Clade-specific forebrain cytoarchitectures of the extinct Tasmanian tiger.

The thylacine, or Tasmanian tiger, is the largest of modern-day carnivorous marsupials and was hunted to extinction by European settlers in Australia. Its physical resemblance to eutherian wolves is a striking example of evolutionary convergence to similar ecological niches. However, whether the neuroanatomical organization of the thylacine brain resembles that of canids and how it compares with other mammals remain unknown due to the scarcity of available samples. Here, we gained access to a century-old hematoxylin-stained histological series of a thylacine brain, digitalized it at high resolution, and compared its forebrain cellular architecture with 34 extant species of monotremes, marsupials, and eutherians. Phylogenetically informed comparisons of cortical folding, regional volumes, and cell sizes and densities across cortical areas and layers provide evidence against brain convergences with canids, instead demonstrating features typical of marsupials, and more specifically Dasyuridae, along with traits that scale similarly with brain size across mammals. Enlarged olfactory, limbic, and neocortical areas suggest a small-prey predator and/or scavenging lifestyle, similar to extant quolls and Tasmanian devils. These findings are consistent with a nonuniformity of trait convergences, with brain traits clustering more with phylogeny and head/body traits with lifestyle. By making this resource publicly available as rapid web-accessible, hierarchically organized, multiresolution images for perpetuity, we anticipate that additional comparative insights might arise from detailed studies of the thylacine brain and encourage researchers and curators to share, annotate, and preserve understudied material of outstanding biological relevance.

Differential timing of a conserved transcriptional network underlies divergent cortical projection routes across mammalian brain evolution.

A unique combination of transcription factor expression and projection neuron identity demarcates each layer of the cerebral cortex. During mouse and human cortical development, the transcription factor CTIP2 specifies neurons that project subcerebrally, while SATB2 specifies neuronal projections via the corpus callosum, a large axon tract connecting the two neocortical hemispheres that emerged exclusively in eutherian mammals. Marsupials comprise the sister taxon of eutherians but do not have a corpus callosum; their intercortical commissural neurons instead project via the anterior commissure, similar to egg-laying monotreme mammals. It remains unknown whether divergent transcriptional networks underlie these cortical wiring differences. Here, we combine birth-dating analysis, retrograde tracing, gene overexpression and knockdown, and axonal quantification to compare the functions of CTIP2 and SATB2 in neocortical development, between the eutherian mouse and the marsupial fat-tailed dunnart. We demonstrate a striking degree of structural and functional homology, whereby CTIP2 or SATB2 of either species is sufficient to promote a subcerebral or commissural fate, respectively. Remarkably, we reveal a substantial delay in the onset of developmental SATB2 expression in mice as compared to the equivalent stage in dunnarts, with premature SATB2 overexpression in mice to match that of dunnarts resulting in a marsupial-like projection fate via the anterior commissure. Our results suggest that small alterations in the timing of regulatory gene expression may underlie interspecies differences in neuronal projection fate specification.

Open science, communal culture, and women's participation in the movement to improve science.

Science is undergoing rapid change with the movement to improve science focused largely on reproducibility/replicability and open science practices. This moment of change-in which science turns inward to examine its methods and practices-provides an opportunity to address its historic lack of diversity and noninclusive culture. Through network modeling and semantic analysis, we provide an initial exploration of the structure, cultural frames, and women's participation in the open science and reproducibility literatures (n = 2,926 articles and conference proceedings). Network analyses suggest that the open science and reproducibility literatures are emerging relatively independently of each other, sharing few common papers or authors. We next examine whether the literatures differentially incorporate collaborative, prosocial ideals that are known to engage members of underrepresented groups more than independent, winner-takes-all approaches. We find that open science has a more connected, collaborative structure than does reproducibility. Semantic analyses of paper abstracts reveal that these literatures have adopted different cultural frames: open science includes more explicitly communal and prosocial language than does reproducibility. Finally, consistent with literature suggesting the diversity benefits of communal and prosocial purposes, we find that women publish more frequently in high-status author positions (first or last) within open science (vs. reproducibility). Furthermore, this finding is further patterned by team size and time. Women are more represented in larger teams within reproducibility, and women's participation is increasing in open science over time and decreasing in reproducibility. We conclude with actionable suggestions for cultivating a more prosocial and diverse culture of science.

