Distinguishing between translational science and translational research in CTSA pilot studies: A collaborative project across 12 CTSA hubs.

Introduction: The institutions (i.e., hubs) making up the National Institutes of Health (NIH)-funded network of Clinical and Translational Science Awards (CTSAs) share a mission to turn observations into interventions to improve public health. Recently, the focus of the CTSAs has turned increasingly from translational research (TR) to translational science (TS). The current NIH Funding Opportunity Announcement (PAR-21-293) for CTSAs stipulates that pilot studies funded through the CTSAs must be "focused on understanding a scientific or operational principle underlying a step of the translational process with the goal of developing generalizable solutions to accelerate translational research." This new directive places Pilot Program administrators in the position of arbiters with the task of distinguishing between TR and TS projects. The purpose of this study was to explore the utility of a set of TS principles set forth by NCATS for distinguishing between TR and TS. Methods: Twelve CTSA hubs collaborated to generate a list of Translational Science Principles questions. Twenty-nine Pilot Program administrators used these questions to evaluate 26 CTSA-funded pilot studies. Results: Factor analysis yielded three factors: Generalizability/Efficiency, Disruptive Innovation, and Team Science. The Generalizability/Efficiency factor explained the largest amount of variance in the questions and was significantly able to distinguish between projects that were verified as TS or TR (t = 6.92, p < .001) by an expert panel. Conclusions: The seven questions in this factor may be useful for informing deliberations regarding whether a study addresses a question that aligns with NCATS' vision of TS.

Improvement in Resident Scholarly Output with Implementation of a Scholarly Activity Guideline and Point System.

Introduction: Ensuring high-quality scholarly output by graduate medical trainees can be a challenge. Within many specialties, including emergency medicine (EM), it is unclear what constitutes appropriate resident scholarly activity. We hypothesized that the quantity and quality of scholarly activity would improve with a clearer guideline, including a point system for eligible scholarly activities. Methods: A resident Scholarly Activity Guideline was implemented for EM residents in a university setting. The guideline consists of a point system in which point values, ranging from 1-10, are assigned to various types of scholarly activities. Residents must earn at least 10 points and present their work to meet their scholarly graduation requirement. We tracked scholarly activities for graduates from the classes of 2014-2020, with the guideline being implemented for the class of 2016. In a blind analysis, we compared median total points per resident, mean counts of the Boyer model of scholarship components per resident, and mean counts of significant scholarly output per resident before vs after the guideline was implemented. Significant scholarly output was defined as an implemented protocol, a research project with data collection and analysis, a research abstract presentation, or an oral abstract presentation. Results: Among 64 residents analyzed, 48 residents used the guideline. We found that median points per resident increased after the guideline was implemented (median, interquartile range: before 7 [7], after 11 [10, 13], P = 0.002). Post-guideline scholarly activities were found to represent more of Boyer's components of scholarship [mean before 0.81 [SD 0.40], mean after 1.52 [SD 0.71], mean difference 0.71, 95% confidence interval [CI] 0.332 ± 1.09, P < 0.001. There was no difference in the mean significant scholarly output per resident (mean before 1.38 [SD 1.02], mean after 1.02 [SD 1.00], mean difference 0.35, 95% CI 0.93 ± 0.23, P = 0.23). Conclusion: Implementation of a Scholarly Activity Guideline point system significantly increased the quantity and, by one of two measures, increased the quality of scholarly output in our program. Our point-based guideline successfully incorporated traditional and modern forms of scholarship that can be tailored to resident interests.

Vaccine Acceptance During a Novel Student-led Emergency Department COVID-19 Vaccination Program.

INTRODUCTION: The coronavirus 2019 (COVID-19) pandemic not only exacerbated barriers to healthcare but has also highlighted the trend toward increased vaccine hesitancy. Our goal was to improve COVID-19 vaccine uptake through a student-led, emergency department-based (ED) vaccination program. METHODS: This prospective, quality-improvement pilot program used medical and pharmacy student volunteers as COVID-19 vaccine screeners in a southern, urban, academic ED. Patients eligible for vaccination were offered either the Janssen-Johnson & Johnson or the Pfizer-BioNTech COVID-19 vaccine and were educated about vaccine concerns. Vaccine acceptance rates were recorded, as well as reasons for vaccine hesitancy, vaccine brand preferences, and demographics. The primary and secondary quantitative outcomes were overall vaccine acceptance and change in vaccine acceptance after student-provided education, respectively. We performed logistic regression to identify potential variables that correlated with vaccine acceptance. Guided by the Consolidated Framework for Implementation Research, focus group interviews with four key stakeholder groups explored implementation facilitators and barriers. RESULTS: We screened 406 patients for COVID-19 vaccination eligibility and current vaccine status, the majority of whom were unvaccinated. Of unvaccinated or partially vaccinated patients, vaccine acceptance before education was 28.3% (81/286), and vaccine acceptance after education was 31.5% (90/286) (% difference, 3.1% [95% CI 0.3%-5.9%], P=0.03). The most common hesitancy factors cited were concerns about side effects and safety. Results from the regression analysis indicated that increasing age and Black race were associated with an increased odds of vaccine acceptance. Focus groups revealed implementation barriers, including patient resistance and workflow issues, and facilitators, including student involvement and public health promotion. CONCLUSION: Using medical and pharmacy student volunteers as COVID-19 vaccine screeners was successful, and brief education provided by the students led to a modest increase in vaccine acceptance, with overall acceptance of 31.5%. Numerous educational benefits are described.

