Compressive stress gradients direct mechanoregulation of anisotropic growth in the zebrafish jaw joint.

Mechanical stimuli arising from fetal movements are critical factors underlying joint growth. Abnormal fetal movements negatively affect joint shape features with important implications for joint health, but the mechanisms by which mechanical forces from fetal movements influence joint growth are still unclear. In this research, we quantify zebrafish jaw joint growth in 3D in free-to-move and immobilised fish larvae between four and five days post fertilisation. We found that the main changes in size and shape in normally moving fish were in the ventrodorsal axis, while growth anisotropy was lost in the immobilised larvae. We next sought to determine the cell level activities underlying mechanoregulated growth anisotropy by tracking individual cells in the presence or absence of jaw movements, finding that the most dramatic changes in growth rates due to jaw immobility were in the ventrodorsal axis. Finally, we implemented mechanobiological simulations of joint growth with which we tested hypotheses relating specific mechanical stimuli to mechanoregulated growth anisotropy. Different types of mechanical stimulation were incorporated into the simulation to provide the mechanoregulated component of growth, in addition to the baseline (non-mechanoregulated) growth which occurs in the immobilised animals. We found that when average tissue stress over the opening and closing cycle of the joint was used as the stimulus for mechanoregulated growth, joint morphogenesis was not accurately predicted. Predictions were improved when using the stress gradients along the rudiment axes (i.e., the variation in magnitude of compression to magnitude of tension between local regions). However, the most accurate predictions were obtained when using the compressive stress gradients (i.e., the variation in compressive stress magnitude) along the rudiment axes. We conclude therefore that the dominant biophysical stimulus contributing to growth anisotropy during early joint development is the gradient of compressive stress experienced along the growth axes under cyclical loading.

More is different: Reconstituting complexity in microtubule regulation.

Microtubules are dynamic cytoskeletal filaments that undergo stochastic switching between phases of polymerization and depolymerization-a behavior known as dynamic instability. Many important cellular processes, including cell motility, chromosome segregation, and intracellular transport, require complex spatiotemporal regulation of microtubule dynamics. This coordinated regulation is achieved through the interactions of numerous microtubule-associated proteins (MAPs) with microtubule ends and lattices. Here, we review the recent advances in our understanding of microtubule regulation, focusing on results arising from biochemical in vitro reconstitution approaches using purified multiprotein ensembles. We discuss how the combinatory effects of MAPs affect both the dynamics of individual microtubule ends, as well as the stability and turnover of the microtubule lattice. In addition, we highlight new results demonstrating the roles of protein condensates in microtubule regulation. Our overall intent is to showcase how lessons learned from reconstitution approaches help unravel the regulatory mechanisms at play in complex cellular environments.

Global assessment of effective population sizes: Consistent taxonomic differences in meeting the 50/500 rule.

Effective population size (Ne) is a particularly useful metric for conservation as it affects genetic drift, inbreeding and adaptive potential within populations. Current guidelines recommend a minimum Ne of 50 and 500 to avoid short-term inbreeding and to preserve long-term adaptive potential respectively. However, the extent to which wild populations reach these thresholds globally has not been investigated, nor has the relationship between Ne and human activities. Through a quantitative review, we generated a dataset with 4610 georeferenced Ne estimates from 3829 populations, extracted from 723 articles. These data show that certain taxonomic groups are less likely to meet 50/500 thresholds and are disproportionately impacted by human activities; plant, mammal and amphibian populations had a <54% probability of reaching N ̂ e = 50 and a <9% probability of reaching N ̂ e = 500. Populations listed as being of conservation concern according to the IUCN Red List had a smaller median N ̂ e than unlisted populations, and this was consistent across all taxonomic groups. N ̂ e was reduced in areas with a greater Global Human Footprint, especially for amphibians, birds and mammals, however relationships varied between taxa. We also highlight several considerations for future works, including the role that gene flow and subpopulation structure plays in the estimation of N ̂ e in wild populations, and the need for finer-scale taxonomic analyses. Our findings provide guidance for more specific thresholds based on Ne and help prioritise assessment of populations from taxa most at risk of failing to meet conservation thresholds.

Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer's disease risk.

