Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk.

Background: Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment. Methods: Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed. Results: CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells. Conclusion: There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

How environmental impact is considered in economic evaluations of critical care: a scoping review.

PURPOSE: Health care is a major contributor to climate change, and critical care is one of the sector's highest carbon emitters. Health economic evaluations form an important component of critical care and may be useful in identifying economically efficient and environmentally sustainable strategies. The purpose of this scoping review was to synthesise available literature on whether and how environmental impact is considered in health economic evaluations of critical care. METHODS: A robust scoping review methodology was used to identify studies reporting on environmental impact in health economic evaluations of critical care. We searched six academic databases to locate health economic evaluations, costing studies and life cycle assessments of critical care from 1993 to present. RESULTS: Four studies met the review's inclusion criteria. Of the 278 health economic evaluations of critical care identified, none incorporated environmental impact into their assessments. Most included studies (n = 3/4) were life cycle assessments, and the remaining study was a prospective observational study. Life cycle assessments used a combination of process-based data collection and modelling to incorporate environmental impact into their economic assessments. CONCLUSIONS: Health economic evaluations of critical care have not yet incorporated environmental impact into their assessments, and few life cycle assessments exist that are specific to critical care therapies and treatments. Guidelines and standardisation regarding environmental data collection and reporting in health care are needed to support further research in the field. In the meantime, those planning health economic evaluations should include a process-based life cycle assessment to establish key environmental impacts specific to critical care.

Perceptions of gender equity among critical care and other health professionals: A cross-sectional survey.

OBJECTIVE: The objective of this study was to determine the association between gender and perceived gender equity in the critical care workforce and other health specialties. DESIGN AND SETTING: We conducted an online cross-sectional survey between September and November 2020. Data on demographics and perceptions of equity including the representation of women across departments and in leadership roles, knowledge of and access to flexible work practices and carers leave, and opportunities for promotion were collected. PARTICIPANTS: The study population included health professionals from critical care (defined as intensive care and emergency) and other specialties. We conducted a descriptive gender-disaggregated analysis. RESULTS: A total of 478 respondents (70% women) completed the survey. The mean age of respondents was 43.9 ± 11.2 years. Approximately half of respondents were medical practitioners (n = 235, 54%), followed by nurses (n = 135, 36%)-the remainder were from other professions. The critical care workforce accounted for 280 (64%) of responder practice settings. Statistically significant differences were reported between genders on issues such as having confidence that their department would resolve equity issues (87 [70.7%] men vs. 146 [48.2%] women; p = 0.007), access to flexible work practices (5/124 [4.0%] men vs. 20/305 [6.6%] women p = 0.001), and taking unpaid leave for carer responsibilities (91 [30.3%] women vs 9 [7.4%] men, p < 0.001). CONCLUSIONS: This work highlights differences in how men and women perceive gender equity, particularly in the critical care workforce. These findings are important to understand health care practitioners' perceptions of gender equity, as these perceptions inform behaviour.

Sepsis-coded hospitalisations and associated costs in Australia: a retrospective analysis.

OBJECTIVE: To report trends in Australian hospitalisations coded for sepsis and their associated costs. DESIGN: Retrospective analysis of Australian national hospitalisation data from 2002 to 2021. METHODS: Sepsis-coded hospitalisations were identified using the Global Burden of Disease study sepsis-specific ICD-10 codes modified for Australia. Costs were calculated using Australian-Refined Diagnosis Related Group codes and National Hospital Cost Data Collection. RESULTS: Sepsis-coded hospitalisations increased from 36,628 in 2002-03 to 131,826 in 2020-21, an annual rate of 7.8%. Principal admission diagnosis codes contributed 13,843 (37.8%) in 2002-03 and 44,186 (33.5%) in 2020-21; secondary diagnosis codes contributed 22,785 (62.2%) in 2002-03 and 87,640 (66.5%) in 2020-21. Unspecified sepsis was the most common sepsis code, increasing from 15,178 hospitalisations in 2002-03 to 68,910 in 2020-21. The population-based incidence of sepsis-coded hospitalisations increased from 18.6 to 10,000 population (2002-03) to 51.3 per 10,000 (2021-21); representing an increase from 55.1 to 10,000 hospitalisations in 2002-03 to 111.4 in 2020-21. Sepsis-coded hospitalisations occurred more commonly in the elderly; those aged 65 years or above accounting for 20,573 (55.6%) sepsis-coded hospitalisations in 2002-03 and 86,135 (65.3%) in 2020-21. The cost of sepsis-coded hospitalisations increased at an annual rate of 20.6%, from AUD199M (€127 M) in financial year 2012 to AUD711M (€455 M) in 2019. CONCLUSION: Hospitalisations coded for sepsis and associated costs increased significantly from 2002 to 2021 and from 2012 to 2019, respectively.

Communication functions of adult patients admitted to intensive care: A multicentre, binational point prevalence study.

BACKGROUND: Patient communication is profoundly impacted during the intensive care unit (ICU) stay. While the impacts of altered communication are recognised, there is a paucity of data on the prevalence of communication attempts as well as modes utilised by patients and unit practices to manage communication function. OBJECTIVE: The objectives of this study were to describe the prevalence and characteristics of observed communication attempts (nonverbal, verbal, and use of the staff call bell) in adult ICU patients and report on unit-level practices on communication management. METHODS: A prospective, binational, cross-sectional point-prevalence study was conducted across 44 Australia and New Zealand adult ICUs. Data on communication attempts, modes, ICU-level guidelines, training, and resources were collected in June 2019. RESULTS: Across 44 ICUs, 470 of 623 (75%) participants, including ventilated and nonventilated patients, were attempting to communicate on the study day. Of those invasively ventilated via an endotracheal tube for the entire study day, 42 of 172 (24%) were attempting to communicate and 39 of 45 (87%) patients with a tracheostomy were attempting to communicate. Across the cohort, the primary mode of communication was verbal communication, with 395 of 470 (84%) patients using speech; of those 371 of 395 (94%) spoke English and 24 of 395 (6%) spoke a language other than English. Participants attempting to communicate on the study day had a shorter length of stay (LOS), a mean difference of 3.8 days (95% confidence interval: 0.2; 5.1) shorter LOS in the ICU than those not attempting to communicate, and a mean difference 7.9 days (95% confidence interval: 3.1; 12.6) shorter LOS in hospital overall. Unit-level practices and supports were collected. Six of 44 (14%) ICUs had a protocol for communication management, training was available in 11 of 44 (25%) ICUs, and communication resources were available in 37 of 44 (84%) ICUs. CONCLUSION: Three-quarters of patients admitted to the ICU were attempting to communicate on the study day, with multiple methods used to support verbal and nonverbal communication regardless of ventilation status. Guidance and training were absent from the majority of ICUs, indicating a need for development and implementation of policies, training, and resources.

Dysphagia in adult intensive care patients: Results of a prospective, multicentre binational point prevalence study.

BACKGROUND: Dysphagia occurs in intensive care unit (ICU) patients. However, there is a lack of epidemiological data on the prevalence of dysphagia in adult ICU patients. OBJECTIVES: The objective of this study was to describe the prevalence of dysphagia in nonintubated adult patients in the ICU. METHODS: A prospective, multicentre, binational, cross-sectional point prevalence study was conducted in 44 adult ICUs in Australia and New Zealand. Data were collected in June 2019 on documentation of dysphagia, oral intake, and ICU guidelines and training. Descriptive statistics were used to report demographic, admission, and swallowing data. Continuous variables are reported as means and standard deviations (SDs). Precisions of estimates were reported as 95% confidence intervals (CIs). RESULTS: Of the 451 eligible participants, 36 (7.9%) were documented as having dysphagia on the study day. In the dysphagia cohort, the mean age was 60.3 years (SD: 16.37) vs 59.6 years (SD: 17.1) and almost two-thirds were female (61.1% vs 40.1%). The most common admission source for those patients with dysphagia were from the emergency department (14/36, 38.9%), and seven of 36 (19.4%) had a primary diagnosis of trauma (odds ratio: 3.10, 95% CI 1.25 - 7.66). There were no statistical differences in Acute Physiology and Chronic Health Evaluation (APACHE II) scores between those with and without a dysphagia diagnosis. Patients with dysphagia were more likely to have a lower mean body weight of 73.3 kg vs 82.1 kg than patients not documented as having dysphagia (95% CI of mean difference: 0.43 to 17.07) and require respiratory support (odds ratio: 2.12, 95% 1.06 to 4.25). The majority of patients with dysphagia were prescribed modified food and fluids in the ICU. Less than half of ICUs surveyed reported unit-level guidelines, resources, or training for management of dysphagia. CONCLUSIONS: The prevalence of documented dysphagia in adult ICU nonintubated patients was 7.9%. There were a higher proportion of females with dysphagia than previously reported. Approximately two-thirds of patients with dysphagia were prescribed oral intake, and the majority were receiving texture-modified food and fluids. Dysphagia management protocols, resources, and training are lacking across Australian and New Zealand ICUs.

Sex differences in long-term survival after intensive care unit treatment for sepsis: A cohort study.

OBJECTIVE: To determine the effect of sex on sepsis-related ICU admission and survival for up to 3-years. METHODS: Retrospective cohort study of adults admitted to Australian ICUs between 2018 and 2020. Men and women with a primary diagnosis of sepsis were included. The primary outcome of time to death for up to 3-years was examined using Kaplan Meier plots. Secondary outcomes included the duration of ICU and hospital stay. RESULTS: Of 523,576 admissions, there were 63,039 (12·0%) sepsis-related ICU admissions. Of these, there were 50,956 patients (43·4% women) with 3-year survival data. Men were older (mean age 66·5 vs 63·6 years), more commonly received mechanical ventilation (27·4% vs 24·7%) and renal replacement therapy (8·2% vs 6·8%) and had worse survival (Hazard Ratio [HR] 1·11; 95% Confidence Interval [CI] 1·07 to 1·14, P<0·001) compared to women. The duration of hospital and ICU stay was longer for men, compared to women (median hospital stay, 9.8 vs 9.4 days; p<0.001 and ICU stay, 2.7 vs 2.6 days; p<0.001). CONCLUSION: Men are more likely to be admitted to ICU with sepsis and have worse survival for up to 3-years. Understanding causal mechanisms of sex differences may facilitate the development of targeted sepsis strategies.

Sex and gender reporting in Australian health and medical research publications.

OBJECTIVE: This study aimed to determine how sex and gender are being incorporated into Australian medical research publications and if this is influenced by journals endorsing the International Committee of Medical Journal Editors (ICMJE) guidelines, which contain criteria for sex and gender reporting. METHODS: Analysis of original research articles published in Australia's top 10 medical journals in 2020. RESULTS: From the 10 leading journals, 1,136 articles were eligible for analysis, including 990 human participant populations. Sex and/or gender were reported for 873 (88.2%) human populations, with 480 using conflicting terminology. Only 14 (1.6%) described how sex and gender were determined. The primary outcome, or key aim, was stratified by sex and/or gender for 249 (29.2%) participant groups and the influence of sex and/or gender on the results was discussed for only 171 (17.3%). There was no significant association between endorsement of the ICMJE guidelines and adherence to any sex and gender criteria. CONCLUSIONS: Sex and gender are poorly incorporated into Australian medical research publications and was not improved by journals endorsing the ICMJE guidelines. IMPLICATIONS FOR PUBLIC HEALTH: Reporting and analysis of sex and gender data in health research in Australian medical journals requires improvement, for better health for all.

Sepsis, critical illness, communication, swallowing and Sustainable Development Goals 3, 4, 10.

PURPOSE: Sepsis is a major global health problem with an estimated 49 million cases globally each year causing as many as 11 million deaths. The primary objective of this commentary is to describe the impacts of sepsis and critical illness on communication and swallowing function, and to discuss management strategies considering the Sustainable Development Goals (SDGs). RESULT: Communication and swallowing disabilities can occur with sepsis and critical illness. A holistic framework to optimise function, recovery, and future research priorities across the lifespan can be developed through the SDGs. CONCLUSION: Communication and swallowing disabilities following critical illness associated with sepsis have global impacts. Early multidisciplinary engagement is key to optimising individuals' function. Collaborative research, education, and public awareness is urgently needed to increase equity in health outcomes across populations. This commentary paper supports progress towards good health and well-being (SDG 3), quality education (SDG 4) and reduced inequalities (SDG 10).

Economic evaluations for intensive care unit randomised clinical trials in Australia and New Zealand: Practical recommendations for researchers.

