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Objective: Pediatric Environmental Health Specialty Units (PEHSUs) address health concerns impacting children and their families related to environmental hazards by providing consultation and education to families, communities, and health care professionals. This analysis evaluated the productivity of the national PEHSU program., Methods: PEHSUs reported data on services provided to US communities between October 1, 2014 and September 30, 2019. Descriptive statistics and qualitative analysis are presented., Results: During this period, 6102 consultations and 4644 educational outreach activities were recorded. PEHSU faculty and staff published 462 articles, reviews, book chapters, fact sheets, commentaries, short informational pieces, and other materials between 2014 and 2019. These included 190 articles in scientific peer-reviewed journals and 29 textbook chapters to increase professional capacity in pediatric and reproductive environmental health. Lead, other metals, substances of abuse, pesticides, mold, and air pollution were frequently reported as agents of concern and educational topics. Requests for an overview of pediatric environmental health and outdoor pollutants were other frequently reported topics., Conclusions: PEHSUs work to decrease harmful exposures and improve children's health. They serve as expert resources for families, health care professionals, and communities on health effects related to environmental exposures. Data show the breadth and depth of concerns addressed and demonstrate the productivity and impact of this national program., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Academic Pediatric Association. All rights reserved.)

The stereochemistry of the uncatalyzed chlorolactonization of 4-phenylpent-4-enoic acid at room temperature was examined to probe the reaction's intrinsic diastereoselectivities as a function of chlorenium ion donor, solvent polarity, and reactant concentration ranges. Kinetic studies using Variable Time Normalization Analysis (VTNA) revealed differing reaction orders for the syn and anti alkene addition processes. Aided and illustrated by quantum chemical modeling, this detailed mechanistic analysis of the substrate's intrinsic chlorolactonization reactions points to concerted AdE3-type paths for both syn and anti additions. By illuminating the factors selecting for syn- vs anti-addition paths, the results provide key reference points for future studies of stereocontrol in halofunctionalization reactions., (© 2024 Wiley‐VCH GmbH.)

Various structural elements of the Cinchona alkaloid dimers are interrogated to establish a structure-enantioselectivity relationship (SER) in three different halocyclization reactions. SER for chlorocyclizations of a 1,1-disubstituted alkenoic acid, a 1,1-disubstituted alkeneamide, and a trans -1,2-disubstituted alkeneamide showed variable sensitivities to linker rigidity and polarity, aspects of the alkaloid structure, and the presence of two or only one alkaloid side group defining the catalyst pocket. The conformational rigidity of the linker-ether connections was probed via DFT calculations on the methoxylated models, uncovering especially high barriers to ether rotation out of plane in the arene systems that include the pyridazine ring. These linkers are also found in the catalysts with the highest enantioinduction. The diversity of the SER results suggested that the three apparently analogous test reactions may proceed by significantly different mechanisms. Based on these findings, a stripped-down analogue of (DHQD) 2 PYDZ, termed "(trunc) 2 PYDZ", was designed, synthesized, and evaluated, showing modest but considerable asymmetric induction in the three test reactions, with the best performance on the 1,1-disubstituted alkeneamide cyclization. This first effort to map out the factors essential to effective stereocontrol and reaction promotion offers guidance for the simplified design and systematic refinement of new, selective organocatalysts.

Background: The methodologies for clinical research trials are evolving to greater usage of social media platforms, providing opportunities to incorporate smart technologies in their delivery. Research Nurses should consider how they can utilise platforms for public engagement in trials., Aim: To explore the experiences of social media platforms and clinical research trials in a healthy population group, to gain insight into how clinical researchers can utilise these platforms professionally and ethically., Methods: Using a critical realist qualitative focus group design with template analysis, we recruited 16 healthy members of the public aged 18-75 years. The data expands upon their thoughts and behaviours regarding social media platforms with their understanding of clinical research., Results: Three main themes along with their specific subthemes (1) Design: Patient and Public Involvement (Subtheme: Understanding of clinical research, Diversity of social media users), (2) Implementation: Recruitment to active studies, (Subtheme: Motivators for volunteering, Trustworthy), (3) Dissemination: Impact and Awareness of Results, (Subtheme: Information overload, Motivations for users to share information)., Conclusions: This study has highlighted the need to consider the way different population groups use social media platforms and the information they share when looking to engage them in clinical research trials., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

In recent work to develop cyanine dyes with especially large Stokes shifts, we encountered a "blueing" reaction, in which the heptamethine cyanine dye Cy7 (IUPAC: 1,3,3-trimethyl-2-((1 E ,3 E ,5 E )-7-(( E )-1,3,3-trimethylindolin-2-ylidene)hepta-1,3,5-trien-1-yl)-3 H -indol-1-ium) undergoes shortening in two-carbon steps to form the pentamethine ( Cy5 ) and trimethine ( Cy3 ) analogs. Each step blue-shifts the resulting absorbance wavelength by ca. 100 nm. Though photochemical and oxidative chain-shortening reactions had been noted previously, it is simple heating alone or with amine bases that effects this unexpected net C 2 H 2 excision. Explicit acetylene loss would be too endothermic to merit consideration. Our mechanistic studies using 2 H labeling, mass spectrometric and NMR spectroscopic analyses, and quantum chemical modeling point instead to electrocyclic closure and aromatization of the heptamethine chain in Cy7 forming Fischer's base FB (1,3,3-trimethyl-2-methyleneindoline), a reactive carbon nucleophile that initiates chain shortening of the cyanine dyes by attack on their polymethine backbones. The byproduct is the cationic indolium species TMP (IUPAC: 1,3,3 trimethyl-2-phenyl indolium).

Background: Programmed cell death ligand 1 (PD-L1) inhibitors have limited efficacy as monotherapy in patients with recurrent/metastatic (R/M) Human Papilloma Virus (HPV) oropharyngeal squamous cell carcinoma (OPSCC). A phase I study of the therapeutic HPV-16 DNA vaccine AMV002 in curatively treated patients with OPSCC demonstrated a measurable immune response against HPV while being associated with high safety and tolerability. This prospective phase Ib single centre pilot study aims to test the safety and tolerability of combined PD-L1 inhibitor, Durvalumab, with AMV002 in 12 patients with recurrent OPSCC., Methods: Participants had evidence of R/M HPV-associated OPSCC. They received three intradermal administrations of AMV002 with Durvalumab followed by Durvalumab maintenance. Safety and tolerability data was the primary endpoint. The study was conducted with ethical approval (HREC/2018/QMS/47293) in Brisbane, Australia., Findings: The most common adverse event (AE) related to vaccine administration was erythema at the injection site. There were no grade 3 or 4 vaccine related AEs. There was one presumed immune-related grade 3 elevation in lipase secondary to Durvalumab with no intervention required. No patient ceased study due to treatment-related AEs. At week 16, objective response rate was 8% (N=1) and disease control rate was 17% (N=2). At a median follow up of 25.6 (20.0-26.6) months there was one long term complete response while all other participants developed progressive disease. Of the 11 evaluated patients, 9, (82%) had E6 and/or E7-specific T cell responses to the vaccine., Conclusion: The combination of AMV002 therapeutic HPV-16 vaccine and Durvalumab was found to be safe and well tolerated with no increased safety signals generated. T cell responses to vaccine were observed but further work will be required to improve efficacy., Competing Interests: Author NF was employed by the company Jingang Medicine (Australia) Pty Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ladwa, Chandra, Woo, Finlayson, Liu, McGrath, See, Hughes, Cooper, Jackson, Dzienis, Xu, Panizza, Frazer and Porceddu.)

