'Une aventure novele est en cele sale venue': dynamics of narrative, people and place in old French literature

This thesis analyses twelfth- and thirteenth-century French texts from a range of genres to demonstrate how the inter-relation of narrative and place is a catalyst for the production of vernacular literary works. Rooted in close criticism of the texts in question (the Roman d’Eneas, lives of the martyrs Christina of Tyre and Catherine of Alexandria, the Voyage de saint Brendan, lives of the ascetics Alexis and Mary of Egypt, and the Roman de Brut), this study examines the ways in which narration both generates and delimits place. In tandem with this it interrogates the representations of, and disturbances to, the spatial organization of these texts, encompassing such themes as empire-building, genealogy, travel and exile. This juxtaposition of diverse materials opens up mutually illuminating spaces, demonstrating the instability of the entrenched generic categories applied to them and prompting consideration of the ambiguous principles of medieval poetic craft. Hagiography is a particularly pertinent crossing-point for multiple thematic concerns, from the tension between revelation and concealment of the body to the relationship between a state and its citizens. Its location at the confluence of liturgy, lay spirituality and entertainment makes it an apt focus for a study such as this. The thesis also considers questions of cultural and political appropriation and re-appropriation of place, drawing on medieval writers’ and thinkers’ conflicted relationship with their classical antecedents and non-Christian ‘others’. The many and varied journeys undertaken in these texts, meanwhile, offer critical meeting points between practices of writing about place across a range of modes, and they invite consideration of the historical contexts for their production. Foremost in this study, however, is a concern with the ways in which medieval narratives reify story; through close attention to how narratives are produced, preserved and transmitted in these texts, I examine the ethics and efficacy of storytelling as a means for creating place. Whether they re-present foundation myths, the trials of saints, or the fantastical journeys of adventurers, these stories are both container and content for reflections on how authors can relate to their world, and it this sense of the two faces of narrative that underpins my interpretation of these texts and their representations of places and spaces

Neurohumoral control of sinoatrial node activity and heart rate: insight from experimental models and findings from humans

The sinoatrial node is perhaps one of the most important tissues in the entire body: it is the natural pacemaker of the heart, making it responsible for initiating each-and-every normal heartbeat. As such, its activity is heavily controlled, allowing heart rate to rapidly adapt to changes in physiological demand. Control of sinoatrial node activity, however, is complex, occurring through the autonomic nervous system and various circulating and locally released factors. In this review we discuss the coupled-clock pacemaker system and how its manipulation by neurohumoral signaling alters heart rate, considering the multitude of canonical and non-canonical agents that are known to modulate sinoatrial node activity. For each, we discuss the principal receptors involved and known intracellular signaling and protein targets, highlighting gaps in our knowledge and understanding from experimental models and human studies that represent areas for future research

A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long-COVID in Scotland: Part I

Background: Commonly reported symptoms of long COVID may have different patterns of prevalence and presentation across different countries. While some limited data have been reported for the United Kingdom, national specificity for Scotland is less clear. We present a cross-sectional survey to examine the symptom prevalence, frequency, and severity of long COVID for people living with the condition in Scotland. Methods: An online survey was created in the English language and was available between April 21, 2022 and August 5, 2022. Participants were included if they were ≥18 years old, living in Scotland, and had self-diagnosed or confirmed long COVID; and excluded if they were hospitalized during their initial infection. Within this article we quantify symptom prevalence, frequency, severity, and duration. Results: Participants (n = 253) reported the most prevalent long-COVID symptoms to be post-exertional malaise (95%), fatigue/tiredness (85%), and cognitive impairment (68%). Fatigue/tiredness, problems with activities of daily living (ADL), and general pain were most frequently occurring, while sleep difficulties, problems with ADL, and nausea were the most severe. Scottish Index of Multiple Deprivation associated with symptom number, severity, and frequency, whereas vaccine status, age, sex, and smoking status had limited or no association. Conclusions: These findings outline the challenges faced for those living with long COVID and highlight the need for longitudinal research to ascertain a better understanding of the condition and its longer-term societal impact

A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long COVID in Scotland: Part II

Background: There has been some effort to map the prevalence, frequency, and severity of symptoms of long COVID at local and national levels. However, what is frequently absent from such accounts is details of the impact the disease and its symptoms have had on those living with the condition. In this article, we present details of the impact on work, caring, and mental health gathered using a cross-sectional survey. Methods: Data were collected using an online survey that was available from April 21, 2022, to August 5, 2022. Included participants had either self-diagnosed or confirmed long COVID, were living in Scotland, and were aged ≥18 years. Hospitalization during initial COVID-19 infection was an exclusion criterion. Participants were asked to report on the impact of their illness on everyday activities such as working, studying, or caring. They also completed an assessment of their current mood. Results: People with long COVID were often severely impacted in their ability to work and study. Severe impact on work and study were predicted by more severe and more frequent fatigue, more severe pain, and more severe cognitive impairment. Respondents’ ability to care for child dependents was also associated with more severe and more frequent fatigue, and more severe cognitive impairments. More severe pain associated with greater impact on adult care. Negative mood correlated most strongly with frequency and severity of neurological symptoms, including lack of attention, loss of smell, impaired sense of smell, loss of taste, impaired sense of taste, and loss of appetite. Conclusions: Long COVID has a significant impact on ability to work, study, and care for dependents. The severity of this impact is associated with specific symptom burden, including fatigue, pain, and cognitive impairment

Preclinical models of myocardial infarction: from mechanism to translation

Approximately 7 million people are affected by acute myocardial infarction (MI) each year, and despite significant therapeutic and diagnostic advancements, MI remains a leading cause of mortality worldwide. Pre-clinical animal models have significantly advanced our understanding of MI and enable the development of therapeutic strategies to combat this debilitating disease. Notably, some drugs currently used to treat MI and heart failure (HF) in patients had initially been studied in pre-clinical animal models. Despite this, pre-clinical models are limited in their ability to fully recapitulate the complexity of MI in humans. The pre-clinical model must be carefully selected to maximise the translational potential of experimental findings. This review describes current experimental models of MI and considers how they have been used to understand drug mechanisms of action (MOA) and support translational medicine development

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes