OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

From 2014 to 2020, we compiled radiocarbon ages from the lower 48 states, creating a database of more than 100,000 archaeological, geological, and paleontological ages that will be freely available to researchers through the Canadian Archaeological Radiocarbon Database. Here, we discuss the process used to compile ages, general characteristics of the database, and lessons learned from this exercise in “big data” compilation.

Archaeologists have long subjected Clovis megafauna kill/scavenge sites to the highest level of scrutiny. In 1987, a Columbian mammoth (Mammuthus columbi) was found in spatial association with a small artifact assemblage in Converse County, Wyoming. However, due to the small tool assemblage, limited nature of the excavations, and questions about the security of the association between the artifacts and mammoth remains, the site was never included in summaries of human-killed/scavenged megafauna in North America. Here we present the results of four field seasons of new excavations at the La Prele Mammoth site that confirm the presence of an associated cultural occupation based on geologic context, artifact attributes, spatial distributions, protein residue analysis, and lithic microwear analysis. This new work identified a more extensive cultural occupation including the presence of multiple discrete artifact clusters in close proximity to the mammoth bone bed. This study confirms the presence of a second Clovis mammoth kill/scavenge site in Wyoming and shows the value in revisiting proposed terminal Pleistocene kill/scavenge sites.

With generous support from the National Science Foundation, we have spent the past four years developing an archaeological radiocarbon database for the United States. Here, we highlight the importance of spatial data for open-access, national-scale archaeological databases and the development of paleodemography research. We propose a new method for analyzing radiocarbon time series in the context of paleoclimate models. This method forces us to confront one of the central challenges to realizing the full potential of national-scale databases: the quality of the spatial data accompanying radiocarbon dates. We seek to open a national discussion on the use of spatial data in open-source archaeological databases.

Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.

OBJECTIVES/SPECIFIC AIMS: Deep brain stimulation is currently being evaluated as an experimental therapy for various psychiatric disorders, as well as being investigated as a method for mapping emotional brain functions. This growing area of research requires sensitive measures to quantify effects of stimulation on emotional processing. The current study examined the effects of acute stimulation to 2 limbic regions—the subcallosal cingulate (SCC) and the amygdala—on bias in the perception and evaluation of emotional facial expressions. We hypothesized that transient electrical stimulation to the limbic system would produce acute reductions in negative bias, consistent with its antidepressant effects in patients with severe depression. METHODS/STUDY POPULATION: The current study uses a novel affective bias task, developed to rapidly and covertly quantify emotional state. Over 4–6 minutes, patients rate the intensity and valence of static images of emotional facial expressions. We examined effects of electrical brain stimulation in 2 groups: patients with treatment-refractory depression undergoing SCC DBS therapy, and epilepsy patients undergoing amygdala stimulation via stereo-EEG electrodes during inpatient intracranial monitoring. DBS patients completed the task under stimulation and sham conditions during monthly visits over the first 6 months of therapy, as well as daily during a 1 week, blinded period of DBS discontinuation at the 6-month time point. Epilepsy patients completed the task under stimulation and sham conditions at a single visit. Mixed linear models and paired-samples t-test were used to investigate effects of stimulation as well as depression scale scores on affective bias ratings. RESULTS/ANTICIPATED RESULTS: Four SCC DBS patients showed significant effects of stimulation (p<0.0001) and depressive state (p<0.0001) on affective bias scores across 6 months of chronic DBS therapy, where emotional faces were perceived as less sad with stimulation ON, as well as during visits in which patients were nondepressed (typically later in the treatment course). Furthermore, 2 DBS patients showed rapid negative shifts in bias following acute blinded discontinuation of chronic stimulation, an effect which persisted over the 1-week period of discontinuation (t29=−2.58, p=0.015), in the absence of any self-reported change in mood. Likewise, 6 epilepsy patients showed significant positive shifts in affective bias with acute amygdala stimulation (t5=−4.75, p=0.005). Current analyses are investigating electrophysiological, autonomic and facial motor correlates to affective bias in these patients. DISCUSSION/SIGNIFICANCE OF IMPACT: Affective bias has revealed rapid, significant changes with stimulation at 2 limbic targets—one a white matter hub and one a nuclear subcortical structure—suggesting the task’s utility as an emotional outcome measure in brain stimulation studies. These stimulation-sensitive measures may provide a new metric to track treatment response to deep brain stimulation therapy for affective disorders. Future studies will determine whether affective bias can predict neuropsychiatric complications in patients undergoing stimulation mapping of brain circuitry ahead of resection surgery for epilepsy.

Over the last decade, archaeologists have turned to large radiocarbon (14C) data sets to infer prehistoric population size and change. An outstanding question concerns just how direct of an estimate 14C dates are for human populations. In this paper we propose that 14C dates are a better estimate of energy consumption, rather than an unmediated, proportional estimate of population size. We use a parametric model to describe the relationship between population size, economic complexity and energy consumption in human societies, and then parametrize the model using data from modern contexts. Our results suggest that energy consumption scales sub-linearly with population size, which means that the analysis of a large 14C time-series has the potential to misestimate rates of population change and absolute population size. Energy consumption is also an exponential function of economic complexity. Thus, the 14C record could change semi-independent of population as complexity grows or declines. Scaling models are an important tool for stimulating future research to tease apart the different effects of population and social complexity on energy consumption, and explain variation in the forms of 14C date time-series in different regions.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Urban riparian plant communities exist at the interface between terrestrial and aquatic habitats, and they are rich sources of species biodiversity and ecosystem services. The periodic floods that promote species diversity in riparian plant communities also increase their vulnerability to nonnative plant invasions. Plant invasions are constrained by seed and suitable habitat availability. However, how seed dispersal and establishment limitations interact to shape nonnative plant invasions in riparian communities is poorly understood. We use Stream Visual Assessment Protocol data to evaluate the hydrological and geomorphological parameters that influence the seeding and establishment of six common nonnative species in urban riparian habitats: garlic mustard, purple loosestrife, reed canarygrass, common reed, Japanese knotweed, and multiflora rose. To address this objective, we analyzed stream reach data collected during a basin-wide environmental assessment of the extensively urbanized upper Niagara River watershed. We found limited support for our prediction that propagule limitation constrains the distribution of nonnative riparian species, likely because these species are well established in the study area. Instead, we found that opportune stream reach characteristics better predict the distribution of the common invasive riparian species—most notably open tree canopy. Given that there is widespread investment in urban riparian forest restoration to improve water quality, increase stream-bank stability, enhance wildlife habitat and promote recreation, our data suggest that riparian forests may provide the additional benefit of reducing the abundance of some, but not all, invasive plants.