The role of emotional regulation on early child school adjustment outcomes.

Emotional regulation involves managing attention, affect, and behavior, and is essential for long-term health and well-being, including positive school adjustment. The purpose of this secondary data analysis from the Durham Child Health and Development Study was to explore how parent and teacher reported emotional regulation behaviors related to school adjustment outcomes (social skills, academic performance, and academic achievement) during early childhood. Parent and teacher reports on emotional regulation behaviors showed mixed concordance, however they correlated with critical aspects of school adjustment. Clinical and practical implications are discussed, including the role of psychiatric nurses in promoting positive emotional regulation and school adjustment outcomes across settings.

Social Support Is Protective Against the Effects of Discrimination on Parental Mental Health Outcomes.

BACKGROUND: Discrimination, or unfair treatment based on individual characteristics such as gender, race, skin color, and or sexual orientation, is a pervasive social stressor that perpetuates health disparities by limiting social and economic opportunity and is associated with poor mental and physical health outcomes. AIMS: The purpose of the present study is to (1) examine the association between maternal experiences of discrimination and paternal experiences of discrimination; (2) explore how discrimination relates to parental (maternal and paternal) stress and depressive symptoms; and (3) examine whether social support exerts protective effects. METHODS: The sample was 2,510 mothers and 1,249 fathers from the Child Community Health Network study. Linear regression models were conducted to explore associations between maternal and paternal discrimination. In addition, mediation analyses were conducted to explore if social support functioned as a mediator between discrimination on parental stress and depressive symptoms. RESULTS: Most mothers (40.3%) and fathers (50.7%) identified race as the predominant reason for discrimination. Experiencing discrimination was significantly related to stress and depressive symptoms for both parents, and all forms of social support mediated these relationships. Our findings suggest that social support can act as a protective factor against the negative association between discrimination and both stress and depressive symptoms. CONCLUSIONS: These findings highlight the need to integrate social support into existing interventions and include fathers in mental health screenings in primary-care settings. Finally, we briefly describe the role of nurses and other allied health professionals in addressing discrimination in health care and health policy implications.

A deep neural network framework to derive interpretable decision rules for accurate traumatic brain injury identification of infants.

OBJECTIVE: We aimed to develop a robust framework to model the complex association between clinical features and traumatic brain injury (TBI) risk in children under age two, and identify significant features to derive clinical decision rules for triage decisions. METHODS: In this retrospective study, four frequently used machine learning models, i.e., support vector machine (SVM), random forest (RF), deep neural network (DNN), and XGBoost (XGB), were compared to identify significant clinical features from 24 input features associated with the TBI risk in children under age two under the permutation feature importance test (PermFIT) framework by using the publicly available data set from the Pediatric Emergency Care Applied Research Network (PECARN) study. The prediction accuracy was determined by comparing the predicted TBI status with the computed tomography (CT) scan results since CT scan is the gold standard for diagnosing TBI. RESULTS: At a significance level of [Formula: see text], DNN, RF, XGB, and SVM identified 9, 1, 2,  and 4 significant features, respectively. In a comparison of accuracy (Accuracy), the area under the curve (AUC), and the precision-recall area under the curve (PR-AUC), the permutation feature importance test for DNN model was the most powerful framework for identifying significant features and outperformed other methods, i.e., RF, XGB, and SVM, with Accuracy, AUC, and PR-AUC as 0.915, 0.794, and 0.974, respectively. CONCLUSION: These results indicate that the PermFIT-DNN framework robustly identifies significant clinical features associated with TBI status and improves prediction performance. The findings could be used to inform the development of clinical decision tools designed to inform triage decisions.

The role of social adversity on emotional dysregulation during infancy and early childhood.

