Risk of not being in employment, education or training (NEET) in late adolescence is signalled by school readiness measures at 4-5 years.

BACKGROUND: Not being in employment, education, or training (NEET) is associated with poor health (physical and mental) and social exclusion. We investigated whether England's statutory school readiness measure conducted at 4-5 years provides a risk signal for NEET in late adolescence. METHODS: We identified 8,118 individuals with school readiness measures at 4-5 years and NEET records at 16-17 years using Connected Bradford, a bank of linked routinely collected datasets. Children were categorised as 'school ready' if they reached a 'Good Level of Development' on the Early Years Foundation Stage Profile. We used probit regression and structural equation modelling to investigate the relationship between school readiness and NEET status and whether it primarily relates to academic attainment. RESULTS: School readiness was significantly associated with NEET status. A larger proportion of young people who were not school ready were later NEET (11%) compared to those who were school ready (4%). Most of this effect was attributable to shared relationships with academic attainment, but there was also a direct effect. Measures of deprivation and Special Educational Needs were also strong predictors of NEET status. CONCLUSIONS: NEET risk factors occur early in life. School readiness measures could be used as early indicators of risk, with interventions targeted to prevent the long-term physical and mental health problems associated with NEET, especially in disadvantaged areas. Primary schools are therefore well placed to be public health partners in early intervention strategies.

Click detection rate variability of central North Pacific sperm whales from passive acoustic towed arrays.

Passive acoustic monitoring (PAM) is an optimal method for detecting and monitoring cetaceans as they frequently produce sound while underwater. Cue counting, counting acoustic cues of deep-diving cetaceans instead of animals, is an alternative method for density estimation, but requires an average cue production rate to convert cue density to animal density. Limited information about click rates exists for sperm whales in the central North Pacific Ocean. In the absence of acoustic tag data, we used towed hydrophone array data to calculate the first sperm whale click rates from this region and examined their variability based on click type, location, distance of whales from the array, and group size estimated by visual observers. Our findings show click type to be the most important variable, with groups that include codas yielding the highest click rates. We also found a positive relationship between group size and click detection rates that may be useful for acoustic predictions of group size in future studies. Echolocation clicks detected using PAM methods are often the only indicator of deep-diving cetacean presence. Understanding the factors affecting their click rates provides important information for acoustic density estimation.

α-catenin middle- and actin-binding domain unfolding mutants differentially impact epithelial strength and sheet migration.

α-catenin (α-cat) displays force-dependent unfolding and binding to actin filaments through direct and indirect means, but features of adherens junction structure and function most vulnerable to loss of these allosteric mechanisms have not been directly compared. By reconstituting an α-cat F-actin-binding domain unfolding mutant known to exhibit enhanced binding to actin (α-cat-H0-FABD+) into α-cat knockout Madin Darby Canine Kidney (MDCK) cells, we show that partial loss of the α-cat catch bond mechanism (via an altered H0 α-helix) leads to stronger epithelial sheet integrity with greater colocalization between the α-cat-H0-FABD+ mutant and actin. α-cat-H0-FABD+ -expressing cells are less efficient at closing scratch-wounds, suggesting reduced capacity for more dynamic cell-cell coordination. Evidence that α-cat-H0-FABD+ is equally accessible to the conformationally sensitive α18 antibody epitope as WT α-cat and shows similar vinculin recruitment suggests this mutant engages lower tension cortical actin networks, as its M-domain is not persistently open. Conversely, α-cat-M-domain salt-bridge mutants with persistent recruitment of vinculin and phosphorylated myosin light chain show only intermediate monolayer adhesive strengths, but display less directionally coordinated and thereby slower migration speeds during wound-repair. These data show α-cat M- and FABD-unfolding mutants differentially impact cell-cell cohesion and migration properties, and suggest signals favoring α-cat-cortical actin interaction without persistent M-domain opening may improve epithelial monolayer strength through enhanced coupling to lower tension actin networks.

Damage-evoked signals in cochlear neurons and supporting cells.

In addition to hearing loss, damage to the cochlea can lead to gain of function pathologies such as hyperacusis. It has been proposed that painful hyperacusis, noxacusis, may be carried to the central nervous system by type II cochlear afferents, sparse, unmyelinated neurons that share morphological and neurochemical traits with nociceptive C-fibers of the somatic nervous system. Also like in skin, damage elicits spreading calcium waves within cochlear epithelia. These are mediated by extracellular ATP combined with IP3-driven release from intracellular calcium stores. Type II afferents are excited by ATP released from damaged epithelia. Thus, the genesis and propagation of epithelial calcium waves is central to cochlear pathology, and presumably hyperacusis. Damage-evoked signals in type II afferents and epithelial cells have been recorded in cochlear explants or semi-intact otic capsules. These efforts have included intracellular electrical recording, use of fluorescent calcium indicators, and visualization of an activity-dependent, intrinsic fluorescent signal. Of relevance to hyperacusis, prior noise-induced hearing loss leads to the generation of prolonged and repetitive activity in type II neurons and surrounding epithelia.

Programmed Death Ligand 1-Expressing Macrophages and Their Protective Role in the Joint During Arthritis.

OBJECTIVE: Arthritis associated with immune checkpoint inhibitor therapies highlights the importance of immune checkpoint expression for joint homeostasis. We investigated the role of programmed death ligand (PD-L) 1 in the synovium using a collagen-induced arthritis (CIA) mouse model. METHODS: We blocked PD-L1 using blocking antibodies during CIA and assessed the arthritis severity by clinical and histologic scoring. PD-L1 expression and the origin of synovial macrophages were investigated using flow cytometry and parabiosis. We used Cre-Lox mice to ascertain the protective role of PD-L1-expressing macrophages in arthritis. The immune profile of human and murine synovial PD-L1+ macrophages was determined by reverse transcriptase-polymerase chain reaction, flow cytometry, and single-cell RNA sequencing. RESULTS: Anti-PD-L1 antibody treatment during CIA worsened arthritis with increased immune cell infiltration compared with isotype control, supporting the regulatory role of PD-L1 in the joint. The main cells expressing PD-L1 in the synovium were macrophages. Using parabiosis, we showed that synovial PD-L1+ macrophages were both locally proliferating and partially replaced by the circulation. PD-L1+ macrophages had increased levels of MER proto-oncogene tyrosine kinase (MerTK) and interleukin (IL)-10 expression during acute CIA. Genetic depletion of PD-L1 on macrophages in LyzcrePD-L1fl/fl mice resulted in worsened CIA compared with controls. We found that human PD-L1+ macrophages in the synovium of healthy individuals and patients with rheumatoid arthritis express MerTK and IL-10. CONCLUSION: PD-L1+ macrophages with efferocytotic and anti-inflammatory characteristics protect the synovium from severe arthritis in the CIA mouse model. Tissue-protective, PD-L1-expressing macrophages are also present in the human synovium at homeostasis and during rheumatoid arthritis.

Successful Crizotinib-targeted Therapy of Pediatric Unresectable ERC1::ALK Fusion Sarcoma.

Anaplastic lymphoma kinase ( ALK )-fusion sarcomas are rare part of the emerging theoretically targetable tyrosine kinase RAS::MAPK pathway fusion myopericytic-ovoid sarcomas. We report our clinicopathologic and treatment experience with an ALK fusion sarcoma. A novel ELKS/RAB6-interacting/CAST family member 1 - unaligned ALK fusion infiltrative nonmetastatic low-grade sarcoma of the right hand of a 15-month-old male was treated with crizotinib, an ALK tyrosine kinase inhibitor as oral monotherapy, inducing complete radiographic and clinical resolution by 10 months and sustained response now over 12 months after elective discontinuation. Crizotinib can successfully be used to treat unresectable novel ALK fusion sarcomas.

Potential for England's statutory school entry assessment to identify special educational needs and reveal structural inequalities: a population-based study.

OBJECTIVE: To investigate at a population level whether England's universal assessment of 'school readiness' is associated with later identification of special educational needs (SEN). Also, whether ethnic differences exist in SEN identification (white British versus ethnic minority) and whether this varies as a function of school readiness. METHOD: Analysis included 53 229 individuals aged 5-12 years from the Connected Bradford Database (2012/2013-2019/2020). Logistic regression analyses examined: (1) whether reaching a 'good level of development' on England's 'school readiness' assessment was associated with later SEN identification; and (2) whether interactions exist between school readiness and ethnicity. RESULTS: 32 515 of 53 229 children reached a good level of development, of which 3036 (9.3%) were identified as having SEN. In contrast, 10 171 of 20 714 (49.1%) of children who did not reach a good level of development were later identified as having SEN. Children not reaching a good level of development had increased odds of being later identified as having SEN after controlling for covariates (OR: 8.50, 95% CI: 8.10 to 8.91). In children who did not reach a good level of development, white British children had higher odds of being identified as having SEN compared with ethnic minority peers (OR: 1.22, 95% CI: 1.11 to 1.34). No ethnic differences of having SEN were observed in children reaching a good level of development (OR: 1.04, 95% CI: 0.93 to 1.16). CONCLUSIONS: School readiness assessments are associated with later SEN identification. Structural inequalities may exist in SEN identification in children not entering formal education 'school ready'. Such assessments could facilitate earlier identification of SEN and reduce structural inequalities in its identification.

Hypereosinophilia causes progressive cardiac pathologies in mice.

Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development. Here, we describe the cardiac pathologies that developed in a mouse model of hypereosinophilic syndrome. These IL-5 transgenic mice exhibited decreased left ventricular function at a young age which worsened with age. Mechanistically, we demonstrated infiltration of activated eosinophils into the heart tissue that led to an inflammatory environment. Gene expression signatures showed tissue damage as well as repair and remodeling processes. Cardiomyocytes from IL-5Tg mice exhibited significantly reduced contractility relative to wild type (WT) controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca2+ reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice.

Engineering olivocochlear inhibition to reduce acoustic trauma.

Efferent brain-stem neurons release acetylcholine to desensitize cochlear hair cells and can protect the inner ear from acoustic trauma. That protection is absent from knockout mice lacking efferent inhibition and is stronger in mice with a gain-of-function point mutation of the hair cell-specific nicotinic acetylcholine receptor. The present work uses viral transduction of gain-of-function receptors to restore acoustic prophylaxis to the knockout mice. Widespread postsynaptic expression of the transgene was visualized in excised tissue with a fluorophore-conjugated peptide toxin that binds selectively to hair cell acetylcholine receptors. Viral transduction into efferent knockout mice reduced the temporary hearing loss measured 1 day post acoustic trauma. The acoustic evoked-response waveform (auditory brain-stem response) recovered more rapidly in treated mice than in control mice. Thus, both cochlear amplification by outer hair cells (threshold shift) and afferent signaling (evoked-response amplitude) in knockout mice were protected by viral transduction of hair cell acetylcholine receptors. Gene therapy to strengthen efferent cochlear feedback could be complementary to existing and future therapies to prevent hearing loss, including ear coverings, hearing aids, single-gene repair, or small-molecule therapies.

Connected Bradford: a Whole System Data Linkage Accelerator.

The richness of linked population data provides exciting opportunities to understand local health needs, identify and predict those in most need of support and evaluate health interventions. There has been extensive investment to unlock the potential of clinical data for health research in the UK. However, most of the determinants of our health are social, economic, education, environmental, housing, food systems and are influenced by local authorities. The Connected Bradford Whole System Data Linkage Accelerator was set up to link health, education, social care, environmental and other local government data to drive learning health systems, prevention and population health management. Data spanning a period of over forty years has been linked for 800,000 individuals using the pseudonymised NHS number and other data variables. This prospective data collection captures near real time activity. This paper describes the dataset and our Connected Bradford Whole System Data Accelerator Framework that covers public engagement; practitioner and policy integration; legal and ethical approvals; information governance; technicalities of data linkage; data curation and guardianship; data validity and visualisation.

Cardiac myosin-specific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis.

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased in mice with myocarditis. Notably, cardiac myosin-specific T cells are present in naive mice, showing a phenotype of antigen-experienced T cells. Collectively, we establish a clinically relevant mouse model for ICI-associated myocarditis and find a contribution of cardiac myosin-specific T cells to ICI-associated myocarditis development and pathogenesis.

Exclusion of Reproductive-aged Women in COVID-19 Vaccination and Clinical Trials.

