21827 research outputs found
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Geometry driven fluid dynamics and cytocompatibility of 3D printed TPMS bone scaffolds
Get PDFTriply Periodic Minimal Surfaces (TPMS) can mimic the complex architecture of trabecular bone while facilitating controlled fluid transport and cellular colonisation. This study integrates computational fluid dynamics (CFD), laser powder bed fusion (L-PBF), and in vitro cell assays to evaluate the structure-function relationship of four Ti6Al4V TPMS scaffolds informed by Schwartz Primitive (SSC), Lidinoid (LSC), Gyroid (GSC), and Diamond (DSC) featuring 60% porosity. CFD simulations at inlet velocities ranging from 0.001 to 0.01 m/s revealed architecture-specific permeability ranging from 1.89 × 10 −9 m 2 (DSC) to 4.29 × 10 −9 m 2 (SSC) at low flow rates, with a consistent inverse relationship between flow velocity and permeability (R 2 > 0.99). Mid-plane velocity fields highlighted scaffold-specific vortex formations and nutrient mixing dynamics, with SSC exhibiting pronounced swirling zones, promoting fluid homogenisation. In vitro cytocompatibility assessed via MTT assay on U-2OS osteosarcoma cells showed >85% viability across all geometries after 24 h and >88% after 7 days, with the LSC scaffold exhibiting the most consistent viability (101.8 ± 7.7%) and SSC showing significant improvement over time (87.2 ± 3.3% to 121.4 ± 6.2%, p < 0.015). Immunofluorescence imaging confirmed cell attachment across all architectures, with GSC and DSC supporting uniform cytoskeletal spreading and enhanced cell-pore integration. Degradation studies in PBS at 37 °C showed that DSC scaffolds underwent the highest mass loss (4.42% at day 7), correlating with their larger surface area, while pH monitoring suggested early ion release followed by buffering over time. These results demonstrate that scaffold topology significantly impacts permeability, degradation, and biological performance with SSC and GSC emerging as promising 3D printed microenvironments
PLGA-Encapsulated Mitochondrial Hydrogen Sulphide Donor, AP39, Resolve Endothelial Inflammation via Mitochondria-Targeted Bioenergetic and Redox Modulation
Get PDFVascular inflammation and endothelial dysfunction are key drivers in the development of cardiovascular and neurovascular diseases. Mitochondrial dysfunction and oxidative stress further amplify inflammatory cascades, emphasising the need for targeted strategies that restore endothelial homeostasis at the subcellular level. Hydrogen sulphide (H2S) donors, such as AP39, offer cytoprotective benefits but are limited by short half-life and rapid release of the active compound, H2S. We developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating AP39 (PLGA-AP39) to achieve sustained, mitochondria-targeted H2S delivery. Nanoparticles were characterised by size, polydispersity, zeta potential, encapsulation efficiency, and in vitro release kinetics. Human umbilical vein endothelial cells (HUVEC) were exposed to TNF-α to induce inflammation, followed by treatment with free AP39 or PLGA-AP39. Anti-inflammatory effects were assessed by measuring IL-6, IL-8, and TGF-β levels. Mitochondrial function was evaluated using a Seahorse XFe24 Analyser, membrane potential assays, and mitochondrial ROS detection. Moreover, we investigated vascular function by analysing capillary-like tube formation and wound closure in response to treatments. PLGA-AP39 nanoparticles displayed a uniform size (~227 nm), low PDI, and high encapsulation efficiency (>78%). Sustained AP39 release was observed over seven days. Treatment with PLGA-AP39 significantly restored TNF-α-induced endothelial dysfunction and reduced TNF-α-induced release of IL-6, IL-8, and TGF-β compared to untreated controls. Seahorse analysis revealed restoration of maximal respiration and increased spare respiratory capacity. Encapsulated AP39 also preserved mitochondrial membrane potential and reduced mitochondrial ROS production, demonstrating enhanced protection against inflammation-induced metabolic dysfunction. This work establishes a novel nanoparticle-based strategy for prolonged, mitochondria-specific H2S delivery to counteract vascular inflammation and enhance endothelial bioenergetics. The results from this work are pioneering in the generation of a novel delivery method for H2S donors employing PLGA and represent a promising therapeutic avenue for treating chronic vascular inflammatory disorders
Familial pneumothorax in twins with Tatton-Brown-Rahman DNMT3A overgrowth syndrome
Get PDFSpontaneous pneumothorax is a common respiratory presentation that may signal underlying genetic disease. Familial pneumothorax occurs in ~10% of primary cases, yet 75% remain genetically unclassified. We report identical twin brothers presenting with spontaneous pneumothoraces in adulthood, leading to a diagnosis of Tatton-Brown-Rahman syndrome (TBRS), a DNMT3A-related overgrowth disorder not previously associated with pneumothorax. Both individuals exhibited tall stature, mild intellectual disability, hypermobility, and cardiac abnormalities. Whole genome sequencing identified a rare de novo DNMT3A missense variant (c.1585 G > A, p.D529N) absent from population databases and predicted to be damaging. Methylation profiling confirmed genome-wide hypomethylation consistent with impaired DNMT3A function, supporting pathogenicity. No variants were found in known familial pneumothorax genes. Apical blebs observed at surgery and connective tissue features suggest a mechanistic link between TBRS and pneumothorax, analogous to other monogenic connective tissue disorders. This case expands the phenotypic spectrum of TBRS and highlights the importance of genetic evaluation in familial pneumothorax. Diagnosis enables personalised care, including surveillance for extrapulmonary complications such as aortic root dilatation and haematological malignancy. Our findings suggest that TBRS should be considered in patients presenting with pneumothorax, tall stature, and neurodevelopmental features. Further cases are needed to confirm this association and refine clinical management strategies
