the adaptation task but attractive effects in the spatial context task. In Experiment 2 (n = 40), we measured the tuning of spatial contextual modulation across a wide range of flanker deviation magnitudes ranging from 15° to 165° in 15° intervals. Our results showed significant attractive effects across a wide range of flanker walking directions with the peak effect at around 30°. The assimilative versus repulsive effects of spatial contextual modulation and temporal adaptation suggest dissociable neural mechanisms, but they may operate on the same population of sensory channels coding for walking direction, as evidenced by similarity in the peak tuning across the walking direction of the inducers.

Background: Chronic subdural hematoma (cSDH) is a common sequela of traumatic brain injury. Middle meningeal artery embolization (MMAE) has shown promising results as an emerging minimally invasive alternative treatment. The purpose of this study is to examine the safety and efficacy of MMAE performed in patients with cSDH, acute-on-chronic, and subacute SDH with a traumatic etiology., Methods: This retrospective study included cases performed at a Level II Trauma Center between January 2019 and December 2020 for MMAE of cSDHs. Data collected included patient demographic characteristics and comorbidities, SDH characteristics, complications, and efficacy outcomes. The lesion measurements were collected before the procedure, 4-6 weeks and 3-6 months post-procedure., Results: In our patient population, 78% (39) either had lesions improve or completely resolved. The sample included 50 patients with a mean age of 74 years old. Statistically significant reductions in lesion size were found from pre- to post-procedure in the left lesions, right lesions, and midline shifts. The left lesions decreased from 13.88 ± 5.70 mm to 3.19 ± 4.89 mm at 3-6 months with P < 0.001. The right lesions decreased from 13.74 ± 5.28 mm to 4.93 ± 7.46 mm at 3-6 months with P = 0.02. Midline shifts decreased from 3.78 ± 3.98 mm to 0.48 ± 1.31 mm at 3-6 months with P = 0.02. No complications were experienced for bleeding, hematoma, worsening SDH, pseudoaneurysm, or stroke., Conclusion: Our pilot study from a single center utilizing MMAE demonstrates that MMAE is successful without increasing treatment-related complications not only for cSDH but also in acute-on-cSDH and SDH with a subacute component., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Background and Objective: Evidence on the economic value of rotavirus vaccines in middle-income countries is limited. We aimed to model the implementation of three vaccines (human rotavirus, live, attenuated, oral vaccine [HRV, 2 doses]; rotavirus vaccine, live, oral, pentavalent [HBRV, 3 doses] and rotavirus vaccine, live attenuated oral, freeze-dried [BRV-PV, 3 doses] presented in 1-dose and 2-dose vials) into the South African National Immunisation Programme., Methods: Cost and cost-effectiveness analyses were conducted to compare three rotavirus vaccines using a static, deterministic, population model in children aged <5 years in South Africa from country payer and societal perspectives. Deterministic and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model inputs., Results: The human rotavirus, live, attenuated, oral vaccine (HRV) was associated with cost savings versus HBRV from both perspectives, and versus BRV-PV 1-dose vial from the societal perspective. In the cost-effectiveness analysis, HRV was estimated to avoid 1,107 home care rotavirus gastroenteritis (RVGE) events, 247 medical visits, 35 hospitalisations, and 4 RVGE-related deaths versus HBRV and BRV-PV. This translated to 73 quality-adjusted life years gained. HRV was associated with lower costs versus HBRV from both payer (-$3.9M) and societal (-$11.5M) perspectives and versus BRV-PV 1-dose vial from the societal perspective (-$3.8M), dominating those options. HRV was associated with higher costs versus BRV-PV 1-dose vial from the payer perspective and versus BRV-PV 2‑dose vial from both payer and societal perspectives (ICERs: $51,834, $121,171, and $16,717, respectively), exceeding the assumed cost-effectiveness threshold of 0.5 GDP per capita., Conclusion: Vaccination with a 2-dose schedule of HRV may lead to better health outcomes for children in South Africa compared with the 3-dose schedule rotavirus vaccines., (© 2023. The Author(s).)

Objective: Fat-infiltrated axillary lymph nodes (LNs) are unique sites for ectopic fat deposition. Early studies showed a strong correlation between fatty LNs and obesity-related diseases. Confirming this correlation requires large-scale studies, hindered by scarce labeled data. With the long-term goal of developing a rapid and generalizable tool to aid data labeling, we developed an automated deep learning (DL)-based pipeline to classify the status of fatty LNs on screening mammograms., Methods: Our internal data set included 886 mammograms from a tertiary academic medical institution, with a binary status of the fat-infiltrated LNs based on the size and morphology of the largest visible axillary LN. A two-stage DL model training and fine-tuning pipeline was developed to classify the fat-infiltrated LN status using the internal training and development data set. The model was evaluated on a held-out internal test set and a subset of the Digital Database for Screening Mammography., Results: Our model achieved 0.97 (95% CI: 0.94-0.99) accuracy and 1.00 (95% CI: 1.00-1.00) area under the receiver operator characteristic curve on 264 internal testing mammograms, and 0.82 (95% CI: 0.77-0.86) accuracy and 0.87 (95% CI: 0.82-0.91) area under the receiver operator characteristic curve on 70 external testing mammograms., Conclusion: This study confirmed the feasibility of using a DL model for fat-infiltrated LN classification. The model provides a practical tool to identify fatty LNs on mammograms and to allow for future large-scale studies to evaluate the role of fatty LNs as an imaging biomarker of obesity-associated pathologies., Advances in Knowledge: Our study is the first to classify fatty LNs using an automated DL approach., Competing Interests: Competing interestsThe authors declare no competing interests.

Age estimation is a perceptual task that people perform automatically and effortlessly on a daily basis. Colour has been identified as one of the facial cues that contributes to age perception. To investigate further the role of colour in age perception, we manipulated the chromatic content of facial images holistically. In Experiment 1, images were shown in colour or grey scale; in Experiment 2, images were shown with red-green contrast increased or decreased; in Experiment 3, images were shown with modified yellow-blue contrast. We examined whether the presence of chromatic information biases the perception of age and/or affects inter-observer variability in age judgements, and whether specific chromatic information affects the perception of age. We found that the same face tended to be judged as younger with increased red-green contrast compared to decreased red-green contrast, suggesting that red-green contrast directly affects age perception. Inter-observer variability in age ratings was significantly lower when participants were asked to rate colour compared with grey scale versions of images. This finding indicates that colour carries information useful cues for age estimation., (© 2023. Springer Nature Limited.)

