A total of 123 tumor-infiltrating T lymphocyte (TIL) cultures established from patients with HLA-A1, -A2, -A3, -A24, or -A31 metastatic melanoma in the Surgery Branch, National Cancer Institute, were screened for recognition of shared melanoma antigens including five melanosomal proteins (tyrosinase, MART-1/melan-A, gp100, TRP1, TRP2) as well as peptides derived from MAGE-1 and MAGE-3. Examination of the specificity of these T cells indicated that 16% of HLA-A1 TIL, 57% of HLA-A2 TIL, 7% of HLA-A3 TIL, 13% of HLA-A24 TIL, and 27% of HLA-A31 TIL recognized shared melanoma antigens restricted by major histocompatibility complex class I. Melanosomal proteins were frequently recognized by these TIL, and MART-1(27-35), gp100(154-162), gp100(209-217), and gp100(280-288) represent highly immunogenic epitopes that were recognized by a high percentage of HLA-A2 restricted melanoma reactive TIL. Recognition of gp100 by HLA-A2 restricted TIL significantly correlated with clinical response to adoptive immunotherapy with TIL in 21 HLA-A2 melanoma patients (p = 0.024). Four HLA-A1, two HLA-A2, two HLA-A3, one HLA-A24, and two HLA-A31 restricted shared antigen-specific TIL did not recognize the previously identified antigens tested in this study, and may be useful for the identification of new melanoma antigens. The observation that TILs isolated from patients with metastatic melanoma recognized melanosomal proteins in the context of predominant HLA-A alleles implies that it may be possible to develop immunotherapies for patients with melanoma expressing diverse HLA types.

No abstract

Background: Short-term experiences in global health (STEGH) are increasingly common in medical education, as they can provide learners with opportunities for service, learning, and sharing perspectives. Academic institutions need high-quality preparatory curricula and mentorship to prepare learners for potential challenges in ethics, cultural sensitivity, and personal safety; however, availability and quality of these are variable.Objective: The objective of this study is to create and evaluate an open-access, interactive massive open online course (MOOC) that prepares learners to safely and effectively participate in STEGH, permits flexible and asynchronous learning, is free of charge, and provides a certificate upon successful completion.Methods: Global health experts from 8 countries, 42 institutions, and 7 specialties collaborated to create The Practitioner’s Guide to Global Health (PGGH): the first course of this kind on the edX platform. Demographic data, pre- and posttests, and course evaluations were collected and analyzed.Results: Within its first year, PGGH enrolled 5935 learners from 163 countries. In a limited sample of 109 learners, mean posttest scores were significantly improved (p < 0.01). In the course’s second year, 213 sampled learners had significant improvement (p < 0.001).Conclusion: We created and evaluated the first interactive, asynchronous, free-of-charge global health preparation MOOC. The course has had significant interest from US-based and international learners, and posttest scores have shown significant improvement.

A major barrier to successful integration of acute care into health systems is the lack of consensus on the essential components of emergency care within resource-limited environments. The 2013 African Federation of Emergency Medicine Consensus Conference was convened to address the growing need for practical solutions to further implementation of emergency care in sub-Saharan Africa. Over 40 participants from 15 countries participated in the working group that focused on emergency care delivery at health facilities. Using the well-established approach developed in the WHO's Monitoring Emergency Obstetric Care, the workgroup identified the essential services delivered-signal functions-associated with each emergency care sentinel condition. Levels of emergency care were assigned based on the expected capacity of the facility to perform signal functions, and the necessary human, equipment and infrastructure resources identified. These consensus-based recommendations provide the foundation for objective facility capacity assessment in developing emergency health systems that can bolster strategic planning as well as facilitate monitoring and evaluation of service delivery.

Background: Morbidity and mortality due to the lack of an organized emergency medical care system are currently high in Ethiopia. Doctors, nurses, and other medical staff often have limited or no formal training on how to handle emergencies. Because of insufficient human and resource capacity needed to assess and treat acutely ill patients, many who are injured may die unnecessarily, at the site of injury, during transport, or at the hospital.

