Improved arteriogenesis with simultaneous skeletal muscle repair in ischemic tissue by SCL plus multipotent adult progenitor cell clones from peripheral blood

Background: The CD34- murine stem cell line RM26 cloned from peripheral blood mononuclear cells has been shown to generate hematopoietic progeny in lethally irradiated animals. The peripheral blood-derived cell clones expresses a variety of mesodermal and erythroid/myeloid transcription factors suggesting a multipotent differentiation potential like the bone marrow-derived `multipotent adult progenitor cells' (MAP-C). Methods: SCL+ CD34- RM26 cells were transfused intravenously into mice suffering from chronic hind-limb ischemia, evaluating the effect of stem cells on collateral artery growth and simultaneous skeletal muscle repair. Results: RM26 cells are capable of differentiating in vitro into endothelial cells when cultured on the appropriate collagen matrix. Activation of the SCL stem cell enhancer (SCL+) is mediated through the binding to two Ets and one GATA site and cells start to express milieu- and growth condition-dependent levels of the endothelial markers CD31 (PECAM) and Flt-1 (VEGF-R1). Intravenously infused RM26 cells significantly improved the collateral blood flow (arteriogenesis) and neo-angiogenesis formation in a murine hind-limb ischemia transplant model. Although transplanted RM26 cells did not integrate into the growing collateral arteries, cells were found adjacent to local arteriogenesis, but instead integrated into the ischemic skeletal muscle exclusively in the affected limb for simultaneous tissue repair. Conclusion: These data suggest that molecularly primed hem-/mesangioblast-type adult progenitor cells can circulate in the peripheral blood improving perfusion of tissues with chronic ischemia and extending beyond the vascular compartment. Copyright (C) 2004 S. Karger AG, Basel

The role of purple pens in learning to prescribe.

BACKGROUND: Medical doctors are required to prescribe drugs safely and effectively upon qualification, a skill that many feel poorly prepared to undertake. To better prepare doctors, a whole-task approach that develops knowledge and skills, but that also considers the effect of the complex clinical workplace on prescribing, is optimal. We describe an evaluation of an experiential learning programme that allows senior medical students to gain experience with inpatient prescribing during their hospital assistantship. METHODS: A standard operating procedure (SOP) for medical student transcribing was implemented by the teaching hospitals associated with a single medical school. This included medical student prescriptions being written in purple ink. The evaluation consisted of an audit of transcribing activity and a student survey. We evaluated the usage of the initiative, adherence to the SOP and the propensity for error. RESULTS: The survey was completed by 38 out of a possible 108 fifth-year students. All respondents agreed that the programme was helpful in aiding them to learn about prescribing. A total of 247 prescriptions for 50 patients were audited: 25.1% of the prescriptions written by students required some form of amendment by the supervising doctor or pharmacist; three (1.2%) prescription errors remained unidentified; and none presented a patient safety risk. CONCLUSIONS: The purple-pen scheme affords medical students the opportunity to prescribe in the workplace, where they face authentic challenges when safely contributing to patient care. The identification of prescribing errors, feedback and the learners' own reflections helped the learners to focus on areas for improvement in prescribing prior to qualification

‘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

How well do UK assistantships equip medical students for graduate practice? Think EPAs

The goal of better medical student preparation for clinical practice drives curricular initiatives worldwide. Learning theory underpins Entrustable Professional Activities (EPAs) as a means of safe transition to independent practice. Regulators mandate senior assistantships to improve practice readiness. It is important to know whether meaningful EPAs occur in assistantships, and with what impact. Final year students at one UK medical school kept learning logs and audio-diaries for six one-week periods during a year-long assistantship. Further data were also obtained through interviewing participants when students and after three months as junior doctors. This was combined with data from new doctors from 17 other UK schools. Realist methods explored what worked for whom and why. 32 medical students and 70 junior doctors participated. All assistantship students reported engaging with EPAs but gaps in the types of EPAs undertaken exist, with level of entrustment and frequency of access depending on the context. Engagement is enhanced by integration into the team and shared understanding of what constitutes legitimate activities. Improving the shared understanding between student and supervisor of what constitutes important assistantship activity may result in an increase in the amount and/or quality of EPAs achieved

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

Improved arteriogenesis with simultaneous skeletal muscle repair in ischemic tissue by SCL plus multipotent adult progenitor cell clones from peripheral blood

Background: The CD34- murine stem cell line RM26 cloned from peripheral blood mononuclear cells has been shown to generate hematopoietic progeny in lethally irradiated animals. The peripheral blood-derived cell clones expresses a variety of mesodermal and erythroid/myeloid transcription factors suggesting a multipotent differentiation potential like the bone marrow-derived `multipotent adult progenitor cells' (MAP-C). Methods: SCL+ CD34- RM26 cells were transfused intravenously into mice suffering from chronic hind-limb ischemia, evaluating the effect of stem cells on collateral artery growth and simultaneous skeletal muscle repair. Results: RM26 cells are capable of differentiating in vitro into endothelial cells when cultured on the appropriate collagen matrix. Activation of the SCL stem cell enhancer (SCL+) is mediated through the binding to two Ets and one GATA site and cells start to express milieu- and growth condition-dependent levels of the endothelial markers CD31 (PECAM) and Flt-1 (VEGF-R1). Intravenously infused RM26 cells significantly improved the collateral blood flow (arteriogenesis) and neo-angiogenesis formation in a murine hind-limb ischemia transplant model. Although transplanted RM26 cells did not integrate into the growing collateral arteries, cells were found adjacent to local arteriogenesis, but instead integrated into the ischemic skeletal muscle exclusively in the affected limb for simultaneous tissue repair. Conclusion: These data suggest that molecularly primed hem-/mesangioblast-type adult progenitor cells can circulate in the peripheral blood improving perfusion of tissues with chronic ischemia and extending beyond the vascular compartment. Copyright (C) 2004 S. Karger AG, Basel

A bidirectional examination of expressed emotion among families of adolescents with bulimia nervosa

ObjectiveThe purpose of this paper was to examine expressed emotion (EE) measured from adolescents with bulimia nervosa (BN) toward their parents, in addition to measuring EE from parents toward patients.MethodFifty‐four adolescents and their parents who were receiving treatment for BN participated in a videotaped family interview, from which ratings of EE were made.ResultsParent and patient scores were highly correlated. Four family profiles were created (Low Patient EE/Low Parent EE; High Patient EE/High Parent EE; Low Patient EE/High Parent EE; High Patient EE/Low Parent EE) to determine whether the match between parent and patient EE was related to treatment outcome. The Low Patient EE/Low Parent EE group demonstrated the greatest reduction in purging from baseline to end‐of‐treatment; the High Patient EE/Low Parent EE group showed the smallest reduction in purging.DiscussionEE has historically been rated from relatives toward patients, but patients' own EE may also be related to treatment outcome. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:249–252)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110765/1/eat22306.pd