The direction that we see another person walking provides us with an important cue to their intentions, but little is known about how the brain encodes walking direction across a neuronal population. The current study used an adaptation technique to investigate the sensory coding of perceived walking direction. We measured perceived walking direction of point-light stimuli before and after adaptation, and found that adaptation to a specific walking direction resulted in repulsive perceptual aftereffects. The magnitude of these aftereffects was tuned to the walking direction of the adaptor relative to the test, with local repulsion of perceived walking direction for test stimuli oriented on either side of the adapted walking direction. The specific tuning profiles that we observed are well explained by a population-coding model, in which perceived walking direction is coded in terms of the relative activity across a bank of sensory channels with peak tuning distributed across the full 360° range of walking directions. Further experiments showed specificity in how horizontal (azimuth) walking direction is coded when moving away from the observer compared to when moving toward the observer. Moreover, there was clear specificity in these perceptual aftereffects for walking direction compared to a nonbiological form of 3D motion (a rotating sphere). These results indicate the existence of neural mechanisms in the human visual system tuned to specific walking directions, provide insight into the number of sensory channels and how their responses are combined to encode walking direction, and demonstrate the specificity of adaptation to biological motion. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

This longitudinal study investigated how kindergartners' position in the classroom social hierarchy and cortisol response relate to their change in school engagement across the first year of kindergarten (N = 332, M = 5.3 years, 51% boys, 41% White, 18% Black). We used naturalistic classroom observations of social hierarchy positions, laboratory-based challenges to elicit salivary cortisol response, and teacher, parent, and child reports of emotional engagement with school. Robust, clustered regression models revealed that in the fall, lower cortisol response (but not social hierarchy position) was associated with greater school engagement. However, by spring, significant interactions emerged. Highly reactive, subordinate children showed increases in school engagement from fall to spring of the kindergarten year, whereas highly reactive, dominant children showed decreases in school engagement. This is some of the first evidence that higher cortisol response marks biological sensitivity to early peer-based social contexts., (© 2023 Wiley Periodicals LLC.)

Here we present what we believe to be a novel geometric illusion where identical lines are perceived as being of differing lengths. Participants were asked to report which of the two parallel rows of horizontal lines contained the longer individual lines (two lines on one row and 15 on the other). Using an adaptive staircase we adjusted the length of the lines on the row containing two to estimate the point of subjective equality (PSE). At the PSE, the two lines were consistently shorter than the row containing the fixed length of 15 lines demonstrating a disparity in perceived length such that lines of identical length are perceived as longer in a row of two than in a row of 15. The illusion magnitude was unaffected by which row was presented above the other. Additionally, the effect persisted when using one as opposed to two test lines, and when the line stimuli on both rows were presented with alternating luminance polarity the illusion magnitude decreased, but was not abolished. The data indicate a robust geometric illusion that may be modulated by perceptual grouping processes.

This report from the field describes the development of the HIV & Faith Ambassadors Program to cultivate a cohort of Black faith leaders/communities and Black medical providers to address HIV-related stigma in African American faith communities in North Carolina.

As the science of adversity and resilience advances, and public awareness of the health consequences of stress grows, primary care providers are being increasingly asked to address the effects of adverse experiences on child wellbeing. Given limited tools for assessing these effects early in life, the authors explore how enhanced capacity to measure stress activation directly in young children could transform the role and scope of pediatric practice. When employed within a trusted relationship between caregivers and clinicians, selective use of biological measures of stress responses would help address the documented limitations of rating scales of adverse childhood experiences as a primary indicator of individual risk and strengthen the ability to focus on variation in intervention needs, assess their effectiveness, and guide ongoing management. The authors provide an overview of the potential benefits and risks of such expanded measurement capacity, as well as an introduction to candidate indicators that might be employed in an office setting. The ultimate value of such measures for both pediatricians and parents will require vigilant attention to the ethical responsibilities of assuring their correct interpretation and minimizing the harm of inappropriate labeling, especially for children and families experiencing the hardships and threats of racism, poverty, and other structural inequities. Whereas much work remains to be done to advance measurement development and ensure its equitable use, the potential of validated markers of stress activation and resilience to strengthen the impact of primary health care on the lives of young children facing significant adversity demands increased attention., (Copyright © 2022 by the American Academy of Pediatrics.)

UK online casino games are presently not subject to any limitations on speed-of-play or stakes. One recent policy proposal is to ensure that no online casino game can be played faster than its in-person equivalent. Another policy proposal is to limit the maximum stakes on online casino games to £2, to match the current stake limit on electronic gambling machines. This research experimentally investigated the speed-of-play proposal subject to a £2 stake limit, in an online experiment using incentivized payouts based on £4 endowments and a commercial online roulette game, which was slowed-down in one condition to enforce a speed-of-play limit of one spin every 60 seconds. UK residents, aged 18 years and over and with experience in playing online roulette (N = 1,002), were recruited from an online crowdsourcing panel. In the slowed-down condition there was a credible reduction in the amount gambled. This effect occurred via a credible reduction in the mean number of spins which outweighed any potential increases in bet sizes. Speed-of-play limits may be effective in reducing gambling expenditure for online roulette., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The interplay of genes and environments (GxE) is a fundamental source of variation in behavioral and developmental outcomes. Although the role of developmental time (T) in the unfolding of such interactions has yet to be fully considered, GxE operates within a temporal frame of reference across multiple timescales and degrees of biological complexity. Here, we consider GxExT interactions to understand adversity-induced developmental acceleration or deceleration whereby environmental conditions hasten or hinder children's development. To date, developmental pace changes have been largely explained through a focus on the individual: for example, how adversity "wears down" aging biological systems or how adversity accelerates or decelerates maturation to optimize reproductive fitness. We broaden such theories by positing shifts in developmental pace in response to the parent-child dyad's capacity or incapacity for meeting children's early, physiological and safety needs. We describe empirical evidence and potential neurobiological mechanisms supporting this new conceptualization of developmental acceleration and deceleration. We conclude with suggestions for future research on the developmental consequences of early adverse exposures., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Visual illusions are fascinating phenomena that have been used and studied by artists and scientists for centuries, leading to important discoveries about the neurocognitive underpinnings of perception, consciousness, and neuropsychiatric disorders such as schizophrenia or autism. Surprisingly, despite their historical and theoretical importance as psychological stimuli, there is no dedicated software, nor consistent approach, to generate illusions in a systematic fashion. Instead, scientists have to craft them by hand in an idiosyncratic fashion, or use pre-made images not tailored for the specific needs of their studies. This, in turn, hinders the reproducibility of illusion-based research, narrowing possibilities for scientific breakthroughs and their applications. With the aim of addressing this gap, Pyllusion is a Python-based open-source software (freely available at https://github.com/RealityBending/Pyllusion), that offers a framework to manipulate and generate illusions in a systematic way, compatible with different output formats such as image files (.png, .jpg, .tiff, etc.) or experimental software (such as PsychoPy ).