Strategic Sustainability Reporting, Impression Management and Board Gender Diversity: Evidence From Luxury Fashion Industry
Get PDFThe study aims to examine the impression management (IM) of the luxury fashion industry through communications using annual reports and the influence of board gender diversity (BGD). Using a computational approach with Python and Natural Language Processing on sustainability practices and performance of 19 luxury fashion companies from Top 100 global luxury brands over the period 2020 to 2022, it evaluates sustainability dimensions and the BGD's influence on IM practices. The findings reveal a notable increase in IM disclosure over the years and highlight a positive association between IM and sustainability disclosures, illustrating the use of disclosure language strategically to enhance corporate sustainability and reputation. They uncover that the boards with a higher proportion of female directors are positively associated with IM practices. This study contributes to the understanding of IM strategies in sustainability disclosure within the luxury fashion industry and underlines the crucial role of female directors in fostering ethics
Understanding the quality-of-life impacts of ocular surface disease
Get PDFPURPOSE: This study aimed to explore the lived experience of adults with different types of ocular surface disease (OSD) to understand their quality of life (QoL) impacts. METHODS: Lived experiences of participants diagnosed with aqueous deficient dry eye disease (DED), meibomian gland dysfunction (MGD), anterior blepharitis, neuropathic corneal pain (NCP), ocular surface involvement of autoimmune disease and contact lens discomfort (CLD) were explored using in-depth, semi-structured interviews. Participants were recruited from specialized dry eye clinics in Australia, United Kingdom, as well as online support groups. Thematic analysis of interviews was performed to identify key QoL themes. RESULTS: Sixty-two participants participated in an in-depth interview (median age: 46 years, range 22-78). There were 16 male participants (median age: 38.5 years; range: 23-74) and 46 female participants (median age: 50 years; range 22-78). The distribution of participants by condition as follows: DED - 9, MGD - 12, anterior blepharitis - 8, NCP - 8, ocular surface involvement of autoimmune disease - 14, and CLD - 11. Thirteen major QoL themes emerged. The most significant impact observed was on the emotional wellbeing with participants describing feelings of annoyance, depression, frustration, reduced self-confidence, worry, and anxiety related to their condition. Many expressed concerns about the chronic nature of OSDs, characterised by persistent symptoms and lifelong treatment. Economic impact extended beyond direct medical expenses, affecting employment, and productivity. Participants also described difficulties with daily activities, driving and mobility. Coping strategies included adjustments to their daily routine and environment. CONCLUSION: OSDs significantly impact multiple aspects of an individual's life. These findings lay the foundation for developing a comprehensive and technologically advanced patient reported outcome measure (PROM) tailored to individuals with OSDs. Addressing these QoL concerns through targeted interventions and policy updates will be crucial in enhancing patient care and optimizing disease management
Robust multi-period blood inventory routing under multiple uncertainties
No full textWe study a multi-period blood inventory routing problem that integrates production, inventory, and distribution decisions under uncertainties in demand, donation supply, and travel times, all while accounting for the limited shelf life of blood products. Our model captures transportation efficiency through a disutility measure based on vehicles’ arrival times at hospitals, and addresses supply–demand imbalances by allowing selective rejection of service requests at a high penalty cost. We formulate a robust optimization model that simultaneously determines production quantities, inventory levels, hospital service selections, and vehicle routing for each period. The objective is to minimize the total cost over the planning horizon, which includes worst-case inventory holding, wastage, and transportation costs, unserved demand penalties, and overall transportation disutility. To obtain an exact solution,we propose an integrated algorithm within the L-shaped framework that combines Benders decomposition with a branch-and-price-and-cut (BPC) scheme. This approach decomposes the robust model into a master problem and period-specific subproblems. For a given master solution, we first use constraint programming to verify the feasibility of the subproblems, and then, if feasible, solve them with a tailored BPC algorithm to generate Benders cuts that eliminate suboptimal master solutions. Extensive numerical experiments, including a case study at the Blood Center in Chongqing, demonstrate the effectiveness of our approach. Our analysis quantifies the benefits of incorporating uncertainty and robustness while providing managerial insights through a systematic evaluation of various parameters
