Deborah L. Engle

Requirement for Ca2+/Calmodulin-Dependent Kinase Type IV/Gr in Setting the Thymocyte Selection Threshold

The outcome of thymocyte selection is influenced by the nature of Ca2+ signals transduced by the TCR. Robust Ca2+ responses characterize high-affinity, negatively selecting peptide/TCR interactions, while modest responses typify lower-affinity, positively selecting interactions. To elucidate mechanisms by which thymocytes decode distinct Ca2+ signals, we examined selection events in mice lacking Ca2+/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes. CaMKIV/Gr-deficient thymocytes exhibited impaired positive selection and defective Ca2+-dependent gene transcription. Significantly, CaMKIV/Gr deficiency raised the selection threshold of peptide/TCR interactions such that a peptide that normally induced weak negative selection instead promoted positive selection. These results demonstrate an important role for CaMKIV/Gr in sensitizing thymocytes to selection by low-affinity peptides.

A Threshold for Central T Cell Tolerance to an Inducible Serum Protein

We report an inducible system of self Ag expression that examines the relationship between serum protein levels and central T cell tolerance. This transgenic approach is based on tetracycline-regulated expression of a secreted form of hen egg lysozyme, tagged with a murine hemoglobin (Hb) epitope. In the absence of the tetracycline-regulated transactivator, serum levels of the chimeric protein are extremely low (≤0.1 ng/ml) and the mice show partial tolerance to both Hb(64–76) and lysozyme epitopes. In the presence of the transactivator, expression increases to 1.5 ng/ml and the mice are completely tolerant. Partial tolerance was further investigated by crossing these mice to strains expressing transgenic TCRs. At the lowest Ag levels, 3.L2tg T cells (specific for Hb(64–76)/I-Ek) escape the thymus and ∼10% of CD4+ splenocytes express the 3.L2 TCR. In contrast, 3A9 T cells (specific for hen egg lysozyme(46–61)/I-Ak) are completely eliminated by negative selection. These data define a tolerogenic threshold for negative selection of Ag-specific T cells by circulating self proteins that are 100-fold more sensitive than previously demonstrated. They suggest that partial tolerance at extremely low levels of self Ag exposure is the result of a restricted repertoire of responding T cells, rather than a simple reduction in precursor frequency; tolerogenic thresholds are T cell specific.

Ligand-Specific Selection of MHC Class II-Restricted Thymocytes in Fetal Thymic Organ Culture

Positive and negative selection of thymocytes is determined by the specificity of the TCR and signaling through its associated molecules. We have studied selection of thymocytes bearing a MHC class II-restricted TCR using fetal thymic organ culture. This system allows the addition of peptides to the already diverse panoply of endogenous peptide ligands and is useful for analyzing ligand-specific negative selection of CD4 single positive (CD4SP) thymocytes. The data reveal that the ability of a given ligand to mediate negative selection is related to its dissociation rate from the TCR. We find that negative selection is very sensitive, and only the weakest ligand that we can identify fails to induce negative selection. None of the numerous peptides tested were able to induce an increase in CD4SP thymocytes. In addition, the ligands that induce negative selection of CD4SP thymocytes also cause an increase in numbers of CD8SP thymocytes bearing high levels of the class II-restricted TCR. Although these cells have a cell surface phenotype consistent with positive selection, they most likely represent cells in the process of negative selection. Further analysis reveals that these cells are not induced by these ligands in intact adult animals and that their induction is probably only revealed in the organ culture system.

The Primary Care Leadership Track at the Duke University School of Medicine: creating change agents to improve population health.

PROBLEM Physicians need training in community engagement, leadership, and population health to prepare them to work with partners within the community and to adapt medical care to address population health needs. APPROACH With an overall goal of training primary care practitioners to be change agents for improving population health, the Duke University School of Medicine launched the Primary Care Leadership Track (PCLT) in 2011. The four-year PCLT curriculum requires students to contribute to existing community health initiatives, perform community-engaged research, and participate in leadership training. The clinical curriculum incorporates a longitudinal approach to allow students to follow patient outcomes. In addition, students regularly interact with faculty to explore population health issues, review patient cases, and adjust individual learning opportunities as needed. OUTCOMES The first cohort of PCLT students will graduate in 2015. Prospective comparisons with traditional track students are planned on performance on standardized tests and career choices. NEXT STEPS The authors created the PCLT as a laboratory in which students can engage with the community and explore solutions to address the health of the public and the future delivery of health care. To meet the goal of training change agents, PCLT leaders need to expand opportunities for students to learn from providers and organizations that are successfully bridging the gap between medical care and public health.

