G-CSF - A double edge sword in neutrophil mediated immunity.

Neutrophils are vital for the innate immune system's control of pathogens and neutrophil deficiency can render the host susceptible to life-threatening infections. Neutrophil responses must also be tightly regulated because excessive production, recruitment or activation of neutrophils can cause tissue damage in both acute and chronic inflammatory diseases. Granulocyte colony stimulating factor (G-CSF) is a key regulator of neutrophil biology, from production, differentiation, and release of neutrophil precursors in the bone marrow (BM) to modulating the function of mature neutrophils outside of the BM, particularly at sites of inflammation. G-CSF acts by binding to its cognate cell surface receptor on target cells, causing the activation of intracellular signalling pathways mediating the proliferation, differentiation, function, and survival of cells in the neutrophil lineage. Studies in humans and mice demonstrate that G-CSF contributes to protecting the host against infection, but conversely, it can play a deleterious role in inflammatory diseases. As such, neutrophils and the G-CSF pathway may provide novel therapeutic targets. This review will focus on understanding the role G-CSF plays in the balance between effective neutrophil mediated host defence versus neutrophil-mediated inflammation and tissue damage in various inflammatory and infectious diseases.

Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor.

While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of ß-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.

Dysregulation of neutrophil oxidant production and interleukin-1-related cytokines in granulomatosis with polyangiitis.

OBJECTIVES: Neutrophils play a key role in ANCA-associated vasculitis, both as targets of autoimmunity and facilitators of vascular damage. In granulomatosis with polyangiitis (GPA), data regarding the production of reactive oxygen species (ROS) in neutrophils are unclear. Further, recent data suggests that ROS production could have an anti-inflammatory effect through the regulation of the inflammasome and IL-1-related cytokines. We aimed to analyse the ROS production in neutrophils from patients with GPA and investigate its association with IL-1-related cytokines and the autoantigen proteinase 3 (PR3). METHODS: Seventy-two GPA patients with disease flare were included in the NEUTROVASC prospective cohort study. ROS production was evaluated in whole blood of patients with active GPA and compared with the same patients in remission or healthy controls. Associations between ROS production, PR3 membrane expression on neutrophils, serum levels of IL-1-related cytokines as well as inflammasome-related proteins were analyzed. RESULTS: We observed a robust defect in ROS production by neutrophils from patients with active GPA compared with healthy controls, independent of glucocorticoid treatment. Serum levels of IL-1-related cytokines were significantly increased in GPA patients, particularly in patients with kidney involvement, and levels of these cytokines returned to normal after patients achieved remission. Further, inflammasome-related proteins were significantly dysregulated in the cytosol of neutrophils as well as the serum from GPA patients. CONCLUSION: Our data suggests that ROS production and regulation of the inflammasome in neutrophils from patients with GPA are disturbed and may be a potential therapeutic target. CLINICAL TRIAL REGISTRATION NUMBER: NCT01862068, clinicaltrials.gov, https://www.clinicaltrials.gov.

Risks of opioid overdose among New York State Medicaid recipients with chronic pain before and during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic contributed to healthcare disruptions for patients with chronic pain. Following initial disruptions, national policies were enacted to expand access to long-term opioid therapy (LTOT) for chronic pain and opioid use disorder (OUD) treatment services, which may have modified risk of opioid overdose. We examined associations between LTOT and/or OUD with fatal and non-fatal opioid overdoses, and whether the pandemic moderated overdose risk in these groups. METHODS: We analyzed New York State Medicaid claims data (3/1/2019-12/31/20) of patients with chronic pain (N = 236,391). We used generalized estimating equations models to assess associations between LTOT and/or OUD (neither LTOT or OUD [ref], LTOT only, OUD only, and LTOT and OUD) and the pandemic (03/2020-12/2020) with opioid overdose. RESULTS: The pandemic did not significantly (ns) affect opioid overdose among patients with LTOT and/or OUD. While patients with LTOT (vs. no LTOT) had a slight increase in opioid overdose during the pandemic (pre-pandemic: aOR:1.65, 95% CI:1.05, 2.57; pandemic: aOR:2.43, CI:1.75,3.37, ns), patients with OUD had a slightly attenuated odds of overdose during the pandemic (pre-pandemic: aOR:5.65, CI:4.73, 6.75; pandemic: aOR:5.16, CI:4.33, 6.14, ns). Patients with both LTOT and OUD also experienced a slightly reduced odds of opioid overdose during the pandemic (pre-pandemic: aOR:5.82, CI:3.58, 9.44; pandemic: aOR:3.70, CI:2.11, 6.50, ns). CONCLUSIONS: Findings demonstrated no significant effect of the pandemic on opioid overdose among people with chronic pain and LTOT and/or OUD, suggesting pandemic policies expanding access to chronic pain and OUD treatment services may have mitigated the risk of opioid overdose.