The APOE 2/3/4 polymorphism is the greatest genetic risk factor for Alzheimer's disease (AD). This polymorphism is also associated with variation in plasma ApoE level; while APOE*4 lowers, APOE*2 increases ApoE level. Lower plasma ApoE level has also been suggested to be a risk factor for incident dementia. To our knowledge, no large genome-wide association study (GWAS) has been reported on plasma ApoE level. This study aimed to identify new genetic variants affecting plasma ApoE level as well as to test if baseline ApoE level is associated with cognitive function and incident dementia in a longitudinally followed cohort of the Ginkgo Evaluation of Memory (GEM) study. Baseline plasma ApoE concentration was measured in 3031 participants (95.4% European Americans (EAs)). GWAS analysis was performed on 2580 self-identified EAs where both genotype and plasma ApoE data were available. Lower ApoE concentration was associated with worse cognitive function, but not with incident dementia. As expected, the risk for AD increased from E2/2 through to E4/4 genotypes (P for trend = 4.8E-75). In addition to confirming the expected and opposite associations of APOE*2 (P = 4.73E-79) and APOE*4 (P = 8.73E-12) with ApoE level, GWAS analysis revealed nine additional independent signals in the APOE region, and together they explained about 22% of the variance in plasma ApoE level. We also identified seven new loci on chromosomes 1, 4, 5, 7, 11, 12 and 20 (P range = 5.49E-08 to 5.36E-10) that explained about 9% of the variance in ApoE level. Plasma ApoE level-associated independent variants, especially in the APOE region, were also associated with AD risk and amyloid deposition in the brain, indicating that genetically determined ApoE level variation may be a risk factor for developing AD. These results improve our understanding of the genetic determinants of plasma ApoE level and their potential value in affecting AD risk.

General Surgery Resident Participation in a Mandatory Wellness Program: Six Years Later.

INTRODUCTION: Following the approval of a resident-created physician wellness program in 2016, an initial survey demonstrated majority support for the implementation of a mandatory curriculum. The purpose of this study is to survey surgical residents about the wellness curriculum six years after implementation and re-evaluate preference for mandatory participation. METHODS: In 2016, the CORE7 Wellness Program didactic sessions were integrated into the general surgery resident education curriculum. A comparison between 2016 and 2022 resident survey results was done to examine overall approval and resident experience. RESULTS: A total of 25 general surgery residents responded to the 2022 survey which equaled to a response rate of 67.5% compared to a response rate of 87.1% in 2016. Similar to the results in 2016, there was unanimous support (100%, n = 25) in favor of the ongoing development of a general surgery wellness program. The majority of residents (88% versus 85.2% in 2016) preferred quarterly "wellness half-days" remain a mandatory component of the program. In 2016, most of the residents (50%) stated that the reason for mandatory preference for wellness half-days was ease of explanation to faculty. In 2022, the reason changed to a combination of reasons with most residents (59%) selecting ease of explanation to attendings, feeling too guilty otherwise to leave the shift, and forcing the resident to think about self-care. Complaints about taking a wellness half-day from other team members increased from 29% in 2016 to 48% in 2022. CONCLUSIONS: Six years after implementation, there is unanimous support for the mandatory components of a general surgery residency wellness curriculum. Increased perceived complaints from faculty and staff about resident wellness present an opportunity for improvement.

Factors associated with prior completion of colorectal cancer and hepatitis C virus screenings among community health center patients: a cross-sectional study to inform a multi-behavioral educational intervention.

BACKGROUND: Colorectal cancer (CRC) and liver cancer are two of the leading causes of cancer death in the United States and persistent disparities in CRC and liver cancer incidence and outcomes exist. Chronic hepatitis C virus (HCV) infection is one of the main contributors to liver cancer. Effective screening for both CRC and HCV exist and are recommended for individuals based upon age, regardless of gender or sex assigned at birth. Recommendations for both screening behaviors have been recently updated. However, screening rates for both CRC and HCV are suboptimal. Targeting adoption of multiple screening behaviors has the potential to reduce cancer mortality and disparities. OBJECTIVE: To examine psychosocial factors associated with completion of CRC and HCV screenings in order to inform a multi-behavioral educational intervention that pairs CRC and HCV screening information. METHODS: A cross-sectional survey was conducted with participants (N = 50) recruited at two community health centers in Florida (United States). Kruskal-Wallis and Fisher's exact tests were used to examine associations between completion of both CRC and HCV screening, CRC and HCV knowledge, Preventive Health Model constructs (e.g., salience and coherence, response efficacy, social influence), and sociodemographic variables. RESULTS: Most participants were White (84%), female (56%), insured (80%), and reported a household income of $25,000 or less (53%). 30% reported ever previously completing both CRC and HCV screenings. Prior completion of both screening behaviors was associated with higher educational attainment (p = .014), having health insurance (p = .022), being U.S.-born (p = .043), and higher salience and coherence scores for CRC (p = .040) and HCV (p = .004). CONCLUSIONS: Findings demonstrate limited uptake of both CRC and HCV screenings among adults born between 1945 and 1965. Uptake was associated with multiple sociodemographic factors and health beliefs related to salience and coherence. Salience and coherence are modifiable factors associated with completion of both screening tests, suggesting the importance of incorporating these health beliefs in a multi-behavioral cancer education intervention. Additionally, health providers could simultaneously recommend and order CRC and HCV screening to improve uptake among this age cohort.

Evaluation and Treatment of Nausea and Vomiting in Adults.

Nausea and vomiting are common symptoms that can reduce quality of life and indicate life-threatening illness. Acute nausea and vomiting last up to 7 days. In the absence of alarm symptoms, they are typically treated symptomatically and without an extensive evaluation. Typical causes include gastroenteritis or other viral syndromes, foodborne illness, acute migraine headaches, vestibular disturbances, early pregnancy, and adverse effects of medication. Chronic nausea and vomiting last 4 weeks or longer and have a broad differential diagnosis. Causes can be gastrointestinal, infectious, metabolic, neurologic, psychiatric, or related to medications and toxins. A careful history of related factors is essential to guide the initial evaluation and narrow the differential diagnosis. These factors include associated symptoms, timing of onset and duration of symptoms, exacerbating or relieving factors, alarm symptoms, medication and substance use, relationship with recent food ingestion, and comorbidities. Nonpharmacologic management options include fluid and electrolyte replacement; small, frequent meals; and avoidance of trigger foods. Antiemetic drugs effectively reduce symptoms of acute nausea and vomiting, but chronic symptoms are often more challenging to treat. When a specific etiology is not identified, a serotonin antagonist or dopamine antagonist can be used. However, medications may also target the suspected cause of symptoms and the neurotransmitters involved in central and peripheral pathways of nausea and vomiting. Pharmacologic therapy should be used for the shortest time necessary to control symptoms.

NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss.

Hearing loss is a frequent sensory impairment in humans and genetic factors account for an elevated fraction of the cases. We have investigated a large family of five generations, with 15 reported individuals presenting non-syndromic, sensorineural, bilateral and progressive hearing loss, segregating as an autosomal dominant condition. Linkage analysis, using SNP-array and selected microsatellites, identified a region of near 13 cM in chromosome 20 as the best candidate to harbour the causative mutation. After exome sequencing and filtering of variants, only one predicted deleterious variant in the NCOA3 gene (NM_181659, c.2810C > G; p.Ser937Cys) fit in with our linkage data. RT-PCR, immunostaining and in situ hybridization showed expression of ncoa3 in the inner ear of mice and zebrafish. We generated a stable homozygous zebrafish mutant line using the CRISPR/Cas9 system. ncoa3-/- did not display any major morphological abnormalities in the ear, however, anterior macular hair cells showed altered orientation. Surprisingly, chondrocytes forming the ear cartilage showed abnormal behaviour in ncoa3-/-, detaching from their location, invading the ear canal and blocking the cristae. Adult mutants displayed accumulation of denser material wrapping the otoliths of ncoa3-/- and increased bone mineral density. Altered zebrafish swimming behaviour corroborates a potential role of ncoa3 in hearing loss. In conclusion, we identified a potential candidate gene to explain hereditary hearing loss, and our functional analyses suggest subtle and abnormal skeletal behaviour as mechanisms involved in the pathogenesis of progressive sensory function impairment.

Macrogenetics reveals multifaceted influences of environmental variation on vertebrate population genetic diversity across the Americas.

The broad scale distribution of population-specific genetic diversity (GDP ) across taxa remains understudied relative to species diversity gradients, despite its relevance for systematic conservation planning. We used nuclear DNA data collected from 3678 vertebrate populations across the Americas to assess the role of environmental and spatial variables in structuring the distribution of GDP , a key component of adaptive potential in the face of environmental change. We specifically assessed non-linear trends for a metric of GDP, expected heterozygosity (HE ), and found more evidence for spatial hotspots and cold spots in HE rather than a strict pattern with latitude. We also detected inconsistent relationships between HE and environmental variables, where only 11 of 30 environmental comparisons among taxa groups were statistically significant at the .05 level, and the shape of significant trends differed substantially across vertebrate groups. Only one of six taxonomic groups, freshwater fishes, consistently showed significant relationships between HE and most (four of five) environmental variables. The remaining groups had statistically significant relationships for either two (amphibians, reptiles), one (birds, mammals), or no variables (anadromous fishes). Our study highlights gaps in the theoretical foundation upon which macrogenetic predictions have been made thus far in the literature, as well as the nuances for assessing broad patterns in GDP among vertebrate groups. Overall, our results suggest a disconnect between patterns of species and genetic diversity, and underscores that large-scale factors affecting genetic diversity may not be the same factors as those shaping taxonomic diversity. Thus, careful spatial and taxonomic-specific considerations are needed for applying macrogenetics to conservation planning.

