Publications by authors named "W Thomas Boyce"

581 Publications

Optimality and Limitations of Audio-Visual Integration for Cognitive Systems.

Front Robot AI 2020 17;7:94. Epub 2020 Jul 17.

Intelligent Systems Research Centre, Ulster University, Magee Campus, Derry Londonderry, Northern Ireland, United Kingdom.

Multimodal integration is an important process in perceptual decision-making. In humans, this process has often been shown to be statistically optimal, or near optimal: sensory information is combined in a fashion that minimizes the average error in perceptual representation of stimuli. However, sometimes there are costs that come with the optimization, manifesting as illusory percepts. We review audio-visual facilitations and illusions that are products of multisensory integration, and the computational models that account for these phenomena. In particular, the same optimal computational model can lead to illusory percepts, and we suggest that more studies should be needed to detect and mitigate these illusions, as artifacts in artificial cognitive systems. We provide cautionary considerations when designing artificial cognitive systems with the view of avoiding such artifacts. Finally, we suggest avenues of research toward solutions to potential pitfalls in system design. We conclude that detailed understanding of multisensory integration and the mechanisms behind audio-visual illusions can benefit the design of artificial cognitive systems.
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http://dx.doi.org/10.3389/frobt.2020.00094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805627PMC
July 2020

Genes, Environments, and Time: The Biology of Adversity and Resilience.

Pediatrics 2021 Feb;147(2)

Center on the Developing Child and

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.
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http://dx.doi.org/10.1542/peds.2020-1651DOI Listing
February 2021

Leveraging the Biology of Adversity and Resilience to Transform Pediatric Practice.

Pediatrics 2021 Feb 25;147(2). Epub 2021 Jan 25.

The Rockefeller University, New York, New York.

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.
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http://dx.doi.org/10.1542/peds.2019-3845DOI Listing
February 2021

Externalizing and Internalizing Problems: Associations with Family Adversity and Young Children's Adrenocortical and Autonomic Functioning.

Res Child Adolesc Psychopathol 2021 May 14;49(5):629-642. Epub 2021 Jan 14.

University of California San Francisco, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1007/s10802-020-00762-0DOI Listing
May 2021

Associations between multisystem stress reactivity and peer nominated aggression in early childhood vary by sex.

Dev Psychopathol 2020 12;32(5):1888-1898

Departments of Psychiatry and Pediatrics, University of California, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1017/S0954579420001406DOI Listing
December 2020

Genes and environments, development and time.

Proc Natl Acad Sci U S A 2020 09;117(38):23235-23241

Program in Child and Brain Development, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada.

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.
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http://dx.doi.org/10.1073/pnas.2016710117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519332PMC
September 2020

Immunogenicity of a single-dose compared with a two-dose primary series followed by a booster dose of ten-valent or 13-valent pneumococcal conjugate vaccine in South African children: an open-label, randomised, non-inferiority trial.

Lancet Infect Dis 2020 12 25;20(12):1426-1436. Epub 2020 Aug 25.

South African Medical Research Council Vaccines and Infectious Diseases Analytical Research Unit, University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa; Department of Science, National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa.

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).
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http://dx.doi.org/10.1016/S1473-3099(20)30289-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689288PMC
December 2020

Maternal Stress During Pregnancy Predicts Infant Infectious and Noninfectious Illness.

J Pediatr 2021 01 19;228:117-125.e2. Epub 2020 Aug 19.

Weill Institute for Neurosciences, Center for Health and Community, Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA.

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.
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http://dx.doi.org/10.1016/j.jpeds.2020.08.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752845PMC
January 2021

How a Pandemic Could Advance the Science of Early Adversity.

JAMA Pediatr 2020 Jul 27. Epub 2020 Jul 27.

Department of Psychiatry, University of California, San Francisco, San Francisco.

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http://dx.doi.org/10.1001/jamapediatrics.2020.2354DOI Listing
July 2020

PyTrack: An end-to-end analysis toolkit for eye tracking.

Behav Res Methods 2020 12;52(6):2588-2603

School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore.

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.
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http://dx.doi.org/10.3758/s13428-020-01392-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725757PMC
December 2020

The Ethical Triage and Management Guidelines of the Entrapped and Mangled Extremity in Resource Scarce Environments: A Systematic Literature Review.

