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Effects of High Dose Bolus Cholecalciferol on Free Vitamin D Metabolites, Bone Turnover Markers and Physical Function
Get PDFHigh dose bolus cholecalciferol supplementation has been associated with falls and fracture, and this does not appear to be due to hypercalcaemia. The primary aim of this study was to determine the change in free vitamin D and metabolites after high dose bolus supplementation. This was a single centre, double-blinded, randomised, controlled trial of three different oral bolus doses of vitamin D3 (50,000 IU, 150,000 IU, and 500,000 IU) in otherwise healthy, vitamin D deficient (total 25-hydroxylated vitamin 25(OH)D 50 nmol/L) postmenopausal women were recruited as a concurrent control group. Participants attended five study visits over three months. We measured total 25(OH)D3 and free 25(OH)D, total and free 1,25(OH)2D, parathyroid hormone, fibroblast-growth factor-23, serum calcium, ionised calcium, urinary calcium excretion, and bone turnover markers (procollagen I N-propeptide (PINP), serum C-telopeptides of type I collagen (CTX-I) and Osteocalcin (OC)). We assessed muscle strength and function with grip strength and a short physical performance battery. Postural blood pressure and aldosterone:renin ratio (ARR) was also measured. Total 25(OH)D3 and free 25(OH)D increased in response to dose, and there were proportionate increases in total and free metabolites. Treatment did not affect serum calcium, postural blood pressure, ARR, or physical function. Bone turnover markers increased transiently one week after administration of 500,000 IU. High dose bolus cholecalciferol supplementation does not cause disproportionate increases in free vitamin D or metabolites. We did not identify any effect on blood pressure regulation or physical function that would explain increased falls after high dose treatment. A transient increase in bone turnover markers one week after a 500,000 IU bolus suggests that very high doses can have acute effects on bone metabolism, but the clinical significance of this transient increase is uncertain
Reading Digital Fiction
Get PDFReading Digital Fiction offers the first comprehensive and systematic theoretical, methodological, and analytical examination of digital fiction from a cognitive and empirical perspective. Proposing the new concept of “medial reading”, it argues for the centrality of an audience’s interest in, awareness of and/or attention to the medium in which a text is produced and received, and which we argue should be applied to reader data across media. The book analyses and theorises five generations of digital fiction and their reading including hypertext fiction, hypermedia fiction, narrative video games, app fiction, and virtual reality. It showcases medium- and platform-specific methods of qualitative reader response research across a variety of contexts and settings from screen-based and embodied interaction to gallery installation, and from reading group and individual interview to think-aloud methodologies. The book thus addresses the unique affordances of digital fiction reading by designing and reporting on new empirical studies focusing on hypertextuality, interactivity, immersion, as well as medium-specific forms of textual “you”, ontological ambiguity, reader orientation and empathy. In so doing, the book refines, critiques, and expands cognitive, transmedial, and empirical narratology and stylistics by placing the reader of these new narratives front and centre
The Postdigital as Theme in Narrative Fiction across Media
Get PDFThis article argues that a sceptical attitude towards the role of digital technology in contemporary life is becoming increasingly prevalent in twenty-first century fiction and offers a new way of theorising this thematic trend via refining the concept of the ‘postdigital’. Proving a critical overview of the way that the ‘postdigital’ has been interpreted in aesthetics, critical theory, and literary criticism, I show how the scepticism towards digital media that is a tenet of postdigital visual arts can now also be seen in some narrative fiction of the twenty-first century written in English. I thus show how what I define as postdigital fiction interrogates the way in which the digital and nondigital have become hybridised in digitised societies and questions the universal benefits digital media bring. Taking examples from print and digital fiction, I show how a postdigital perspective can manifest both thematically and aesthetically in fiction and argue that there is an increasing prevalence of postdigital ethics in narrative fiction across media
Postdigital Reading Strategies in Emersive VR Fiction: Empirical Insights
Get PDFIn this article we induce a theory of ambimedial reading as a distinctive postdigital reading strategy from an empirical study with readers of Virtual Reality (VR) fiction. VR is known for its immersive, experiential qualities yet less for its affordances for literary fiction and verbal art. In experimental VR fiction, 360-degree, fully embodied spatial experiences can engender diverse ontological spheres, leaving readers straddling multiple diegetic and extradiegetic layers of storytelling. These ontological ruptures, evoked by what we call ambispatial design, can lend VR fiction an e-mersive quality constructing readers as self-conscious voyeurs rather than granting them an unreflected, immersive experience. To illustrate these emersive effects, we consider participants’ discursive responses to reading Randall Okita’s VR memoir, The Book of Distance. We show how readers attempt to make sense of an unfamiliar postdigital storytelling experience by means of ambimedial responses, in which they attempt to reconcile an unfamiliar medial experience with more familiar ones. Our data shows that emersed readers conceptualize their doubly embodied and hybridized position as a constituent of both the actual world and digital VR world, a phenomenon we refer to as dual embodied metalepsis
Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors
Get PDFThe generation of the post-cranial embryonic body relies on the coordinated production of spinal cord neurectoderm and presomitic mesoderm cells from neuromesodermal progenitors (NMPs). This process is orchestrated by pro-neural and pro-mesodermal transcription factors that are co-expressed in NMPs together with Hox genes, which are essential for axial allocation of NMP derivatives. NMPs reside in a posterior growth region, which is marked by the expression of Wnt, FGF and Notch signalling components. Although the importance of Wnt and FGF in influencing the induction and differentiation of NMPs is well established, the precise role of Notch remains unclear. Here, we show that the Wnt/FGF-driven induction of NMPs from human embryonic stem cells (hESCs) relies on Notch signalling. Using hESC-derived NMPs and chick embryo grafting, we demonstrate that Notch directs a pro-mesodermal character at the expense of neural fate. We show that Notch also contributes to activation of HOX gene expression in human NMPs, partly in a non-cell-autonomous manner. Finally, we provide evidence that Notch exerts its effects via the establishment of a negative-feedback loop with FGF signalling
Digitally enabled business models for a circular plastic economy in Africa.
Get PDFIn recognition of the need for an economic logic that complements and reinforces the ecological imperative for the circular plastic economy, this paper explores the importance and impact of digitally enabled circular plastic business models across retailing and distribution systems. The paper draws from 16 focus group discussions, complemented by 17 semi-structured interviews of frontline organisations incorporating digital innovations in their businesses to enable the management of plastic waste in Africa. The study finds that, across African countries, the transition to a circular plastic economy has been hampered by the limited uptake of circular products by consumers. In order to accelerate the transition, innovative business models are required to invigorate the ecosystem and simplify the logistics of retailing and distribution systems. The paper proposes a new conceptual framework that explicates the impact of digital innovations in the processes of value creation and value capture across a whole spectrum of circular economy reverse logistics activities: recycling, redistribution, and remanufacture. The study also highlights two important social and policy implications of digitally-enabled circular business models: Firstly, the creation of new employment opportunities through the empowerment of a new labour force for the circular plastic economy; secondly, the heightened opportunity to enact an innovative sharing economy in typically resource-constrained contexts in which otherwise idle products and resources are more efficiently used in a process of collaborative consumption
Where is My Favourite Toy? Inferring the Mental States of Users in False Belief Understanding
Get PDFThe increasing prevalence of social robots in today's world has made it crucial to have autonomous systems that can interact with humans and adjust to their behaviour. Doing so requires a deep understanding of the human mind, including complex mental states such as beliefs and preferences. To tackle this issue, we have developed a model that can identify false beliefs using the principles of Theory of Mind (ToM), a unique human cognitive mechanism that attributes mental states to others. False belief understanding has always been the primary benchmark used to evaluate ToM in psychology, and this still remain true when testing it in machine systems such as robots. Our model is a modified version of the Bayesian Theory of Mind (BToM), a probabilistic model that reasons on agents' mental states regarding their interactions within the environment. To test the model's performance, we set up a complex assistive scenario with a robot and two human agents playing with toys. In this scenario, the model serves as the cognitive component of the robot, responsible for organising a room with toys while considering the preferences and beliefs of the agents regarding the toys' locations. We have provided results to demonstrate the model's performance in different conditions. Additionally, we have used the Unity Engine as a platform to simulate the cleaning scenario and show the robot's role in such situations
Lecturers don’t know everything: students listening to the thought processes of lecturers on unfamiliar ground
No full textDue to the nature of the teaching environment, students may often develop perceptions of their lecturers’ ability as mathematicians, based on the pre-prepared and well-rehearsed content they present. In reality, performing mathematical calculations and solving problems is a difficult skill, and students may compare their own experiences unfavourably with the ease they see lecturers display. To interrogate this disparity, an exercise was included in an undergraduate maths session during which lecturers attempted unseen problems from A-level maths papers, so the students could see them describing the process of problem-solving—including making mistakes, applying helpful strategies and techniques, correcting their own errors and identifying gaps in their knowledge. As well as describing these positive behaviours for students, the session aimed to develop the students’ understanding that their own experiences of struggling with maths are normal and healthy. The activity formed part of a broader session on making mistakes in maths, which also included some advice and opportunities to find mistakes in mathematical working-out. The students were invited to participate in questionnaires and focus groups to explore their perceptions and attitudes towards their lecturers’ knowledge and capacity to make mistakes, and in this paper we analyse these responses and consider how this relates to teaching, and to students’ personal development
Normalising the Implementation of Pharmacogenomic (PGx) Testing in Adult Mental Health Settings: A Theory-Based Systematic Review
Get PDFPharmacogenomic (PGx) testing can help personalise psychiatric prescribing and improve on the currently adopted trial-and-error prescribing approach. However, widespread implementation is yet to occur. Understanding factors influencing implementation is pertinent to the psychiatric PGx field. Normalisation Process Theory (NPT) seeks to understand the work involved during intervention implementation and is used by this review (PROSPERO: CRD42023399926) to explore factors influencing PGx implementation in psychiatry. Four databases were systematically searched for relevant records and assessed for eligibility following PRISMA guidance. The QuADS tool was applied during quality assessment of included records. Using an abductive approach to codebook thematic analysis, barrier and facilitator themes were developed using NPT as a theoretical framework. Twenty-nine records were included in the data synthesis. Key barrier themes included a PGx knowledge gap, a lack of consensus in policy and guidance, and uncertainty towards the use of PGx. Facilitator themes included an interest in PGx use as a new and improved approach to prescribing, a desire for a multidisciplinary approach to PGx implementation, and the importance of fostering a climate for PGx implementation. Using NPT, this novel review systematically summarises the literature in the psychiatric PGx implementation field. The findings highlight a need to develop national policies on using PGx, and an education and training workforce plan for mental health professionals. By understanding factors influencing implementation, the findings help to address the psychiatric PGx implementation gap. This helps move clinical practice closer towards a personalised psychotropic prescribing approach and associated improvements in patient outcomes. Future policy and research should focus on the appraisal of PGx implementation in psychiatry and the role of pharmacists in PGx service design, implementation, and delivery