Interobserver Agreement of Inferior Vena Cava Ultrasound Collapse Duration and Correlated Outcomes in Children With Dehydration.

OBJECTIVE: Dehydration is a common concern in children presenting to pediatric emergency departments and other acute care settings. Ultrasound (US) of the inferior vena cava (IVC) may be a fast, noninvasive tool to gauge volume status, but its utility is unclear. Our objectives were to determine the interobserver agreement of IVC collapse and collapse duration, then correlate IVC collapse with the outcome of intravenous (IV) versus oral (PO) rehydration. METHODS: We conducted a prospective study by enrolling patients 0 to 21 years old with emesis requiring ondansetron or diarrhea requiring IV hydration. Clinical operators interpreted US examinations in real time to determine whether the IVC was collapsed. Two blinded reviewers interpreted the US videos to determine IVC collapse and collapse duration. Cohen's kappa(κ) was calculated for reviewer-reviewer and reviewer-operator agreement. Primary outcomes were PO versus IV rehydration, and admitted versus discharged. RESULTS: One hundred twelve patients were enrolled, and 102 had complete data for analysis. The mean age was 7.2 years with 51% female. Twenty-nine patients received IV hydration. The reviewer-operator agreement for IVC collapse was κ = 0.57 (95% confidence interval [CI], 0.38-0.75) and interreviewer agreement was κ = 0.93 (95% CI, 0.83-1.0). The interreviewer agreement for collapse duration was κ = 0.66 (95% CI, 0.51-0.82). All patients with noncollapsed IVCs tolerated PO hydration. The likelihood of receiving IV hydration was correlated with the duration of IVC collapse (P = 0.034). CONCLUSIONS: Based on a novel dynamic measure of IVC collapse duration, children with increasing duration of IVC collapse correlated positively with the need for IV rehydration. Noncollapsing IVCs on US were associated with successful PO rehydration without need for IV fluids or emergency department revisits.

Racial and ethnic disparities in common inpatient safety outcomes in a children's hospital cohort.

BACKGROUND: Emerging evidence has shown racial and ethnic disparities in rates of harm for hospitalised children. Previous work has also demonstrated how highly heterogeneous approaches to collection of race and ethnicity data pose challenges to population-level analyses. This work aims to both create an approach to aggregating safety data from multiple hospitals by race and ethnicity and apply the approach to the examination of potential disparities in high-frequency harm conditions. METHODS: In this cross-sectional, multicentre study, a cohort of hospitals from the Solutions for Patient Safety network with varying race and ethnicity data collection systems submitted validated central line-associated bloodstream infection (CLABSI) and unplanned extubation (UE) data stratified by patient race and ethnicity categories. Data were submitted using a crosswalk created by the study team that reconciled varying approaches to race and ethnicity data collection by participating hospitals. Harm rates for race and ethnicity categories were compared with reference values reflective of the cohort and broader children's hospital population. RESULTS: Racial and ethnic disparities were identified in both harm types. Multiracial Hispanic, Combined Hispanic and Native Hawaiian or other Pacific Islander patients had CLABSI rates of 2.6-3.6 SD above reference values. For Black or African American patients, UE rates were 3.2-4.4 SD higher. Rates of both events in White patients were significantly lower than reference values. CONCLUSIONS: The combination of harm data across hospitals with varying race and ethnicity collection systems was accomplished through iterative development of a race and ethnicity category framework. We identified racial and ethnic disparities in CLABSI and UE that can be addressed in future improvement work by identifying and modifying care delivery factors that contribute to safety disparities.

