The E5 protein of BPV-4 interacts with the heavy chain of MHC class I and irreversibly retains the MHC complex in the Golgi apparatus

BPV-4 E5 inhibits transcription of the bovine MHC class I heavy chain (HC) gene, increases degradation of HC and downregulates surface expression of MHC class I by retaining the complex in the Golgi apparatus (GA). Here we report that transcription inhibition can be alleviated by interferon treatment and the degradation of HC can be reversed by treatment with inhibitors of proteasomes and lysosomes. However, the inhibition of transport of MHC class I to the cell surface is irreversible. We show that E5 is capable of physically interacting with HC. Together with the inhibition of the vacuolar ATPase (due to the interaction between E5 and 16k subunit c), the interaction between E5 and HC is likely to be responsible for retention of MHC class I in the GA. C-terminus deletion mutants of E5 are incapable of either downregulating surface MHC class I or interacting with HC, establishing that the C-terminus domain of E5 is important in the inhibition of MHC class I

What supervisors say in their feedback:construction of CanMEDS roles in workplace settings

The CanMEDS framework has been widely adopted in residency education and feedback processes are guided by it. It is, however, only one of many influences on what is actually discussed in feedback. The sociohistorical culture of medicine and individual supervisors' contexts, experiences and beliefs are also influential. Our aim was to find how CanMEDS roles are constructed in feedback in a postgraduate curriculum-in-action. We applied a set of discourse analytic tools to written feedback from 591 feedback forms from 7 hospitals, including 3150 feedback comments in which 126 supervisors provided feedback to 120 residents after observing their performance in authentic settings. The role of Collaborator was constructed in two different ways: a cooperative discourse of equality with other workers and patients; and a discourse, which gave residents positions of power-delegating, asserting and 'taking a firm stance'. Efficiency-being fast and to the point emerged as an important attribute of physicians. Patients were seldom part of the discourses and, when they were, they were constructed as objects of communication and collaboration rather than partners. Although some of the discourses are in line with what might be expected, others were in striking contrast to the spirit of CanMEDS. This study's findings suggest that it takes more than a competency framework, evaluation instruments, and supervisor training to change the culture of workplaces. The impact on residents of training in such demanding, efficiency-focused clinical environments is an important topic for future research

The E5 oncoprotein of BPV-4 does not interfere with the biosynthetic pathway of non-classical MHC class I

The major histocompatibility complex (MHC) class I region in mammals contains both classical and non-classical MHC class I genes. Classical MHC class I molecules present antigenic peptides to cytotoxic T lymphocytes, whereas non-classical MHC class I molecules have a variety of functions. Both classical and non-classical MHC molecules interact with natural killer cell receptors and may under some circumstances prevent cell death by natural killer cytotoxicity. The E5 oncoprotein of BPV-4 down-regulates the expression of classical MHC class I on the cell surface and retains the complex in the Golgi apparatus. The inhibition of classical MHC class I to the cell surface results from both the impaired acidification of the Golgi, due to the interaction of E5 with subunit c of the H+ V-ATPase, and to the physical binding of E5 to the heavy chain of MHC class I. Despite the profound effect of E5 on classical MHC class I, E5 does not retain a non-classical MHC class I in the Golgi, does not inhibit its transport to the cell surface and does not bind its heavy chain. We conclude that, as is the case for HPV-16 E5, BPV-4 E5 does not down-regulate certain non-classical MHC class I, potentially providing a mechanism for the escape of the infected cell from attack by both cytotoxic T lymphocytes and NK cells

Report of the Working Group on `W Mass and QCD' (Phenomenology Workshop on LEP2 Physics, Oxford, April 1997)

The W Mass and QCD Working Group discussed a wide variety of topics relating to present and future measurements of M(W) at LEP2, including QCD backgrounds to W+W- production. Particular attention was focused on experimental issues concerning the direct reconstruction and threshold mass measurements, and on theoretical and experimental issues concerning the four jet final state. This report summarises the main conclusions.Comment: 43 pages LaTeX and 15 encapsulated postscript figures. Uses epsfig and ioplppt macros. Full Proceedings to be published in Journal of Physics

"I couldn't do this with opposition from my colleagues": A qualitative study of physicians' experiences as clinical tutors

