Mpox infection protects against re-challenge in rhesus macaques.

The mpox outbreak of 2022-2023 involved rapid global spread in men who have sex with men. We infected 18 rhesus macaques with mpox by the intravenous, intradermal, and intrarectal routes and observed robust antibody and T cell responses following all three routes of infection. Numerous skin lesions and high plasma viral loads were observed following intravenous and intradermal infection. Skin lesions peaked on day 10 and resolved by day 28 following infection. On day 28, we re-challenged all convalescent and 3 naive animals with mpox. All convalescent animals were protected against re-challenge. Transcriptomic studies showed upregulation of innate and inflammatory responses and downregulation of collagen formation and extracellular matrix organization following challenge, as well as rapid activation of T cell and plasma cell responses following re-challenge. These data suggest key mechanistic insights into mpox pathogenesis and immunity. This macaque model should prove useful for evaluating mpox vaccines and therapeutics.

Vaccine protection against the SARS-CoV-2 Omicron variant in macaques.

The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. In this study, we show that the mRNA-based BNT162b2 vaccine and the adenovirus-vector-based Ad26.COV2.S vaccine provide robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in cynomolgus macaques. We vaccinated 30 macaques with homologous and heterologous prime-boost regimens with BNT162b2 and Ad26.COV2.S. Following Omicron challenge, vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs. However, 4 vaccinated animals that had moderate Omicron-neutralizing antibody titers and undetectable Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Moreover, virologic control correlated with both antibody and T cell responses. These data suggest that both humoral and cellular immune responses contribute to vaccine protection against a highly mutated SARS-CoV-2 variant.

Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques.

A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants1,2, although they still provide protection against severe disease. Enhanced mucosal immunity may be required to block infection and onward transmission. Intranasal administration of current vaccines has proven inconsistent3-7, suggesting that alternative immunization strategies may be required. Here we show that intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 challenge. A total of 40 previously immunized rhesus macaques were boosted with a bivalent Ad26 vaccine by the intramuscular, intranasal and intratracheal routes, or with a bivalent mRNA vaccine by the intranasal route. Ad26 boosting by the intratracheal route led to a substantial expansion of mucosal neutralizing antibodies, IgG and IgA binding antibodies, and CD8+ and CD4+ T cell responses, which exceeded those induced by Ad26 boosting by the intramuscular and intranasal routes. Intratracheal Ad26 boosting also led to robust upregulation of cytokine, natural killer, and T and B cell pathways in the lungs. After challenge with a high dose of SARS-CoV-2 BQ.1.1, intratracheal Ad26 boosting provided near-complete protection, whereas the other boosting strategies proved less effective. Protective efficacy correlated best with mucosal humoral and cellular immune responses. These data demonstrate that these immunization strategies induce robust mucosal immunity, suggesting the feasibility of developing vaccines that block respiratory viral infections.

Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine.

The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 µg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.

Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques.

The emergence of SARS-CoV-2 variants that partially evade neutralizing antibodies poses a threat to the efficacy of current COVID-19 vaccines1,2. The Ad26.COV2.S vaccine expresses a stabilized spike protein from the WA1/2020 strain of SARS-CoV-2, and has recently demonstrated protective efficacy against symptomatic COVID-19 in humans in several geographical regions-including in South Africa, where 95% of sequenced viruses in cases of COVID-19 were the B.1.351 variant3. Here we show that Ad26.COV2.S elicits humoral and cellular immune responses that cross-react with the B.1.351 variant and protects against B.1.351 challenge in rhesus macaques. Ad26.COV2.S induced lower binding and neutralizing antibodies against B.1.351 as compared to WA1/2020, but elicited comparable CD8 and CD4 T cell responses against the WA1/2020, B.1.351, B.1.1.7, P.1 and CAL.20C variants. B.1.351 infection of control rhesus macaques resulted in higher levels of virus replication in bronchoalveolar lavage and nasal swabs than did WA1/2020 infection. Ad26.COV2.S provided robust protection against both WA1/2020 and B.1.351, although we observed higher levels of virus in vaccinated macaques after B.1.351 challenge. These data demonstrate that Ad26.COV2.S provided robust protection against B.1.351 challenge in rhesus macaques. Our findings have important implications for vaccine control of SARS-CoV-2 variants of concern.

Adaptive infusion of a glucagon-like peptide-1/glucagon receptor co-agonist G3215, in adults with overweight or obesity: Results from a phase 1 randomized clinical trial.

