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The inert anaesthetic gas xenon is neuroprotective and is about to begin clinical trials as a treatment for ischaemic brain injury. We have previously shown that xenon inhibits N-methyl-D-aspartate (NMDA) receptors. NMDA receptor antagonism is plausible as a mechanism underlying xenon neuroprotection. Nevertheless, other molecular targets for xenon have been identified, the two-pore-domain potassium channel TREK-1 and the ATP-sensitive potassium channel KATP. Whether any of these putative targets are relevant to acute xenon neuroprotection is not known. We recently showed that xenon inhibits NMDA receptors by competing with the co-agonist glycine at the glycine-binding site. Here we test the hypothesis that inhibition of the NMDA receptor at the glycine site underlies xenon neuroprotection against hypoxia/ischaemia. If this hypothesis is correct, xenon neuroprotection should be attenuated at elevated glycine concentrations. We use an in vitro model of hypoxia/ischaemia using organotypic hippocampal brain-slices from mice, subjected to oxygen-glucose deprivation (OGD). Neuronal injury is quantified by propidiumiodide (PI) fluorescence. PI is a membrane impermeable dye that only enters cells with compromised cell membranes where it binds to DNA and RNA and emits a characteristic red fluorescence. We show that 50% atm xenon is neuroprotective against hypoxia/ischaemia when applied immediately after injury or even after a delay of 3 h after injury. To validate our method, we show that neuroprotection by gavestinel is abolished when glycine is added, confirming that NMDA-receptor glycine-site antagonism underlies gavestinel neuroprotection. We then show that adding glycine abolishes the neuroprotective effect of xenon, consistent with competitive inhibition at the NMDA-receptor glycine-site mediating xenon neuroprotection. Results are shown in Table 6. We have shown that xenon neuroprotection against hypoxia/ischaemia can be reversed by elevating the glycine concentration. This is consistent with competitive inhibition by xenon at the NMDA-receptor glycine-site mediating xenon neuroprotection. Not only does this provide a molecular mechanism (competitive inhibition), but it also, for the first time, clearly identifies the NMDA-receptor as playing a major role in xenon neuroprotection. This finding may have important implications for xenon's clinical use as an anaesthetic and neuroprotectant. [ABSTRACT FROM AUTHOR]

The army ant Eciton burchellii is probably the most important arthropod predator in the Neotropics, and many animal species depend upon it. Sex-biased dispersal with winged males and permanently wingless queens may render this species especially sensitive to habitat fragmentation and natural barriers, which might have severe impacts on population structure and lead to population decline. Using nuclear microsatellite markers and mitochondrial sequences, we investigated genetic differentiation in a fragmented population in the Panama Canal area. While nuclear markers showed little differentiation between subpopulations ( FST = 0.017), mitochondrial differentiation was maximal in some cases ( ΦST = 1). This suggests that, while females are not capable of crossing barriers such as large rivers, flying males are able to promote nuclear gene flow between the studied forest patches. Consistent with this interpretation, we did not find any evidence for inbreeding or genetic deterioration on Barro Colorado Island over the last 90 years since its formation. [ABSTRACT FROM AUTHOR]

Background: Neonatal asphyxia causes long-term neurological and behavioural impairment in the developing brain. Concurrent administration of xenon and hypothermia synergistically reduces long-term damage in a rat model of neonatal asphyxia. This study sought to investigate whether asynchronous administration of xenon and hypothermia is capable of combining synergistically to provide neuroprotection.Methods: Seven-day-old rats were subjected to right common carotid artery occlusion followed by 90 min hypoxia with 8% oxygen. After a 1 h recovery period, rats received asynchronous administration of mild hypothermia (35 degrees C) and xenon (20%) with a 1 or 5 h gap between interventions, xenon (20%) alone, or mild hypothermia (35 degrees C) alone. Infarct volume in the brain was measured 4 days after injury.Results: Administration of hypothermia or xenon alone, 1 and 6 h after the hypoxic ischaemic insult, respectively, provided no neuroprotection. Asynchronous administration of xenon and hypothermia at a 1 h interval produced a significant reduction in infarct volume [93 (7) vs 74 (8); P < 0.05]. Reduction in infarct volume was also present when hypothermia and xenon were asynchronously administered with an intervening gap of 5 h [97 (5) vs 83 (3); P < 0.05].Conclusions: This finding provides a rationale for investigating the combined use of hypothermia and xenon in a progressive manner for the management of neonatal asphyxia. Thus, hypothermia can be administrated at the site of delivery and xenon can be administered later. [ABSTRACT FROM AUTHOR]

The ability of animals to adjust their behaviour according to seasonal changes in their ecology is crucial for their fitness. Eusocial insects display strong collective behavioural seasonality, yet the mechanisms underlying such changes are poorly understood. We show that nest preference by emigrating Temnothorax albipennis ant colonies is influenced by a season-specific modulatory pheromone that may help tune decision-making according to seasonal constraints. The modulatory pheromone triggers aversion towards low-quality nests and enhances colony cohesion in summer and autumn, but not after overwintering—in agreement with reports that field colonies split in spring and reunite in summer. Interestingly, we show that the pheromone acts by downgrading the perceived value of marked nests by informed and naive individuals. This contrasts with theories of collective intelligence, stating that accurate collective decision-making requires independent evaluation of options by individuals. The violation of independence highlighted here was accordingly shown to increase error rate during emigrations. However, this is counterbalanced by enhanced cohesion and the transmission of valuable information through the colony. Our results support recent claims that optimal decisions are not necessarily those that maximize accuracy. Other criteria—such as cohesion or reward rate—may be more relevant in animal decision-making. [ABSTRACT FROM AUTHOR]