Expanding Group Peer Review: A Proposal for Medical Education Scholarship

After participating in a group peer-review exercise at a workshop presented by Academic Medicine and MedEdPORTAL editors at the 2015 Association of American Medical Colleges Medical Education Meeting, the authors realized that the way their work group reviewed a manuscript was very different from the way by which they each would have reviewed the paper as an individual. Further, the group peer-review process yielded more robust feedback for the manuscripts authors than did the traditional individual peer-review process. This realization motivated the authors to reconvene and collaborate to write this Commentary to share their experience and propose the expanded use of group peer review in medical education scholarship.The authors consider the benefits of a peer-review process for reviewers, including learning how to improve their own manuscripts. They suggest that the benefits of a team review model may be similar to those of teamwork and team-based learning in medicine and medical education. They call for research to investigate this, to provide evidence to support group review, and to determine whether specific paper types would benefit most from team review (e.g., particularly complex manuscripts, those receiving widely disparate initial individual reviews). In addition, the authors propose ways in which a team-based approach to peer review could be expanded by journals and institutions. They believe that exploring the use of group peer review potentially could create a new methodology for skill development in research and scholarly writing and could enhance the quality of medical education scholarship.

It Takes a Village”: An Interprofessional Patient Safety Experience for Nursing and Medical Students

Background: Interprofessional education (IPE) is a “core” competency in professional school education. Challenges to successful collaboration include: aligning student abilities/experience, providing meaningful clinically-based interaction, and the need for extensive planning. Methods: Curriculum. A 3-1/2 hour IPE patient safety experience for final-semester medical and nursing students was developed. The content included an introduction, small-group low-fidelity simulation, and a large-group discussion of patient safety events observed by students during clinical rotations. Logistics. A planning committee met monthly to plan the curriculum and train faculty facilitators. Four sessions were held, accommodating 92 medical and 82 nursing students. Thirty faculty facilitators and 10 support personnel were needed for each session. Results: Over 70% students reported that the experience resulted in new learning and prompted self-reflection; 57% said it would change their practice. Students confirmed that the experience taught them about the importance of patient involvement in the team, the development of a shared mental model, and the importance of everyone’s role on the team. Conclusions: This collaboration successfully aligned students with similar levels of clinical experience, involved many faculty from both professional schools, and gave students opportunities to discuss differences in their roles and responsibilities, while highlighting patient-centered care.

A comparison of the effectiveness of the team-based learning readiness assessments completed at home to those completed in class.

Purpose: The readiness assurance process (RAP) of team-based learning (TBL) is an important element that ensures that students come prepared to learn. However, the RAP can use a significant amount of class time which could otherwise be used for application exercises. The authors administered the TBL-associated RAP in class or individual readiness assurance tests (iRATs) at home to compare medical student performance and learning preference for physiology content. Methods: Using cross-over study design, the first year medical student TBL teams were divided into two groups. One group was administered iRATs and group readiness assurance tests (gRATs) consisting of physiology questions during scheduled class time. The other group was administered the same iRAT questions at home, and did not complete a gRAT. To compare effectiveness of the two administration methods, both groups completed the same 12-question physiology assessment during dedicated class time. Four weeks later, the entire process was repeated, with each group administered the RAP using the opposite method. Results: The performance on the physiology assessment after at-home administration of the iRAT was equivalent to performance after traditional in-class administration of the RAP. In addition, a majority of students preferred the at-home method of administration and reported that the at-home method was more effective in helping them learn course content. Conclusion: The at-home administration of the iRAT proved effective. The at-home administration method is a promising alternative to conventional iRATs and gRATs with the goal of preserving valuable in-class time for TBL application exercises.

From the coliseum to the convention centre: a reflection on the current state of medical education conferences and conference-goers.

