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Impact of myocardial fibrosis on cardiovascular structure, function and functional status in heart failure with preserved ejection fraction
No full textMyocardial fibrosis, measured using cardiovascular magnetic resonance extracellular volume (ECV), is associated with adverse outcome in heart failure with preserved ejection fraction but the mechanisms by which myocardial fibrosis exerts this deleterious effect are unclear. We performed mediation analyses of data from the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial to determine whether myocardial fibrotic regression causes changes in cardiovascular function and functional status following antifibrotic therapy. Regression of myocardial fibrosis correlated with improvements in 6-minute walk test and KCCQ clinical summary score. The only outcome variable that demonstrated a treatment effect was an increase in left ventricular ejection fraction (LVEF). The estimated average causal mediation effects of myocardial ECV, absolute myocardial extracellular matrix volume and absolute myocardial cellular volume on LVEF were 6.1%, 21.5%, and 13.7% respectively, none of which were significant and therefore not mediated by myocardial fibrosis. (PIROUETTE; NCT02932566)
Depression and anxiety in a real-world psoriatic arthritis longitudinal study. Should we focus more on patients’ perception?
No full textObjectives: Longitudinal studies using validated tools to evaluate depression and anxiety in psoriatic arthritis (PsA) are lacking. We aimed to estimate their course in PsA and to examine possible associations with disease-related parameters and patient-reported outcomes (PROs).Methods: PsA patients attending two outpatient rheumatology clinics were consecutively enrolled (January 2019-June 2021, n=128). The hospital anxiety and depression scale (HADS) was used at two sequential visits (mean±SD: 10±6 months) to prospectively assess depression (HADS-Depression) and anxiety (HADS-Anxiety) (cut-off scores≥11). Associations with demographic, clinical, laboratory features and PROs for quality of life (QoL) (EQ-5D), functional status (HAQ-DI) and nocebo-behaviour (Q-No) were examined. ‘Change’ was the difference between values at the first and second visit.Results: Prevalence of depression and anxiety at the first visit was 19.5% and 21.1%, respectively. Depression was associated with EQ-5D [OR (95% CI): 1.70 (1.02-2.59), p=0.019] and anxiety with EQ-5D [1.81 (1.20 to 2.72), p=0.005], nocebo-behaviour [1.19 (1.01-1.40), p=0.04] and current corticosteroid use [6.95 (1.75-27.59), p=0.006]. At the second visit, HADS-Depression and HADS-Anxiety scores were improved in 40.9% and 41.9% of patients, respectively. While no associations were found for HADS-Anxiety score change, changes in HADS-Depression score correlated with changes in subjective (tender joint count, r= 0.204, p=0.049; PtG, r= 0.236, p=0.023; patient pain assessment, r= 0.266, p=0.01) but not objective (swollen joint count, ESR, CRP) parameters of disease activity.Conclusion: In PsA, depression and anxiety are associated with worse PROs, including QoL. Subjective parameters of disease activity parallel course of depression.<br/
Holes, Piers and Canyons: Absence as Emancipatory Space in Ulysses
No full textIn this article, I suggest that James Joyce creates newly active reading practices through his use of textual gaps in Ulysses. Instead of presenting readers with difficulties or frustrations, these gaps can be seen as emancipatory, asking readers to choose their own path, create their own meanings, and sit with uncertainty. I focus on how textual gaps are created within the ostensibly traditional forms of ‘Circe’ and ‘Ithaca’, represented as a play-script and a catechism respectively. I metaphorically characterise these empty spaces in the text as a hole in rock, a pier, and a canyon to think through the different readerly responses they facilitate and inspire. Whether readers choose to move through the hole in rock, remain contemplative at the end of the pier, or shout across Joyce’s authorial canyon represents a democratic choice, giving us the important space to engage with Ulysses on our own terms
Responding to the Ockenden Review: safe care for all needs evidence-based system change - and strengthened midwifery
No full textHybrid Autoregressive Inference for Scalable Multi-hop Explanation Regeneration
No full textRegenerating natural language explanations in the scientific domain has been proposed as a benchmark to evaluate complex multi-hop and explainable inference. In this context, large language models can achieve state-of-the-art performance when employed as cross-encoder architectures and fine-tuned on human-annotated explanations. However, while much attention has been devoted to the quality of the explanations, the problem of performing inference efficiently is largely under-studied. Cross-encoders, in fact, are intrinsically not scalable, possessing limited applicability to real world scenarios that require inference on massive facts banks.To enable complex multi-hop reasoning at scale, this paper focuses on bi-encoder architectures, investigating the problem of scientific explanation regeneration at the intersection of dense and sparse models. Specifically, we present SCAR (for Scalable Autoregressive Inference), a hybrid framework that iteratively combines a Transformer-based bi-encoder with a sparse model of explanatory power, designed to leverage explicit inference patterns in the explanations. Our experiments demonstrate that the hybrid framework significantly outperforms previous sparse models, achieving performance comparable with that of state-of-the-art cross-encoders while being ≈ 50 times faster and scalable to corpora of millions of facts. Further analyses on semantic drift and multi-hop question answering reveal that the proposed hybridisation boosts the quality of the most challenging explanations, contributing to improved performance on downstream inference tasks
Predictors of myocardial fibrosis and response to anti-fibrotic therapy in heart failure with preserved ejection fraction