Impact of COVID-19 pandemic on delivery of pediatric radiotherapy: A critical review.

The COVID-19 pandemic has prevented the timely diagnosis and treatment of many diseases, including pediatric cancer. Its impact on pediatric oncologic treatments warrants investigation. As radiotherapy is an integral component of cancer care, we reviewed the published data regarding the impact of COVID-19 on the delivery of pediatric radiotherapy to inform actions for future global events. We found that disruptions in radiotherapy were reported amongst interruptions in other therapies. Disruptions were more common in low-income countries (78%) and low middle-income countries (68%) compared with upper middle-income countries (46%) and high-income countries (10%). Several papers included recommendations for mitigation strategies. Altered treatment regimens were common, including increasing the use of active surveillance and systemic therapy to delay local therapies, and accelerated/hypofractionated dose delivery. Our findings suggest that COVID-19 has impacted radiotherapy delivery in the pediatric population globally. Countries with limited resources may be more affected. Various mitigation strategies have been developed. The efficacy of mitigation measures warrants further investigation.

Evaluating chronic pain as a risk factor for COVID-19 complications among New York State Medicaid beneficiaries: a retrospective claims analysis.

OBJECTIVE: To assess whether chronic pain increases the risk of COVID-19 complications and whether opioid use disorder (OUD) differentiates this risk among New York State Medicaid beneficiaries. DESIGN, SETTING, AND SUBJECTS: This was a retrospective cohort study of New York State Medicaid claims data. We evaluated Medicaid claims from March 2019 through December 2020 to determine whether chronic pain increased the risk of COVID-19 emergency department (ED) visits, hospitalizations, and complications and whether this relationship differed by OUD status. We included beneficiaries 18-64 years of age with 10 months of prior enrollment. Patients with chronic pain were propensity score-matched to those without chronic pain on demographics, utilization, and comorbidities to control for confounders and were stratified by OUD. Complementary log-log regressions estimated hazard ratios (HRs) of COVID-19 ED visits and hospitalizations; logistic regressions estimated odds ratios (ORs) of hospital complications and readmissions within 0-30, 31-60, and 61-90 days. RESULTS: Among 773 880 adults, chronic pain was associated with greater hazards of COVID-related ED visits (HR = 1.22 [95% CI: 1.16-1.29]) and hospitalizations (HR = 1.19 [95% CI: 1.12-1.27]). Patients with chronic pain and OUD had even greater hazards of hospitalization (HR = 1.25 [95% CI: 1.07-1.47]) and increased odds of hepatic- and cardiac-related events (OR = 1.74 [95% CI: 1.10-2.74]). CONCLUSIONS: Chronic pain increased the risk of COVID-19 ED visits and hospitalizations. Presence of OUD further increased the risk of COVID-19 hospitalizations and the odds of hepatic- and cardiac-related events. Results highlight intersecting risks among a vulnerable population and can inform tailored COVID-19 management.

Largest comparative analysis: Novel large spot size 595 nm, high-energy, pulsed dye laser reduces number of treatments for improvement of adult and pediatric port wine birthmarks.

OBJECTIVE: Port wine birthmarks (PWBs) are vascular malformations affecting 0.3%-0.5% of newborns with the tendency to persist into adulthood without adequate treatment of the heterogenous ectatic vessels. This study compares treatment outcomes and parameters of the prior generation pulsed dye laser (PPDL) and the larger spot novel generation pulsed dye laser (NPDL) to establish whether a larger spot size laser provides greater clearance with fewer treatments. METHODS: One hundred and sixty patients were treated with either the PPDL (80 patients) and NPDL (80 patients) with retrospective review of age, body site, laser treatment parameters, number of treatments, and improvement following laser therapy. RESULTS: Patients treated with PPDL were older on average than patients treated with NPDL (mean 24.8 ± 19.7 vs. mean 17.1± 19.3 years, p < 0.05). The majority of lesions treated with PPDL were located on the face and neck, whereas truncal and extremity sites were more frequently treated with the NPDL. Use of NPDL was associated with a mean maximum spot size of 13.1 mm and mean maximum fluence of 7.3 J/cm2 with pulse durations of 0.45-3 ms, whereas use of the PPDL was associated with a mean spot size of 10.8 mm and mean maximum fluence of 8.8 J/cm2 with pulse durations of 0.45-6 ms. Fifty percent improvement was seen with 8.8 PPDL treatments compared to 4.3 NPDL treatments (p ≤ 0.01) with no significant difference in overall mean improvement between both devices at the chosen parameters. Multiple regression analysis showed that device type, not age or lesion location, was the only statistically significant independent variable to affect the endpoint of at least 50% improvement of the lesion. CONCLUSIONS: Use of the larger spot NPDL is associated with achieving 50% improvement with fewer treatments.