Investigating the origins and evolution of a glyphosate-resistant weed invasion in South America.

The global invasion, and subsequent spread and evolution of weeds provides unique opportunities to address fundamental questions in evolutionary and invasion ecology. Amaranthus palmeri is a widespread glyphosate-resistant (GR) weed in the USA. Since 2015, GR populations of A. palmeri have been confirmed in South America, raising questions about introduction pathways and the importance of pre- vs. post-invasion evolution of GR traits. We used RAD-sequencing genotyping to characterize genetic structure of populations from Brazil, Argentina, Uruguay and the USA. We also quantified gene copy number of the glyphosate target, 5-enolpyruvyl-3-shikimate phosphate synthase (EPSPS), and the presence of an extrachromosomal circular DNA (eccDNA) replicon known to confer glyphosate resistance in USA populations. Populations in Brazil, Argentina and Uruguay were only weakly differentiated (pairwise FST  ≤0.043) in comparison to USA populations (mean pairwise FST  =0.161, range =0.068-0.258), suggesting a single major invasion event. However, elevated EPSPS copy number and the EPSPS replicon were identified in all populations from Brazil and Uruguay, but only in a single Argentinean population. These observations are consistent with independent in situ evolution of glyphosate resistance in Argentina, followed by some limited recent migration of the eccDNA-based mechanism from Brazil to Argentina. Taken together, our results are consistent with an initial introduction of A. palmeri into South America sometime before the 1980s, and local evolution of GR in Argentina, followed by a secondary invasion of GR A. palmeri with the unique eccDNA-based mechanism from the USA into Brazil and Uruguay during the 2010s.

Genomic-based epidemiology reveals independent origins and gene flow of glyphosate resistance in Bassia scoparia populations across North America.

Genomic-based epidemiology can provide insight into the origins and spread of herbicide resistance mechanisms in weeds. We used kochia (Bassia scoparia) populations resistant to the herbicide glyphosate from across western North America to test the alternative hypotheses that (i) a single EPSPS gene duplication event occurred initially in the Central Great Plains and then subsequently spread to all other geographical areas now exhibiting glyphosate-resistant kochia populations or that (ii) gene duplication occurred multiple times in independent events in a case of parallel evolution. We used qPCR markers previously developed for measuring the structure of the EPSPS tandem duplication to investigate whether all glyphosate-resistant individuals had the same EPSPS repeat structure. We also investigated population structure using simple sequence repeat markers to determine the relatedness of kochia populations from across the Central Great Plains, Northern Plains and the Pacific Northwest. We found that the original EPSPS duplication genotype was predominant in the Central Great Plains where glyphosate resistance was first reported. We identified two additional EPSPS duplication genotypes, one having geographical associations with the Northern Plains and the other with the Pacific Northwest. The EPSPS duplication genotype from the Pacific Northwest seems likely to represent a second, independent evolutionary origin of a resistance allele. We found evidence of gene flow across populations and a general lack of population structure. The results support at least two independent evolutionary origins of glyphosate resistance in kochia, followed by substantial and mostly geographically localized gene flow to spread the resistance alleles into diverse genetic backgrounds.

A needle in a seedstack: an improved method for detection of rare alleles in bulk seed testing through KASP.

BACKGROUND: Amaranthus palmeri is an aggressive and prolific weed species with major impact on agricultural yield and is a prohibited noxious weed across the Midwest. Morphological identification of A. palmeri from other Amaranthus species is extremely difficult in seeds, which has led to genetic testing for seed identification in commercial seed lots. RESULTS: We created an inexpensive and reliable genetic test based on novel, species-specific, single nucleotide polymorphisms (SNPs) from GBS (Genotyping by Sequencing) data. We report three SNP-based genetic tests for identifying A. palmeri alone or in a mixed pool of Amaranthus spp. Sensitivity ranged from 99.8 to 100%, specificity from 99.59 to 100%. Accuracy for all three tests is > 99.7%. All three are capable of reliably detecting one A. palmeri seed in a pool of 200 Amaranthus spp. seeds. The test was validated across 20 populations of A. palmeri, along with eight other Amaranthus species, the largest and most genetically diverse panel of Amaranthus samples to date. CONCLUSION: Our work represents a marked improvement over existing commercial assays resulting in an identification assay that is (i) accurate, (ii) robust, (iii) easy to interpret and (iv) applicable to both leaf tissue and pools of up to 200 seeds. Included is a data transformation method for calling of closely grouped competitive fluorescence assays. We also present a comprehensive GBS dataset from the largest geographic panel of Amaranthus populations sequenced. Our approach serves as a model for developing markers for other difficult to identify species. © 2021 Society of Chemical Industry.