Background: Bronchial artery embolization (BAE) using particles is an established treatment for hemoptysis. The use of polyvinyl alcohol (PVA) with a particle size of 300 µm or larger is thought to reduce the risk of non-target embolization but may result in more proximal vessel occlusion than is ideal, resulting in a high rate of early recurrent hemorrhage., Objective: This study evaluates the safety and efficacy of BAE using PVA particles with a size of less than 300 µm., Methods: All patients who underwent BAE between 2010 and 2022 at a tertiary center were included. Demographic data, etiology and volume of hemoptysis, technical and clinical success, procedure-related complications, and follow-up information were collected from patients' electronic records. 150-250 µm PVA particles were used to commence embolization in all patients with the subsequent use of larger-sized particles in some individuals. The Kaplan-Meier method was used to estimate recurrence and survival rates., Results: One hundred forty-four patients underwent 189 embolization procedures between 2010 and 2022 and were followed up for a median of 35 months [IQR 19-89]. 150 µm to 250 µm PVA particles were used as the sole embolic agent in 137 cases. Hemoptysis recurred within 30 days in 7%. The median time to repeat intervention was 144 days [IQR 42-441]. Seventeen out of 144 patients had a pulmonary artery branch pseudoaneurysm. The rate of major complications was 1% with no instances of stroke or spinal artery ischemia. Thirty-day mortality was 2% (4/189)., Conclusion: BAE using 150-250 µm PVA particles is safe and effective with few complications and low rates of early hemoptysis recurrence., Clinical Relevance Statement: BAE using small particles is likely to improve outcomes, particularly the rate of early recurrence, in patients with hemoptysis, without an increase in procedural complications., Key Points: BAE is a safe and effective treatment for patients with hemoptysis. Using small PVA particles in BAE has few complications and low rates of early recurrence. Pulmonary artery pseudoaneurysms should be actively sought in those with hemoptysis undergoing BAE., (© 2024. The Author(s).)

Background: Pediatric patients treated at trauma centers demonstrate improved outcomes, but investigation of optimal resource utilization surrounding the transfer is ongoing. We evaluated characteristics of operative pediatric trauma transfer patients for resource optimization., Methods: A retrospective review of pediatric trauma patients transferred to a level 1 pediatric trauma center from 2009 to 2019 was performed. Patients were categorized by initial operative subspecialty., Results: Of 4164 transferred patients, 33.9 ​% required operative intervention. 65 ​% of operations were performed on orthopedic patients, who were significantly less injured compared to other patients. General surgery patients were more likely to undergo surgery on day of transfer compared to orthopedic patients (39.4%vs 56.3 ​%, OR 2.0, CI 1.4-2.8)., Conclusions: One-third of pediatric trauma transfer patients required operative intervention. The majority of surgeries were on orthopedic patients, who were less likely to undergo surgery on day of transfer. Critical evaluation of this patient population is required to safely utilize a less resource-intensive transfer process., Competing Interests: Declaration of competing interest The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (grant number UL1 TR001860) for author EGB. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was presented at Pediatric Trauma Society 8th annual meeting. This project represents original work by the authors. During the preparation of this work, the authors did not use generative AI and AI-assisted technologies in the writing process., (Copyright © 2023. Published by Elsevier Inc.)

COVID-19 impacted the mental health of many people in the UK. The negative impact was especially substantial among vulnerable population groups, including migrants. While research has focused on the negative aspects of mental health during the pandemic, the positive mental health of migrants in the UK during COVID-19 remained to be evaluated. This review aimed to identify literature that focused on positive mental health, and thematically synthesise the findings to understand what positive mental health approaches were employed to support specific outcomes during the pandemic for them to survive in this difficult time. Medline, Embase, and PsycINFO were searched using terms including "mental health", "migrants", and "COVID-19". The Critical Appraisal Skills Programme checklist was used to assess the quality of the included studies. There were only two studies examining the positive mental health of UK migrants during this period. They describe approaches such as religious beliefs, passion for and acknowledgement of their job, learning new things, being physically active, social media, and social activities, producing outcomes such as inner peace, confidence, well-being, and a sense of belonging. The quality of the included studies was high. More research about positive mental health in migrants in the UK during the pandemic is needed.

Background: Trans and/or non-binary parents experience structural exclusion in family healthcare and there is a need for specialist training for healthcare professionals so that they are able to create a gender inclusive environment. Aim: As part of a continued effort to address health inequity this study explores the body experiences of infant feeding within trans and non binary communities. Method: Semi structured interviews were conducted with seven trans or non-binary parents, based in the United Kingdom, who have experienced chestfeeding or breastfeeding. Results: A reflexive thematic analysis was utlitised to identify three main themes which centered around baby, body and support in health care settings. Parents were informed of the benefits of their milk and were strongly motivated by their child's needs. However, body feeding was emotionally and physically challenging. Conclusion: Person-centered care with consistent attention to language is required when supporting lactation., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Purpose: This secondary analysis of clinical trial TROG 12.01, involving patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma, aimed to identify patient-reported outcome (PRO) trajectories before, during, and after chemoradiotherapy., Methods and Materials: Head and neck cancer symptom severity (HNSS) and interference (HNSI), generic health-related quality of life (HRQL), and emotional distress were assessed with the MD Anderson Symptom Inventory-Head and Neck, Functional Assessment of Cancer Therapy-General, and Hospital Anxiety and Depression Scale questionnaires, respectively. Latent class growth mixture modeling (LCGMM) was used to identify distinct underlying trajectories. Baseline and treatment variables were compared between trajectory groups., Results: The LCGMM identified latent trajectories for all PROs: HNSS, HNSI, HRQL, anxiety, and depression. Four HNSS trajectories (HNSS1-4) were identified, distinguished by differences in HNSS at baseline, during the peak of treatment symptoms, and during early and intermediate recovery. All trajectories were stable beyond 12 months. The reference trajectory (HNSS4, n = 74) score was 0.1 (95% confidence interval [CI], 0.1-0.2) at baseline, peaking at 4.6 (95% CI, 4.2-5.0), with rapid early recovery (1.1; 95% CI, 0.8-2.2) and gradual improvement to 12 months (0.6; 95% CI, 0.5-0.8). Patients in HNSS2 (high baseline, n = 30) reported higher baseline scores (1.4; 95% CI, 0.8-2.0) but were otherwise similar to HNSS4. Patients in HNSS3 (low acute, n = 53) reported reduced acute symptoms (2.5; 95% CI, 2.2-2.9) with stable scores beyond 9 weeks after chemoradiotherapy (1.1; 95% CI, 0.9-1.4). Patients in HNSS1 (slow recovery, n = 25) had slower recovery from an acute peak of 4.9 (95% CI, 4.3-5.6) to 0.9 (95% CI, 0.6-1.3) at 12 months. Age, performance status, education, receipt of cetuximab, and baseline anxiety varied between trajectories. The other PRO models demonstrated clinically relevant trajectories, with distinct associations with baseline factors., Conclusions: LCGMM identified distinct PRO trajectories during and after chemoradiotherapy. These and their associations with variations in the characteristics and treatment factors of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma provide clinically relevant insights into identifying patients who may require increased support before, during, or after chemoradiotherapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Poor mental health of healthcare students is a cause for concern in many universities. Though previous research has identified mental health shame and self-compassion as critical in this student group, how these variables differ across different healthcare disciplines remains to be evaluated. Healthcare students ( n  = 344; counselling, occupational therapy, social work and nursing) completed measures regarding these variables. MANOVA and regression analyses were performed. (1) Counselling and nursing students were more depressed than occupational therapy students; (2) nursing students were more anxious than occupational therapy and social work students; (3) occupational therapy students had more positive attitudes towards mental health than the others; and (4) nursing students worried about their own reputation associated with their family more than counselling students. Self-compassion was the strongest predictor of mental health in all groups; however, the effect sizes varied: largest in nursing and smallest in social work students. Findings will help inform effective interventions for students in each healthcare discipline., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2023.)