Distribution, Diversity, and Soil Associations of Wine Grape Plant-Parasitic Nematodes in Georgia, U.S.A., Vineyards.

Wine grape (Vitis vinifera and V. vinifera hybrids) production in Georgia occurs in three distinct regions (North, West, and South) which can be characterized by sandy, sandy-loam, or sandy clay-loam soils. We studied plant-parasitic nematode (PPN) communities in 15 wine grape vineyards from the three primary growing regions to understand which nematodes are a concern and what soil characteristics are associated with their occurrence and relative abundance. Twelve genera of PPNs were detected throughout the state: Belonolaimus, Helicotylenchus, Hemicycliophora, Heterodera, Hoplolaimus, Meloidogyne, Mesocriconema, Paratrichodorus, Paratylenchus, Pratylenchus, Tylenchorhynchus, and Xiphinema. Nonmetric multidimensional scaling ordination and multirank permutation procedure identified PPN community differences and soil characteristics that were associated by region. Indicator species analysis identified Helicotylenchus, Mesocriconema, Tylenchorhynchus, and Xiphinema as statistically associated with the West while Meloidogyne and Paratrichodorus were associated with the South. Our analyses further suggested that soil texture (percent sand, percent clay, and percent silt) and the lime buffer capacity at equilibrium (LBCEQ) were associated with PPN community structure while pH was not. When focused on a single vineyard in the North, multiple logistic regression analysis suggested a statistically significant association between Meloidogyne spp. and soil characteristics, including percentages of sand, pH, and LBCEQ. Our study supports the association between soil characteristics and specific nematode genera, as well as the emergence of LBCEQ, the soil measurement with the strongest statistical association with nematode community structure and Meloidogyne presence.

Soil infiltration rates are underestimated by models in an urban watershed in central North Carolina, USA.

Stormwater management problems are expanding as urbanization continues and precipitation patterns are increasingly extreme. Urban soils are often more disturbed and compacted than non-urban soils, therefore, rainfall run-off estimates based on models designed for non-urban soils may not be accurate due to altered soil infiltration rates. Our objective was to quantify soil infiltration rates across an urban watershed and compare them to estimates from rainfall-runoff models commonly used in stormwater management (Horton and Green-Ampt) as well as an alternate, random-forest model created using available geospatial data. We measured infiltration rates and collected data on soil properties (texture, bulk density) and context (land use, ground cover, time since development) at 89 points across the 102 ha Walnut Creek watershed in Raleigh, North Carolina (USA). Forest land covers and forest ground covers (leaf litter) had the highest infiltration capacities; however, all of our measurements indicate that urban soils in the Walnut Creek watershed are able to absorb most precipitation events and are likely capable of infiltrating additional urban stormwater runoff. Comparisons between observations and the rainfall-runoff model estimates reveal that both underestimated urban soil infiltration rates. Despite higher than expected urban soil infiltration capacity, stormwater management remains a challenge in this urban watershed. Therefore, to reduce stormwater runoff from impervious surfaces through soil infiltration, impervious surfaces should be disconnected, especially adjacent to new development, and urban forests should be conserved. Further, because our random forest model more accurately captured watershed infiltration rates than the rainfall-runoff models, we propose this type of machine learning approach as an alternative method for informing stormwater management and prioritizing areas for impervious disconnection.

Transatlantic Collaborations: Baccalaureate Nursing Students' Experiences of Participating in a Semester-Long Study Abroad Program.

AIM: The aim of this study was to describe students' experiences during a 15-week semester involving clinical placement in an Irish university. BACKGROUND: Internationalization is promoted and facilitated through study abroad initiatives within nurse education. Collaborations were developed between one university in the United States, an Irish university, and service partners. This study abroad initiative involved planning logistics, curriculum learning opportunities, and negotiating clinical placement in meeting state professional requirements. METHOD: A qualitative descriptive approach was used. Following ethical approval, 19 fourth-year students participated in focus group and individual semistructured interviews. Data analysis followed a thematic approach. RESULTS: Connecting our worlds details a process of acclimatizing, navigating learning, and using person-centered practices, illustrating meaningful learning in a journey of personal and professional development. CONCLUSION: Moving beyond the rhetoric of globalization is critical in future proofing initiatives in developing nursing practitioners while balancing potential safety risks in a post-COVID-19 era.