Marla Sokolowski's work and humanity has influenced the careers of hundreds, perhaps thousands, of younger scientists. Her fundamental research on the neurogenetic underpinnings of behavior in Drosophila melanogaster is remarkable not only for its scientific brilliance, but for the humility, care, and humor with which it was conducted.

Objective: A systematic literature review (SLR) was performed to elucidate the current triage and treatment of an entrapped or mangled extremity in resource scarce environments (RSEs)., Methods: A lead researcher followed the search strategy following inclusion and exclusion criteria. A first reviewer (FR) was randomly assigned sources. One of the 2 lead researchers was the second reviewer (SR). Each determined the level of evidence (LOE) and quality of evidence (QE) from each source. Any differing opinions between the FR and SR were discussed between them, and if differing opinions remained, then a third reviewer (the other lead researcher) discussed the article until a consensus was reached. The final opinion of each article was entered for analysis., Results: Fifty-eight (58) articles were entered into the final study. There was 1 study determined to be LOE 1, 29 LOE 2, and 28 LOE 3, with 15 determined to achieve QE 1, 37 QE 2, and 6 QE 3., Conclusion: This SLR showed that there is a lack of studies producing strong evidence to support the triage and treatment of the mangled extremity in RSE. Therefore, a Delphi process is suggested to adapt and modify current civilian and military triage and treatment guidelines to the RSE.

The development of child mental health problems has been associated with experiences of adversity and dysregulation of stress response systems; however, past research has largely focused on externalizing or internalizing problems (rather than their co-occurrence) and single physiological systems in high-risk adolescent samples. The present study examined whether cumulative family adversity, functioning in the hypothalamic-pituitary-adrenal axis (i.e., cortisol) and the parasympathetic nervous system (i.e., respiratory sinus arrhythmia [RSA]), and their interactions, predicted trajectories of co-occurring externalizing and internalizing problems among young children. Participants included 338 socioeconomically and racially diverse children (M age = 5.32 years, SD = .32; male = 51.8%) from a community sample. Family adversity (assessed with six measures) and child daily cortisol output and resting RSA were assessed in kindergarten. Parents, teachers, and children reported on children's externalizing and internalizing psychopathology up to three times from kindergarten to grade 1. Latent class growth analyses identified stable trajectories of externalizing and internalizing psychopathology. Trajectories were combined to create groups: co-occurring externalizing and internalizing (13.1%), externalizing-only (14.0%), internalizing-only (11.3%), and low problems (61.3%). Family adversity and resting RSA significantly positively predicted co-occurring group membership. Tests for interactions showed adversity did not significantly interact with physiological indicators to predict group membership. However, the two physiological systems interacted, such that higher and lower daily cortisol predicted internalizing group membership for children with lower and higher resting RSA, respectively. Findings support the importance of considering family context and multiple physiological systems to inform understanding of the development of mental health problems, and their co-occurrence, in early childhood.