Quantifying the mid-range infrared hydroxyl stretch absorbance region has traditionally been a challenge due to the wavenumber dependence of the attenuation coefficient. Interpretation often assigns a single attenuation coefficient to each type of hydrogen-bonded aggregate. This work leverages a recently developed technique of scaling hydroxyl stretching absorbances in the mid-infrared region with a continuous attenuation coefficient function that produces integrated areas which directly correlate to hydroxyl concentrations. After scaling, the hydroxyl absorbance is fitted with five curves, of which four are dominant. These four curves represent unique hydroxyl configurations and translate to specific aggregate structures. The technique is applied to ethanol and 1-butanol. The resulting population distributions of hydrogen-bonded hydroxyl configurations are compared with the resummed thermodynamic perturbation theory (RTPT) model for linear chains as a function of concentration and temperature. The model is demonstrated to capture the critical features of the distributions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: There has not been a recent evaluation of the association between racial and gender and surgical outcomes in children. We aimed to evaluate improvements in race- and gender-related pediatric postoperative outcomes since a report utilizing the Kids' Inpatient Database data from 2003 to 2006., Methods: Using Kids' Inpatient Database (2009, 2012, 2016), we identified 245,976 pediatric patients who underwent appendectomy for acute appendicitis (93.6%), pyloromyotomy for pyloric stenosis (2.7%), empyema decortication (1.6%), congenital diaphragmatic hernia repair (0.7%), small bowel resection for intussusception (0.5%), or colonic resection for Hirschsprung disease (0.2%). The primary outcome was the development of postoperative complications. Multivariable logistic regression was used to evaluate risk-adjusted associations among race, gender, income, and postoperative complications., Results: Most patients were male (61.5%) and 45.7% were White. Postoperative complications were significantly associated with male gender (P < 0.0001) and race (P < 0.0001). After adjustment, Black patients were more likely to experience any complication than White patients (adjusted odds ratio 1.3, confidence interval 1.2-1.4), and males were more likely than females (adjusted odds ratio 1.3, confidence interval 1.2-1.4)., Conclusions: No clear progress has been made in eliminating race- or gender-based disparities in pediatric postoperative outcomes. New strategies are needed to better understand and address these disparities., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this TROG 12.01 substudy was to report longitudinal variations in patient- (PRO) and clinician-reported outcomes based on receipt of unilateral (URT) or bilateral radiation therapy (BRT)., Methods and Materials: Patients with lateralized T1-2 N1-2b human papillomavirus-associated tonsillar carcinoma (AJCC7) enrolled on TROG 12.01 were eligible. The primary endpoint was patient-reported radiation symptom severity score (MDASI-RSS) at 2 years, a composite of 9 MDASI-Head and Neck (HN) symptom items. Secondary endpoints included patient-reported symptom burden and interference (MDASI-HN), quality of life (FACT-HN), emotional distress (HADS), return to work (RTW), clinician-reported performance status scale (PSS-HN), and late adverse events (CTCAE). Mean MDASI-RSS, symptom severity (MDASI-SS), symptom interference (MDASI-SI) and selected single items were compared 1 week, 3 months, and 2 years post-RT., Results: Seventy-four patients were eligible for analysis (26 URT, 48 BRT). Median follow-up was 3.7 years (1.8-5.2 years). Sociodemographic, staging, and treatment variables were mostly balanced, with larger primaries observed in the BRT group. Four regional failures were reported (3 URT, 1 BRT), including one isolated contralateral regional failure in the URT cohort. Mean MDASI-RSS scores did not differ at 2 years (URT vs BRT, 1.1 vs 1.3; difference 0.1 [95% CI: -0.7 to 0.9], P = .75) or at any other time points for the MDASI-RSS, MDASI-SS, and MDASI-SI scores, except for worse MDASI-SI 1 week after treatment in the BRT group (4.7 vs 5.6). Fatigue (6.6 vs 5.4) at 1 week and dry mouth (3.5 vs 2.0) at 2 years were also worse in the BRT group. FACT-HN, HADS, RTW, PSS-HN, and CTCAE results were similar across the follow-up period., Conclusions: In this favorable-risk cohort, treatment laterality resulted in fewer differences than anticipated in patient-reported or clinician-reported outcomes. Two years after treatment patients treated with BRT reported significantly worse dry mouth. Longer follow-up is needed to determine the impact of treatment laterality on late effects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Research suggests that an early connection with nature can benefit wellbeing into adulthood. However, there is less research assessing whether adolescents benefit from formal nature connection interventions such as forest bathing (slow mindful nature walks). This research aimed to assess whether an urban nature connection intervention (called ParkBathe) could improve adolescents' nature connection and wellbeing., Method: In an experimental repeated measures design, 44 adolescents sampled opportunistically from Scouts groups, completed surveys and interviews before and after experiencing an urban nature connection intervention., Results: Paired-samples t -tests between baseline and post-intervention survey scores revealed statistically significant improvements in anxiety (13% reduction); rumination (44% reduction); scepticism (17% reduction); nature connection (25% increase); and social connection (12% increase). The largest effect size was found for nature connection. Interviews revealed that before the session, participants had a mixed understanding and expectations of the intervention., Conclusions: After the session, the participants expressed enjoying the social aspects of being part of a group and being present in the moment by noticing nature. They expressed the effects of this as immediately calming and relaxing. Urban forest bathing improved nature connection and wellbeing in adolescents and could be implemented and/or signposted by schools and youth charities.

Background: Long-COVID affects over 144 million people globally. In the absence of treatments, there is a need to establish the efficacy of therapies that improve patient outcomes. Forest bathing has been demonstrated to improve physical and mental outcomes but there is no evidence in Long-COVID patients. Accordingly, this pilot study sought to determine the feasibility and effectiveness of online forest bathing in adults with Long-COVID., Methods: Feasibility was assessed by monitoring retention rates and participant feedback. In a waitlist controlled, repeated measures design, 22 Long-COVID patients completed weekly online surveys during a four-week waitlist control period, before engaging in four weekly online forest bathing sessions, completing post-intervention surveys following each session., Results: In terms of retention, 27% did not provide post-intervention data, reasons for non-adherence were: feeling too ill, having medical appointments, or having career responsibilities. Compared with the waitlist control period, there were statistically significant improvements in Anxiety (49% decrease), Rumination (48% decrease), Social Connection (78% increase), and Long-COVID symptoms (22% decrease). Written qualitative comments indicated that participants experienced feelings of calm and joy, felt more connected socially and with nature, and experienced a break from the pain and rumination surrounding their illness., Conclusions: Online Forest bathing resulted in significant improvements in well-being and symptom severity and could be considered an accessible and inexpensive adjunct therapy for Long-COVID patients. Where people have limited access to in-person nature, virtual nature may offer an alternative to improve health and well-being outcomes.

Introduction: In attempts to quell the spread of COVID-19, shelter-in-place orders were employed in most states. Increased time at home, in combination with parents potentially balancing childcare and work-from-home duties, may have had unintended consequences on pediatric falls from windows. We aimed to investigate rates of falls from windows among children during the first 6 mo of the COVID-19 pandemic., Methods: Patients <18 y old admitted to three pediatric trauma centers (two - level 1, one - level 2) between 3/19/20 and 9/19/20 (COVID-era) were compared to a pre-COVID cohort (3/19/19 to 9/19/19). The primary outcome was the rate of falls from windows. Secondary outcomes included injury severity score (ISS), injuries sustained, and mortality., Results: Of 1011 total COVID-era pediatric trauma patients, 36 (3.6%) sustained falls from windows compared to 23 of 1108 (2.1%) pre-COVID era patients (OR 1.7, P = 0.05). The median ISS was seven pre-COVID versus four COVID-era (P = 0.43). The most common injuries sustained were skull fractures (30.5%), extremity injuries (30.5%), and intracranial hemorrhage (23.7%). One-fifth of patients underwent surgery (21.7% pre-COVID versus 19.4% COVID-era, P = 1.0). There was one mortality in the COVID-era cohort and none in the pre-COVID cohort (P = 1.0)., Conclusions: Despite overall fewer trauma admissions during the first 6 mo of the COVID-19 pandemic, the rate of falls from windows nearly doubled compared to the prior year, with substantial associated morbidity. These findings suggest a potential unintended consequence of shelter-in-place orders and support increased education on home safety and increased support for parents potentially juggling multiple responsibilities in the home., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: One of the most competitive surgical sub-specialty fellowships remains Pediatric Surgery (PS), which requires candidates to develop a strong and research-oriented curriculum vitae. Although some objective factors of matriculation are known, factors for the interview selection and ranking per the program directors (PDs) have not been reviewed in over a decade., Methods: A web-based survey of US and Canadian PS program directors (PDs) (n = 58) was used to evaluate a comprehensive list of factors in the selection criteria for PS fellowships. A mix of dichotomous, ranking, five-point Likert scale, and open-ended questions evaluated applicant characteristics, ABSITE scores, research productivity, interview day, and rank order criteria., Results: Fifty-five programs responded to the survey for a 95% participation rate. PDs desired an average of two years in dedicated research and weighted first authorship and total number of publications heavily. Only 38% of programs used an ABSITE score cutoff for offering interviews; however, the majority agreed that an overall upward trend was important. Quality letters of recommendation, especially from known colleagues, carried weight when deciding to offer interviews. Interview performance, being a team player, observed interpersonal interactions, perceived operative skills and patient care, and leadership were some of the notable factors when finalizing rank lists., Conclusions: A multitude of factors define a successful matriculant, including quality of letters of recommendation, quality and quantity of publications, supportive phone calls, observed interactions, interview performance, perceptions of being team player with leadership skills as well as perceptions of good operative skills and patient care., Level of Evidence: Type II., Type of Study: Prognostic (retrospective)., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: The COVID-19 pandemic has widespread effects, including enhanced psychosocial stressors and stay-at-home orders which may be associated with higher rates of child abuse. We aimed to evaluate rates of child abuse, neglect, and inadequate supervision during the COVID-19 pandemic., Methods: Patients ≤5 y old admitted to a level one pediatric trauma center between 3/19/20-9/19/20 (COVID-era) were compared to a pre-COVID cohort (3/19/19-9/19/19). The primary outcome was the rate of child abuse, neglect, or inadequate supervision, determined by Child Protection Team and Social Work consultations. Secondary outcomes included injury severity score (ISS), mortality, and discharge disposition., Results: Of 163 total COVID-era pediatric trauma patients, 22 (13.5%) sustained child abuse/neglect, compared to 17 of 206 (8.3%) pre-COVID era patients (P = 0.13). The ISS was similar between cohorts (median 9 pre-COVID versus 5 COVID-era, P = 0.23). There was one mortality in the pre-COVID era and none during COVID (P = 0.45). The rate of discharge with someone other than the primary caregiver at time of injury was significantly higher pre-COVID (94.1% versus 59.1%, P = 0.02). In addition, foster family placement rate was twice as high pre-COVID (50.0% versus 22.7%, P = 0.10)., Conclusions: The rate of abuse/neglect among young pediatric trauma patients during COVID did not differ compared to pre-pandemic, but discharge to a new caregiver was significantly lower. While likely multifactorial, this data suggests that resources during COVID may have been limited and the clinical significance of this is concerning. Larger studies are warranted to further evaluate COVID-19's effect on this vulnerable population., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown., Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC., Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up., Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings)., Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects., Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively)., Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes., Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration. However, current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration, thus leading to adverse tissue formation and decreased regenerative efficiency. Here, we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration. The biomaterial works by presenting two synthetic ligands, LLP2A and LXW7, explicitly targeting integrins α4β1 and αvβ3, respectively, expressed on the surfaces of the cells related to bone formation and vascularization, such as mesenchymal stem cells (MSCs), osteoblasts, endothelial progenitor cells (EPCs), and endothelial cells (ECs). In vitro, the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs, osteoblasts, EPCs, and ECs via integrin α4β1 and αvβ3, respectively. In an adult rat calvarial bone defect model, the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials, such as DLX5 + cells, osteocalcin + cells, CD34 + /CD45 - cells and CD31 + cells. In a fetal sheep spinal bone defect model, the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects. This innovative biomaterial offers an off-the-shelf, easy-to-use, and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. © RSNA, 2022.

Background: There are over 150,000 transgender adolescents in the United States, yet research on outcomes following gender-affirming mastectomy in this age group is limited. We evaluated gender-affirming mastectomy incidence, as well as postoperative complications, including regret, in adolescents within our integrated health care system., Methods: Gender-affirming mastectomies performed from January 1, 2013 - July 31, 2020 in adolescents 12-17 years of age at the time of referral were identified. The incidence of gender-affirming mastectomy was calculated by dividing the number of patients undergoing these procedures by the number of adolescents assigned female at birth ages 12-17 within our system at the beginning of each year and amount of follow-up time within that year. Demographic information, clinical characteristics (comorbidities, mental health history, testosterone use), surgical technique, and complications, including mention of regret, of patients who underwent surgery were summarized. Patients with and without complications were compared to evaluate for differences in demographic or clinical characteristics using chi-squared tests., Results: The incidence of gender-affirming mastectomy increased 13-fold (3.7 to 47.7 per 100,000 person-years) during the study period. Of the 209 patients who underwent surgery, the median age at referral was 16 years (range 12-17) and the most common technique was double-incision (85%). For patients with greater than 1-year follow-up (n=137, 65.6%), at least one complication was found in 7.3% (n=10), which included hematoma (3.6%), infection (2.9%), hypertrophic scars requiring steroid injection (2.9%), seroma (0.7%), and suture granuloma (0.7%); 10.9 % underwent revision (n=15). There were no statistically significant differences in patient demographics and clinical characteristics between those with and without complications (p>0.05). Two patients (0.95%) had documented postoperative regret but neither underwent reversal surgery at follow-up of 3 and 7 years postoperatively., Conclusion: Between 2013-2020, we observed a marked increase in gender-affirming mastectomies in adolescents. The prevalence of surgical complications was low and of over 200 adolescents who underwent surgery, only two expressed regret, neither of which underwent a reversal operation. Our study provides useful and positive guidance for adolescent patients, their families, and providers regarding favorable outcomes with gender-affirming mastectomy., Competing Interests: Conflicts of Interests: The authors have no conflicts of interests.