A Closer Look: Examination of Suicide Risk Screening Results and Outcomes for Minoritized Youth in Subspecialty Pediatrics.

OBJECTIVE: To describe a sample of minoritized youth who screened positive for suicide risk within medical subspecialty pediatrics, compared to non-minoritized youth and describe the screening outcomes of these youth. METHODS: This retrospective chart review from October 2018 to April 2021 used electronic medical record data from an academic pediatric medical subspecialty clinic that screens universally for suicide risk for all patients ages 9 and up. Chart reviews were conducted for 237 minoritized youth (operationalized as identifying as non-White or Hispanic/Latinx, identifying as a gender minority, and having a preferred language other than English) who screened positive for suicide risk. Descriptive statistics include need for escalation to an emergency room, connection to mental health care, receival of a mental health referral, and attendance at follow-up visits. RESULTS: Minoritized youth were more likely to screen positive and report a history of suicide attempt when compared to non-minoritized peers. Youth identifying as gender expansive had significant elevation in suicide risk. The majority of youth in this sample were already connected to mental health care, with youth preferring a language other than English being the least likely to be connected. CONCLUSIONS: Findings indicate heightened suicide risk for minoritized youth, with gender expansive youth having particularly elevated suicide risk. A need to support youth with a preferred language other than English in getting connected to mental health care was also revealed.

Non-uniform temporal scaling of developmental processes in the mammalian cortex.

The time that it takes the brain to develop is highly variable across animals. Although staging systems equate major developmental milestones between mammalian species, it remains unclear how distinct processes of cortical development scale within these timeframes. Here, we compare the timing of cortical development in two mammals of similar size but different developmental pace: eutherian mice and marsupial fat-tailed dunnarts. Our results reveal that the temporal relationship between cell birth and laminar specification aligns to equivalent stages between these species, but that migration and axon extension do not scale uniformly according to the developmental stages, and are relatively more advanced in dunnarts. We identify a lack of basal intermediate progenitor cells in dunnarts that likely contributes in part to this timing difference. These findings demonstrate temporal limitations and differential plasticity of cortical developmental processes between similarly sized Therians and provide insight into subtle temporal changes that may have contributed to the early diversification of the mammalian brain.

Omphalitis and Concurrent Serious Bacterial Infection.

OBJECTIVE: Describe the clinical presentation, prevalence of concurrent serious bacterial infection (SBI), and outcomes among infants with omphalitis. METHODS: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants ≤90 days of age with omphalitis seen in the emergency department from January 1, 2008, to December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized. RESULTS: Among 566 infants (median age 16 days), 537 (95%) were well-appearing, 64 (11%) had fever at home or in the emergency department, and 143 (25%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 472 (83%), 326 (58%), and 222 (39%) infants, respectively. Pathogens grew in 1.1% (95% confidence interval [CI], 0.3%-2.5%) of blood, 0.9% (95% CI, 0.2%-2.7%) of urine, and 0.9% (95% CI, 0.1%-3.2%) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 320 (57%) infants, with 85% (95% CI, 80%-88%) growing a pathogen, most commonly methicillin-sensitive Staphylococcus aureus (62%), followed by methicillin-resistant Staphylococcus aureus (11%) and Escherichia coli (10%). Four hundred ninety-eight (88%) were hospitalized, 81 (16%) to an ICU. Twelve (2.1% [95% CI, 1.1%-3.7%]) had sepsis or shock, and 2 (0.4% [95% CI, 0.0%-1.3%]) had severe cellulitis or necrotizing soft tissue infection. There was 1 death. Serious complications occurred only in infants aged <28 days. CONCLUSIONS: In this multicenter cohort, mild, localized disease was typical of omphalitis. SBI and adverse outcomes were uncommon. Depending on age, routine testing for SBI is likely unnecessary in most afebrile, well-appearing infants with omphalitis.

Psychological Science in the Wake of COVID-19: Social, Methodological, and Metascientific Considerations.

The COVID-19 pandemic has extensively changed the state of psychological science from what research questions psychologists can ask to which methodologies psychologists can use to investigate them. In this article, we offer a perspective on how to optimize new research in the pandemic's wake. Because this pandemic is inherently a social phenomenon-an event that hinges on human-to-human contact-we focus on socially relevant subfields of psychology. We highlight specific psychological phenomena that have likely shifted as a result of the pandemic and discuss theoretical, methodological, and practical considerations of conducting research on these phenomena. After this discussion, we evaluate metascientific issues that have been amplified by the pandemic. We aim to demonstrate how theoretically grounded views on the COVID-19 pandemic can help make psychological science stronger-not weaker-in its wake.

Estimating the clinical impact of bringing a multimarker cardiac panel to the bedside in the ED.

OBJECTIVES: We examined the use of point-of-care (POC) testing of cardiac biomarkers against standard core laboratory testing to determine the time-savings and estimate a cost-benefit ratio at our institution. METHODS: We prospectively enrolled 151 patients presenting to the emergency department undergoing evaluation for acute coronary syndrome and conducted both central laboratory troponin T (TnT) testing at baseline and 6 hours as well as POC assays of creatine kinase MB, troponin I (TnI), and myoglobin at baseline and 2 hours. Sensitivity/specificity was calculated to measure the ability of the POC-accelerated pathway to identify enzyme elevations at rates parallel to our core laboratory. The time-savings were calculated as the difference between the median of the current protocol and the accelerated POC pathway. RESULTS: Troponin T tests were elevated in 12 patients, which were all detected by the accelerated pathway yielding a relative sensitivity of 100%. Time-saving between the accelerated pathway and core laboratory showed a saving of 390 minutes (6.5 hours). The accelerated POC pathway would have benefited 60% (95% confidence interval [CI], 52%-68%) of our patients with an estimated cost of $7.40 (95% CI, $6.40-$8.70) per direct patient care hour saved. CONCLUSION: Our data suggest that the use of an accelerated cardiac POC pathway could have dramatically impacted the care provided to a large percentage of our patients at a minimal cost per direct patient care hour saved.

Prediction of Resuscitation for Pediatric Sepsis from Data Available at Triage.

Pediatric sepsis imposes a significant burden of morbidity and mortality among children. While the speedy application of existing supportive care measures can substantially improve outcomes, further improvements in delivering that care require tools that go beyond recognizing sepsis and towards predicting its development. Machine learning techniques have great potential as predictive tools, but their application to pediatric sepsis has been stymied by several factors, particularly the relative rarity of its occurrence. We propose an alternate approach which focuses on predicting the provision of resuscitative care, rather than sepsis diagnoses or criteria themselves. Using three years of Emergency Department data from a large academic medical center, we developed a boosted tree model that predicts resuscitation within 6 hours of triage, and significantly outperforms existing rule-based sepsis alerts.

Virtual Urgent Care Quality and Safety in the Time of Coronavirus.