Gender-affirming hormone therapy (GAHT) comes with many physical, psychological, and social changes that are often considered in isolation. This research uses a socioecological lens with a sample of 15 Australian transfeminine individuals to investigate the changes experienced during GAHT. Semi-structured interviews were conducted in 2022, with verbatim transcripts analysed using deductive thematic analysis with Bronfenbrenner's Socioecological Model (SEM) as a framework. Analyses revealed two themes intersecting multiple levels of the SEM. Theme 1 contained two sub-themes and broadly encapsulated how interactions with others influenced GAHT experiences. Sub-theme 1 spoke to how stigma creates positive or negative experiences (through the macrosystem, the exosystem, and proximal processes), while sub-theme 2 described how GAHT causes internal changes that promoted stronger interpersonal relationships (person and proximal processes). Theme 2 described how changes occurred over time, with some changes being temporary, and others being delayed (person and time). These themes highlight the interconnected nature of the physical, psychological, and social changes and experiences that can occur during GAHT. Best-practice care for trans people undergoing GAHT needs to be multi-faceted and holistic in order to embed support across different SEM components.

Importance: Intravenous fluids are an essential part of treatment in sepsis, but there remains clinical equipoise on which type of crystalloid fluids to use in sepsis. A previously reported sepsis subphenotype (ie, group D) has demonstrated a substantial mortality benefit from balanced crystalloids compared with normal saline., Objective: To test the hypothesis that targeting balanced crystalloids to patients with group D sepsis through an electronic health record (EHR) alert will reduce 30-day inpatient mortality., Design, Setting, and Participants: The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) trial is a parallel-group, multihospital, single-blind, pragmatic randomized clinical trial to be conducted at 6 hospitals in the Emory Healthcare system. Patients with suspicion of group D infection in whom a clinician initiates an order for normal saline in the emergency department (ED) or intensive care unit (ICU) will be randomized to usual care and intervention arms., Intervention: An EHR alert that appears in the ED and ICUs to nudge clinicians to use balanced crystalloids instead of normal saline., Main Outcomes and Measures: The primary outcome is 30-day inpatient mortality. Secondary outcomes are ICU admission, in-hospital mortality, receipt of vasoactive drugs, receipt of new kidney replacement therapy, and receipt of mechanical ventilation (vasoactive drugs, kidney replacement therapy, and mechanical ventilation are counted if they occur after randomization and within the 30-day study period). Intention-to-treat analysis will be conducted., Discussion: The PRECISE trial may be one of the first precision medicine trials of crystalloid fluids in sepsis. Using routine vital signs (temperature, heart rate, respiratory rate, and blood pressure), available even in low-resource settings, a validated machine learning algorithm will prospectively identify and enroll patients with group D sepsis who may have a substantial mortality reduction from used of balanced crystalloids compared with normal saline., Results: On finalizing participant enrollment and analyzing the data, the study's findings will be shared with the public through publication in a peer-reviewed journal., Conclusions: With use of a validated machine learning algorithm, precision resuscitation in sepsis could fundamentally redefine international standards for intravenous fluid resuscitation., Trial Registration: ClinicalTrials.gov Identifier: NCT06253585.

Gender Affirming Hormone Therapy (GAHT) is a key therapeutic approach which aims to help trans and gender diverse (or simply "trans") individuals' transition from their sex-presumed-at-birth to their experienced gender identity. Previous reviews have focused on synthesizing quantitative experiences; however, a qualitative lens is important to understand the personal journey of GAHT. This review provides a qualitative meta-synthesis of the experiences of trans people around the world who have undergone GAHT to elicit contextualized understanding of the changes experienced. Systematic searches of eight databases identified an initial 2670 papers, refined to a final 28 papers. Overall, findings suggested that the GAHT journey is unique and elicited a myriad of changes which, whilst challenging at times, were life-changing and brought about positive psychological, physical, and social changes. Other themes explored GAHT not being treated as a fix-all for associated mental health issues, the rules that govern appraisal of physical changes, how privilege and social identity evolve, and the power of affirmation. This work offers important recommendations to improve the care offered to trans people undergoing GAHT. Namely, person-centered support is essential, and peer-navigation may be a useful future direction to explore.

Achieving health equity requires creating evidence that reflects the nuance and diversity of experiences among populations disproportionately impacted by age- and race-related disparities. Community-engaged research (CEnR) is one way to pursue equity in research on health and aging to ensure the relevance and translational potential of findings. The current review synthesizes best practices regarding CEnR that promote health equity among older adults, including an overview of CEnR, benefits, and fundamental principles, and three research exemplars from the authors' CEnR. Finally, we discuss these best practices and considerations for advancing CEnR to reduce health disparities experienced by historically underserved older adults and their families. [ Research in Gerontological Nursing, 17 (1), 9-16.].

Background: For many trans folks, gender-affirming hormone therapy (GAHT) is a desired affirming procedure that has been linked with positive health outcomes, however literature has had little focus on the journeys of trans people as they access GAHT., Aim: To understand trans people's journey of accessing GAHT to delineate supports necessary to better engage trans individuals into gender-affirming care., Method: This study conducted semi-structured interviews with a sample of 15 Australian trans adults who participated in a larger study investigating the effects of a cyproterone acetate titration protocol., Findings: A four-factor thematic structure was created from the data. Theme one describes early cognizance of being trans and the pivotal moments in their trans realization. The second theme explores the rapid engagement with community to begin accessing information and affirming healthcare, including GAHT. The third theme explores barriers to engaging in GAHT and theme four reflects on advice participants have for other trans people who are considering GAHT., Conclusion: Findings from this study emphasize the importance of providing support to young trans people to help reconcile their gender identity and assist them to engage into care as early as possible. It also highlights the key role that community plays in providing links to affirming information and providers of GAHT - but also emphasizes the importance of considering how to engage with community who may be missed. The experience of accessing GAHT is personal and contextual, but signaling of affirming safe spaces and access to salient information may be key strategies to better support trans people choosing to access GAHT., Competing Interests: The authors report that are no competing interests to declare., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

While the visible population of trans and gender diverse Australians has grown significantly in recent years, primary health-care access remains hindered by a lack of practitioner competency and stigmatization. This article draws on qualitative research of purposively selected gender-affirming general practitioners (GPs) in Australia to explore barriers, and enablers when treating trans and gender diverse patients. Perspectives and behaviors during the gender-affirming clinical encounter were theoretically informed through minority stress theory, and master narrative frameworks. Reflexive thematic analysis facilitated a rich description of exemplary gender-affirming primary care. A considerable gap exists between structural, clinical, and cultural behaviors among competent gender-affirming GPs in Australia, and the majority of practitioners evidenced in the literature. This critical analysis contributes to better understanding how gender-affirming Australian GPs diffuse minority stress, negotiate cis-normative biases, and foster a person-centered longitudinal therapeutic relationship with their trans and gender diverse patients. An encounter the article argues may also provide an essential buffer for GPs in Australia against the risk of professional burnout. Gender-affirming practice should be taught as a core competency and be required as professional development for GPs in Australia, to ensure a beneficial clinical encounter for the growing trans and gender diverse population.

Introduction: Innovative discovery begins with diverse perspectives; research teams should harness this model. Black, Indigenous, and other People of Color (BIPOC) and women are underrepresented as researchers. Team science leverages collaborative and cross-disciplinary approaches to diversify the research workforce, and introduces academic (and non-academic) faculty with limited research exposure/experience to clinical research., Methods: In 2020, two Black women academic physicians implemented an academic collaborative - COVID-19 Characteristics, Readmissions, Outcomes, and Social Determinants of Health (CROSS) - to investigate COVID-19 health inequities, with intentional recruitment of BIPOC and women. The 37 CROSS team members were of diverse races, ethnicities, sex, specialties, and disciplines, and represented eight hospitals. Team members were electronically surveyed to determine their interest, desired activities, and level of participation in research activities; concurrently, self-identified demographics (including race, ethnicity, sex, and language(s) spoken) were obtained., Results: All team members completed the survey: 78.4% ( n  = 29) were BIPOC and 78.4% ( n  = 29) were women. Team members spoke 18 languages (including English). Academic medical ranks included Assistant Professor (32.4%; n  = 12), Associate Professor (16.2%; n  = 6), and Full Professor (2.7%; n  = 1). Each member identified desired activities (data collection, data analytics, manuscript development, abstract development/poster presentation, serving as a consultant) and the percentage of time they intended to allocate to each. Between June 2020 and February 2023, the team produced five original peer-reviewed manuscripts (including this article); five members served as first or senior authors. Twenty-one abstracts were presented at local conferences, and 10 at national and regional conferences. Five members achieved academic promotion, and team members were awarded three intramural grants resulting directly from team collaborations., Conclusion: Intentional recruitment and assessment of team members' desired levels of participation in an integrated clinical research team is an effective strategy to engage BIPOC and women. The CROSS Collaborative is a model for diversity and inclusion in team science and clinical research., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

There is limited information regarding how telemedicine visits compare with in-person visits regarding diabetes outcomes in an ambulatory care setting. Our objective was to compare proportions of patients in ambulatory setting with uncontrolled diabetes among those with telemedicine visits versus in-person only visits and examine differences by age, race, gender, ethnicity, and insurance status. Adults with diabetes who attended an ambulatory primary or specialty clinic visit between May 2020 and May 2021 were included. Demographics including age, race, ethnicity, gender, insurance, and comorbidities were extracted from the electronic medical record. Patients were compared among three visit groups: those with in-person only visits, those with only one telemedicine visit, and those with 2 + telemedicine visits. The primary outcome was uncontrolled diabetes, defined as HbA1c ≥ 9.0 %. Multivariable logistic regression was used to assess differences in uncontrolled diabetes between visit groups following risk adjustment. A total of 18,148 patients met inclusion criteria and 2,101 (11.6 %) had uncontrolled diabetes. There was no difference in proportion of patients with uncontrolled diabetes between visit groups (in-person only visits: 834 (11.6 %); one telemedicine visit: 558 (11.8 %); 2 + telemedicine visits: 709 (11.4 %); p  = 0.80)). Patients with 2 + telemedicine visits had significantly lower odds of uncontrolled diabetes compared to in-person only visits after risk adjustment (OR: 0.88; 95 % CI: 0.79-0.99, p  = 0.03). Compared with in-person ambulatory visits, telemedicine visits were associated with a lower odds of uncontrolled diabetes. Further work is warranted to explore the relationship between telemedicine visits and diabetes outcomes., Competing Interests: 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., (© 2022 The Authors.)

