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Background: Rising ED boarding and visit volumes are challenges to maintaining patient flow and avoiding patients leaving without being seen. Objectives: We aimed to decrease left without being seen and improve ED patient flow by minimizing time patients spent in the waiting room in the early hours of the day when treatment spaces are usually available. Methods: We implemented a “Waiting room zero before noon” campaign in our urban community emergency department. Providers and nurses were messaged about this goal and the expectation was set that patients should be brought to a room even if a nurse was not immediately available to care for them. Results: In the three months following this campaign, we experienced a significant decrease in left without being seen. This decrease persisted over the subsequent two years, despite increasing patient volume. Conclusion: A simple, cost-neutral campaign aimed at changing workflow culture was able to achieve improvements in patient flow despite continued challenges of rising boarding and volume.

About 40 trans-Neptunian binaries (TNBs) have fully determined orbits with about 10 others being solved except for breaking the mirror ambiguity. Despite decades of study, almost all TNBs have only ever been analyzed with a model that assumes perfect Keplerian motion (e.g., two point masses). In reality, all TNB systems are non-Keplerian due to nonspherical shapes, possible presence of undetected system components, and/or solar perturbations. In this work, we focus on identifying candidates for detectable non-Keplerian motion based on sample of 45 well-characterized binaries. We use MultiMoon , a non-Keplerian Bayesian inference tool, to analyze published relative astrometry allowing for nonspherical shapes of each TNB system’s primary. We first reproduce the results of previous Keplerian fitting efforts with MultiMoon , which serves as a comparison for the non-Keplerian fits and confirms that these fits are not biased by the assumption of a Keplerian orbit. We unambiguously detect non-Keplerian motion in eight TNB systems across a range of primary radii, mutual orbit separations, and system masses. As a proof of concept for non-Keplerian fitting, we perform detailed fits for (66652) Borasisi-Pabu, possibly revealing a J _2 ≈ 0.44, implying Borasisi (and/or Pabu) may be a contact binary or an unresolved compact binary. However, full confirmation of this result will require new observations. This work begins the next generation of TNB analyses that go beyond the point mass assumption to provide unique and valuable information on the physical properties of TNBs with implications for their formation and evolution.

Abstract Objectives Previous studies have demonstrated that infants are typically born with a left‐greater‐than‐right forebrain asymmetry that reverses throughout the first year of life. We hypothesized that critically ill term‐born and premature patients following surgical and critical care for long‐gap esophageal atresia (LGEA) would exhibit alteration in expected forebrain asymmetry. Methods Term‐born (n = 13) and premature (n = 13) patients, and term‐born controls (n = 23)

Abstract. Objective: To determine whether local aqueous tobramycin injection in combination with systemic perioperative IV antibiotic prophylaxis will reduce the rate of fracture-related infection (FRI) after open fracture fixation. Other Outcomes of Interest: (1) To compare fracture nonunion rates and report differences between treatment and control groups and (2) compare bacterial speciation and antibiotic sensitivity among groups that develop FRI. Design: Phase 3 prospective, randomized clinical trial. Setting: Two level 1 trauma centers. Participants: Six hundred subjects (300 in study/tobramycin group and 300 in control/standard practice group) will be enrolled and assigned to the study group or control group using a randomization table. Patients with open extremity fractures that receive definitive internal surgical fixation will be considered. Intervention: Aqueous local tobramycin will be injected into the wound cavity (down to bone) after debridement, irrigation, and fixation, following closure. Main Outcome Measurements: Outcomes will look at the presence or absence of FRI, the rate of fracture nonunion, and determine speciation of gram-negative and Staph bacteria in each group with a FRI. Results: Not applicable. Conclusion: The proposed work will determine whether local tobramycin delivery plus perioperative standard antibiotic synergism will minimize the occurrence of open extremity FRI. Level of Evidence: Level 1.

Previously, we reported quantitatively smaller total corpus callosum (CC) and total forebrain size in critically ill term-born and premature patients following complex perioperative critical care for long-gap esophageal atresia (LGEA) that included Foker process repair. We extended our cross-sectional pilot study to determine sub-regional volumes of CC and forebrain using structural brain MRI. Our objective was to evaluate region-specific CC as an in-vivo marker for decreased myelination and/or cortical neural loss of homotopic-like sub-regions of the forebrain. Term-born (n = 13) and premature (n = 13) patients, and healthy naïve controls (n = 21)

Modeling human breast tissue architecture is essential to study the pathophysiological conditions of the breast. We report that normal mammary epithelial cells grown in human breast extracellular matrix (ECM) hydrogel formed acini structurally similar to those of human and pig mammary tissues. Type I, II, III and V collagens were commonly identified in human, pig, and mouse breast ECM. Mammary epithelial cells formed acini on certain types or combinations of the four collagens at normal levels of breast tissue elasticity. Comparison of the collagen species in mouse normal breast and breast tumor ECM revealed common and distinct sets of collagens within the two types of tissues. Elevated expression of collagen type I alpha 1 chain (Col1a1) was found in mouse and human breast cancers. Collagen type XXV alpha 1 chain (Col25a1) was identified in mouse breast tumors but not in normal breast tissues. Our data provide strategies for modeling human breast pathophysiological structures and functions using native tissue-derived hydrogels and offer insight into the potential contributions of different collagen types in breast cancer development.

