Underrepresentation of people from racial and ethnic minoritized groups in clinical trials threatens external validity of clinical and translational science, diminishes uptake of innovations into practice, and restricts access to the potential benefits of participation. Despite efforts to increase diversity in clinical trials, children and adults from Latino backgrounds remain underrepresented. Quality improvement concepts, strategies, and tools demonstrate promise in enhancing recruitment and enrollment in clinical trials. To demonstrate this promise, we draw upon our team’s experience conducting a randomized clinical trial that tests three behavioral interventions designed to promote equity in language and social-emotional skill acquisition among Latino parent–infant dyads from under-resourced communities. The recruitment activities took place during the COVID-19 pandemic, which intensified the need for responsive strategies and procedures. We used the Model for Improvement to achieve our recruitment goals. Across study stages, we engaged strategies such as (1) intentional team formation, (2) participatory approaches to setting goals, monitoring achievement, selecting change strategies, and (3) small iterative tests that informed additional efforts. These strategies helped our team overcome several barriers. These strategies may help other researchers apply quality improvement tools to increase participation in clinical and translational research among people from minoritized groups.

Background: Alberta Health Services (AHS) measures hand hygiene compliance through direct observations performed by trained site-based reviewers (SBRs) and facilitated by the Infection Prevention and Control (IPC) program. Within AHS there are >100 acute care facilities, ranging in bed size from four beds to more than 1,000, with catchment populations ranging from one million. A time-in-motion study using trained AHS IPC staff was proposed to validate the completeness and accuracy of data being collected by the SBRs. Methods: The AHS IPC staff performed direct observations at pre-selected facilities across all five zones and four different unit types (emergency, medical, surgical, and intensive care) for four 30-minute periods during weekdays between June and September 2023. An iPad app was used to capture results from all four moments of hand hygiene. The reviewer indicated the day and time of the review and captured as many representative hand hygiene moments and healthcare providers as possible. The distributions of the four moments of hand hygiene, healthcare provider group and overall compliance were compared at the unit type and facility level (tertiary, large urban, regional, pediatric, and small sites) between this time-in-motion study and SBR data collected June-September 2023. Results: The study collected 175 reviews and 4,683 observations from 14 facilities and 48 units. Between June and September 2023, SBRs collected 2,625 reviews and 61,506 observations from these same facility and unit types. Across all facility and unit types, the distribution of the four moments was similar between the study and SBRs. Similar proportions of healthcare providers were also observed. However, the overall hand hygiene compliance collected in the study was approximately 10% lower across all unit types as compared to that collected by the SBRs (study: 63%-84%; SBRs: 75%-92%). Conclusions: In public health surveillance, completeness and accuracy are two characteristics of high-quality data. A time-in-motion study identified that the hand hygiene observations collected by SBRs were complete, as the range of healthcare providers observed, and the distribution of their moments, mirrored that collected in the study. However, the SBRs reported higher compliance than the study participants and the true hand hygiene compliance is likely lower than what is currently being reported. Since this difference was seen consistently across all unit and facility types, trending data over time should still identify areas in need of improvement and may help to suggest causes of the over-reporting.

OBJECTIVES/GOALS: To determine whether cardioprotective effects observed in individuals taking dietary supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid, are realized by altering platelet function, and if these effects are mediated through the 12-lipoxygenase derived metabolite, 12-hydroxyeicosapentaenoic acid (12-HEPE). METHODS/STUDY POPULATION: Washed platelets or platelet rich plasma from healthy human donors were treated with EPA and 12-HEPE to assess their ability to inhibit platelet activation. Platelets were stimulated with agonists targeting different steps of the hemostatic response to vascular injury. Platelet aggregation, dense granule secretion, surface expression of integrin αIIbβ3 and P-selectin, and clot retraction were analyzed. To assess signaling through Gαs-GPCRs and protein kinase A activity, phosphorylation of vasodilator-stimulated phosphoprotein (VASP) was examined via western blot following treatment with EPA or 12-HEPE. RESULTS/ANTICIPATED RESULTS: EPA and 12-HEPE dose-dependently inhibit both collagen and thrombin-induced platelet aggregation. Furthermore, 12-HEPE more potently attenuates dense granule secretion and surface expression of platelet activation markers, integrin αIIbβ3 and P-selectin, in comparison to EPA. Plasma treated with EPA delayed thrombin-induced clot retraction, while 12-HEPE had no effect. Additionally, treatment with 12-HEPE increases phosphorylation of VASP, suggesting it could signal through the activation of the eicosanoid Gαs-GPCRs. DISCUSSION/SIGNIFICANCE: Here, we show for the first time that EPA directly inhibits platelet activation through its 12-LOX metabolite, 12-HEPE. These findings provide further insight into the mechanisms underlying the cardioprotective effects of EPA. A better understanding of current PUFA supplementations can inform treatment and prevention of cardiovascular diseases.

OBJECTIVES/GOALS: Untargeted metabolomics platforms are powerful biomarker discovery tools. However, the absence of uniform study design, data analysis, and reporting standards limits translation of this research into the clinical lab. The goal was to critically appraise existing untargeted metabolomics platforms that analyzed inborn errors of metabolism. METHODS/STUDY POPULATION: A search strategy was conducted in MEDLINE via PubMed from January 16, 2013, to January 16, 2023. The search strategy was limited to primary literature articles written in English that evaluated human subjects with inborn errors of metabolism (IEMs). Articles that performed targeted metabolomic analysis or analyzed non-human samples were excluded. Information on patient cohorts analyzed, sample types, and method design were extracted using a template. Categorical data are summarized as frequencies and percentages. RESULTS/ANTICIPATED RESULTS: A total of 96 distinct IEMs were evaluated by the different untargeted metabolomics methods included in this review. However, most IEMs (55/96, 57%) were evaluated by a single platform, in a single study, with a limited cohort size. Only one study validated their results using a separate, validation cohort. There was considerable diversity in the separation techniques and mass spectrometry instrumentation used by the studies to create their untargeted metabolomics methods. Slightly over half (59%) of the studies identified at least some of the metabolites detected in their samples with the highest level of confidence. Importantly, most of the included studies reported adherence to quality metrics, including use of quality control material (65%) and internal standards in their analysis (61%). DISCUSSION/SIGNIFICANCE: Future studies analyzing IEM patient samples with untargeted metabolomics platforms should progress beyond single-subject studies and evaluate the reproducibility of the research using a prospective, or validation cohort as well as confirm metabolite annotations with reference metabolites standards to generate clinically useful data.

OBJECTIVES/GOALS: Our overarching aim is to examine, in an African American population, cognitive, affective, and neurophysiological processes, as well as risk-taking behavior, in response to racial stigma cues. While accounting for individual differences, we aim to see how these processes and drug-cue reactivity are impacted or altered by exposure to racial cues. METHODS/STUDY POPULATION: Participants will be African Americans between 18 and 25 years of age, equally distributed across genders. We will recruit 75 participants in order to have adequate power to conduct our intended analyses—particularly pertaining to individual differences in risk behavior outcomes. Participants will be asked to complete demographic and self-report questionnaires. Participants will also be asked to complete computerized tasks while their physiological responses (heart rate, skin conductance, and electroencephalographic (EEG) data) are recorded. The tasks are as follow: resting, gambling, go/no-go, picture viewing (positive, negative, and neutral images), and a drug cue image set. These tasks will be repeated after the participant views a racial stigma image set to evaluate the impact of discrimination. RESULTS/ANTICIPATED RESULTS: Data from 18 participants has been collected. Data will be periodically preprocessed and validated (e.g., 1 participant was removed due to data recording errors, so the current valid Nis 17). Generally, we anticipate that behaviors and neural activity will be modulated across all tasks after viewing the racial stigma image set. Specifically, (a) cognitive and affective processing of singular events of racial stigma may indicate a stress response, (b) modulation from chronic experiences of racial stigma render neural systems increasingly sensitive to stigma cues, and thereby less equipped to regulate stress response, (c) the impact of these processes on altering risk behavior (may increase such behaviors), and (d) the impact of these modulations on altering drug-cue reactivity (may amplify reactivity). DISCUSSION/SIGNIFICANCE: The study will identify factors that contribute to stress and risk behavior among African Americans. A substantial gap continues to exist regarding the nature of risk behavior among African Americans, despite the fact that African Americans represent a health disparity population with unique vulnerabilities to health-relevant risk behavior.

