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Agomelatine 3D-printed microneedles as a potential drug delivery system for the treatment of depression
No full textMicroneedles (MNs) are small devices that help to overcome the skin barrier and, thus, increase the effectiveness of transdermal drug delivery. This approach could be beneficial, especially for drugs characterised by low oral bioavailability, such as the antidepressant agomelatine (AGM), which is now only available on the market as an oral tablet. The aim of this study was to obtain agomelatine-loaded microneedle systems for potential use in the treatment of depression, using the 3D-printing methods. 3D-printing is an emerging technology enabling the manufacture of drug dosage forms or devices in a personalised, fast, and cost-efficient manner. Three 3D-printing techniques, different drug loading methods, and various shapes of microneedles were investigated along with the mechanical and physicochemical evaluation, release, stability, and toxicity studies of the obtained samples. Masked Stereolithography (MSLA) and PolyJet methods were successful in obtaining good-quality microneedle systems. Additionally, the MSLA method allowed for easy combining of the resin with the drug. The presence of the drug in the product was confirmed, and the drug release pattern depended on the loading method. Mechanical testing showed that Pyramid and Cone geometries were the most promising in puncture tests, and stability testing revealed the need for light- and moisture-resistant packaging. The formulations selected based on the obtained results will be further investigated on the way to create a transdermal alternative to agomelatine oral tablets and increase the effectiveness of depression treatment
Carbon trading markets: literature review on mechanisms, accounting, and market models coupled with energy markets
No full textTo tackle the climate change, various decarbonization strategies and approaches have been adopted to achieve low-carbon transition in the energy systems. Among them, carbon pricing plays a significant role in emission reduction through the carbon trading markets. This paper establishes a unified analytical framework that connects three core components: carbon market policies and mechanisms, demand-side carbon accounting methods, and coupled energy and carbon market models. It analyzes carbon trading market policy, mechanisms, and current practices in both primary and secondary trading, which is the basis of carbon accounting and market models coupled with energy markets. Then, the carbon accounting methods in the energy systems are reviewed from the demand side to support market clearing. Based on the mechanism and accounting, the coupled energy and carbon trading market models are reviewed by market participants, scope, structure, mechanisms, and coupled operation modes, serving as the foundation of energy and carbon market coupling. By integrating insights across policy, accounting, and modeling, this paper provides a coherent basis and practical implications for designing coupled energy and carbon markets. Key research directions of carbon-energy systems are identified to support the transition toward net-zero energy systems.javascript:void(0)
A scoping review of interventions to target anxiety in autistic adolescents
No full textAutistic adolescents experience anxiety at a higher rate than their non-autistic peers. A scoping review was conducted to explore what interventions have been examined in addressing anxiety in autistic adolescents. The present study utilised methodological guidelines for scoping reviews outlined by PRISMA. PsychINFO, Web of Science and ERIC were subject to a systematic search in February 2024. From an initial identification of 2,795 reports, 18 were included in the study based on the presence of: both pre- and post-quantitative measures of anxiety; the implementation of a specified intervention; and a sample of autistic adolescents. Categories of interventions, intervention efficacy and measures used to establish efficacy were explored. Findings suggest that the currently available studies are inadequate in terms of methodology: including sample size; lack of appropriate standardised measures; and follow-up. Implications for professionals are discussed.<br/
CRISPR/Cas9 methods for identification and validation of genes regulating BCR-mediated antigen uptake
No full textGenome-wide CRISPR screens are a powerful tool to interrogate and identify gene function in a wide variety of applications and cell types. CRISPR-Cas9 technology using pooled CRISPR single guide RNA (sgRNA) libraries enables genetic editing in bulk in a large population of cells of interest. After selection of gene-edited cells, phenotyping effects can be evaluated by quantifying abundance (over- or under-representation) of individual sgRNAs using DNA sequencing. In addition to cell survival, these assays can be applied to investigations of drug sensitivity, as well as almost any cellular process with a clear phenotypic read out, for example, receptor internalization, migration, autophagy, and differentiation. Here, taking as an example the identification of molecular components governing B-cell antigen uptake through the B-cell receptor, we describe whole-genome, small-scale, and in vivo validation methods to identify and validate genes regulating BCR-mediated antigen uptake.</p
Characterizing ‘Atmosphere’: exploring determinants of regular service attendance amongst integrated supervised consumption site clients in Vancouver’s Downtown Eastside
No full textBackgroundResearch has explored barriers and facilitators to supervised consumption sites (SCS) in Canadian settings. Despite this, little is known about what factors drive individuals to initiate and repeatedly attend specific SCS where multiple SCS options are available, such as in Vancouver’s Downtown Eastside (DTES). The aim of this study was to understand the structural, contextual, and operational determinants of regular SCS attendance during Canada's ongoing overdose crisis.MethodsRapid-ethnographic fieldwork was conducted over a six-week period at an integrated SCS in Vancouver’s DTES. This comprised an initial five-week period of non-participant observation (≈200 h) followed by a community consultation regarding the research design and question protocols. Qualitative data were then collected through five focus groups (n = 25) and 20 semi-structured interviews with regular service attendees with data analysed using thematic analysis.ResultsOur findings highlight four important factors related to regular service attendance. The service had a regular clientele who described their attendance as routinized, which they attributed to four distinct factors: (1) the accessible location, (2) the on-site auxiliary health and support services, (3) the diversity of harm reduction provision, and (4) the atmosphere. Exploring the concept of atmosphere in more depth showed that it was characterized by the safety, familiarity, and inclusivity experienced within the service. Together, these factors facilitated a strong sense of belonging among attendees regarding the service and its community of staff and clients.ConclusionWithin the context of an ongoing overdose crisis, our findings highlight SCS service characteristics which facilitate routinized engagement including accessibility, wrap-around support, comprehensive and tailored harm reduction, and an inclusive welcoming atmosphere. These insights can inform policy makers and service providers in scaling and developing effective, client-centred SCSs to reduce harm and promote wellbeing.<br/