PURPOSE: The purpose of this study was to investigate if social adversity is associated with mother reported emotional dysregulation behaviors and trajectories during infancy and early childhood. DESIGN & METHODS: A secondary data analysis from the Durham Child Health and Development study study included 206 child-mother dyads. Three models were used to explore the relationship between social adversity and mother reported emotional dysregulation during infancy (Infant Behavior Questionnaire-Revised) and early childhood (Child Behavior Checklist - Dysregulation Profile). Linear mixed effects models were adopted to investigate if social adversity was associated with mother reported emotional dysregulation longitudinally. Regression analysis was conducted to explore if social adversity was associated with maternal reported emotional dysregulation trajectory slope scores and maternal reported emotional dysregulation trajectory class. Maternal psychological distress and the child's sex assigned at birth were included as covariates in each analysis. RESULTS: Infants with greater social adversity scores had significantly higher maternal reported fear responses across the first year of life. Social adversity was associated with maternal reported distress to limitations trajectory, dysregulated recovery class, and dysregulated distress to limitations class. During early childhood social adversity was significantly associated with maternal reported emotional dysregulation but not trajectories which showed little variability. CONCLUSION & PRACTICAL IMPLICATIONS: Our results indicate that social adversity is associated with maternal reported emotional dysregulation during infancy and early childhood. Nursing and other professionals can participate in early screening to determine risk and provide intervention.

Visual Outcomes and Prognostic Factors for Pediatric Open Globe Injuries.

OBJECTIVES: Open globe injuries (OGIs) in children can be visually devastating traumas and are a common cause of unilateral blindness in children. Three commonly used ocular trauma scores (Ocular Trauma Score [OTS], Pediatric Penetrating Ocular Trauma Score [POTS], and Toddler/Infant Ocular Trauma Score [TOTS]) can be used to help predict visual outcomes in ocular injuries. Each has strengths and weaknesses, but these scores have not been studied extensively in the pediatric population. METHODS: The medical records of all pediatric patients presenting at a single institution with OGIs from 2011 to 2016 were retrospectively reviewed. Initial clinical presentation and subsequent examinations were reviewed. The 3 trauma scoring systems were applied to patient data to determine the effectiveness at predicting final visual acuity (VA). RESULTS: A total of 15 patients met inclusion criteria. The mean age at presentation was 6.97 years. Seven of 15 (47%) of the patients had a final VA of 20/40 or better. The OTS was applied to 8 of 15 patients, as the OTS requires initial VA, which could not be obtained in 7 patients. The POTS and TOTS were applied to all 15 patients. The POTS, TOTS, and OTS were all significantly correlated to final VA. Incidence of relative afferent pupillary defect and more posterior zone of injury were correlated with poorer visual outcomes. CONCLUSIONS: All 3 available ocular trauma scores were effective at predicting final VA in our cohort of pediatric patients with OGIs even outside of the age ranges for which they have been created. Of all the factors included in the scores, relative afferent pupillary defect and zone of injury were most closely correlated with poor final VA.

Sucrase-isomaltase Gene Variants in Patients With Abnormal Sucrase Activity and Functional Gastrointestinal Disorders.

OBJECTIVES: The aim of the study was to determine prevalence and characterize sucrase-isomaltase (SI) gene variants of congenital sucrase-isomaltase deficiency in non-Hispanic white pediatric and young adult patients with functional gastrointestinal disorders (FGIDs), and abnormal sucrase activity on histologically normal duodenal biopsy. METHODS: Clinical symptoms and disaccharidase activities data were collected for an abnormal (low) sucrase (≤25.8 U, n = 125) activity group, and 2 normal sucrase activity groups with moderate (≥25.8-≤55 U, n = 250) and high (>55 U, n = 250) sucrase activities. SI gene variants were detected by next-generation sequencing of DNA from formalin-fixed paraffin-embedded tissues of these patients. FGIDs symptoms based on Rome IV criteria and subsequent clinical management of abnormal sucrase activity cases with pathogenic SI gene variants were analyzed. RESULTS: Thirteen SI gene variants were found to be significantly higher in abnormal sucrase cases with FGIDs symptoms (36/125, 29%; 71% did not have a pathogenic variant) compared to moderate normal (16/250, 6.4%, P < 0.001) or high normal (5/250, 2.0%, P < 0.001) sucrase groups. Clinical management data were available in 26 of abnormal sucrase cases, and only 10 (38%) were correctly diagnosed and managed by the clinicians. Concomitant lactase deficiency (24%; 23/97) and pan-disaccharidase deficiency (25%; 13/51) were found in the abnormal sucrase group. CONCLUSIONS: Heterozygous and compound heterozygous mutations in the SI gene were more prevalent in cases with abnormal sucrase activity presenting with FGIDs, and normal histopathology. This suggests heterozygous pathogenic variants of congenital sucrase-isomaltase deficiency may present as FGIDs. Concomitant lactase or pan-disaccharidase deficiencies were common in abnormal sucrase cases with SI gene variants.