BACKGROUND: Telemedicine use rapidly increased during the COVID-19 pandemic. This study assessed quality aspects of rapid expansion of a virtual urgent care (VUC) telehealth system and the effects of a secondary telephonic screening initiative during the pandemic. METHODS: A retrospective cohort analysis was performed in a single health care network of VUC patients from March 1, 2020, through April 20, 2020. Researchers abstracted demographic data, comorbidities, VUC return visits, emergency department (ED) referrals and ED visits, dispositions, intubations, and deaths. The team also reviewed incomplete visits. For comparison, the study evaluated outcomes of non-admission dispositions from the ED: return visits with and without admission and deaths. We separately analyzed the effects of enhanced callback system targeting higher-risk patients with COVID-like illness during the last two weeks of the study period. RESULTS: A total of 18,278 unique adult patients completed 22,413 VUC visits. Separately, 718 patient-scheduled visits were incomplete; the majority were no-shows. The study found that 50.9% of all patients and 74.1% of patients aged 60 years or older had comorbidities. Of VUC visits, 6.8% had a subsequent VUC encounter within 72 hours; 1.8% had a subsequent ED visit. Of patients with enhanced follow-up, 4.3% were referred for ED evaluation. Mortality was 0.20% overall; 0.21% initially and 0.16% with enhanced follow-up (p = 0.59). Males and black patients were significantly overrepresented in decedents. CONCLUSION: Appropriately deployed VUC services can provide a pragmatic strategy to care for large numbers of patients. Ongoing surveillance of operational, technical, and clinical factors is critical for patient quality and safety with this modality.

Neonatal Mastitis and Concurrent Serious Bacterial Infection.

OBJECTIVES: Describe the clinical presentation, prevalence, and outcomes of concurrent serious bacterial infection (SBI) among infants with mastitis. METHODS: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants aged ≤90 days with mastitis who were seen in the emergency department between January 1, 2008, and December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized. RESULTS: Among 657 infants (median age 21 days), 641 (98%) were well appearing, 138 (21%) had history of fever at home or in the emergency department, and 63 (10%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 581 (88%), 274 (42%), and 216 (33%) infants, respectively. Pathogens grew in 0.3% (95% confidence interval [CI] 0.04-1.2) of blood, 1.1% (95% CI 0.2-3.2) of urine, and 0.4% (95% CI 0.01-2.5) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 335 (51%) infants, with 77% (95% CI 72-81) growing a pathogen, most commonly methicillin-resistant Staphylococcus aureus (54%), followed by methicillin-susceptible S aureus (29%), and unspecified S aureus (8%). A total of 591 (90%) infants were admitted to the hospital, with 22 (3.7%) admitted to an ICU. Overall, 10 (1.5% [95% CI 0.7-2.8]) had sepsis or shock, and 2 (0.3% [95% CI 0.04-1.1]) had severe cellulitis or necrotizing soft tissue infection. None received vasopressors or endotracheal intubation. There were no deaths. CONCLUSIONS: In this multicenter cohort, mild localized disease was typical of neonatal mastitis. SBI and adverse outcomes were rare. Evaluation for SBI is likely unnecessary in most afebrile, well-appearing infants with mastitis.

Optimizing emergency management to reduce morbidity and mortality in pediatric burn patients.

Burns are a significant cause of injury-induced morbidity and mortality in pediatric patients. The spectrum of management for pediatric burn victims is vast and relies heavily on both the classification of the burn and the body systems involved. The immediate focus of management includes resuscitation and stabilization, fluid management, and pain control. Additional focus includes decreasing the risk of infection as well as improving healing and cosmetic outcomes. Discharge care and appropriate follow-up instructions need to be communicated carefully in order to avoid long-standing complications. This supplement reviews methods for accurate classification and management of the full range of burns seen in pediatric patients.

Evaluation and management of pediatric patients with penetrating trauma to the torso.

Children with penetrating trauma to the torso require careful evaluation of the chest, abdomen, pelvis, and genital structures for system-specific injuries that may contribute to rapid decompensation and influence the order of emergent resuscitation. Care of the injured child and the effect on clinical outcomes starts in the prehospital setting, with hemorrhage control and IV fluid resuscitation. The evaluation and disposition of the patient in the ED will depend on the mechanism of injury and the severity of trauma. This issue reviews the diagnostic evaluation and management of pediatric patients with penetrating injuries to the torso.

