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Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment of patients with FDA-approved inhibitors of BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression of BRAFV600E in the lung epithelium initiates growth of benign lung tumors that, without additional genetic alterations, rarely progress to malignant lung adenocarcinoma. To identify genes that cooperate with BRAFV600E for malignant progression, we used Sleeping Beauty-mediated transposon mutagenesis, which dramatically accelerated the emergence of lethal lung cancers. Among the genes identified was Rbms3, which encodes an RNA-binding protein previously implicated as a putative tumor suppressor. Silencing of RBMS3 via CRISPR/Cas9 gene editing promoted growth of BRAFV600E lung organoids and promoted development of malignant lung cancers with a distinct micropapillary architecture in BRAFV600E and EGFRL858R GEM models. BRAFV600E/RBMS3Null lung tumors displayed elevated expression of Ctnnb1, Ccnd1, Axin2, Lgr5, and c-Myc mRNAs, suggesting that RBMS3 silencing elevates signaling through the WNT/β-catenin signaling axis. Although RBMS3 silencing rendered BRAFV600E-driven lung tumors resistant to the effects of dabrafenib plus trametinib, the tumors were sensitive to inhibition of porcupine, an acyltransferase of WNT ligands necessary for their secretion. Analysis of The Cancer Genome Atlas patient samples revealed that chromosome 3p24, which encompasses RBMS3, is frequently lost in non-small cell lung cancer and correlates with poor prognosis. Collectively, these data reveal the role of RBMS3 as a lung cancer suppressor and suggest that RBMS3 silencing may contribute to malignant NSCLC progression.SignificanceLoss of RBMS3 cooperates with BRAFV600E to induce lung tumorigenesis, providing a deeper understanding of the molecular mechanisms underlying mutant BRAF-driven lung cancer and potential strategies to more effectively target this disease.

Distributed medical education (DME) is becoming increasingly prevalent. Much of the published literature on DME has focused on the experiences of learners in distributed programs; however, our empirical work leads us to believe that DME changes the context significantly, not only for learners, but also for other important members of the educational community including audiovisual professionals, administrative professionals and faculty teachers. Based on a three-year ethnographic study, we provide a detailed account of how alliances between various workers involved in DME develop to produce and deliver an undergraduate medical curriculum across geographically separate campuses. We explore the question "What is the work involved in the delivery of a DME program?" and cast a critical gaze on the essential but invisible, and therefore potentially unrecognized and underappreciated, contributions of AV professionals, administrative professionals, and faculty teachers. Our goal is to make visible the complexity of DME, including the essential contributions of these workers. The study was theoretically framed in sociomateriality and conceptually framed in Star and Strauss' notion of articulation work.

Assessors' scores in performance assessments are known to be highly variable. Attempted improvements through training or rating format have achieved minimal gains. The mechanisms that contribute to variability in assessors' scoring remain unclear. This study investigated these mechanisms. We used a qualitative approach to study assessors' judgements whilst they observed common simulated videoed performances of junior doctors obtaining clinical histories. Assessors commented concurrently and retrospectively on performances, provided scores and follow-up interviews. Data were analysed using principles of grounded theory. We developed three themes that help to explain how variability arises: "Differential Salience"--assessors paid attention to (or valued) different aspects of the performances to different degrees; "Criterion Uncertainty"--assessors' criteria were differently constructed, uncertain, and were influenced by recent exemplars; "Information Integration"--assessors described the valence of their comments in their own unique narrative terms, usually forming global impressions. Our results (whilst not precluding the operation of established biases) describe mechanisms by which assessors' judgements become meaningfully-different or unique. Our results have theoretical relevance to understanding the formative educational messages that performance assessments provide. They give insight relevant to assessor training, assessors' ability to be observationally "objective" and to the educational value of narrative comments (in contrast to numerical ratings).

Although education about culture, race and ethnicity has increasingly been viewed as an important addition to the medical undergraduate curriculum, internationally the evidence of its effectiveness is mixed. Research to date fails to show why. We chose to explore how contrasting approaches to learning about cultural diversity impacted on medical students. The views of second year students towards teaching about cultural diversity at two UK medical schools, with differently structured curricula, were explored using a series of focus groups (7). The findings, using a methodology based on a combination of grounded theory and thematic analysis identified two potentially competing views espoused by the students at both sites. First, they claimed that although cultural diversity was important, their medical schools marginalised and failed to adequately support effective teaching. Second, in contrast, they claimed that the medical school was an "inappropriate" setting for successful teaching about cultural diversity. Students did not consider the subject matter to be of central relevance to biomedicine. They felt it should be learnt experientially in the workplace and socially among peers. These narratives represent two potentially conflicting standpoints, which might be understood through the sociological concept of "habitus", where students conform to the institution's dominant values in order to succeed. The tensions identified in this study cannot be ignored if effective learning about race, ethnicity and culture is to be achieved. Early introduction to understanding the delivery of health care to diverse populations is needed. This should be accompanied by more open collaborative debate between tutors and students on the issues raised. (Contains 1 table.)

Evidence supporting Problem-based learning (PBL) fostering students' self-directed learning (SDL) in hybrid PBL curricula is inconsistent. To explore the influence of PBL in a hybrid curriculum on students' SDL, the authors investigated the following: (1) students' self-assessed SDL ability, (2) students' perceptions of the influence of curricular components on SDL, and (3) the relationships between curricular elements and SDL. The research questions were explored both quantitatively and qualitatively. All year 1 (n = 93) and year 2 (n = 93) students in 2004 were invited to participate. Participants completed a 53-item questionnaire addressing (a) self-assessment of their SDL ability, and (b) perceived influence of individual curriculum elements on individual study and SDL. Student and faculty focus group interviews (FGIs) were conducted. Students rated their SDL skills highly, particularly identifying knowledge deficits, learning skills and strategies, and managing study time. Students thought lectures helped in selecting study topics and learning for the tutorial case. Other components including tutors, unit/case objectives, tests, and tutorial discussions, were seen as influencing what to study and the learning process. No significant difference was observed in the responses between year 1 and 2 students. Among the six curriculum components, tutorial discussion and objectives were weakly correlated with with SDL ability. Findings from students and faculty focus group supported the perceived positive influence of the curriculum on SDL. This study found that students' perceived SDL ability was positively influenced by several components of the hybrid PBL curriculum. However, further investigations are needed for a clearer understanding of the specific effects of the hybrid PBL curriculum on students' SDL.

Problem statement and background: Feedback is essential to learning and practice improvement, yet challenging both to provide and receive. The purpose of this paper was to explore reflective processes which physicians described as they considered their assessment feedback and the perceived utility of that reflective process. Methods: This is a qualitative study using principles of grounded theory. We conducted interviews with 28 family physicians participating in a multi-source feedback program and receiving scores across the spectrum from high to low. Results: Feedback, especially negative feedback, evoked reflective responses. Reflection seemed to be the process through which feedback was or was not assimilated and appeared integral to decisions to accept and use the feedback. Facilitated reflection upon feedback was viewed as a positive influence for assimilation and acceptance. Conclusions: Receiving feedback inconsistent with self-perceptions stimulated physicians' reflective processes. The process of reflection appeared instrumental to feedback acceptance and use, suggesting that reflection may be an important educational focus in the formative assessment and feedback process.

Introduction: Receiving negative performance feedback can elicit negative emotional reactions which can interfere with feedback acceptance and use. This study investigated emotional responses of family physicians' participating in a multi-source feedback (MSF) program, sources of these emotions, and their influence upon feedback acceptance and use. Methods: The authors interviewed 28 volunteer family physician participants in a pilot study of MSF, purposefully recruited to represent the range of scores. The study was conducted in 2003-2004 at Dalhousie University. Results: Participants' emotional reactions to feedback appeared to be elicited in response to an internal comparison of their feedback with self-perceptions of performance. Those agreeing with their feedback; i.e., perceiving it as generally consistent with or higher than self-perceptions responded positively, while those disagreeing with their feedback; i.e., seeing it as generally inconsistent with or lower than self-perceptions, generally responded with distress. For the latter group, these feelings were often strong and long-lasting. Some eventually accepted their feedback and used it for change following a long period of reflection. Others did not and described an equally long reflective period but one which focused on and questioned MSF procedures rather than addressed feedback use. Participants suggested providing facilitated reflection on feedback to enhance assimilation of troubling emotions and interpretation and use of feedback. Conclusions: Negative feedback can evoke negative feelings and interfere with its acceptance. To overcome this, helpful interventions may include raising awareness of the influence of emotions, assisting recipients to focus their feedback on performance tasks, and providing facilitated reflection on feedback.

In developing curricula for undergraduate and graduate medical education, educators have become increasingly aware of an interweaving of the formal, informal, and hidden curricula and their influences on the outcomes of teaching and learning. But, to date, there is little in the literature about the hidden curriculum of medical practice, which takes place after graduation and certification. This article initiates that discussion with influences of the hidden curriculum on the actions physicians take or do not take in caring for patients. Hafferty's framework of institutional policies, evaluation activities, resource-allocation decisions, and institutional slang, along with our knowledge of health services research and the continuing medical education (CME) research literature, suggests that there is a hidden and powerful curriculum that affects physician performance. Determining whether the hidden curriculum conflicts with the messages that we are delivering through formal CME (courses, clinical practice guidelines, peer review journals) may contribute to improving our impact on physician performance.

