Medical researchers are increasingly prioritizing the inclusion of underserved communities in clinical studies. However, mere inclusion is not enough. People from underserved communities frequently experience chronic stress that may lead to accelerated biological aging and early morbidity and mortality. It is our hope and intent that the medical community come together to engineer improved health outcomes for vulnerable populations. Here, we introduce Health Equity Engineering (HEE), a comprehensive scientific framework to guide research on the development of tools to identify individuals at risk of poor health outcomes due to chronic stress, the integration of these tools within existing healthcare system infrastructures, and a robust assessment of their effectiveness and sustainability. HEE is anchored in the premise that strategic intervention at the individual level, tailored to the needs of the most at-risk people, can pave the way for achieving equitable health standards at a broader population level. HEE provides a scientific framework guiding health equity research to equip the medical community with a robust set of tools to enhance health equity for current and future generations.

Sharks are scarce in much of the Caribbean due to widespread depletion. Trinidad and Tobago, in the southern Caribbean, is a shark meat consumer and international exporter of dried shark fins. Despite limited fisheries management there is a small Marine Protected Area (MPA; 7 km2) in urbanised southwest Tobago, but its effect on sharks and rays (elasmobranchs) is unknown. The rural northeast is a recently designated UNESCO Man and the Biosphere Reserve with a significant marine component and plans for a large MPA, but no baseline data for elasmobranchs exist. Given the local importance of elasmobranchs and a newly drafted Sustainable Shark and Ray Management Plan, we used baited remote underwater video stations within a 40 m depth contour at 270 randomly generated points around Tobago to: (i) establish a baseline of species richness and relative abundance, (ii) investigate the influence of season, habitat relief, depth and water temperature on relative abundance, and (iii) investigate spatial variation in relative abundance. Caribbean reef sharks, nurse sharks, and southern stingrays were observed at all sites, the latter two more frequently in the urbanised southwest. Shark diversity was unexpectedly high in the northeast, driven by rarer species (sharpnose, smoothhound, tiger, scalloped hammerhead, great hammerhead) only observed there. Habitat relief, depth and season likely influence relative abundance of elasmobranchs around Tobago, but research is needed to elucidate species-level effects. Shark species richness in northeast Tobago is high for the Caribbean, warranting research attention, while the larger MPA presents an opportunity to strengthen elasmobranch management.

OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI ≥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 ± 3.2 kg, P<0.01; liraglutide -2.7 ± 3.2, P<0.01), while sitagliptin did not (-0.7 ± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.

Rigorous scientific review of research protocols is critical to making funding decisions, and to the protection of both human and non-human research participants. Given the increasing complexity of research designs and data analysis methods, quantitative experts, such as biostatisticians, play an essential role in evaluating the rigor and reproducibility of proposed methods. However, there is a common misconception that a statistician’s input is relevant only to sample size/power and statistical analysis sections of a protocol. The comprehensive nature of a biostatistical review coupled with limited guidance on key components of protocol review motived this work. Members of the Biostatistics, Epidemiology, and Research Design Special Interest Group of the Association for Clinical and Translational Science used a consensus approach to identify the elements of research protocols that a biostatistician should consider in a review, and provide specific guidance on how each element should be reviewed. We present the resulting review framework as an educational tool and guideline for biostatisticians navigating review boards and panels. We briefly describe the approach to developing the framework, and we provide a comprehensive checklist and guidance on review of each protocol element. We posit that the biostatistical reviewer, through their breadth of engagement across multiple disciplines and experience with a range of research designs, can and should contribute significantly beyond review of the statistical analysis plan and sample size justification. Through careful scientific review, we hope to prevent excess resource expenditure and risk to humans and animals on poorly planned studies.

The triarchic model was advanced as an integrative, trait-based framework for investigating psychopathy using different assessment methods and across developmental periods. Recent research has shown that the triarchic traits of boldness, meanness, and disinhibition can be operationalized effectively in youth, but longitudinal research is needed to realize the model's potential to advance developmental understanding of psychopathy. We report on the creation and validation of scale measures of the triarchic traits using questionnaire items available in the University of Southern California Risk Factors for Antisocial Behavior (RFAB) project, a large-scale longitudinal study of the development of antisocial behavior that includes measures from multiple modalities (self-report, informant rating, clinical-diagnostic, task-behavioral, physiological). Using a construct-rating and psychometric refinement approach, we developed triarchic scales that showed acceptable reliability, expected intercorrelations, and good temporal stability. The scales showed theory-consistent relations with external criteria including measures of psychopathy, internalizing/externalizing psychopathology, antisocial behavior, and substance use. Findings demonstrate the viability of measuring triarchic traits in the RFAB sample, extend the known nomological network of these traits into the developmental realm, and provide a foundation for follow-up studies examining the etiology of psychopathic traits and their relations with multimodal measures of cognitive-affective function and proneness to clinical problems.

