A Rare Complication of Anomalous Left Coronary Artery From the Pulmonary Artery Identified by Point-of-Care Ultrasound.

ABSTRACT: Point-of-care ultrasound is a valuable tool in the evaluation of undifferentiated respiratory distress in children. This case report describes a 9-month-old male infant who presented with 4 months of progressively worsening cough and was found to be tachypneic in the emergency department. Chest radiography revealed complete opacification of the left hemithorax with cardiomegaly. Point-of-care ultrasound demonstrated atelectasis of the entire left lung and severe dilation of the left ventricle with poor function. Electrocardiogram and echocardiogram findings were consistent with a diagnosis of anomalous left coronary artery from the pulmonary artery. The patient underwent successful cardiac surgery to improve myocardial perfusion. Bronchoscopy visualized the etiology of his atelectasis, pulsatile compression of the left mainstem bronchus by the dilated heart. Focused cardiac and lung ultrasound techniques, as well as pertinent sonographic findings, are reviewed.

A Global Outlook on Child Sexual Abuse and Sexually Explicit Material Online During COVID-19: Trends and Interdisciplinary Prevention Methods.

This scoping review investigates the impact of COVID-19 on global and national trends in online child sexually explicit material (CSEM) trafficking and production in addition to online child sexual abuse (OCSA). Globally, CSEM consumption increased dramatically during the pandemic, as well as trafficking of self-generated material. The hypothesized reasons for the increase in OCSA and CSEM that guided this review included stay-at-home orders, COVID-19-related precautions, technology use increase, economic instability, and lack of available victim and legal resources. Current global and national law enforcement procedures to prevent the proliferation of online sexual abuse are reviewed with suggestions for preventing further increases in CSEM production, distribution, and consumption at the micro and macro levels.

Lessons learned through crisis: the effect of Covid-19 on pre-service Technology Education teacher development.

The Covid-19 pandemic forced post-secondary institutions to shift their technical offerings to blended and/or remote delivery. The Pandemic was a catalyst for pre-service Technology Education programs, traditionally designed for face-to-face learning, to explore innovative pedagogical arrangements. The purpose of this study was to understand the experiences and perceptions of pre-service teachers as they navigated their way through their Pandemic-impacted Technology Education Diploma program. In particular, pre-service teachers were asked about the challenges, benefits, and lessons learned through their lived experiences dealing with the re-organization for remote and blended learning in response to the various waves of the Covid-19 Pandemic. An exploration of the learner experience within pre-service Technology Education programs contributes to a growing body of literature that continues to offer meaningful insight on the institutional arrangements to cope with the limitations brought on by the Pandemic. Interviews from a purposeful sample of nine (N = 9) pre-service teachers was the primary data source within this qualitative study that sought to understand the following research question: How have institutional responses to Covid-19 impacted the experiences and perceptions of pre-service teachers enrolled in a re-organized Technology Education Diploma program? Thematic analysis was used to identify and explore recurring nodes within the data. The findings of this study suggest that the shift in instructional modality had significant impacts on how pre-service teachers experienced their Technology Education program. The reorganization delayed the development of peer relationships within the program cohorts and disrupted lines of communication.

The preoperative management of meibomian gland dysfunction prior to corneal refractive surgery.

PURPOSE OF REVIEW: To describe the significance of meibomian gland dysfunction (MGD) in corneal refractive surgery and to describe available approaches to preoperative evaluation and treatment based on current research. RECENT FINDINGS: There are several methods available for the evaluation and treatment of MGD. These are relevant for refractive surgeons to understand, as the presence of MGD preoperatively plays a role in the severity of MGD after corneal refractive surgery. Refractive surgery itself can exacerbate MGD. Treatment of MGD prior to surgery may have a meaningful impact on postoperative MGD. SUMMARY: Surgeons should include meibomian gland assessment in the preoperative refractive evaluation and should treat MGD proactively prior to performing refractive surgery. Relevant information in this field is growing; additional prospectively designed studies are needed to further enhance our understanding.

Polysulfated Hyaluronan GlycoMira-1111 Inhibits Elastase and Improves Rheology in Cystic Fibrosis Sputum.