Exposures to adverse environments, both psychosocial and physicochemical, are prevalent and consequential across a broad range of childhood populations. Such adversity, especially early in life, conveys measurable risk to learning and behavior and to the foundations of both mental and physical health. Using an interactive gene-environment-time (GET) framework, we survey the independent and interactive roles of genetic variation, environmental context, and developmental timing in light of advances in the biology of adversity and resilience, as well as new discoveries in biomedical research. Drawing on this rich evidence base, we identify 4 core concepts that provide a powerful catalyst for fresh thinking about primary health care for young children: (1) all biological systems are inextricably integrated, continuously "reading" and adapting to the environment and "talking back" to the brain and each other through highly regulated channels of cross-system communication; (2) adverse environmental exposures induce alterations in developmental trajectories that can lead to persistent disruptions of organ function and structure; (3) children vary in their sensitivity to context, and this variation is influenced by interactions among genetic factors, family and community environments, and developmental timing; and (4) critical or sensitive periods provide unmatched windows of opportunity for both positive and negative influences on multiple biological systems. These rapidly moving frontiers of investigation provide a powerful framework for new, science-informed thinking about health promotion and disease prevention in the early childhood period., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Advances in science are fundamentally changing the way we understand how inextricable interactions among genetic predispositions, physical and social environments, and developmental timing influence early childhood development and the foundations of health and how significant early adversity can lead to a lifetime of chronic health impairments. This article and companion article illustrate the extent to which differential outcomes are shaped by ongoing interactive adaptations to context that begin at or even before conception and continue throughout life, with increasing evidence pointing to the importance of the prenatal period and early infancy for the developing brain, the immune system, and metabolic regulation. Although new discoveries in the basic sciences are transforming tertiary medical care and producing breakthrough outcomes in treating disease, this knowledge is not being leveraged effectively to inform new approaches to promoting whole-child development and preventing illness. The opportunity for pediatrics to serve as the leading edge of science-based innovation across the early childhood ecosystem has never been more compelling. In this article, we present a framework for leveraging the frontiers of scientific discovery to inform new strategies in pediatric practice and advocacy to protect all developing biological systems from the disruptive effects of excessive early adversity beyond providing information on child development for parents and enriched learning experiences for young children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: To examine the association between prenatal stress and infant physical health in the first year of life within an understudied, racially and ethnically diverse, highly stressed community sample. We expected that greater stress exposure would predict higher rates of infant illness., Study Design: Low-income, racially/ethnically diverse, overweight women with low medical risk pregnancies were recruited (2011-2014) during pregnancy. Pregnancy Stressful Life Events were assessed retrospectively (mean, 11.88 months postpartum). Perceived stress was assessed twice during pregnancy (at a mean of 17.4 weeks and again at a mean of 25.6 weeks) and at 6 months postpartum. Women with live births (n = 202) were invited; 162 consented to the offspring study. Medical records from pediatric clinics and emergency departments for 148 infants were abstracted for counts of total infectious illnesses, total noninfectious illness, and diversity of illnesses over the first year of life., Results: The final analytic sample included 109 women (mean age, 28.08 years) and their infants. In covariate-adjusted negative binomial models, maternal perceptions of stress across pregnancy were positively associated with infant illness. Each 1-point increase in average stress was associated with a 38% increase in incidence of infant infections (Incidence rate ratio, 1.38; 95% CI, 1.01-1.88; P < .05), a 73% increase in noninfectious illness (IRR, 1.73; 95% CI, 1.34-2.23; P < .05), and a 53% increase in illness diversity (IRR, 1.53; 95% CI, 1.25, 1.88; P < .01); effect sizes were larger for perceived stress later in pregnancy. Stressful life events count and postnatal stress were not uniquely associated with illness., Conclusions: In line with recommendations from the American Academy of Pediatrics to screen for maternal perinatal depression, screening and support for stress reduction during pregnancy may benefit both maternal and child health., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Routine childhood immunisation with pneumococcal conjugate vaccine (PCV) has changed the epidemiology of pneumococcal disease across age groups, providing an opportunity to reconsider PCV dosing schedules. We aimed to evaluate the post-booster dose immunogenicity of ten-valent (PCV10) and 13-valent (PCV13) PCVs between infants randomly assigned to receive a single-dose compared with a two-dose primary series., Methods: We did an open-label, non-inferiority, randomised study in HIV-unexposed infants at a single centre in Soweto, South Africa. Infants were randomly assigned to receive one priming dose of PCV10 or PCV13 at ages 6 weeks (6w + 1 PCV10 and 6w + 1 PCV13 groups) or 14 weeks (14w + 1 PCV10 and 14w + 1 PCV13 groups) or two priming doses of PCV10 or PCV13, one each at ages 6 weeks and 14 weeks (2 + 1 PCV10 and 2 + 1 PCV13 groups); all participants then received a booster dose of PCV10 or PCV13 at 40 weeks of age. The primary endpoint was geometric mean concentrations (GMCs) of serotype-specific IgG 1 month after the booster dose, which was assessed in all participants who received PCV10 or PCV13 as per the assigned randomisation group and for whom laboratory results were available at that timepoint. The 1 + 1 vaccine schedule was considered non-inferior to the 2 + 1 vaccine schedule if the lower bound of the 96% CI for the GMC ratio was greater than 0·5 for at least ten PCV13 serotypes and eight PCV10 serotypes. Safety was a secondary endpoint. This trial is registered with ClinicalTrials.gov (NCT02943902) and is ongoing., Findings: Of 1695 children assessed, 600 were enrolled and randomly assigned to one of the six groups between Jan 9 and Sept 20, 2017; 542 were included in the final analysis of the primary endpoint (86-93 per group). For both PCV13 and PCV10, a 1+1 dosing schedule (either beginning at 6 or 14 weeks) was non-inferior to a 2 + 1 schedule. For PCV13, the lower limit of the 96% CI for the ratio of GMCs between the 1 + 1 and 2 + 1 groups was higher than 0·5 for ten serotypes in the 6w+1 group (excluding 6B, 14, and 23F) and 11 serotypes in the 14w + 1 group (excluding 6B and 23F). For PCV10, the lower limit of the 96% CI for the ratio of GMCs was higher than 0·5 for all ten serotypes in the 6w+1 and 14w + 1 groups. 84 serious adverse events were reported in 72 (12%) of 600 participants. 15 occurred within 28 days of vaccination, but none were considered to be related to PCV injection. There were no cases of culture-confirmed invasive pneumococcal disease., Interpretation: The non-inferiority in post-booster immune responses following a single-dose compared with a two-dose primary series of PCV13 or PCV10 indicates the potential for reducing PCV dosing schedules from a 2 + 1 to 1 + 1 series in low-income and middle-income settings with well established PCV immunisation programmes., Funding: The Bill & Melinda Gates Foundation (OPP1 + 152352)., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Eye tracking is a widely used tool for behavioral research in the field of psychology. With technological advancement, we now have specialized eye-tracking devices that offer high sampling rates, up to 2000 Hz, and allow for measuring eye movements with high accuracy. They also offer high spatial resolution, which enables the recording of very small movements, like drifts and microsaccades. Features and parameters of interest that characterize eye movements need to be algorithmically extracted from raw data as most eye trackers identify only basic parameters, such as blinks, fixations, and saccades. Eye-tracking experiments may investigate eye movement behavior in different groups of participants and in varying stimuli conditions. Hence, the analysis stage of such experiments typically involves two phases, (i) extraction of parameters of interest and (ii) statistical analysis between different participants or stimuli conditions using these parameters. Furthermore, the datasets collected in these experiments are usually very large in size, owing to the high temporal resolution of the eye trackers, and hence would benefit from an automated analysis toolkit. In this work, we present PyTrack, an end-to-end open-source solution for the analysis and visualization of eye-tracking data. It can be used to extract parameters of interest, generate and visualize a variety of gaze plots from raw eye-tracking data, and conduct statistical analysis between stimuli conditions and subject groups.

There is emerging evidence that the development of problematic aggression in childhood may be associated with specific physiological stress response patterns, with both biological overactivation and underactivation implicated. This study tested associations between sex-specific patterns of stress responses across the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis and peer nominations of aggression among 271 kindergarten children (Mean age = 5.32 years; 52% Female; 44% White). Upon entry to kindergarten, children participated in a multidomain standardized stress paradigm. Changes in pre-ejection period (PEP) and salivary cortisol were assessed. On a separate day, children provided peer ratings of physical and relational aggression in a standardized interview. As expected, there was a significant three-way interaction between PEP, cortisol reactivity, and sex, but only for physical aggression. Among boys, cortisol reactivity was positively associated with physical aggression only for those with higher SNS reactivity. Findings suggest that for boys, asymmetrical and symmetrical HPA/SNS reactivity may be associated with lower and higher risk for peer-directed physical aggression, respectively. Understanding the complex associations between multisystem physiology, child sex and peer-directed aggression in early childhood may offer insight into individual differences underlying the emergence of behavioral dysregulation in early peer contexts.

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset ( n = 1,032), with performance assessed in a separate test dataset ( n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease., Competing Interests: The authors declare no competing interest.

A now substantial body of science implicates a dynamic interplay between genetic and environmental variation in the development of individual differences in behavior and health. Such outcomes are affected by molecular, often epigenetic, processes involving gene-environment (G-E) interplay that can influence gene expression. Early environments with exposures to poverty, chronic adversities, and acutely stressful events have been linked to maladaptive development and compromised health and behavior. Genetic differences can impart either enhanced or blunted susceptibility to the effects of such pathogenic environments. However, largely missing from present discourse regarding G-E interplay is the role of time, a "third factor" guiding the emergence of complex developmental endpoints across different scales of time. Trajectories of development increasingly appear best accounted for by a complex, dynamic interchange among the highly linked elements of genes, contexts, and time at multiple scales, including neurobiological (minutes to milliseconds), genomic (hours to minutes), developmental (years and months), and evolutionary (centuries and millennia) time. This special issue of PNAS thus explores time and timing among G-E transactions: The importance of timing and timescales in plasticity and critical periods of brain development; epigenetics and the molecular underpinnings of biologically embedded experience; the encoding of experience across time and biological levels of organization; and gene-regulatory networks in behavior and development and their linkages to neuronal networks. Taken together, the collection of papers offers perspectives on how G-E interplay operates contingently within and against a backdrop of time and timescales., Competing Interests: The authors declare no competing interest.

We conducted signal detection analyses to test for curvilinear, U-shaped relations between early experiences of adversity and heightened physiological responses to challenge, as proposed by biological sensitivity to context theory. Based on analysis of an ethnically diverse sample of 338 kindergarten children (4-6 years old) and their families, we identified levels and types of adversity that, singly and interactively, predicted high (top 25%) and low (bottom 25%) rates of stress reactivity. The results offered support for the hypothesized U-shaped curve and conceptually replicated and extended the work of Ellis, Essex, and Boyce (2005). Across both sympathetic and adrenocortical systems, a disproportionate number of children growing up under conditions characterized by either low or high adversity (as indexed by restrictive parenting, family stress, and family economic condition) displayed heightened stress reactivity, compared with peers growing up under conditions of moderate adversity. Finally, as hypothesized by the adaptive calibration model, a disproportionate number of children who experienced exceptionally stressful family conditions displayed blunted cortisol reactivity to stress.

Classrooms are key social settings that impact children's mental health, though individual differences in physiological reactivity may render children more or less susceptible to classroom environments. In a diverse sample of children from 19 kindergarten classrooms (N = 338, 48% female, M age = 5.32 years), we examined whether children's parasympathetic reactivity moderated the association between classroom climate and externalizing symptoms. Independent observers coded teachers' use of child-centered and teacher-directed instructional practices across classroom social and management domains. Children's respiratory sinus arrhythmia reactivity to challenge tasks was assessed in fall and a multi-informant measure of externalizing was collected in fall and spring. Both the social and the management domains of classroom climate significantly interacted with children's respiratory sinus arrhythmia reactivity to predict spring externalizing symptoms, controlling for fall symptoms. For more reactive children, as classrooms shifted toward greater proportional use of child-centered methods, externalizing symptoms declined, whereas greater use of teacher-dominated practices was associated with increased symptoms. Conversely, among less reactive children, exposure to more teacher-dominated classroom management practices was associated with lower externalizing. Consistent with the theory of biological sensitivity to context, considering variability in children's physiological reactivity aids understanding of the salience of the classroom environment for children's mental health.

Auditory stimuli have been shown to alter visual temporal perception. For example, illusory temporal order is perceived when an auditory tone cues one side of space prior to the onset of simultaneously presented visual stimuli. Competing accounts attempt to explain such effects. The spatial gradient account of attention suggests speeded processing of visual stimuli in the cued space, whereas the impletion account suggests a Gestalt-like process where an attempt is made to arrive at a "realistic" representation of an event given ambiguous conditions. Temporal ventriloquism-where visual temporal order judgment performance is enhanced when a spatially uninformative tone is presented prior to, and after, visual stimuli onset-argues that the temporal relationship of the auditory stimuli to visual stimuli, as well as the number of auditory stimuli equaling the visual stimuli, drives the mechanisms underlying these and related effects. Results from a series of experiments highlight putative inconsistencies in both the spatial gradient account of attention and the classical temporal ventriloquism account. We present novel behavioral effects-illusory temporal order via spatially uninformative tones, and illusory simultaneity via a single tone prior to visual stimuli onset-that can be accounted for by an expanded version of the impletion account. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Harsh and restrictive parenting are well-established contributors to the development of oppositional defiant disorder (ODD) among children. However, few studies have explored whether interpersonal relationships that develop outside the family environment attenuate the risk for ODD that is associated with harsh parenting. The current study tested multireporter measures of teacher-child closeness and peer acceptance as moderators of the association between harsh parenting and children's ODD as children's social worlds widen during the kindergarten year (N = 338 children, 48% girls, M age = 5.32 years). Harsh parenting interacted with peer nominations of peer acceptance and children's report of teacher-child closeness to predict children's ODD symptoms in the spring, adjusting for fall symptoms. Children exposed to harsh parenting exhibited greater symptom increases when they were less liked/accepted playmates and in the context of lower teacher-child closeness. However, harsh parenting was not associated with symptom change among children with higher levels of peer-nominated acceptance and those who reported closer relationships with teachers. There were no significant interactions using teacher's report of peer acceptance or teacher's report of teacher-child closeness. Findings highlight positive peer and teacher relationships as promising targets of intervention among children exposed to harsh parenting and support the importance of assessing multiple perspectives of children's social functioning.