Collective effects of XMAP215, EB1, CLASP2, and MCAK lead to robust microtubule treadmilling.

Microtubule network remodeling is essential for fundamental cellular processes including cell division, differentiation, and motility. Microtubules are active biological polymers whose ends stochastically and independently switch between phases of growth and shrinkage. Microtubule treadmilling, in which the microtubule plus end grows while the minus end shrinks, is observed in cells; however, the underlying mechanisms are not known. Here, we use a combination of computational and in vitro reconstitution approaches to determine the conditions leading to robust microtubule treadmilling. We find that microtubules polymerized from tubulin alone can treadmill, albeit with opposite directionality and order-of-magnitude slower rates than observed in cells. We then employ computational simulations to predict that the combinatory effects of four microtubule-associated proteins (MAPs), namely EB1, XMAP215, CLASP2, and MCAK, can promote fast and sustained plus-end-leading treadmilling. Finally, we experimentally confirm the predictions of our computational model using a multi-MAP, in vitro microtubule dynamics assay to reconstitute robust plus-end-leading treadmilling, consistent with observations in cells. Our results demonstrate how microtubule dynamics can be modulated to achieve a dynamic balance between assembly and disassembly at opposite polymer ends, resulting in treadmilling over long periods of time. Overall, we show how the collective effects of multiple components give rise to complex microtubule behavior that may be used for global network remodeling in cells.

CLASPs at a glance.

CLIP-associating proteins (CLASPs) form an evolutionarily conserved family of regulatory factors that control microtubule dynamics and the organization of microtubule networks. The importance of CLASP activity has been appreciated for some time, but until recently our understanding of the underlying molecular mechanisms remained basic. Over the past few years, studies of, for example, migrating cells, neuronal development, and microtubule reorganization in plants, along with in vitro reconstitutions, have provided new insights into the cellular roles and molecular basis of CLASP activity. In this Cell Science at a Glance article and the accompanying poster, we will summarize some of these recent advances, emphasizing how they impact our current understanding of CLASP-mediated microtubule regulation.

Growth orientations, rather than heterogeneous growth rates, dominate jaw joint morphogenesis in the larval zebrafish.

In early limb embryogenesis, synovial joints acquire specific shapes which determine joint motion and function. The process by which the opposing cartilaginous joint surfaces are moulded into reciprocal and interlocking shapes, called joint morphogenesis, is one of the least understood aspects of joint formation and the cell-level dynamics underlying it are yet to be unravelled. In this research, we quantified key cellular dynamics involved in growth and morphogenesis of the zebrafish jaw joint and synthesised them in a predictive computational simulation of joint development. Cells in larval zebrafish jaw joints labelled with cartilage markers were tracked over a 48-h time window using confocal imaging. Changes in distance and angle between adjacent cell centroids resulting from cell rearrangement, volume expansion and extracellular matrix (ECM) deposition were measured and used to calculate the rate and direction of local tissue deformations. We observed spatially and temporally heterogeneous growth patterns with marked anisotropy over the developmental period assessed. There was notably elevated growth at the level of the retroarticular process of the Meckel's cartilage, a feature known to undergo pronounced shape changes during zebrafish development. Analysis of cell dynamics indicated a dominant role for cell volume expansion in growth, with minor influences from ECM volume increases and cell intercalation. Cell proliferation in the joint was minimal over the timeframe of interest. Synthesising the dynamic cell data into a finite element model of jaw joint development resulted in accurate shape predictions. Our biofidelic computational simulation demonstrated that zebrafish jaw joint growth can be reasonably approximated based on cell positional information over time, where cell positional information derives mainly from cell orientation and cell volume expansion. By modifying the input parameters of the simulation, we were able to assess the relative contributions of heterogeneous growth rates and of growth orientation. The use of uniform rather than heterogeneous growth rates only minorly impacted the shape predictions, whereas isotropic growth fields resulted in altered shape predictions. The simulation results suggest that growth anisotropy is the dominant influence on joint growth and morphogenesis. This study addresses the gap of the cellular processes underlying joint morphogenesis, with implications for understanding the aetiology of developmental joint disorders such as developmental dysplasia of the hip and arthrogryposis.

