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Correspondence on “Implementing palliative care in the intensive care unit: a systematic review and mapping of knowledge to the implementation research logic model” Authors’ reply
No full textO-GlcNAcylation and Phosphorylation Crosstalk in Vascular Smooth Muscle Cells: Cellular and Therapeutic Significance in Cardiac and Vascular Pathologies
Get PDFMore than 400 different types of post-translational modifications (PTMs), including O-GlcNAcylation and phosphorylation, combine to co-ordinate almost all aspects of protein function. Often, these PTMs overlap and the specific relationship between O-GlcNAcylation and phosphorylation has drawn much attention. In the last decade, the significance of this dynamic crosstalk has been linked to several chronic pathologies of cardiovascular origin. However, very little is known about the pathophysiological significance of this crosstalk for vascular smooth muscle cell dysfunction in cardiovascular disease. O-GlcNAcylation occurs on serine and threonine residues which are also targets for phosphorylation. A growing body of research has now emerged linking altered vascular integrity and homeostasis with highly regulated crosstalk between these PTMs. Additionally, a significant body of evidence indicates that O-GlcNAcylation is an important contributor to the pathogenesis of neointimal hyperplasia and vascular restenosis responsible for long-term vein graft failure. In this review, we evaluate the significance of this dynamic crosstalk and its role in cardiovascular pathologies, and the prospects of identifying possible targets for more effective therapeutic interventions
Evaluation of a panel of 105 cytokines from human glioblastoma (GBM) tissue maintained, and treated, on a unique microfluidic platform
No full textGBM remains a therapeutically challenging malignancy, partly due to its complex cytokine mediated microenvironment. This study established a novel microfluidic platform to maintain patient derived GBM tissue biopsies ex vivo for up to 12 days, enabling the dynamic profiling of cytokine responses under treatment (1μM GSK (Glycogen Synthase Kinase) 3368715 + 10μM Temozolomide). The combination of biochemical assays (LDH activity), histological analysis (H&E staining and Immunohistochemistry (IHC) for apoptotic markers), cytokine proteome profiling and ELISA assays provides evidence that GBM tissues can be maintained in a viable state within the novel microfluidic perfusion device for at least 12 days. Cytokine profiling was performed using Proteome Profiler array for 105 different cytokines, followed by ELISA validation for seven key cytokines (VEGF, MMP9, CHI3L1, IL6, IL8, Serpin E1, and Angiopoietin-2).Multivariate analysis showed time significantly influenced cytokine profiles (p = 0.0288), with an overall downregulation over time. Treatment (temozolomide plus arginine methylation inhibitor) had no significant global effect on all cytokines expression level (p = 0.1977), but did significantly affect the seven selected cytokines (p = 0.0048). Univariate analysis confirmed VEGF (p = 0.0004) and MMP9 (p = 0.0046) were significantly downregulated with treatment, while CHI3L1 was upregulated (p = 0.0088). Additionally, gender (p = 0.0050) and age group (60 years; p = 0.0021) were both significant covariates influencing cytokine expression. However, these findings should be interpreted with caution given the small sample size (n=13), particularly the underrepresentation of female patients (3 females vs. 10 males) and the age imbalance (4 under 60 vs. 9 over 60).Three of the study cytokines, VEGF, MMP9, and CHI3L1, were identified as responsive biomarkers under drug treatment, supporting further exploration of these targets. The platform provides a valuable tool for preclinical therapeutic screening and biomarker discovery. With further optimisation, it could support personalised treatment strategies and contribute to the development of more effective, patient-tailored approaches for managing GBM
Epigenetics and its application in forensic analysis
No full textForensic epigenetics applies epigenetic techniques to address questions relevant to legal and criminal investigations. Current research in forensic epigenetics focuses on four primary areas: identifying body fluids (using microRNA and DNA methylation), estimating an individual's age (based on DNA methylation), distinguishing monozygotic twins, and potentially predicting the age of biological stains (using a variety of markers). This chapter examines the challenges faced in forensic investigations, current technological capabilities, and ongoing research aimed at enhancing these capabilities. MicroRNA and DNA methylation have shown significant success in identifying forensic body fluids, with DNA methylation–based methods already implemented in casework. Substantial advancements have been made in age prediction using DNA methylation, with publicly available models aiding this process. Techniques such as Massively Parallel Sequencing and High-Resolution Melting Curve Analysis have been explored to distinguish between monozygotic twins. While limited progress has been made in estimating the age of body fluid stains, environmentally responsive DNA methylation profiling holds promising potential for future applications
The influence of Artificial Intelligence Cognitive Biases on Corporate Governance in Making Financial Decisions: Examined Via Throughput Model
No full textAs businesses work to leverage artificial intelligence (AI) promise to boost productivity and efficiency, its position in corporate governance (CG) is becoming increasingly important, where AI can be used to streamline fraud detection and compliance procedures, enhancing the entire structure of CG. However, cognitive bias, a prevalent issue in AI systems utilised by businesses for decision-making, is a significant concern. Accordingly, the main aim of this study is to explain the influence of AI cognitive biases on CG in making financial decisions by using throughput model (TM). AI cognitive biases include base-rate neglect, insensitivity to sample size, confirmation bias, availability heuristic, and ambiguity aversion. To achieve this aim, this study adopted the quantitative model, where the questionnaire was designed and distributed to research sample, which consisted of 1491 mangers in British banks, and 141 managers in Iraqi Banks. Then, the questionnaire was analysed by using Statistical Package for the Social Sciences (SPSS) program. The results show that financial decisions will be affected by the existence of AI cognitive biases in both British and Iraqi banks. In addition, the availability of reliable financial information will affect positively on financial decisions in both British and Iraqi banks. Moreover, the results show that the decline of the decision maker's level of knowledge and experience will lead to poor financial decisions in both British and Iraqi banks. Finally, the analysis shows that the disruption of digital technological training will lead to poor financial decisions in both British and Iraqi banks. Based on these findings, this study contributes to a deeper understanding by British and Iraqi banks of AI cognitive biases that affect effective financial decision-making. The study also recommended that British and Iraqi banks should train their employees to use modern technology and improve their cognitive skills