Objectives Effective real-time feedback is critical to medical education. This study tested the hypothesis that an educational intervention related to feedback would improve emergency medicine (EM) faculty and resident physician satisfaction with feedback. Methods This was a cluster-randomized, controlled study of 15 EM residency programs in 2007-2008. An educational intervention was created that combined a feedback curriculum with a card system designed to promote timely, effective feedback. Sites were randomized either to receive the intervention or to continue their current feedback method. All participants completed a web-based survey before and after the intervention period. The primary outcome was overall feedback satisfaction on a 10-point scale. Additional items addressed specific aspects of feedback. Responses were compared using a generalized estimating equations model, adjusting for confounders and baseline differences between groups. The study was designed to achieve at least 80% power to detect a one-point difference in overall satisfaction (α = 0.05). Results Response rates for pre- and post-intervention surveys were 65.9% and 47.3% (faculty), and 64.7% and 56.9% (residents). Residents in the intervention group reported a mean overall increase in feedback satisfaction scores compared to those in the control group (mean increase 0.96 points, SE ± 0.44, p = 0.03), and significantly higher satisfaction with the quality, amount, and timeliness of feedback. There were no significant differences in mean scores for overall and specific aspects of satisfaction between the faculty physician intervention and control groups. Conclusions An intervention designed to improve real-time feedback in the ED resulted in higher resident satisfaction with feedback received, but did not affect faculty satisfaction with the feedback given.

Objectives: In medical education and training, increasing numbers of institutions and learners are participating in global health experiences. Within the context of competency-based education and assessment methodologies, a standardized assessment tool may prove valuable to all of the aforementioned stakeholders. Milestones are now used as the standard for trainee assessment in graduate medical education. Thus, the development of a similar, milestone-based tool was undertaken, with learners in emergency medicine (EM) and global health in mind.Results: Milestones were developed in each of the 11 domains, with five competency levels for each domain.Specific learning resources were identified for each competency level and assessment methodologies were aligned with the milestones framework. The Global Health Milestones Tool for learners in EM is designed for continuous usage by learners and mentors across a career.Conclusions: This Global Health Milestones Tool for learners in EM may prove valuable to numerous stakeholders. The next steps include a formalized pilot program for testing the tool's validity and usability across training programs, as well as an assessment of perceived utility and applicability by collaborating colleagues working in training sites abroad.

Using cDNA expression cloning, a cDNA encoding a novel human melanoma Ag, MART-2 (melanoma Ag recognized by T cells-2), recognized by HLA-A1-restricted CD8+ T cells from tumor-infiltrating lymphocytes (TIL1362) was isolated from an autologous melanoma cell line, 1362 mel. Homologous sequences to the cDNA had been registered in the EST database. This gene encoded an uncharacterized protein expressed ubiquitously in most normal and cancer cells. A mutation (A to G transition) was found in the cDNA obtained from the1362 mel melanoma cell line in the sequences encoding the phosphate binding loop (P-loop) that resulted in loss of the ability to bind GTP. Transfection of NIH-3T3 with the mutated MART-2 did not result in the development of significant foci. By screening 36 various cancer cell lines using single-strand conformation polymorphism, a possible mutation in the P-loop of MART-2 was found in one squamous cell lung cancer cell line, EBC1. The T cell epitope for TIL1362, FLEGNEVGKTY, was identified to be encoded by the mutated sequence of the MART-2 Ag. The mutation substituted glycine in the normal peptide with glutamic acid at the third amino acid of the epitope, which is an important primary anchor amino acid for HLA-A1 peptide binding. The normal peptide, FLGGNEVGKTY, was not recognized by TIL1362, suggesting that this T cell response was specific for the autologous tumor. Although transforming activity was not detected in the NIH-3T3 assay, MART-2 with the mutation in the P-loop may be involved in the generation of melanoma through a loss of GTP binding activity.