Background: Measles morbidity and mortality rates are greatest in children <12 months old, with increased susceptibility in human immunodeficiency virus (HIV)-exposed children. We evaluated the immunogenicity and safety of an early 2-dose measles vaccine regimen administered at 6 and 12 months of age in South Africa., Methods: HIV-unexposed (HU) (n = 212) and HIV-exposed, uninfected (HEU) (n = 71) children received measles vaccination (CAM-70) at 6 and 12 months of age. Measles immunoglobulin G titers were measured by means of enzyme-linked immunosorbent assay before and 1 month after each vaccine dose., Results: The majority of children (88.2% HU and 95.8% HEU; P = .04) were seronegative (<150 mIU/mL) to measles at 4.2 months of age. This was particularly evident among infants of mothers born from 1992 onwards (year of public nationwide measles vaccine availability). One month after the first measles vaccine, 42.3% of HU and 46.4% of HEU children were seropositive (≥330 mIU/mL). After the second dose, the proportion seropositive increased to 99.0% in HU and 95.3% in HEU children. Safety profiles were similar between HU and HEU children., Conclusions: Early 2-dose measles vaccination at 6 and 12 months of age was safe and induced antibody responses in HU and HEU children, which could partly offset the early loss of maternally derived antibodies in infants born to predominantly measles-vaccinated mothers., Clinical Trials Registration: NCT03330171., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To examine the moderating role of restrictive parenting on the relation of socioeconomic status (SES) to febrile illnesses (FIs) and upper respiratory illnesses (URIs) among ethnic minority and non-minority children., Methods: Children from diverse ethnic backgrounds (Caucasian, African American, Asian, Latino, other, or multiethnic) were followed across the course of the kindergarten year. Parents reported on SES and parenting. A nurse completed 13 physical exams per child over the year to assess FIs and URIs., Results: During the school year, 28% of children (n = 199, 56% ethnic minority) exhibited one or more FIs (range, 0-6) and 90% exhibited one or more URIs (range, 0-10). No main or moderating effects of SES or restrictive parenting on FIs or URIs were found among Caucasian children; however, among ethnic minority children, the relation of SES to FIs was conditional upon restrictive parenting (β = .66; P = .02), as the fewest FIs were found for lower SES minority children whose parents reported more restrictive practices. Additionally, among minority children, more restrictive parenting was marginally associated with fewer URIs (β = -.21; P = .05)., Conclusions: Unexpectedly, among minority children the fewest illnesses occurred among lower SES children whose parents endorsed more restrictive parenting. This may be due to unique appraisals of this rearing style among minority children in lower SES environments and its potential to influence immune functioning. Results suggest variability in the effects of parenting on offspring health and support context-specific evaluations of parenting in efforts to ameliorate early health disparities., (Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment., (© 2018 John Wiley & Sons Ltd.)

Background: The widespread use of accessible peripheral tissues for epigenetic analyses has prompted increasing interest in the study of tissue-specific DNA methylation (DNAm) variation in human populations. To date, characterizations of inter-individual DNAm variability and DNAm concordance across tissues have been largely performed in adult tissues and therefore are limited in their relevance to DNAm profiles from pediatric samples. Given that DNAm patterns in early life undergo rapid changes and have been linked to a wide range of health outcomes and environmental exposures, direct investigations of tissue-specific DNAm variation in pediatric samples may help inform the design and interpretation of DNAm analyses from early life cohorts. In this study, we present a systematic comparison of genome-wide DNAm patterns between matched pediatric buccal epithelial cells (BECs) and peripheral blood mononuclear cells (PBMCs), two of the most widely used peripheral tissues in human epigenetic studies. Specifically, we assessed DNAm variability, cross-tissue DNAm concordance and genetic determinants of DNAm across two independent early life cohorts encompassing different ages., Results: BECs had greater inter-individual DNAm variability compared to PBMCs and highly the variable CpGs are more likely to be positively correlated between the matched tissues compared to less variable CpGs. These sites were enriched for CpGs under genetic influence, suggesting that a substantial proportion of DNAm covariation between tissues can be attributed to genetic variation. Finally, we demonstrated the relevance of our findings to human epigenetic studies by categorizing CpGs from published DNAm association studies of pediatric BECs and peripheral blood., Conclusions: Taken together, our results highlight a number of important considerations and practical implications in the design and interpretation of EWAS analyses performed in pediatric peripheral tissues.

Aim: To examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course., Materials & Methods: In a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined., Results: Family income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions., Conclusion: Findings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans.

Objective: Children from families with lower socioeconomic status (SES) evidence greater physiological dysregulation and poorer health. Despite recognition of environmental contributors, little is known about the influence of neighborhood characteristics. The present study examined the moderating role of community-level risks and resources on the relation of family SES to children's daily cortisol output and physical health during the kindergarten year., Methods: In fall and spring of kindergarten, children's (N = 338) daily total cortisol was measured and parents and teachers rated children's global physical health. Parents reported family SES. Neighborhood characteristics were assessed using the Child Opportunity Index, a population-level tool that evaluates the quality of multiple domains of neighborhood attributes., Results: In fall, children reared in lower SES family environments had higher cortisol when residing in lower quality (lower opportunity) neighborhoods (b = -.097, p < .001), but there was no relation between family SES and children's cortisol in more advantaged (higher opportunity) neighborhoods (b = -.023, p = .36). Lower family SES was prospectively associated with poorer physical health in spring (controlling for fall health) only among children living in lower opportunity neighborhoods (b = -.250, p = .018) and was unrelated to physical health among children residing in higher opportunity neighborhoods (b = .042, p = .70)., Conclusions: Higher opportunity neighborhoods may protect against the negative consequences of low family SES on children's stress physiology and physical health. Public health interventions that bolster neighborhood opportunities may benefit young children reared in socioeconomically disadvantaged family environments.

