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Expression of extracellular matrix protein in advanced keratoconus and the normal human cornea
No full textBackground: The pre-Descemet layer (Dua’s layer) (PDL/DL) and the Descemet membrane (DM) have the highest expression of elastin in normal corneas. Reduced expression of elastin occurs in the corneal stroma of patients with keratoconus (KC). This study aimed to examine the expression of elastin and that of other extracellular matrix (ECM) components, and proteoglycan proteins in the PDL/DL and DM in advanced KC. Methods: Corneal tissue obtained from four subjects with KC who underwent penetrating keratoplasty was compared with tissue from four normal corneas. The tissues were sectioned and analyzed with specific markers for extracellular matrix proteins and proteoglycans—namely, elastin, collagens I, IV, and VI, fibulin-2, and decorin—using immunohistochemical analysis. Fluorescence intensity was measured using ImageJ software and compared to controls. Results: The expression of elastin was significantly reduced in the PDL/DL and DM in KC cases compared to controls. Concurrently, an increased expression of elastin was noted anteriorly in the subepithelial region. Expression of collagen IV, collagen VI, and decorin was reduced in the PDL/DL and DM, whereas expression of collagen I and fibulin-2 was unaltered in KC cases compared to controls. Conclusion: The significant reduction of elastin in the PDL/DL and DM in cases of advanced keratoconus with acute corneal hydrops (ACH) may play a crucial role in the pathology of KC and the subsequent onset of ACH. Furthermore, elastin is considered to be pivotal in the disease progression, as keratoconus typically starts with a posterior elevation affecting these two layers
Regional Differences in Calcium Dynamics in the Intact Lens: The Role of TRPV Channels in Lens Calcium Regulation
Get PDFPurpose: To establish an imaging approach capable of mapping Ca²⁺ dynamics across different regions of the intact ocular lens, and to determine the functional contributions of TRPV1 and TRPV4 channels to extracellular Ca²⁺ influx in epithelial and differentiating fiber cells.Methods: Rat lenses were mounted in a recording chamber with zonular attachments intact and imaged using confocal laser-scanning microscopy. Epithelial cells were loaded with Cal520 AM, while fiber cells were microinjected with Fluo-8 pentapotassium salt. Region-specific changes in intracellular Ca²⁺ were monitored in response to pharmacological manipulations designed to deplete endoplasmic reticulum (ER) Ca²⁺ stores, activate G-protein coupled receptors, or stimulate extracellular Ca²⁺ influx via mechanosensitive TRPV1 and TRPV4 channels.Results: Central and equatorial epithelial cells exhibited biphasic Ca²⁺ responses to thapsigargin, consistent with ER-dependent release and store-operated Ca²⁺ entry, whereas differentiating fiber cells lacked detectable ER-dependent Ca²⁺ mobilization. In epithelial cells, TRPV4 activation with GSK1016790A (GSK) induced transient Ca²⁺ influx, whereas exposure to the TRPV1 agonist capsaicin (Cap) had no effect. In contrast, fiber cells displayed robust extracellular Ca²⁺ entry in response to TRPV1 and TRPV4 activation by Cap and GSK, respectively. These responses were abolished in Ca²⁺-free conditions or by pre-incubation with TRPV1- or TRPV4-specific antagonists.Conclusions: This study establishes a confocal imaging approach for simultaneous analysis of Ca²⁺ dynamics in epithelial and fiber cells of the intact lens. Our findings reveal region-specific differences in Ca²⁺ regulation and provide insight into how TRPV1 and TRPV4 activate signaling pathways that regulate lens ion homeostasis and water transport to maintain optical properties
Centrifuge modelling considerations of laterally loaded monopiles in sand
Get PDFThe large-diameter monopile is a commonly used foundation concept for offshore wind turbines. The advantages of geometrical simplicity and reliable performance make it often the most attractive solution. Despite the concept’s high popularity, optimisation of the current design models can still be made. To address fundamental understanding of modelling effects in centrifuge testing of laterally loaded monopiles in sand, a large coordinated centrifuge-testing programme across nine different centrifuge centres worldwide has been conducted. This paper presents firstly the results of a local benchmark modelling of model test series performed in two centrifuges and secondly the results of global benchmark testing across the nine centrifuges. The results highlight the reliability of centrifuge testing as it was possible to model a similar prototype response in both the local and global benchmark tests, despite differences in the experimental setups and pile geometries. Furthermore, as examples of the modelling technique, two different cases are presented, one showing the effect of installation and one showing the effect of pile penetration depth. Finally, recommendations are provided to enhance centrifuge testing of monopile response under complex loading
A Systematic Review of Articles in the Leadership and Policy in Schools Journal Published Between 2010 and 2024: Future Directions for the Journal and the Field
