Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.

Objectives/Goals: Chronic stress may accelerate biological aging yet is often overlooked in clinical settings. Many tools to assess stress exist, but a comprehensive measure of cumulative stress across the lifespan is unavailable. This study validates a novel measure of lifetime stress for use as a screening tool in clinical practice. Methods/Study Population: Patients (n > 220) enrolled in brain health research registry at the Washington University St. Louis Knight Alzheimer Disease Research Center completed in-person surveys at baseline and after six months. Baseline measures included the everyday discrimination scale (EDS), total adverse experience (TAE), and demographics. Age and evaluating life course stress experience (ELSE) scores were measured six months later. Ongoing analysis includes age-adjusted correlations of ELSE scores with TAE and EDS scores. We will investigate the correlation with race and ethnicity and sex assigned at birth. We will explore the relationship between ELSE score and multidimensional intersectionality. Results/Anticipated Results: The sample was 87% Black or African American, 8% White, 4% Hispanic, 82% female, and 18% male, with a mean age of 66 ± 10 years. Age-adjusted relationships between patient characteristics and ELSE scores will be analyzed. Additionally, ELSE responses will be compared against age, EDS, and TAE measurements. Intersectionality between race-ethnicity, sex, and gender will be examined. We hypothesize ELSE scores will vary by demographic. Preliminary results indicate the ELSE scale correlates with established life stress measures, accounting for cumulative stress exposure across a lifespan independent of specific stressor topics. Discussion/Significance of Impact: The ELSE scale is a viable tool for clinical screening of chronic stress exposure over a lifespan. Its implementation will allow clinicians to identify patients at high risk for accelerated aging, facilitating targeted interventions and advancing equity in healthcare delivery.

Fifty-three tests designed to measure aspects of creative thinking were administered to 410 air cadets and student officers. The scores were intercorrelated and 16 factors were extracted. Orthogonal rotations resulted in 14 identifiable factors, a doublet, and a residual. Nine previously identified factors were: verbal comprehension, numerical facility, perceptual speed, visualization, general reasoning, word fluency, associational fluency, ideational fluency, and a factor combining Thurstone's closure I and II. Five new factors were identified as originality, redefinition, adaptive flexibility, spontaneous flexibility, and sensitivity to problems.

Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.

The optimum parameters for the generation of synchrotron radiation in ultraintense laser pulse interactions with planar foils are investigated with the application of Bayesian optimization, via Gaussian process regression, to 2D particle-in-cell simulations. Individual properties of the synchrotron emission, such as the yield, are maximized, and simultaneous mitigation of bremsstrahlung emission is achieved with multi-variate objective functions. The angle-of-incidence of the laser pulse onto the target is shown to strongly influence the synchrotron yield and angular profile, with oblique incidence producing the optimal results. This is further explored in 3D simulations, in which additional control of the spatial profile of synchrotron emission is demonstrated by varying the polarization of the laser light. The results demonstrate the utility of applying a machine learning-based optimization approach and provide new insights into the physics of radiation generation in laser–foil interactions, which will inform the design of experiments in the quantum electrodynamics (QED)-plasma regime.

Some physiological variables which could aid in assessing the welfare of beef cattle in feedlots were screened in this exploratory study. In two experiments, each of 42 days duration, the physiological responses of Bos taurus steers to three treatments were investigated: pasture (rotation between 1.5 hectare paddocks); a feedlot yard stocked at 12.0 m2 per head with a dry, firm pen surface; and a ‘high-density’ feedlot yard stocked at 6.0 m2 per head with a wet and muddy pen surface. Fourteen steers were used per group per experiment. Relative adrenal mass in both feedlot groups was 8-10% higher than in the pasture group, and this finding was supported by morphological measurements of the adrenal glands. Out of 17 immune variables examined, only serum IgA and the T-cell lymphocytes subpopulation WC+1 showed consistent differences between the feedlot and pasture groups. Interestingly, no differences were observed between the two feedlot treatments. It was concluded that although there may have been some disruption of epithelial/mucosal immunity, more support was required from other immune variables before it could be stated that the immune system was depressed and that pre-pathological states existed in the feedlot groups. However, measures of relative adrenal weight, adrenal index, serum IgA and WC1+ lymphocytes are good candidates for use in future welfare investigations of feedlot cattle.

Two introduced carnivores, the European red fox Vulpes vulpes and domestic cat Felis catus, have had extensive impacts on Australian biodiversity. In this study, we collate information on consumption of Australian birds by the fox, paralleling a recent study reporting on birds consumed by cats. We found records of consumption by foxes on 128 native bird species (18% of the non-vagrant bird fauna and 25% of those species within the fox’s range), a smaller tally than for cats (343 species, including 297 within the fox’s Australian range, a subset of that of the cat). Most (81%) bird species eaten by foxes are also eaten by cats, suggesting that predation impacts are compounded. As with consumption by cats, birds that nest or forage on the ground are most likely to be consumed by foxes. However, there is also some partitioning, with records of consumption by foxes but not cats for 25 bird species, indicating that impacts of the two predators may also be complementary. Bird species ≥3.4 kg were more likely to be eaten by foxes, and those <3.4 kg by cats. Our compilation provides an inventory and describes characteristics of Australian bird species known to be consumed by foxes, but we acknowledge that records of predation do not imply population-level impacts. Nonetheless, there is sufficient information from other studies to demonstrate that fox predation has significant impacts on the population viability of some Australian birds, especially larger birds, and those that nest or forage on the ground.

