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Nutrient restriction protects against valve interstitial cell calcification by upregulating ubiquitin mediated proteolysis.
No full textIntroduction: Calcific aortic valve disease (CAVD) is a common and progressive valvular heart disease characterised by the pathological calcification of valve interstitial cells (VICs). Current clinical treatments, such as surgical valve replacement and transcatheter valve implantation, are invasive and do not target the underlying molecular mechanisms of calcification. Emerging evidence suggests that metabolic interventions may modulate cellular calcification processes. In this study, we investigated the potential of nutrient restriction (NR) as a non-invasive strategy to mitigate VIC calcification, with a particular focus on the role of the ubiquitin-proteasome system (UPS).Methods: Primary rat valvular interstitial cells (RVICs) were cultured and subjected to in vitro calcification using calcium- and phosphate-enriched media. Nutrient restriction was induced by incubating cells in Hank's Balanced Salt Solution (HBSS). Calcification was assessed by quantifying calcium deposition and osteogenic marker expression. To explore the underlying molecular changes, a stable isotope labelling by amino acids in cell culture (SILAC)-based proteomic analysis was performed. The role of the UPS was further examined using pharmacological inhibition with MG132 and siRNA-mediated knockdown of key UPS components, including Cullin-2 (Cul2) and Ubiquitin-conjugating enzyme E2 H (Ube2H).Results: Nutrient restriction significantly downregulated the expression of osteogenic markers and reduced calcium deposition in RVICs. SILAC-based proteomics revealed the upregulation of multiple components of the UPS in nutrient-restricted cells. Notably, Cul2 and Ube2H were identified as potential key mediators of the anti-calcification effects observed. Inhibition of the proteasome with MG132 exacerbated calcification, while knockdown of Cul2 using siRNA increased osteogenic marker expression and calcium deposition, indicating the essential role of Cul2 in modulating VIC calcification under nutrient-restricted conditions.Conclusion: This study demonstrates that nutrient restriction effectively attenuates VIC calcification through the modulation of the ubiquitin-proteasome system. The protective role of UPS components, particularly Cul2 and Ube2H, suggests that targeting this pathway could represent a novel therapeutic approach for the management of CAVD. These findings also raise the possibility of employing dietary or metabolic interventions as non-invasive strategies to prevent or delay valve calcification.</p
Intimacy Coordination as a Call to Action: Embedding Processes of Care in the UK TV Industry
No full textNo description supplied</p
Renegotiating HRM practices and delivering service transformation of frontline workers: insights from the UK’s NHS Ambulance Trust during a significant disruption
No full textWe note that while the institutional environment determines the actions and structures of constituent organizations, there are still limited insights available in the literature on the nature and process of interactions between key stakeholders in ambulance services, especially as they respond during a significant crisis. This study specifically examines how a positive social exchange between senior leadership, managers and frontline staff, accompanied by changes to the leadership style and HR practices, resulted in significant service transformation. An in-depth qualitative case study design was used to interview 52 frontline staff and leaders from the UK National Health Service’s (NHS) Ambulance Service over a prolonged period of eight months (October 2020 to May 2021). Interviews and secondary data were abductively analyzed, showing how changes to HRM and leadership practices shaped service transformation’s content, process, and logic. The findings suggest that an iterative social exchange between senior leadership, managers and frontline staff of the Ambulance Trust led to adaptations to the nature of HRM and leadership practices, which positively impacted the changes to service delivery, leading to service transformation and improved health and well-being of paramedics. Our conceptual framework contributes to the literature by integrating how the use of agency, new HRM, and leadership practices in the context of institutionalized structures can result in service transformation. Implications for theory and practice are also discussed.</p
The effect of anthropogenic noise on captive pied tamarins
No full textHuman (anthropogenic) noise has strong negative impacts on animal health and welfare. Although this is increasingly acknowledged in wildlife, there are very few studies of the impacts of noise on animals in captive settings, even though they are permanently surrounded by a wide variety of such noises. This thesis investigated the impacts of noise on the critically endangered pied tamarin (Saguinus bicolor) at Jersey Zoo, using a multidisciplinary approach. The first part consisted of an in-depth soundscape analysis at different pied tamarin enclosures. For this, we collected audio data over a one-year period and employed multiple sound measures, including broad and defined frequency bands, as well as acoustic indices. The study highlighted the complexity of the soundscape with significant differences between location, time of day, and time of year. The second part investigated the impact of anthropogenic noise on pied tamarins in a cognitive foraging task. When they were provided access to the forage box in noise and non-noise conditions, the results revealed that noise exposure led to a reduction in foraging frequency, but had no effect on vigilance or foraging success. A final experiment disentangled the impacts of the visual and acoustic components of two different anthropogenic stimuli: zoo visitors and construction. We exposed the pied tamarins to either no stimulus (baseline), individual components (visual or acoustic stimuli only), or a combination of components (which could be congruent or incongruent). The pied tamarins varied in their responses to both the different stimuli and the different components, especially when presented in isolation; however, the combined presentation of congruent visitor components (visual and acoustic) weakened the responses. The combined findings of this thesis highlight the importance of challenging assumptions about soundscapes and the different components of anthropogenic stimuli, and have important implications for animal management and noise mitigation strategies in zoos.</p
Exercise as a transdiagnostic intervention for improving mental health: an umbrella review
No full textExercise is beneficial for mental health in general, but no review has systematically assessed its potential transdiagnostic nature, i.e. whether it is beneficial across specific disorders. We performed a systematic umbrella review of meta-analyses of randomized controlled trials (RCTs) of exercise in participants with mental disorders defined according to the International Classification of Diseases (ICD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM), assessing exercise's transdiagnostic nature with TRANSD criteria, including eight meta-analyses (six included in the TRANSD meta-analysis), encompassing 99 RCTs (n = 5,656) across 11 disorders. Moderate/vigorous aerobic exercise was an effective transdiagnostic intervention for disease-specific primary symptoms across 11 disorders (recurrent depressive disorder, social phobia, panic disorder, generalized anxiety disorder, post-traumatic stress disorder, brief psychotic disorder, schizophrenia, schizoaffective disorder, delusional disorder, schizophreniform disorder, attention-deficit/hyperactivity disorder) and four spectra (depressive disorders, anxiety disorders, schizophrenia-spectrum disorders, neurodevelopmental disorders) with a medium effect size (SMD = −0.67, 95%CI = −0.84, -0.50). Moderate/vigorous aerobic exercise also improved cognition across two disorders (schizophrenia, attention-deficit/hyperactivity disorder) and two spectra (schizophrenia-spectrum disorders, neurodevelopmental disorders), with a large effect size (SMD = 0.92, 95%CI = 0.52, 1.33). According to TRANSD criteria, moderate/vigorous aerobic exercise is a transdiagnostic intervention to improve disease-specific primary symptoms of 11 mental disorders, and cognition in two mental disorders.</p
Disability, Dissymmetry, Death Activism
No full textThis article uses queer death studies, and death activism, to explore how certain disabilities, especially degenerative, chronic disabilities with a diagnosis of a likely shortened life, challenge social understandings of bodies. The resonances between disability and queer create an alternative to the theoretical structures of opposition between the normal and abnormal/pathological, something which queer theory and Critical Disability Studies share.</p
Rivers are increasingly being given legal rights. Now they need people who will defend these rights in court
No full textA district council in England has passed a motion to grant its local river the rights to flow freely, to be free from pollution and to enjoy its native biodiversity. The move by Lewes District Council in East Sussex to recognise the fundamental rights of the River Ouse is the first of its kind in the UK...</p
Graph-Regularized Orthogonal Non-Negative Matrix Factorization with Itakura–Saito (IS) Divergence for Fault Detection
No full textIn modern industrial environments, quickly and accurately identifying faults is crucial for ensuring the smooth operation of production processes. Non-negative Matrix Factorization (NMF)-based fault detection technology has garnered attention due to its wide application in industrial process monitoring and machinery fault diagnosis. As an effective dimensionality reduction tool, NMF can decompose complex datasets into non-negative matrices with practical and physical significance, thereby extracting key features of the process. This paper presents a novel approach to fault detection in industrial processes, called Graph-Regularized Orthogonal Non-negative Matrix Factorization with Itakura–Saito Divergence (GONMF-IS). The proposed method addresses the challenges of fault detection in complex, non-Gaussian industrial environments. By using Itakura–Saito divergence, GONMF-IS effectively handles data with probabilistic distribution characteristics, improving the model’s ability to process non-Gaussian data. Additionally, graph regularization leverages the structural relationships among data points to refine the matrix factorization process, enhancing the robustness and adaptability of the algorithm. The incorporation of orthogonality constraints further enhances the independence and interpretability of the resulting factors. Through extensive experiments, the GONMF-IS method demonstrates superior performance in fault detection tasks, providing an effective and reliable tool for industrial applications. The results suggest that GONMF-IS offers significant improvements over traditional methods, offering a more robust and accurate solution for fault diagnosis in complex industrial settings.</p
Transcriptomic Profiling of iPS Cell-Derived Hepatocyte-like Cells Reveals Their Close Similarity to Primary Liver Hepatocytes
No full textHuman-induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) have been shown to be useful for the development of cell-based regenerative strategies and for modelling drug discovery. However, stem cell-derived HLCs are not identical in nature to primary human hepatocytes (PHHs), which could affect the cell phenotype and, potentially, model reliability. Therefore, we employed the in-depth gene expression profiling of HLCs and other important and relevant cell types, which led to the identification of clear similarities and differences between them at the transcriptional level. Through gene set enrichment analysis, we identified that genes that are critical for immune signalling pathways become downregulated upon HLC differentiation. Our analysis also found that TAV.HLCs exhibit a mild gene signature characteristic of acute lymphoblastic leukaemia, but not other selected cancers. Importantly, HLCs present significant similarity to PHHs, making them genuinely valuable for modelling human liver biology in vitro and for the development of prototype cell-based therapies for pre-clinical testing.</p
Beyond the labels. classifying countries by child health outcomes. A cluster analysis of child mortality and child-health data
No full textBackground: Most health service classification systems are based on organisational components such as service provision, financing, and regulation. This study considers health systems using data focusing on child health outcomes, service provision, and selected social characteristics. This more accurately reflects the reality of health service provision for children, young people, and their families.Objective: To classify health systems based on child health data through cluster analysis and exploratory and descriptive data analysis.Method: Data were extracted from the current version of the UNICEF (2023) State of the World’s Children full dataset, concentrating on outcomes related to mortality. Cluster analyses were conducted, and a heatmap was produced to identify patterns and groups among countries and child health indicators. Row and column distances were calculated using the Euclidean distance, and clustering was performed using the complete linkage method. Each variable was centred and scaled using the scale command, allowing variables measured on different scales to be compared without those with large values being weighted more heavily. Countries that performed better or were less healthy than expected were identified through linear regression analysis using the ggplot2 package.Results: Analysis of countries by cluster reveals six main groups, characterised by child and maternal mortality rates, vaccination levels, access to maternal and child healthcare, access to water and sanitation, and population migration levels.Conclusion: Identifying patterns in outcomes and identifying countries that perform above or below expectations concerning child health can inform a more nuanced approach to improving a country's child health outcomes.</p
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