Search

Nanostructured metallic materials with abundant high-angle grain boundaries exhibit high strength and good radiation resistance. While the nanoscale grains induce high strength, they also degrade tensile ductility. We show that a gradient nanostructured ferritic steel exhibits simultaneous improvement in yield strength by 36% and uniform elongation by 50% compared to the homogenously structured counterpart. In situ tension studies coupled with electron backscattered diffraction analyses reveal intricate coordinated deformation mechanisms in the gradient structures. The outermost nanolaminate grains sustain a substantial plastic strain via a profound deformation mechanism involving prominent grain reorientation. This synergistic plastic co-deformation process alters the rupture mode in the post-necking regime, thus delaying the onset of fracture. The present discovery highlights the intrinsic plasticity of nanolaminate grains and their significance in simultaneous improvement of strength and tensile ductility of structural metallic materials.

The split-Gal4 system allows for intersectional genetic labeling of highly specific cell-types and tissues inDrosophila. However, the existing split-Gal4 system, unlike the standard Gal4 system, cannot be repressed by Gal80, and therefore cannot be controlled temporally. This lack of temporal control precludes split-Gal4 experiments in which a genetic manipulation must be restricted to specific timepoints. Here, we describe a new split-Gal4 system based on a self-excising split-intein, which drives transgene expression as strongly as the current split-Gal4 system and Gal4 reagents, yet which is fully repressible by Gal80. We demonstrate the potent inducibility of “split-intein Gal4”in vivousing both fluorescent reporters and via reversible tumor induction in the gut. Further, we show that our split-intein Gal4 can be extended to the drug-inducible GeneSwitch system, providing an independent method for intersectional labeling with inducible control. We also show that the split-intein Gal4 system can be used to generate highly cell-type specific genetic drivers based onin silicopredictions generated by single cell RNAseq (scRNAseq) datasets, and we describe a new algorithm (“Two Against Background” or TAB) to predict cluster-specific gene pairs across multiple tissue-specific scRNA datasets. We provide a plasmid toolkit to efficiently create split-intein Gal4 drivers based on either CRISPR knock-ins to target genes or using enhancer fragments. Altogether, the split-intein Gal4 system allows for the creation of highly specific intersectional genetic drivers that are inducible/repressible.Significance statementThe split-Gal4 system allowsDrosophilaresearchers to drive transgene expression with extraordinary cell type specificity. However, the existing split-Gal4 system cannot be controlled temporally, and therefore cannot be applied to many important areas of research. Here, we present a new split-Gal4 system based on a self-excising split-intein, which is fully controllable by Gal80, as well as a related drug-inducible split GeneSwitch system. This approach can both leverage and inform single-cell RNAseq datasets, and we introduce an algorithm to identify pairs of genes that precisely and narrowly mark a desired cell cluster. Our split-intein Gal4 system will be of value to theDrosophilaresearch community, and allow for the creation of highly specific genetic drivers that are also inducible/repressible.

Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England’s National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73–5.90) to 10.26 (6.6–14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.

SUMMARY PARAGRAPHDisease-causing mutations in genes encoding transcription factors (TFs) are a recurrent finding in hematopoietic malignancies and might involve key regulators of lineage adherence and cellular differentiation1–3. Such mutations can affect TF-interactions with their cognate DNA-binding motifs4, 5. Whether and how TF-mutations impact upon the nature of binding to TF composite elements (CE) and influence their interaction with other TFs is unclear. Here, we report a new mechanism of TF alteration in human lymphomas with perturbed B cell identity. It is caused by a recurrent somatic missense mutation c.295T>C (p.Cys99Arg; p.C99R) targeting the center of the DNA-binding domain of Interferon Regulatory Factor 4 (IRF4), a key TF in immune cell-differentiation and -activation6, 7. IRF4-C99R fundamentally alters IRF4 DNA-binding, with loss-of-binding to canonical IRF motifs and neomorphic gain-of-binding to canonical and non-canonical IRF composite elements (CEs). Furthermore, IRF4-C99R thoroughly modifies IRF4 function, by blocking IRF4-dependent plasma cell induction, and up-regulating disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single arginine mutation creates a complex switch of TF specificity and gene regulation. These data open the possibility of designing specific inhibitors to block the neomorphic, disease-causing DNA-binding activities of a mutant transcription factor.