Introduction: Fetal myelomeningocele (MMC) repair improves lower extremity motor function. We have previously demonstrated that augmentation of fetal MMC repair with placental mesenchymal stromal cells (PMSCs) seeded on extracellular matrix (PMSC-ECM) further improves motor function in the ovine model. However, little progress has been made in improving bowel and bladder function, with many patients suffering from neurogenic bowel and bladder. We hypothesized that fetal MMC repair with PMSC-ECM would also improve bowel and bladder function., Methods: MMC defects were surgically created in twelve ovine fetuses at median gestational age (GA) 73 days, followed by defect repair at GA101 with PMSC-ECM. Fetuses were delivered at GA141. Primary bladder function outcomes were voiding posture and void volumes. Primary bowel function outcome was anorectal manometry findings including resting anal pressure and presence of rectoanal inhibitory reflex (RAIR). Secondary outcomes were anorectal and bladder detrusor muscle thickness. PMSC-ECM lambs were compared to normal lambs (n = 3)., Results: Eighty percent of PMSC-ECM lambs displayed normal voiding posture compared to 100% of normal lambs (p = 1). Void volumes were similar (PMSC-ECM 6.1 ml/kg vs. normal 8.8 ml/kg, p = 0.4). Resting mean anal pressures were similar between cohorts (27.0 mmHg PMSC-ECM vs. normal 23.5 mmHg, p = 0.57). RAIR was present in 3/5 PMSC-ECM lambs that underwent anorectal manometry and all normal lambs (p = 0.46). Thicknesses of anal sphincter complex, rectal wall muscles, and bladder detrusor muscles were similar between cohorts., Conclusion: Ovine fetal MMC repair augmented with PMSC-ECM results in near-normal bowel and bladder function. Further work is needed to evaluate these outcomes in human patients., Competing Interests: Declarations of Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Diaryl ethers undergo electrocatalytic hydrogenolysis (ECH) over skeletal Ni cathodes in a mild, aqueous process that achieves direct C-O cleavage without initial benzene ring saturation. Mechanistic studies find that aryl phenyl ethers with a single para or meta functional group (methyl, methoxy, or hydroxy) are selectively cleaved to the substituted benzene and phenol, in contrast to recently reported homogeneous catalytic cleavage processes. Ortho positioning of substituents reverses this C-O bond selectivity, except for the 2-phenoxyphenol case. Together with isotope labeling and co-solvent studies, these results point to two distinct cleavage mechanisms: (a) dual-ring coordination and C-H activation, leading to vicinal elimination to form phenol and a surface-bound aryne intermediate which is then hydrogenated and released as the arene; and (b) surface binding in keto form by the phenolic ring of the hydroxy-substituted substrates, followed by direct displacement of the departing phenol. Notably, acetone inhibits the well-known reduction of phenol to cyclohexanol, affording control of product ring saturation. A byproduct of this work is the discovery that the ECH treatment completely defluorinates substrates bearing aromatic C-F and C-CF 3 groupings., (© 2022. The Author(s).)

Background: While fetal repair of myelomeningocele (MMC) revolutionized management, many children are still unable to walk independently. Preclinical studies demonstrated that research-grade placental mesenchymal stromal cells (PMSCs) prevent paralysis in fetal ovine MMC, however this had not been replicated with clinical-grade cells that could be used in an upcoming human clinical trial. We tested clinical-grade PMSCs seeded on an extracellular matrix (PMSC-ECM) in the gold standard fetal ovine model of MMC., Methods: Thirty-five ovine fetuses underwent MMC defect creation at a median of 76 days gestational age, and defect repair at 101 days gestational age with application of clinical-grade PMSC-ECM (3 × 10 5 cells/cm 2 , n = 12 fetuses), research-grade PMSC-ECM (3 × 10 5 cells/cm 2 , three cell lines with n = 6 (Group 1), n = 6 (Group 2), and n = 3 (Group 3) fetuses, respectively) or ECM without PMSCs (n = 8 fetuses). Three normal lambs underwent no surgical interventions. The primary outcome was motor function measured by the Sheep Locomotor Rating scale (SLR, range 0: complete paralysis to 15: normal ambulation) at 24 h of life. Correlation of lumbar spine large neuron density with SLR was evaluated., Results: Clinical-grade PMSC-ECM lambs had significantly better motor function than ECM-only lambs (SLR 14.5 vs. 6.5, p = 0.04) and were similar to normal lambs (14.5 vs. 15, p = 0.2) and research-grade PMSC-ECM lambs (Group 1: 14.5 vs. 15, p = 0.63; Group 2: 14.5 vs. 14.5, p = 0.86; Group 3: 14.5 vs. 15, p = 0.50). Lumbar spine large neuron density was strongly correlated with motor function (r = 0.753, p<0.001)., Conclusions: Clinical-grade placental mesenchymal stromal cells seeded on an extracellular matrix rescued ambulation in a fetal ovine myelomeningocele model. Lumbar spine large neuron density correlated with motor function, suggesting a neuroprotective effect of the PMSC-ECM in prevention of paralysis. A first-in-human clinical trial of PMSCs in human fetal myelomeningocele repair is underway., Competing Interests: Declarations of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Identifying pediatric patients who may benefit from gastrostomy tube (GT) placement can be challenging. We hypothesized that many GTs would no longer be in use after 6 months., Methods: Inpatient GT placements in patients < 18 years old at a tertiary children's hospital from 9/2014 to 2/2020 were included. The primary outcome was GT use <6 months (short-term). Secondary outcomes included age at placement, indication for GT, and operations for GT-related issues., Results: Fifteen percent (22/142) of GTs were used for <6 months post-operatively. The median duration of short-term GT use was 1.6 months (IQR 0.9-3.4 months). Short-term GTs were more likely to be placed in patients with traumatic brain injury (TBI) (18.2% vs. 4.2%, p = 0.03) and adolescents (≥12 years old, 22.7% vs. 4.0%, p = 0.005). Gastrocutaneous fistula closure was required in 33.3% of short-term patients who had their GTs removed (n = 6/18), with median total hospital charges of $29,989 per patient., Conclusion: Fifteen percent of pediatric GTs placed as inpatients were used for <6 months, more commonly among adolescents and in TBI patients. One-third of patients with short-term GTs required gastrocutaneous fistula closure. Adolescents and TBI patients may benefit from consideration of short-term nasogastric tube (NGT) feeds rather than surgical GT placement., Level of Evidence: III., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Augmentation of in utero myelomeningocele repair with human placental mesenchymal stromal cells seeded onto extracellular matrix (PMSC-ECM) improves motor outcomes in an ovine myelomeningocele model. This study evaluated the safety of PMSC-ECM application directly onto the fetal spinal cord in preparation for a clinical trial., Methods: Laminectomy of L5-L6 with PMSC-ECM placement directly onto the spinal cord was performed in five fetal lambs at gestational age (GA) 100-106 days. Lambs and ewes were monitored for three months following delivery. Lambs underwent magnetic resonance imaging (MRI) of the brain and spine at birth and at three months. All organs from lambs and uteri from ewes underwent histologic evaluation. Lamb spinal cords and brains and ewe placentas were evaluated for persistence of PMSCs by polymerase chain reaction for presence of human DNA., Results: MRIs demonstrated no evidence of abnormal tissue growth or spinal cord tethering. Histological analysis demonstrated no evidence of abnormal tissue growth or treatment related adverse effects. No human DNA was identified in evaluated tissues., Conclusion: There was no evidence of abnormal tissue growth or PMSC persistence at three months following in utero application of PMSC-ECM to the spinal cord. This supports proceeding with clinical trials of PMSC-ECM for in utero myelomeningocele repair., Level of Evidence: N/A TYPE OF STUDY: Basic science., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)

Background: Trauma patients undergo a standardized history and physical, however identification of mental health risk factors is not typically included. We aimed to assess the feasibility of using a modified version of Psychological Simple Triage and Rapid Treatment (PsySTART) to identify post-traumatic stress disorder (PTSD) risk factors in pediatric trauma patients. We hypothesized that PsySTART could identify risk factors and be integrated into the electronic medical record (EMR)., Methods: Trauma patients 10-17 years old at a level II pediatric trauma center from 2014 to 2015 were screened. PsySTART was used on a pilot cohort to determine if risk factors were present. PsySTART was then integrated into an automated EMR workflow and completion rates were evaluated., Results: PsySTART was completed in a pilot cohort of 63 patients with the following findings: 33.3% (n = 21) with 1 risk factor, 22.2% (n = 14) with 2 risk factors, and 19.1% (n = 12) with ≥3 risk factors. The most commonly identified risk factor was, "felt or expressed extreme fear or panic" (n = 27, 43.0%). After EMR integration, PsySTART was successfully completed with automatic consults in 156 of 198 patients (78.8%)., Conclusions: PsySTART identified risk factors in pediatric trauma patients. EMR integration was feasible and led to proactive psychological management and intervention., Level of Evidence: IV., (Copyright © 2021. Published by Elsevier Inc.)