Promoting inclusive recruitment within children’s social care research trials: lessons from the Reflective Fostering Study’s InCLUDE project
No full textIt is widely acknowledged that those participating in clinical trials generally do not represent the intended beneficiaries of that research. This pattern is mirrored in trials within children’s social care settings, where underserved communities are often not adequately represented. This paper shares learning from the Reflective Fostering Study, a clinical trial that evaluated the clinical and cost-effectiveness of the Reflective Fostering Programme, a support programme for foster and kinship carers. The trial included a distinct workstream, the ‘InCLUDE project’, aiming to better understand the barriers preventing specific underserved groups (male carers, South Asian and kinship carers) from taking part in the study, as well as identifying facilitators for their active and meaningful involvement. Learning was used to iteratively modify the recruitment processes within the trial, with the aim of improving representation of groups initially underrepresented. Over the course of the trial, representation of specific underserved groups improved, as evidenced by the analysis of study data from the later phases of the study and compared to national data. Drawing on all the learning from InCLUDE, the paper presents broader recommendations for enhancing inclusion and representation in future children’s social care research trials
Patients’ and carers’ perspectives on unrestricted weight-bearing and early mobilisation after hip fracture surgery in Saudi Arabia: a qualitative study
Get PDFPurpose This study explored how patients and carers experienced weight-bearing instructions and mobilisation timing following hip fracture surgery. It also examined their views on unrestricted weight-bearing and early mobilisation and perceived barriers to these practices. Methods Semi-structured interviews were conducted with 25 participants (18 carers, 7 patients) from Saudi Arabia’s healthcare systems. The data were analysed using inductive thematic analysis. Results Participants viewed unrestricted weight-bearing and early mobilisation as important when prescribed by clinicians, reflecting strong trust in professional judgement. However, their experiences showed inconsistency in clinical instructions and how these were understood and implemented. Implementation was shaped by clinical instructions, clarity of communication, perceived safety, and patients’ physical capacity and psychological state. Concerns about falls were mostly reported by carers as barriers to mobilisation, although some patients also described fear shaped by past injuries, difficult recoveries, or uncertainty about undiagnosed complications. Carers played a key role in encouraging mobilisation, adapting instructions, and maintaining continuity of care when weight-bearing and mobilisation were challenging for patients. Conclusion To support adherence to weight-bearing and mobilisation instructions, clinicians should provide timely, consistent prescriptions aligned with evidence-based guidance. Communication must be inclusive to support understanding, confidence, and autonomy among patients and carer
The securitized synagogue: antisemitism, security, and Jewish places of worship in contemporary Europe
Get PDFThis research paper examines safety perceptions among Jewish minorities at European places of worship (PoWs) between October 2023 and April 2024. The study utilizes PROTONE survey data from Belgium (N = 571), Germany (N = 734), Spain (N = 1198), and Italy (N = 895), specifically comparing 79 Jewish and 3,318 non-Jewish respondents. Qualitative components include 43 interviews with faith leaders (including 16 Rabbis) and five focus groups conducted in Brussels, Berlin, Rome, and Madrid. Grounded in postsecularism, vulnerability assessment models, and securitization theories, the research explores how threats and security measures shape feelings of insecurity. Key findings indicate that violent attacks and property damage strongly predict perceived unsafety. Comparative analysis reveals that Jewish respondents perceive significantly higher levels of anti-Semitic hostility and hate crimes than non-Jewish groups perceive regarding their own communities. While positive community and authority relations marginally mitigate fear, structural vulnerabilities like outdated infrastructure persist. Attitudes toward security vary; CCTV is universally accepted, but armed guards raise concerns about carization. Generational differences appear, with younger Jewish individuals reporting notably higher anxiety and avoidance behaviors. The study contextualizes these findings within broader socio-cultural and political processes, highlighting the dual role of Jewish PoWs as essential and sacred sites for spiritual fulfillment and robust local communal resilience
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