Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment.

Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1+ ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants.

Telemedicine services in higher education: a review of college and university websites.

OBJECTIVES: To identify rates of telemedicine provision during the COVID-19 pandemic and predictive institutional factors among 4-year and graduate colleges and universities. PARTICIPANTS: The study (n = 364) included the websites (.edu) of accredited public nonprofit, private nonprofit, and private for-profit institutions of higher education in the United States that award bachelors, masters, or doctoral degrees. METHODS: Using digital content analysis, human coders analyzed institution websites for informational text indicating student telemedicine services. RESULTS: Findings indicate that a minority of 4-year and above institutions offer telemedicine access. Institution type, institution size, and the presence of campus student health services were predictive. Endowment size and Minority Serving Institution status were not predictive. CONCLUSION: This study illustrates the ongoing need for increased access to remote health services across higher education, especially among smaller private and public nonprofit colleges and universities and all private for-profit institutions.

Using the American College of Radiology Thyroid Imaging Reporting and Data System at the Point of Care: Sonographer Performance and Interobserver Variability.

The purpose of this study was to assess inter-observer variability and performance when sonographers assign features to thyroid nodules on ultrasound using the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS). Fifteen sonographers retrospectively evaluated 100 thyroid nodules and assigned features to each nodule according to ACR TI-RADS lexicon. Ratings were compared with one another and to a gold standard using Fleiss' and Cohen's kappa statistics, respectively. Sonographers were also asked subjective questions regarding their comfort level assessing each feature, and opinions were compared with performance using a mixed effects model. Sonographers demonstrated only slight agreement for margin (κ = 0.18, 95% confidence interval [CI]: 0.16-0.20) and large comet tail artifact (κ = 0.08, 95% CI: 0.06-0.10) but better performance for macrocalcification (κ = 0.41, 95% CI: 0.39-0.43) and no echogenic foci (κ = 0.52, 95% CI: 0.50-0.54). Sonographer comfort level with different feature assignments did not statistically correlate with performance for a given feature. In conclusion, sonographers using ACR TI-RADS to assign thyroid nodule features on ultrasound demonstrate a range of agreement across features, with margin and large comet tail artifact showing the most variability. These results highlight potential areas of focus for sonographer education efforts as ACR TI-RADS continues to be implemented in radiology departments.

Estimating the causal effect of conduct disorder on the time from first substance use to substance use disorders using g-estimation.

BACKGROUND: The effect of conduct disorder (CD) as a major risk factor of substance use disorder (SUD), controlling for other psychiatric problems, has been well established in the literature. However, other psychiatric problems are associated as confounders with an increased risk of SUD. When confounding exists, the use of the standard survival analysis approach would lead to a biased estimate of the effect of a time-varying exposure on the time to event. METHODS: The authors used a G-estimation approach to estimate the causal effect of CD while controlling for time-varying confounders. RESULTS: The present study (N = 1420) found a substantial difference in the estimated hazard ratio of CD (4.49 vs. 1.93) when the results from G-estimation and Cox regression were compared. CONCLUSIONS: G-estimation fixed the problem of underestimating the hazard ratio of conduct disorder (CD) while controlling for all measured covariates.

Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection.

Biomarkers for early detection of epithelial ovarian cancer (EOC) are urgently needed. Patients can generate antibodies to tumor-associated antigens (TAAs). We tested multiplex detection of antibodies to candidate ovarian TAAs and statistical modeling for discrimination of sera of EOC patients and controls. Binding of serum antibody of women with EOC or healthy controls to candidate TAA-coated microspheres was assayed in parallel. A Bayesian model/variable selection approach using Markov Chain Monte Carlo computations was applied to these data, and serum CA125 values, to determine the best predictive model. The selected model was subjected to area under the receiver-operator curve (AUC) analysis. The best model generated an AUC of 0.86 [95% confidence interval (95% CI), 0.78-0.90] for discrimination between sera of EOC patients and healthy patients using antibody specific to p53, NY-CO-8, and HOXB7. Inclusion of CA125 in the model provided an AUC of 0.89 (95% CI, 0.84-0.92) compared with an AUC of 0.83 (95% CI, 0.81-0.85) using CA125 alone. However, using TAA responses alone, the model discriminated between independent sera of women with nonmalignant gynecologic conditions and those with advanced-stage or early-stage EOC with AUCs of 0.71 (95% CI, 0.67-0.76) and 0.70 (95% CI, 0.48-0.75), respectively. Serum antibody to p53 and HOXB7 is positively associated with EOC, whereas NY-CO-8-specific antibody shows negative association. Bayesian modeling of these TAA-specific serum antibody responses exhibits similar discrimination of patients with early-stage and advanced-stage EOC from women with nonmalignant gynecologic conditions and may be complementary to CA125.

Effects of age at first substance use and psychiatric comorbidity on the development of substance use disorders.

In this paper, we examine the effects of age at first substance use, and history of psychiatric disorders, on the development of substance use disorder (SUD) by age 16. We use a prospective, longitudinal design to disaggregate the effects of age at first use and time since first use on the development of adolescent SUD. Second, we test the hypothesis that adolescent SUD is an unlikely progression from early substance use unless children also show other early conduct problems. A population sample of 1,420 children from the Great Smoky Mountains Study (GSMS) was assessed annually between ages 9 and 16. Logistic regression models were applied within the hierarchical Bayesian framework, where the covariate effects were described by time-varying parameters having a first-order auto-regressive prior distribution. Posterior analyses based on a Gibbs sampling approach revealed that, controlling for years of exposure, the risk of transition to SUD increased with age at onset for onsets before age 13, but began to fall for onset at 14. Among users, use alone, without early conduct problems, led to a 11% prevalence of SUD by age 16. Past conduct disorder (CD) had a strong additive effect at ages 13-15, but at age 16, when substance use and abuse became more normative, the excess risk from prior CD decreased. Boys, but not girls, with a history of depression were at increased risk of SUD. Anxiety increased the risk of SUD in girls at age 16, but not before that. Results only partially support the study hypothesis; early use was a major predictor of adolescent SUD even in the absence of CD.