Automated specular reflection detection using weak annotation for deep learning training
No full textThe presence of specular reflection on endoscopic images can hide important underlying features and limit extraction of clinically relevant information. To address this challenge, software-based solutions to remove specular reflection can be applied, which requires the specular reflection detection and removal. In this paper, we proposed an automated detection of specular reflection using ResUNet++, which was trained using weakly annotated data to overcome the lack of annotated data and the requirement of repetitive parameter adjustment. Analytical specular reflection detection methods: K-means clustering and histogram thresholding were evaluated to provide weak annotations to train the ResUNet++. The performance of ResUNet++ when trained using the weak annotations was compared with convolutional-based model, the simple Unet, and the state-of-the-art transformer-based model. Experimental results showed that fully unsupervised K-means clustering and histogram thresholding were sufficient to provide weak annotation for training the deep learning models. This shows that the fully analytical method can minimize human supervision on the creation of training data and on the training of the deep learning models. Moreover, we showed that ResUNet++ had better performance than the state-of-the-art when trained solely using weakly annotated data and faster inference time, making it suitable for future near-real-time applications. Our code is available at https://github.com/ajsugiarti/Weak-Annotation-Specs.<br/
Debate: Response to ‘Studying the regulatory space of public sector audit—the historical turn’ and the need for local government accounting history
No full textLocal governments play a vital role in managing and delivering services that directly impact the lives of citizens. In order to ensure that the allocation of public funds is delivering value for money and local governments are held to account for their decisions, the system requires good, audited accounting information. In the UK, however, local government audit is in crisis and is ‘hampering efforts to ensure that the billions of pounds per year spent by councils is properly accounted’ for (UK Parliament, Citation2023). As of 2025, the picture is no better. For example, the City of Birmingham, Europe’s largest local authority, remains technically bankrupt (Brackley, Citation2025) and, in 2024, the UK’s National Audit Office (NAO) was unable to obtain sufficient evidence from local governments to contribute to the UK’s Whole of Government Accounts for the financial year ending 31 March 2023 (HM Treasury, Citation2024). This resulted in a disclaimed audit opinion—an outcome the NAO described as unprecedented. Given that some form of UK local government audit has existed for centuries, with a more formalized system in place since the 1800s (Chandler, Citation2007; Dewar & Funnell, Citation2016; Midgley et al., Citation2024), these developments raise important historical and institutional questions. While Ferry et al. (Citation2025) note that researchers have long identified issues with UK local government audit and advocate for historical analysis to deepen our understanding of public sector institutions, we argue this historical lens should extend beyond audit. Local government financial management also includes accounting practices—for example financial reporting, budgeting, and management accounting—which shape governance and decision-making. The evolution of these practices over time has influenced today’s challenges in transparency, accountability, and financial sustainability. Therefore, we support the call in Public Money & Management by Ferry et al. (Citation2025) for a historical turn, but suggest expanding it to encompass the broader financial and management accounting practices of local governments. A more comprehensive historical perspective could yield deeper insights into the systemic issues facing local government management today
Art in an age of Non-Fungible Tokens: authenticity, value, and counterfeit
No full textThis chapter offers a comprehensive exploration of Non-Fungible Tokens (NFTs) within the art world, dissecting their implications on authenticity, value, and counterfeit. Drawing upon Walter Benjamin's seminal essay, "The Work of Art in the Age of Mechanical Reproduction," the chapter juxtaposes the realm of NFTs with Benjamin's observations on how mechanical reproduction influences the aura and politicization of art. The analysis is further enriched by a case study—Yuga Labs v. Ryder Ripps—examining the role of NFTs in political discourse and legal contexts. The chapter is organized into five key sections: 1) Revisiting the concept of 'aura' in the age of digital technology; 2) Tokenization and its impact on perceptions of authenticity; 3) Exploring the balance between value and reproducibility in NFTs; 4) Investigating how status and deception evolve in this new art ecosystem; and 5) A critical case study elucidating the intersection of NFTs and politics, thereby offering a nuanced understanding of art's politicization in the digital age. Conclusively, the chapter identifies NFTs as both a continuation and subversion of Benjamin's theories on mechanical reproduction, engaging in a complex interplay of democratization and exclusivity. The social transformation driven by NFTs not only disrupts traditional art paradigms but also introduces new layers of complexity to the intersections of community, commodity, and reality in the digital age. The rise of NFTs underscores a seismic shift in socio-political dynamics, potentially signaling a burgeoning culture war online that both democratizes and complicates the art world