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The protective effect of ambroxol against cyclophosphamide-induced acute kidney injury involves Nrf2/HO-1 signaling upregulation and suppression of oxidative and inflammatory damage
Get PDFCyclophosphamide (CP) is a widely used chemotherapeutic agent whose clinical efficacy is often limited by its side effects, including nephrotoxicity. Oxidative stress and inflammation are central to CP-induced acute kidney injury (AKI). Ambroxol (ABX), a clinically approved mucolytic agent, has demonstrated antioxidant and anti-inflammatory properties that may be repurposed for nephroprotection. This study investigated the protective effects of ABX against CP-induced nephrotoxicity in rats and explored the underlying molecular mechanisms. Adult male rats received ABX (20 mg/kg/day) orally for seven consecutive days, with CP (100 mg/kg, i.p.) given on the fifth day. CP administration resulted in significant renal dysfunction, as indicated by elevated serum creatinine, BUN, uric acid, and Kim-1 levels. Histopathological analysis revealed glomerular degeneration, tubular damage, collagen deposition, and iron accumulation. CP also induced oxidative stress, evidenced by increased MDA and decreased GSH, SOD, and catalase, along with upregulation of NF-κB, elevated TNF-α and IL-1β levels, and increased cleaved caspase-3 expression. ABX reduced MDA, enhanced antioxidant defenses, and suppressed NF-κB and pro-inflammatory cytokines. ABX attenuated apoptosis as evidenced by reduced caspase-3 expression and concurrently modulated redox-sensitive signaling by upregulating Nrf2 and HO-1 expression and activity while downregulating Keap-1. ABX showed in silico binding affinity toward NF-κB, Keap-1, and HO-1. In conclusion, these findings suggest that ABX confers nephroprotection against CP-induced injury primarily through its antioxidant, anti-inflammatory, and anti-apoptotic actions, partly via modulation of the Keap-1/Nrf2/HO-1 pathway. These findings support potential repurposing of ABX as a nephroprotective adjuvant during CP chemotherapy and warrant further clinical investigation
The Subsistence of Copyright in Dynamic Creations: A Proposal for the Fusion of Works
Get PDFThe fictitious world has become increasingly dynamic, with creative works being continuously expanded by sequels, spin-offs and supplementary material. Modern franchises such as Marvel and Star Trek describe an ever-growing and changing universe developed through numerous films, television programs, video games and books, where each entry forms part of the same overall creation. Despite this interrelationship between different creations, the law of copyright has been slow to acknowledge the interconnectivity of modern works and possesses no mechanism to protect the evolving creation. Characters and fictional worlds are constantly annexed with new information and are being continuously written to the extent they may be unrecognisable from their first appearance. However, it is questionable whether the current approach to the protection of these creations under copyright is adequate. This thesis adopts a hybridised methodical approach utilising doctrinal analysis and comparative legal research to assess the protection of dynamic works in the United Kingdom, the United States and the European Union. These systems are critiqued for their ability to protect creations such as the fictional universe and the evolving character for their full creative value, and from this, a new theory of copyright is developed. This thesis ultimately proposes that copyright can be reimagined as a living right that grows alongside a creation as it is further developed over time. In the case of universes such as Star Trek, it is argued that the accumulation of all entries in the canon fuses to form a single overarching copyright that is continuously expanded by new material. Similarly, the characters that change over time are protected for their entire evolution throughout the works in which they appear. As new material is added to a copyrightable work, these additions merely fuse to the existing right, allowing for a new and expansive form of copyright that protects the creative expression developed between works
A Systematic Mapping Review of Core Outcome Reporting in Surgical Research for Oesophageal Cancer
Get PDFOesophageal carcinoma is a rising global health burden, with surgical resection and perioperative chemotherapy forming the cornerstone of curative treatment. However, uncertainty persists regarding the optimal surgical approach, partly due to heterogeneity in outcome reporting, which hinders data synthesis and evidence-based decision-making. To address this, a core outcome set (COS) for oesophageal cancer surgery was developed through international consensus among clinicians and patients. This study systematically evaluates the uptake of these core outcomes in contemporary surgical research. A systematic review was conducted of randomised controlled trials and prospective cohort studies investigating oesophagectomy for oesophageal cancer, published between 2010 and 2024. The reporting of ten COS-recommended outcomes was assessed across eligible studies. Fifty-eight studies involving 22 260 patients were included (39 cohort studies; 19 RCTs). No study reported all 10 core outcomes. The median number of core outcomes reported was 4 (interquartile range 3–5). The frequency of individual core outcome reporting was as follows: in-hospital mortality (86%), conduit necrosis/leak (81%), respiratory complications (79%), overall survival (30%), ability to eat and drink (44%), quality of life (26%), inoperability (23%), reflux symptoms (21%), severe nutritional effects (19%), and need for reintervention (16%). No improvement in core outcome reporting was observed over the study period. Promoting COS implementation and improving methodological rigour is essential to ensure that future research reflects the priorities of both clinicians and patients, and facilitates meaningful evidence synthesis
Developing participant engagement within a MAT to empower senior leaders within schools and across the Trust
Get PDFThe thesis examines how a new multi-academy trust (MAT) facilitates the use of
participatory engagement (Woods, 2004) within and across a group of schools through
working with leadership teams. More specifically the study reviews how democratic
leadership (Liggett, 2025) can be applied to adapt the MAT operating model to increase
participation of senior leaders in decision making, to impact positively on their
relationships and role (Myers, 1993). This element of the research challenges and seeks
solutions to the top-down model of decision making inherent in MAT structures (Woods
and Simkins, 2014:42) which are unsuitable for a multisite organisation. To this end the
research study questions how the process of empowerment (Herrenkohl, 1999) can
enable senior leader contribution and collaboration for improvement, to support the
strategic development of each school and the Trust.
The research is presented from an insider perspective of a researcher, who is also the
CEO of the MAT. This study applies an ethnographic methodology framed within an
interpretivist approach over the phases of the MAT’s development. A range of qualitative
methods, including semi-structured interviews and focus groups were used to capture
participant voices, on their leadership journey where roles and responsibilities changed,
alongside the MAT’s growth and development. A Foucauldian lens was applied to the
analyse of data collected, focusing on the elements connected to power, which provided
a useful tool of analysis.
The findings highlight how MAT operating models can be adapted to facilitate democratic
leadership, while being flexible to respond to changing neoliberal agendas. The research
study highlights ways senior leaders can make a significant contribution to the strategic
development of a MAT and build a strong culture of interconnectedness (Kaplan and
Owings, 2013). Further, there is evidence of how senior leaders use these supportive
MAT structures to strategically respond to government agendas and align this to the
agreed vision for the MAT. However, the findings highlight the need for clarification on
future government policy direction in a diverse education system particularly at a local
level. This study offers an original contribution to knowledge in the leadership field within
a multi-site setting and adds to the existing understanding of leadership in multi-academy
trusts (MATs), particularly the senior leaders to make a significant contribution in the
leadership of an organisation
Label-Free Electrochemical Levodopa Detection via Dummy Imprinted Polymers for Advanced Disease Monitoring
Get PDFCurrent estimates see 25.2 million people living with from Parkinson’s disease (PD) worldwide by 2050, with no cure close to being available. With therapeutic LDp (LDp) use being the mainstay treatment for a vast proportion of individuals with PD, an effective protocol for managing medication in real-time, is not only essential but long overdue. Presented hereafter is a highly reproducible polymeric electrochemical detection platform with an economically viable production process that can specifically and selectively detect LDp at the relevant physiological range. Computational modelling of target-monomer interactions is employed to direct monomer selection and polymer synthesis. Testing the sensor platform within a dynamic range (5-50 μM) of LDp and its metabolite Dp (Dp) in a range of different sample media affords a 42% higher response of current change upon binding to LDp compared to Dp despite high structural similarity between the compounds. Furthermore, the sensor shows no significant difference when tested in different sample media, allowing this electrochemical sensor to operate across a range of different sample sources, further enhancing its adaptability and applicability in an ever-changing landscape of medical technology
Archetypes of SME Resilience: A Systematic Literature Review of Antecedents, Types and Outcomes of Resilience in SMEs
Get PDFThis systematic literature review makes three key contributions to resilience research in SMEs. First, it advances theory by synthesizing the Resource‐Based View and Dynamic Capabilities perspective to develop a novel two‐dimensional framework of SME resilience (Adaptability × Resource availability), identifying four distinct resilience archetypes: dynamic, complacent, vulnerable, and proactive. This framework addresses the theoretical fragmentation in existing resilience literature and provides a coherent classification system. Second, through rigorous analysis of 217 peer‐reviewed publications from 2019 to 2025 across multiple national contexts, the study systematically categorizes 11 primary antecedent groups, including innovation, dynamic capabilities, and organizational resources such as ambidexterity, adaptability, and absorptive capacity, offering the most comprehensive taxonomy of resilience determinants to date. Third, the research establishes empirically grounded linkages between resilience archetypes and performance outcomes, demonstrating that resilience drives creativity, operational efficiency, corporate performance, digital transformation, and reduces external dependency. The findings reveal a critical insight: effective resilience requires SMEs to balance adaptation speed against resource constraints, with prior crisis experiences enabling better institutionalization of learning and superior recovery outcomes. This framework provides scholars with a structured lens for future resilience research while offering practitioners actionable guidance on building context‐appropriate resilience capabilities. The study's multi‐national scope and crisis‐focused temporal frame enhance generalizability and practical relevance for SME managers navigating turbulent environments
AI adoption in Greater Manchester SMEs: challenges and opportunities
Get PDFThis research examines AI adoption among SMEs in Greater Manchester through a mixed-method approach combining interviews, focus groups, and survey data from Centre for Digital Innovation (CDI) participants.
The study reveals that while 65% of firms currently use AI for content creation, 55% for research, and 42% for data analysis, adoption remains significantly constrained by systemic barriers that extend beyond surface-level technical challenges. The primary obstacles to wider adoption are knowledge gaps, with 77% of respondents citing lack of understanding as a critical barrier, alongside time and resource constraints affecting 70% of firms, and cost uncertainty impacting 61%. Notably, privacy concerns emerged as far more significant than initially apparent: while only 30% of survey respondents explicitly cited privacy as a barrier, 83% of interview participants raised substantive privacy issues during in-depth discussions, suggesting that surface-level responses systematically understate deeper anxieties that intensify as firms progress towards implementation. Firms that successfully implemented AI through ecosystem engagement report substantial operational improvements, with 86% achieving productivity gains, 63% realising cost reductions, and 58% gaining competitive advantages. Success correlates strongly with participation in Greater Manchester’s AI ecosystem, particularly CDI programmes, peer learning groups, and structured networking. The most effective adoption model positions AI as a collaborator rather than competitor, exemplified by firms achieving efficiency gains with complete workforce acceptance by involving employees in identifying bottlenecks and co-developing solutions. Despite these successes, critical gaps persist in training provision, automation skills development, and executive engagement. While 94% of respondents seek practical workshops, current training is criticised as too intensive, too general, and lacking follow-up support. Additionally, 68% identify automation tools training (Power BI, Power Automate) as essential yet under-served, while 84% cite mentoring as crucial despite it remaining largely informal and unstructured. At the executive level, boardroom resistance driven by isolation from peer validation continues to block adoption even among firms that participate in awareness programmes. To accelerate Greater Manchester’s position as a leading AI innovation hub, the research recommends restructuring training for practical implementation rather than awareness-building, formalising mentoring systems to create sustainable peer support networks, addressing cost transparency and executive-level engagement through targeted interventions, and bridging public-private AI ecosystems to enhance visibility and community trust in AI deployment
The missing link in connective tissue diseases care: addressing the shortage of specialist nurses in the UK
Get PDFConnective tissue diseases (CTDs), such as systemic lupus erythematosus (SLE),
systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), and overlap
syndromes, are among the most complex, high-risk, and resource-intensive conditions
in rheumatology. SSc remains the rheumatic disease with the highest morbidity and
mortality, despite improved survival. [1] Despite advances in pharmacological
therapies, a critical workforce gap persists in the UK: the shortage of specialist nurses
dedicated to CTD care, which limits the translation of medical advances into improved
outcomes
L’esperienza della Collana Diritto e Religioni (Luigi Pellegrini Editore) a venti anni dalla sua fondazione
No full textLe Collane di diritto ecclesiastico e canonic
Il ricorso per violazione di norme di diritto
No full text1. Violazione di legge e funzione cassatoria – 2. Quando la violazione delle norme processuali configura un error in iudicando (de iure procedendi) deducibile con il n. 3 e quando invece rifluisce nell’error in procedendo da censurare nell’ambito del n. 4 dell’art. 360? – 3. Le norme di diritto rilevanti – 3.1. Norme di legge, regolamenti, usi 3.2. – Diritto straniero, diritto antico, diritto europeo – 3.3. Consuetudine giudiziaria, soft law – 3.4. Diritto vivente – 4. Contratti e accordi collettivi nazionali di lavoro – 5. Violazione e falsa applicazione: progressivo venir meno dello spessore teorico di un risalente distinguo concettuale, odiernamente privo di ricadute pratiche concrete – 6. Violazione di legge e contenuto-forma del ricorso – 7. (Segue) L’art. 360, comma 1°, n. 3, c.p.c. e le “zone grigie” – 7.1. Norme elastiche, clausole generali, concetti giuridici indeterminati – 7.2. Applicazione delle norme di interpretazione degli atti negoziali diversi dai contratti collettivi (artt. 1362 ss. c.c.) – 7.3. Violazioni della regola dell’onere della prova (2697 c.c.), delle norme sulle prove presuntive (presunzioni semplici) e sulle massime di esperienza (art. 115, comma 2°, c.p.c.) – 7.4. Violazione delle norme sulle prove legali – 7.5. Violazione delle regole che pongono limitazioni alla prova – 7.6. Violazione del giudicato “esterno” (e la sua prova) – 8. Il controllo del giudizio di equità – 9. Effetti della decisione di accoglimento del motivo di cui al n. 3: le due ipotesi previste dall’art. 384 c.p.c. – 10. Violazione di legge e filtro di ammissibilità