INTRODUCTION: We analyzed the exclusion of pregnant and breastfeeding individuals and those capable of pregnancy in COVID-19 vaccine and clinical treatment trials. METHODS: Inclusion and exclusion criteria were extracted from all listed COVID-19 vaccine and treatment clinical trials from May 1, 2020, to October 31, 2020, using the U.S. National Library of Medicine database. We report rates of rates of exclusion for pregnant and lactating individuals and requirements for contraception for pregnancy-capable participants in COVID-19 vaccine and treatment clinical trials. The analysis included the association between clinical trial exclusion and vaccine and treatment type, study location, sponsor, and phase. RESULTS: Pregnant and lactating individuals were explicitly excluded from most COVID-19 vaccine and treatment clinical trials. Of the 90 vaccine trials, 88 (97.8%) excluded pregnant individuals, 73 (81.1%) excluded lactating individuals, and 56 (62.2%) required contraception use. Of the 495 treatment trials, 350 (70.7%) excluded pregnant individuals, 269 (54.3%) excluded lactating individuals, and 91 (18.4%) required contraception use. Although vaccine type was not associated with pregnancy exclusion, it was associated with lactation exclusion (p = .01) and contraception requirement (p < .001). Treatment type was associated with pregnancy exclusion, lactation exclusion, and contraception requirement (all p < .001). CONCLUSIONS: COVID-19 vaccination and treatment clinical trials mirrored historical trends restricting participation owing to pregnancy, lactation, and contraception nonuse, despite known safety profiles. People of childbearing potential should be considered for and afforded the same opportunity as males to make informed decisions on study participation, particularly in the setting of a global pandemic.

High-Speed Human Temporal Bone Sectioning for the Assessment of COVID-19-Associated Middle Ear Pathology.

Histopathologic analysis of human temporal bone sections is a fundamental technique for studying inner and middle ear pathology. Temporal bone sections are prepared by postmortem temporal bone harvest, fixation, decalcification, embedding, and staining. Due to the density of the temporal bone, decalcification is a time-consuming and resource-intensive process; complete tissue preparation may take 9-10 months on average. This slows otopathology research and hinders time-sensitive studies, such as those relevant to the COVID-19 pandemic. This paper describes a technique for the rapid preparation and decalcification of temporal bone sections to speed tissue processing. Temporal bones were harvested postmortem using standard techniques and fixed in 10% formalin. A precision microsaw with twin diamond blades was used to cut each section into three thick sections. Thick temporal bone sections were then decalcified in decalcifying solution for 7-10 days before being embedded in paraffin, sectioned into thin (10 µm) sections using a cryotome, and mounted on uncharged slides. Tissue samples were then deparaffinized and rehydrated for antibody staining (ACE2, TMPRSS2, Furin) and imaged. This technique reduced the time from harvest to tissue analysis from 9-10 months to 10-14 days. High-speed temporal bone sectioning may increase the speed of otopathology research and reduce the resources necessary for tissue preparation, while also facilitating time-sensitive studies such as those related to COVID-19.

Patterns and Predictors of Air Cleaner Adherence Among Adults with COPD.

Rational: Poor indoor air quality has been associated with worse chronic obstructive pulmonary disease (COPD) morbidity. In-home portable air cleaners reduce indoor pollutants and could improve respiratory health. Factors associated with air cleaner adherence among adults with COPD remains unknown. Methods: In a 6-month trial of former smokers with COPD, participants (n=116) received active or sham portable air cleaners. Air cleaner adherence was measured by electronic monitors. Potential baseline predictors of adherence included individual factors (demographics, socioeconomic status, smoking history, psychological well-being), COPD disease severity, and housing characteristics. Time and season were also considered. Stepwise logistic regression and longitudinal fixed effect analysis were performed to assess independent predictors of adherence. Results: A total of 109 participants had an objective measure of adherence, and 76.1% used at least 1 air cleaner 80% of the time (defined a priori as adherent). Higher annual household income ≥$35,000 (odds ratio [OR]=4.4, 95% confidence interval [CI], 1.1-18.0) and use of heat pump/electricity (versus gas) for heating (OR=6.1, 95%CI, 1.7-22.4) were associated with higher odds of adherence. Further, poor quality of life (St George's Respiratory Questionnaire, per 10-point increase) and prior year exacerbations were associated with lower odds of adherence (OR=0.65, 95%CI, 0.4-1.0) and (OR=0.26, 95%CI, 0.1-0.9), respectively. Adherence was highest during the first month and lower during winter compared to other seasons. Conclusion: These findings suggest that cold weather season, use of gas for home heating, and lower annual income negatively impact adherence. Poor quality of life and worse disease control may also decrease adherence. Addressing factors associated with air cleaner adherence should be considered when designing future environmental studies.

Non-native red alga Gracilaria vermiculophylla compensates for seagrass loss as blue crab nursery habitat in the emerging Chesapeake Bay ecosystem.

Non-native species can become deleterious or potentially beneficial as components of novel ecosystems. The non-native red macroalga Gracilaria vermiculophylla may provide nursery habitat where eelgrass Zostera marina has been extirpated in Chesapeake Bay. A mensurative experiment was conducted monthly May-October 2013 and 2014 in the York River, Chesapeake Bay, to evaluate hypotheses that Gracilaria (1) can compensate for the loss of seagrass nurseries by colonizing habitats where seagrass has been eliminated by environmental stress, and (2) is utilized by juvenile blue crabs (Callinectes sapidus) as nursery habitat. We quantified Gracilaria presence, percent cover, and biomass as a function of region (upriver, midriver, and downriver) and seagrass presence or absence using stratified random sampling, 20-m transects, and 0.0625-m2 quadrats. Gracilaria volume was measured and converted to dry weight. Effects of the factors and covariates temperature, salinity, dissolved oxygen, month, and year were analyzed using generalized linear models. Juvenile blue crab density was quantified in summer 2013 using suction sampling in Gracilaria and seagrass. A model with the collective effect of region and seagrass presence or absence (downriver seagrass, downriver unvegetated bottom, midriver unvegetated bottom) best predicted Gracilaria abundance. Gracilaria presence, percent cover, and biomass were highest in downriver seagrass, followed by downriver unvegetated bottom, and then midriver unvegetated bottom, where seagrass has been extirpated, supporting hypothesis (1). Gracilaria did not occur upriver, likely due to a lack of recruitment. Seagrass and Gracilaria housed similar densities of juvenile blue crabs, supporting hypothesis (2). We estimated that a single 40-ha cove system with Gracilaria could house 200,000 juvenile crabs as would a single 2.4-ha seagrass bed. Consequently, the numerous midriver and downriver cove systems in the York River could support millions of young juvenile blue crabs and thereby compensate for the loss of seagrass in the river and in other areas of Chesapeake Bay. At present, Gracilaria has no widespread negative impacts on seagrass in the York River or most regions of Chesapeake Bay, likely because percent cover and biomass are not excessively high at present. We posit that Gracilaria has become an important alternative nursery habitat for the blue crab in Chesapeake Bay and can potentially mitigate impacts of climate change on seagrass nursery habitats.

Update on frequency decline of Northeast Pacific blue whale (Balaenoptera musculus) calls.

Worldwide, the frequency (pitch) of blue whale (Balaenoptera musculus) calls has been decreasing since first recorded in the 1960s. This frequency decline occurs over annual and inter-annual timescales and has recently been documented in other baleen whale species, yet it remains unexplained. In the Northeast Pacific, blue whales produce two calls, or units, that, when regularly repeated, are referred to as song: A and B calls. In this population, frequency decline has thus far only been examined in B calls. In this work, passive acoustic data collected in the Southern California Bight from 2006 to 2019 were examined to determine if A calls are also declining in frequency and whether the call pulse rate was similarly impacted. Additionally, frequency measurements were made for B calls to determine whether the rate of frequency decline is the same as was calculated when this phenomenon was first reported in 2009. We found that A calls decreased at a rate of 0.32 Hz yr-1 during this period and that B calls were still decreasing, albeit at a slower rate (0.27 Hz yr-1) than reported previously. The A call pulse rate also declined over the course of the study, at a rate of 0.006 pulses/s yr-1. With this updated information, we consider the various theories that have been proposed to explain frequency decline in blue whales. We conclude that no current theory adequately accounts for all aspects of this phenomenon and consider the role that individual perception of song frequency may play. To understand the cause behind call frequency decline, future studies might want to explore the function of these songs and the mechanism for their synchronization. The ubiquitous nature of the frequency shift phenomenon may indicate a consistent level of vocal plasticity and fine auditory processing abilities across baleen whale species.

Characterization of fin whale song off the Western Antarctic Peninsula.

