Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.

OBJECTIVES/GOALS: The objective was to examine the American Heart Association’s (AHA) Essential Eight metrics of cardiovascular (CV) health among Black and White adults with peripheral arterial disease (PAD) collected via validated surveys and medical records. Each metric was examined in association with available social determinants of health (SDoH) factors. METHODS/STUDY POPULATION: This observational study completed data collection through surveys and medical record review. Validated surveys were used to collect Essential Eight metrics of diet, physical activity, sleep, and smoking status. Medical records were used to collect data on body mass index, blood lipids, blood glucose, and blood pressure. Participants with a diagnosis of lower extremity PAD, ability to complete surveys, and provided informed written consent were eligible. Equal numbers of Black and White participants were enrolled. Essential Eight metrics were used to calculate CV health scores for each participant. Scores were examined for association with SDoH factors and by race using Student’s T-test or ANOVA for continuous variables or Chi-Square tests for categorical variables. RESULTS/ANTICIPATED RESULTS: A total of 50 participants will be enrolled, with the expected majority being men and half self-reporting as Black individuals. Worse SDoH is expected to be associated with lower CV health metrics, including lower levels of physical activity and higher levels of saturated fatty food consumption. Higher levels of blood lipids, blood glucose, and blood pressure are expected to be associated with worse SDoH factors. We expect this association to be attenuated by rates of CV medications, such as statin therapy, antiglycemic medications, and antihypertensive medications. No effect modification by rurality is expected, although our projected sample size is small and may impact the ability to examine this interaction. DISCUSSION/SIGNIFICANCE: Black Americans, particularly in the Deep South, are at elevated risk for PAD and critical limb ischemic events, such as amputation. Understanding CV health metrics and SDoH characteristics among adults with PAD is essential to reduce disparities in care and provide valuable information for those at highest risk for complications.

In a survey of infection prevention programs, leaders reported frequent clinical and infection prevention practice modifications to avoid coronavirus disease 2019 (COVID-19) exposure that exceeded national guidance. Future pandemic responses should emphasize balanced approaches to precautions, prioritize educational campaigns to manage safety concerns, and generate an evidence-base that can guide appropriate infection prevention practices.

Research has suggested that children who speak African American English (AAE) have difficulty using features produced in Mainstream American English (MAE) but not AAE, to comprehend sentences in MAE. However, past studies mainly examined dialect features, such as verbal -s, that are produced as final consonants with shorter durations when produced in conversation which impacts their phonetic saliency. Therefore, it is unclear if previous results are due to the phonetic saliency of the feature or how AAE speakers process MAE dialect features more generally. This study evaluated if there were group differences in how AAE- and MAE-speaking children used the auxiliary verbs was and were, a dialect feature with increased phonetic saliency but produced differently between the dialects, to interpret sentences in MAE. Participants aged 6, 5–10, and 0 years, who spoke MAE or AAE, completed the DELV-ST, a vocabulary measure (PVT), and a sentence comprehension task. In the sentence comprehension task, participants heard sentences in MAE that had either unambiguous or ambiguous subjects. Sentences with ambiguous subjects were used to evaluate group differences in sentence comprehension. AAE-speaking children were less likely than MAE-speaking children to use the auxiliary verbs was and were to interpret sentences in MAE. Furthermore, dialect density was predictive of Black participant’s sensitivity to the auxiliary verb. This finding is consistent with how the auxiliary verb is produced between the two dialects: was is used to mark both singular and plural subjects in AAE, while MAE uses was for singular and were for plural subjects. This study demonstrated that even when the dialect feature is more phonetically salient, differences between how verb morphology is produced in AAE and MAE impact how AAE-speaking children comprehend MAE sentences.

Customer churn, which insurance companies use to describe the non-renewal of existing customers, is a widespread and expensive problem in general insurance, particularly because contracts are usually short-term and are renewed periodically. Traditionally, customer churn analyses have employed models which utilise only a binary outcome (churn or not churn) in one period. However, real business relationships are multi-period, and policyholders may reside and transition between a wider range of states beyond that of the simply churn/not churn throughout this relationship. To better encapsulate the richness of policyholder behaviours through time, we propose multi-state customer churn analysis, which aims to model behaviour over a larger number of states (defined by different combinations of insurance coverage taken) and across multiple periods (thereby making use of readily available longitudinal data). Using multinomial logistic regression (MLR) with a second-order Markov assumption, we demonstrate how multi-state customer churn analysis offers deeper insights into how a policyholder’s transition history is associated with their decision making, whether that be to retain the current set of policies, churn, or add/drop a coverage. Applying this model to commercial insurance data from the Wisconsin Local Government Property Insurance Fund, we illustrate how transition probabilities between states are affected by differing sets of explanatory variables and that a multi-state analysis can potentially offer stronger predictive performance and more accurate calculations of customer lifetime value (say), compared to the traditional customer churn analysis techniques.