A growing body of research supports the value of a multimodal assessment approach, drawing on measures from different response modalities, for clarifying how core biobehavioral processes relate to various clinical problems and dimensions of psychopathology. Using data for 507 healthy adults, the current study was undertaken to integrate self-report and neurophysiological (brain potential) measures as a step toward a multimodal measurement model for the trait of affiliative capacity (AFF) – a biobehavioral construct relevant to adaptive and maladaptive social-interpersonal functioning. Individuals low in AFF exhibit a lack of interpersonal connectedness, deficient empathy, and an exploitative-aggressive social style that may be expressed transdiagnostically in antagonistic externalizing or distress psychopathology. Specific aims were to (1) integrate trait scale and brain potential indicators into a multimodal measure of AFF and (2) evaluate associations of this multimodal measure with criterion variables of different types. Results demonstrated (1) success in creating a multimodal measure of AFF from self-report and neural indicators, (2) effectiveness of this measure in predicting both clinical-diagnostic and neurophysiological criterion variables, and (3) transdiagnostic utility of the multimodal measure at both specific-disorder and broad symptom-dimension levels. Our findings further illustrate the value of psychoneurometric operationalizations of biobehavioral trait dimensions as referents for clarifying transdiagnostic relationships between biological systems variables and empirically defined dimensions of psychopathology.

Field studies were conducted in 2018 and 2019 in Arkansas, Indiana, Illinois, Missouri, and Tennessee to determine if cover-crop residue interfered with herbicides that provide residual control of Palmer amaranth and waterhemp in no-till soybean. The experiments were established in the fall with planting of cover crops (cereal rye + hairy vetch). Herbicide treatments consisted of a nontreated or no residual, acetochlor, dimethenamid-P, flumioxazin, pyroxasulfone + flumioxazin, pendimethalin, metribuzin, pyroxasulfone, and S-metolachlor. Palmer amaranth took 18 d and waterhemp took 24 d in the cover crop–alone (nontreated) treatment to reach a height of 10 cm. Compared with this treatment, all herbicides except metribuzin increased the number of days until 10-cm Palmer amaranth was present. Flumioxazin applied alone or in a mixture with pyroxasulfone were the best at delaying Palmer amaranth growing to a height of 10 cm (35 d and 33 d, respectively). The herbicides that resulted in the lowest Palmer amaranth density (1.5 to 4 times less) integrated with a cover crop were pyroxasulfone + flumioxazin, flumioxazin, pyroxasulfone, and acetochlor. Those four herbicide treatments also delayed Palmer amaranth emergence for the longest period (27 to 34 d). Waterhemp density was 7 to 14 times less with acetochlor than all the other herbicides present. Yield differences were observed for locations with waterhemp. This research supports previous research indicating that utilizing soil-residual herbicides along with cover crops improves control of Palmer amaranth and/or waterhemp.

This article aims at predicting the oscillation frequency of open-channel lateral cavities, which are common sheltered zones of riverine environments, and have important ecological impact. Using a theoretical analysis based on an existing model for acoustic cavities and a free-surface lateral cavity experiment, we show that the vortex shedding in the mixing layer between the cavity and the open channel is always constrained by gravity waves even for low Froude numbers ($F<0.6$). This expands previous results from the literature showing the impact of gravity waves on the vortex shedding frequency for high Froude number ($F>0.6$). Measurements of the free-surface oscillation and transverse velocity oscillation frequencies reveal a unique frequency along the mixing layer, equal to the free-surface oscillation frequency anywhere in the cavity. Hence, it is shown that the vortex shedding frequency in an open-channel lateral cavity always equals a match between a natural frequency of the cavity and a solution of the feedback model developed herein for low to moderate Froude numbers.

Evidence suggests that early trauma may have a negative effect on cognitive functioning in individuals with psychosis, yet the relationship between childhood trauma and cognition among those at clinical high risk (CHR) for psychosis remains unexplored. Our sample consisted of 626 CHR children and 279 healthy controls who were recruited as part of the North American Prodrome Longitudinal Study 2. Childhood trauma up to the age of 16 (psychological, physical, and sexual abuse, emotional neglect, and bullying) was assessed by using the Childhood Trauma and Abuse Scale. Multiple domains of cognition were measured at baseline and at the time of psychosis conversion, using standardized assessments. In the CHR group, there was a trend for better performance in individuals who reported a history of multiple types of childhood trauma compared with those with no/one type of trauma (Cohen d = 0.16). A history of multiple trauma types was not associated with greater cognitive change in CHR converters over time. Our findings tentatively suggest there may be different mechanisms that lead to CHR states. Individuals who are at clinical high risk who have experienced multiple types of childhood trauma may have more typically developing premorbid cognitive functioning than those who reported minimal trauma do. Further research is needed to unravel the complexity of factors underlying the development of at-risk states.

Background: High levels of uric acid (UA) are associated with various peripheral neuropathies. Furthermore, uric acid levels have been found to correlate with both the clinical and electrophysiological severity of diabetic sensorimotor polyneuropathy, mainly with sensory functions. Objectives: To determine whether higher UA levels are associated negatively with nerve function in healthy subjects. Methods: A total of 126 healthy subjects recruited prospectively for another study were included. We extracted demographic data, body mass index (BMI), blood pressure, Toronto Clinical Neuropathy Score (TCNS), electrophysiological findings, vibration perception thresholds (VPT), and laboratory test results including UA, hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and lipid levels. Results: The mean age of the cohort was 56 ± 17 years with 56% females. Males had higher UA values compared with females. Univariate beta regression coefficient analysis between UA levels and demographic, clinical, electrophysiological, and laboratory findings showed significant positive correlations with male gender, components of the metabolic syndrome, and with VPT, while an inverse correlation was found with electrophysiological sensory parameters. A multivariate regression model showed positive correlations only with BMI, finger VPT, and triglycerides. Conclusion: Higher UA levels correlate with lower sensory nerve function in healthy subjects, expanding the evidence of possible negative influence of UA on peripheral nerves, although a causative role has not yet established.