<p>Abstract</p> <p>Background</p> <p>Clinical contact in the early curriculum and workplace learning with active tutorship are important parts of modern medical education. In a previously published study, we found that medical students' tutors experienced a heavier workload, less reasonable demands and less encouragement, than students. The aim of this interview study was to further illuminate physicians' experiences as clinical tutors.</p> <p>Methods</p> <p>Twelve tutors in the Early Professional Contact course were interviewed. In the explorative interviews, they were asked to reflect upon their experiences of working as tutors in this course. Systematic text condensation was used as the analysis method.</p> <p>Results</p> <p>In the analysis, five main themes of physicians' experiences as clinical tutors in the medical education emerged: <it>(a) Pleasure and stimulation</it>. Informants appreciated tutorship and meeting both students and fellow tutors, <it>(b) Disappointment and stagnation</it>. Occasionally, tutors were frustrated and expressed negative feelings, <it>(c) Demands and duty</it>. Informants articulated an ambition to give students their best; a desire to provide better medical education but also a duty to meet demands of the course management, <it>(d) Impact of workplace relations</it>. Tutoring was made easier when the clinic's management provided active support and colleagues accepted students at the clinic, and <it>(e) Multitasking difficulties</it>. Combining several duties with those of a tutorship was often reported as difficult.</p> <p>Conclusions</p> <p>It is important that tutors' tasks are given adequate time, support and preparation. Accordingly, it appears highly important to avoid multitasking and too heavy a workload among tutors in order to facilitate tutoring. A crucial factor is acceptance and active organizational support from the clinic's management. This implies that tutoring by workplace learning in medical education should play an integrated and accepted role in the healthcare system.</p

Constraints and affordances for UK doctors-in-training to exercise agency: A dialogical analysis

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: Data sharing is not applicable to this article as no new data were created or analyzed in this study.INTRODUCTION: The goal of medical education is to develop clinicians who have sufficient agency (capacity to act) to practise effectively in clinical workplaces and to learn from work throughout their careers. Little research has focused on experiences of organisational structures and the role of these in constraining or affording agency. The aim of this study was to identify priorities for organisational change, by identifying and analysing key moments of agency described by doctors-in-training. METHODS: This was a secondary qualitative analysis of data from a large national mixed methods research programme, which examined the work and wellbeing of UK doctors-in-training. Using a dialogical approach, we identified 56 key moments of agency within the transcripts of 22 semi-structured interviews with doctors based across the UK in their first year after graduation. By analysing action within the key moments from a sociocultural theoretical perspective, we identified tangible changes that healthcare organisations can make to afford agency. RESULTS: When talking about team working, participants gave specific descriptions of agency (or lack thereof) and used adversarial metaphors, but when talking about the wider healthcare system, their dialogue was disengaged and they appeared resigned to having no agency to shape the agenda. Organisational changes that could afford greater agency to doctors-in-training were improving induction, smoothing peaks and troughs of responsibility and providing a means of timely feedback on patient care. CONCLUSIONS: Our findings identified some organisational changes needed for doctors-in-training to practise effectively and learn from work. The findings also highlight a need to improve workplace-based team dynamics and empower trainees to influence policy. By targeting change, healthcare organisations can better support doctors-in-training, which will ultimately benefit patients.General Medical Counci

Introducing an online community into a clinical education setting: a pilot study of student and staff engagement and outcomes using blended learning

<p>Abstract</p> <p>Background</p> <p>There are growing reasons to use both information and communication functions of learning technologies as part of clinical education, but the literature offers few accounts of such implementations or evaluations of their impact. This paper details the process of implementing a blend of online and face-to-face learning and teaching in a clinical education setting and it reports on the educational impact of this innovation.</p> <p>Methods</p> <p>This study designed an online community to complement a series of on-site workshops and monitored its use over a semester. Quantitative and qualitative data recording 43 final-year medical students' and 13 clinical educators' experiences with this blended approach to learning and teaching were analysed using access, adoption and quality criteria as measures of impact.</p> <p>Results</p> <p>The introduction of the online community produced high student ratings of the quality of learning and teaching and it produced student academic results that were equivalent to those from face-to-face-only learning and teaching. Staff had mixed views about using blended learning.</p> <p>Conclusions</p> <p>Projects such as this take skilled effort and time. Strong incentives are required to encourage clinical staff and students to use a new mode of communication. A more synchronous or multi-channel communication feedback system might stimulate increased adoption. Cultural change in clinical teaching is also required before clinical education can benefit more widely from initiatives such as this.</p

The design, construction and performance of the MICE scintillating fibre trackers

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2011 ElsevierCharged-particle tracking in the international Muon Ionisation Cooling Experiment (MICE) will be performed using two solenoidal spectrometers, each instrumented with a tracking detector based on diameter scintillating fibres. The design and construction of the trackers is described along with the quality-assurance procedures, photon-detection system, readout electronics, reconstruction and simulation software and the data-acquisition system. Finally, the performance of the MICE tracker, determined using cosmic rays, is presented.This work was supported by the Science and Technology Facilities Council under grant numbers PP/E003214/1, PP/E000479/1, PP/E000509/1, PP/E000444/1, and through SLAs with STFC-supported laboratories. This work was also supportedby the Fermi National Accelerator Laboratory, which is operated by the Fermi Research Alliance, under contract No. DE-AC02-76CH03000 with the U.S. Department of Energy, and by the U.S. National Science Foundation under grants PHY-0301737,PHY-0521313, PHY-0758173 and PHY-0630052. The authors also acknowledge the support of the World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan