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Causation, historiographic approaches and the investigation of serious adverse incidents in mental health settings
No full textThis article is not available on ChesterRepTo improve the safety of healthcare systems, it is necessary to understand harm-related events that occur in these systems. In mental health services, particular attention is paid to harm arising from the actions of patients against themselves or others. The primary intention of examining these adverse events is to inform changes to care provision so as to reduce the likelihood of the recurrence of such events. The predominant approach to investigating adverse incidents has relied on the cause-and-effect conceptualisation of past events. Whilst the merits of approaches which are reliant on cause-and-effect narratives have been questioned, alternatives models to explain adverse incidents in health settings have not been theoretically or empirically tested. This novel article (i) examines the notion of causation (and the related notion of omission) in the context of explaining adverse events in mental health settings, and (ii) draws on a long-established discipline devoted to the study of how the past is interpreted (namely historiography) to theoretically investigate the innovative application of two historiographical approaches (i.e. counterfactual analysis and historical materialism) to understanding adverse events in mental health settings
Cucumeropsis mannii seed oil protects against bisphenol A-induced hepatotoxicity by mitigating inflammation and oxidative stress in rats
Get PDF© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.OBJECTIVES This study looked at how CMSO affected male Wistar albino rats' liver damage caused by bisphenol A. METHODS The standard HPLC method was used to assess the CMSO's phenolic content. Then, six (n = 8) groups of forty-eight (48) male Wistar rats (150 20 g) each received either CMSO or olive oil before being exposed to BPA for 42 days. Groups: A (one milliliter of olive oil, regardless of weight), B (BPA 100 mg/kg body weight (BW)), C (CMSO 7.5 mg/kg BW), D (CMSO 7.5 mg/kg BW + BPA 100 mg/kg BW), E (CMSO 5.0 mg/kg BW + BPA 100 mg/kg BW), and F (CMSO 2.5 mg/kg BW + BPA 100 mg/kg BW). KEY FINDINGS A surprising abundance of flavonoids, totaling 17.8006 10.95 g/100 g, were found in the HPLC data. Malondialdehyde, liver enzymes, reactive oxygen species, total bilirubin, and direct bilirubin levels were all significantly elevated by BPA (p 0.05). Additionally, nuclear factor-B, interleukin-6, interleukin-1, tumor necrosis factor, and histological alterations were all considerably (p 0.05) caused by BPA. The altered biochemical markers and histology were, however, noticeably recovered by CMSO to a level that was comparable to the control. CONCLUSION Due to the abundance of flavonoid components in the oil, CMSO protects the liver from BPA-induced hepatotoxicity by lowering oxidative stress and inflammatory reactions.Acknowledgements: We appreciate the management of the Department of Biochemistry Institutional Research Ethics Committee, Ebonyi State University, Abakaliki, Nigeria
Performativity and self-efficacy of A-level students during a period of discontinuity
Get PDFThis exploratory case study investigates the impact that the discontinuity to education caused by the COVID-19 pandemic, had on the students who were unable to take two series of high-stake examinations. The study examines student self-efficacy in the build-up to final A-level exams, interrogating how the teacher allocated grade process and the periods of lockdown impacted on the student body. The study reflects growing concerns about how government decisions aimed to control the COVID-19 virus have manifested in educational settings and may well effect schools and colleges for many years to come. The conceptual framework that underpinned this research arose from the work of Bandura (1977) on self-efficacy with the specific field of interest being how levels of Academic Self-Efficacy (Zimmerman, 1995) were impacted by a disjointed educational journey. An interpretive approach is adopted, utilising mixed method case study to focus on the students at one educational institution. The empirical data was collected through five stages with the first involving longitudinal quantitative analysis of the student body, followed by two focus groups, which enabled purposive sampling to select five final cases. After interviewing the five students to gain a deeper understanding of their experience, three staff from different institutions were interviewed to triangulate the data.
The quantitative and qualitative data was scrutinised using inductive content analysis with three resultant themes emerging. The first was the wider impact on wellbeing that the discontinuity has created, the second was a decline in students' attitudes toward education and the third regarded changes to future plans following the experiences of the pandemic. The findings indicate that for some students the return to ‘normal’ education and the potentially inflated GCSE’s, have been as much of a
challenge as the pandemic itself. Accordingly, this thesis begins to ask questions about the culture of neoliberalism and performativity which transcends education and whether the pandemic has given us an opportunity to rethink. This will bring into scope Foucault’s (1982) concepts of power, surveillance, and regulation and Ball’s (2015) work about educational discourse. This research falls at a time where there is limited existing literature which substantively explores the impact of the pandemic on the
‘COVID-19 class’, therefore the novel findings from this research offer a unique window into the lived experiences of students during the COVID-19 discontinuity. Although this research offers no practical guidance about how to alter educational policy or practice, all educational institutions could apply the findings noted as they set out on strategic planning for the future
Lost, Found, Reimagined - Roberto Gerhard’s Viola/Cello Sonata(s)
No full textThe Viola Sonata (1948) sits at a pivotal time in Gerhard’s output. Through the 1940s he had composed his Symphony: Homenaje a Pedrell (1940-41), Don Quixote (1940), Alegrías Suite (1942), Concerto for Violin and Orchestra (1942-43), Pandora Suite (1944-45) culminating in the tour de force which is The Duenna (1945-47). The Sonata marks the point at which Gerhard starts to seriously style his method of adopting serial technique leading to the exploration of its use beyond mere pitch manipulation.
The Viola Sonata had been lost for a number of years until deposited at the Cambridge University Library as part of the Roberto Gerhard archive in 2016. There are two manuscripts, the full score and the solo viola part. It consists of 33 pages on 12 stave landscape manuscript paper. The dedication is to the viola player Anatole Mines (1915-1993) who performed the premiere of the work in 1950 accompanied by Gerhard. Until 2016, the only available legacy of this work was its revision in the form of the Cello Sonata (1956). This paper investigates the differences between the Viola and the Cello Sonata to discover the extent to which the later work arranges or reimagines the former
Humankind: Writing from the Cheshire Prize for Literature 2022
No full textThis edited book collection is not available on ChesterRepCollected writings from the Cheshire Prize for Literatur
QSAR-driven screening uncovers and designs novel pyrimidine-4,6-diamine derivatives as potent JAK3 inhibitors
Get PDFThis study presents a robust and integrated methodology that harnesses a range of computational techniques to facilitate the design and prediction of new inhibitors targeting the JAK3/STAT pathway. This methodology encompasses several strategies, including QSAR analysis, pharmacophore modeling, ADMET prediction, covalent docking, molecular dynamics (MD) simulations, and the calculation of binding free energies (MM/GBSA). An efficacious QSAR model was meticulously crafted through the employment of multiple linear regression (MLR). The initial MLR model underwent further refinement employing an artificial neural network (ANN) methodology aimed at minimizing predictive errors. Notably, both MLR and ANN exhibited commendable performance, showcasing R2 values of 0.89 and 0.95, respectively. The model's precision was assessed via leave-one-out cross-validation (CV) yielding a Q2 value of 0.65, supplemented by rigorous Y-randomization. , The pharmacophore model effectively differentiated between active and inactive drugs, identifying potential JAK3 inhibitors, and demonstrated validity with an ROC value of 0.86. The newly discovered and designed inhibitors exhibited high inhibitory potency, ranging from 6 to 8, as accurately predicted by the QSAR models. Comparative analysis with FDA-approved Tofacitinib revealed that the new compounds exhibited promising ADMET properties and strong covalent docking (CovDock) interactions. The stability of the new discovered and designed inhibitors within the JAK3 binding site was confirmed through 500 ns MD simulations, while MM/GBSA calculations supported their binding affinity. Additionally, a retrosynthetic study was conducted to facilitate the synthesis of these potential JAK3/STAT inhibitors. The overall integrated approach demonstrates the feasibility of designing novel JAK3/STAT inhibitors with robust efficacy and excellent ADMET characteristics that surpass Tofacitinib by a significant margin.HD record - metadata record only. VoR not uploaded to ChesterRep until 18/12/202
An investigation of the effects of repurposed drugs on human neuroblastoma and glioblastoma cell lines
Get PDFNeuroblastoma is an aggressive and highly metastatic extracranial tumour of the sympathetic nervous system commonly seen in children, whereas, glioblastoma multiforme is an aggressive and highly proliferative intracranial tumour of the central nervous system seen more in adults. The cellular heterogeneity and molecular pathogenesis of both of these tumours have limited the development of successful treatments.
The combined effects of the lipid-lowering drug, bezafibrate (BEZ) and the contraceptive drug, medroxyprogesterone acetate (MPA) (combined as BaP) has shown promising anti-cancer effects on blood cancers like myeloid leukaemia, Burkitt’s lymphoma and chronic lymphoid leukaemia, and osteosarcoma, with elevated levels of reactive oxygen species and down-regulation of lipogenic enzymes implicated in the mechanisms of action for these drug treatments.
The aim of this study was to determine the effects of these combined drugs on neuronal cancers, using the SH-SY5Y neuroblastoma and U-87MG glioblastoma cell lines as model systems. BEZ treatment alone was shown to have a significant and BEZ concentration-dependent inhibitory effect on SH-SY5Y and U-87MG viable cell proliferation, whereas MPA treatment alone was shown to have very little effect on the cells. The combination of the drugs was shown to have a significant and drug concentration-dependent inhibitory effect on SH-SY5Y and U-87MG viable cell proliferation to a greater extent than BEZ treatment alone. These anti-cancerous effects were associated with increased cell death, and elevated levels of reactive oxygen species (ROS) in both cell lines after 24 hours of treatment. Levels of the lipogenic enzymes, stearoyl CoA desaturase-1 and fatty acid synthase were seen to be significantly lower in SH-SY5Y and U-87MG cells than in blood cancer cell lines. Further, oleic acid supplementation rescued SH-SY5Y neuroblastoma cells, but in serum not serum free conditions only. Oleic acid supplementation of U-87MG cells did not rescue their susceptibility to BaP treatment.
Inclusion of valproic acid combined with BaP (termed VBaP) enhanced the effects of BaP treatment on SH-SY5Y and U-87MG cells, as well as U266 multiple myeloma cells. This is important, as higher concentrations of BEZ are nephrotoxic. The effects of VBaP on U-87MG cells also were explored in a 3D alginate culture system to mimic the microenvironment of the brain. In this situation, VBaP treatment still inhibited U-87MG cell growth and also was effective at inhibited established tumour spheroids.
Hence, this thesis has examined whether drug repurposed drug treatments that have been established in blood cancers may also have application in neuronal cancers, and demonstrated that this is possible
ST2-conditioned medium fosters dorsal horn cell excitability and synaptic transmission in cultured mouse spinal cord
Get PDF© The Author(s) 2023.The version of record of this article, first published in [Stem Cell Reviews and Reports], is available online at Publisher’s website: http://dx.doi.org/10.1007/s12015-023-10618-xConditioned medium obtained from bone marrow-derived stem cells has been proposed as a novel cell-free therapy in spinal cord injury and neuropathic pain, yet the direct effect on spinal neuron function has never been investigated. Here, we adopted spinal cord organotypic cultures (SCOCs) as an experimental model to probe the effect of ST2 murine mesenchymal stem cells-conditioned medium (ST2-CM) on dorsal horn (DH) neuron functional properties. Three days of SCOC exposure to ST2-CM increased neuronal activity measured by Fos expression, as well as spontaneous or induced firing. We showed that the increase in neuronal excitability was associated with changes in both intrinsic membrane properties and an enhanced excitatory drive. The increased excitability at the single-cell level was substantiated at the network level by detecting synchronous bursts of calcium waves across DH neurons. Altogether, SCOCs represent a viable tool to probe mesenchymal cells' effect on intact neuronal networks. Our findings indicate that ST2-CM enhances neuronal activity and synaptic wiring in the spinal dorsal horn. Our data also support the trophic role of mesenchymal cells CM in maintaining network activity in spinal circuits. [Abstract copyright: © 2023. The Author(s).
To what extent, if any, can person-centred counsellors who also hold feminist values, integrate these with Person-Centred Counselling Practice?
Get PDFWhile sexism has long been established in our patriarchal society, gender difference has become an increasingly political issue. The continued inequality experienced as a direct result of gender is unsurprisingly the cause of much individual distress. This study aimed to explore the experiences of feminist women who are person-centred counsellors, with a focus on the extent to which their feminist values influence their counsellor practice. The qualitative method of Interpretative Phenomenological Analysis was used. Through purposive sampling, three participants were recruited and rich data was generated through semi-structured interviews. Analysis resulted in the emergence of two Group Experiential Themes: Gender and Inequality, and Being person-centred. Reviewing the findings in light of the literature review highlighted the uncertainty that can occur when counsellors who are aware of their feminist values, question their person-centred practice
Sustainable Silica Sols from Geothermal Sources and their Potential as Thermal Heat Storage Materials
No full textGeothermal energy is a renewable energy source but faces challenges such as silica scaling. This scaling leads to corrosion within process equipment and injection wells, ultimately reducing power generation efficiency and increasing maintenance costs. Therefore, extracting silica from geothermal sources is essential. A company, GeO40 TM, has developed a process for extracting silica as colloidal dispersion, which can be also converted into high value dry products such as composite adsorbents. This study aimed to establish an innovative, cost-effective, practical method for converting geothermal colloidal silica sol, into
environmentally friendly and sustainable CaCl2/Silica gel composite adsorbents to be used for thermochemical heat storage (TCHS) applications. Solar energy is also a renewable energy and is abundant during summer but insufficient in winter. TCHS systems can be incorporated into solar energy harvesting systems to address the seasonal energy imbalance by storing
excess energy and using it later. Composite adsorbents can be utilised in TCHS systems because they can store heat through exothermic adsorption and endothermic desorption reactions. By storing solar energy in TCHS systems, the need for fossil fuels for heating applications can be mitigated. In this study, composite adsorbents by using CaCl2 and geothermally derived colloidal silica were successfully prepared to be used for TCHS applications. The developed method involves precipitating colloidal silica in an alkaline medium with CaCl2 salt. The ions of the salt change the stability of the silica particles and simultaneously combine with the silica particles to produce composite adsorbents. Furthermore, CaCl2 is a very hygroscopic component that
raises the final composite adsorbent's water adsorption capacity (WAC), a desirable property of TCHS materials. The thermochemical characteristics of the composite adsorbents were evaluated at 55% RH between 20 and 150°C using simultaneous TG and DSC analysis. Sample 0.50-SD, with the highest salt concentration (48.2 wt.% CaCl2), exhibited the highest heat of desorption (1207.2J/g) and water adsorption capacity (90 wt.%), without any salt leakage. The volumetric heat
storage density (Qv) of the samples was calculated to be 172.7 kWh/m3. Using the imbibition technique, the sample's pore volume (Vp) was determined to be 108 cm3. Ten consecutive cycles of adsorption and desorption were conducted on the sample, showing no significant performance loss. Additionally, the sample was characterized by XRD, SEM, and FTIR. An open-type TCHS prototype was designed and built to assess the sample's TCHS performance on a larger scale. Under the conditions of input air at a 10 L/min flow rate, 60 % RH at 20°C for adsorption, and 150°C for desorption, only 38.674 g of 0.50 SD released 53.434 (± 1.215)
kJ of heat. Consequently, the adsorption bed's temperature rose by 21°C, while the exhaust air's temperature increased by 16°C, which could be utilized for space heating. Gravimetric heat storage density (QM) of 1382 (± 27) J/g and Qv of 155 (± 4) kWh/m3 were obtained for the sample, exceeding the minimal QV value of TCHS materials (150 kWh/m3) as suggested by
Courbon et al. (2017)1. The study suggests that composite adsorbents prepared using geothermally derived colloidal silica could offer an eco-friendly option for TCHS applications
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