Disaster Med Public Health Prep 2020 May 27:1-9. Epub 2020 May 27.

MS3 Medical University of South Carolina, Charleston, SC.

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.
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http://dx.doi.org/10.1017/dmp.2020.49DOI Listing
May 2020

Evidence for discrete profiles of children's physiological activity across three neurobiological system and their transitions over time.

Dev Sci 2021 Jan 28;24(1):e12989. Epub 2020 May 28.

Department of Psychiatry, University of California, California, USA.

The conceptualization of stress-responsive physiological systems as operating in an integrated manner is evident in several theoretical models of cross-system functioning. However, limited empirical research has modeled the complexity of multisystem activity. Moreover few studies have explored developmentally regulated changes in multisystem activity during early childhood when plasticity is particularly pronounced. The current study used latent profile analysis (LPA) to evaluate multisystem activity during fall and spring of children's transition to kindergarten in three biological systems: the parasympathetic nervous system (PNS), sympathetic nervous system (SNS), and hypothalamic pituitary adrenal (HPA) axis. Latent transition analysis (LTA) was then used to examine the stability of profile classification across time. Across both timepoints, three distinct profiles of multisystem activity emerged. One profile was characterized by heightened HPA axis activity (HPA Axis Responders), a second profile was characterized by moderate, typically adaptive patterns across the PNS, SNS, and HPA axis (Active Copers/Mobilizers), and a third profile was characterized by heightened baseline activity, particularly in the PNS and SNS (Anticipatory Arousal/ANS Responders). LTA of fall-to-spring profile classifications indicated higher probabilities that children remained in the same profile over time compared to probabilities of profile changes, suggesting stability in certain patterns of cross-system responsivity. Patterns of profile stability and change were associated with socioemotional outcomes at the end of the school year. Findings highlight the utility of LPA and LTA to detect meaningful patterns of complex multisystem physiological activity across three systems and their associations with early adjustment during an important developmental transition.
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http://dx.doi.org/10.1111/desc.12989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669674PMC
January 2021

Splitting time: Sound-induced illusory visual temporal fission and fusion.

J Exp Psychol Hum Percept Perform 2020 Feb;46(2):172-201

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).
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http://dx.doi.org/10.1037/xhp0000703DOI Listing
February 2020

Conserving ecological roles of top predators in isolated mountains.

Ecol Appl 2020 01 25;30(1):e02029. Epub 2019 Nov 25.

Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, California, 95616, USA.

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http://dx.doi.org/10.1002/eap.2029DOI Listing
January 2020

The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.

Proc Natl Acad Sci U S A 2020 09 14;117(38):23329-23335. Epub 2019 Oct 14.

Department of Medical Genetics, University of British Columbia-BC Children's Hospital Research Institute, Vancouver, BC, Canada V5Z 4H4;

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 ( = 1,032), with performance assessed in a separate test dataset ( = 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.
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http://dx.doi.org/10.1073/pnas.1820843116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519312PMC
September 2020

LIMITED DETECTION OF ANTIBODIES TO CLADE 2.3.4.4 A/GOOSE/GUANGDONG/1/1996 LINEAGE HIGHLY PATHOGENIC H5 AVIAN INFLUENZA VIRUS IN NORTH AMERICAN WATERFOWL.

J Wildl Dis 2020 01 26;56(1):47-57. Epub 2019 Sep 26.

Southeastern Cooperative Wildlife Disease Study, Department of Population Health, College of Veterinary Medicine, University of Georgia, 589 D. W. Brooks Drive, Athens, Georgia 30602, USA.

During 2014, highly pathogenic (HP) influenza A viruses (IAVs) of the A/Goose/Guangdong/1/1996 lineage (GsGD-HP-H5), originating from Asia, were detected in domestic poultry and wild birds in Canada and the US. These clade 2.3.4.4 GsGD-HP-H5 viruses included reassortants possessing North American lineage gene segments; were detected in wild birds in the Pacific, Central, and Mississippi flyways; and caused the largest HP IAV outbreak in poultry in US history. To determine if an antibody response indicative of previous infection with clade 2.3.4.4 GsGD-HP-H5 IAV could be detected in North American wild waterfowl sampled before, during, and after the 2014-15 outbreak, sera from 2,793 geese and 3,715 ducks were tested by blocking enzyme-linked immunosorbent assay and hemagglutination inhibition (HI) tests using both clade 2.3.4.4 GsGD-HPH5 and North American lineage low pathogenic (LP) H5 IAV antigens. We detected an antibody response meeting a comparative titer-based criteria (HI titer observed with 2.3.4.4 GsGD-HP-H5 antigens exceeded the titer observed for LP H5 antigen by two or more dilutions) for previous infection with clade 2.3.4.4 GsGD-HP-H5 IAV in only five birds, one Blue-winged Teal () sampled during the outbreak and three Mallards () and one Canada Goose () sampled during the post-outbreak period. These serologic results are consistent with the spatiotemporal extent of the outbreak in wild birds in North America during 2014 and 2015 and limited exposure of waterfowl to GsGD-HP-H5 IAV, particularly in the central and eastern US.
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January 2020

Biological sensitivity to context: A test of the hypothesized U-shaped relation between early adversity and stress responsivity.

Dev Psychopathol 2020 05;32(2):641-660

Departments of Psychiatry and Pediatrics, University of California, San Francisco, Division of Developmental Medicine, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1017/S0954579419000518DOI Listing
May 2020

Immunogenicity and Safety of an Early Measles Vaccination Schedule at 6 and 12 Months of Age in Human Immunodeficiency Virus (HIV)-Unexposed and HIV-Exposed, Uninfected South African Children.

J Infect Dis 2019 09;220(9):1529-1538

Medical Research Council, Respiratory and Meningeal Pathogens Research Unit.

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.
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http://dx.doi.org/10.1093/infdis/jiz348DOI Listing
September 2019

Associations between classroom climate and children's externalizing symptoms: The moderating effect of kindergarten children's parasympathetic reactivity.

Dev Psychopathol 2020 05;32(2):661-672

Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1017/S095457941900052XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957767PMC
May 2020

Extinction vortex dynamics of top predators isolated by urbanization.

Ecol Appl 2019 04 20;29(3):e01868. Epub 2019 Mar 20.

Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, California, 95616, USA.

Extinction risk is elevated in small, isolated populations due to demographic and genetic interactions. Therefore, it is critical to model these processes realistically in population viability analyses (PVA) to inform local management and contribute to a greater understanding of mechanisms within the extinction vortex. We conducted PVA's for two small mountain lion populations isolated by urbanization in southern California to predict population growth, extinction probability, and loss of genetic diversity with empirical data. Specifically, we (1) provide the first PVA for isolated mountain lions in the Santa Ana Mountains (SAM) that considers both demographic and genetic risk factors and (2) test the hypothesis that variation in abundance and mortality between the SAM and Santa Monica Mountains (SMM) result in differences in population growth, loss of heterozygosity, and extinction probability. Our models predicted 16-21% probability of local extinction in the SAM due purely to demographic processes over 50 yr with current low levels or no immigration. Our models also predicted that genetic diversity will further erode in the SAM such that concern regarding inbreeding depression is warranted unless gene flow is increased, and that if inbreeding depression occurs, rapid local extinction will be highly likely. Dynamics of the two populations were broadly similar, but they also exhibited differences driven by larger population size and higher mortality in the SAM. Density-independent scenarios predicted a rapidly increasing population in the SMM, whereas growth potential did not differ from a stable trend in the SAM. Demographic extinction probability and loss of heterozygosity were greater in the SMM for density-dependent scenarios without immigration. However, higher levels of immigration had stronger, positive influences on both demographic viability and retention of genetic diversity in the SMM driven by lower abundance and higher adult survival. Our results elucidate demographic and genetic threats to small populations within the extinction vortex, and how these vary relative to demographic structure. Importantly, simulating seemingly attainable increases in connectivity was sufficient to greatly reduce extinction probability. Our work highlights that conservation of large carnivores is achievable within urbanized landscapes, but requires land protection, connectivity, and strategies to promote coexistence with humans.
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http://dx.doi.org/10.1002/eap.1868DOI Listing
April 2019

Integration of DNA methylation patterns and genetic variation in human pediatric tissues help inform EWAS design and interpretation.