Slow Dynamics of Acute Postoperative Pain Intensity Time Series Determined via Wavelet Analysis Are Associated With the Risk of Severe Postoperative Day 30 Pain.

BACKGROUND: Evidence suggests that increased early postoperative pain (POP) intensities are associated with increased pain in the weeks following surgery. However, it remains unclear which temporal aspects of this early POP relate to later pain experience. In this prospective cohort study, we used wavelet analysis of clinically captured POP intensity data on postoperative days 1 and 2 to characterize slow/fast dynamics of POP intensities and predict pain outcomes on postoperative day 30. METHODS: The study used clinical POP time series from the first 48 hours following surgery from 218 patients to predict their mean POP on postoperative day 30. We first used wavelet analysis to approximate the POP series and to represent the series at different time scales to characterize the early temporal profile of acute POP in the first 2 postoperative days. We then used the wavelet coefficients alongside demographic parameters as inputs to a neural network to predict the risk of severe pain 30 days after surgery. RESULTS: Slow dynamic approximation components, but not fast dynamic detailed components, were linked to pain intensity on postoperative day 30. Despite imbalanced outcome rates, using wavelet decomposition along with a neural network for classification, the model achieved an F score of 0.79 and area under the receiver operating characteristic curve of 0.74 on test-set data for classifying pain intensities on postoperative day 30. The wavelet-based approach outperformed logistic regression (F score of 0.31) and neural network (F score of 0.22) classifiers that were restricted to sociodemographic variables and linear trajectories of pain intensities. CONCLUSIONS: These findings identify latent mechanistic information within the temporal domain of clinically documented acute POP intensity ratings, which are accessible via wavelet analysis, and demonstrate that such temporal patterns inform pain outcomes at postoperative day 30.

On kernel machine learning for propensity score estimation under complex confounding structures.

Post marketing data offer rich information and cost-effective resources for physicians and policy-makers to address some critical scientific questions in clinical practice. However, the complex confounding structures (e.g., nonlinear and nonadditive interactions) embedded in these observational data often pose major analytical challenges for proper analysis to draw valid conclusions. Furthermore, often made available as electronic health records (EHRs), these data are usually massive with hundreds of thousands observational records, which introduce additional computational challenges. In this paper, for comparative effectiveness analysis, we propose a statistically robust yet computationally efficient propensity score (PS) approach to adjust for the complex confounding structures. Specifically, we propose a kernel-based machine learning method for flexibly and robustly PS modeling to obtain valid PS estimation from observational data with complex confounding structures. The estimated propensity score is then used in the second stage analysis to obtain the consistent average treatment effect estimate. An empirical variance estimator based on the bootstrap is adopted. A split-and-merge algorithm is further developed to reduce the computational workload of the proposed method for big data, and to obtain a valid variance estimator of the average treatment effect estimate as a by-product. As shown by extensive numerical studies and an application to postoperative pain EHR data comparative effectiveness analysis, the proposed approach consistently outperforms other competing methods, demonstrating its practical utility.

A Systematic Review on Outcomes of Preterm Small for Gestational Infants Born to Women With Hypertensive Disorders in Pregnancy.

