This article is based on feedback I submitted in response to the Office of Management and Budget’s (OMB’s) April 2023 request for comments on its draft revisions to Circular A-4, “Regulatory Analysis.” Much has changed since I submitted my comments in June 2023. OMB issued a final circular in November 2023 and subsequently rescinded it in February 2025. This article includes my comments as submitted, along with an introductory “prologue” and an “epilogue” that reflects on the decision to abandon the 2023 revisions and return to the 2003 Circular. My comment addressed key elements of regulatory analysis, suggested areas where OMB could provide more guidance, and identified several aspects of the 2023 Circular that appeared to be internally inconsistent or contradictory. It concluded that some of the 2023 revisions were worthwhile, while others would have obfuscated for policymakers important information on the welfare effects of regulatory actions.

Objectives/Goals: The goal of this work is to understand the physiological profile of phage susceptibility and identify candidate phage defense mechanisms. Additionally, it aims to determine the host receptors targeted by bacteriophages to infect E. coli O157:H7 through random bar code transposon-site sequencing (RB-TnSeq). Methods/Study Population: A collection of 109 E. coli O157:H7 strains from environmental, food, and animal sources were analyzed, representing phylogenetic lineages corresponding to clades 2, 3, 5, 6, 7, and 8. Phage susceptibility profiles were determined using 23 bacteriophages, assessing plaque morphology. Using the O157:H7 genomes, a genomic analysis was conducted with the Prokaryotic Antiviral Defense Locator (PADLOC), which identified putative phage defense systems through sequence homology. Additionally, 5 RB-TnSeq libraries were generated in representative strains to study loss-of-function mutations. These libraries will be screened against a subset of diverse phage to identify the receptors involved in phage adsorption. Results/Anticipated Results: The phage resistance patterns showed susceptibility varied across clades, suggesting distinct mechanisms. Several defense systems were identified using PADLOC, including restriction-modification, Cas, Lamassu, and Druantia. Phage defense candidate (PDC) systems were identified, showing homology to known systems, though their specific function remains unknown. Clade 7.2 exhibited higher phage resistance and a greater presence of PDCs compared to the other clades. Five saturated RB-TnSeq libraries were constructed in O157:H7, achieving 84.5–89% gene coverage. These libraries will facilitate the identification of receptors involved in phage adsorption and resistance. Discussion/Significance of Impact: This study deepens our understanding of phage resistance in E. coli O157:H7 by identifying key defense systems and receptors. The discovery of novel antiviral mechanisms offers promising targets for phage-based interventions, potentially enhancing strategies for controlling this dangerous pathogen.

Research on campaign finance suggests that Americans prefer candidates who are not funded by Political Action Committees (PACs). However, prior research has not examined how perceptions of a candidate who is PAC-funded vs. PAC-free might differ for racial minority and female candidates compared to White, male candidates. Using experimental vignettes, we test the causal impact of PAC funding, race, and gender on voter perceptions of the candidate. We find that refusing PAC funds, for example, is associated with appearing more ethical and more likely to work for voters’ interests over special interests, less corrupt, and more capable of winning elections. However, we show that race, more than gender, interacts with PAC funding to impact voter perceptions. We find that White female and male candidates benefit the most from PAC refusal. While Black female and male candidates receive little or no significant change in perceptions, Black PAC-funded candidates are perceived favorably compared to White PAC-funded candidates. Our results have implications for White and Black political candidates considering their funding strategies. Additionally, we contribute to existing literature by showing that refusing PAC funds status does not signal the same qualities for all candidates.

This special issue of the Journal of Benefit–Cost Analysis is dedicated to the memory of Jerry Ellig, a brilliant economist whose untimely death in 2021 cut short a productive and influential career in government and academia. Jerry was adept at applying economic concepts and empirical analysis to improve public policy, and he enjoyed not only studying real policy problems, but finding practical solutions to them. He was also a generous mentor, supporting and collaborating with graduate students and colleagues to publish prolifically in peer-reviewed economics, public administration, and political science journals, as well as law reviews and more popular outlets. He was a great communicator, able to take his academic work and translate it for different audiences, including through testimony, seminars, op-eds, short presentations, and classroom teaching. In addition to these immense talents, Jerry was genuinely kind and unpretentious; he wore Wal-Mart suits and garish ties. And he was laugh-out-loud funny, a master at diffusing difficult situations with a witty, but never mean, quip.