Primary renal neuroendocrine neoplasms (NEN) are rare. We aimed to conduct a systematic review, present local cases, and analyse data from the England's National Cancer Registration and Analysis Service (NCRAS) to provide comprehensive evidence on clinical experience, incidence, and survival to better characterize these tumours. First, a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method; second, a synthesis of local cases; and, finally, a retrospective population-based cohort analysis of renal NEN recorded between 2012 and 2018 on NCRAS were performed. Kaplan-Meier estimator was used to calculate overall survival and Cox proportional hazard regression to identify prognostic factors. Systematic review identified 48 articles and the evidence was summarized and presented. We reported data from four local cases presenting with abdominal and back pain but without carcinoid syndrome. In population-based analysis, we identified 63 cases of renal NEN between 2012 and 2018 from the registry. Age-standardized incidence was 0.09-0.32 per million with a median age of 64 years (interquartile range = 48-72 years). Survival was worse in males and those aged 64 years and over. Five-year survival for renal neuroendocrine tumours (NET) was 69.8% (95% confidence interval = 66.6-72.7) and neuroendocrine carcinomas (NEC) was 38.4% (95% confidence interval = 34.6-42.0). No independent predictive factor was identified in the multivariable analyses. We have given a systematic review of evidence, published local experience, and reported incidence and survival of renal NEN in England for the first time. We have provided clinicians with evidence on diagnosis and proposed a treatment algorithm of theses rare tumours. The incidence and median age of presentation in England is similar to other published series. Renal NET has better survival than renal NEC as expected. A uniform classification system would reduce inconsistencies in reporting and standardize treatment decisions for this neoplasia.

The stability of default effects to contextual features is critical to their use in policy. In this paper, decision time was investigated as a contextual factor that may pose limits on the efficacy of defaults. Consistent with the hypothesis that time constraints may increase reliance on contextual cues, four experiments, including a preregistered one of a nationally representative sample, and a meta-analysis that included four additional pilot experiments, indicated that short decision times increased the advantage of action defaults (i.e., the default option automatically endorsed the desired behavior) and that the default advantage was trivial or nonexistent when decision times were longer. These effects replicated for naturalistic as well as externally induced decision times and were present even when participants were unaware that time was limited. This research has critical implications for psychological science and allied disciplines concerned with policy in the domains of public health, finance and economics, marketing, and environmental sciences.

OBJECTIVE The purpose of this meta-analysis was to examine the success of multiple-behavior interventions and to identify whether the efficacy of such programs depends on the number of recommendations prescribed and the type of outcomes measured. METHOD We conducted a synthesis of 136 research reports (N = 59,330) using a robust variance estimate model (Tanner-Smith et al., 2016) to study change between baseline and the first follow-up across multiple-behavior interventions, single-behavior interventions, and passive controls. RESULTS Multiple-behavior interventions were more efficacious than their single-behavior counterparts (multiple-behaviors: d = .44 [95% confidence interval, CI [.27, .60]); single-behavior: d = .21 [95% CI [.00, .43]), with efficacy varying based on the type of outcomes measured. Publication bias analysis revealed a small asymmetry but controlling for it did not eliminate these effects. There was a strong linear relation between the number of recommendations prescribed by an intervention and intervention efficacy (B = .07, SE = .01, p < .001), with strongest improvements observed for interventions making five or more recommendations. These patterns remained when controlling for other intervention and population characteristics. CONCLUSIONS Multiple-behavior interventions are successful in the HIV domain and increasing the number of recommendations made in the intervention generally maximizes improvements. These findings provide insights that may guide the design and implementation of integrated interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Introduction Patients with neuroendocrine neoplasms (NENs) may often develop other malignancies. This study aimed to identify the frequency at which these second malignancies occurred in England. Methods Data was extracted from the National Cancer Registration and Analysis Service (NCRAS) on all patients diagnosed with a NEN at one of eight NEN site groups between 2012-2018: appendix, caecum, colon, lung, pancreas, rectum, small intestine and stomach. WHO International Classification of Disease edition 10 (ICD-10) codes were used to identify patients who had been diagnosed with an additional non-NEN cancer. Standardised incidence ratios (SIRs) for tumours diagnosed after the index NEN were produced for each non-NEN cancer type by sex and site. Results A total of 20,579 patients were included in the study. The most commonly occurring non-NEN cancers after NEN diagnosis were prostate (20%), lung (20%) and breast (15%). Statistically significant SIRs were observed for non-NEN cancer of the lung (SIR=1.85, 95%CI:1.55-2.22), colon (SIR=1.78, 95%CI:1.40-2.27), prostate (SIR=1.56, 95%CI:1.31-1.86), kidney (SIR=3.53, 95%CI:2.72-4.59) and thyroid (SIR=6.31, 95%CI:4.26-9.33). When stratified by sex, statistically significant SIRs remained for lung, renal, colon and thyroid tumours. Additionally, females had a statistically significant SIR for stomach cancer (2.65, 95%CI:1.26-5.57) and bladder cancer (SIR=2.61, 95%CI:1.36-5.02). Discussion/Conclusion This study found that patients with a NEN experienced a metachronous tumour of the lung, prostate, kidney, colon and thyroid at a higher rate than the general population of England. Surveillance and engagement in existing screening programmes is required to enable earlier diagnosis of second non-NEN tumours in these patients.

The geneticist Thomas Dobzhansky famously declared: 'Nothing in biology makes sense except in the light of evolution'. A key evolutionary adaptation of Metazoa is directed movement, which has been elaborated into a spectacularly varied number of behaviours in animal clades. The mechanisms by which animal behaviours have evolved, however, remain unresolved. This is due, in part, to the indirect control of behaviour by the genome, which provides the components for both building and operating the brain circuits that generate behaviour. These brain circuits are adapted to respond flexibly to environmental contingencies and physiological needs and can change as a function of experience. The resulting plasticity of behavioural expression makes it difficult to characterize homologous elements of behaviour and to track their evolution. Here, we evaluate progress in identifying the genetic substrates of behavioural evolution and suggest that examining adaptive changes in neuromodulatory signalling may be a particularly productive focus for future studies. We propose that the behavioural sequences used by ecdysozoans to moult are an attractive model for studying the role of neuromodulation in behavioural evolution.

Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time.A retrospective, population-based study using nationally representative data between 1995 and 2018 from the National Cancer Registry and Analysis Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized incidence was calculated using Office for National Statistics (ONS) data. Overall survival (OS) was calculated using the Kaplan-Meier estimator. Multivariable analysis was performed using an accelerated failure time model.Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018, highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per 100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In multivariable analysis, age, sex, morphology, stage, site and deprivation were independent predictors of survival (NEN incidence continues to rise in England with survival improving over time. Relatively high survival compared to other cancers is an issue for long-term outcomes and funding of care.Data were extracted and transferred using a grant from Neuroendocrine cancer UK.

Patients with opioid use disorder (OUD) are frequently seen in the ED for opioid-related reasons, which creates an opportunity for ED providers to discuss medications for OUD with their patients. Buprenorphine is a partial mu-opioid agonist that is FDA approved to treat OUD and may be initiated in the ED. Traditionally, buprenorphine therapy was initiated under healthcare provider observation; however, other strategies such as at-home induction have also emerged.This was a retrospective descriptive analysis of patients aged 18 years or older who received a take-home supply of buprenorphine-naloxone from an urban, academic ED between March 2018 and March 2020. The primary outcome was the proportion of patients who filled a prescription for buprenorphine at three months after index ED visit. The proportion of patients that filled a prescription for buprenorphine at six months was also evaluated. The primary safety endpoint was the proportion of patients with return ED visit within six months related to opioid overdose.There were 242 patient records reviewed with 155 patients included in final analysis. Seventy (45.2%) patients filled buprenorphine prescriptions at three months, with 64 (41.3%) who filled buprenorphine prescriptions at six months. Seventeen (11%) patients had a return ED visit related to opioid overdose within six months.Dispensing buprenorphine take-home kits from the ED resulted in continuation of outpatient buprenorphine in almost 50% of patients. Further studies are warranted to define the role of ED-dispensed buprenorphine.

Background Advance care planning (ACP) conversations may result in preferences for medical care being documented. Objective To explore the uptake and quality of advance care directives (ACDs) among older Australians accessing health and aged care services, by overall ACP documentation prevalence, person-level predictors and ACD quality indicators. Design and setting National multi-centre health record audit in general practices (GP), hospitals and residential aged care facilities (RACF). Participants A total of 4187 people aged ≥65 years attending their GP (n = 676), admitted to hospital (n = 1122) or residing in a RACF (n = 2389). Main outcome measures ACP documentation prevalence by setting and type including person-completed ACDs and non-ACD documents (completed by a health professional or someone else); person-level predictors and quality indicators of ACDs. Results Overall ACP documentation prevalence was 46.5% (29.2% weighted). ACD prevalence was 25.3% (14.2% weighted). Unweighted ACD prevalence was higher in RACFs (37.7%) than in hospitals (11.1%) and GPs (5.5%). 35.8% of ACP documentation was completed by a health professional (9.7% weighted), and 18.1% was completed by someone else (10.6% weighted). Having an ACD was positively associated with being female, older, having two or more medical conditions, receiving palliative care, being divorced/separated and being in a RACF. Only 73% of ACDs included full name, signature, document date and witnessing. Conclusions and contribution Low ACP documentation prevalence and a lack of accessible, person-completed and quality ACDs represent an important ACP implementation issue. Low prevalence is complicated by poor document quality and a higher prevalence of documents being completed by someone other than the person.

Introduction Emergency department (ED) initiated opioid use disorder (OUD) care is effective; however, real-world predictors of patient engagement are lacking. Objective This program evaluation examined predictors of ED-based OUD treatment and subsequent engagement. Method Program evaluation in Boston, MA. Adult patients who met criteria for OUD during an ED visit in 2019 were included. Patients were included if a diagnosis of OUD or opioid-related overdose was associated with the ED visit or if they met previously validated criteria for OUD within the previous 12 months. We assessed predictors of ED-OUD treatment receipt and subsequent engagement, using Healthcare Effectiveness Data and Information Set definition of initial encounter within 14 days of discharge and either 2 subsequent encounters or a subsequent buprenorphine prescription within 34 days of the initial encounter. We used generalized estimating equations for panel data. Results During 2019, 1946 patients met criteria for OUD. Referrals to Bridge Clinic were made for 207 (11%), buprenorphine initiated for 106 (5%), and home induction buprenorphine kits given to 56 (3%). Following ED discharge, 237 patients (12%) had a visit within 14 days, 122 (6%) had ≥2 additional visits, and 207 (11%) received a subsequent buprenorphine prescription. Young, White, male patients were most likely to receive ED-OUD care. Patients who received ED-OUD care were more likely to have subsequent treatment engagement (adjusted rate ratio: 2.30, 95% confidence intervals: 1.62-3.27). Referrals were made less often than predicted for Black (-49%) or Hispanic/Latinx (-25%) patients. Conclusions Initiating treatment for OUD in the ED was associated with increased engagement in outpatient addiction care.

BackgroundGoblet cell adenocarcinoma (GCA) of the appendix is a rare and aggressive tumour with varying nomenclature and classification systems. This has led to heterogeneity in published data, and there is a lack of consensus on incidence, survival, and management.MethodsWe provide an overview of GCA with a comprehensive systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and a retrospective analysis of all cases recorded in the English National Cancer Registration and Analysis Service database between 1995 and 2018. The Kaplan–Meier estimator was used to calculate overall survival, and Cox proportional hazards regression was used to identify prognostic factors.ResultsThe systematic review demonstrated an incidence of 0.05–0.3 per 100,000 per year among North American registry studies. The 1-, 3-, and 5-year survival rate was 95.5%, 85.9%–87.6%, and 76.0%–80.6%, respectively. Age, stage, and grade were identified as prognostic factors for survival. Our analysis included 1,225 cases. Age-standardised incidence was 0.0335 per year in 1995 and gradually rose to 0.158 per year in 2018. The 1-, 3-, and 5-year survival rate was 90.0% [95% confidence interval (95% CI): 85.4–94.0], 76.0% (95% CI: 73.8–80.9), and 68.6% (95% CI: 65.9–72.2), respectively. On univariate Cox regression analyses, female sex, stage, and grade were associated with worse overall survival. On multivariate analysis, only stage remained a statistically significant prognostic factor.ConclusionsGCA of the appendix is rare, but incidence is increasing. We report a lower incidence and survival than North American registry studies. Higher stage was associated with decreased survival. Further prospective studies are required to establish optimal management.

BACKGROUND: High-frequency percussive ventilation (HFPV) is an alternative mode of mechanical ventilation that has been shown to improve gas exchange in subjects with severe respiratory failure. We hypothesized that HFPV use would improve ventilation and oxygenation in intubated children with acute bronchiolitis. METHODS: In this single-center prospective cohort study we included mechanically ventilated children in the pediatric ICU with bronchiolitis 1–24 months old who were transitioned to HFPV from conventional invasive mechanical ventilation from November 2018–April 2020. Patients with congenital heart disease, on extracorporeal membrane oxygenation (ECMO), and with HFPV duration < 12 h were excluded. Subject gas exchange metrics and ventilator parameters were compared before and after HFPV initiation. RESULTS: Forty-one of 192 (21%) patients intubated with bronchiolitis underwent HFPV, and 35 met inclusion criteria. Median age of cohort was 4 months, and 60% were previously healthy. All subjects with available oxygenation saturation index (OSI) measurements pre-HFPV met pediatric ARDS criteria (31/35, 89%). Mean CO(2) decreased from 65.4 in the 24 h pre-HFPV to 51 (P < .001) in the 24 h post initiation. S(pO(2))/F(IO(2)) was significantly improved at 24 h post-HFPV (153.3 to 209.7, P = .001), whereas the decrease in mean OSI at 24 h did not meet statistical significance (11.9 to 10.2, P = .15). The mean peak inspiratory pressure (PIP) decreased post-HFPV from 29.7 to 25.0 at 24 h (P < .001). No subjects developed an air leak or hemodynamic instability secondary to HFPV. Two subjects required ECMO, and of these, one subject died. CONCLUSIONS: HFPV was associated with significant improvement in ventilation and decreased exposure to high PIPs for mechanically ventilated children with bronchiolitis in our cohort and had a potential association with improved oxygenation. Our study shows that HFPV may be an effective alternative mode of ventilation in patients with bronchiolitis who have poor gas exchange on conventional invasive mechanical ventilation.

Work Relative Value Units (wRVUs) are a component of many compensation models, and a proxy for the effort required to care for a patient. Accurate prediction of wRVUs generated per patient at triage could facilitate real-time load balancing between physicians and provide many practical operational and clinical benefits.We examined whether deep-learning approaches could predict the wRVUs generated by a patient's visit using data commonly available at triage.Adult patients presenting to an urban, academic emergency department from July 1, 2016-March 1, 2020 were included. Deidentified triage information included structured data (age, sex, vital signs, Emergency Severity Index score, language, race, standardized chief complaint) and unstructured data (free-text chief complaint) with wRVUs as outcome. Five models were examined: average wRVUs per chief complaint, linear regression, neural network and gradient-boosted tree on structured data, and neural network on unstructured textual data. Models were evaluated using mean absolute error.We analyzed 204,064 visits between July 1, 2016 and March 1, 2020. The median wRVUs were 3.80 (interquartile range 2.56-4.21), with significant effects of age, gender, and race. Models demonstrated lower error as complexity increased. Predictions using averages from chief complaints alone demonstrated a mean error of 2.17 predicted wRVUs per visit (95% confidence interval [CI] 2.07-2.27), the linear regression model: 1.00 wRVUs (95% CI 0.97-1.04), gradient-boosted tree: 0.85 wRVUs (95% CI 0.84-0.86), neural network with structured data: 0.86 wRVUs (95% CI 0.85-0.87), and neural network with unstructured data: 0.78 wRVUs (95% CI 0.76-0.80).Chief complaints are a poor predictor of the effort needed to evaluate a patient; however, deep-learning techniques show promise. These algorithms have the potential to provide many practical applications, including balancing workloads and compensation between emergency physicians, quantify crowding and mobilizing resources, and reducing bias in the triage process.

This work examines the grain refinement and mechanical properties of additive friction stir layer welding (AFSLW) of a Mg Alloy. The AFSLW process was used to additively fabricate a seven-layer tall build using 5-mm-thick plates of AZ31 Mg alloy, with each layer containing three parallel welding passes. This multipass AFSLW process demonstrates the ability of this additive method to produce tall and wide structures free of volumetric defects. While the AFSLW material was found to have lower monotonic tensile and fatigue strengths as compared to wrought Mg AZ31-H24, this result was expected due to the heat input from the additive layer welding process that relaxed the cold work strengthening mechanisms. Metallography cross sections and analysis via scanning electron microscopy revealed that the AFSLW build did not contain any detectable defects in any of the 21 weld passes. Furthermore, postmortem fractography found fatigue crack initiation mechanisms to be similar in both the AFSLW and wrought AZ31-H24. The results of this study indicate that large, defect-free builds with predictable mechanical properties can be achieved using the AFSLW process.

Sepsis is a significant public health crisis in the United States, contributing to 50% of inpatient hospital deaths. Given its dramatic health effects and implications in the setting of new CMS care guidelines, ED leaders have renewed focus on appropriate and timely sepsis care, including timely administration of antibiotics in patients at risk for sepsis. Modeling the success of multidisciplinary bedside huddles in improving compliance with appropriate care in other healthcare settings, a Sepsis Huddle was implemented in a large, academic ED, with the goal of driving compliance with standardized sepsis care as described in the CMS SEP-1 measure. A retrospective cohort analysis was performed, with the primary finding that utilization of the Sepsis Huddle resulted in antibiotics being administered on average 41 min sooner than when the Sepsis Huddle was not performed. Given that literature suggests that early administration of appropriate antibiotic therapy is a major driver of mortality reduction in patients with sepsis, this study represents a proof of concept that utilization of a Sepsis Huddle may serve to improve outcomes among ED patients at risk for sepsis.

Emergency department (ED) crowding is associated with increased mortality and delays in care. We developed a rapid admission pathway targeting critically-ill trauma patients in the ED. This study investigates the sustainability of the pathway, as well as its effectiveness in times of increased ED crowding.This was a retrospective cohort study assessing the admission of critically-ill trauma patients with and without the use of a rapid admission pathway from 2013 to 2018. We accessed demographic and clinical data from trauma registry data and ED capacity logs. Statistical analyses included univariate and multivariate testing.A total of 1700 patients were included. Of this cohort, 434 patients were admitted using the rapid admission pathway, whereas 1266 were admitted using the traditional pathway. In bivariate analysis, mean ED LOS was 1.54 h (95% Confidence Interval [CI]: 1.41, 1.66) with the rapid pathway, compared with 5.88 h (95% CI: 5.64, 6.12) with the traditional pathway (p 0.01). We found no statistically significant relationship between rapid admission pathway use and survival to hospital discharge. During times of increased crowding, rapid pathway use continued to be associated with reduction in ED LOS (p 0.01). The reduction in ED LOS was sustained when comparing initial results (2013-2014) to recent data (2015-2018).This study found that a streamlined process to admit critically-ill trauma patients is sustainable and associated with reduction in ED LOS. As ED crowding remains pervasive, these findings support restructured care processes to limit prolonged ED boarding times for critically-ill patients.

Reproduction induces increased food intake across females of many animal species1–4, providing a physiologically relevant paradigm for the exploration of appetite regulation. Here, by examining the diversity of enteric neurons in Drosophila melanogaster, we identify a key role for gut-innervating neurons with sex- and reproductive state-specific activity in sustaining the increased food intake of mothers during reproduction. Steroid and enteroendocrine hormones functionally remodel these neurons, which leads to the release of their neuropeptide onto the muscles of the crop—a stomach-like organ—after mating. Neuropeptide release changes the dynamics of crop enlargement, resulting in increased food intake, and preventing the post-mating remodelling of enteric neurons reduces both reproductive hyperphagia and reproductive fitness. The plasticity of enteric neurons is therefore key to reproductive success. Our findings provide a mechanism to attain the positive energy balance that sustains gestation, dysregulation of which could contribute to infertility or weight gain. A multi-organ circuit is activated in female flies after mating, leading to changes in enteric neurons that increase food intake.

Particle characteristics can drastically influence the process-structure-property-performance aspects of granular materials in compression. We aim to computationally simulate the mechanical processes of stress redistribution in compacts including the kinematics of particle rearrangement during densification and particle deformation leading to fragmentation. Confined compression experiments are conducted with three sets of commercial microcrystalline cellulose particles nearly spherical in shape with different mean particle size. Experimentally measured compression curves from tall powder columns are fitted with the Kenkre et al. (J. of American Chemical Society, Vol. 79, No. 12) model. This model provides a basis to derive several common two-parameter literature models and as a framework to incorporate statistical representations of critical particle behaviors. We focus on the low-stress compression data and the model comparisons typically not discussed in the literature. Additional single particle compressions report fracture strength with particle size for comparison to the apparent particle strength extracted from bulk compression data.

Objectives This study explored associations between birth region, sociodemographic predictors, and advance care planning (ACP) uptake. Methods A prospective, multicenter, cross-sectional audit study of 100 sites across 8 Australian jurisdictions. ACP documentation was audited in the health records of people aged 65 years or older accessing general practice (GP), hospital, and long-term care facility (LTCF) settings. Advance care directives (ACDs) completed by the person (“person completed ACDs”) and ACP documents completed by a health professional or other person (“health professional or someone else ACP”) were counted. Hierarchical multilevel logistic regression assessed associations with birth region. Results From 4,187 audited records, 30.0% (1,152/3,839) were born outside Australia. “Person completed ACDs” were less common among those born outside Australia (21.9% vs 28.9%, X2 (1, N = 3,840) = 20.3, p < .001), while “health professional or someone else ACP” was more common among those born outside Australia (46.4% vs 34.8%, X2 (1, N = 3,840) = 45.5, p < .001). Strongest associations were found for those born in Southern Europe: “person completed ACD” (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.36–0.88), and “health professional or someone else ACP” (OR = 1.41, 95% CI = 1.01–1.98). English-language proficiency and increased age significantly predicted both ACP outcomes. Discussion Region of birth is associated with the rate and type of ACP uptake for some older Australians. Approaches to ACP should facilitate access to interpreters and be sensitive to diverse preferences for individual and family involvement in ACP.

Emergency department (ED) crowding continues to be a major challenge and has important ramifications for patient care quality. One strategy to decrease ED crowding has been to implement alternative pathways to traditional hospital admission. Through a survey-based retrospective cohort study, we aimed to assess the patient experience for those who agreed to transfer and admission to an affiliated community hospital from a large, academic center’s ED. In all, 85% of participants rated their overall experience as either great or good, 92% did not find it hard to make the decision to be transferred, and 95% found the transfer process itself to be easy.

Emergency department (ED) patient experience is a growing area of focus for leaders in the ED and throughout health care. While many factors intrinsic to the ED care environment add to the challenge of providing patients with an excellent experience, doing so holds many benefits, including improved patient compliance and health outcomes, improved workplace satisfaction and reduced provider and staff burnout, decreased malpractice risk, and increased revenue. Although wait time is a major driver of patient experience, provider and staff communication are critically important and excellent communication and perceived empathy may mitigate long waits, overcrowded environments, and other challenges.

Emergency department (ED) operations reflect the intersection of factors external and internal to the ED itself, with unique problems posed by community and academic environments. ED crowding is primarily caused by a lack of inpatient beds for patients admitted through the ED. Changes to front-end operations, such as point-of-care testing and putting physicians in triage, can yield benefits in throughput, but require individual cost analyses. Balancing physician workloads can lead to substantial improvements in throughput. Observation pathways can reduce crowding while maintaining safety. Physician and nurse well-being is an underappreciated topic within operations, and demands close attention and further research.