Protocol for a realist review of workplace learning in postgraduate medical education and training

Postgraduate medical education and training (PGMET) is a complex social process which happens predominantly during the delivery of patient care. The clinical learning environment (CLE), the context for PGMET, shapes the development of the doctors who learn and work within it, ultimately impacting the quality and safety of patient care. Clinical workplaces are complex, dynamic systems in which learning emerges from non-linear interactions within a network of related factors and activities. Those tasked with the design and delivery of postgraduate medical education and training need to understand the relationship between the processes of medical workplace learning and these contextual elements in order to optimise conditions for learning. We propose to conduct a realist synthesis of the literature to address the overarching questions; how, why and in what circumstances do doctors learn in clinical environments? This review is part of a funded projected with the overall aim of producing guidelines and recommendations for the design of high quality clinical learning environments for postgraduate medical education and training

Ubiquitylation activates a peptidase that promotes cleavage and destabilization of its activating E3 ligases and diverse growth regulatory proteins to limit cell proliferation in Arabidopsis

The characteristic shapes and sizes of organs are established by cell proliferation patterns and final cell sizes, but the underlying molecular mechanisms coordinating these are poorly understood. Here we characterize a ubiquitin-activated peptidase called DA1 that limits the duration of cell proliferation during organ growth in Arabidopsis thaliana. The peptidase is activated by two RING E3 ligases, Big Brother (BB) and DA2, which are subsequently cleaved by the activated peptidase and destabilized. In the case of BB, cleavage leads to destabilization by the RING E3 ligase PROTEOLYSIS 1 (PRT1) of the N-end rule pathway. DA1 peptidase activity also cleaves the deubiquitylase UBP15, which promotes cell proliferation, and the transcription factors TEOSINTE BRANCED 1/ CYCLOIDEA/PCF 15 (TCP15) and TCP22, which promote cell proliferation and repress endoreduplication. We propose that DA1 peptidase activity regulates the duration of cell proliferation and the transition to endoreduplication and differentiation during organ formation in plants by coordinating the destabilization of regulatory proteins

Energy-Flow – A New Perspective on James MacGregor Burns’ Transforming Leadership: A New Pursuit of Happiness

This theoretical dissertation documents a personal transforming leadership experience; during which, I explored my Leadership as Energy-Flow model by having a virtual dialogue with the polymathic works of theorists and thinkers to corroborate and refine it. The model consists of a theory and a conceptual scheme. The energy-flow theory, based on the laws of physics and Chinese philosophy and cosmological science, fashions the energy-flow conceptual scheme. Using the conceptual scheme, I delve into the Premise of the Dialogue, “In what ways and to what extent would using the energy-flow frame of reference describe and stimulate new meanings in Transforming Leadership: A New Pursuit of Happiness?” I venture forth in this exploration, sparked by Bertrand Russell’s (1938) and James MacGregor Burns’ (1979) on leadership power, to discover how one might use energy-flow abstractions to represent leadership phenomena. Energy-flow abstractions are images of events captured in thought, within which one unfolds and enfolds new meanings and deepens understanding of transforming leadership. The dialogue with six different traditions includes the works of: Alfred North Whitehead on philosophy and science, Ilya Prigogine on physics, Abraham H. Maslow on human potentials, need hierarchy, and management, Mihaly Csikszentmihalyi on psychological energy-flow, Richard Gerber on physiological energy-flow and vibrational medicine, and Ralph H.G. Siu on quantum and the Tao of science of leadership. The dialogue then continues into the work of Burns (2003). Many of my epiphanies, using the energy-flow conceptual scheme to fathom transforming leadership theory, induce some propitious ideas for further exploration in viewing leadership as energy-flow and using energy-flow as a basis for deciphering human affairs. The electronic version of this dissertation is available at the OhioLINK ETD Center, https://etd.ohiolink.edu

Energy-Flow – A New Perspective on James MacGregor Burns’ Transforming Leadership: A New Pursuit of Happiness

This theoretical dissertation documents a personal transforming leadership experience; during which, I explored my Leadership as Energy-Flow model by having a virtual dialogue with the polymathic works of theorists and thinkers to corroborate and refine it. The model consists of a theory and a conceptual scheme. The energy-flow theory, based on the laws of physics and Chinese philosophy and cosmological science, fashions the energy-flow conceptual scheme. Using the conceptual scheme, I delve into the Premise of the Dialogue, “In what ways and to what extent would using the energy-flow frame of reference describe and stimulate new meanings in Transforming Leadership: A New Pursuit of Happiness?” I venture forth in this exploration, sparked by Bertrand Russell’s (1938) and James MacGregor Burns’ (1979) on leadership power, to discover how one might use energy-flow abstractions to represent leadership phenomena. Energy-flow abstractions are images of events captured in thought, within which one unfolds and enfolds new meanings and deepens understanding of transforming leadership. The dialogue with six different traditions includes the works of: Alfred North Whitehead on philosophy and science, Ilya Prigogine on physics, Abraham H. Maslow on human potentials, need hierarchy, and management, Mihaly Csikszentmihalyi on psychological energy-flow, Richard Gerber on physiological energy-flow and vibrational medicine, and Ralph H.G. Siu on quantum and the Tao of science of leadership. The dialogue then continues into the work of Burns (2003). Many of my epiphanies, using the energy-flow conceptual scheme to fathom transforming leadership theory, induce some propitious ideas for further exploration in viewing leadership as energy-flow and using energy-flow as a basis for deciphering human affairs. The electronic version of this dissertation is available at the OhioLINK ETD Center, https://etd.ohiolink.edu

Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics.

We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Standardised framework for quantitative analysisof fibrillation dynamics

The analysis of complex mechanisms underlying ventricular fibrillation (VF) and atrial fibrillation (AF) requires sophisticatedtools for studying spatio-temporal action potential (AP) propagation dynamics. However, fibrillation analysis tools are oftencustom-made or proprietary, and vary between research groups. With no optimal standardised framework for analysis, resultsfrom different studies have led to disparate findings. Given the technical gap, here we present a comprehensive framework andset of principles for quantifying properties of wavefront dynamics in phase-processed data recorded during myocardial fibrillationwith potentiometric dyes. Phase transformation of the fibrillatory data is particularly useful for identifying self-perpetuating spiralwaves or rotational drivers (RDs) rotating around a phase singularity (PS). RDs have been implicated in sustaining fibrillation,and thus accurate localisation and quantification of RDs is crucial for understanding specific fibrillatory mechanisms. In thiswork, we assess how variation of analysis parameters and thresholds in the tracking of PSs and quantification of RDs couldresult in different interpretations of the underlying fibrillation mechanism. These techniques have been described and appliedto experimental AF and VF data, and AF simulations, and examples are provided from each of these data sets to demonstratethe range of fibrillatory behaviours and adaptability of these tools. The presented methodologies are available as an opensource software and offer an off-the-shelf research toolkit for quantifying and analysing fibrillatory mechanisms

Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.

BACKGROUND.: There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. METHODS.: In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. RESULTS.: Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. CONCLUSIONS.: There is evidence for an association between H. influenzae colonization density and H. influenzae-confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings