Objectives/Goals: People with insulin-treated diabetes face hypoglycemia risk due to imperfect insulin replacement and impaired counterregulation. We identified the dopamine antagonist, metoclopramide, as a potential treatment. Hypothesis: Treatment with metoclopramide will prevent the development of impaired counterregulatory response to hypoglycemia. Methods/Study Population: In a pre-clinical model, diabetes was induced in 10-week-old Sprague-Dawley rats with streptozotocin (STZ, 65 mg/kg IP). Rats were divided into three groups: 1) diabetic controls (STZ+RS, n = 6), 2) recurrent hypoglycemia (STZ+RH, n = 7), and 3) recurrent hypoglycemia + metoclopramide (STZ+RH+MET, 3 mg/kg IP, n = 7). After 3 days, all rats underwent a hyperinsulinemic (50 mU/kg/min) and hypoglycemic (~45 mg/dl) clamp. In the clinical trial, adults with Type 1 diabetes (age 20–60, ≥5 years duration) were enrolled in a phase II, double-blinded, placebo-controlled trial. Awareness status was assessed via Gold score, and subjects maintained drug regimens and underwent two hyperinsulinemic-hypoglycemic clamps (where blood glucose was lowered to 100, 65, 55, and 45 mg/dl) to assess counterregulation. Results/Anticipated Results: In the pre-clinical model, glucose infusion rates (GIR) to maintain hypoglycemia were higher in STZ+RH (27±0.9 mg/kg/min) than STZ+RS (19±0.8 mg/kg/min, p Discussion/Significance of Impact: Metoclopramide improves glucoregulatory, sympathoadrenal, and counterregulatory responses to hypoglycemia in pre-clinical models, suggesting dopaminergic regulation. While clinical data are still blinded, increased epinephrine and growth hormone responses suggest treatment may preserve or restore counterregulation.

We conducted a systematic review of the medical, nursing, forensic, and social science literature describing events and processes associated with what happens after a traumatic death in the socio-cultural context of largely Western and high-income societies. These include death notification, why survivors choose to view or not view the body, forensic practices affecting viewing the body, alternatives to viewing, and social and cultural practices following the death. We also describe how elements of these processes may act to increase or lessen some of the negative cognitive and emotional consequences for both survivors and providers. The information presented is applicable to those who may be faced with traumatic deaths, including those who work in medicine, nursing, and law enforcement, as well as first responders, forensic investigators, funeral directors, and the families of the deceased.

Schizotypal traits include abnormalities in cognition, behavior, and interpersonal relationships that are similar, yet less severe than psychotic symptomology. It is estimated that approximately 5% of the general population displays psychotic symptoms and experiences that can be considered schizotypal in nature, but there is little research examining the neurological correlates of these traits. The mismatch negativity (MMN) event-related potential is an objective measure of auditory change detection derived from electroencephalography. The current study contributes to the limited body of evidence examining the neurobiological underpinnings of schizotypy in a non-clinical sample using the MMN. Participants were recruited from the general population and divided into high and low-schizotypy groups for comparison. Individuals with high schizotypal traits displayed reduced MMN amplitudes in response to frequency and location deviants, and longer MMN latencies in response to location deviants. Specific sub-traits of schizotypy were uniquely related to frequency and location amplitudes, suggesting the previously reported inconsistencies in the literature may be due to diverse samples and differing deviant tone types. Finally, impulsivity and sensation-seeking likely contributed to the slower processing seen in location deviance detection. Ultimately, the current results provide evidence that the neurobiological abnormalities seen in clinical populations of schizotypal personality disorder and psychosis also extend to non-clinical populations.

Background: Surgical delays are in common in Canada. Wait times in elective spine surgery and their impact on outcomes remain uncharacterized. Methods: This was a single-center analysis of elective spine surgery data between 2009-2020. Wait times between referral and consultation (T1), consultation and surgical booking (Ti), and booking and surgery (T2) were assessed. Results: 2041 patients were included. Longitudinal analyses were adjusted for age, sex, diagnosis, surgical volume, while outcomes analyses were age and sex-adjusted. Total T1+Ti+T2 increased 8.1% annually (p<0.001). T1 decreased 4.3% annually (p=0.032). It was not associated with adverse events (AEs) or disposition. Every 100 days of T1 was associated with 1.0% longer hospitalization (p=0.001). Ti increased 21.0% annually (p<0.001). Every 100 days of Ti was associated with 2.9% increased odds of an adverse event (p=0.002), 1.8% longer hospitalization (p<0.001), and 15.9% increased likelihood of discharge home (p<0.001). T2 increased 7.0% annually (p<0.001) and was not associated with AEs. Every 100 days of T2 was associated with 11.6% longer hospitalization (p<0.001) and 76.5% increased likelihood of discharge home (p<0.001). Conclusions: Total wait times for elective spine surgery have increased between 2009-2020. Notably, Ti increased ninefold and was associated with AEs. This study highlights areas of delay and targets for healthcare optimization.