Political instability is commonly thought to discourage investment and reduce economic growth. We challenge this consensus by showing that instability does not systematically depress investment. Using an event study approach, we examine daily returns of national financial indices in every country that experienced an irregular regime change subject to data availability. Returns following resignations are large and positive (+4 percent), while those following assassinations are negative and smaller in magnitude (−2 percent). The impact of coups tends to be negative (−2 percent), but we show that a pro-business coup results in large positive returns (+10 percent). We also find evidence that authoritarian or anti-business regime changes are more likely to lead to capital flight than democratic or pro-business changes. The immediate impact of political instability on investment is therefore dependent on the type of regime change and its expected impact on future growth.

Why do citizens support or reject climate change mitigation policies? This is not an easy choice: citizens need to support the government in making these decisions, accept potentially radical behavior change, and have altruism across borders and for future generations. A substantial literature argues that political trust facilitates citizen support for these complex policy decisions by mitigating the cost and uncertainty that policies impose on individuals and buttressing support for government intervention. We test whether this is the case with a pre-registered conjoint experiment fielded in Germany in which we vary fundamental aspects of policy design that are related to the cost, uncertainty, and implementation of climate change policies. Contrary to strong theoretical expectations and previous work, we find no difference between those with low and high trust on their support for different policy attributes, assuaging the concern that low and declining trust inhibits climate policymaking.

Megasphaera elsdenii has been correlated with gas production by human faecal microbiota during fermentation. The objective of this study was to determine the role of M. elsdenii in gas production by the microbiome. Kidney beans and sweet potatoes were subjected to in vitro digestion and dialysis followed by fermentation with ten faecal microbiomes: three with detectable M. elsdenii (Me_D) and seven with no detectable M. elsdenii (Me_ND). Me_D microbiomes produced more gas than the Me_ND microbiomes (p < 0.001). Me_D microbiomes produced more gas during fermentation of sweet potatoes than kidney beans (p < 0.001), while the opposite was true for the Me_ND microbiomes (p < 0.001). Among amplicon sequence variants that were associated with gas production, M. elsdenii had the strongest association (p < 0.001). Me_D microbiomes consumed more acetate and produced more butyrate than Me_ND microbiomes (p < 0.001). Gas production by M. elsdenii was confirmed by fermentation of sweet potatoes and acetate with human and rumen M. elsdenii isolates. The human isolate produced gas on sweet potatoes and acetate. This study suggests that M. elsdenii may be involved in gas production during the fermentation of flatulogenic foods through utilisation of undigestible substrates or cross-feeding on acetate.

Dance for older adults is increasingly being used to support health and well-being. While dance may be enjoyable for many, understanding its benefits for those with limited physical and cognitive abilities may provide further support for how dance may be used in these contexts. This was a study of Sharing Dance Older Adults, a dance program with remotely streamed sessions. Data were collected from 48 older adults who took part in the On Your Feet version of the program, and from 38 who took part in the In Your Seat version. Measures included interviews, physical fitness tests and surveys on mood, quality of life, and program satisfaction. Physical fitness significantly improved for both groups, unlike for mood, social well-being, or quality of life. This contrasts with qualitative findings, with participants reporting how the program enhanced their mood, social interactions, and quality of life.

Risk of bias assessment is a critical step of any meta-analysis or systematic review. Given the low sample count of many microbiome studies, especially observational or cohort studies involving human subjects, many microbiome studies have low power. This increases the importance of performing meta-analysis and systematic review for microbiome research in order to enhance the relevance and applicability of microbiome results. This work proposes a method based on the ROBINS-I tool to systematically consider sources of bias in microbiome research seeking to perform meta-analysis or systematic review for microbiome studies.