Epigenetics Chromatin 2019 01 2;12(1). Epub 2019 Jan 2.

Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.

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.
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http://dx.doi.org/10.1186/s13072-018-0245-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314079PMC
January 2019

Informant-specific reports of peer and teacher relationships buffer the effects of harsh parenting on children's oppositional defiant disorder during kindergarten.

Dev Psychopathol 2020 02;32(1):163-174

Departments of Psychiatry and Pediatrics, University of California, San Francisco.

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.
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http://dx.doi.org/10.1017/S0954579418001499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529298PMC
February 2020

An exploratory qualitative study of life trajectories from preschool-age to young adulthood: Identifying early biologic sensitivity, facing challenges and moving forward.

Adv Pediatr Res 2018 ;5(2)

Department of Family Health Care Nursing, UCSF School of Nursing, CA, USA.

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.
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http://dx.doi.org/10.24105/apr.2018.5.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201258PMC
January 2018

The Cloacal Microbiome of Five Wild Duck Species Varies by Species and Influenza A Virus Infection Status.

mSphere 2018 10 24;3(5). Epub 2018 Oct 24.

Pathology, Microbiology and Immunology, University of California, Davis, Davis, California, USA.

Waterfowl, especially ducks of the genus , are natural reservoir species for influenza A virus (IAV). Duck populations contain nearly all the known diversity of IAVs, and the birds are asymptomatic to infection. Previous work established that IAV infection status is correlated with changes in the cloacal microbiome in juvenile mallards. Here, we analyze five species to determine whether these duck species have similar IAV and IAV cloacal microbiomes, or if the relationships among a host, influenza virus, and the microbiome are species specific. We assessed taxonomic composition of the microbiome, alpha diversity, and beta diversity and found very few patterns related to microbiome and infection status across species, while detecting strong differences within species. A host species-specific signal was stronger in IAV ducks than IAV ducks, and the effect size of host species on the microbiome was three times higher in IAV birds than IAV birds. The mallards and the northern shovelers, the species with highest sample sizes but also with differing feeding ecology, showed especially contrasting patterns in microbiome composition, alpha diversity, and beta diversity. Our results indicate that the microbiome may have a unique relationship with influenza virus infection at the species level. Waterfowl are natural reservoir species for influenza A virus (IAV). Thus, they maintain high levels of pathogen diversity, are asymptomatic to the infection, and also contribute to the risk of a global influenza pandemic. An individual's microbiome is a critical part in how a vertebrate manages pathogens and illness. Here, we describe the cloacal microbiome of 300 wild ducks, from five species (four with previously undescribed microbiomes), including both IAV-negative and IAV-positive individuals. We demonstrate that there is not one consistent "flu-like" microbiome or response to flu across species. Individual duck species appear to have unique relationships between their microbiomes and IAV, and IAV-negative birds have a stronger tie to host species than the IAV-positive birds. In a broad context, understanding the role of the microbiome in IAV reservoir species may have future implications for avian disease management.
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http://dx.doi.org/10.1128/mSphere.00382-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200988PMC
October 2018

The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.

Epigenomics 2018 11 23;10(11):1445-1461. Epub 2018 Oct 23.

Department of Psychiatry, Center for Health & Community, Weill Neuroscience Institute, University of California, San Francisco, 3333 California Street, Suite 465, San Francisco, CA 94118, USA.

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.
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http://dx.doi.org/10.2217/epi-2018-0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462839PMC
November 2018

Links between blood parasites, blood chemistry, and the survival of nestling American crows.

Ecol Evol 2018 Sep 7;8(17):8779-8790. Epub 2018 Aug 7.

Department of Pathology, Microbiology, and Immunology School of Veterinary Medicine University of California Davis California.