Points & Pearls: Evaluation and management of pediatric patients with penetrating trauma to the torso

Children with penetrating trauma to the torso require careful evaluation of the chest, abdomen, pelvis, and genital structures for system-specific injuries that may contribute to rapid decompensation and influence the order of emergent resuscitation. Care of the injured child and the effect on clinical outcomes starts in the prehospital setting, with hemorrhage control and IV fluid resuscitation. The evaluation and disposition of the patient in the ED will depend on the mechanism of injury and the severity of trauma. This issue reviews the diagnostic evaluation and management of pediatric patients with penetrating injuries to the torso. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice.]

Whole family-based physical activity promotion intervention: the Families Reporting Every Step to Health pilot randomised controlled trial protocol.

INTRODUCTION: Family-based physical activity (PA) interventions present a promising avenue to promote children's activity; however, high-quality experimental research is lacking. This paper describes the protocol for the FRESH (Families Reporting Every Step to Health) pilot trial, a child-led family-based PA intervention delivered online. METHODS AND ANALYSIS: FRESH is a three-armed, parallel-group, randomised controlled pilot trial using a 1:1:1 allocation ratio with follow-up assessments at 8 and 52 weeks postbaseline. Families will be eligible if a minimum of one child in school Years 3-6 (aged 7-11 years) and at least one adult responsible for that child are willing to participate. Family members can take part in the intervention irrespective of their participation in the accompanying evaluation and vice versa.Following baseline assessment, families will be randomly allocated to one of three arms: (1) FRESH; (2) pedometer-only or (3) no-intervention control. All family members in the pedometer-only and FRESH arms receive pedometers and generic PA promotion information. FRESH families additionally receive access to the intervention website; allowing participants to select step challenges to 'travel' to target cities around the world, log steps and track progress as they virtually globetrot. Control families will receive no treatment. All family members will be eligible to participate in the evaluation with two follow-ups (8 and 52 weeks). Physical (eg, fitness and blood pressure), psychosocial (eg, social support) and behavioural (eg, objectively measured family PA) measures will be collected at each time point. At 8-week follow-up, a mixed methods process evaluation will be conducted (questionnaires and family focus groups) assessing acceptability of the intervention and evaluation. FRESH families' website engagement will also be explored. ETHICS AND DISSEMINATION: This study received ethical approval from the Ethics Committee for the School of the Humanities and Social Sciences at the University of Cambridge. Findings will be disseminated via peer-reviewed publications, conferences and to participating families. TRIAL REGISTRATION NUMBER: ISRCTN12789422.

Optimizing emergency management to reduce morbidity and mortality in pediatric burn patients.

Burns in patients aged < 14 years are consistently among the top causes of injury-induced mortality in pediatric patients. Pediatric burn victims with large body surface area involvement have a multisystem physiologic response that differs from that of adult patients. The spectrum of management is vast and relies heavily on both the classification of the burn and the anatomy involved. Immediate goals for emergency clinicians include resuscitation and stabilization, fluid management, and pain control. Additional goals include decreasing the risk of infection along with improving healing and cosmetic outcomes. Discharge care and appropriate follow-up instructions need to be carefully constructed in order to avoid long-standing complications. This article reviews methods for accurate classification and management of the full range of burns seen in pediatric patients.

Evaluating outcomes associated with a discharge action plan employing single-dose home use of ondansetron in patients with acute gastroenteritis.

Acute gastroenteritis accounts for 1-2 million annual pediatric emergency department visits in the US. The current literature supports the use of antiemetics, such as ondansetron, in the emergency department, reporting improved oral rehydration, cessation of vomiting, and reduction in the need for intravenous rehydration. However, there remains concern that using these agents may "mask alternative diagnoses" and negatively impact patient care. We present a case series of 29 patients who received a pediatric emergency department discharge action plan which allowed for a dose of ondansetron to be dispensed by the clinician at the time of discharge. Patients were instructed to administer the ondansetron at home for treatment of ongoing nausea and vomiting any time after 6 hours from the time of emergency department discharge. These patients were followed up at 3-5 days following discharge to assess for outcomes. Implications of this discharge action plan and future directions are discussed.