OBJECTIVES: Economic evaluations of intensive care unit (ICU) interventions have specific considerations, including how to cost ICU stays and accurately measure quality of life in survivors. The aim of this article was to develop best practice recommendations for economic evaluations alongside future ICU randomised controlled trials (RCTs). REVIEW METHODS: We collated our experience based on expert consensus across several recent economic evaluations to provide best-practice, practical recommendations for researchers conducting economic evaluations alongside RCTs in the ICU. Recommendations were structured according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) Task Force Report. RESULTS: We discuss recommendations across the components of economic evaluations, including: types of economic evaluation, the population and sample size, study perspective, comparators, time horizon, choice of health outcomes, measurement of effectiveness, measurement and valuation of quality of life, estimating resources and costs, analytical methods, and the increment cost-effectiveness ratio. We also provide future directions for research with regard to developing more robust economic evaluations for the ICU. CONCLUSION: Economic evaluations should be built alongside ICU RCTs and should be designed a priori using appropriate follow-up and data collection to capture patient-relevant outcomes. Further work is needed to improve the quality of data available for linkage in Australia as well as developing costing methods for the ICU and appropriate quality of life measurements.

A New Strategy for Linking U.S. Historical Censuses: A Case Study for the IPUMS Multigenerational Longitudinal Panel.

This paper presents a probabilistic method of record linkage, developed using the U.S. full count censuses of 1900 and 1910 but applicable to many sources of digitized historical records. The method links records using a two-step approach, first establishing high confidence matches among men by exploiting a comprehensive set of individual and contextual characteristics. The method then proceeds to link both men and women by leveraging links between households established in the first step. While only the first stage links can be directly comparable to other popular methods in research on the U.S., our method yields both considerably higher linkage rates and greater accuracy while only performing negligibly worse than other algorithms in resembling the target population.

Study protocol of a randomized controlled trial comparing two linkage models for HIV prevention and treatment in justice-involved persons.

BACKGROUND: Persons involved in the justice system are at high risk for HIV and drug overdose upon release to the community. This manuscript describes a randomized controlled trial of two evidence-based linkage interventions for provision of HIV prevention and treatment and substance use disorder (SUD) services in four high risk communities to assess which is more effective at addressing these needs upon reentry to the community from the justice system. METHODS: This is a 5-year hybrid type 1 effectiveness-implementation randomized controlled trial that compares two models (Patient Navigation [PN] or Mobile Health Unit [MHU] service delivery) of linking justice-involved individuals to the continuum of community-based HIV and SUD prevention and treatment service cascades of care. A total of 864 justice-involved individuals in four US communities with pre-arrest histories of opioid and/or stimulant use who are living with or at-risk of HIV will be randomized to receive either: (a) PN, wherein patient navigators will link study participants to community-based service providers; or (b) services delivered via an MHU, wherein study participants will be provided integrated HIV prevention/ treatment services and SUD services. The six-month post-release intervention will focus on access to pre-exposure prophylaxis (PrEP) for those without HIV and antiretroviral treatment (ART) for people living with HIV (PLH). Secondary outcomes will examine the continuum of PrEP and HIV care, including: HIV viral load, PrEP/ ART adherence; HIV risk behaviors; HCV testing and linkage to treatment; and sexually transmitted infection incidence and treatment. Additionally, opioid and other substance use disorder diagnoses, prescription, receipt, and retention on medication for opioid use disorder; opioid and stimulant use; and overdose will also be assessed. Primary implementation outcomes include feasibility, acceptability, sustainability, and costs required to implement and sustain the approaches as well as to scale-up in additional communities. DISCUSSION: Results from this project will help inform future methods of delivery of prevention, testing, and treatment of HIV, HCV, substance use disorders (particularly for opioids and stimulants), and sexually transmitted infections for justice-involved individuals in the community. TRIAL REGISTRATION: Clincialtrials.gov NCT05286879 March 18, 2022.

Sex differences in sepsis hospitalisations and outcomes in older women and men: A prospective cohort study.