Spatiotemporal Analysis of the Association Between Pain Management Clinic Laws and Opioid Prescribing and Overdose Deaths.

Pain management clinic (PMC) laws were enacted by 12 states to promote appropriate opioid prescribing, but their impact is inadequately understood. We analyzed county-level opioid overdose deaths (National Vital Statistics System) and patients filling long-duration (≥30 day) or high-dose (≥90 morphine milligram equivalents per day) opioid prescriptions (IQVIA, Inc.) in the United States in 2010-2018. We fitted Besag-York-Mollié spatiotemporal models to estimate annual relative rates (RRs) of overdose and prevalence ratios (PRs) of high-risk prescribing associated with any PMC law and 3 provisions: payment restrictions, site inspections, and criminal penalties. Laws with criminal penalties were significantly associated with reduced PRs of long-duration and high-dose opioid prescriptions (adjusted PR = 0.82, 95% credible interval (CrI): 0.82, 0.82, and adjusted PR = 0.73, 95% CI: 0.73, 0.74 respectively) and reduced RRs of total and natural/semisynthetic opioid overdoses (adjusted RR = 0.86, 95% CrI: 0.80, 0.92, and adjusted RR = 0.84, and 95% CrI: 0.77, 0.92, respectively). Conversely, PMC laws were associated with increased relative rates of synthetic opioid and heroin overdose deaths, especially criminal penalties (adjusted RR = 1.83, 95% CrI: 1.59, 2.11, and adjusted RR = 2.59, 95% CrI: 2.22, 3.02, respectively). Findings suggest that laws with criminal penalties were associated with intended reductions in high-risk opioid prescribing and some opioid overdoses but raise concerns regarding unintended consequences on heroin/synthetic overdoses.

Predicting the Future Course of Opioid Overdose Mortality: An Example From Two US States.

BACKGROUND: The rapid growth of opioid abuse and the related mortality across the United States has spurred the development of predictive models for the allocation of public health resources. These models should characterize heterogeneous growth across states using a drug epidemic framework that enables assessments of epidemic onset, rates of growth, and limited capacities for epidemic growth. METHODS: We used opioid overdose mortality data for 146 North and South Carolina counties from 2001 through 2014 to compare the retrodictive and predictive performance of a logistic growth model that parameterizes onsets, growth, and carrying capacity within a traditional Bayesian Poisson space-time model. RESULTS: In fitting the models to past data, the performance of the logistic growth model was superior to the standard Bayesian Poisson space-time model (deviance information criterion: 8,088 vs. 8,256), with reduced spatial and independent errors. Predictively, the logistic model more accurately estimated fatality rates 1, 2, and 3 years in the future (root mean squared error medians were lower for 95.7% of counties from 2012 to 2014). Capacity limits were higher in counties with greater population size, percent population age 45-64, and percent white population. Epidemic onset was associated with greater same-year and past-year incidence of overdose hospitalizations. CONCLUSION: Growth in annual rates of opioid fatalities was capacity limited, heterogeneous across counties, and spatially correlated, requiring spatial epidemic models for the accurate and reliable prediction of future outcomes related to opioid abuse. Indicators of risk are identifiable and can be used to predict future mortality outcomes.

Prescription Opioid Laws and Opioid Dispensing in US Counties: Identifying Salient Law Provisions With Machine Learning.