Background: Traumatic diaphragmatic hernia (TDH) is rare in children, most often occurring following blunt thoracoabdominal trauma from high energy mechanisms, such as motor vehicle collisions (MVC). We performed a systematic review to describe injury details and management., Methods: Following PRISMA guidelines, a systematic literature search was performed to identify publications of blunt TDH in patients < 18 y old. Conflicts were resolved by consensus. Data were collected on demographics, TDH location, mechanism of injury, associated intraabdominal injuries (IAI), management, and outcomes. Denominators vary depending on number of patients with such information reported., Results: Fifty-eight articles were reviewed with 142 patients with TDH. The median age was seven y (range 0.25-16). Most were left-sided (85 of 126, 67.5%). MVC was the most common mechanism (66 of 142, 46.5%). IAI was present in 50.0% (57 of 114), most commonly liver injuries (25 of 57, 43.9%). Delayed diagnoses occurred in 49.6% (57 of 115, range 8 h-10 y), and were more common with right-sided TDH (76.0% versus 48.5%, P = 0.02). Chest radiography was 59.0% sensitive for TDH, while computed tomography sensitivity was 65.8%. Operative repair was performed on all surviving patients, and all underwent primary diaphragm repair. The overall mortality was 11.3% (n = 16), with four attributable to the TDH. There were no reported recurrences over a median follow-up of 12 mo., Conclusions: Pediatric TDH is a rare diagnosis with a high rate of associated IAI and delayed diagnosis. Primary diaphragm repair was performed in all cases. Surgeons should maintain a high suspicion for diaphragm injury in blunt thoracoabdominal trauma., (Copyright © 2021. Published by Elsevier Inc.)

Background: Abusive head trauma (AHT) is a leading cause of morbidity and mortality among young children. We aimed to evaluate the long-term impact of AHT., Methods: Using administrative claims from 2000-2018, children <3 years old with documented AHT who had follow-up through ages 5 and 11 years were identified. The primary outcome was incidence of neurodevelopmental disability and the secondary outcome was the effect of age at time of AHT on long-term outcomes., Results:   1,165 children were identified with follow-up through age 5; 358 also had follow-up through age 11.  The incidence of neurodevelopmental disability was 68.0% (792/1165) at 5 years of age and 81.6% (292/358) at 11 years of age.  The incidence of disability significantly increased for the 358 children followed from 5 to 11 years old (+14.3 percentage points, p<0.0001).  Children <1 year old at the time of AHT were more likely to develop disabilities when compared to 2 year olds., Conclusions: AHT is associated with significant long-term disability by age 5 and the incidence increased by age 11 years.  There is an association between age at time of AHT and long-term outcomes. Efforts to improve comprehensive follow-up as children continue to age is important., Level of Evidence: IV., (Copyright © 2021. Published by Elsevier Inc.)

Several fluorene derivatives exhibit excited-state reactivity and relaxation dynamics that remain to be understood fully. We report here the spectral relaxation dynamics of two fluorene derivatives to evaluate the role of structural modification in the intramolecular relaxation dynamics and intermolecular interactions that characterize this family of chromophores. We have examined the time-resolved spectral relaxation dynamics of two compounds, NCy- FR0 and MK- FR0 , in protic and aprotic solvents using steady-state and time-resolved emission spectroscopy and quantum chemical computations. Both compounds exhibit spectral relaxation characteristics similar to those seen in FR0 , indicating that hydrogen bonding interactions between the chromophore and solvent protons play a significant role in determining the relaxation pathways available to three excited electronic states.

Purpose: The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin., Methods and Materials: TROG12.01, a randomized, multicenter trial involving 15 sites in Australia and New Zealand enrolled patients with HPV-associated oropharyngeal squamous cell carcinoma, American Joint Committee on Cancer 7th edition stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomized (1:1) to receive radiation therapy (70 Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40 mg/m 2 , or cetuximab, loading dose of 400 mg/m 2 followed by 7 weekly doses of 250 mg/m 2 . The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks postcompletion of radiation therapy using the area under the curve. Trial was registered on ClinicalTrials.gov: NCT01855451., Results: Between June 17, 2013, and June 7, 2018, 189 patients were enrolled, with 92 in cisplatin arm and 90 in cetuximab included in the main analysis. There was no difference in the primary endpoint of symptom severity; difference in area under the curve cetuximab-cisplatin was 0.05 (95% confidence interval [CI], -0.19, 0.30), P = .66. The T-score (mean number of ≥grade 3 acute adverse events) was 4.35 (standard deviation 2.48) in the cisplatin arm and 3.82 (standard deviation 1.8) in the cetuximab arm, P = .108. The 3-year failure-free survival rates were 93% (95% CI, 86%-97%) in the cisplatin arm and 80% (95% CI, 70%-87%) in the cetuximab arm (hazard ratio = 3.0 [95% CI, 1.2-7.7]); P = .015., Conclusions: For patients with low-risk HPV-associated oropharyngeal cancer, radiation therapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared with radiation therapy and weekly cisplatin. Radiation therapy and cisplatin remain the standard of care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Substituted fluorene structures have demonstrated unusual photochemical properties. Previous reports on the substituted fluorene Schiff base FR0 -SB demonstrated super photobase behavior with a Δp K b of ∼14 upon photoexcitation. In an effort to understand the basis for this unusual behavior, we have examined the electronic structure and relaxation dynamics of the structural precursor of FR0 -SB, the aldehyde FR0 , in protic and aprotic solvents using time-resolved fluorescence spectroscopy and quantum chemical calculations. The calculations show three excited singlet states in relatively close energetic proximity. The spectroscopic data are consistent with relaxation dynamics from these electronic states that depend on the presence and concentration of solvent hydroxyl functionality. These results underscore the central role of solvent hydrogen bonding to the FR0 aldehyde oxygen in mediating the relaxation dynamics within this molecule.

Background: Limited English proficiency (LEP) is associated with decreased access to healthcare. We hypothesized that LEP children with appendicitis would experience more delays in care than EP children., Methods: Retrospective review of patients <18 y presenting to a tertiary pediatric hospital July 2014-July 2019 with appendicitis. LEP patients were compared to EP patients. The primary outcome was appendiceal perforation. Secondary outcomes included prior pediatrician or emergency department (ED) visits without definitive management, duration of symptoms, length of stay (LOS), initial operative or non-operative management, time from presentation to operation and return to the ED within 30 d. Multivariable regression was performed to evaluate LEP as a predictor of study outcomes., Results: A total of 893 patients with appendicitis were identified, 15.6% (n = 140) had LEP. On multivariate regression LEP was not a significant predictor of appendiceal perforation (AOR 1.20, 95% CI 0.79, 1.80, P = 0.390). LEP was a significant predictor of a prior ED or pediatrician visit without definitive management (AOR 2.05, 95 % CI 1.05, 3.98, P= 0.034) and longer LOS (Coefficient 1.01, 95% CI 0.41, 1.61, P= 0.001). LEP was associated with a minimal increase in duration of pain prior to presentation that was not clinically significant and was not associated with initial operative or non-operative management or a significantly longer time between presentation and operation., Conclusions: LEP children did not experience higher rates of appendiceal perforation at our institution, but were more frequently initially evaluated by a pediatrician or at an ED and discharged without definitive management and had longer LOS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Inc.)