Introduced mammalian predators are responsible for the decline and extinction of many native species, with rats (genus Rattus) being among the most widespread and damaging invaders worldwide. In a naturally fragmented landscape, we demonstrate the multi-year effectiveness of snap traps in the removal of Rattus rattus and Rattus exulans from lava-surrounded forest fragments ranging in size from <0.1 to >10 ha. Relative to other studies, we observed low levels of fragment recolonization. Larger rats were the first to be trapped, with the average size of trapped rats decreasing over time. Rat removal led to distinct shifts in the foraging height and location of mongooses and mice, emphasizing the need to focus control efforts on multiple invasive species at once. Furthermore, because of a specially designed trap casing, we observed low non-target capture rates, suggesting that on Hawai‘i and similar islands lacking native rodents the risk of killing non-target species in snap traps may be lower than the application of rodenticides, which have the potential to contaminate food webs. These efforts demonstrate that targeted snap-trapping is an effective removal method for invasive rats in fragmented habitats and that, where used, monitoring of recolonization should be included as part of a comprehensive biodiversity management strategy.

Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.

Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.

Introduction: Acute aortic syndrome (AAS) is a time sensitive aortic catastrophe that is often misdiagnosed. There are currently no Canadian guidelines to aid in diagnosis. Our goal was to adapt the existing American Heart Association (AHA) and European Society of Cardiology (ESC) diagnostic algorithms for AAS into a Canadian evidence based best practices algorithm targeted for emergency medicine physicians. Methods: We chose to adapt existing high-quality clinical practice guidelines (CPG) previously developed by the AHA/ESC using the GRADE ADOLOPMENT approach. We created a National Advisory Committee consisting of 21 members from across Canada including academic, community and remote/rural emergency physicians/nurses, cardiothoracic and cardiovascular surgeons, cardiac anesthesiologists, critical care physicians, cardiologist, radiologists and patient representatives. The Advisory Committee communicated through multiple teleconference meetings, emails and a one-day in person meeting. The panel prioritized questions and outcomes, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations. The algorithm was prepared and revised through feedback and discussions and through an iterative process until consensus was achieved. Results: The diagnostic algorithm is comprised of an updated pre test probability assessment tool with further testing recommendations based on risk level. The updated tool incorporates likelihood of an alternative diagnosis and point of care ultrasound. The final best practice diagnostic algorithm defined risk levels as Low (0.5% no further testing), Moderate (0.6-5% further testing required) and High ( >5% computed tomography, magnetic resonance imaging, trans esophageal echocardiography). During the consensus and feedback processes, we addressed a number of issues and concerns. D-dimer can be used to reduce probability of AAS in an intermediate risk group, but should not be used in a low or high-risk group. Ultrasound was incorporated as a bedside clinical examination option in pre test probability assessment for aortic insufficiency, abdominal/thoracic aortic aneurysms. Conclusion: We have created the first Canadian best practice diagnostic algorithm for AAS. We hope this diagnostic algorithm will standardize and improve diagnosis of AAS in all emergency departments across Canada.

Declining mortality following invasive pneumococcal disease (IPD) has been observed concurrent with a reduced incidence due to effective pneumococcal conjugate vaccines. However, with IPD now increasing due to serotype replacement, we undertook a statistical analysis to estimate the trend in all-cause 30-day case fatality rate (CFR) in the North East of England (NEE) following IPD. Clinical, microbiological and demographic data were obtained for all laboratory-confirmed IPD cases (April 2006–March 2016) and the adjusted association between CFR and epidemiological year estimated using logistic regression. Of the 2510 episodes of IPD included in the analysis, 486 died within 30 days of IPD (CFR 19%). Increasing age, male sex, a diagnosis of septicaemia, being in ⩾1 clinical risk groups, alcohol abuse and individual serotypes were independently associated with increased CFR. A significant decline in CFR over time was observed following adjustment for these significant predictors (adjusted odds ratio 0.93, 95% confidence interval 0.89–0.98; P = 0.003). A small but significant decline in 30-day all-cause CFR following IPD has been observed in the NEE. Nonetheless, certain population groups remain at increased risk of dying following IPD. Despite the introduction of effective vaccines, further strategies to reduce the ongoing burden of mortality from IPD are needed.

Filamentary structures can form within the beam of protons accelerated during the interaction of an intense laser pulse with an ultrathin foil target. Such behaviour is shown to be dependent upon the formation time of quasi-static magnetic field structures throughout the target volume and the extent of the rear surface proton expansion over the same period. This is observed via both numerical and experimental investigations. By controlling the intensity profile of the laser drive, via the use of two temporally separated pulses, both the initial rear surface proton expansion and magnetic field formation time can be varied, resulting in modification to the degree of filamentary structure present within the laser-driven proton beam.