AIMS: To determine whether a continuous infusion of a glucagon-like peptide receptor (GLP-1R)/glucagon receptor (GCGR) co-agonist, G3215 is safe and well tolerated in adults with overweight or obesity. METHODS: A phase 1 randomized, double blind, placebo-controlled trial of G3215 in overweight or obese participants, with or without type 2 diabetes. RESULTS: Twenty-six participants were recruited and randomized with 23 completing a 14-day subcutaneous infusion of G3215 or placebo. The most common adverse events were nausea or vomiting, which were mild in most cases and mitigated by real-time adjustment of drug infusion. There were no cardiovascular concerns with G3215 infusion. The pharmacokinetic characteristics were in keeping with a continuous infusion over 14 days. A least-squares mean body weight loss of 2.39 kg was achieved with a 14-day infusion of G3215, compared with 0.84 kg with placebo infusion (p < .05). A reduction in food consumption was also observed in participants receiving G3215 and there was no deterioration in glycaemia. An improved lipid profile was seen in G3215-treated participants and consistent with GCGR activation, a broad reduction in circulating amino acids was seen during the infusion period. CONCLUSION: An adaptive continuous infusion of the GLP-1/GCGR co-agonist, G3215, is safe and well tolerated offering a unique strategy to control drug exposure. By allowing rapid, response-directed titration, this strategy may allow for mitigation of adverse effects and afford significant weight loss within shorter time horizons than is presently possible with weekly GLP-1R and multi-agonists. These results support ongoing development of G3215 for the treatment of obesity and metabolic disease.

A "Red Flag" system adds value to medical school admissions interviews.

INTRODUCTION: Non-cognitive traits should be considered when selecting candidates to study medicine. However, evaluating these traits remains difficult. We explored whether measuring undesirable non-cognitive behaviour ('Red Flags') added value to a medical school admissions system. Red Flags included rudeness, ignoring the contributions of others, disrespectful behaviour, or poor communication. METHODS: Following an admissions interview testing non-cognitive attributes in 648 applicants to a UK medical school, we measured the association between interview score and Red Flag frequency. We tested linear and polynomial regression models to evaluate whether the association was linear or non-linear. RESULTS: In total, 1126 Red Flags were observed. While Red Flags were concentrated among low-scorers, candidates in the highest- and second-highest deciles for interview score still received Red Flags (six and twenty-two, respectively). The polynomial regression model indicated candidates with higher scores received fewer Red Flags, but the association was not linear (F(3644) = 159.8, p = .001, adjusted R2 = 0.42). CONCLUSIONS: The non-linear association between interview score and Red Flag frequency shows some candidates with desirable non-cognitive attributes will still display undesirable-or even exclusionary-non-cognitive attributes. Recording Red Flag behaviour reduces the likelihood such candidates will be offered a place at medical school.

Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques.

Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge. Postpyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage fluid. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage fluid following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that postpyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques. IMPORTANCE SARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution, and improved coverage may offer significant public health benefits, especially in resource-limited settings. Live oral vaccines have the potential to address some of these limitations; however, no studies have yet been conducted to assess the immunogenicity and protective efficacy of a live oral vaccine against SARS-CoV-2. Here, we report that oral administration of live SARS-CoV-2 in nonhuman primates may offer prophylactic benefits, but the formulation and route of administration will require further optimization.

Sleeve gastrectomy causes weight-loss independent improvements in hepatic steatosis.

BACKGROUND AND AIMS: Sleeve gastrectomy (VSG) leads to improvement in hepatic steatosis, associated with weight loss. The aims of this study were to investigate whether VSG leads to weight-loss independent improvements in liver steatosis in mice with diet-induced obesity (DIO); and to metabolically and transcriptomically profile hepatic changes in mice undergoing VSG. METHODS: Mice with DIO were treated with VSG, sham surgery with subsequent food restriction to weight-match to the VSG group (Sham-WM), or sham surgery with return to unrestricted diet (Sham-Ad lib). Hepatic steatosis, glucose tolerance, insulin and glucagon resistance, and hepatic transcriptomics were investigated at the end of the study period and treatment groups were compared with mice undergoing sham surgery only (Sham-Ad lib). RESULTS: VSG led to much greater improvement in liver steatosis than Sham-WM (liver triglyceride mg/mg 2.5 ± 0.1, 2.1 ± 0.2, 1.6 ± 0.1 for Sham-AL, Sham-WM and VSG respectively; p = 0.003). Homeostatic model assessment of insulin resistance was improved following VSG only (51.2 ± 8.8, 36.3 ± 5.3, 22.3 ± 6.1 for Sham-AL, Sham-WM and VSG respectively; p = 0.03). The glucagon-alanine index, a measure of glucagon resistance, fell with VSG but was significantly increased in Sham-WM (9.8 ± 1.7, 25.8 ± 4.6 and 5.2 ± 1.2 in Sham Ad-lib, Sham-WM and VSG respectively; p = 0.0003). Genes downstream of glucagon receptor signalling which govern fatty acid synthesis (Acaca, Acacb, Me1, Acly, Fasn and Elovl6) were downregulated following VSG but upregulated in Sham-WM. CONCLUSIONS: Changes in glucagon sensitivity may contribute to weight-loss independent improvements in hepatic steatosis following VSG.

Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune sera: Quantitative image analysis in pathologic assessments.

There is a need to standardize pathologic endpoints in animal models of SARS-CoV-2 infection to help benchmark study quality, improve cross-institutional comparison of data, and assess therapeutic efficacy so that potential drugs and vaccines for SARS-CoV-2 can rapidly advance. The Syrian hamster model is a tractable small animal model for COVID-19 that models clinical disease in humans. Using the hamster model, the authors used traditional pathologic assessment with quantitative image analysis to assess disease outcomes in hamsters administered polyclonal immune sera from previously challenged rhesus macaques. The authors then used quantitative image analysis to assess pathologic endpoints across studies performed at different institutions using different tissue processing protocols. The authors detail pathological features of SARS-CoV-2 infection longitudinally and use immunohistochemistry to quantify myeloid cells and T lymphocyte infiltrates during SARS-CoV-2 infection. High-dose immune sera protected hamsters from weight loss and diminished viral replication in tissues and reduced lung lesions. Cumulative pathology scoring correlated with weight loss and was robust in distinguishing IgG efficacy. In formalin-infused lungs, quantitative measurement of percent area affected also correlated with weight loss but was less robust in non-formalin-infused lungs. Longitudinal immunohistochemical assessment of interstitial macrophage infiltrates showed that peak infiltration corresponded to weight loss, yet quantitative assessment of macrophage, neutrophil, and CD3+ T lymphocyte numbers did not distinguish IgG treatment effects. Here, the authors show that quantitative image analysis was a useful adjunct tool for assessing SARS-CoV-2 treatment outcomes in the hamster model.

Can borderline regression method be used to standard set OSCEs in small cohorts?

INTRODUCTION: Absolute methods of standard setting (SS) are more suitable for OSCEs. However, previous studies have theorised that borderline regression method (BRM) is not reliable for small sample sizes. MATERIALS AND METHODS: OSCE results for the 2017-2019 cohorts were analysed to compare BRM versus Modified Angoff. We reported on whether the stations in multiple cohorts were sufficiently equivalent to aggregate the results together to calculate which method of SS was more reliable. We finally used the bootstrapping method to compare the accuracy of BRM for small versus simulated larger cohorts. RESULTS: BRM was a valid method for SS OSCEs in this dataset when station quality was sufficiently high. However, a large gap between the Angoff and BRM in some of the OSCEs was observed, which could be explained by poor use of the grading scale. Model fit statistics were generally adequate even with low sample sizes. Using the bootstrap of datasets, the error rate was much higher for low-quality stations but was not an issue in high-quality ones. DISCUSSION: This study adds to the evidence that well-designed OSCEs can use BRM for small cohorts. However, there is a need for the institutions to properly assess their stations and their assessors, before embarking into using this method, to prevent from having to remove stations. CONCLUSIONS: This analysis suggests that BRM is an acceptable replacement for Angoff SS in small cohorts, where there is a range of candidates undertaking the assessments and there are well-designed OSCES with well-trained examiners.

Medical students' perception of e-learning approach (MeSPeLA) - a mixed method research.