The coexistence of different types of poultry operations such as free range and backyard flocks, large commercial indoor farms and live bird markets, as well as the presence of many areas where wild and domestic birds co-exist, make California susceptible to avian influenza outbreaks. The 2014-2015 highly pathogenic Avian Influenza (HPAI) outbreaks affecting California and other states in the United States have underscored the need for solutions to protect the US poultry industry against this devastating disease. We applied disease distribution models to predict where Avian influenza is likely to occur and the risk for HPAI outbreaks is highest. We used observations on the presence of Low Pathogenic Avian influenza virus (LPAI) in waterfowl or water samples at 355 locations throughout the state and environmental variables relevant to the disease epidemiology. We used two algorithms, Random Forest and MaxEnt, and two data-sets Presence-Background and Presence-Absence data. The models performed well (AUCc > 0.7 for testing data), particularly those using Presence-Background data (AUCc > 0.85). Spatial predictions were similar between algorithms, but there were large differences between the predictions with Presence-Absence and Presence-Background data. Overall, predictors that contributed most to the models included land cover, distance to coast, and broiler farm density. Models successfully identified several counties as high-to-intermediate risk out of the 8 counties with observed outbreaks during the 2014-2015 HPAI epizootics. This study provides further insights into the spatial epidemiology of AI in California, and the high spatial resolution maps may be useful to guide risk-based surveillance and outreach efforts.

Background: This exploratory qualitative study explored the life experiences of young adults who participated in a cohort study in their child care center 26 years ago.The purpose of the study was to: (1) Describe the life trajectories of study participants who exhibited the extremes of high or low cardiovascular reactivity during their preschool ages. (2) Identify the life courses, processes, or outcomes for these young adults. (3) Describe exemplar cases of children with high and low reactivity who illustrated patterns of resilience or vulnerability., Methods: Eight out of the 137 children who had combinations of extreme high or low reactivity and environmental adversity were identified and interviewed by a blinded researcher. Data were analyzed through iterative coding, development of major categories, matrix analysis and thematic analysis., Results: The overall theme for all of the participants was facing challenges, and moving forward. The major categories which showed some variation between those with high and low reactivity were developing sources of support, overcoming adversity, and finding satisfaction/ dissatisfaction with life., Conclusion: These life histories provide a further understanding of how biologic sensitivity to challenges identified early in life may have impacted participants' trajectories from preschool to young adulthood, and indicate that further study would be warranted across the life course., Competing Interests: Competing interests: The authors do not have any competing interests.

Animal models of early postnatal mother-infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4-5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), μ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.

Entry into kindergarten is a developmental milestone that children may differentially experience as stressful, with implications for variability in neurobiological functioning. Guided by the goodness-of-fit framework, this study tested the hypothesis that kindergarten children's (N = 338) daily cortisol would be affected by the "match" or "mismatch" between children's temperament and qualities of the classroom relational context. The robustness of these associations was also explored among a separate sample of children in third grade (N = 165). Results among kindergarten children showed negative affectivity and overcontrolled temperament were positively related to cortisol expression within classrooms characterized by lower levels of teacher motivational support, but there was no relation between temperament and cortisol when motivational support was higher. Among third-grade children, negative affectivity was marginally positively related to cortisol at lower levels of teacher-child closeness and unrelated at higher levels of teacher-child closeness. Findings suggest children's cortisol expression depends on the extent to which specific temperamental characteristics "fit" within the relational and contextual qualities of the classroom environment, particularly as children navigate the new roles and relationships that emerge during the transition to formal schooling. Developmentally informed neurobiological research in classrooms may contribute to tailored programmatic efforts to support children's school adjustment.

This article-presented on the celebratory occasion of Dr Robert Haggerty's 91st birthday-describes how a 1962 article by Dr Haggerty and his colleague Dr Roger Meyer launched a previously unexplored, pediatric research enterprise by asserting that: "There are little precise data to explain why one person becomes ill with an infecting agent and another not." Noting a prospective association between family stressors and the acquisition of β-hemolytic streptococcal infections, the article introduced a generation of young academic pediatricians-the author of the present article among them-to the possibility of causal linkages among children's adversity exposures, compromised immunological processes, and the development of immune-mediated, acute or chronic diseases of childhood. That research agenda has led, over the past 40 years, to the advent of psychoneuroimmunology as a field of study, to the recognition of childhood stress and adversity as potential etiologic agents among childhood morbidities, and to the discovery of differential susceptibility to social adversities within populations of children., (Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Sleep problems are common for young children especially if they live in adverse home environments. Some studies investigate if young children may also be at a higher risk of sleep problems if they have a specific biological sensitivity to adversity. This paper addresses the research question, does the relations between children's exposure to family adversities and their sleep problems differ depending on their autonomic nervous system's sensitivity to challenges? As part of a larger cohort study of Latino, low-income families, we assessed the cross-sectional relations among family demographics (education, marital status), adversities [routines, major life events (MLE)], and biological sensitivity as measured by autonomic nervous system (ANS) reactivity associated with parent-rated sleep problems when the children were 5 years old. Mothers were interviewed in English or Spanish and completed demographic, family, and child measures. The children completed a 15-min standardized protocol while continuous cardiac measures of the ANS [respiratory sinus arrhythmia (RSA), preejection period (PEP)] were collected during resting and four challenge conditions. Reactivity was defined as the mean of the responses to the four challenge conditions minus the first resting condition. Four ANS profiles, co-activation, co-inhibition, reciprocal low RSA and PEP reactivity, and reciprocal high RSA and PEP reactivity, were created by dichotomizing the reactivity scores as high or low reactivity. Logistic regression models showed there were significant main effects for children living in families with fewer daily routines having more sleep problems than for children living in families with daily routines. There were significant interactions for children with low PEP reactivity and for children with the reciprocal, low reactivity profiles who experienced major family life events in predicting children's sleep problems. Children who had a reciprocal, low reactivity ANS profile had more sleep problems if they also experienced MLE than children who experienced fewer MLE. These findings suggest that children who experience family adversities have different risks for developing sleep problems depending on their biological sensitivity. Interventions are needed for young Latino children that support family routines and reduce the impact of family adversities to help them develop healthy sleep practices.

