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Taming the Achilles’ heel: A chemical and structural design to address off-target effects in siRNA therapeutics
Full text linkTreat-to-target: optimising outcomes for hidradenitis suppurativa
No full textThe concept of Treat-to-Target (T2T) is described in the setting of hidradenitis suppurativa (HS), a condition requiring this approach to improve current symptoms and potentially prevent disease progression and scarring. A T2T algorithm is outlined using investigator global assessment and HS-specific quality of life to measure disease activity and drive treatment switches when the response is insufficient
Digital storytelling as a memory-making intervention for children and families in paediatric palliative care in Ireland: an adaptation study
Full text linkMemory making is a core component of holistic paediatric palliative care. However, traditional artifact-based keepsakes (e.g., handprints) are often passive and lack the developmental and cultural sensitivity needed for meaningful engagement. A more participatory, narrative-based, multimedia approach, such as digital storytelling, is therefore required. Following the ADAPT framework (Steps 1–2: Intervention-Context Fit and Planning Adaptations), this study adapted a U.S. developed digital storytelling intervention for children with life-limiting and life-threatening conditions and their families in Ireland. Methods included a literature review, stakeholder consultations (n = 21), co-production workshops, and the development of a facilitator training programme and delivery manual. The adaptation team comprised diverse stakeholders, including paediatric palliative care clinicians, creative practitioners, bereaved parents, and representatives from national children’s palliative care organisations. The adaptation, conducted in partnership with Barretstown Children’s Charity, yielded six key principles for the final intervention: emotionally safe framing, family and sibling inclusive design, flexible and multimodal participation methods, selective integration of therapeutic recreation, family-led pacing and facilitator preparedness. The final design incorporates play, visual, and audio elements to support meaningful, co-created engagement from all family members. Comprehensive training materials and a facilitator manual were developed to ensure fidelity and safety. This adaptation study presents a culturally and developmentally resonant digital storytelling intervention for Irish paediatric palliative care. Findings highlight the critical role of co-production, cultural fit, and emotional flexibility in successfully implementing complex psychosocial interventions for this population. Future pilot testing will evaluate the intervention’s feasibility, acceptability, and psychosocial impact
The island of Ireland and the European Union: Past, present and future
Full text linkThis Special Collection explores the evolving relationship between the island of Ireland and the European Union (EU) against a backdrop of profound political, economic and geopolitical change. Brexit, shifting EU security priorities, growing global trade uncertainty and other challenges have disrupted long‐standing patterns of Irish engagement with Europe, with distinct consequences for both the Republic of Ireland and Northern Ireland. Addressing themes ranging from crisis governance and external relations to peacebuilding, taxation and identity politics, the contributions highlight the diverse ways in which Ireland's European future is being reshaped. Organised around the dual contexts of the Republic and Northern Ireland, and complemented by cross‐border analyses, this Special Collection highlights the importance of an all‐island perspective. Collectively, the articles shed light on broader questions concerning small states in the EU, the management of crises, the long and demanding journey of building peace and the interplay between domestic and European change, while emphasising both Ireland's vulnerabilities and its agency as it navigates an uncertain European and global order
Molecular genotype-phenotype correlation in ACTB- and ACTG1-related non-muscle actinopathies
Full text linkRecent advances in Mendelian genomics reveal the importance of variant-level characterization of allelic disorders. Non-muscle actin isoforms, encoded by the genes ACTB and ACTG1, are the most abundant intracellular proteins, but historically, they are often regarded as merely being “housekeeping” molecules. Here, we illuminate the extraordinary clinical heterogeneity and complex pathobiology of genetic non-muscle actinopathies. To do this, we combine human genomics studies with molecular biology. Strikingly, variants in ACTB and ACTG1 isoforms generate at least eight distinct clinical disorders. A subset of disease-associated missense variants causes dysregulated actin polymerization-depolymerization and neuronal migration defects. In contrast, nonsense, frameshift, and missense variants enhancing protein degradation cause milder phenotypes or are benign. These results emphasize the essential functional aspects of the non-muscle actin isoforms. Critically, they additionally constitute a template for the personalized genetic variant-level-driven management of the pleiotropic allelic single-gene disorders
Exploring recovery from anorexia in autistic adults: a qualitative study
Full text linkObjectives To examine the barriers and facilitators of anorexia nervosa (AN) recovery in adults with autism.
Design Qualitative study using semi-structured interviews with autistic adults who identified as being in recovery or having recovered from AN.