Background: Myelomeningocele (MMC) is the congenital failure of neural tube closure in utero, for which the standard of care is prenatal surgical repair. We developed clinical-grade placental mesenchymal stromal cells seeded on a dural extracellular matrix (PMSC-ECM), which have been shown to improve motor outcomes in preclinical ovine models. To evaluate the long-term safety of this product prior to use in a clinical trial, we conducted safety testing in a murine model., Methods: Clinical grade PMSCs obtained from donor human placentas were seeded onto a 6 mm diameter ECM at a density of 3 × 10 5 cells/cm 2 . Immunodeficient mice were randomized to receive either an ECM only or PMSC-ECM administered into a subcutaneous pocket. Mice were monitored for tumor formation until two study endpoints: 4 wk and 6 mo. Pathology and histology on all tissues was performed to evaluate for tumors. Quantitative polymerase chain reaction (qPCR) was performed to evaluate for the presence of human DNA, which would indicate persistence of PMSCs., Results: Fifty-four mice were included; 13 received ECM only and 14 received PMSC-ECM in both the 4-wk and 6-mo groups. No mice had gross or microscopic evidence of tumor development. A nodular focus of mature fibrous connective tissue was identified at the subcutaneous implantation pocket in the majority of mice with no significant difference between ECM only and PMSC-ECM groups (P = 0.32 at 4 wk, P > 0.99 at 6 mo). Additionally, no human DNA was detected by qPCR in any mice at either time point., Conclusions: Subcutaneous implantation of the PMSC-ECM product did not result in tumor formation and we found no evidence that PMSCs persisted. These results support the safety of the PMSC-ECM product for use in a Phase 1/2a human clinical trial evaluating fetal MMC repair augmented with PMSC-ECM., (Copyright © 2021. Published by Elsevier Inc.)

Aim: To describe the causes and computed tomography (CT) and angiographic appearances of transpleural systemic artery-to-pulmonary artery shunts in patients without chronic inflammatory lung disease and determine their best management., Materials and Methods: All patients referred to a tertiary referral unit between January 2009 and January 2020 in whom a diagnosis of a systemic-to-pulmonary artery communication without underlying chronic inflammatory lung disease was subsequently made have been included in this report. Medical records and imaging findings were reviewed retrospectively., Results: Ten patients (male: female ratio = 7:3; median age 42 years [range 22-70 years]) with systemic artery-to-pulmonary artery shunts without chronic inflammatory lung disease were identified. Five were misdiagnosed as having a pulmonary arteriovenous malformation and had been referred for embolisation. In six patients, there was either a history of accidental or iatrogenic thoracic trauma or of inflammatory disease involving the pleura, and in two patients, in whom a previous medical history could not be obtained, there were CT features suggesting previous pleural inflammatory disease. Two shunts were thought to be congenital. All individuals were asymptomatic other than one with localised thoracic discomfort that dated from the time of surgery. All patients were managed conservatively and have remained well with a median follow-up of 4.5 years (range 1-11.3 years)., Conclusions: Localised transpleural systemic artery-to-pulmonary artery shunts in the absence of chronic inflammatory lung disease are usually related to previous thoracic trauma/intervention or abdominal or pulmonary sepsis involving a pleural or diaphragmatic surface. Congenital shunts are rare. The present study and much of the literature supports conservative management., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Pediatric patients immobilized for certain procedures, such as extracorporeal membrane oxygenation (ECMO), are at high risk for developing hospital-acquired pressure injuries (HAPIs)., Purpose: To evaluate the rate of HAPI occurrence in ECMO patients before and after implementation of prevention interventions., Methods: Patients younger than 18 years of age who were placed on ECMO from January 2012 through March 2020 were identified, and patient data, including the development of a stage 3, 4, or unstageable pressure injuries, were abstracted. From August 2018 through December 2018, HAPI prevention interventions were implemented, which included targeted HAPI prevention and ECMO provider education, fluidized positioner provider education, and the addition of 2 wound care interventions for ECMO patients., Results: Of the 120 ECMO patients identified, 5 (4.2%) developed a HAPI. All patients developed HAPI in the occipital region, and 1 patient developed an additional HAPI on their back. The median age of patients with HAPI was 1 month (interquartile range [IQR], 0.3-6.8 months). The median duration from ECMO cannulation to identification of HAPI was 9.5 days (IQR, 4.8-32.3 days). The median total run time was 4.9 days (IQR, 2.5-7.6 days): 8.5 days for patients who did develop a HAPI and 4.8 days for those who did not develop a HAPI (P = .02). The overall HAPI rate dropped from 4.8% of ECMO patients before quality improvement interventions to 0% of ECMO patients after quality improvement interventions., Conclusions: The development of stage 3, 4, or unstageable HAPIs in pediatric ECMO patients was low (4.2%) over the period studied (January 2012 through March 2020). As of the time of this writing, no HAPIs occurred after implementation of provider education in 2018.

Introduction: Translational models of myelomeningocele (MMC) are needed to test novel in utero interventions. An ideal animal model for MMC has locomotor function at birth and is low cost enough to allow for high throughput. The rat MMC model is limited by immature locomotor function at birth. The ovine MMC model is a costly surgical model. Guinea pigs are uniquely suited for an MMC model being a small animal model with locomotor function at birth. We aimed to develop a retinoic acid (RA) model of MMC in the guinea pig and to evaluate if pregnant guinea pigs could tolerate uterine manipulation., Methods: Time-mated Dunkin Hartley guinea pig dams were dosed with 60 mg/kg of RA between gestation age (GA) 12 and 15 days in the development of an RA model. Fetuses were grossly evaluated for MMC lesions at Cesarean section after GA 31 days. Evaluation of the ability of pregnant guinea pig dams to tolerate uterine surgical intervention was performed by hysterotomy of a separated group of time-mated guinea pigs at GA 45, 50, and 55., Results: Forty-two pregnant guinea pigs were dosed with RA, with a total of 189 fetuses. The fetal demise rate was 38% ( n = 71). A total of 118 fetuses were viable, 83% ( n = 98) were normal fetuses, 8% ( n = 10) had a neural tube defect, and 8% ( n = 10) had a hematoma or other anomalies. No fetuses developed an MMC defect. None of the fetuses that underwent hysterotomy survived to term., Conclusion: RA dosed at 60 mg/kg in guinea pigs between GA 12 and 15 did not result in MMC. Dunkin Hartley guinea pigs did not tolerate a hysterotomy near term in our surgical model. Further work is needed to determine if MMC can be induced in guinea pigs with alternate RA dosing., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Sarah C. Stokes et al.)

Responding to identified needs for increased veterans' access to healthcare, in 2010 the United States Department of Veterans Affairs (VA) launched the Veteran Community Partnership (VCP) initiative to "foster seamless access to, and transitions among, the full continuum of non-institutional extended care and support services in VA and the community". This initiative represents an important effort by VA to promote collaboration with a broad range of community organizations as equal partners in the service of veteran needs. The purpose of the study is an initial assessment of the VCP program. Focus group interviews conducted in six sites in 2015 included 53 representatives of the local VA and community organizations involved with rural and urban VCPs across the US. Interview topics included the experiences and practices of VCP members, perceived benefits and challenges, and the characteristics and dynamics of rural and urban areas served by VCPs. Using a community-oriented conceptual framework, the analyses address VCP processes and preliminary outcomes, including VCP goals and activities, and VCP members' perceptions of their efforts, benefits, challenges, and achievements. The results indicate largely positive perceptions of the VCP initiative and its early outcomes by both community and VA participants. Benefits and challenges vary by rural-urban community context and include resource limitations and the potential for VA dominance of other VCP partners. Although all VCPs identified significant benefits and challenges, time and resource constraints and local organizational dynamics varied by rural and urban context. Significant investments in VCPs will be required to increase their impacts.

