Serum albumin (SA) is the most abundant plasma protein in mammals. SA is a multifunctional protein with extraordinary ligand binding capacity, making it a transporter molecule for a diverse range of metabolites, drugs, nutrients, metals and other molecules. Due to its ligand binding properties, albumins have wide clinical, pharmaceutical, and biochemical applications. Albumins are also allergenic, and exhibit a high degree of cross-reactivity due to significant sequence and structure similarity of SAs from different organisms. Here we present crystal structures of albumins from cattle (BSA), horse (ESA) and rabbit (RSA) serums. The structural data are correlated with the results of immunological studies of SAs. We also analyze the conservation or divergence of structures and sequences of SAs in the context of their potential allergenicity and cross-reactivity. In addition, we identified a previously uncharacterized ligand binding site in the structure of RSA, and calcium binding sites in the structure of BSA, which is the first serum albumin structure to contain metal ions.

IMPORTANCE Although implicit bias in medical training has long been suspected, it has been difficult to study using objective measures, and the influence of sex and gender in the evaluation of medical trainees is unknown. The emergency medicine (EM) milestones provide a standardized framework for longitudinal resident assessment, allowing for analysis of resident performance across all years and programs at a scope and level of detail never previously possible. OBJECTIVE To compare faculty-observed training milestone attainment of male vs female residency training DESIGN, SETTING, AND PARTICIPANTS This multicenter, longitudinal, retrospective cohort study took place at 8 community and academic EM training programs across the United States from July 1, 2013, to July 1, 2015, using a real-time, mobile-based, direct-observation evaluation tool. The study examined 33 456 direct-observation subcompetency evaluations of 359 EM residents by 285 faculty members. MAIN OUTCOMES AND MEASURES Milestone attainment for male and female EM residents as observed by male and female faculty throughout residency and analyzed using multilevel mixed-effects linear regression modeling. RESULTS A total of 33 456 direct-observation evaluations were collected from 359 EM residents (237 men [66.0%] and 122 women [34.0%]) by 285 faculty members (194 men [68.1%] and 91 women [31.9%]) during the study period. Female and male residents achieved similar milestone levels during the first year of residency. However, the rate of milestone attainment was 12.7% (0.07 levels per year) higher for male residents through all of residency (95% CI, 0.04-0.09). By graduation, men scored approximately 0.15 milestone levels higher than women, which is equivalent to 3 to 4 months of additional training, given that the average resident gains approximately 0.52 levels per year using our model (95% CI, 0.49-0.54). No statistically significant differences in scores were found based on faculty evaluator gender (effect size difference, 0.02 milestone levels; 95% CI for males, −0.09 to 0.11) or evaluator-evaluatee gender pairing (effect size difference, −0.02 milestone levels; 95% CI for interaction, −0.05 to 0.01). CONCLUSIONS AND RELEVANCEAlthough male and female residents receive similar evaluations at the beginning of residency, the rate of milestone attainment throughout training was higher for male than female residents across all EM subcompetencies, leading to a gender gap in evaluations that continues until graduation. Faculty should be cognizant of possible gender bias when evaluating medical trainees.

Our study revealed qualitative differences in the kind of feedback that male and female EM residents received from attending physicians. The findings suggest that attending physicians should endeavor to provide male and female residents with consistent feedback and guard against gender bias in their perceptions of residents' capabilities.