Many studies have used the avian hemosporidians (, , and ) to test hypotheses of host-parasite co-evolution, yet documented health and survival consequences of these blood parasites vary among studies and generalizations about their pathogenicity are debatable. In general, the negative effects of the hemosporidians are likely to be greatest during acute infections of young birds, yet most previous studies in wild passerines have examined chronic effects in adults. Here, we evaluated responses of nestling American crows () to acute infection (prevalence and burden), as well as its short- and long-term survival consequences. We used panel of nine hematological and biochemical parameters that are regularly used to evaluate the health of domestic animals, including leukocyte profiles, hematocrit, and plasma proteins. We assessed the effects of infection on survival in a mark-recapture framework. Overall, 56% of crows (=321 samples) were infected by at least one of the three genera. Infections by all genera were associated with elevated plasma proteins and globulins, which could indicate an adaptive immune response. However, only infections were associated with low hematocrit (anemia) and lower fledging success, possibly mediated by the negative effect of low hematocrit values on body condition. Moreover, early infection (<40 days of age) had long-term survival implications: it was associated with lower apparent survival probability within 3 years after fledging. These results suggest that young crows mounted an adaptive immune response to all three genera. Short- and long-term pathological effects, however, were only apparent with infections.
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http://dx.doi.org/10.1002/ece3.4287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157653PMC
September 2018

Differences in Febrile and Respiratory Illnesses in Minority Children: The Sociodemographic Context of Restrictive Parenting.

Acad Pediatr 2019 07 27;19(5):534-541. Epub 2018 Sep 27.

Department of Psychiatry (DS Roubinov, NR Bush, N Adler, and WT Boyce), Weill Institute for Neurosciences, University of California, San Francisco; Department of Pediatrics (NR Bush, N Adler, and WT Boyce), University of California, San Francisco.

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.
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http://dx.doi.org/10.1016/j.acap.2018.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437018PMC
July 2019

Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood.

Dev Sci 2019 03 21;22(2):e12739. Epub 2018 Sep 21.

Psychiatry, University of California, San Francisco, California.

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.
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http://dx.doi.org/10.1111/desc.12739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433477PMC
March 2019

Family Socioeconomic Status, Cortisol, and Physical Health in Early Childhood: The Role of Advantageous Neighborhood Characteristics.

Psychosom Med 2018 06;80(5):492-501

From the Department of Psychiatry (Roubinov, Hagan, Boyce, Adler, Bush), Weill Institute for Neurosciences, University of California, San Francisco; Department of Psychology (Hagan), San Francisco State University; and Department of Pediatrics (Boyce, Adler, Bush), University of California, San Francisco.

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.
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http://dx.doi.org/10.1097/PSY.0000000000000585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976531PMC
June 2018

Comparative analysis of Campylobacter isolates from wild birds and chickens using MALDI-TOF MS, biochemical testing, and DNA sequencing.

J Vet Diagn Invest 2018 May 12;30(3):354-361. Epub 2018 Mar 12.

Departments of Pathology, Microbiology and Immunology (Lawton, Byrne, Fritz, Boyce), University of California, Davis, CA.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was compared to conventional biochemical testing methods and nucleic acid analyses (16S rDNA sequencing, hippurate hydrolysis gene testing, whole genome sequencing [WGS]) for species identification of Campylobacter isolates obtained from chickens ( Gallus gallus domesticus, n = 8), American crows ( Corvus brachyrhynchos, n = 17), a mallard duck ( Anas platyrhynchos, n = 1), and a western scrub-jay ( Aphelocoma californica, n = 1). The test results for all 27 isolates were in 100% agreement between MALDI-TOF MS, the combined results of 16S rDNA sequencing, and the hippurate hydrolysis gene PCR ( p = 0.0027, kappa = 1). Likewise, the identifications derived from WGS from a subset of 14 isolates were in 100% agreement with the MALDI-TOF MS identification. In contrast, biochemical testing misclassified 5 isolates of C. jejuni as C. coli, and 16S rDNA sequencing alone was not able to differentiate between C. coli and C. jejuni for 11 sequences ( p = 0.1573, kappa = 0.0857) when compared to MALDI-TOF MS and WGS. No agreement was observed between MALDI-TOF MS dendrograms and the phylogenetic relationships revealed by rDNA sequencing or WGS. Our results confirm that MALDI-TOF MS is a fast and reliable method for identifying Campylobacter isolates to the species level from wild birds and chickens, but not for elucidating phylogenetic relationships among Campylobacter isolates.
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http://dx.doi.org/10.1177/1040638718762562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505823PMC
May 2018