Gaps in patient reported outcome measures in randomised clinical trials of cardiac catheter ablation: a systematic review

Aims: To systematically evaluate randomised clinical trials of cardiac catheter ablation and to assess the prevalence, characteristics and reporting standards of clinically relevant patient reported outcome measures (PROMs). / Methods and Results: Electronic database searches of Medline, Embase, CENTRAL and the WHO Trial Registry were conducted in March 2019. The study protocol was registered on PROSPERO (CRD42019133086). Of 7,125 records identified, 237 RCTs were included for analysis, representing 35,427 patients with a mean age of 59 years. Only 43 RCTs (18%) reported PROMs of which 27 included a generic PROM that measured health-related quality of life (HRQL) necessary to conduct comparative effectiveness research. There was notable under-representation of certain patient groups - only 31% were women and only 8% were of non-Caucasian ethnicity, in trials which reported such data. The reporting standard of PROMs was highly variable with 8-62% adherence against CONSORT PRO specific items. / Conclusion: PROMs play a crucial role in determining the clinical and cost effectiveness of treatments which primarily offer symptomatic improvement, such as cardiac catheter ablation (CCA). Their underuse significantly limits evaluation of the comparative effectiveness of treatments. Using CCA as an exemplar, there are additional issues of infrequent assessment, poor reporting and under-representation of many population groups. Greater use of PROMs, and specifically validated HRQL questionnaires, is paramount in giving patients a voice in studies, generating more meaningful comparisons between treatments and driving better patient-centred clinical and policy-level decision making

Transcriptomic Profiling Reveals Discrete Poststroke Dementia Neuronal and Gliovascular Signatures

\ua9 2022, The Author(s). Poststroke dementia (PSD) is associated with pathology in frontal brain regions, in particular dorsolateral prefrontal cortex (DLPFC) neurons and white matter, remote from the infarct. We hypothesised that PSD results from progressive DLPFC neuronal damage, associated with frontal white matter gliovascular unit (GVU) alterations. We investigated the transcriptomic profile of the neurons and white matter GVU cells previously implicated in pathology. Laser-capture microdissected neurons, astrocytes and endothelial cells were obtained from the Cognitive Function After Stroke cohort of control, PSD and poststroke non-dementia (PSND) human subjects. Gene expression was assessed using microarrays and pathway analysis to compare changes in PSD with controls and PSND. Neuronal findings were validated using NanoString technology and compared with those in the bilateral common carotid artery stenosis (BCAS) mouse model. Comparing changes in PSD compared to controls with changes in PSND compared to controls identified transcriptomic changes associated specifically with dementia. DLPFC neurons showed defects in energy production (tricarboxylic acid (TCA) cycle, adenosine triphosphate (ATP) binding and mitochondria), signalling and communication (MAPK signalling, Toll-like receptor signalling, endocytosis). Similar changes were identified in neurons isolated from BCAS mice. Neuronal findings accompanied by altered astrocyte communication and endothelium immune changes in the frontal white matter, suggesting GVU dysfunction. We propose a pathogenic model in PSD whereby neuronal changes are associated with frontal white matter GVU dysfunction leading to astrocyte failure in supporting neuronal circuits resulting in delayed cognitive decline associated with PSD. Therefore, targeting these processes could potentially ameliorate the dementia seen in PSD

The role of team compassion in mitigating the impact of hierarchical bullying

Copyright © The Author(s), 2023. Hierarchical bullying in public healthcare organizations is an entrenched negative behaviour that results in a range of adverse outcomes for staff, including diminished wellbeing. This study integrates social exchange and conservation of resources theories as a lens for formulating hypotheses and employs multilevel statistical modelling to examine whether team-level compassion moderates the impact of hierarchical bullying on wellbeing. Using multilevel statistical modelling, the study analysed cross-sectional data from 632 healthcare workers nested within 48 teams in a single public health district in Australia. The findings indicate that work teams with higher levels of team compassion can mitigate the negative effects of hierarchical bullying on employee wellbeing. The results imply that investing in developing compassion within teams is an effective strategy for mitigating some harmful effects of hierarchical bullying on employee outcomes

Emotions in business-to-business service relationships

Emotion in business-to-business service relationships regarding cargo services is explored. The service relationship is characterised by mutual trust and cooperation. Contact is mainly via telephone or e-mail with some face-to-face interactions and participants providing a complex, multi-skilled seamless service. Experience rather than training plays a vital role with long-term service relationships built up and maintained. Emotional sensitivity is acquired partly by experience and a repeat customer base but mainly through a genuine desire to help and get to know others. In contrast to the view of emotional labour bringing managerial control or adverse affects to service staff, the emotion engendered by this work is authentic expression bringing personal satisfaction

Gene transfer into hepatocytes using asialoglycoprotein receptor mediated endocytosis of DNA complexed with an artificial tetra-antennary galactose ligand

We have constructed an artificial ligand for the hepatocyte-specific asialoglycoprotein receptor for the purpose of generating a synthetic delivery system for DNA. This ligand has a tetra-antennary structure, containing four terminal galactose residues on a branched carrier peptide. The carbohydrate residues of this glycopeptide were introduced by reductive coupling of lactose to the alpha- and epsilon-amino groups of the two N-terminal lysines on the carrier peptide. The C-terminus of the peptide, containing a cysteine separated from the branched N-terminus by a 10 amino acid spacer sequence, was used for conjugation to 3-(2-pyridyldithio)propionate-modified polylysine via disulfide bond formation. Complexes containing plasmid DNA bound to these galactose-polylysine conjugates have been used for asialoglycoprotein receptor-mediated transfer of a luciferase gene into human (HepG2) and murine (BNL CL.2) hepatocyte cell lines. Gene transfer was strongly promoted when amphipathic peptides with pH-controlled membrane-disruption activity, derived from the N-terminal sequence of influenza virus hemagglutinin HA-2, were also present in these DNA complexes. Thus, we have essentially borrowed the small functional domains of two large proteins, asialoglycoprotein and hemagglutinin, and assembled them into a supramolecular complex to generate an efficient gene-transfer system

Quantifying MRI frequency shifts due to structures with anisotropic magnetic susceptibility using pyrolytic graphite sheet

Magnetic susceptibility is an important source of contrast in magnetic resonance imaging (MRI), with spatial variations in the susceptibility of tissue affecting both the magnitude and phase of the measured signals. This contrast has generally been interpreted by assuming that tissues have isotropic magnetic susceptibility, but recent work has shown that the anisotropic magnetic susceptibility of ordered biological tissues, such as myelinated nerves and cardiac muscle fibers, gives rise to unexpected image contrast. This behavior occurs because the pattern of field variation generated by microstructural elements formed from material of anisotropic susceptibility can be very different from that predicted by modelling the effects in terms of isotropic susceptibility. In MR images of tissue, such elements are manifested at a sub-voxel length-scale, so the patterns of field variation that they generate cannot be directly visualized. Here, we used pyrolytic graphite sheet which has a large magnetic susceptibility anisotropy to form structures of known geometry with sizes large enough that the pattern of field variation could be mapped directly using MRI. This allowed direct validation of theoretical expressions describing the pattern of field variation from anisotropic structures with biologically relevant shapes (slabs, spherical shells and cylindrical shells)

Designing Chatbots for Crises: A Case Study Contrasting Potential and Reality

Chatbots are becoming ubiquitous technologies, and their popularity and adoption are rapidly spreading. The potential of chatbots in engaging people with digital services is fully recognised. However, the reputation of this technology with regards to usefulness and real impact remains rather questionable. Studies that evaluate how people perceive and utilise chatbots are generally lacking. During the last Kenyan elections, we deployed a chatbot on Facebook Messenger to help people submit reports of violence and misconduct experienced in the polling stations. Even though the chatbot was visited by more than 3,000 times, there was a clear mismatch between the users’ perception of the technology and its design. In this paper, we analyse the user interactions and content generated through this application and discuss the challenges and directions for designing more effective chatbots

A mechanism for morphogen-controlled domain growth

Many developmental systems are organised via the action of graded distributions of morphogens. In the Drosophila wing disc, for example, recent experimental evidence has shown that graded expression of the morphogen Dpp controls cell proliferation and hence disc growth. Our goal is to explore a simple model for regulation of wing growth via the Dpp gradient: we use a system of reaction-diffusion equations to model the dynamics of Dpp and its receptor Tkv, with advection arising as a result of the flow generated by cell proliferation. We analyse the model both numerically and analytically, showing that uniform domain growth across the disc produces an exponentially growing wing disc

Control of CNS midline transcription by asymmetric E-box-like elements: Similarity to xenobiotic responsive regulation

Central nervous system midline cells constitute a discrete group of Drosophila embryonic cells with numerous functional and developmental roles. Corresponding to their separate identity, the midline cells display patterns of gene expression distinct from the lateral central nervous system. A conserved 5 base pair sequence (ACGTG) was identified in central nervous system midline transcriptional enhancers of three genes. Germ-line transformation experiments indicate that this motif forms the core of an element required for central nervous system midline transcription. The central nervous system midline element is related to the mammalian xenobiotic response element, which regulates transcription of genes that metabolize aromatic hydrocarbons. These data suggest a model whereby related basic-helix-loop-helix-PAS proteins interact with asymmetric E-box-like target sequences to control these disparate processes

Can pictures have explicatures?

This paper considers the question of whether pictures can be understood to give rise to explicit meanings. In relevance-theoretic terms, this means asking whether pictures give rise to ‘explicatures’. The definition of the term ‘explicature’ seems to rule out this possibility except in cases where pictures include or are accompanied by material with coded meanings. The paper considers a range of non-verbal phenomena with coded meanings, including pictograms (Forceville 2011, Forceville et al 2014). It then considers whether the explicature-implicature distinction could be relevant to pictures without such elements. Some assumptions communicated by pictures seem to be more ‘explicature-like’ than others, so it is possible that the distinction will be useful. The question is not merely terminological as the discussion leads to a fuller understanding of ways in which pictures communicate