COVID-19 readmissions are associated with increased patient mortality and healthcare system strain. This retrospective cohort study of PCR-confirmed COVID-19 positive adults ( > 18 years) hospitalized and readmitted within 30 days of discharge from index admission was performed at eight Atlanta hospitals from March to December 2020. The objective was to describe COVID-19 patient-level demographics and clinical characteristics, and community-level social determinants of health (SDoH) that contribute to 30-day readmissions. Demographics, comorbidities, COVID-19 treatment, and discharge disposition data were extracted from the index admission. ZIP codes were linked to a demographic/lifestyle database interpolating to community-level SDoH. Of 7155 patients with COVID-19, 463 (6.5%) had 30-day, unplanned, all-cause hospital readmissions. Statistically significant differences were not found in readmissions stratified by age, sex, race, or ethnicity. Patients with a high-risk Charlson Comorbidity Index had higher odds of readmission (OR 4.8 (95% CI: 2.1 to 11.0)). Remdesivir treatment and intensive care unit (ICU) care were associated with lower odds of readmission (OR 0.5 (95% CI: 0.4 to 0.8) and OR 0.5 (95% CI: 0.4 to 0.7), respectively). Patients residing in communities with larger average household size were less likely to be readmitted (OR 0.7 (95% CI: 0.5 to 0.9). In this cohort, patients who received remdesivir, were cared for in an ICU, and resided in ZIP codes with higher proportions of residents with increased social support had lower odds of readmission. These patient-level factors and community-level SDoH may be used to identify patients with COVID-19 who are at increased risk of readmission., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Black patients are disproportionately affected by COVID-19. The purpose of this study was to compare risks of hospitalization of Black and non-Black COVID-19 patients presenting to the emergency department and, of those hospitalized, to compare mortality and acute kidney injury., Methods: A retrospective cohort of 831 adult COVID-19 patients (68.5% Black) who presented to the emergency departments of four academic hospitals, March 1, 2020-May 31, 2020. The primary outcome was risk of hospitalization among Blacks vs. non-Blacks. Secondary outcomes were mortality and acute kidney injury, among hospitalized patients., Results: The crude odds of hospitalization were not different in Black vs. non-Black patients; however, with adjustment for age, Blacks had 55% higher odds of hospitalization. Mortality differed most in the model adjusted for age alone. Acute kidney injury was more common in the Black hospitalized patients, regardless of adjustment. Stratified analyses suggested that disparities in the risk of hospitalization and of in-hospital acute kidney injury were highest in the youngest patients., Conclusions: Our report shows that Black and non-Black patients presenting to the emergency department with COVID-19 had similar risks of hospitalization and, of those who were hospitalized, similar mortality when adjusted for multiple factors. Blacks had higher risk of acute kidney injury. Our results suggest that examination of disparities without exploration of the individual effects of age and comorbidities may mask important patterns. While stratified analyses suggest that disparities in outcomes may differ substantially by age and comorbid conditions, further exploration among these important subgroups is needed to better target interventions to reduce disparities in COVID-19 clinical outcomes., (© 2021. W. Montague Cobb-NMA Health Institute.)

Abstract: Patients with chronic renal failure (CRF) are at high risk of being readmitted to hospitals within 30 days. Routinely collected electronic health record (EHR) data may enable hospitals to predict CRF readmission and target interventions to increase quality and reduce readmissions. We compared the ability of manually extracted variables to predict readmission compared with EHR-based prediction using multivariate logistic regression on 1 year of admission data from an academic medical center. Categorizing three routinely collected variables (creatinine, B-type natriuretic peptide, and length of stay) increased readmission prediction by 30% compared with paper-based methods as measured by C-statistic (AUC). Marginal effects analysis using the final multivariate model provided patient-specific risk scores from 0% to 44.3%. These findings support the use of routinely collected EHR data for effectively stratifying readmission risk for patients with CRF. Generic readmission risk tools may be evidence-based but are designed for general populations and may not account for unique traits of specific patient populations-such as those with CRF. Routinely collected EHR data are a rapid, more efficient strategy for risk stratifying and strategically targeting care. Earlier risk stratification and reallocation of clinician effort may reduce readmissions. Testing this risk model in additional populations and settings is warranted., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 National Association for Healthcare Quality.)

Equity in the promotion of women and underrepresented minorities (URiM) is essential for the advancement of academic emergency medicine and the specialty as a whole. Forward-thinking healthcare organizations can best position themselves to optimally care for an increasingly diverse patient population and mentor trainees by championing increased diversity in senior faculty ranks, leadership, and governance roles. This article explores several potential solutions to addressing inequities that hinder the advancement of women and URiM faculty. It is intended to complement the recently approved American College of Emergency Physicians (ACEP) policy statement aimed at overcoming barriers to promotion of women and URiM faculty in academic emergency medicine. This policy statement was jointly released and supported by the Society for Academic Emergency Medicine (SAEM), American Academy of Emergency Medicine (AAEM), and the Association of Academic Chairs of Emergency Medicine (AACEM)., Competing Interests: JF is a member of the ACEP BOD. MDL and AEP are members of the SAEM BOD. ALG is the Chair of ACEP Diversity, Inclusion, and Health Section. AAD was a prior member of the PACEP BOD., (© 2021 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Little is known about cancellation frequencies in telemedicine vs. in-person appointments and its impact on clinical outcomes. Our objective was to examine differences between in-person and video telemedicine appointments in terms of cancellation rates by age, race, ethnicity, gender, and insurance, and compare 30-day inpatient hospitalizations rates and 30-day emergency department visit rates between the two visit types. Demographic characteristics and comorbidities for adults scheduled for an Emory Healthcare ambulatory clinic appointment from June 2020 to December 2020 were extracted from the electronic medical record. Each appointment was identified as either a video telemedicine or in-person clinic appointment. The outcomes were ambulatory clinic cancellation rates, 30-day hospitalization rates, and 30-day emergency department visit rates. Multivariable logistic regression was used to assess differences between appointment types. A total of 1,652,623 ambulatory clinic appointments were scheduled. Ambulatory appointment cancellations rates were significantly lower among telemedicine compared to in-person appointments overall (20.4% vs. 31.0%, p < .001) and regardless of gender, age, race, ethnicity, insurance, or specialty (p < .05 for all sub-groups). Telemedicine appointments were associated with lower 30-day hospitalization rates compared to in-person appointments (AOR: 0.72, 95% CI: 0.71-0.74). There was no difference in 30-day emergency department visit rates between telemedicine and in-person appointment patients (AOR: 1.00, 95% CI: 0.98-1.02). Our findings suggest that there are fewer barriers to attending an ambulatory care visit via telemedicine relative to in-person. Using video telemedicine was not associated with more frequent adverse clinical events compared with in-person visits., Competing Interests: 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., (© 2021 The Authors.)