Objective: To determine brain magnetic resonance imaging (MRI) measures of cerebrospinal fluid (CSF) and whole brain volume of full-term and premature infants following surgical treatment for thoracic non-cardiac congenital anomalies requiring critical care.Methods: Full-term (n = 13) and pre-term (n = 13) patients with long-gap esophageal atresia, and full-term naïve controls (n = 19) < 1 year corrected age, underwent non-sedated brain MRI following completion of thoracic non-cardiac surgery and critical care treatment. Qualitative MRI findings were reviewed and reported by a pediatric neuroradiologist and neurologist. Several linear brain metrics were measured using structural T1-weighted images, while T2-weighted images were required for segmentation of total CSF and whole brain tissue using the Morphologically Adaptive Neonatal Tissue Segmentation (MANTiS) tool. Group differences in absolute (mm, cm3) and normalized (%) data were analyzed using a univariate general linear model with age at scan as a covariate. Mean normalized values were assessed using one-way ANOVA.Results: Qualitative brain findings suggest brain atrophy in both full-term and pre-term patients. Both linear and volumetric MRI analyses confirmed significantly greater total CSF and extra-axial space, and decreased whole brain size in both full-term and pre-term patients compared to naïve controls. Although linear analysis suggests greater ventricular volumes in all patients, volumetric analysis showed that normalized ventricular volumes were higher only in premature patients compared to controls.Discussion: Linear brain metrics paralleled volumetric MRI analysis of total CSF and extra-axial space, but not ventricular size. Full-term infants appear to demonstrate similar brain vulnerability in the context of life-saving thoracic non-cardiac surgery requiring critical care as premature infants.

Rodent models have opened the door to a better understanding of the neurobiology of brain disorders and increased our ability to evaluate novel treatments. Resting-state functional magnetic resonance imaging (rs-fMRI) allows for in vivo exploration of large-scale brain networks with high spatial resolution. Its application in rodents affords researchers a powerful translational tool to directly assess/explore the effects of various pharmacological, lesion, and/or disease states on known neural circuits within highly controlled settings. Integration of animal and human research at the molecular-, systems-, and behavioral-levels using diverse neuroimaging techniques empowers more robust interrogations of abnormal/ pathological processes, critical for evolving our understanding of neuroscience. We present a comprehensive protocol to evaluate resting-state brain networks using Independent Component Analysis (ICA) in rodent model. Specifically, we begin with a brief review of the physiological basis for rs-fMRI technique and overview of rs-fMRI studies in rodents to date, following which we provide a robust step-by-step approach for rs-fMRI investigation including data collection, computational preprocessing, and brain network analysis. Pipelines are interwoven with underlying theory behind each step and summarized methodological considerations, such as alternative methods available and current consensus in the literature for optimal results. The presented protocol is designed in such a way that investigators without previous knowledge in the field can implement the analysis and obtain viable results that reliably detect significant differences in functional connectivity between experimental groups. Our goal is to empower researchers to implement rs-fMRI in their respective fields by incorporating technical considerations to date into a workable methodological framework.

Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Postnatal brain plasticity is associated with increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Over the past decade, its application has expanded to infant populations providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal states. However, many methodological issues of rs-fMRI analysis need to be resolved prior to standardization of the technique to infant populations. As a primary goal, this methodological manuscript will (1) present a robust methodological protocol to extract and assess resting-state networks in early infancy using independent component analysis (ICA), such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature; (2) review the current methodological challenges and ethical considerations associated with emerging field of infant rs-fMRI analysis; and (3) discuss the significance of rs-fMRI application in infants for future investigations of neurodevelopment in the context of early life stressors and pathological processes. The overarching goal is to catalyze efforts toward development of robust, infant-specific acquisition, and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used.