No full textThis systematic review examines the contribution of the *Leadership and Policy in Schools* (LPS) journal to Educational Management Leadership and Administration (EMLA) from 2010 to 2024. We analyzed publication trends, geographic distribution, high-impact scholars, and the journal’s conceptual and intellectual structure. Using VOSviewer and Excel, we identified 515 peer-reviewed articles, highlighting a sharp growth in publications in 2019, 2022, and 2023. The journal’s knowledge production has been dominated by English-speaking countries, with contributions from Israel, Hong Kong, and Türkiye. Key themes include leadership’s impact on outcomes, instructional leadership, reform, social justice, and school improvement. A qualitative synthesis of the 20 most cited articles revealed three dominant themes: leadership and school outcomes, equality and social justice, and school structures. This review outlines significant contributions and suggests future directions for both the journal and the broader field
Miniaturized High-Throughput Amorphous Solid Dispersion Screening via Picoliter Volume 2D-Inkjet Printing of Formulation Microarrays
No full textMany new drug substances exhibit poor physicochemical properties and therefore require significant time and material resources to develop into safe and efficacious medicinal products. This typically involves exploring a large amount of compositional space and may require excessive amounts of drug compounds, which may not be adequate at the early stage of drug development. Scaled-down screening methods have been used as a cost-effective approach to the early-stage formulation. However, even the most material-efficient methods used in product development require milligrams or grams of drug material, which is often not available until relatively late in the lead optimization process. Herein, we report the application of picoliter inkjet printing of drugs and polymers from solution to create addressable formulation microarrays. This allows the efficient screening of drug-polymer compositions while only requiring micrograms or less of the drug substance. A total of eight model compounds, namely, carbamazepine, griseofulvin, saccharin, theophylline, 4-aminobenzoic acid, caffeine, salicylic acid, and benzocaine, were screened against seven commonly used amorphous solid dispersion (ASD) matrix polymers at 5% w/w composition intervals in the range of 5-80% w/w, with five replicates each. Each dispensed spot contains a total of only 1 μg of material (model compound and/or polymer). Across the tested ASD formulations, we ranked the different polymers based on their ability to hinder drug recrystallization across different compositions. Also, we identified distinct physicochemical behaviors in their crystallization kinetics, such as moisture resolubilization. We expect this approach to enable the rapid time- and material-efficient development of new amorphous solid dispersion formulations in an industrial setting
Optimizing circular economy practices in construction: a systematic review of material management strategies
No full textPurposeAlthough circular economy (CE) principles are gaining increasing attention, a systematic understanding of material management strategies for an effective CE transition in construction is still lacking. This review addresses this gap by examining global construction practices, focusing on waste reduction and recycled materials. The study identifies key material management strategies for optimizing CE practices, supporting an integrated sustainable approach in construction.Design/methodology/approachA bibliometric analysis of 17,600 papers published from 2015 to 2022 was conducted, leading to an in-depth investigation of 44 relevant articles. The systematic review revealed material management strategies such as on-site sorting, deconstruction planning, modular building and reverse logistics, which were evaluated using quantitative and qualitative comparative analysis.FindingsChina emerges as a leader in construction material management research, reflecting significant global interest. Key findings indicate that strategies like design for deconstruction (DfD), minimization at design and modular construction achieve higher waste reduction, while building information modelling and on-site sorting show lower cost-saving potential. This research uniquely validates the structural feasibility of the most common recycled materials through qualitative comparative analysis of studies examined, emphasizing the critical role of CE design principles in sustainable construction.Practical implicationsThe study validates circular design concepts like DfD, minimization of resource use at design and modularization, which facilitate closed-loop planning. Circular construction systems are technically and economically feasible, underscoring the need for mass implementation. Recommendations on material management and transition strategies are provided for stakeholders based on CE principles.Originality/valueThis study synthesizes recent research on sustainable material management, uniquely validating recycled materials’ structural viability and comparing material management strategies for optimal waste reduction and cost savings. It emphasizes multi-stakeholder initiatives spanning policy, industry and academia, providing practical insights to embed CE practices in sustainable construction
A critical review on deactivation dynamics in methane combustion catalysts: challenges and innovations for palladium-based systems