Seeds kept in long-term storage are essential for maintaining genetic resources of crops and other plant materials in seed banks and national germplasm systems. But seeds undergo chemical changes over time as part of the ageing process that result in reduced germination rates and seedling normalcy. For example, oilseed crops such as peanuts are particularly vulnerable to oxidation and rancidification due to their high oil content. To test the effect of storage time on seed oil in peanuts, we grew different accessions and harvested fresh seeds to compare the oil composition of new seeds with seeds aged in storage for varying lengths of time. Out of the nine fatty acids detected and measured by gas chromatography, five including oleic, gadoleic, behenic, lignoceric and cerotic acids differed significantly between new and old seeds. Additionally, old seeds accumulated up to four oxidation products together averaging about 1% of the total oil composition. The concentration of these oxidation products was positively correlated with the age of the seeds, increasing linearly up to more than 6% of the total in the oldest seeds. The presence and concentration of oxidation products measured using simple chromatography techniques can be used as an initial indication of quality and viability in older seed inventories stored in germplasm repositories.

OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.

Introduction: Understanding the spatial distribution of opioid abuse at the local level may facilitate community intervention strategies. The purpose of this analysis was to apply spatial analytical methods to determine clustering of opioid-related emergency medical services (EMS) responses in the City of Calgary. Methods: Using opioid-related EMS responses in the City of Calgary between January 1st through October 31st, 2017, we estimated the dissemination area (DA) specific spatial randomness effects by incorporating the spatial autocorrelation using intrinsic Gaussian conditional autoregressive model and generalized linear mixed models (GLMM). Global spatial autocorrelation was evaluated by Morans I index. Both Getis-Ord Gi and the LISA function in Geoda were used to estimate the local spatial autocorrelation. Two models were applied: 1) Poisson regression with DA-specific non-spatial random effects; 2) Poisson regression with DA-specific G-side spatial random effects. A pseudolikelihood approach was used for model comparison. Two types of cluster analysis were used to identify the spatial clustering. Results: There were 1488 opioid-related EMS responses available for analysis. Of the responses, 74% of the individuals were males. The median age was 33 years ( IQR: 26-42 years) with 65% of individuals between 20 and 39 years, and 27% between 40 and 64 years. In 62% of EMS responses, poisoning/overdose was the chief complaint. The global Morans Index implied the presence of global spatial autocorrelation. Comparing the two models applied suggested that the spatial model provided a better fit for the adjusted opioid-related EMS response rate. Calgary Center and East were identified as hot spots by both types of cluster analysis. Conclusion: Spatial modeling has a better predictability to assess potential high risk areas and identify locations for community intervention strategies. The clusters identified in Calgarys Center and East may have implications for future response strategies.

A stalagmite with high 238U content from Yangkou Cave, China, revealed the evolution of the Asian summer monsoon (ASM) between 49.1 and 59.5 ka, and the δ18O values recorded Dansgaard/Oeschger (D/O) events 13–17. The Yangkou record shows a relatively gradual transition into the D/O 14 and 16 events. The discrepancy between the abrupt and gradual transitions of D/O 14 in the records from northern and southern China, respectively, suggests different responses of the ASM to climate changes in the high northern latitudes. The higher resolution δ18O record and more precise 230Th dating indicate that the timing of D/O 14 and 17 in the Hulu records at 53 and 58 ka should be shifted to 54.3 and 59 ka, respectively. The gradual strengthening of the ASM at the onsets of D/O 16 and 14 in our record is different from the abrupt temperature rise in the northern high latitudes. Some other factors must contribute to this relatively gradual ASM change in southern China, but the actual reason is still unknown.

We present two isotopic (δ18O and δ13C) sequences of a twin-stalagmite from Zhuliuping Cave, southwestern China, with 230Th dates from 14.6 to 4.6 ka. The stalagmite δ18O record characterizes orbital- to decadal-scale variability of Asian summer monsoon (ASM) intensity, with the Holocene optimum period (HOP) between 9.8 and 6.8 ka BP which is reinforced by its co-varying δ13C data. The large multi-decadal scale amplitude of the cave δ18O indicates its high sensitivity to climate change. Four centennial-scale weak ASM events during the early Holocene are centered at 11.2, 10.8, 9.1 and 8.2 ka. They can be correlated to cold periods in the northern high latitudes, possibly resulting from rapid dynamics of atmospheric circulation associated with North Atlantic cooling. The 8.2 ka event has an amplitude more than two-thirds that of the Younger Dryas (YD), and is significantly stronger than other cave records in the Asia monsoon region, likely indicating a more severe dry climate condition at the cave site. At the end of the YD event, the δ13C record lags the δ18O record by 300–500 yr, suggesting a multi-centennial slow response of vegetation and soil processes to monsoon enhancement.

Picea is an important taxon in late-glacial pollen records from eastern North America, but little is known about which species of Picea were present. We apply a recently developed palynological method for discriminating the three Picea species in eastern North America to three records from New England. Picea glauca was dominant at ∼ 14,500–14,000 cal yr BP, followed by a transition to Picea mariana between ∼ 14,000 and 13,500 cal yr BP. Comparison of the pollen data with hydrogen isotope data shows clearly that this transition began before the beginning of the Younger Dryas Chronozone. The ecological changes of the late-glacial interval were not a simple oscillation in the position of a single species' range, but rather major changes in vegetation structure and composition occurring during an interval of variations in several environmental factors, including climate, edaphic conditions, and atmospheric CO2 levels.