The advancement of knowledge and development of policy in the field of medical education require critical academic discourse among the most intelligent medical educators; and critical academic discourse requires coffee. In this essay, we reflect on the state of professional development conferences in the field of medical education and the rituals that surround their success. Having begun in ancient Greece, symposia were ripe with debauchery. Today, sedated by the light brown walls of hotel conference centres, symposia are more serious endeavours, engaging men and women in the sometimes turbulent waters of epistemological debate. The abstract submission process (summed up by: ‘Yay! It was accepted for presentation’ [Deep breath] ‘Oh no…it was accepted for presentation’), the ‘juggling act’ of parent attendees, the acting prowess of abstract presenters and the unapologetic approach to buffet eating are all by‐products of the collision of true intellects among medical education scholars. We hold these rituals in high regard and argue that they are required to advance the field of medical education. These rituals bind the walls supporting true progressive thought and innovative research, all fuelled by the glass of wine purchased with that one coveted drink ticket.

Is it a match? a novel method of evaluating medical school success

ABSTRACT Background: Medical education program evaluation allows for curricular improvements to both Undergraduate (UME) and Graduate Medical Education (GME). UME programs are left with little more than match rates and self-report to evaluate success of graduates in The Match. Objective: This manuscript shares a novel method of program evaluation through a systematic assessment of Match outcomes. Design: Surveys were developed and distributed to Program Training Directors (PTDs) at our institution to classify residency programs into which our UME graduates matched using an ordinal response scale and open-ended responses. Outcomes-based measures for UME graduates were collected and analyzed. The relationship between PTD survey data and UME graduates’ outcomes were explored. Open-ended response data were qualitatively analyzed using iterative cycles of coding and identifying themes. Results: The PTD survey response rate was 100%. 71% of our graduates matched to programs ranked as ‘elite’ (36%) or ‘top’ (35%) tier. The mean total number of ‘Honors’ grades achieved by UME graduates was 2.6. Data showed that graduates entering elite and top GME programs did not consistently earn Honors in their associated clerkships. A positive correlation was identified between USMLE Step 1 score, number of honors, and residency program rankings for a majority of the programs. Qualitative analysis identified research, faculty, and clinical exposure as necessary characteristics of ‘elite’ programs:. Factors considered by PTDs in the rating of programs included reputation, faculty, research, national presence and quality of graduates. Conclusions: This study describes a novel outcomes-based method of evaluating the success of UME programs. Results provided useful feedback about the quality of our UME program and its ability to produce graduates who match in highly-regarded GME programs. The findings from this study can benefit Clerkship Directors, Student Affairs and Curriculam Deans, and residency PTDs as they help students determine their competitiveness forspecialties and specific residency programs.

Mystery behind the match: an undergraduate medical education-graduate medical education collaborative approach to understanding match goals and outcomes.

Background There is a paucity of information regarding institutional targets for the number of undergraduate medical education (UME) graduates being matched to graduate medical education (GME) programs at their home institutions. At our institution, the Duke University, the number of UME graduates matched to GME programs declined dramatically in 2011. To better understand why this decline may have happened, we sought to identify perceived quality metrics for UME and GME learners, evaluate trends in match outcomes and educational program characteristics, and explore whether there is an ideal retention rate for UME graduates in their home institutions’ GME programs. Methods We analyzed the number of Duke University UME graduates remaining at Duke for GME training over the past 5 years. We collected data to assess for changing characteristics of UME and GME, and performed descriptive analysis of trends over time to investigate the potential impact on match outcomes. Results A one-sample t-test analysis showed no statistically significant difference in the number of Duke UME graduates who stayed for GME training. For both UME and GME, no significant changes in the characteristics of either program were found. Discussion We created a process for monitoring data related to the characteristics or perceived quality of UME and GME programs and developed a shared understanding of what may impact match lists for both UME graduates and GME programs, leaving the Match somewhat less mysterious. While we understand the trend of graduates remaining at their home institutions for GME training, we are uncertain whether setting a goal for retention is reasonable, and so some mystery remains. We believe there is an invaluable opportunity for collaboration between UME and GME stakeholders to facilitate discussion about setting shared institutional goals.