BACKGROUND: Hundreds of laws aimed at reducing inappropriate prescription opioid dispensing have been implemented in the United States, yet heterogeneity in provisions and their simultaneous implementation have complicated evaluation of impacts. We apply a hypothesis-generating, multistage, machine-learning approach to identify salient law provisions and combinations associated with dispensing rates to test in future research. METHODS: Using 162 prescription opioid law provisions capturing prescription drug monitoring program (PDMP) access, reporting and administration features, pain management clinic provisions, and prescription opioid limits, we used regularization approaches and random forest models to identify laws most predictive of county-level and high-dose dispensing. We stratified analyses by overdose epidemic phases-the prescription opioid phase (2006-2009), heroin phase (2010-2012), and fentanyl phase (2013-2016)-to further explore pattern shifts over time. RESULTS: PDMP patient data access provisions most consistently predicted high-dispensing and high-dose dispensing counties. Pain management clinic-related provisions did not generally predict dispensing measures in the prescription opioid phase but became more discriminant of high dispensing and high-dose dispensing counties over time, especially in the fentanyl period. Predictive performance across models was poor, suggesting prescription opioid laws alone do not strongly predict dispensing. CONCLUSIONS: Our systematic analysis of 162 law provisions identified patient data access and several pain management clinic provisions as predictive of county prescription opioid dispensing patterns. Future research employing other types of study designs is needed to test these provisions' causal relationships with inappropriate dispensing and to examine potential interactions between PDMP access and pain management clinic provisions. See video abstract at, http://links.lww.com/EDE/B861.

Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications.

PURPOSE OF REVIEW: Non-alcoholic fatty liver disease (NAFLD) is a major and increasing health burden, with the potential to overwhelm hepatology services. However, only a minority of patients develop advanced liver disease. The challenge is early identification of patients at risk of progression. This review aims to summarize current knowledge on the genetic predisposition to NAFLD, and its implications for prognostication and risk stratification. RECENT FINDINGS: PNPLA3-I148M is the most robustly associated genetic variant with NAFLD. Recently, variants in TM6SF2, MBOAT7, GCKR and HSD17B13 have also been implicated. NAFLD is a complex disease, and any one genetic variant alone is insufficient for risk stratification, but combining multiple genetic variants with other parameters is a promising strategy. It is anticipated that, in the near future, analysis of data from large-scale prospective cohorts will reveal NAFLD subtypes and enable the development of prognostic models. This will facilitate risk stratification of patients, enabling optimisation of resources to effectively manage the NAFLD epidemic.

Homeless people and health: a qualitative enquiry into their practices and perceptions.

BACKGROUND: Homeless people experience poorer health and shorter life expectancies than the UK average, but their health needs and expectations have received little attention in research. This study aims to understand homeless people's health perceptions and experiences. METHODS: Semi-structured interviews took place with 28 homeless people in Gloucestershire. The transcripts were thematically analysed drawing out key themes. RESULTS: Homelessness was often rooted in early trauma or an unstable family unit. Participants described poor support on leaving prison, termination of a cohabiting relationship or financial issues as factors precipitating homelessness. There was an expansive and positive understanding of health and its determinants. Mental health issues were common, often linked to traumatic life-events. Substance misuse issues were expressed as a mechanism to manage mental health issues. Participants were frustrated that this co-dependency was not recognized by support services. Participants' living situation curtailed their ability to make health-enhancing choices, which was compounded by issues accessing mainstream healthcare services. CONCLUSIONS: Mental health in homeless people must be recognized in the context of substance misuse and early trauma. Dealing with housing and addiction are critical to enable prioritisation of healthy behaviours. Healthcare services should recognize the chaotic nature of homeless people and their competing issues.

Provider Satisfaction from a New Telepsychiatry Inpatient Consultation Service.

Background:Telepsychiatry is a well-studied modality that has been shown to perform as well as, if not better than, in-person mental health services. However, acceptability of this modality to practitioners, especially as it relates to the type of consult, has not been well studied. To address barriers to implementing a new telepsychiatry consultation-liaison (CL) service at a rural campus of a large tertiary care health network, authors designed a survey to assess consultee attitudes before and after the service launch. A secondary objective was to examine the consult data.Materials and Methods:The new telepsychiatry CL service at the rural hospital was delivered by providers at the main campus of the health network. Authors surveyed all consultees before the launch and every 3 months for 12 months thereafter. Consult data was also tracked in that same period.Results:Over a 12-month period, 442 initial and follow-up consults were completed. Consultees were most concerned with assessing delirium, agitation, and neurocognitive disorder over live video. Consultees generally held their belief that telepsychiatry consults are not as enjoyable as in-person consults, but they recognized its value, specifically regarding improved access for patients.Discussion:The service was successfully launched and was well received as evidenced by the continued use of the service.Conclusions:The project revealed valuable insight which has been used to improve the service and to replicate it at another campus within the health network.

Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics.

OBJECTIVES: Animal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3-4 months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB). METHODS: A series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28 days, intracellular bacilli treated daily for 28 days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56 days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6 months with each regimen. RESULTS: Using linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56 days were 0.18 (95% credible interval=0.13-0.23) versus 0.15 (95% credible interval=0.08-0.21) log10 cfu/mL/day, compared with 0.16 (95% credible interval=0.13-0.18) versus 0.11 (95% credible interval=0.09-0.13) log10 cfu/mL/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1-41.34) and 72.30% (95% credible interval=71.41-73.17) at 3 and 4 months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18-94.13) at 6 months for standard therapy. CONCLUSIONS: The kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6 months in most patients.