Cystic fibrosis (CF) lung disease is marked by high concentrations of neutrophil elastase (NE) and DNA polymers; both factors contribute to airway disease. Although inhaled recombinant human dornase alfa reduces the frequency of CF pulmonary exacerbations, it also increases free NE activity in the sputum. There are no approved anti-NE therapies for patients with CF. We investigated whether synthetic, low-molecular weight polysulfated hyaluronan GlycoMira-1111 (GM-1111) would be effective as an anti-NE drug using ex vivo CF sputum. Anti-NE activity of GM-1111 was tested in CF sputum in the presence or absence of dornase alfa and/or hypertonic saline using a spectrophotometric assay specific for human NE and was compared with unfractionated heparin. We tested whether GM-1111 disaggregated DNA from CF sputum (using gel electrophoresis analysis) or modified CF sputum viscoelastic properties (using a dynamic rheometer). GM-1111 and unfractionated heparin had near equivalent anti-NE activity in CF sputum in the presence of dornase alfa. Both GM-1111 and unfractionated heparin retained anti-NE activity in hypertonic saline but with decreased activity. GM-1111 increased the release of soluble DNA in CF sputum, resulting in improved depolymerization efficacy of dornase alfa. GM-1111 decreased CF sputum elasticity. GM-1111 inhibited NE activity, enhanced DNA depolymerization by deoxyribonuclease, and decreased viscoelastic properties of CF sputum, similar to effects reported previously for unfractionated heparin. Unlike heparins, GM-1111 is synthetic, with minimal anticoagulant activity, and is not derived from animal products. These key attributes provide advantages over unfractionated heparin as a potential therapeutic for CF.

2-O, 3-O desulfated heparin (ODSH) increases bacterial clearance and attenuates lung injury in cystic fibrosis by restoring HMGB1-compromised macrophage function.

BACKGROUND: High mobility group box 1 protein (HMGB1) is an alarmin following its release by immune cells upon cellular activation or stress. High levels of extracellular HMGB1 play a critical role in impairing the clearance of invading pulmonary pathogens and dying neutrophils in the injured lungs of cystic fibrosis (CF) and acute respiratory distress syndrome (ARDS). A heparin derivative, 2-O, 3-O desulfated heparin (ODSH), has been shown to inhibit HMGB1 release from a macrophage cell line and is efficacious in increasing bacterial clearance in a mouse model of pneumonia. Thus, we hypothesized that ODSH can attenuate the bacterial burden and inflammatory lung injury in CF and we conducted experiments to determine the underlying mechanisms. METHODS: We determined the effects of ODSH on lung injury produced by Pseudomonas aeruginosa (PA) infection in CF mice with the transmembrane conductance regulator gene knockout (CFTR-/-). Mice were given ODSH or normal saline intraperitoneally, followed by the determination of the bacterial load and lung injury in the airways and lung tissues. ODSH binding to HMGB1 was determined using surface plasmon resonance and in silico docking analysis of the interaction of the pentasaccharide form of ODSH with HMGB1. RESULTS: CF mice given 25 mg/kg i.p. of ODSH had significantly lower PA-induced lung injury compared to mice given vehicle alone. The CF mice infected with PA had decreased levels of nitric oxide (NO), increased levels of airway HMGB1 and HMGB1-impaired macrophage phagocytic function. ODSH partially attenuated the PA-induced alteration in the levels of NO and airway HMGB1 in CF mice. In addition, ODSH reversed HMGB1-impaired macrophage phagocytic function. These effects of ODSH subsequently decreased the bacterial burden in the CF lungs. In a surface plasmon resonance assay, ODSH interacted with HMGB1 with high affinity (KD = 3.89 × 10-8 M) and induced conformational changes that may decrease HMGB1's binding to its membrane receptors, thus attenuating HMGB1-induced macrophage dysfunction. CONCLUSIONS: The results suggest that ODSH can significantly decrease bacterial infection-induced lung injury in CF mice by decreasing both HMGB1-mediated impairment of macrophage function and the interaction of HMGB1 with membrane receptors. Thus, ODSH could represent a novel approach for treating CF and ARDS patients that have HMGB1-mediated lung injury.

A Phase 1 dose-escalation study of disulfiram and copper gluconate in patients with advanced solid tumors involving the liver using S-glutathionylation as a biomarker.