No full textPurpose: Myocardial fibrosis, measured using magnetic resonance extracellular volume (ECV), associates with adverse outcome in heart failure with preserved ejection fraction (HFpEF). In the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial, the novel anti-fibrotic agent pirfenidone reduced myocardial fibrosis. We sought to identify baseline characteristics that associate with myocardial fibrotic burden, the change in myocardial fibrosis over a year, and predict response to pirfenidone in patients with HFpEF. Methods: Amongst patients enrolled in the PIROUETTE trial (n=107), linear regression models were used to assess the relationship between baseline variables and baseline myocardial ECV, with change in myocardial ECV adjusting for treatment allocation, and to identify variables that modified the pirfenidone treatment effect.Results: Body mass index, left atrial reservoir strain, haemoglobin and aortic distensibility were associated with baseline ECV in stepwise modelling, and systolic blood pressure, and log N-terminal pro B-type natriuretic peptide were associated with baseline ECV in clinically-guided modelling. QRS duration, left ventricular mass and presence of an infarct at baseline were associated with an increase in ECV from baseline to week 52. Whilst QRS duration, presence of an infarct, global longitudinal strain and left atrial strain modified the treatment effect of pirfenidone when considered individually, no variable modified treatment effect on multivariable modelling.Conclusion: Baseline characteristics were identified that associate with myocardial fibrosis and predict change in myocardial fibrosis. No variables that independently modify the treatment effect of pirfenidone were identified (PIROUETTE, NCT02932566). Keywords: Heart failure, myocardial fibrosis, magnetic resonance imaging (MRI), extracellular volume (ECV)<br/
Women, gender, and the professionalisation of French cultural diplomacy in Britain, 1900–40
No full textSonOpt: Sonifying Bi-objective Population-Based Optimization Algorithms
No full textWe propose SonOpt, the first (open source) data sonification application for monitoring the progress of bi-objective populationbased optimization algorithms during search, to facilitate algorithm understanding. SonOpt provides insights into convergence/stagnation of search, the evolution of the approximation set shape, location of recurring points in the approximation set, and population diversity. The benefits of data sonification have been shown for various non-optimization related monitoring tasks. However, very few attempts have been made in the context of optimization and their focus has been exclusively on single-objective problems. In comparison, SonOpt is designed for biobjective optimization problems, relies on objective function values ofnon-dominated solutions only, and is designed with the user (listener) in mind; avoiding convolution of multiple sounds and prioritising ease of familiarizing with the system. This is achieved using two sonification paths relying on the concepts of wavetable and additive synthesis.This paper motivates and describes the architecture of SonOpt, and then validates SonOpt for two popular multi-objective optimization algorithms (NSGA-II and MOEA/D). Experience SonOpt yourself viahttps://github.com/tasos-a/SonOpt-1.0.Keywords: sonification · optimization · algorithmic behaviour · metaheuristics · evolutionary computation · process monitoring · SonOpt
Young children rely on gossip when jointly reasoning about whom to believe
No full textPeople rely on reputational information communicated via gossip when deciding about with whom to cooperate, whom to believe, and whom to trust. In two studies, we investigated whether 5 and 7-yearold children trust in gossip when determining a course of action. In Study 1, 5 and 7-year-old Germanspeaking peer dyads (N = 64 dyads, 32 female dyads) were presented with a collaborative problem-solving task (e.g., deciding together what a creature eats). Each child individually received conflicting information about the solution from a different informant (e.g., one proposed rocks; the other proposed sand). Each child additionally heard gossip about the informant’s reputation: one informant had a good reputation; the other had a bad reputation. In the experimental condition, the reputation was relevant to the task (honesty), whereas it was irrelevant in the control condition (tidiness). Seven-year-old dyads, and 5-year-old dyads to a lesser extent, settled on the items suggested by the informant with good reputation in the experimental but not in the control condition. Only 7-year-old children explicitly referred to the information conveyed via gossip, engaging in metatalk about the reputations of the informants. In Study 2, we replicated these findings in a more controlled experiment in which 5 and 7-year-old American English-speaking children (N = 48, 27 girls) tried to convince an adult partner who proposed the item suggested by the informant with bad reputation. Thus, starting around age 5, and more reliably at age 7, children selectively rely on gossip in identifying trustworthy individuals in their collaborative reasoning with partners.</p
Clinical challenges associated with utility of neoadjuvant treatment in patients with pancreatic ductal adenocarcinoma
No full textPancreatic ductal adenocarcinoma (PDAC) is an increasingly common cancer with a persistently poor prognosis, and only approximately 20% of patients are clearly anatomically resectable at diagnosis. Historically, a paucity of effective therapy made it inappropriate to forego the traditional gold standard of upfront surgery in favour of neoadjuvant treatment; however, modern combination chemotherapy regimens have made neoadjuvant therapy increasingly viable. As its use has expanded, the rationale for neoadjuvant therapy has evolved from one of `downstaging` to one of early treatment of micro-metastases and selection of patients with favourable tumour biology for resection. Defining resectability in PDAC is problematic; multiple differing definitions exist. Multidisciplinary input, both in initial assessment of resectability and in supervision of multimodality therapy, is therefore advised. European and North American guidelines recommend the use of neoadjuvant chemotherapy in borderline resectable (BR)-PDAC. Similar regimens may be applied in locally advanced (LA)-PDAC with the aim of improving potential access to curative-intent resection, but appropriate patient selection is key due to significant rates of recurrence after excision of LA disease. Upfront surgery and adjuvant chemotherapy remain standard-of-care in clearly resectable PDAC, but multiple trials evaluating the use of neoadjuvant therapy in this and other localised settings are ongoing