Development and Validation of a Google Street View Pedestrian Safety Audit Tool.

BACKGROUND: Assessing aspects of intersections that may affect the risk of pedestrian injury is critical to developing child pedestrian injury prevention strategies, but visiting intersections to inspect them is costly and time-consuming. Several research teams have validated the use of Google Street View to conduct virtual neighborhood audits that remove the need for field teams to conduct in-person audits. METHODS: We developed a 38-item virtual audit instrument to assess intersections for pedestrian injury risk and tested it on intersections within 700 m of 26 schools in New York City using the Computer-assisted Neighborhood Visual Assessment System (CANVAS) with Google Street View imagery. RESULTS: Six trained auditors tested this instrument for inter-rater reliability on 111 randomly selected intersections and for test-retest reliability on 264 other intersections. Inter-rater kappa scores ranged from -0.01 to 0.92, with nearly half falling above 0.41, the conventional threshold for moderate agreement. Test-retest kappa scores were slightly higher than but highly correlated with inter-rater scores (Spearman rho = 0.83). Items that were highly reliable included the presence of a pedestrian signal (K = 0.92), presence of an overhead structure such as an elevated train or a highway (K = 0.81), and intersection complexity (K = 0.76). CONCLUSIONS: Built environment features of intersections relevant to pedestrian safety can be reliably measured using a virtual audit protocol implemented via CANVAS and Google Street View.

Attachment security differs by later autism spectrum disorder: A prospective study.

Although difficulties with social relationships are key to autism spectrum disorder (ASD), no previous study has examined infant attachment security prior to ASD diagnosis. We prospectively assessed attachment security at 15 months in high-risk infants with later ASD (high-risk/ASD, n = 16), high-risk infants without later ASD (high-risk/no-ASD, n = 40), and low-risk infants without later ASD (low-risk/no-ASD, n = 39) using the Strange Situation Procedure. High-risk/ASD infants were disproportionately more likely to be classified as insecure (versus secure) and more likely to be classified as insecure-resistant (versus secure or avoidant) than high-risk/no-ASD and low-risk/no-ASD infants. High-risk infants with insecure-resistant attachments were over nine times more likely to receive an ASD diagnosis than high-risk infants with secure attachments. Insecure-resistant attachment in high-risk infants suggests a propensity toward negative affect with the parent in conditions of stress. Insecure-resistant attachment may prove useful as a potential early index of propensity toward ASD diagnosis in high-risk siblings, while insecure-resistant attachment in the context of emergent autism may contribute to difficulties experienced by children with ASD and their families.

Trends in school-age pedestrian and pedalcyclist crashes in the USA: 26 states, 2000-2014.

BACKGROUND: Despite substantial progress, motor vehicle crashes remain a leading killer of US children. Previously, we documented significant positive impacts of Safe Routes to School interventions on school-age pedestrian and pedalcyclist crashes. OBJECTIVE: To expand our analysis of US trends in motor vehicle crashes involving school-age pedestrians and pedalcyclists, exploring heterogeneity by age and geography. METHODS: We obtained recent police-reported crash data from 26 states, calculating population rates of pedestrian and pedalcyclist crashes, crash fatality rates and pedestrian commuter-adjusted crash rates ('pedestrian danger index') for school-age children as compared with other age groups. We estimated national and statewide trends by age, injury status, day and travel hour using hierarchical linear modeling. RESULTS: School-age children accounted for nearly one in three pedestrians and one in two pedalcyclists struck in motor vehicle crashes from 2000 to 2014. Yet, the rates of these crashes declined 40% and 53%, respectively, over that time, on average, even as adult rates rose. Average crash rates varied geographically from 24.4 to 100.8 pedestrians and 15.6 to 56.7 pedalcyclists struck per 100 000 youth. Crash rates and fatality rates were inversely correlated. CONCLUSIONS: Despite recent increases in adult pedestrian crashes, school-age and younger pedestrians experienced ongoing declines in motor vehicle crashes through 2014 across the USA. There was no evidence of displacement in crash severity; declines were observed in all outcomes. The growing body of state crash data resources can present analytic challenges but also provides unique insights into national and local pedestrian crash trends for all crash outcomes.