There is a lack of knowledge on the intersection between prematurity, small for gestational age, and hypertensive disorders of pregnancy (HDP). Therefore, the aim of this systematic review was to examine the outcomes of preterm infants who were small for gestational age born to women with HDP. Searches were conducted with no date restriction through the final search date of May 13, 2020, in the following databases: PubMed, Web of Science Core Collection, Cumulative Index of Nursing and Allied Health Literature Plus with Full Text (EBSCOhost), and Embase (Elsevier). A total of 6 studies were eligible for this review. The adjusted odds of mortality and necrotizing enterocolitis were significantly lower in the pregnancy-induced hypertension (PIH)/HDP group than in the non-PIH/HDP group. There was no significant difference in the odds of respiratory distress syndrome, bronchopulmonary dysplasia, and intraventricular hemorrhage between PIH/HDP and non-PIH/HDP groups. There was no significant difference between PIH/HDP and non-PIH/HDP groups in cystic periventricular leukomalacia, retinopathy of prematurity, late-onset sepsis, patent ductus arteriosus, length of hospital stays, duration of supplemental oxygen use, duration of mechanical ventilation, and continuous airway pressure. The studies included in this systematic review demonstrated that PIH/HDP is associated with lower infant mortality and necrotizing enterocolitis.

Pulmonary Embolism in Acute Asthma Exacerbation: Clinical Characteristics, Prediction Model and Hospital Outcomes.

PURPOSE: Little is known about the characteristics and impact of acute pulmonary embolism (PE) during episodes of asthma exacerbation. We aimed to characterize patients diagnosed with acute PE in the setting of asthma exacerbation, develop a prediction model to help identify future patients and assess the impact of acute PE on hospital outcomes. METHODS: We included 758 patients who were treated for asthma exacerbation and underwent a computed tomographic pulmonary angiography (CTA) during the same encounter at a university-based hospital between June 2011 and October 2018. We compared clinical characteristics of patients with and without acute PE and developed a machine learning prediction model to classify the PE status based on the clinical variables. We used multivariable regression analysis to evaluate the impact of acute PE on hospital outcomes. RESULTS: Twenty percent of the asthma exacerbation patients who underwent CTA had an acute PE. Factors associated with acute PE included previous history of PE, high CHA2DS2-VASc score, hyperlipidemia, history of deep vein thrombosis, malignancy, chronic systemic corticosteroids use, high body mass index and atrial fibrillation. Using these factors, we developed a random forest machine learning prediction model which had an 88% accuracy in classifying the acute PE status of the patients (area under the receiver operating characteristic curve = 0.899; 95% confidence interval: 0.885-0.913). Acute PE in asthma exacerbation was associated with longer hospital stay and intensive care unit stay. CONCLUSION: It is important to consider acute PE, a potentially life-threatening event, in the setting of asthma exacerbation especially when other risk factors are present.

Neurodevelopmental outcomes at 9-14 months gestational age after treatment of neonatal seizures due to brain injury.

PURPOSE: Infants with brain injury are susceptible to developmental delays. Survivors of neonatal seizures are at risk for developmental delay, epilepsy, and further neurological comorbidities. Despite advances in neonatal critical care, the prevalence of adverse long-term outcomes and seizure recurrence remains unchanged. Our goal is to determine if early treatment of neonatal seizures with phenobarbital or levetiracetam is associated with worse neurodevelopmental outcomes in brain-injured infants. METHODS: We conducted a retrospective cohort study of 119 infants admitted between 2013 and 2017 who were at risk for developmental delay and assessed in our clinic. We compared brain injury infants with neonatal seizures to brain injury infants without neonatal seizures using Bayley scores (BSID III) at 9-14 months gestational age. A comparison of Bayley scores between those exposed to phenobarbital and levetiracetam was conducted. RESULTS: Twenty-two children with neonatal seizures scored lower than 53 children without seizures in all domains with significant values in composite scores for cognitive function (p = 0.003) and language (p = 0.031). We found no difference in scores at 9-14 months between infants exposed to phenobarbital versus levetiracetam. CONCLUSIONS: Our results suggest that in infants with brain injury, the occurrence of neonatal seizures has an adverse effect on neurodevelopmental outcomes. The choice of antiseizure medication may not play a significant role in their outcomes.

Soluble antigens in plasma allow mismatched transfusion without hemolysis.