BACKGROUND: Disulfiram and metals inactivate key oncoproteins resulting in anti-neoplastic activity. The goal of this study was to determine the maximum tolerated dose of copper when administered with disulfiram in patients with advanced solid tumors and liver involvement. METHODS: Disulfiram 250 mg was administered daily in 28-day cycles. Four doses of copper gluconate were tested (2, 4, 6, and 8 mg of elemental copper) in a standard 3 + 3 dose escalation design. Patients were evaluated for dose limiting toxicities and response. Protein S-glutathionylation was evaluated as a pharmacodynamic marker. RESULTS: Twenty-one patients were enrolled and 16 patients were evaluable for dose limiting toxicities. Among the 21 patients, there was a median of 4 lines of prior chemotherapy. Five Grade 3 toxicities were observed (anorexia, elevated aspartate aminotransferase or AST, elevated alkaline phosphatase, fever, and fatigue). Response data was available for 15 patients. Four patients had stable disease with the longest duration of disease control being 116 days. The median duration of treatment for evaluable patients was 55 days (range 28-124). Reasons for discontinuation included functional decline, disease progression, and disease-associated death. Increased S-glutathionylation of serum proteins was observed with treatment. CONCLUSION: Disulfiram 250 mg daily with copper gluconate (8 mg of elemental copper) was well-tolerated in patients with solid tumors involving the liver and was not associated with dose limiting toxicities. While temporary disease stabilization was noted in some patients, no objective responses were observed. Treatment was associated with an increase in S-glutathionylation suggesting that this combination could exert a suppressive effect on cellular growth and protein function. TRIAL REGISTRATION: NCT00742911 , first posted 28/08/2008.

Pediatric Heatstroke Fatalities Caused by Being Left in Motor Vehicles.

OBJECTIVES: Fatalities due to being left in motor vehicles is an important cause of pediatric mortality. Few studies in the medical literature focus on this topic. This study aims to describe the circumstances surrounding these deaths, to determine their geographic distribution, and to evaluate the legal consequences for those responsible. METHODS: This is a retrospective cohort study of individuals ≤14 years old who died of heatstroke after being left in motor vehicles from 1990 through 2016 using a database provided by KidsAndCars.org. Descriptive data and specified outcomes regarding victims and responsible individuals were recorded. RESULTS: Of the 541 cases included for analysis, 528 fatalities involved a single victim and 26 fatalities involved 2 or more victims left in a vehicle. Of all fatalities, 54.4% were male and the mean age was 16.4 (±13.7) months. The responsible individual(s) unknowingly left the victim(s) in the vehicle in 78.2% of cases and knowingly left the victim(s) in 16.6% of cases. A single individual was responsible for leaving the victim(s) in 88.9% of cases. The cases were noted in 45 of 50 states and most commonly occurred in Texas (15%), Florida (12%), and California (7%). Criminal charges against the responsible individual(s) occurred in 58.2% of cases. CONCLUSIONS: Pediatric fatalities due to being left in motor vehicles most commonly occur when a caregiver leaves a child unknowingly in a home parking area. These fatalities occur most often in Texas, Florida, and California. Responsible individuals are frequently charged with a crime.

Point-of-Care Ultrasound Findings in Multisystem Inflammatory Syndrome in Children: A Cross-Sectional Study.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 is a novel pediatric condition with significant morbidity and mortality. The primary objective of this investigation was to describe the point-of-care ultrasound (POCUS) findings in patients evaluated in the emergency department (ED) who were diagnosed with MIS-C. METHODS: A retrospective cross-sectional study was conducted including patients <21-years-old who had POCUS performed for clinical care in a pediatric ED and were diagnosed with MIS-C. Point-of-care ultrasound studies were performed by pediatric emergency medicine attending physicians or fellows. Data abstracted by chart review included patient demographics, clinical history, physical examination findings, diagnostic test results, the time POCUS studies and echocardiograms were performed, therapies administered, and clinical course after admission. RESULTS: For the 24 patients included, 17 focused cardiac ultrasound, 9 lung POCUS, 7 pediatric modified rapid ultrasound for shock and hypotension, 1 focused assessment with sonography for trauma, 1 POCUS for suspected appendicitis, and 1 ocular POCUS were performed by 13 physicians. Point-of-care ultrasound identified impaired cardiac contractility in 5 patients, large intraperitoneal free fluid with inflamed bowel in 1 patient, and increased optic nerve sheath diameters with elevation of the optic discs in 1 patient. Trace or small pericardial effusions, pleural effusions, and intraperitoneal free fluid were seen in 3 patients, 6 patients, and 4 patients, respectively. CONCLUSIONS: This study demonstrates the spectrum of POCUS findings in MIS-C. Prospective studies are needed to help delineate the utility of incorporating POCUS into an ED management pathway for patients with suspected MIS-C.

Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population-based sample.

BACKGROUND: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings. OBJECTIVE: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample. METHODS: We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRSS ) was based on guideline criteria, and objective radiologic inflammation (CRSO ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRSS+O . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRSS+O . Using weighted analysis, we calculated estimates for the source population. RESULTS: The proportion of women with L-M scores ≥ 3, 4, or 6 (CRSO ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRSS+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRSS+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses. CONCLUSION: In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRSS+O .

Lung Point-of-Care Ultrasound in Pediatric COVID-19: A Case Series.

Lung point-of-care ultrasound (POCUS) has been shown to be useful for identifying pulmonary pathology in adult patients with coronavirus disease 2019 (COVID-19). However, pediatric literature for POCUS in COVID-19 is limited. The objective of this case series was to describe lung POCUS findings in pediatric patients with COVID-19. Three patients with COVID-19 who had lung POCUS performed in a pediatric emergency department were included. Point-of-care ultrasound revealed bilateral abnormalities in all patients, including pleural line irregularities, scattered and coalescing B-lines, consolidations, and pleural effusions. Additional pediatric studies are necessary to gain a broader understanding of COVID-19's sonographic appearance in this age group and to determine whether POCUS may be helpful to facilitate diagnosis and expedite management decisions.

Molecular principles for heparin oligosaccharide-based inhibition of neutrophil elastase in cystic fibrosis.

Cystic fibrosis (CF) is a multifactorial disease in which dysfunction of protease-antiprotease balance plays a key role. The current CF therapy relies on dornase α, hypertonic saline, and antibiotics and does not address the high neutrophil elastase (NE) activity observed in the lung and sputum of CF patients. Our hypothesis is that variants of heparin, which potently inhibit NE but are not anticoagulant, would help restore the protease-antiprotease balance in CF. To realize this concept, we studied molecular principles governing the effectiveness of different heparins, especially 2-O,3-O-desulfated heparin (ODSH), in the presence of sputum components and therapeutic agents. Using sputa from CF patients and an NE activity assay, we found that heparins are ineffective if used in the absence of dornase. This is true even when mucolytics, such as DTT or N-acetylcysteine, were used. Computational modeling suggested that ODSH and DNA compete for binding to an overlapping allosteric site on NE, which reduces the anti-NE potential of ODSH. NE inhibition of both DNA and ODSH is chain length-dependent, but ODSH chains exhibit higher potency per unit residue length. Likewise, ODSH chains exhibit higher NE inhibition potential compared with DNA chains in the presence of saline. These studies suggest fundamental differences in DNA and ODSH recognition and inhibition of NE despite engaging overlapping sites and offer unique insights into molecular principles that could be used in developing antiprotease agents in the presence of current treatments, such as dornase and hypertonic saline.

Utility of applying white blood cell cutoffs to non-diagnostic MRI and ultrasound studies for suspected pediatric appendicitis.

BACKGROUND: Non-contrast magnetic resonance imaging (MRI) and ultrasound studies in pediatric patients with suspected appendicitis are often non-diagnostic. The primary objective of this investigation was to determine if combining these non-diagnostic imaging results with white blood cell (WBC) cutoffs improves their negative predictive values (NPVs). METHODS: A retrospective chart review was conducted including patients ≤18 years old with suspected appendicitis who had MRI performed with or without a preceding ultrasound study in a pediatric emergency department. Imaging results were sorted into 2 diagnostic and 5 non-diagnostic categories. NPVs were calculated for the non-diagnostic MRI and ultrasound categories with and without combining them with WBC cutoffs of <10.0 and <7.5 × 109/L. RESULTS: Of the 612 patients with MRI studies included, 402 had ultrasound studies performed. MRI with incomplete visualization of a normal appendix without secondary signs of appendicitis had an NPV of 97.9% that changed to 98.1% and 98.2% when combined with WBC cutoffs of <10.0 and <7.5, respectively. Ultrasound studies with incomplete visualization of a normal appendix without secondary signs had an NPV of 85.3% that improved to 94.8% and 96.5% when combined with WBC cutoffs of <10.0 and <7.5, respectively. CONCLUSIONS: In pediatric patients with suspected appendicitis, MRI studies with incomplete visualization of a normal appendix without secondary signs have a high NPV that does not significantly change with the use of these WBC cutoffs. In contrast, combining WBC cutoffs with ultrasound studies with the same interpretation identifies low-risk groups.

2-O, 3-O Desulfated Heparin Blocks High Mobility Group Box 1 Release by Inhibition of p300 Acetyltransferase Activity.

High mobility group box 1 (HMGB1) is an alarmin released from macrophages after infection or inflammation and is a biomarker of lung disease progression in patients with cystic fibrosis. We reported that 2-O, 3-O desulfated heparin (ODSH) inhibits the release of HMGB1 from murine macrophages triggered by neutrophil elastase both in vivo and in vitro. HMGB1 shuttles between the nucleus and the cytoplasm. When acetylated at lysine residues in the nuclear localization signal domains, HMGB1 is sequestered in the cytoplasm and is fated for secretion. In this study, we investigated the mechanism by which ODSH blocks HMGB1 secretion. We tested whether ODSH inhibits the activity of p300, a histone acetyltransferase that has been linked to HMGB1 acetylation and release. ODSH inhibited both neutrophil elastase and LPS-triggered HMGB1 release from the murine macrophage cell line RAW264.7 in a concentration-dependent manner. Fluorescein-labeled ODSH was taken up by RAW264.7 cells into the cytoplasm as well as the nucleus, suggesting an intracellular site of action of ODSH for blocking HMGB1 release. ODSH inhibited RAW264.7 cell nuclear extract, human macrophage nuclear extract, and recombinant p300 HAT activity in vitro, resulting in the failure to acetylate HMGB1. In silico molecular modeling predicted that of the numerous possible ODSH sequences, a small number preferentially recognizes a specific binding site on p300. Fluorescence binding studies showed that ODSH bound p300 tightly (dissociation constant ∼1 nM) in a highly cooperative manner. These results suggest that ODSH inhibited HMGB1 release, at least in part, by direct molecular inhibition of p300 HAT activity.

2-O, 3-O-desulfated heparin inhibits neutrophil elastase-induced HMGB-1 secretion and airway inflammation.

Neutrophil elastase (NE) is a major inflammatory mediator in cystic fibrosis (CF) that is a robust predictor of lung disease progression. NE directly causes airway injury via protease activity, and propagates persistent neutrophilic inflammation by up-regulation of neutrophil chemokine expression. Despite its key role in the pathogenesis of CF lung disease, there are currently no effective antiprotease therapies available to patients with CF. Although heparin is an effective antiprotease and anti-inflammatory agent, its anticoagulant activity prohibits its use in CF, due to risk of pulmonary hemorrhage. In this report, we demonstrate the efficacy of a 2-O, 3-O-desulfated heparin (ODSH), a modified heparin with minimal anticoagulant activity, to inhibit NE activity and to block NE-induced airway inflammation. Using an established murine model of intratracheal NE-induced airway inflammation, we tested the efficacy of intratracheal ODSH to block NE-generated neutrophil chemoattractants and NE-triggered airway neutrophilic inflammation. ODSH inhibited NE-induced keratinocyte-derived chemoattractant and high-mobility group box 1 release in bronchoalveolar lavage. ODSH also blocked NE-stimulated high-mobility group box 1 release from murine macrophages in vitro, and inhibited NE activity in functional assays consistent with prior reports of antiprotease activity. In summary, this report suggests that ODSH is a promising antiprotease and anti-inflammatory agent that may be useful as an airway therapy in CF.

RETINAL VASCULAR DISEASE IN LIMB-GIRDLE MUSCULAR DYSTROPHY.

PURPOSE: To report bilateral retinal vascular occlusive disease in limb-girdle muscular dystrophy (LGMD). METHODS: Case report. RESULTS: A 34-year-old Asian woman was referred for evaluation and management of central retinal vein occlusion. Ultra-wide-field fluorescein angiography showed resolving initial peripheral retinal vein occlusion in one eye and peripheral venular segmental staining in the fellow asymmetric eye. Genetic testing established the diagnosis of LGMD. CONCLUSION: Similar to other forms of muscular dystrophy, LGMD is caused by genetic abnormalities in sarcolemma proteins, a key structural component that connects the intracellular cytoskeleton of a myofiber to the extracellular matrix. Like other muscular dystrophies, LGMD may be associated with retinal vascular abnormalities noted. In this case, retinal vascular smooth muscle dysfunction was seen in LGMD, analogous to reported vascular abnormalities in other muscular dystrophies such as facioscapulohumeral dystrophy and Duchenne muscular dystrophy.