Song is produced by a variety of terrestrial and marine animals and is particularly common among baleen whales. Fin whale (Balaenoptera physalus) song is comprised of relatively simple 20 Hz pulses produced at regular intervals. The timing of these intervals, in addition to the presence and frequency of overtones, appears to be unique to each population. The purpose of this study was to characterize Western Antarctic Peninsula fin whale song and describe temporal pattern variations in song type and occurrence. Recordings were collected in the area from 2001-2004 and again 2014-2016. One song type was identified with a primary inter-pulse interval (IPI) of approximately 14 s and secondary IPI of 12.5 s. This song occurred in three pattern variants: singlet, doublet, and long triplet. The interval between pulses increased by 1.5 s between recording periods while the frequency of the overtones decreased from 89 Hz to 86 Hz. Song was never recorded in August and while it was recorded at other times in some years, it was consistently present in recordings from April through June across all years. While multiple pattern variants were present each year, singlets were generally the most prevalent variant. Doublets and triplets occurred from February through June, with highest levels of variants in February. In later years the triplet variant presence increased and in 2016 it comprised 53% of recorded song bouts. Further research is needed to understand the reasons why song changes over time and to examine the feasibility of using song to delineate and identify populations.

Increased Interleukin 18-Dependent Immune Responses Are Associated With Myopericarditis After COVID-19 mRNA Vaccination.

Myocarditis and myopericarditis may occur after COVID-19 vaccination with an incidence of two to twenty cases per 100,000 individuals, but underlying mechanisms related to disease onset and progression remain unclear. Here, we report a case of myopericarditis following the first dose of the mRNA-1273 COVID-19 vaccine in a young man who had a history of mild COVID-19 three months before vaccination. The patient presented with chest pain, elevated troponin I level, and electrocardiogram abnormality. His endomyocardial biopsy revealed diffuse CD68+ cell infiltration. We characterized the immune profile of the patient using multiplex cytokine assay and flow cytometry analysis. Sex-matched vaccinated individuals and healthy individuals were used as controls. IL-18 and IL-27, Th1-type cytokines, were highly increased in the patient with COVID-19 vaccine-related myopericarditis compared with vaccinated controls who experienced no cardiac complications. In the patient, circulating NK cells and T cells showed an activated phenotype and mRNA profile, and monocytes expressed increased levels of IL-18 and its upstream NLRP3 inflammasome. We found that recombinant IL-18 administration into mice caused mild cardiac dysfunction and activation of NK cells and T cells in the hearts, similar to the findings in the patient with myopericarditis after COVID-19 mRNA vaccination. Collectively, myopericarditis following COVID-19 mRNA vaccination may be associated with increased IL-18-mediated immune responses and cardiotoxicity.

Spatial analysis of tobacco outlet density on secondhand smoke exposure and asthma health among children in Baltimore City.

RATIONALE: Tobacco outlets are concentrated in low-income neighbourhoods; higher tobacco outlet density is associated with increased smoking prevalence. Secondhand smoke (SHS) exposure has significant detrimental effects on childhood asthma. We hypothesised there was an association between higher tobacco outlet density, indoor air pollution and worse childhood asthma. METHODS: Baseline data from a home intervention study of 139 children (8-17 years) with asthma in Baltimore City included residential air nicotine monitoring, paired with serum cotinine and asthma control assessment. Participant addresses and tobacco outlets were geocoded and mapped. Multivariable regression modelling was used to describe the relationships between tobacco outlet density, SHS exposure and asthma control. RESULTS: Within a 500 m radius of each participant home, there were on average six tobacco outlets. Each additional tobacco outlet in a 500 m radius was associated with a 12% increase in air nicotine (p<0.01) and an 8% increase in serum cotinine (p=0.01). For every 10-fold increase in air nicotine levels, there was a 0.25-point increase in Asthma Therapy Assessment Questionnaire (ATAQ) score (p=0.01), and for every 10-fold increase in serum cotinine levels, there was a 0.54-point increase in ATAQ score (p<0.05). CONCLUSIONS: Increased tobacco outlet density is associated with higher levels of bedroom air nicotine and serum cotinine. Increasing levels of SHS exposure (air nicotine and serum cotinine) are associated with less controlled childhood asthma. In Baltimore City, the health of children with asthma is adversely impacted in neighbourhoods where tobacco outlets are concentrated. The implications of our findings can inform community-level interventions to address these health disparities.