BACKGROUND: Universal plasma is a scarce resource when a massive transfusion protocol has been initiated. Previous studies have reported success using group A plasma in place of the universal plasma, group AB. It is unclear why there are not more reports of hemolytic reactions occurring from this practice. One possible explanation is the presence of water-soluble antigens in the patient plasma that bind to, and neutralize, the soluble antibodies present in the transfused plasma. STUDY DESIGN AND METHODS: Expired units of plasma were used to make dilutions that consisted of mixtures of group A and B plasma and saline. Serial dilutions of these samples were performed starting from undiluted up to 1024. The dilutions were titrated using a group B red blood cell preparation. The titrations were read after incubation. RESULTS: The titers that resulted from the mixed plasma dilutions were significantly lower or showed no agglutination when compared to the group A-specific saline dilutions. The differences between the saline dilutions and mixed group dilutions were significant (p < 0.001). CONCLUSION: Our study shows that secretor status would provide protection from isoantibodies. The dissolved B antigens in the group B plasma absorb and/or bind to the group B isoantibodies in the group A plasma. This mechanism gives a protective effect against hemolytic reactions in massive transfusion situations in the trauma setting when group A plasma is used instead of group AB plasma. This protective effect is revealed with the paucity of intravascular hemolysis observed in these out-of-group massive transfusions.

A model-based conditional power assessment for decision making in randomized controlled trial studies.

Conditional power based on summary statistic by comparing outcomes (such as the sample mean) directly between 2 groups is a convenient tool for decision making in randomized controlled trial studies. In this paper, we extend the traditional summary statistic-based conditional power with a general model-based assessment strategy, where the test statistic is based on a regression model. Asymptotic relationships between parameter estimates based on the observed interim data and final unobserved data are established, from which we develop an analytic model-based conditional power assessment for both Gaussian and non-Gaussian data. The model-based strategy is not only flexible in handling baseline covariates and more powerful in detecting the treatment effects compared with the conventional method but also more robust in controlling the overall type I error under certain missing data mechanisms. The performance of the proposed method is evaluated by extensive simulation studies and illustrated with an application to a clinical study.

On variance estimate for covariate adjustment by propensity score analysis.

Propensity score (PS) methods have been used extensively to adjust for confounding factors in the statistical analysis of observational data in comparative effectiveness research. There are four major PS-based adjustment approaches: PS matching, PS stratification, covariate adjustment by PS, and PS-based inverse probability weighting. Though covariate adjustment by PS is one of the most frequently used PS-based methods in clinical research, the conventional variance estimation of the treatment effects estimate under covariate adjustment by PS is biased. As Stampf et al. have shown, this bias in variance estimation is likely to lead to invalid statistical inference and could result in erroneous public health conclusions (e.g., food and drug safety and adverse events surveillance). To address this issue, we propose a two-stage analytic procedure to develop a valid variance estimator for the covariate adjustment by PS analysis strategy. We also carry out a simple empirical bootstrap resampling scheme. Both proposed procedures are implemented in an R function for public use. Extensive simulation results demonstrate the bias in the conventional variance estimator and show that both proposed variance estimators offer valid estimates for the true variance, and they are robust to complex confounding structures. The proposed methods are illustrated for a post-surgery pain study. Copyright © 2016 John Wiley & Sons, Ltd.

On model selections for repeated measurement data in clinical studies.

Repeated measurement designs have been widely used in various randomized controlled trials for evaluating long-term intervention efficacies. For some clinical trials, the primary research question is how to compare two treatments at a fixed time, using a t-test. Although simple, robust, and convenient, this type of analysis fails to utilize a large amount of collected information. Alternatively, the mixed-effects model is commonly used for repeated measurement data. It models all available data jointly and allows explicit assessment of the overall treatment effects across the entire time spectrum. In this paper, we propose an analytic strategy for longitudinal clinical trial data where the mixed-effects model is coupled with a model selection scheme. The proposed test statistics not only make full use of all available data but also utilize the information from the optimal model deemed for the data. The performance of the proposed method under various setups, including different data missing mechanisms, is evaluated via extensive Monte Carlo simulations. Our numerical results demonstrate that the proposed analytic procedure is more powerful than the t-test when the primary interest is to test for the treatment effect at the last time point. Simulations also reveal that the proposed method outperforms the usual mixed-effects model for testing the overall treatment effects across time. In addition, the proposed framework is more robust and flexible in dealing with missing data compared with several competing methods. The utility of the proposed method is demonstrated by analyzing a clinical trial on the cognitive effect of testosterone in geriatric men with low baseline testosterone levels.

Testosterone alters iron metabolism and stimulates red blood cell production independently of dihydrotestosterone.

Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis. However, it remains unknown whether the (type II) 5α-reduction of T to dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some other tissues. Our purpose was to determine whether inhibition of type II 5α-reductase (via finasteride) alters red blood cell (RBC) production and serum markers of iron homeostasis subsequent to testosterone-enanthate (TE) administration in older hypogonadal men. Sixty men aged ≥60 yr with serum T <300 ng/dl or bioavailable T <70 ng/dl received treatment with TE (125 mg/wk) vs. vehicle paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased RBC count 9%, hematocrit 4%, and hemoglobin 8% while suppressing serum hepcidin 57% (P < 0.001 for all measurements). Most of the aforementioned changes occurred in the first 3 mo of treatment, and finasteride coadministration did not significantly alter any of these effects. TE also reduced serum ferritin 32% (P = 0.002) within 3 mo of treatment initiation without altering iron, transferrin, or transferrin saturation. We conclude that TE stimulates erythropoiesis and alters iron homeostasis independently of the type II 5α-reductase enzyme. These results demonstrate that elevated DHT is not required for androgen-mediated erythropoiesis or for alterations in iron homeostasis that would appear to support iron incorporation into RBCs.

Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: a systematic review and meta-analysis.

BACKGROUND: Potential cardiovascular (CV) risks of testosterone replacement therapy (TRT) are currently a topic of intense interest. However, no studies have addressed CV risk as a function of the route of administration of TRT. METHODS: Two meta-analyses were conducted, one of CV adverse events (AEs) in 35 randomized controlled trials (RCTs) of TRT lasting 12 weeks or more, and one of 32 studies reporting the effect of TRT on serum testosterone and dihydrotestosterone (DHT). RESULTS: CV risks of TRT: Of 2,313 studies identified, 35 were eligible and included 3,703 mostly older men who experienced 218 CV-related AEs. No significant risk for CV AEs was present when all TRT administration routes were grouped (relative risk (RR) = 1.28, 95% confidence interval (CI): 0.76 to 2.13, P = 0.34). When analyzed separately, oral TRT produced significant CV risk (RR = 2.20, 95% CI: 1.45 to 3.55, P = 0.015), while neither intramuscular (RR = 0.66, 95% CI: 0.28 to 1.56, P = 0.32) nor transdermal (gel or patch) TRT (RR = 1.27, 95% CI: 0.62 to 2.62, P = 0.48) significantly altered CV risk. Serum testosterone/DHT following TRT: Of 419 studies identified, 32 were eligible which included 1,152 men receiving TRT. No significant difference in the elevation of serum testosterone was present between intramuscular or transdermal TRT. However, transdermal TRT elevated serum DHT (5.46-fold, 95% CI: 4.51 to 6.60) to a greater magnitude than intramuscular TRT (2.20-fold, 95% CI: 1.74 to 2.77). CONCLUSIONS: Oral TRT produces significant CV risk. While no significant effects on CV risk were observed with either injected or transdermal TRT, the point estimates suggest that further research is needed to establish whether administration by these routes is protective or detrimental, respectively. Differences in the degree to which serum DHT is elevated may underlie the varying CV risk by TRT administration route, as elevated serum dihydrotestosterone has been shown to be associated with CV risk in observational studies.

An efficient machine learning framework to identify important clinical features associated with pulmonary embolism.