New allanite geochronology is presented for four mineral deposits in the Mount Isa Inlier (SWAN, Mary Kathleen, Koppany and Elaine Dorothy). The data indicate the occurrence of multiple phases of allanite formation: one at 1732 ± 8 Ma at Koppany, one at ca 1520 Ma at Mary Kathleen, Koppany and SWAN, and one at ca 1473 Ma at Mary Kathleen and Elaine Dorothy associated with vein calcite. In the Mary Kathleen–Koppany–Elaine Dorothy skarn system, there are chemical and textural differences between the three allanite generations; the ca 1520 Ma generation formed by dissolution–reprecipitation of 1732 Ma allanite, with no addition of externally sourced rare earth elements, as shown by the identical Nd isotopic compositions of these two populations. Allanite at SWAN yielded a 207Pb/206Pb ID-TIMS age of 1519.6 ± 1.1 Ma; its homogeneity, low common Pb contents and near-concordance make it a suitable reference material. Repeated remobilisation of rare earth elements in the Mary Kathleen system is surprising, given the widely accepted low solubility of these elements, but may have been restricted in spatial extent. KEY POINTS: New ages for allanite formation at four REE-rich deposits near Mount Isa. Some localities show multiple generations of allanite with distinct compositions. Nd isotopes link these generations to each other and to the source of the ore-forming fluids. [ABSTRACT FROM AUTHOR]

Simple Summary: The Aerococcus viridans bacterial lactate oxidase (LOX) is an enzyme absent in mammalian cells. LOX catalyzes lactate to pyruvate and hydrogen peroxide (H2O2), a function that was recently used for tumor microenvironment (TME) lactate removal and H2O2 production to induce cancer cell death. However, the functions of TME lactate other than being a metabolic intermediate or an energy source and the mechanism of LOX disruption of lactate-mediated cancer cell survival remain unknown. Our study aims at addressing these important cancer-related biological questions. We identified a novel onco-signaling nexus initiated by TME lactate activation of its cellular receptor hydroxycarboxylic acid receptor 1 (HCAR1) and amplified by HCAR-associated proteins that mediate the RAS and the PI3K pathways. This signaling model could explain many key survival strategies exerted by RAS, PI3K, and their effectors for cancer cell adaptation to TME changes, especially in the cells' use of lactate beyond an energy source. LOX was recently shown to inhibit cancer cell proliferation and tumor growth. The mechanism of this inhibition, however, has been exclusively attributed to LOX depletion of TME lactate, a cancer cell energy source, and production of H2O2, an oxidative stressor. We report that TME lactate triggers the assembly of the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1)-associated protein complex, which includes GRB2, SOS1, KRAS, GAB1, and PI3K, for the activation of both the RAS and the PI3K oncogenic signaling pathways in breast cancer (BCa) cells. LOX treatment decreased the levels of the proteins in the protein complex via induction of their proteasomal degradation. In addition, LOX inhibited lactate-stimulated expression of the lactate transporters MCT1 and MCT4. Our data suggest that HCAR1 activation by lactate is crucial for the assembly and function of the RAS and PI3K signaling nexus. Shutting down lactate signaling by disrupting this nexus could be detrimental to cancer cells. HCAR1 is therefore a promising target for the control of the RAS and the PI3K signaling required for BCa progression. Thus, our study provides insights into lactate signaling regulation of cancer progression and extends our understanding of LOX's functional mechanisms that are fundamental for exploring its therapeutic potential. [ABSTRACT FROM AUTHOR]

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Purpose: Early reports of 30-day mortality in COVID-positive patients with hip fracture were often over 30% and were higher than historical rates of 10% in pre-COVID studies. We conducted a multi-institutional retrospective cohort study to determine whether the incidence of 30-day mortality and complications in COVID-positive patients undergoing hip fracture surgery is as high as initially reported. Methods: A retrospective chart review was performed at 11 level I trauma centers from January 1, 2020 to May 1, 2022. Patients 50 years or older undergoing hip fracture surgery with a positive COVID test at the time of surgery were included. The primary outcome measurements were the incidence of 30-day mortality and complications. Post-operative outcomes were reported using proportions with 95% confidence interval (C.I.). Results: Forty patients with a median age of 71.5 years (interquartile range, 50–87 years) met the criteria. Within 30-days, four patients (10%; 95% C.I. 3–24%) died, four developed pneumonia, three developed thromboembolism, and three remained intubated post-operatively. Increased age was a statistically significant predictor of 30-day mortality (p = 0.01), with all deaths occurring in patients over 80 years. Conclusion: In this multi-institutional analysis of COVID-positive patients undergoing hip fracture surgery, 30-day mortality was 10%. The 95% C.I. did not include 30%, suggesting that survival may be better than initially reported. While COVID-positive patients with hip fractures have high short-term mortality, the clinical situation may not be as dire as initially described, which may reflect initial publication bias, selection bias introduced by testing, or other issues. Levels of Evidence: Therapeutic Level III. [ABSTRACT FROM AUTHOR]