Despite the existence of many approaches to understanding learning and change and attempts to incorporate these into continuing education research and practice, the search continues for a comprehensive understanding of how learning is engendered in professional practice and the processes by which learning and change occur. This article considers four broad questions in relation to the practice of continuing education: (1) What can be expected of theory? (2) How does theory relate to the educational practice of those in continuing education and the goals of continuing medical education? (3) How have practice and theory mutually informed our current understandings? (4) How can theory serve the field more effectively in the future? Broad orientations to understanding learning provide a framework for examining the contributions of theory and practice. The orientations include behaviorist, cognitivist, social learning, humanist, and constructivist: for each, an example is presented. Newer understandings also are introduced. The article concludes by considering reasons as to why theory appears not to have served us better and by offering ways in which those in continuing education can ensure greater usefulness of theory while contributing to its continued development.

Physicians in three communities (n=31) participated in four problem-based learning modules via videoconferencing. Posttest scores were 20% higher and learners reported an average of nine practice changes. Facilitators and observers reported a number of technical difficulties. Facilitators found videoconferencing slightly more difficult than face-to-face facilitation. (SK)

Cognitive teaching and learning principles include activation of prior knowledge, elaboration of new knowledge, contextual learning, knowledge transfer, and knowledge organization. Social-environmental principles include dynamic learner-environment interaction, observational learning, environmental incentives and rewards, goal setting, self-monitoring, self-efficacy, and situated learning. Both sets should be applied in designing continuing medical education. (Contains 24 references.) (SK)

Describes experiences at Western Illinois University where faculty members in the humanities have developed a successful approach to assessing general education learning in the humanities. The approach (CATS, or classroom assessment techniques) stresses faculty participation and collaboration. A table lists assessment techniques for nine humanities disciplines. An excerpt from the manual for faculty is appended. (DB)

Reports on the development and use at Western Illinois University of a survey to examine students' (n=787) knowledge of and attitudes toward the humanities. Students generally did not understand the reasoning behind the humanities requirement, could not explain differences between the humanities and social studies, and saw little relevance of the humanities to their lives. (DB)

Compared four standard-setting procedures for an objective structure clinical examination (OSCE) in medical education. Applied Angoff, borderline, relative, and holistic procedures to the data used to establish a cutoff score for a pass/fail decision. The Angoff and borderline procedures gave similar results; however, the relative and holistic methods gave widely divergent results. (Author/DB)

In literature on problem-based learning (PBL), it is often difficult to determine whether the educational approach being described is actually PBL. Provides planners and assessors of PBL curricula with a framework for analysis. Educational activities can be categorized as PBL according to three core principles and four criteria concerning their effect on student learning. Contains 38 references. (Author/PVD)

Reviews advantages and disadvantages of questionnaires for continuing-education needs-assessment. Outlines considerations for effective questionnaire design--understanding the learning context and how learning and change occur in medical practice--as well as practical strategies for instrument development. (SK)

Four years of experience with an objective structured clinical examination (OSCE) following an eight-week surgical clerkship (n=356 students) are reported, including data on mean student performance across years, reliability coefficients, and generalizability. Implications for improvement and development of OSCE are discussed. (Author/MSE)

Social Cognitive Theory describes an ongoing dynamic interaction of individual, environment, and behavior as well as five basic capabilities of individuals: symbolizing, forethought, vicarious, self-regulatory, and self-reflective. These capabilities are considered as they affect human thought and action. Implications of these theories for practice and research in continuing education are explored. (Author)

Accurate assessment of tissues for hematolymphoid neoplasms requires an integrated multiparameter approach. Although morphologic examination by light microscopy remains the mainstay of initial assessment for hematolymphoid neoplasms, immunophenotypic analysis by immunohistochemistry and/or flow cytometry is essential to determine the pattern of differentiation and to detect minimal disease when morphology is inconclusive. In some cases, immunophenotypic analysis provides additional information for targeted immunotherapy and prognostication. Genotypic studies, including cytogenetics, fluorescence in situ hybridization, DNA microarray, polymerase chain reaction, and/or next-generation sequencing, are also imperative for subclassification of the genetically defined disease entities in the current World Health Organization classification of hematolymphoid neoplasms. Moreover, genotypic studies can establish clonality, stratify patients to determine appropriate treatment, and monitor patients for treatment response. doi: 10.5858/arpa.2016-0260-SA), In the last several decades, technologic advances have dramatically increased our understanding of the biology of normal hematopoiesis and the pathogenesis of hematolymphoid neoplasms. In parallel, a variety of powerful [...]