No full textPalladium-based catalysts are pivotal for catalytic methane combustion, crucial for decarbonization efforts. Yet, industrial use is limited by three critical deactivation mechanisms: water inhibition, thermal sintering, and sulfur poisoning. This review synthesizes mechanistic insights and mitigation strategies holistically. Water inhibition below 500°C arises from hydroxyl species blocking active Pd sites, reversible via hydrophobic supports (e.g. zeolites) or oxygen- mobile promoters (Ce-Zr oxides) to enhance lattice oxygen mobility. Sintering from PdO agglomeration above 300°C, is countered by core-shell architectures (e.g. Pd-CeOx@SiO₂) and strong metal-support interactions with reducible oxides (CeO₂, perovskites). Sulfur poisoning via sulfate formation is mitigated through sulfur-resistant perovskites and dynamic Pd-perovskite frameworks that prevent PdSO₄ accumulation. Key innovations include engineered bimetallic alloys (Pd-Pt) to stabilize active Pd⁰ states, hydrophobic coatings to limit hydroxyl adsorption, and sorbents (CaO) for in situ water removal. Advanced characterization (AP-XPS, DRIFTS) reveals water’s dual role in hydroxylation and sulfur mobility, while regeneration strategies (pulsed redox cycles) extend catalyst lifetimes. By integrating material design, mechanistic understanding, and operational optimization, this work establishes a roadmap for durable Pd-based catalysts, advancing methane utilization in turbines, vehicles, and industrial systems. These breakthroughs address a critical gap in catalysis science, enabling efficient methane abatement to support global emission reduction goals
A LSTM-model based approach for long-term forecasting of high-rise residential building integrated photovoltaic system
No full textBuilding Integrated Photovoltaic (BIPV) is a promising technology for increasing large-scale building energy efficiency. However, most of the previous studies focus on short-term prediction due to limitations in the amount of data or the buildings themselves. This paper explores the potential of long short-term memory (LSTM) modeling for long-term prediction of high-rise residential BIPV systems. By utilizing a scale model of a real high-rise BIPV building in Shanghai, a high-density city in China, and combining simulated power generation data with on-site meteorological data, the effectiveness of LSTM in capturing complex patterns in PV system data is demonstrated. In addition, the integration of LSTM modeling with rigorous data preprocessing and simulation with the Ladybug plugin in Grasshopper can improve the reliability and efficiency of long-term solar forecasts. The results indicate that predictions spanning up to one year provide valuable insights into the planning and construction of BIPV high-rise residential communities in high-density cities in China. The proposed novel methodology is effective in long-term forecasting of high-rise residential BIPV systems, which contributes to the widespread adoption of renewable energy technologies in urban environments
“All that I've been through has made me who I am”: youth conceptualisations of personal recovery in mental health
No full textBackground: Youth is a transitional period from 15 to 24 years involving developmental milestones that may be adversely affected by mental health (MH) concerns. Clinical interventions tend to focus on the reduction or cure of illness-based psychiatric symptoms. However, national and international mental policy focuses on promoting well-being and self-management through personal recovery. The leading framework of personal recovery in adults is CHIME, an acronym used to denote five key processes – Connectedness, Hope, Identity, Meaning and Empowerment. The extent to which CHIME reflects the experience of personal recovery in youth is under-researched, yet the framework often underpins youth mental health services. Method: The present study uses a qualitative methodology to analyse interviews with 16 youth referred for treatment. Interviews focused on the lived experiences of youth recovery and its alignment with the CHIME processes and were analysed using a hybrid inductive and deductive reflexive thematic analysis. Results: The CHIME framework was relevant to youth recovery in two ways: restoring what was perceived to be lost (restorative processes) and encouraging resilience (resilience processes). Adaptations to the CHIME framework for youth included an increased emphasis on the role of family and friends, support for grieving processes and support for identity formation during the recovery journey. Conclusion: An adapted CHIME framework for youth can underpin targeted recovery-oriented care to support youth in moving towards emerging adulthood successfully while managing mental health concerns
"Joining the dots" Exploring issues of health, work and climate in Nottingham City
Get PDFClimate change, decent work and health outcomes have been linked within the academic discourse, but what does this mean for communities on a local scale? Here we present findings from two community-focused workshops with participants from The Meadows and Sneinton in Nottingham City, that combined digital data presentation and graphic facilitation to aid discussion of the complex topics. The main findings highlight how there are clear and well-defined links between health and work, but the relationships between work and climate, and climate and health are less clear in Nottingham City. Overall, the participants highlighted community, access, waste, housing and greenspaces as key areas associated with the issues of climate, work and health. Participants also called for more creative solutions to addressing intersectional risks and the need for more research to greater establish links between the three issues
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