A misdiagnosis of pulmonary embolism (PE) can have severe consequences such as disability or death. It's crucial to accurately identify key clinical features of PE in clinical practice to promptly identify potential PE patients who may present asymptomatically, and to prevent misdiagnosing PE as asthma exacerbation in patients with symptoms like dyspnea or chest pain. However, reliably identifying these important features can be challenging due to many factors influencing the likelihood of PE development in complex fashions (e.g., the interactions among these factors). To address this difficulty, we presented an effective framework using the deep neural network (DNN) model and the permutation-based feature importance test (PermFIT) procedure, i.e., PermFIT-DNN. We applied the PermFIT-DNN framework to the analysis of data from a PE study for asthma exacerbation patients. Our analysis results show that the PermFIT-DNN framework can robustly identify key features for classifying PE status. The important features identified can also aid in accurately predicting the PE risk.

Individuals with increased inflammatory response to ozone demonstrate muted signaling of immune cell trafficking pathways.

BACKGROUND: Exposure to ozone activates innate immune function and causes neutrophilic (PMN) airway inflammation that in some individuals is robustly elevated. The interplay between immuno-inflammatory function and genomic signaling in those with heightened inflammatory responsiveness to ozone is not well understood. OBJECTIVES: Determine baseline predictors and post exposure discriminators for the immuno-inflammatory response to ozone in inflammatory responsive adult volunteers. METHODS: Sputum induction was performed on 27 individuals before and after a two hour chamber exposure to 0.4 ppm ozone. Subjects were classified as inflammatory responders or non-responders to ozone based on their PMN response. Innate immune function, inflammatory cell and cytokine modulation and transcriptional signaling pathways were measured in sputum. RESULTS: Post exposure, responders showed activated innate immune function (CD16: 31,004 MFI vs 8988 MFI; CD11b: 44,986 MFI vs 24,770 MFI; CD80: 2236 MFI vs 1506 MFI; IL-8: 37,603 pg/ml vs 2828 pg/ml; and IL-1ß: 1380 pg/ml vs 318 pg/ml) with muted signaling of immune cell trafficking pathways. In contrast, non-responders displayed decreased innate immune activity (CD16, CD80; phagocytosis: 2 particles/PMN vs 4 particles/PMN) post exposure that was accompanied by a heightened signaling of immune cell trafficking pathways. CONCLUSIONS: Inflammatory responsive and non responsive individuals to ozone show an inverse relationship between immune cell trafficking and immuno-inflammatory functional responses to ozone. These distinct genomic signatures may further our understanding about ozone-induced morbidity in individuals with different levels of inflammatory responsiveness.

Factors and reasons associated with low COVID-19 vaccine uptake among highly hesitant communities in the US.

BACKGROUND: The inability to achieve high COVID-19 vaccination rates can continue to have serious harm to our communities. Vaccine hesitancy is a major barrier towards high vaccination rates. We evaluated the relationship between COVID-19 vaccine uptake and vaccine hesitancy, and then examined whether community factors were associated with COVID-19 vaccine uptake and hesitancy. METHODS: We constructed and evaluated a cross-sectional, county-level dataset that included the levels of vaccination uptake and vaccine hesitancy, and population characteristics based on those included in the CDC's Social Vulnerability Index. RESULTS: Across 3142 US counties, vaccine hesitancy was significantly and negatively correlated with vaccine uptake rates (r = -0.06, P value <.01). The 2 predictors associated with a low vaccination level within highly hesitant communities were: no high school education (OR:0.70, P value <.001), and concern on vaccine availability and distribution (CVAC) (OR:0.00, P value <.001). The most common reason driving vaccine hesitancy was lack of trust in COVID-19 vaccines (55%), followed by concerns around side effects of the vaccine (48%), and lack of trust in government (46%). CONCLUSIONS: COVID-19 vaccine hesitancy is a public health threat. Our findings suggest that low education levels are a major contributor to vaccine hesitancy and ultimately vaccination levels. Since education levels are not easily modifiable, our results suggest that policymakers would be best served by closing knowledge gaps to overcome negative perceptions of the vaccine through tailored interventions.