Detection of Circulating Tumor DNA After Stereotactic Ablative Radiotherapy in Patients With Unbiopsied Lung Tumors (SABR-DETECT).

For patients with stage I/IIA non-small-cell lung cancer (NSCLC), surgical resection is the standard treatment. However, some of these patients are not candidates for surgery or refuse a surgical option. Definitive stereotactic ablative radiotherapy (SABR) is a standard approach in these patients. Approximately 15% of patients undergoing SABR for localized NSCLC will experience a recurrence within 2 years. Furthermore, many of these patients are deemed appropriate for SABR without a tissue diagnosis, based on the likelihood of malignancy which can be calculated by validated models. A liquid biopsy, detecting ctDNA, would be useful in early detection of recurrences, and documenting a cancer diagnosis in patients without a biopsy. This is a multi-institutional study enrolling patients with suspected stage I/IIA NSCLC and a pretreatment likelihood of malignancy of ≥60% using the validated models for patients without a tissue diagnosis, in cohort 1 (n = 45). The second cohort will consist of biopsied patients (n = 30-60). SABR will be delivered as per risk-adapted protocol. Plasma will be collected for ctDNA analysis prior to the first fraction of SABR, 24 to 72 hours after first fraction, and at 3, 6, 9, 12, 18, and 24-months. The patients will be followed up with imaging at 3, 6, 9, 12, 18, and 24-months. The primary objective is to assess whether a cancer detection liquid biopsy platform can predict recurrence of NSCLC. The secondary objectives are to assess the impact of SABR on detection rates of ctDNA in patients undergoing SABR and to correlate ctDNA positivity and pretreatment probability of malignancy (NCT05921474).

The Association Between Screen Time and Outdoor Time on Adolescent Mental Health and Academic Performance: Evidence from Rural China.

Purpose: We examine how adolescent free time allocation-namely, screen time and outdoor time-is associated with mental health and academic performance in rural China. Methods: This paper used a large random sample of rural junior high school students in Ningxia (n = 20,375; age=13.22), with data collected from self-reported demographic questionnaires (to assess free time allocation), the Strengths and Difficulties Questionnaire (to assess mental health), and a standardized math test (to measure academic performance). We utilized a multivariate OLS regression model to examine associations between free time allocation and adolescent outcomes, controlling for individual and family characteristics. Results: Our sample's screen time and outdoor time both averaged around 1 hour. About 10% of the sample adolescents reported behavioral difficulties, while a similar percentage (11%) reported abnormal prosocial behaviors. Adolescents with higher levels of screen time (>2 hours) were 3 percentage points more likely to have higher levels of behavioral difficulties (p<0.001), indicating that excessive screen time was associated with worse mental health. Meanwhile, outdoor time was associated with better mental health, and positive correlations were observed at all levels of outdoor time (compared to no outdoor time, decreasing the likelihood of higher levels of behavioral difficulties by between 3 and 4 percentage points and of lower prosocial scores by between 6 and 8 percentage points; all p's<0.001). For academic performance, average daily screen times of up to 1 hour and 1-2 hours were both positively associated with standardized math scores (0.08 SD, p<0.001; 0.07 SD, p<0.01, respectively), whereas there were no significant associations between outdoor time and academic performance. Conclusion: Using a large sample size, this study was the first to examine the association between adolescent free time allocation with mental health and academic performance, providing initial insights into how rural Chinese adolescents can optimize their free time.

Barriers to Access: Global Variability in Implementing Treatment Advances in Lung Cancer.

Globally, lung cancer is the second most-diagnosed cancer and is the leading cause of cancer death. Advances in science and technology have contributed to improvements in primary cancer prevention, cancer diagnosis, and cancer therapy, leading to an increase in survival and improvement in quality of life. Many of these advances have been seen in high-income countries. Accessibility, availability, and affordability are key domains in barriers to access of care between countries and within countries. The impact of these domains, as they relate to molecular testing, radiation therapy, and systemic therapy, are discussed.