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.

The financial burden of hospitalization from life-threatening infectious diseases on the U.S. healthcare system is substantial and continues to increase. The purpose of this study was to identify key predictors of high hospital charges for infective endocarditis at a major university-affiliated cardiac care centre in West Virginia.

A retrospective electronic medical records’ review was undertaken of all adult patients admitted for endocarditis between 2014–2018. Multiple linear regression analysis assessed the total charges billed to the patient account for their endocarditis hospitalization in the medical record.

Hospital charges have increased 12-fold during 2014–2018. Among the 486 patients, the median hospital charge was $198 678. About 47% of the patients underwent surgery incurring 70% of the total charges. Patients with hospital stays of ≥50 days accounted for a third of all charges. The multiple linear regression model accounted for 85% of the linear variance in the hospital charges. Median charges increased by 30.87% for patients with ≥9 consultations, 60.32% for those who died in the hospital, and 81.85% for those who underwent surgical intervention.

The study findings showed that complex care requiring multiple consultations, surgical interventions, and longer hospital stays were significantly associated with higher hospital charges for endocarditis treatment.

According to International Union for the Conservation of Nature (IUCN) guidelines, all species must be assessed against all criteria during the Red Listing process. For organismal groups that are diverse and understudied, assessors face considerable challenges in assembling evidence due to difficulty in applying definitions of key terms used in the guidelines. Challenges also arise because of uncertainty in population sizes (Criteria A, C, D) and distributions (Criteria A2/3/4c, B). Lichens, which are often small, difficult to identify, or overlooked during biodiversity inventories, are one such group for which specific difficulties arise in applying Red List criteria. Here, we offer approaches and examples that address challenges in completing Red List assessments for lichens in a rapidly changing arena of data availability and analysis strategies. While assessors still contend with far from perfect information about individual species, we propose practical solutions for completing robust assessments given the currently available knowledge of individual lichen life-histories.

Improving community attitudes and behaviours is core to improving inclusion for people with disability. To identify ways to achieve such change, we analysed data from qualitative interviews with sixty-one expert stakeholders in Australia, informed by our preceding literature review on effective interventions. We identified five themes describing factors with the potential to change attitudes and behaviours to improve inclusion and reduce discrimination: ensuring people with disability have active presence across all life domains; leadership by people with disability, together with organisational and governmental leadership that values the diverse contribution of people with disability; a holistic approach to policy and interventions that targets multiple levels of change; long-term and adequately resourced initiatives to achieve structural and sustained change; and commitment to measuring and monitoring change interventions, to inform decisions and maintain accountability.

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.

OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.

We present new stable oxygen and carbon isotope composite records (δ18O, δ13C) of speleothems from Sandkraal Cave 1 (SK1) on the South African south coast for the time interval between 104 and 18 ka (with a hiatus between 48 and 41 ka). Statistical comparisons using kernel-based correlation analyses and semblance analyses based on continuous wavelet transforms inform the relationships of the new speleothem records to other proxies and their changes through time. Between 105 and ~70 ka, changes of speleothem δ18O values at SK1 are likely related to rainfall seasonality. Variations of δ13C values are associated with changes of vegetation density, prior carbonate precipitation (PCP), CO2 degassing in the cave, and possibly variations of the abundance of C3 and C4 grasses in the vegetation. The relationships of δ18O with other proxies shift between ~70 and 48 ka (Marine Isotope Stages 4–3) so that both stable isotope records now reflect CO2 degassing, evaporation, and PCP. Similar relationships also continue after the hiatus for the deposition phase between 42 and 18 ka. Our findings support modeling results suggesting drier conditions in the study area when the Southern Hemisphere westerlies are shifted north and the paleo–Agulhas Plain is exposed.

Self-perception in early childhood and self-esteem in adulthood are related to a variety of aspects of psychological wellbeing. The goal of the present study was to examine genetic and familial influences on self-perception and self-esteem in separate samples of children (153 twin pairs of 5-year-olds) and adults (753 twin pairs between the ages of 25–75 years). Genetic common factor modeling showed that three facets of self-perception (physical competence, peer acceptance, and maternal acceptance) loaded onto a single heritable factor in children. Multilevel modeling showed no effects of self or co-twin sex on self-perception, but authoritative parenting style was negatively related to self-perception in boys. Similarly, in Study 2, with the adult sample, five self-esteem items loaded on a single heritable factor with no effects of co-twin sex on adult self-esteem. Remembered maternal affection, paternal affection, and maternal discipline were positively related to self-esteem in adults; maternal affection was especially significant for women. The reversal in direction of parenting effects between early childhood and adulthood suggests that parents may play different roles in shaping how children and adults think of themselves. These results suggest that self-perception in childhood and self-esteem in adulthood are both influenced by genetic and environmental factors and that parenting is an important environmental factor for both children and adults.

China adopted neoliberal approaches to improve the supply of quality social services in the early 2000s. How did the Chinese government manage the financial and quality risks of increasing the provision via government purchasing and how did it differ from other countries? The article examines the policy trajectory of early childhood education and care in China and Australia on this question. Policy analysis of the effect of purchasing on the cost to government and quality of services shows how both countries used subsidy arrangements to engage non-profit and private providers to expand supply. When faced with market risks, they both tightened regulations, but China differed in the speed and strength of their response, restricting the proportion of private providers. The findings have implications for understanding the risks of relying on market forces in other social service sectors, and how policy can effectively respond.

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.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the “Lifespan and Life Course Research: integrating strategies” “Un-Meeting” to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.