Ultrafast tunnel ionization enables femtosecond time-resolved dynamic measurements of the retro-Diels-Alder reactions of positively charged cyclohexene, norbornene, and dicyclopentadiene. Unlike the reaction times of 500-600 ps that are observed following UV excitation of neutral species, on the ionic potential energy surfaces, these reactions occur on a single picosecond timescale and, in some cases, exhibit vibrational coherence. In the case of norbornene, a 270 cm -1 vibrational mode is found to modulate the retro-Diels-Alder reaction.

The rail industry, as with all sectors worldwide, has faced disruptions due to the global COVID-19 pandemic. This commentary considers how rail organizations in Australia have engaged within the early stages of the crisis, outlining the challenges faced and how they were addressed. Relying on our observations, and anecdotes obtained from others across the Australian rail industry, we identified a range of impacts including determining service delivery levels (and the associated running of "ghost trains"), implementing hygiene measures and social distancing, managing training and medical assessments, and changes in the behavior of passengers and members of the public (including aggression toward staff and increased instances of trespass). Within rail organizations, we saw changes to communication and control structures, new challenges related to balancing priorities (managing risk of rail accidents vs. virus transmission risk), and negative impacts on job design offset by increased informal support for frontline workers. Importantly, from the crisis, we gained new insights about culture. Finally, we provide recommendations regarding how the Human Factors and Ergonomics discipline can support safe and effective rail operations in the context of both widespread crises such as pandemics as well as the less dramatic, but ever present, shifts in the physical, social, economic, and political environments in which rail organizations operate., (© 2021 The Authors. Human Factors and Ergonomics in Manufacturing & Service Industries published by Wiley Periodicals LLC.)

Current recommendations state that women should breastfeed their child up to 2 years and beyond. However, the UK has one of the lowest breastfeeding rates in the world. This could in part be explained by the stigma mothers face when breastfeeding an older child. This research aims to provide a detailed understanding of what motivates women to continue breastfeeding beyond infancy and the barriers they face to (i) add to existing research literature which has examined this area and (ii) support and normalize this practice. Semi-structured interviews were conducted between April and June 2018 with 24 women who had breastfed at least one child past 12 months. A theory-driven thematic analysis identified themes that ran through the interviews centering on the benefits of continued breastfeeding, the stigma mothers faced when breastfeeding past infancy and the challenges of returning to work. The women felt that continued breastfeeding enabled them to play a central role in their child's health and develop an attachment led parental style but faced social and cultural stigma due to a lack of public awareness of current breastfeeding recommendations. Interventions which raise awareness of breastfeeding beyond infancy are needed to normalize this practice in the UK.

Background: Recent work has demonstrated that an accelerated pathway for pediatric patients with blunt solid organ injuries is safe; however, this is not well-studied in a dual trauma center. We hypothesized that implementation of an accelerated pathway would decrease length of stay (LOS) and hospitalization cost without increased mortality., Methods: Retrospective review of patients < 15 years presenting to a dual level 1 trauma center between 2015 and 2020 with traumatic blunt liver and splenic injuries. Patients presenting pre- and post-protocol implementation were compared. The primary outcome was total hospital LOS. Secondary outcomes were number of lab draws, intensive care unit (ICU) LOS, cost of hospitalization, readmissions within 30 days, and mortality., Results: 103 patients were evaluated, 67 pre-protocol and 63 post-protocol. LOS was significantly shorter post-protocol (2 days vs. 4 days, p < 0.001). The ICU LOS was unchanged. There was a decrease in direct hospitalization cost per patient from $6,246 pre-protocol to $4,294 post-protocol (p = 0.001). There was one readmission post-protocol and none pre-protocol. There were no deaths., Conclusion: Implementation of an accelerated pathway for management of blunt solid organ injury at a dual trauma center was associated with decreased LOS and decreased costs with no increased morbidity or mortality.

Background: Despite advances to prevent and detect cervical cancer, national targets for screening have not been met in the United States. Previous studies suggested that approximately half of women who developed cervical cancer were not adequately screened. This study aimed to provide an updated examination of women's screening and diagnostic practices five years prior to an invasive cervical cancer diagnosis., Methods: The study included women age 21 years and older diagnosed with invasive cervical cancer in 2013-2016 from three population-based state cancer registries in the United States. Medical records abstraction identified screening history and diagnostic follow-up. A mailed survey provided sociodemographic data. Screening was a Pap or human papillomavirus (HPV) test between 6 months and 5 years before diagnosis. Adequate follow-up was defined per management guidelines., Results: Of the 376 women, 60% (n = 228) had not been screened. Among women who received an abnormal screening result (n = 122), 67% (n = 82) had adequate follow-up. Predictors of: (a) being screened were younger age, having a higher income, and having insurance; (b) adequate follow-up were having a higher income, and (c) stage 1 cervical cancer were being screened and younger age., Conclusion: Unlike other cancer patterns of care studies, this study uses data obtained from medical records supplemented with self-report information to understand a woman's path to diagnosis, her follow-up care, and the stage of her cervical cancer diagnosis. This study provides findings that could be used to reach more unscreened or under screened women and to continue lowering cervical cancer incidence in the United States., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Purpose: Prescription drug monitoring programs (PDMPs) have been established to combat the opioid epidemic, but there is no data on their efficacy in children. We hypothesized that a statewide PDMP mandate would be associated with fewer opioid prescriptions in pediatric surgical patients., Methods: Patients < 18 undergoing inguinal hernia repair, orchiopexy, orchiectomy, appendectomy, or cholecystectomy at a tertiary children's hospital were included. The primary outcome, discharge opioid prescription, was compared for 10 months pre-PDMP (n = 158) to 10 months post-PDMP (n = 228). Interrupted time series analysis was performed to determine the effect of the PDMP on opioid prescribing., Results: Over the 20-month study period, there was an overall decrease in the rate of opioid prescriptions per month (- 3.6% change, p < 0.001). On interrupted time series analysis, PDMP implementation was not associated with a significant decrease in the monthly rate of opioid prescriptions (1.27% change post-PDMP, p = 0.4). However, PDMP implementation was associated with a reduction in opioid prescriptions of greater than 5 days' supply (- 2.7% per month, p = 0.03)., Conclusion: Opioid prescriptions declined in pediatric surgical patients over the study time period. State-wide PDMP implementation was associated with a reduction in postoperative opioid prescriptions of more than 5 days' duration.

Background: Screening and timely follow-up have lowered cervical cancer incidence in the US; however, screening coverage, incidence, and death rates have remained fairly stable in recent years. Studies suggest that half of women diagnosed with cervical cancer don't receive appropriate screening prior to diagnosis; cervical cancer survivors can provide crucial insight into barriers and facilitators to screening., Methods: Participants were cervical cancer survivors ≥21 years, identified through population-based central cancer registries (CR) in 3 US states or a social network (SN), Cervivor. CR participants completed a mailed survey on screening history, barriers, and facilitators to screening and sociodemographic data. SN participants completed the same survey online., Results: CR participants (N = 480) were older, with a lower proportion of non-Hispanic white, married, and insured women compared to SN participants (N = 148). Fifty percent of CR and 79% of SN participants were screened 5 years prior to their diagnoses. Of those screened, 28% in both groups reported not following-up on abnormal results. For both groups, the most frequently identified screening barrier was that participants never imagined they would develop cervical cancer (percent agree CR = 76%; SN = 86%), and the facilitator was wanting to take care of their bodies (CR = 95%; SN = 94%)., Conclusion: Addressing key barriers to obtaining screening and timely follow-up related to lack of knowledge of cervical cancer risk and screening tests and addressing insurance coverage in the design or modification of interventions may increase cervical cancer screening and lower cervical cancer incidence in the US.