Over the last century, the United States has witnessed three approaches to achieving better regulatory outcomes: the removal of “economic” regulations in certain sectors; regulatory impact analysis (RIA) of new “social” regulations; and retrospective analysis of existing regulations. This article reviews the rationale for each approach, the results to date, and the remaining challenges. It finds that both institutional and technical factors influence the success of reform efforts.

Background: Sellar and suprasellar pediatric lesions are uncommon. Endoscopic transnasal transphenoidal surgery (ETTS) is the preferred treatment, but early post-op MRI is hindered by sphenoidal packing. This study aims to assess iMRI safety and efficacy in pediatric ETTS cases. Methods: We performed a retrospective review from Jan 01, 2015 to Dec 31, 2022, evaluating use of iMRI. We determined if the goals of the surgery (biopsy, cyst decompression, subtotal resection, gross total resection) were met, and iMRI’s influence on surgery outcomes. We examined patient age, surgery duration, length of stay, histopathology results, surgical complications, post-op MRIs within 1 month, and tumor progression/recurrence. Results: Over eight years, 20 pediatric ETTS procedures, 14 with iMRI, were conducted. Achieving goals in 13 cases, iMRI prompted extra surgery once. Two adenomas progressed, requiring a second surgery, and craniopharyngioma cases had complications, needing further interventions. Hospital stays varied (1-9 days), with a mean surgery duration of 6 hours and 47 minutes. The study underscores iMRI’s potential impact, stressing the necessity for more research in pediatric transsphenoidal surgeries. Conclusions: While intraoperative MRI in pediatric transsphenoidal surgeries may aid goal verification, this small study doesn’t conclusively demonstrate improved outcomes. Complication rates align with non-IMRI procedures, highlighting the need for further research.

OBJECTIVES/GOALS: 1. Identify candidate AN-SAD-causing variants. 2. Estimate the variant effect size of and genotypic relative risk for arrhythmias and AN-SAD. METHODS/STUDY POPULATION: We performed whole genome sequencing (WGS) on 59 Thoroughbred AN-SAD cases and 58 controls. WGS was mapped and variants identified using a modified version of the Genome Analysis Toolkit best practices. Variants will be selected based on case-control analysis using SnpSift and presence in candidate genes. The top 400 candidate AN-SAD-causing variants will be selected based on being common in cases and rare or absent in controls, and uncommon (allele frequency less than 10%) in a catalog of genetic variation for the horse. The 400 variants will be genotyped in our cohort of 1,200 racehorses to determine variant effect size and genotypic relative risk. RESULTS/ANTICIPATED RESULTS: 17,182,003 variants were identified. 230 variants had significantly different allele frequencies (AF) between cases and controls (SnpSift). 723 high and 4,824 moderate impact variants were identified in 1,072 candidate genes. 3,681 variants were present at an AF 10% in the equine variant catalog. Variant effect prediction is ongoing to select the final 400 variants. Cardiac phenotyping (cardiac auscultation and ECG before, during, and after exercise) was performed on 790 racehorses and we will have 1,200 racehorses with cardiac phenotypes and/or AN-SAD. We will genotype the top 400 candidate AN-SAD-causing variants in these 1,200 horses to identify variants of large effect size. DISCUSSION/SIGNIFICANCE: Identification of candidate AN-SAD variants in a spontaneous animal model can facilitate interpretation of candidate variants in humans and horses. This project will provide further support for the racehorse AN-SAD model and will support future work exploring the genetic and environmental risk factors contributing to AN-SAD in this animal model.

As the venues for professional training and education, universities have always shaped the future of the archaeological discipline—for better but also, in important ways, for worse. Historically, university structures promoted practitioner homogeneity and social inequity and, at the largest research-intensive universities, even managed to turn “service” into a dirty word. However, using the same structures that perpetuated damaging practices in the past, universities can just as readily transform archaeology into the inclusive, community-engaged discipline it should always have been—while serving communities in ways that matter to them. This article explains and illustrates how and why we have tried to do this through the founding and operation of the Oklahoma Public Archaeology Network (OKPAN) at the University of Oklahoma. OKPAN seeks to improve relationships among diverse Oklahoma communities by framing archaeology as a tool that that can serve communities’ interests while creating pathways within universities for members of historically excluded groups to join and help further transform the discipline.