Potential of zebrafish as a model to characterise MicroRNA profiles in mechanically mediated joint degeneration.

Mechanically mediated joint degeneration and cartilage dyshomeostasis is implicated in highly prevalent diseases such as osteoarthritis. Increasingly, MicroRNAs are being associated with maintaining the normal state of cartilage, making them an exciting and potentially key contributor to joint health and disease onset. Here, we present a summary of current in vitro and in vivo models which can be used to study the role of mechanical load and MicroRNAs in joint degeneration, including: non-invasive murine models of PTOA, surgical models which involve ligament transection, and unloading models based around immobilisation of joints or removal of load from the joint through suspension. We also discuss how zebrafish could be used to advance this field, namely through the availability of transgenic lines relevant to cartilage homeostasis and the ability to accurately map strain through the cartilage, enabling the response of downstream MicroRNA targets to be followed dynamically at a cellular level in areas of high and low strain.

Scleraxis genes are required for normal musculoskeletal development and for rib growth and mineralization in zebrafish.

Tendons are an essential part of the musculoskeletal system, connecting muscle and skeletal elements to enable force generation. The transcription factor scleraxis marks vertebrate tendons from early specification. Scleraxis-null mice are viable and have a range of tendon and bone defects in the trunk and limbs but no described cranial phenotype. We report the expression of zebrafish scleraxis orthologs: scleraxis homolog (scx)-a and scxb in cranial and intramuscular tendons and in other skeletal elements. Single mutants for either scxa or scxb, generated by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), are viable and fertile as adult fish. Although scxb mutants show no obvious phenotype, scxa mutant embryos have defects in cranial tendon maturation and muscle misalignment. Mutation of both scleraxis genes results in more severe defects in cranial tendon differentiation, muscle and cartilage dysmorphogenesis and paralysis, and lethality by 2-5 wk, which indicates an essential function of scleraxis for craniofacial development. At juvenile and adult stages, ribs in scxa mutants fail to mineralize and/or are small and heavily fractured. Scxa mutants also have smaller muscle volume, abnormal swim movement, and defects in bone growth and composition. Scleraxis function is therefore essential for normal craniofacial form and function and vital for fish development.-Kague, E., Hughes, S. M., Lawrence, E. A., Cross, S., Martin-Silverstone, E., Hammond, C. L., Hinits, Y. Scleraxis genes are required for normal musculoskeletal development and for rib growth and mineralization in zebrafish.

Greater mortality variability in the United States in comparison with peer countries.

BACKGROUND: Over the past several decades, US mortality declines have lagged behind other high-income countries. However, scant attention has been devoted to how US mortality variability compares with other countries. OBJECTIVE: We examine trends in mortality and mortality variability in the US and 16 peer countries from 1980 through 2016. METHODS: We employ the Human Mortality Database and demographic techniques - with a focus on patterns in the interquartile (IQR), interdecile (IDR), and intercentile (ICR) ranges of survivorship - to better understand US mortality and mortality variability trends in comparative perspective. RESULTS: Compared to other high-income countries, the US: (1) mortality ranking has slipped for nearly all age groups; (2) is losing its old age mortality advantage; (3) has seen growth in relative age-specific mortality gaps from infancy through midlife; and (4) exhibits greater concentrations of deaths from infancy through adulthood, resulting in much greater mortality variability. CONCLUSIONS: We contribute to calls for renewed attention to the relatively low and lagging US life expectancy. The ICR draws particular attention to the comparatively high US early and midlife mortality. CONTRIBUTION: We find comparatively high variability in US mortality. Further reductions in early and midlife mortality could diminish variability, reduce years of potential life lost, and increase life expectancy. Consistent with previous research, we encourage policymakers to focus on reducing the unacceptably high early and midlife mortality in the US. And we urge researchers to more frequently monitor and track mortality variation in conjunction with mortality rates and life expectancy estimates.

The persistent southern disadvantage in US early life mortality, 1965-2014.