The quality of parenting is a complex and multiply determined construct that is strongly influenced by the larger ecological context in which it evolves. A substantial body of literature has documented associations between socioeconomic status (SES) and parenting but has been limited in its consideration of factors that may explain or moderate the nature of this relation. The socioeconomic conditions within which a family lives may powerfully influence parenting through its effects on parental mental health and via differential access to resources. Parents' childrearing knowledge and cultural values may also vary along a socioeconomic gradient, with downstream effects on parenting. Further, both socioeconomic factors and parenting can independently shape children's health and development. A more comprehensive understanding of linkages between SES and parenting may inform preventive intervention efforts to support families from disadvantaged environments.

Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of human immunodeficiency virus (HIV) emergence following human exposures to simian immunodeficiency virus (SIV), an understanding of processes that promote successful cross-species lentiviral transmissions is highly relevant. We previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats ( Lynx rufus ) and mountain lions ( Puma concolor ) for a small number of animals in California and Florida. In this study, we investigate host-specific selection pressures, within-host viral fitness, and inter- versus intraspecies transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analyses of proviral and viral RNA levels demonstrate that PLVA fitness is severely restricted in mountain lions compared to that in bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but we did not detect selection among 20 PLVA isolates from bobcats. These findings support the hypothesis that PLVA is a bobcat-adapted virus which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals that intraspecific PLVA transmission has occurred among panthers ( Puma concolor coryi ) in Florida following the initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to the emergence of HIV from nonhuman primates. IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which outcome will occur are complex, and the risk of new virus emergence is therefore difficult to predict. We used molecular techniques to evaluate the transmission, fitness, and adaptation of puma lentivirus A (PLVA) between bobcats and mountain lions in two geographic regions. Our findings illustrate that mountain lion exposure to PLVA is relatively common but does not routinely result in communicable infections in the new host. This is attributed to efficient species barriers that largely prevent lentiviral adaptation. However, the evolutionary capacity for lentiviruses to adapt to novel environments may ultimately overcome host restriction mechanisms over time and under certain ecological circumstances. This phenomenon provides a unique opportunity to examine cross-species transmission events leading to new lentiviral emergence., (Copyright © 2017 American Society for Microbiology.)

Importance: Pediatricians are paying increased attention to the effects of socioeconomic status (SES) on children's health. Low SES is a robust predictor of obesity across the life course and may interact with genes affecting metabolism to influence obesity risk. Recent animal literature and burgeoning human research suggest that the hormone oxytocin (OT) may be important for metabolic regulation. To date, this association has not been examined in children., Objectives: To examine whether an OT receptor polymorphism (rs53576) interacts with SES, potentially exacerbating and buffering the effects of stress, to predict anthropometry during childhood, and based on differential neurobiological susceptibility theory, to test whether carriers of the A allele of the OXTR gene, compared with GG genotyped individuals, would be most sensitive to the effects of SES on anthropometry for better or for worse., Design, Setting, and Participants: In this observational study, families were recruited from public school classrooms and enrolled in the Peers and Wellness Study (PAWS), which examined the effects of social status on health. Families were assessed during children's kindergarten year (fall semester of 2003, 2004, and 2005) and again during middle childhood (2009-2011) for a follow-up assessment that included anthropometric measures and DNA collection. The dates of the analysis were January 2015 to June 2016., Exposures: Socioeconomic disparities., Main Outcomes and Measures: Child body mass index z score (BMIz) and triceps skinfold thickness. Family SES was collected through questionnaires mailed to homes. Body measurements and DNA were collected in homes by trained research assistants., Results: From the original community sample of 338 typically developing children, participants were 186 socioeconomically and racially/ethnically diverse children (mean age, 10.3 years; age range, 9.4-11.3 years; 93 females [50%]) who had sufficient data at the follow-up assessment for inclusion in this study. Among 97 A allele carriers, a 1-SD increase in SES was associated with a decrease in BMIz of 0.28 (95% CI, -0.47 to -0.09) and a decrease in skinfold thickness of 0.95 (95% CI, -1.77 to -0.12) mm, such that they exhibited the highest BMIz and skinfold thickness in contexts of low SES but exhibited the lowest BMIz and skinfold thickness in contexts of high SES. Socioeconomic status was unrelated to BMIz (95% CI, -0.21 to 0.26) or skinfold thickness (95% CI, -0.42 to 1.45) for 89 GG genotyped children., Conclusions and Relevance: These findings advance etiologic understanding of childhood obesity, highlighting complex effects of SES on child health and adding to growing evidence that OT relates to human obesity risk. The results also support differential neurobiological susceptibility theory, suggesting that the A allele renders individuals more sensitive to both positive and negative health effects of socioecological context.

Background: Exposure to parental chronic illness is associated with adverse developmental outcomes., Objective: We examined the association between parental multiple sclerosis (MS) and parental MS-related clinical factors on developmental health., Methods: We conducted a population-based cohort study in British Columbia, Canada, using linked health databases. The outcome was childhood development at 5 years of age, expressed as vulnerability on the Early Development Instrument (EDI). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression., Results: MS-affected parents (n = 783) were older, more likely to be English speakers, and had higher rates of mental health morbidity (39.6% vs 22.2%, p < 0.001) than unaffected parents (n = 2988). In the adjusted models, children of mothers with MS (aOR = 0.62, 95% CI = 0.44-0.87), but not children of the fathers with MS, had a lower risk of vulnerability on the social development domain of the EDI. However, mental health comorbidity (aOR = 1.62, 95% CI = 1.05-2.50) and physical comorbidity (aOR = 1.67, 95% CI = 1.05-2.64) among mothers with MS were associated with increased vulnerability on the EDI., Conclusion: Maternal MS, but not paternal MS, was associated with lower rates of developmental vulnerability on the social development domain. However, mental and physical comorbidity among MS-affected mothers were associated with increased developmental vulnerability in children., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2015.)