There is a discrepancy between the research exploring e-learning at medical universities in Central/Eastern and Western European countries. The aim of the MeSPeLA study was to explore the understanding, experience and expectations of Polish medical students in terms of e-learning. Questionnaire containing open-ended and closed questions supplemented by focus group discussion was validated and performed among 204 medical students in Poland before COVID-19 pandemia. Several domains: understanding of e-learning definitions; students' experience, preferences, expectations and perceptions of e-learning usefulness, advantages and disadvantages were addressed. The qualitative data were analyzed using an inductive approach. 46.0% of students chose a communication-oriented definition as the most appropriate. 7.4% claimed not to have any experience with e-learning. 76.8% of respondents indicated they had contact with e-learning. The main reported e-learning advantages were time saving and easier time management. The most common drawback was limited social interactions. The acceptance of the usage of e-learning was high. Medical undergraduates in Poland regardless of the year of studies, gender or choice of future specialization showed positive attitudes towards e-learning. Students with advanced IT skills showed a better understanding of the e-learning definition and perceived e-learning to be a more useful approach. The expectations and perceptions about e-learning in Polish medical schools seems similar to some extent to that in Western European and the United States so we can be more confident about applying some lessons from these research to Poland or other post-communist countries. Such application has been accelerated due to COVID-19 pandemia.

Predicting failure before it happens: A 5-year, 1042 participant prospective study.

PURPOSE OF THE ARTICLE: Students who fail assessments are at risk of negative consequences, including emotional distress and cessation of studies. Identifying students at risk of failure before they experience difficulties may considerably improve their outcomes. METHODS: Using a prospective design, we collected simple measures of engagement (formative assessment scores, compliance with routine administrative tasks, and attendance) over the first 6 weeks of Year 1. These measures were combined to form an engagement score which was used to predict a summative examination sat 14 weeks after the start of medical school. The project was repeated for five cohorts, giving a total sample size of 1042. RESULTS: Simple linear regression showed engagement predicted performance (R2adj = 0.03, F(1,1040) = 90.09, p < 0.001) with a small effect size. More than half of failing students had an engagement score in the lowest two deciles. CONCLUSIONS: At-risk medical students can be identified with some accuracy immediately after starting medical school using routinely collected, easily analysed data, allowing for tailored interventions to support students. The toolkit provided here can reproduce the predictive model in any equivalent educational context. Medical educationalists must evaluate how the advantages of early detection are balanced against the potential invasiveness of using student data.

Candidates undertaking (invigilated) assessment online show no differences in performance compared to those undertaking assessment offline.

BACKGROUND: Medical education has historically relied on high stakes knowledge tests sat in examination centres with invigilators monitoring academic malpractice. The COVID-19 pandemic has made such examination formats impossible, and medical educators have explored the use of online assessments as a potential replacement. This shift has in turn led to fears that the change in format or academic malpractice might lead to considerably higher attainment scores on online assessment with no underlying improvement in student competence. METHOD: Here, we present an analysis of 8092 sittings of the Prescribing Safety Assessment (PSA), an assessment designed to test the prescribing skills of final year medical students in the UK. In-person assessments for the PSA were cancelled partway through the academic year 2020, with 6048 sittings delivered in an offline, traditionally invigilated format, and then 2044 sittings delivered in an online, webcam invigilated format. RESULTS: A comparison (able to detect very small effects) showed no attainment gap between online (M = 0.762, SD = 0.34) and offline (M = 0.761, SD = 0.34) performance. CONCLUSIONS: The finding suggests that the transition to online assessment does not affect student performance. The findings should increase confidence in the use of online testing in high-stakes assessment.

Effect of remote online exam delivery on student experience and performance in applied knowledge tests.

BACKGROUND: The use of remote online delivery of summative assessments has been underexplored in medical education. Due to the COVID-19 pandemic, all end of year applied knowledge multiple choice question (MCQ) tests at one UK medical school were switched from on campus to remote assessments. METHODS: We conducted an online survey of student experience with remote exam delivery and compared test performance in remote versus invigilated campus-based forms of similar assessments for Year 4 and 5 students across two academic years. RESULTS: Very few students experienced technical or practical problems in completing their exam remotely. Test anxiety was reduced for some students but increased for others. The majority of students preferred the traditional setting of invigilated exams in a computer lab, feeling this ensured an even playing field for all candidates. Mean score was higher for Year 4 students in the remotely-delivered versus campus-based form of the same exam (76.53% [SD 6.57] vs. 72.81% [6.64]; t438.38 = 5.94, p = 0.001; d = 0.56), whereas candidate performance was equivalent across both forms for Year 5 students. CONCLUSIONS: Remote online MCQ exam delivery is an effective and generally acceptable approach to summative assessment, and could be used again in future without detriment to students if onsite delivery is not possible.

Variation in performance on common content items at UK medical schools.

BACKGROUND: Due to differing assessment systems across UK medical schools, making meaningful cross-school comparisons on undergraduate students' performance in knowledge tests is difficult. Ahead of the introduction of a national licensing assessment in the UK, we evaluate schools' performances on a shared pool of "common content" knowledge test items to compare candidates at different schools and evaluate whether they would pass under different standard setting regimes. Such information can then help develop a cross-school consensus on standard setting shared content. METHODS: We undertook a cross-sectional study in the academic sessions 2016-17 and 2017-18. Sixty "best of five" multiple choice 'common content' items were delivered each year, with five used in both years. In 2016-17 30 (of 31 eligible) medical schools undertook a mean of 52.6 items with 7,177 participants. In 2017-18 the same 30 medical schools undertook a mean of 52.8 items with 7,165 participants, creating a full sample of 14,342 medical students sitting common content prior to graduation. Using mean scores, we compared performance across items and carried out a "like-for-like" comparison of schools who used the same set of items then modelled the impact of different passing standards on these schools. RESULTS: Schools varied substantially on candidate total score. Schools differed in their performance with large (Cohen's d around 1) effects. A passing standard that would see 5 % of candidates at high scoring schools fail left low-scoring schools with fail rates of up to 40 %, whereas a passing standard that would see 5 % of candidates at low scoring schools fail would see virtually no candidates from high scoring schools fail. CONCLUSIONS: Candidates at different schools exhibited significant differences in scores in two separate sittings. Performance varied by enough that standards that produce realistic fail rates in one medical school may produce substantially different pass rates in other medical schools - despite identical content and the candidates being governed by the same regulator. Regardless of which hypothetical standards are "correct" as judged by experts, large institutional differences in pass rates must be explored and understood by medical educators before shared standards are applied. The study results can assist cross-school groups in developing a consensus on standard setting future licensing assessment.

Student perspective on outcomes and process - Recommendations for implementing competency-based medical education.

PURPOSE: Competency-based medical education (CBME) seeks to prepare undergraduate and postgraduate trainees for clinical practice. Its major emphasis is on outcomes, but questions about how best to reach these remain. One key issue is the need to integrate what matters most to students when setting educational goals: this is crucial if we are to design curricula that trainees understand and engage with, and that promote successful achievement of competencies. METHOD: We interviewed medical students in years 4 and 6 of a 6-year medical degree and used thematic analysis to understand their main educational priorities and how these fit with the aims of CBME. RESULTS: Two major themes emerged: features of content and process. For content, students wanted clear guidance on what constitutes competence, finding broad outcome statements abstract and difficult to understand as novices. They also attach critical importance to features of process such as being welcomed, included in clinical teams and being known personally - these promote motivation, understanding, and professional development. CONCLUSIONS: We present recommendations for those designing CBME curricula to emphasize the student perspective: what kind of guidance on outcomes is required, and features of process that must not be neglected if competence is to be achieved.

Using differential item functioning to evaluate potential bias in a high stakes postgraduate knowledge based assessment.

BACKGROUND: Fairness is a critical component of defensible assessment. Candidates should perform according to ability without influence from background characteristics such as ethnicity or sex. However, performance differs by candidate background in many assessment environments. Many potential causes of such differences exist, and examinations must be routinely analysed to ensure they do not present inappropriate progression barriers for any candidate group. By analysing the individual questions of an examination through techniques such as Differential Item Functioning (DIF), we can test whether a subset of unfair questions explains group-level differences. Such items can then be revised or removed. METHODS: We used DIF to investigate fairness for 13,694 candidates sitting a major international summative postgraduate examination in internal medicine. We compared (a) ethnically white UK graduates against ethnically non-white UK graduates and (b) male UK graduates against female UK graduates. DIF was used to test 2773 questions across 14 sittings. RESULTS: Across 2773 questions eight (0.29%) showed notable DIF after correcting for multiple comparisons: seven medium effects and one large effect. Blinded analysis of these questions by a panel of clinician assessors identified no plausible explanations for the differences. These questions were removed from the question bank and we present them here to share knowledge of questions with DIF. These questions did not significantly impact the overall performance of the cohort. Group-level differences in performance between the groups we studied in this examination cannot be explained by a subset of unfair questions. CONCLUSIONS: DIF helps explore fairness in assessment at the question level. This is especially important in high-stakes assessment where a small number of unfair questions may adversely impact the passing rates of some groups. However, very few questions exhibited notable DIF so differences in passing rates for the groups we studied cannot be explained by unfairness at the question level.