BACKGROUND: Recent studies of US adult mortality demonstrate a growing disadvantage among southern states. Few studies have examined long-term trends and geographic patterns in US early life (ages 1 to 24) mortality, ages at which key risk factors and causes of death are quite different than among adults. OBJECTIVE: This article examines trends and variations in early life mortality rates across US states and census divisions. We assess whether those variations have changed over a 50-year time period and which causes of death contribute to contemporary geographic disparities. METHODS: We calculate all-cause and cause-specific death rates using death certificate data from the Multiple Cause of Death files, combining public-use files from 1965-2004 and restricted data with state geographic identifiers from 2005-2014. State population (denominator) data come from US decennial censuses or intercensal estimates. RESULTS: Results demonstrate a persistent mortality disadvantage for young people (ages 1 to 24) living in southern states over the last 50 years, particularly those located in the East South Central and West South Central divisions. Motor vehicle accidents and homicide by firearm account for most of the contemporary southern disadvantage in US early life mortality. CONTRIBUTION: Our results illustrate that US children and youth living in the southern United States have long suffered from higher levels of mortality than children and youth living in other parts of the country. Our findings also suggest the contemporary southern disadvantage in US early life mortality could potentially be reduced with state-level policies designed to prevent deaths involving motor vehicles and firearms.

Family Socioeconomic Status and Early Life Mortality Risk in the United States.

OBJECTIVES: We examine the association between several dimensions of parental socioeconomic status (SES) and all-cause and cause-specific mortality among children and youth (ages 1-24) in the United States. METHODS: We use Cox proportional hazard models to estimate all-cause and cause-specific mortality risk based on data from the 1998 to 2015 National Health Interview Survey-Linked Mortality Files (NHIS-LMFs), restricted to children and youth ages 1-17 at the time of survey followed through age 24, or the end of the follow-up period in 2015 (N = 377,252). RESULTS: Children and youth in families with lower levels of mother's education, father's education, and/or family income-to-needs ratio exhibit significantly higher all-cause mortality risk compared with children and youth living in higher SES families. For example, compared to children and youth living with mothers who earned college degrees, those living with mothers who have not graduated high school experience 40% higher risk of early life mortality over the follow-up period, due in part to higher mortality risks of unintentional injuries and homicides. Similarly, children/youth whose fathers did not graduate high school experience a 41% higher risk of dying before age 25 compared to those with fathers who completed college. CONCLUSIONS: Today's children and youth experience clear disparities in mortality risk across several dimensions of parental SES. As the U.S. continues to lag behind other high-income countries in health and mortality, more attention and resources should be devoted to improving children's health and well-being, including the family and household contexts in which American children live.

The Relationship Between Education and Health: Reducing Disparities Through a Contextual Approach.

Adults with higher educational attainment live healthier and longer lives compared with their less educated peers. The disparities are large and widening. We posit that understanding the educational and macrolevel contexts in which this association occurs is key to reducing health disparities and improving population health. In this article, we briefly review and critically assess the current state of research on the relationship between education and health in the United States. We then outline three directions for further research: We extend the conceptualization of education beyond attainment and demonstrate the centrality of the schooling process to health; we highlight the dual role of education as a driver of opportunity but also as a reproducer of inequality; and we explain the central role of specific historical sociopolitical contexts in which the education-health association is embedded. Findings from this research agenda can inform policies and effective interventions to reduce health disparities and improve health for all Americans.

Residential Mobility Across Early Childhood and Children's Kindergarten Readiness.

Understanding residential mobility in early childhood is important for contextualizing family, school, and neighborhood influences on child well-being. We examined the consequences of residential mobility for socioemotional and cognitive kindergarten readiness using the Early Childhood Longitudinal Study-Birth Cohort, a nationally representative longitudinal survey that followed U.S. children born in 2001 from infancy to kindergarten. We described individual, household, and neighborhood characteristics associated with residential mobility for children aged 0-5. Our residential mobility indicators examined frequency of moves, nonlinearities in move frequency, quality of moves, comparisons between moving houses and moving neighborhoods, and heterogeneity in the consequences of residential mobility. Nearly three-quarters of children moved by kindergarten start. Mobility did not predict cognitive scores. More moves, particularly at relatively high frequencies, predicted lower kindergarten behavior scores. Moves from socioeconomically advantaged to disadvantaged neighborhoods were especially problematic, whereas moves within a ZIP code were not. The implications of moves were similar across socioeconomic status. The behavior findings largely support an instability perspective that highlights potential disruptions from frequent or problematic moves. Our study contributes to literature emphasizing the importance of contextualizing residential mobility. The high prevalence and distinct implications of early childhood moves support the need for further research.