Setting Participants were recruited via advertisements on social media and an eating disorder (ED) forum. Online Zoom interviews with 12 participants were conducted from October to November 2023.
Participants Overall, 12 autistic adults who identified as being in recovery or recovered from AN were included (11 women and 1 man; aged between 18–50 years).
Results Four key themes were identified: ‘Sensory Experiences’, ‘Recovery in progress’, ‘Changing to healthy mindsets’ and ‘Engaging with treatment’. Results indicated that recovery for participants did not follow a linear path, with the role of autistic traits, such as sensory sensitivities, interoception and the internal voice, making recovery challenging.
Conclusion This study provides insight into the challenges and motivations experienced during the recovery process. Findings highlight the need for further research to improve guidelines and autism awareness in ED services
Stellar-mass black holes on the millimetre fundamental plane of black hole accretion
Full text linkRecent work revealed the existence of a galaxy ‘millimetre fundamental plane of black hole accretion’, a tight correlation between nuclear 1 mm luminosity, intrinsic 2 – 10 keV X-ray luminosity and supermassive black hole mass, originally discovered for nearby low- and high-luminosity active galactic nuclei. Here we use mm and X-ray data of 5 X-ray binaries (XRBs) to demonstrate that these stellar-mass black holes also lie on the mm fundamental plane, as they do at radio wavelengths. One source for which we have multi-epoch observations shows evidence of deviations from the plane after a state change, suggesting that the plane only applies to XRBs in the hard state, as is true again at radio wavelengths. We show that both advection-dominated accretion flows and compact jet models predict the existence of the plane across the entire range of black hole masses, although these models vary in their ability to accurately predict the XRB black hole masses
A survey of learning-based intrusion detection systems for in-vehicle networks
Full text linkConnected and Autonomous Vehicles (CAVs) have advanced modern transportation by improving the efficiency, safety, and convenience of mobility through automation and connectivity, yet they remain vulnerable to cybersecurity threats, particularly through the insecure Controller Area Network (CAN) bus. Cyberattacks can have devastating consequences in connected vehicles, including the loss of control over critical systems, necessitating robust security solutions. In-vehicle Intrusion Detection Systems (IDSs) offer a promising approach by detecting malicious activities in real time. This survey provides a comprehensive review of state-of-the-art research on learning-based in-vehicle IDSs, focusing on Machine Learning (ML), Deep Learning (DL), and Federated Learning (FL) approaches. Based on the reviewed studies, we critically examine existing IDS approaches, categorising them by the types of attacks they detect—known, unknown, and combined known-unknown attacks—while identifying their limitations. We also review the evaluation metrics used in research, emphasising the need to consider multiple criteria to meet the requirements of safety-critical systems. Additionally, we analyse FL-based IDSs and highlight their limitations. By doing so, this survey helps identify effective security measures, address existing limitations, and guide future research toward more resilient and adaptive protection mechanisms, ensuring the safety and reliability of CAVs
Strengthening families through family group conferencing
No full textChapter 6 examines the practice of Family Group Conferences (FGCs) in child and family social work, an approach that aims to involve extended family members and other members of a child’s network in decision-making processes. It draws on experience from participating in, delivering and researching FGCs. It also explores how this approach can strengthen families and support positive outcomes for children. The chapter begins by providing an overview of FGCs, including their origins, principles and how they work in practice. It then explores the evidence base for FGCs, drawing on a range of research studies that suggest that FGCs can result in improved outcomes for children and families, including increased family engagement, reduced reliance on statutory services and improved family relationships. The chapter also considers some of the challenges associated with FGCs. Finally, it discusses the potential for FGCs to be used more widely within the child and family social work sector, and the need for effective leadership and training to support the implementation of this approach
Opening reflexive spaces: Maps as an anticipatory tool in expert interviews
Full text linkThe value of maps in geographical and social-scientific research as tools that afford imaginative aesthetic engagement with research topics has become increasingly recognised. We explore here, for the first time, the value of these affordances for interviewing experts. In particular, the imaginative engagement maps can provide may help unsettle routines of thought, and invite reflexivity towards the assumptions on which expert knowledge may rest. This contribution of maps can be particularly valuable in research where anticipating potential future consequences of societal transformations is a central aim. We examine a case study from South Wales, UK, relating to explorations of socio-technical transitions in the field of energy, and show how the imaginative engagements that maps afford for expert participants can facilitate specific ways of anticipating potential futures that avoid simply extrapolating from what is familiar