Importance: Protocol driven ED observation units (EDOU) have been shown to improve outcomes for patients and payers, however their impact on an entire health system is unknown. Two thirds of US hospitals do not have such units., Objective: To determine the impact of a protocol-driven EDOU on health system length of stay, cost, and resource utilization., Methods: A retrospective, observational, cross-sectional study of observation patients managed over 25 consecutive months in a four-hospital academic health system. Patients were identified using the "admit to observation" order and limited to adult, emergent / urgent, non-obstetric patients. Data was retrieved from a cost accounting database. The primary study exposure was the setting for observation care which was broken into three discrete groups: EDOUs (n = 3), hospital medicine observation units (HMSOU, n = 2), and a non-observation unit (NOU) bed located anywhere in the hospital. Outcomes included observation-to-inpatient admission rate, length of stay (LoS), total direct cost, and inpatient bed days saved. Unadjusted outcomes were compared, and outcomes were adjusted using multiple study variables. LoS and cost were compared using quantile regressions. Inpatient admit rate was compared using logistic regressions., Results: The sample consisted of 48,145 patients who were 57.4% female, 48% Black, 46% White, median age of 58, with some variation in most common diagnoses and payer groups. The median unadjusted outcomes favored EDOU over NOU settings for admission rate (13.1% vs 37.1%), LoS [17.9 vs 35.6 h), and cost ($1279 vs $2022). The adjusted outcomes favored EDOU over NOU settings for admission rates [12.3% (95% CI 9.7-15.3) vs 26.4% (CI 21.3-32.3)], LoS differences [11.1 h (CI 10.6-11.5 h)] and cost differences [$127.5 (CI $105.4 - $149.5)]. Adjusted differences were similar and favored EDOU over HMSOU settings. For the health system, the total adjusted annualized savings of the EDOUs was 10,399 bed days and $1,329,443 in total direct cost per year., Conclusion: Within an academic medical center, EDOUs were associated with improved resource utilization and reduced cost. This represents a significant opportunity for hospitals to improve efficiency and contain costs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: This study objective was to describe changes in the utilization of a protocol-driven emergency department observation unit (EDOU) for chest pain over time., Methods: This is a retrospective serial cross-sectional study of data from a clinical data warehouse of a single integrated healthcare system. We estimated long-term trends (2009-2019) in EDOU visits at 4 system hospitals, using monthly proportions as the main outcome, and month of visit as the exposure variable, accounting for age and sex. Rate changes associated with compulsory use of the History, EKG, Age, Risk factors, Troponin (HEART) score in 2016 were analyzed., Results: There were 83,168 EDOU admissions among 1.3 million ED visits during the study interval, with an average admission rate of 5.9% of ED visits. The most common conditions were chest pain (41.2%), transient ischemic attack (7.8%), dehydration (6.3%), syncope (5.8%), and abdominal pain (5.2%). In each hospital, there was a temporal annual decline in the proportion of EDOU visits for chest pain protocols ranging from -7.9% to -2.8%, an average rate of -3.3% per year (95% CI, -4.6% to -2.0%) or a 54% (from 54% to 25%) relative decline in over the 11-year study interval. This decline was significantly steeper in younger middle-aged patients (ages 39-49). The HEART score intervention had a small impact on baseline decline of -3.1% at the 2 intervention hospitals, reducing it by -1.5% (95% CI, -2.2% to -0.8%)., Conclusions: Utilization of the EDOU for chest pain decreased over time, with corresponding increases in other conditions. This decline preceded the introduction of the HEART score., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe the impact of a novel communication and triage pathway called fast track dialysis (FTD) on the length of stay (LOS), resource utilization, and charges for unscheduled hemodialysis for end stage renal disease (ESRD) patients presenting to the emergency department (ED)., Methods: Prospective and retrospective cohorts of ESRD patients meeting requirements of routine or urgent hemodialysis at a tertiary academic hospital from September 25th, 2016 to September 25th, 2018 in 1 year cohorts. Two sample t-tests were used to compare most outcomes of the cohorts with a Mann-Whitney U test used for skewed data. Nephrology group outcomes were analyzed by two-way ANOVA and Kruskal-Wallis and chi-square tests., Results: There were 98 encounters in the historical cohort and 143 encounters in the fast track dialysis cohort. FTD had significantly lowered median ED LOS (4.05 h, vs 5.3 h, p < 0.001), median hospital LOS (12.8 h vs 27 h, p < 0.001), time to hemodialysis (4.78 h vs 7.29 h, p < 0.001), and median hospital charges ($26,040 vs $30,747, p < 0.016). The FTD cohort had increased 30 day ED return for each encounter compared to the historical cohort (1.85 visits vs 0.73 visits, p < 0.001), however no significant increase in 1 year ED visits (6.52 visits vs 5.80, p = 0.4589) or 1 year readmissions (5.89 readmissions vs 4.81 readmissions, p = 0.3584). Most nephrology groups had significantly lower time to hemodialysis order placement and time to start hemodialysis., Conclusion: A multidisciplinary approach with key stakeholders using a standard pathway can lead to improved efficiency in throughput, reduced charges, and hospital resource utilization for patients needing urgent or routine hemodialysis. A study with a dedicated geographic observation unit for protocolized short stay patients including conditions ranging from low risk chest pain to transient ischemic events that incorporates FTD patients under this protocol should be considered., Competing Interests: Declaration of Competing Interest The Authors report no conflicts of interest in regards to this work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The common view of art and science as polar opposites along the educational spectrum can sometimes mask the degree to which they inform one another. In fact, art can also serve as a way to foster interest in querying the natural world, ultimately allowing us to recruit highly creative individuals to join the scientific community. We have experienced firsthand how cellular processes, such as autophagy, which are not usually highlighted or described in detail in foundational cell biology textbooks, have served as an on-ramp for artists at the undergraduate and high school levels in the context of scientific research and science outreach, respectively. We discuss our experiences in this article and highlight the ways in which art's many dimensions are well-suited, not only for forging connections between scientists and their communities but also for encouraging creativity in the way scientists engage with visually and conceptually complex phenomena, such as autophagy. Abbreviations: AP-3: adaptor protein complex 3; Atg27: autophagy related protein 27; STEAM: science, technology, engineering, arts, and mathematics; STEM: science, technology, engineering and math.

Cultural mistrust of government with regard to health issues has pressed the need to engage trusted community leaders with influence and reach in disproportionately affected communities to ensure that essential public health activities related to COVID-19 occur among populations experiencing disproportionate impact from the pandemic. In April of 2020, a Georgia-based integrated academic health care system created a Community Outreach and Health Disparities Collaborative to unite trusted community leaders from faith-based, civic, and health-sector organizations to work with the health system and Emory University to develop tailored approaches and mobilize support within the context of the communities' cultural and individual needs to reduce the burden of COVID-19. We describe the framework used to join health care and academic collaborators with community partners to mobilize efforts to address the disproportionate impact of COVID-19 on racial, ethnic, and socioeconomic minority groups. The framework outlines a series of steps taken that led to a community-driven collaboration designed to engage local influential community leaders as partners in improving access to care for disproportionately affected communities, collaborations that could be replicated by other large health care systems. This framework can also be applied to other chronic diseases or future public health emergencies to improve communication, education, and health care access for communities experiencing disproportionate impact.

Introduction: Pectoralis major muscle injuries are relatively uncommon and occur secondary to weightlifting in nearly 50% of cases. Tendon tears occur almost exclusively in males between 20-40 years old and are heavily associated with anabolic androgenic steroid use. While magnetic resonance imaging is often considered the modality of choice, its availability is often limited in the emergency department (ED). In contrast, point-of-care ultrasound (POCUS) is commonly available in the ED and can be used to help confirm the diagnosis and hasten disposition., Case Report: We report a case of a 28-year-old male competitive weightlifter with a history of chronic anabolic steroid use who presented to the ED with acute left shoulder pain after weightlifting. History and physical exam were concerning for pectoralis major rupture, and POCUS confirmed the diagnosis., Conclusion: Prompt evaluation and radiographic confirmation is key in ensuring good patient outcomes in pectoralis major tears. Therefore, proficiency of emergency physicians in musculoskeletal POCUS as an adjunct to estimate the extent of injury is important for expediting disposition and and promptly involving orthopedic surgery evaluation.

Introduction: Creating a racially and ethnically diverse workforce remains a challenge for medical specialties, including emergency medicine (EM). One area to examine is a partnership between a predominantly white institution (PWI) with a historically black college and university (HBCU) to determine whether this partnership would increase the number of underrepresented in medicine (URiM) in EM who are from a HBCU., Methods: Twenty years ago Emory Department of Emergency Medicine began its collaboration with Morehouse School of Medicine (MSM) to provide guidance to MSM students who were interested in EM. Since its inception, our engagement and intervention has evolved over time to include mentorship and guidance from the EM clerkship director, program director, and key faculty., Results: Since the beginning of the MSM-Emory EM partnership, 115 MSM students have completed an EM clerkship at Emory. Seventy-two of those students (62.6%) have successfully matched into an EM residency program. Of those who matched into EM, 22 (32%) have joined the Emory EM residency program with the remaining 50 students matching at 40 other EM programs across the nation., Conclusion: Based on our experience and outcomes with the Emory-MSM partnership, we are confident that a partnership with an HBCU school without an EM residency should be considered by residency programs to increase the number of URiM students in EM, which could perhaps translate to other specialties.

Current GABAergic sleep-promoting medications were developed pragmatically, without making use of the immense diversity of GABA A receptors. Pharmacogenetic experiments are leading to an understanding of the circuit mechanisms in the hypothalamus by which zolpidem and similar compounds induce sleep at α2βγ2-type GABA A receptors. Drugs acting at more selective receptor types, for example, at receptors containing the α2 and/or α3 subunits expressed in hypothalamic and brain stem areas, could in principle be useful as hypnotics/anxiolytics. A highly promising sleep-promoting drug, gaboxadol, which activates αβδ-type receptors failed in clinical trials. Thus, for the time being, drugs such as zolpidem, which work as positive allosteric modulators at GABA A receptors, continue to be some of the most effective compounds to treat primary insomnia.

Tandem two-pore potassium channels (K2Ps) have widespread expression in the central nervous system and periphery where they contribute to background membrane conductance. Some general anaesthetics promote the opening of some of these channels, enhancing potassium currents and thus producing a reduction in neuronal excitability that contributes to the transition to unconsciousness. Similarly, these channels may be recruited during the normal sleep-wake cycle as downstream effectors of wake-promoting neurotransmitters such as noradrenaline, histamine and acetylcholine. These transmitters promote K2P channel closure and thus an increase in neuronal excitability. Our understanding of the roles of these channels in sleep and anaesthesia has been largely informed by the study of mouse K2P knockout lines and what is currently predicted by in vitro electrophysiology and channel structure and gating.

The purpose of our study was to improve the quality of care in an emergency department (ED) as measured by length of stay (LOS), total turnaround time (TAT) for laboratory result reporting, and the blood culture contamination rate. Data were included for patients who had at least 1 of 5 laboratory tests performed as part of their care. The study was conducted in 2 phases. First, phlebotomy was performed by a dedicated phlebotomist or nonlaboratory personnel. The second phase added a dedicated laboratory technologist. There was a significant reduction in total TAT for all tests (at least 46 and 75 minutes in the respective interventions), and blood culture contamination rates dropped from 5.0% to 1.1%, although the overall LOS did not change. Estimated cost avoidance is more than $400,000 annually. Quality of care in an ED is improved when samples are collected by a dedicated phlebotomist, but overall LOS does not change.

Classical anesthetics of the gamma-aminobutyric acid type A receptor (GABA(A))-enhancing class (e.g., pentobarbital, chloral hydrate, muscimol, and ethanol) produce analgesia and unconsciousness (sedation). Dissociative anesthetics that antagonize the N-methyl-D-aspartate (NMDA) receptor (e.g., ketamine, MK-801, dextromethorphan, and phencyclidine) produce analgesia but do not induce complete loss of consciousness. To understand the mechanisms underlying loss of consciousness and analgesia induced by general anesthetics, we examined the patterns of expression of c-Fos protein in the brain and correlated these with physiological effects of systemically administering GABAergic agents and ketamine at dosages used clinically for anesthesia in rats. We found that GABAergic agents produced predominantly delta activity in the electroencephalogram (EEG) and sedation. In contrast, anesthetic doses of ketamine induced sedation, followed by active arousal behaviors, and produced a faster EEG in the theta range. Consistent with its behavioral effects, ketamine induced Fos expression in cholinergic, monoaminergic, and orexinergic arousal systems and completely suppressed Fos immunoreactivity in the sleep-promoting ventrolateral preoptic nucleus (VLPO). In contrast, GABAergic agents suppressed Fos in the same arousal-promoting systems but increased the number of Fos-immunoreactive neurons in the VLPO compared with waking control animals. All anesthetics tested induced Fos in the spinally projecting noradrenergic A5-7 groups. 6-hydroxydopamine lesions of the A5-7 groups or ibotenic acid lesions of the ventrolateral periaqueductal gray matter (vlPAG) attenuated antinociceptive responses to noxious thermal stimulation (tail-flick test) by both types of anesthetics. We hypothesize that neural substrates of sleep-wake behavior are engaged by low-dose sedative anesthetics and that the mesopontine descending noradrenergic cell groups contribute to the analgesic effects of both NMDA receptor antagonists and GABA(A) receptor-enhancing anesthetics.

To perform tasks, organisms often use multiple procedures. Explaining the breadth of such behavioural repertoires is not always straightforward. During house hunting, colonies of Temnothorax albipennis ants use a range of behaviours to organise their emigrations. In particular, the ants use tandem running to recruit naïve ants to potential nest sites. Initially, they use forward tandem runs (FTRs) in which one leader takes a single follower along the route from the old nest to the new one. Later, they use reverse tandem runs (RTRs) in the opposite direction. Tandem runs are used to teach active ants the route between the nests, so that they can be involved quickly in nest evaluation and subsequent recruitment. When a quorum of decision-makers at the new nest is reached, they switch to carrying nestmates. This is three times faster than tandem running. As a rule, having more FTRs early should thus mean faster emigrations, thereby reducing the colony's vulnerability. So why do ants use RTRs, which are both slow and late? It would seem quicker and simpler for the ants to use more FTRs (and higher quorums) to have enough knowledgeable ants to do all the carrying. In this study, we present the first testable theoretical explanation for the role of RTRs. We set out to find the theoretically fastest emigration strategy for a set of emigration conditions. We conclude that RTRs can have a positive effect on emigration speed if FTRs are limited. In these cases, low quorums together with lots of reverse tandem running give the fastest emigration.

Some organisms maintain a battery of defensive strategies against their exploiters (predators, parasites or parasitoids), while others fail to employ a defence that seems obvious. In this paper, we shall investigate the circumstances under which defence strategies might be expected to evolve. Brood parasites and their hosts provide our main motivation, and we shall discuss why the reed warbler Acrocephalus scirpaceus has evolved an egg-rejection but not a chick-rejection strategy as a defence against the common (Eurasian) cuckoo Cuculus canorus, while the superb fairy-wren Malurus cyaneus has evolved a chick-rejection but not an egg-rejection strategy as a defence against Horsfield's bronze-cuckoo Chrysococcyx basalis. We suggest that the answers lie in strategy-blocking, where one strategy (the blocking strategy) prevents the appearance of another (the blocked strategy) that would be adaptive in its absence. This may be common in exploiter-victim systems.

Background: Neonatal asphyxia causes long-term neurological and behavioural impairment in the developing brain. Concurrent administration of xenon and hypothermia synergistically reduces long-term damage in a rat model of neonatal asphyxia. This study sought to investigate whether asynchronous administration of xenon and hypothermia is capable of combining synergistically to provide neuroprotection., Methods: Seven-day-old rats were subjected to right common carotid artery occlusion followed by 90 min hypoxia with 8% oxygen. After a 1 h recovery period, rats received asynchronous administration of mild hypothermia (35 degrees C) and xenon (20%) with a 1 or 5 h gap between interventions, xenon (20%) alone, or mild hypothermia (35 degrees C) alone. Infarct volume in the brain was measured 4 days after injury., Results: Administration of hypothermia or xenon alone, 1 and 6 h after the hypoxic ischaemic insult, respectively, provided no neuroprotection. Asynchronous administration of xenon and hypothermia at a 1 h interval produced a significant reduction in infarct volume [93 (7) vs 74 (8); P < 0.05]. Reduction in infarct volume was also present when hypothermia and xenon were asynchronously administered with an intervening gap of 5 h [97 (5) vs 83 (3); P < 0.05]., Conclusions: This finding provides a rationale for investigating the combined use of hypothermia and xenon in a progressive manner for the management of neonatal asphyxia. Thus, hypothermia can be administrated at the site of delivery and xenon can be administered later.

Background: Isoflurane and xenon are inhalation general anaesthetics with differing clinical profiles and contrasting synaptic actions. Both agents have been shown to depress excitatory synaptic responses. Whether this is via pre-synaptic or post-synaptic mechanisms has not been determined clearly. N-type calcium channels are a putative pre-synaptic target for these agents. We tested whether N-type calcium channels were sensitive to isoflurane and xenon and whether there was any stereoselectivity in the effect of isoflurane., Methods: We used patch-clamp electrophysiology on isolated HEK293 cells stably expressing N-type calcium channels to investigate the effects of isoflurane and xenon on barium currents mediated by N-type calcium channels., Results: Racemic isoflurane caused a concentration-dependent reduction (11-35%) in the peak current through the N-type channels in the concentration range 0.15-1.22 mM. In the clinically relevant concentration range the inhibition was small. At an isoflurane concentration of 0.31 mM (equivalent to 1 MAC), the peak N-type current was inhibited by 14 (1)%. The optical isomers of isoflurane were found to be equally potent at inhibiting currents through N-type channels. The inert gas anaesthetic xenon was found to have no measureable effect on N-type channels at a concentration of 3.4 mM (approximately 1 MAC)., Conclusions: These results suggest that N-type calcium channels are not the targets mediating general anaesthesia with these two inhalation agents.

The effects of general anaesthetics and temperature on carbachol-evoked gamma oscillations in the rat hippocampal brain slice preparation were investigated. The frequency of the oscillations was found to be dependent on temperature in the range 32-25 degrees C, with a linear reduction in frequency from 40-17 Hz over this temperature range. The volatile anaesthetics isoflurane and halothane, and the intravenous anaesthetics thiopental, propofol and R(+)-etomidate caused a reduction in the frequency of the oscillations, in a concentration-dependent manner, over a range of clinically relevant concentrations. On the other hand, the intravenous agent ketamine and the "inactive" S(-)-isomer of etomidate had no significant effect on the oscillation frequency. The oscillations were markedly asymmetric over one cycle with a relatively rapid "rising" phase followed by a slower "decaying" phase. The decrease in oscillation frequency was due to an increase in the time-course of the "decaying phase" of the oscillation with little effect on the "rising" phase, consistent with the idea that carbachol-evoked gamma oscillations are trains of GABAergic inhibitory postsynaptic potentials and that the anaesthetics are acting postsynaptically at the GABA(A) receptor.

We show how the movement rules of individual ants on trails can lead to a collective choice of direction and the formation of distinct traffic lanes that minimize congestion. We develop and evaluate the results of a new model with a quantitative study of the behaviour of the army ant Eciton burchelli. Colonies of this species have up to 200 000 foragers and transport more than 3000 prey items per hour over raiding columns that exceed 100 m. It is an ideal species in which to test the predictions of our model because it forms pheromone trails that are densely populated with very swift ants. The model explores the influences of turning rates and local perception on traffic flow. The behaviour of real army ants is such that they occupy the specific region of parameter space in which lanes form and traffic flow is maximized.

A swarm of honeybees (Apis mellifera) is capable of selecting one nest-site when faced with a choice of several. We adapt classical mathematical models of disease, information and competing beliefs to such decision-making processes. We show that the collective decision may be arrived at without the necessity for any bee to make any comparison between sites.

The causes of biological gigantism have received much attention, but only for individual organisms. What selection pressures might favour the evolution of gigantic societies? Here we consider the largest single-queen insect societies, those of the Old World army ant Dorylus, single colonies of which can have 20 million workers. We propose that colony gigantism in Dorylus arises as a result of an arms race and test this prediction by developing a size-structured mathematical model. We use this model for exploring and potentially explaining differences in colony size, colony aggression and colony propagation strategies in populations of New World army ants Eciton and Old World army ants Dorylus. The model shows that, by determining evolutionarily stable strategies (ESSs), differences in the trophic levels at which these army ants live feed forwards into differences in their densities and collision rates and, hence, into different strategies of growth, aggression and propagation. The model predicts large colony size and the occurrence of battles and a colony-propagation strategy involving highly asymmetrical divisions in Dorylus and that Eciton colonies should be smaller, non-combative and exhibit equitable binary fission. These ESSs are in excellent agreement with field observations and demonstrate that gargantuan societies can arise through arms races.

We consider mechanisms that may determine certain simple leaf shapes. Compared with other aspects of plant morphogenesis, such as phyllotaxis or spiral leaf arrangement, rather little is known about leaf-shape-determining mechanisms. We develop mathematical models for the gross pattern of leaf shape based on reaction diffusion systems. These models are consistent with what is known about factors that might determine leaf shape. They show that diverse leaf shapes may be obtained from a single reaction diffusion system. This has implications in terms of both convergent and divergent evolution. The models make predictions that can be tested experimentally. We predict the form of pre-patterns of growth promoters in leaf primordia of different sizes when the morphogens either diffuse into the primordia or are produced locally. We also predict the effects on leaf shape of removing parts of primordia at different times. The models can also predict the effects on leaf shape of the topical application of activators and inhibitors to leaf primordia.

We show for the first time, to our knowledge, that ants can measure the size of potential nest sites. Nest size assessment is by individual scouts. Such scouts always make more than one visit to a potential nest before initiating an emigration of their nest mates and they deploy individual-specific trails within the potential new nest on their first visit. We test three alternative hypotheses for the way in which scouts might measure nests. Experiments indicated that individual scouts use the intersection frequency between their own paths to assess nest areas. These results are consistent with ants using a 'Buffon's needle algorithm' to assess nest areas.

Background: The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon., Methods: The actions of isoflurane and xenon on gamma-aminobutyric acid-mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks., Results: Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current. At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor-mediated component of the current but has little effect on the AMPA/kainate receptor-mediated component., Conclusions: For both isoflurane and xenon, the most important targets appear to be postsynaptic. The authors' results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.

Human serum albumin possesses multiple fatty acid binding sites of varying affinities, but the precise locations of these sites have remained elusive. The determination of the crystal structure of human serum albumin complexed with myristic acid recently revealed the positions and architecture of six binding sites on the protein. While the structure of the complex is consistent with a great deal of the biochemical and biophysical data on fatty acid binding, it is not yet possible to provide a completely rigorous correlation between the structural and binding data. The challenge now is to use the new structural information to design experiments that will identify the physiologically important binding sites on HSA and provide a much richer description of fatty acid interactions with the protein.