Holistic care in mild upper respiratory tract infections (MURTIs): an approach to individualized care management
Get PDFAlthough mild upper respiratory tract infections (MURTIs) are typically self-limiting and benign, they can substantially impair a patient’s quality of life. The wide range of pathogens causing MURTIs often necessitates a symptomatic treatment approach rather than a pathogen-specific treatment. The present article introduces a patient-centred classification system that distinguishes between self-care-oriented, pharmacist- oriented and physician-oriented patients. Building on this framework, we propose a 360° holistic care model that considers contextual factors and addresses the whole person, under the premise that the effectiveness, safety and suitability of the treatment are tailored to the individual’s symptoms and circumstances. To support practical implementation, a stepwise guide for MURTI management is presented, encompassing all steps from initial patient assessment to pharmacological and non-pharmacological treatment approaches, lifestyle advice, patient education, and follow-up care. This structured approach not only facilitates symptom resolution but also promotes long-term health by empowering patients with the knowledge, tools and support they need to maintain their well-being. By shifting the focus from isolated symptom management to comprehensive care, our 360° holistic care model may enhance the overall treatment experience and outcome for patients affected by MURTIs
A mermaid’s tail: Exploring water heritage in the city of Hull
Get PDFSample paragraph:The University of Hull Community Waterscapes, in partnership with local communities and organisations (including Hull Maritime & the Living with Water partnership ), is exploring the city’s rich watery heritage [...]. Building on the work of the Risky Cities project, the emphasis in Community Waterscapes has been on working with communities to create a space for dialogue around the city’s past through participatory, history and heritage workshops. In doing so, residents of Hull have been invited to identify, record and share what they consider to be significant watery heritage in the places they live and work reflecting on what it means to live in a dynamic watery environment
Rapid diagnostic tests to inform clinical decision-making for antifungal stewardship in the ICU: a qualitative study with NHS staff, patients, and their legal representatives
Get PDFBackground: Invasive candidiasis is a fungal infection of the blood or organs that is associated with high morbidity and mortality in critically ill patients. Current diagnosis is based on blood culture, which typically takes 2 days to confirm the presence of Candida, and longer for differentiating the species and sensitivities to antifungal drugs. Administration of antifungal treatment is time-critical, hence critically ill patients considered ‘at-risk’ of Candida infection are often started on antifungal treatment pending test results. However, many of these patients may not have empirical treatment stopped when test results become available because of concerns about the sensitivity of blood culture. The Antifungal STewardship Opportunities study is a multisite national diagnostic test accuracy study investigating the use of rapid tests in the intensive care unit that have the potential to influence decision-making.Objective(s), study design, settings and participants: Our aim is to understand patient and physician risk preferences for using the Antifungal STewardship Opportunities testing strategy to discontinue empirical antifungal therapy using semi-structured interviews. An a priori sample size of 30 National Health Service staff and 10 patient interviews was selected to elicit information relating to the aims. Interview schedules were developed, and all interviews were conducted via video or teleconferencing between December 2021 and December 2022 and lasted between 10 and 60 minutes. Interviews were recorded, transcribed and subjected to thematic analysis.Findings: Semi-structured interviews were conducted with 21 National Health Service clinicians and seven patients and legal representatives. National Health Service staff were risk-averse to stopping empirical antifungal therapy, especially if the patient was improving, while patients were risk-neutral. Although there is a clear unmet need for new rapid testing strategy, clinical confidence in its accuracy, clinical utility, cost-effectiveness and usability were strong factors for its consideration for use in decision-making and adoption. Patients did not exhibit strong feelings towards stopping empirical antifungal treatment as they expressed reliance on clinical judgement.Limitations: There was a potential for selection bias as interview participants being from participating sites. The target recruitment numbers of patients and their legal representatives was not achieved due to low retention rates
Ethical counterinsurgency, and the reciprocal nature of strategic ethics
Get PDFIn Western counterinsurgency (COIN) doctrine, ethics is perceived to be a force multiplier, yet counterinsurgents operate in an ethical ‘grey zone’. This work seeks to provide further clarity on the relationship between ethics and strategic outcomes in COIN; known in this work as strategic ethics. Empirically, counterinsurgents have espoused an ethical resort to force but have resorted to unethical practices. This article argues that perceptions of in bello, ad bellum, and post bellum influence one another in a reciprocal fashion. Consequently, this article argues that strategic ethics should be understood as reciprocal and not linear, and restraint remains strategically prudent