PURPOSE: To examine the association of sex with hospitalisation due to sepsis and related outcomes. METHODS: Prospective cohort study of 264,678 adults, average age 62.7 years at recruitment (2006-2009) in Australia. Participants were followed for sepsis hospitalisation identified using the International Classification of Diseases coding. Outcomes included sex differences in the risk of an incident sepsis hospitalisation, mortality, length of ICU and hospital stay and readmissions during the following year. RESULTS: Over 2,070,343 years of follow-up there were 12,912 sepsis hospitalisations, 59.6% in men. Age-standardised risk of hospitalisation was higher in men versus women (10.37 vs 6.77 per 1,000 person years; age-adjusted HR 1.58; 95% CI 1.53-1.59) and did not attenuate after adjusting for sociodemographics, health behaviours and co-morbidities. Relative risks were similar for sepsis-related ICU admissions (adjusted HR 1.72; 95% CI 1.57-1.88). Death at one year was more common in men than women (39.3% vs 33.7% p<0.001). After adjusting for age, men had a longer hospital (12.0 vs 11.2 days; p<0.001) and ICU (6.5 vs 5.8 days; p<0.001) stays and were more likely to be readmitted to hospital for sepsis (22.3 vs 19.4%; p<0.001) or any reason (73.0% vs 70.7%; p<0.001) at one year. CONCLUSION: In older adults, compared to women, men are at an increased risk of sepsis hospitalisation, sepsis-related ICU admission, death and readmission to hospital within one year after a sepsis hospitalisation. Understanding these sex differences and their mechanisms may offer opportunities for better prevention and management and improved patient outcomes.

Renewed rationale for sex- and gender-disaggregated research: A COVID-19 commentary review.

The COVID-19 pandemic provides a contemporaneous illustration of the need to consider sex and gender in research. Using surveillance, treatment and vaccine research examples, in this commentary review, we highlight opportunities for innovation in sex- and gender-sensitive and transformative health and medical research.

Association between intravenous fluid resuscitation and outcome among patients with suspected infection and sepsis: A retrospective cohort study.

OBJECTIVE: To investigate the association between timing and volume of intravenous fluids administered to ED patients with suspected infection and all-cause in-hospital mortality. METHODS: Retrospective cohort study of ED presentations at four metropolitan hospitals in Sydney, Australia, between October 2018 and May 2019. Patients over 16 years of age with suspected infection who received intravenous fluids within 24 h of presentation were included. RESULTS: During the study period, 7533 patients with suspected infection received intravenous fluids. Of these, 1996 (26.5%) and 231 (3.1%) had suspected sepsis and septic shock, respectively. Each 1000 mL increase in intravenous fluids administered was associated with a reduction in risk of in-hospital mortality (adjusted odds ratio [AOR] 0.87, 95% confidence interval [CI] 0.76-0.99). This association was stronger in patients with septic shock (AOR 0.66, 95% CI 0.49-0.89), and those admitted to intensive care unit (ICU) (AOR 0.74, 95% CI 0.56-0.96). Patients with suspected sepsis and septic shock who received a total volume of >3600 mL had lower in-hospital mortality (AOR 0.44, 95% CI 0.22-0.91; AOR 0.16, 95% CI 0.05-0.57) compared to those administered <3600 mL within the first 24 h of presenting to the ED. There was no association between the time of initiation of fluids and in-hospital mortality among survivors and non-survivors (2.3 vs 2.5 h, P = 0.50). CONCLUSION: We observed a reduction in risk of in-hospital mortality for each 1000 mL increase in intravenous fluids administered in patients with septic shock or admitted to ICU suggesting illness severity to be a likely effect modifier.

Long-term costs and cost-effectiveness of adjunctive corticosteroids for patients with septic shock in New Zealand.

OBJECTIVE: The aim of the study was to determine whether adjunctive hydrocortisone reduced healthcare expenditure and was cost-effective compared with placebo in New Zealand patients in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. DESIGN: This is a health economic analysis using data linkage to New Zealand Ministry of Health databases to determine resource use, costs, and cost-effectiveness for a 24-month period. SETTING: The study was conducted in New Zealand. PARTICIPANTS AND INTERVENTION: Patients with septic shock were randomised to receive a 7-day continuous infusion of 200 mg of hydrocortisone or placebo in the ADRENAL trial. MAIN OUTCOME MEASURES: Healthcare expenditure was associated with all hospital admissions, emergency department presentations, outpatient visits, and pharmacy expenditure. Effectiveness outcomes included mortality at 6 months and 24 months and quality of life at 6 months. Cost-effectiveness outcomes were assessed with reference to quality-adjusted life years gained at 6 months and life years gained at 24 months. RESULTS: Of 3800 patients in the ADRENAL trial, 419 (11.0%) were eligible, and 405 (96.7% of those eligible) were included. The mean total costs per patient over 24 months were $143,627 ± 100,890 and $143,772 ± 97,117 for the hydrocortisone and placebo groups, respectively (p = 0.99). Intensive care unit costs for the index admission were $50,492 and $62,288 per patient for the hydrocortisone and placebo groups, respectively (p = 0.09). The mean number of quality-adjusted life years gained at 6 months and mean number of life years gained at 24 months was not significantly different by treatment group, and the probability of hydrocortisone being cost-effective was 55% at 24 months. CONCLUSIONS: In New Zealand, adjunctive hydrocortisone did not reduce total healthcare expenditure or improve outcomes compared with placebo in patients with septic shock.

Estrogenic signaling and sociosexual behavior in wild sex-changing bluehead wrasses, Thalassoma bifasciatum.

Estrogenic signaling is an important focus in studies of gonadal and brain sexual differentiation in fishes and vertebrates generally. This study examined variation in estrogenic signaling (1) across three sexual phenotypes (female, female-mimic initial phase [IP] male, and terminal phase [TP] male), (2) during socially-controlled female-to-male sex change, and (3) during tidally-driven spawning cycles in the protogynous bluehead wrasse (Thalassoma bifasciatum). We analyzed relative abundances of messenger RNAs (mRNAs) for the brain form of aromatase (cyp19a1b) and the three nuclear estrogen receptors (ER) (ERα, ERßa, and ERßb) by qPCR. Consistent with previous reports, forebrain/midbrain cyp19a1b was highest in females, significantly lower in TP males, and lowest in IP males. By contrast, ERα and ERßb mRNA abundances were highest in TP males and increased during sex change. ERßa mRNA did not vary significantly. Across the tidally-driven spawning cycle, cyp19a1b abundances were higher in females than TP males. Interestingly, cyp19a1b levels were higher in TP males close (~1 h) to the daily spawning period when sexual and aggressive behaviors rise than males far from spawning (~10-12 h). Together with earlier findings, our results suggest alterations in neural estrogen signaling are key regulators of socially-controlled sex change and sexual phenotype differences. Additionally, these patterns suggest TP male-typical sociosexual behaviors may depend on intermediate rather than low estrogenic signaling. We discuss these results and the possibility that an inverted-U shaped relationship between neural estrogen and male-typical behaviors is more common than presently appreciated.

Establishing Healthcare Worker Performance and Safety in Providing Critical Care for Patients in a Simulated Ebola Treatment Unit: Non-Randomized Pilot Study.

Improving the provision of supportive care for patients with Ebola is an important quality improvement initiative. We designed a simulated Ebola Treatment Unit (ETU) to assess performance and safety of healthcare workers (HCWs) performing tasks wearing personal protective equipment (PPE) in hot (35 °C, 60% relative humidity) or thermo-neutral (20 °C, 20% relative humidity) conditions. In this pilot phase to determine the feasibility of study procedures, HCWs in PPE were non-randomly allocated to hot or thermo-neutral conditions to perform peripheral intravenous (PIV) and midline catheter (MLC) insertion and endotracheal intubation (ETI) on mannequins. Eighteen HCWs (13 physicians, 4 nurses, 1 nurse practitioner; 2 with prior ETU experience; 10 in hot conditions) spent 69 (10) (mean (SD)) minutes in the simulated ETU. Mean (SD) task completion times were 16 (6) min for PIV insertion; 33 (5) min for MLC insertion; and 16 (8) min for ETI. Satisfactory task completion was numerically higher for physicians vs. nurses. Participants' blood pressure was similar, but heart rate was higher (p = 0.0005) post-simulation vs. baseline. Participants had a median (range) of 2.0 (0.0-10.0) minor PPE breaches, 2.0 (0.0-6.0) near-miss incidents, and 2.0 (0.0-6.0) health symptoms and concerns. There were eight health-assessment triggers in five participants, of whom four were in hot conditions. We terminated the simulation of two participants in hot conditions due to thermal discomfort. In summary, study tasks were suitable for physician participants, but they require redesign to match nurses' expertise for the subsequent randomized phase of the study. One-quarter of participants had a health-assessment trigger. This research model may be useful in future training and research regarding clinical care for patients with highly infectious pathogens in austere settings.