‘What do we do, doctor?’ Transitions of identity and responsibility: a narrative analysis

Transitioning from student to doctor is notoriously challenging. Newly qualified doctors feel required to make decisions before owning their new identity. It is essential to understand how responsibility relates to identity formation to improve transitions for doctors and patients. This multiphase ethnographic study explores realities of transition through anticipatory, lived and reflective stages. We utilised Labov’s narrative framework (Labov in J Narrat Life Hist 7(1–4):395–415, 1997) to conduct in-depth analysis of complex relationships between changes in responsibility and development of professional identity. Our objective was to understand how these concepts interact. Newly qualified doctors acclimatise to their role requirements through participatory experience, perceived as a series of challenges, told as stories of adventure or quest. Rules of interaction within clinical teams were complex, context dependent and rarely explicit. Students, newly qualified and supervising doctors felt tensions around whether responsibility should be grasped or conferred. Perceived clinical necessity was a common determinant of responsibility rather than planned learning. Identity formation was chronologically mismatched to accepting responsibility. We provide a rich illumination of the complex relationship between responsibility and identity pre, during, and post-transition to qualified doctor: the two are inherently intertwined, each generating the other through successful actions in practice. This suggests successful transition requires a supported period of identity reconciliation during which responsibility may feel burdensome. During this, there is a fine line between too much and too little responsibility: seemingly innocuous assumptions can have a significant impact. More effort is needed to facilitate behaviours that delegate authority to the transitioning learner whilst maintaining true oversight

Qualitative research using realist evaluation to explain preparedness for doctors' memorable 'firsts'

CONTEXT: Doctors must be competent from their first day of practice if patients are to be safe. Medical students and new doctors are acutely aware of this, but describe being variably prepared. OBJECTIVES: This study aimed to identify causal chains of the contextual factors and mechanisms that lead to a trainee being capable (or not) of completing tasks for the first time. METHODS: We studied three stages of transition: anticipation; lived experience, and post hoc reflection. In the anticipation stage, medical students kept logbooks and audio diaries and were interviewed. Consenting participants were followed into their first jobs as doctors, during which they made audio diaries to capture the lived experiences of transition. Reflection was captured using interviews and focus groups with other postgraduate trainee doctors. All materials were transcribed and references to first experiences ('firsts') were analysed through the lens of realist evaluation. RESULTS: A total of 32 medical students participated. Eleven participants were followed through the transition to the role of doctor. In addition, 70 postgraduate trainee doctors from three local hospitals who were graduates of 17 UK medical schools participated in 10 focus groups. We identified three categories of firsts (outcomes): firsts that were anticipated and deliberately prepared for in medical school; firsts for which total prior preparedness is not possible as a result of the step change in responsibility between the student and doctor identities, and firsts that represented experiences of failure. Helpful interventions in preparation (context) were opportunities for rehearsal and being given responsibility as a student in the clinical team. Building self-efficacy for tasks was an important mechanism. During transition, the key contextual factor was the provision of appropriate support from colleagues. CONCLUSIONS: Transition is a step change in responsibility for which total preparedness is not achievable. This transition is experienced as a rite of passage when the newly qualified doctor first makes decisions alone. This study extends the existing literature by explaining the mechanisms involved in preparedness for firsts

Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.

Transcriptional dysregulation is associated with haematological malignancy. Although mutations of the key haematopoietic transcription factor PU.1 are rare in human acute myeloid leukaemia (AML), they are common in murine models of radiation-induced AML, and PU.1 downregulation and/or dysfunction has been described in human AML patients carrying the fusion oncogenes RUNX1-ETO and PML-RARA. To study the transcriptional programmes associated with compromised PU.1 activity, we adapted a Pu.1-mutated murine AML cell line with an inducible wild-type PU.1. PU.1 induction caused transition from leukaemia phenotype to monocytic differentiation. Global binding maps for PU.1, CEBPA and the histone mark H3K27Ac with and without PU.1 induction showed that mutant PU.1 retains DNA-binding ability, but the induction of wild-type protein dramatically increases both the number and the height of PU.1-binding peaks. Correlating chromatin immunoprecipitation (ChIP) Seq with gene expression data, we found that PU.1 recruitment coupled with increased histone acetylation induces gene expression and activates a monocyte/macrophage transcriptional programme. PU.1 induction also caused the reorganisation of a subgroup of CEBPA binding peaks. Finally, we show that the PU.1 target gene set defined in our model allows the stratification of primary human AML samples, shedding light on both known and novel AML subtypes that may be driven by PU.1 dysfunction.X18.1.1 cells were kindly donated by Dr Wendy Cook (LaTrobe University, Melbourne). MSCV-puro-PuER plasmid was kindly donated by Dr Peter Laslo (University of Leeds). ChIP sequencing was performed at the Genomics Core Facility, CRUK Cambridge Institute. Research in the Göttgens laboratory is supported by Leukaemia and Lymphoma Research, the MRC, BBSRC, CRUK, Leukemia and Lymphoma Society, NIHR Cambridge Biomedical Research Centre and core infrastructure support by the Wellcome Trust to the Wellcome Trust and MRC Cambridge Stem Cell Institute and CIMR. JIS is supported by CRUK and the Raymond and Beverly Sackler Foundation.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/leu.2015.17