Background: Mountain biking (MTB) is an increasingly popular sport that has been associated with serious spinal injuries, which can have devastating effects on patients and significant impacts on healthcare resources. Herein, we characterized the occurrence of these MTB spinal injuries over a 15-year period and analyzed the affiliated acute-care hospital costs. Methods: Patients seen at Vancouver General Hospital for MTB spinal injuries between 2008-2022 were retrospectively reviewed. Demographics, injury details, treatments, outcomes, and resource requirements for acute hospitalization were collected. The Canadian Institute for Health Information was referenced for cost analysis. Results: Over the 15 years of analysis, 149 MTB spinal injuries occurred. The majority (87.2%) were male. 59 (39.6%) were associated with spinal cord injury; most of these were in the cervical spine (72.3%) and majority were AIS Grade A (36.1%). 102 patients (68.5%) required spine surgery; 26 (17.4%) required intensive care; 34 (22.8%) required inpatient rehabilitation. Mean length of stay was 13.5 days and acute admission costs for the healthcare system averaged $35,251 (95% CI $27,080-$43,424). Conclusions: MTB spinal injuries are associated with significant medical, personal, and financial burden. As injury prevention remains paramount, further investigation of the roles of education and safety measures is recommended.

The aim of this study was to better understand the relation of schizotypy traits with sensory gating ability in a sample of community-dwelling individuals with high and low schizotypy traits. Sensory gating was assessed through the paired click paradigm and mid-latency evoked responses (i.e., P50, N100, P200), while schizotypy traits were assessed through the SPQ-BR which was used to classify participants into “high” and “low” schizotypy groups. Based on prior work, we hypothesized that those with the highest schizotypy scores would have reduced sensory gating ability. While this study does not show differences between relatively low and high schizotypy groups on sensory gating ability, it does suggest that our participants may have been experiencing deficits in attention allocation, a downstream cognitive processing measure. Scores on the SPQ-BR suggest that our sample was not close to the high end of the schizotypy traits which may help explain why no differences were found. This research shows the importance of including all levels of schizotypy ratings in clinical research as we can gain a clearer view of the impact of schizotypy on the brain and cognitive functioning in those with “high” levels of schizotypy. Additionally, this work highlights the importance of including measures of important factors such as impulsivity and sensation-seeking to better understand what aspects of schizotypy may be driving these sensory gating alterations reported in the literature.

A review of the literature was undertaken to consider the possible effects of human intervention (shepherding) at around the time of parturition in extensively farmed sheep. There is little clear empirical evidence to suggest that shepherding ensures either easy births or the integrity of ewe–lamb contact — factors closely linked to the welfare of the animals at this time. There is similarly no clear support for shepherding being harmful. However, the following suggestions are made: first, human presence can inhibit or delay parturition; second, extended parturition can increase the risk of, or is associated with, dystocia; and third, disturbance at birth can compromise ewe-lamb bonding and consequently lamb survival. Furthermore, sheep populations that have undergone rigorous selection for ease of lambing and minimal shepherding in extensive environments have well-documented physical and behavioural traits underlying their predisposition for enhanced lamb survival. Although our cultural legacy may impose a duty to intensively monitor animals at lambing, it is concluded that, at least in some situations, shepherding may not be entirely beneficial. The commonly held view of the necessity for some human intervention in extensive livestock systems is perhaps overly paternalistic, and requires a more comprehensive appraisal.

The current study examines the construct validity of the Maximization Scale (MS; Schwartz et al., 2002) and the Maximization Tendency Scale (MTS; Diab et al., 2008) as well as the nomological net of the maximizing construct. We find that both scales of maximizing suffer psychometrically, especially in their proposed dimensionality. Using confirmatory factor analysis and item response theory (IRT) we identify and remove three problematic items from the MTS and six problematic items from the MS. Additionally, we find that the MS appears to be measuring difficulty and restlessness with the search for the best alternative, whereas the MTS is more focused on the search for the best option, regardless of choice difficulty. We then examined these revised scales in relation to other psychological constructs in the nomological net for maximizing and found that maximizers may not be unhappy but are generally distressed in the decision-making context. Finally, we suggest that future maximizng research use revised form of the MTS that seems to us to be most consistent with the original concept of maximizing/satisficing.

We present GECKOS (Generalising Edge-on galaxies and their Chemical bimodalities, Kinematics, and Outflows out to Solar environments), a new ESO VLT/MUSE large program. The main aim of GECKOS is to reveal the variation in key physical processes of disk formation by connecting Galactic Archaeology with integral field spectroscopic observations of nearby galaxies. Edge-on galaxies are ideal for this task: they allow us to disentangle the assembly history imprinted in thick disks and provide the greatest insights into outflows. The GECKOS sample of 35 nearby edge-on disk galaxies is designed to trace the assembly histories and properties of galaxies across a large range of star formation rates, bulge-to-total ratios, and boxy and non-boxy bulges. GECKOS will deliver spatially resolved measurements of stellar abundances, ages, and kinematics, as well as ionised gas metallicities, ionisation param- eters, pressure, and inflow and outflow kinematics; all key parameters for building a complete chemodynamical picture of disk galaxies. With these data, we aim to extend Galactic analysis methods to the wider galaxy population, reaping the benefits of detailed Milky Way studies, while probing the diverse mechanisms of galaxy evolution.

Background: Mean arterial pressure augmentation is one current established practice for management of patients with SCI. We present the first data investigating the effectiveness of Intrathecal Pressure (ITP) reduction through CSF drainage (CSFD) in managing patients with acute traumatic SCI at a large academic center. Methods: Data from 6 patients with acute traumatic SCI were included. A lumbar intrathecal catheter was used to monitor ITP and volume of CSFD. CSFD was performed and recorded hourly. ITP recordings were collected hourly and the change in ITP was calculated (hour after minus before CSFD). 369 data points were collected and change in ITP was plotted against volume of CSFD. Results: Data across all patients showed variability in the ITP over time without a significant trend (slope=0.016). We found no significant change in ITP with varying amounts of CSFD (slope=0.007, r2=0.00, p=0.88). Changes in ITP were not significantly different across groups of CSFD but the variation in the data decreased with increasing levels of CSFD. Conclusions: We present the first known data on changes in ITP with varying degrees of CSFD in patients with acute traumatic SCI. These results may provide insight into the complexity of ITP changes in patients post-injury and help inform future SCI management.

Background: Length of stay (LOS) is a surrogate for care complexity and a determinant of occupancy and service provision. Our primary goal was to assess changes in and determinants of LOS at a quaternary spinal care center. Secondary goals included identifying opportunities for improvement and determinants of future service planning. Methods: This is a prospective study of patients admitted from 2006 to 2019. Data included demographics, diagnostic category (degenerative, oncology, deformity, trauma, other), LOS (mean, median, interquartile range, standard deviation) and in-hospital adverse events (AEs). Results: 13,493 admissions were included. Mean age has increased from 48.4 (2006) to 58.1 years (2019) (p=<0.001). Mean age increased overtime for patients treated for deformity (p=<0.001), degenerative pathology (p=<0.001) and trauma (p=<0.001), but not oncology (p=0.702). Overall LOS has not changed over time (p=0.451). LOS increased in patients with degenerative pathology (p=0.019) but not deformity (p=0.411), oncology (p=0.051) or trauma (p=0.582). Emergency admissions increased overtime for degenerative pathologies (p=<0.001). AEs and SSIs have decreased temporally (p=<0.001). Conclusions: This is the first North American study to analyze temporal trends in LOS for spine surgery in an academic center. Understanding temporal trends in LOS and patient epidemiology can provide opportunities for intervention, targeted at the geriatric populations, to reduce LOS.

Background: Prolonged length of stay (LOS) is associated with increased resource utilization and worse outcomes. The goal of this study is identifying patient, surgical and systemic factors associated with prolonged LOS overall and per diagnostic category for adults admitted to a quaternary spinal care center. Methods: We performed a retrospective analysis on 13,493 admissions from 2006 to 2019. Factors analyzed included patient age, sex, emergency vs elective admission, diagnostic category (degenerative, deformity, oncology, trauma), presence of neurological deficits in trauma patients, ASIA score, operative management and duration, blood loss, and adverse events (AEs). Univariate and multivariate analyses determined factors associated with prolonged LOS. Results: Overall mean LOS (±SD) was 15.80 (±34.03) days. Through multivariate analyses, predictors of prolonged LOS were advanced age (p<0.001), emergency admission (p<0.001), advanced ASIA score (p<0.001), operative management (p=0.043), and presence of AEs (p<0.001), including SSI (p=0.001), other infections (systemic and UTI) (p<0.001), delirium (p=0.006), and pneumonia (p<0.001). The effects of age, emergency admission, and AEs on LOS differed by diagnostic category. Conclusions: Understanding patient and disease factors that affect LOS provides opportunities for QI intervention and allows for an informed preoperative discussion with patients. Future interventions can be targeted to maximize patient outcomes, optimize care quality, and decrease costs.

We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (${>}7 \times 10^{10} {\mathrm{M}}_\odot$) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ($0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$, as well as hundreds of emission-line sources at $z < 6$. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.

Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.

In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.