Development and face validation of strategies for improving consultation skills

While formative workplace based assessment can improve learners' skills, it often does not because the procedures used do not facilitate feedback which is sufficiently specific to scaffold improvement. Provision of pre-formulated strategies to address predicted learning needs has potential to improve the quality and automate the provision of written feedback. To systematically develop, validate and maximise the utility of a comprehensive list of strategies for improvement of consultation skills through a process involving both medical students and their clinical primary and secondary care tutors. Modified Delphi study with tutors, modified nominal group study with students with moderation of outputs by consensus round table discussion by the authors. 35 hospital and 21 GP tutors participated in the Delphi study and contributed 153 new or modified strategies. After review of these and the 205 original strategies, 265 strategies entered the nominal group study to which 46 year four and five students contributed, resulting in the final list of 249 validated strategies. We have developed a valid and comprehensive set of strategies which are considered useful by medical students. This list can be immediately applied by any school which uses the Calgary Cambridge Framework to inform the content of formative feedback on consultation skills. We consider that the list could also be mapped to alternative skills frameworks and so be utilised by schools which do not use the Calgary Cambridge Framework

Application of unsupervised chemometric analysis and self-organising feature map (SOFM) for the classification of lighter fuels

A variety of lighter fuel samples from different manufacturers (both unevaporated and evaporated) were analysed using conventional gas chromatography-mass spectrometry (GC-MS) analysis. In total 51 characteristic peaks were selected as variables and subjected to data pre-processing prior to subsequent analysis using unsupervised chemometric analysis (PCA and HCA) and a SOFM artificial neural network. The results obtained revealed that SOFM acted as a powerful means of evaluating and linking degraded ignitable liquid sample data to their parent unevaporated liquids

Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML

Abstract: Leukaemogenic mutations commonly disrupt cellular differentiation and/or enhance proliferation, thus perturbing the regulatory programs that control self-renewal and differentiation of stem and progenitor cells. Translocations involving the Mll1 (Kmt2a) gene generate powerful oncogenic fusion proteins, predominantly affecting infant and paediatric AML and ALL patients. The early stages of leukaemogenic transformation are typically inaccessible from human patients and conventional mouse models. Here, we take advantage of cells conditionally blocked at the multipotent haematopoietic progenitor stage to develop a MLL-r model capturing early cellular and molecular consequences of MLL-ENL expression based on a clear clonal relationship between parental and leukaemic cells. Through a combination of scRNA-seq, ATAC-seq and genome-scale CRISPR-Cas9 screening, we identify pathways and genes likely to drive the early phases of leukaemogenesis. Finally, we demonstrate the broad utility of using matched parental and transformed cells for small molecule inhibitor studies by validating both previously known and other potential therapeutic targets

Ontogenic changes in hematopoietic hierarchy determine pediatric specificity and disease phenotype in fusion oncogene-driven myeloid leukemia

Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2–GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2–GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2–GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. SIGNIFICANCE: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state

HOX-mediated LMO2 expression in embryonic mesoderm is recapitulated in acute leukaemias

The Lim Domain Only 2 (LMO2) leukaemia oncogene encodes an LIM domain transcriptional cofactor required for early haematopoiesis. During embryogenesis, LMO2 is also expressed in developing tail and limb buds, an expression pattern we now show to be recapitulated in transgenic mice by an enhancer in LMO2 intron 4. Limb bud expression depended on a cluster of HOX binding sites, while posterior tail expression required the HOX sites and two E-boxes. Given the importance of both LMO2 and HOX genes in acute leukaemias, we further demonstrated that the regulatory hierarchy of HOX control of LMO2 is activated in leukaemia mouse models as well as in patient samples. Moreover, Lmo2 knock-down impaired the growth of leukaemic cells, and high LMO2 expression at diagnosis correlated with poor survival in cytogenetically normal AML patients. Taken together, these results establish a regulatory hierarchy of HOX control of LMO2 in normal development, which can be resurrected during leukaemia development. Redeployment of embryonic regulatory hierarchies in an aberrant context is likely to be relevant in human pathologies beyond the specific example of ectopic activation of LMO2