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Navigating market access after conditional reimbursement : a communication roadmap for disinvesting orphan drugs
No full textObjectives: Disinvesting from rare disease therapies with persistent clinical uncertainties following a managed entry agreement (MEA) may be necessary to ensure an equitable and sustainable healthcare system. To minimize public controversy, communication surrounding such disinvestment decisions must be timely, transparent, and tailored to stakeholder needs. This study develops a structured communication roadmap for disinvestment decisions in the Belgian context, addressing the clinical, financial, ethical, psychological, and social implications. Methods: Three advisory board meetings were conducted with nine experts from academia, clinical practice, health insurance funds, patient organizations, and the Belgian Drug Reimbursement Committee. A targeted review of peer-reviewed literature, legal texts, and policy documents informed the discussion guide. Meetings were transcribed verbatim and analyzed using NVivo 14, following grounded theory principles. Results: Disinvestment decisions should be evidence-based and communicated clearly and pragmatically in a context-specific manner. The proposed five-step roadmap defines the roles, responsibilities, and timelines of key stakeholders and provides guidance for public-facing documents, including a lay summary of the health technology reassessment report and written communications for patients and the public. Effective and timely communication with patients requires close collaboration among stakeholders. Moreover, regular engagement with healthcare providers and patients throughout the MEA period can enhance understanding and acceptance of the final decision. Conclusions: Transparent, collaborative, and adaptable communication strategies can facilitate the implementation of disinvestment decisions and help maintain trust among patients and the public. Although developed for rare disease therapies in Belgium, the proposed principles and roadmap are applicable to disinvestment processes in other healthcare systems
Vibrationally-aided flow of lunar regolith simulants in a hopper-based conveying device
No full textHoppers are expected to play an essential role in handling of lunar regolith for future lunar exploration missions, from collection and storage to in In-Situ-Resource-Utilization (ISRU). This study presents a parametric experimental investigation of regolith discharge dynamics by using the LHS-1 simulant. Results show that vertical vibrations significantly affect the regularity of the flow of granular material through the orifice of the hopper, the average mass flow rate, the spatio-temporal patterning of the material displacement and the occurrence of jamming (clogging) phenomena. While the average mass flow rate is consistently smaller than that obtained in purely gravitational flow, vibrations induce a significant reduction in the probability of arching and make the overall flow of material much more regular and spatially uniform. Four different flow configurations are identified accordingly in the entire space of parameters, i.e. “funnel”, “mass”, “asymmetric” and “ratholing” flow. The “funnel” is the most common, while asymmetric and ratholing regimes are only attained for relatively high shaking frequency and amplitude. Low frequencies universally promote arching, due to insufficient energy to disrupt force chains within the material. In contrast, the role of high frequencies is more complex, with clogging re-emerging at certain thresholds, particularly at low acceleration amplitude. Increasing the vibration amplitude generally mitigates blockage, but its effectiveness weakens with sample mass growth, indicating that additional factors, such as gravity-induced compaction and related particle rearrangement dynamics also play a significant role in governing such events
A modular and convergent "Stick and Click" conjugation platform enables fast antibody conjugate library synthesis
Get PDFThe preparation of antibody drug conjugates (ADC) most often relies on a linear sequence to elaborate the small molecule component, followed by a final bioconjugation step to attach it to its immunoglobulin partner. This linear and iterative approach is incompatible with expedient parallel synthesis and process automation. Here, we describe the design and implementation of a general modular platform for the assembly of ADCs that enables facile variation in the nature of the payload, the linker composition, and the type of bioconjugation technique used. A library of antibody conjugates bringing together several different antibodies and payloads was prepared in a convergent fashion using a range of conjugation methods, as well as cleavable or noncleavable linker technology. Aside from offering a direct comparison of different conjugation method performances, this approach enables a more targeted optimization strategy of conjugate properties by deconvoluting bioconjugation and payload attachment
Editorial: Recent advances in energy systems for sustainable development
Get PDFEditorial on the Research Topic: Recent advances in energy systems for sustainable developmen
The Economic Contribution of Scottish Professional Football
Get PDFThis report examines the economic contribution of professional football to the Scottish economy during the 2023-24 season. It was commissioned by the Scottish Professional Football League (SPFL) and the Scottish Women’s Premier League (SWPL) – the bodies responsible for organising top-tier league football in Scotland – together with the Scottish Football Association (Scottish FA), the governing body for the sport. The analysis was prepared independently by the Fraser of Allander Institute at the University of Strathclyde. Professional football is a significant contributor to the Scottish economy and a major part of the sport and recreation sector. The sport holds a unique place in Scotland’s cultural landscape, with over 6.8 million attendances annually at matches involving Scottish professional football teams and international matches, and the Premiership boasting the highest average weekly attendance per-capita in Europe
Three-dimensional computational homogenization of cracked composite materials using state-based peridynamics and MPI parallelization
Get PDFThis paper presents a scalable three-dimensional computational framework for the homogenization of cracked composite materials using the ordinary state-based peridynamic formulation. The method integrates a generalized bond-breaking algorithm, based on a modified Möller-Trumbore raytracing scheme, which transforms arbitrary crack surfaces into triangle mesh representations, enabling robust and geometry-independent fracture detection. Volumetric periodic boundary conditions are implemented to ensure energetic consistency and compatibility with the Hill–Mandel macro-homogeneity condition. To address the substantial computational cost of 3D nonlocal models, the framework employs MPI-based domain decomposition combined with PETSc iterative solvers, achieving strong parallel scalability for representative volume elements (RVEs) containing millions of material points. Numerical experiments on fibre-reinforced composite RVEs, both intact and pre-cracked, demonstrate the framework’s ability to capture complex three-dimensional fracture patterns and accurately predict effective stiffness properties. The proposed approach offers a robust, general purpose, and high performance solution for microscale fracture analysis and homogenization in composite materials, with potential applicability to broader classes of heterogeneous and damage-prone materials
Feeling unsafe in one's own body : the impact of illness on psychological safety and social engagement
Get PDFThe concept of neuroception of psychological safety, rooted in Polyvagal Theory, offers a framework for understanding how individuals perceive safety at a physiological and psychological level. Illness may disrupt this perception and affect bodily regulation, emotional resilience, social connection, and self-compassion. This study aims to explore how experiences of being unwell, across both acute and chronic contexts, affect individuals’ neuroception of psychological safety. Semi-structured interviews were conducted with eleven adult participants aged 20–79, including individuals with both acute and chronic illness experiences. Interview questions were informed by the Neuroception of Psychological Safety and Polyvagal Theory. Data were analysed using reflexive thematic analysis, following Braun and Clarke’s six-step process. Four key themes were identified: dysregulation and the narrowing window of tolerance (reduced emotional resilience and heightened bodily sensitivity); distrust and disappointment (a rupture in bodily and self-trust); responsibility and internalised guilt (moral and emotional burdens around illness and recovery); and illness demands attention and disrupts social connection (withdrawal, emotional depletion, and compromised compassion). Across these themes, participants described a diminished sense of psychological safety when unwell, shaped by both internal physiological changes and altered social dynamics. Illness can profoundly undermine psychological safety by disrupting neurobiological regulation, altering relational engagement, and eroding trust in one’s body and self. These findings highlight the importance of integrating psychological safety principles into models of care, particularly in how individuals experience and recover from illness
A novel hybrid explainable artificial intelligence modelling approach for smart manufacturing
No full textModelling complex manufacturing processes presents significant challenges related to accuracy and explainability. Physics-based models, while interpretable and generalizable, often suffer from reduced accuracy due to simplifications and incomplete system understanding. On the other hand, purely data-driven models are typically more accurate but lack transparency, limiting their trust and adoption in critical manufacturing applications. Existing hybrid approaches attempt to address these issues but often retain black-box AI components that compromise interpretability. In this study, we propose a novel hybrid modelling framework that intrinsically integrates physics-based models with explainable AI, to correct for modelling inaccuracies. This approach offers both high accuracy and transparent, traceable decision-making. Its effectiveness is demonstrated through a case study predicting the real-time position of cutting tools from accelerometer signals during ultra-precision diamond turning
Translating theory into practice : design gaps and context-sensitive frameworks for fostering nature-based experiences in urban preschools in Scotland and Malaysia
No full textExposure to nature-based experiences (NBE) in urban preschools is increasingly recognized as a vital antidote to children's growing disconnection from nature, often described as nature-deficit disorder. This cross-cultural study examines how NBE can be operationalized within dense urban preschool environments through comparative analysis of policy, spatial design, and pedagogical practices in Scotland and Malaysia. Drawing on a literature review, school audits guided by Biophilic Design Parameters, Leuven Involvement Scale observations, parent surveys, and teacher interviews across five study sites in Glasgow and Selangor, this study investigates how spatial affordances, educator perceptions, and climatic conditions shape children’s opportunities for nature engagement. Findings underscore teachers’ pivotal mediating role, showing that their confidence and influence in implementing structured nature-based activities consistently generated high engagement. In contrast, unstructured engagement varied substantially with spatial quality, accessibility, and familiarity. Sensory-rich landscapes and community green spaces supported the highest level of engagement, while uniform settings constrained autonomous exploration. Parent survey data indicated predominantly indoor lifestyles and limited direct nature exposure, reinforcing preschools’ essential compensatory function, particularly in Malaysia. Key barriers included extreme weather, safety concerns and restricted outdoor access. In responses, the study advances a context-sensitive NBE framework to guide future Malaysian preschool design and policy
Boosting the nucleophilicity of the diphenylphosphide anion with crown ether supported heavy alkali metals to facilitate highly efficient catalytic alkene isomerisation
No full textCaesium and rubidium have long experienced an interest drought in organoelement chemistry in comparison to the vast ocean of applications accomplished mainly by lithium and to a lesser extent, by sodium and potassium in this field. Here, we report a breakthrough study in catalytic alkene isomerisation using crown ether‐supported alkali metal phosphides in which the activity increases sequentially and significantly as Group One is descended with Cs(18‐crown‐6)PPh2 performing best even at 1 mol% loadings with high turnover frequencies (TOFs) and good functional group tolerance. Elevating its profile further, Cs(18‐crown‐6)PPh2 is also successful in a stepwise double catalysis on combining alkene isomerisation with its newly established hydrophosphination (HP) capacity to access challenging to make Markovnikov products. This remote functionalisation approach was also applied to alkynes with terminal alkynes preferentially producing allenes over internal alkynes in one‐pot reactions and then under HP, generating highly functionalised vinyl phosphines. Kinetic studies and DFT calculations have also been performed to shed light on mechanistic aspects of the Cs‐mediated isomerisation of model alkene allylbenzene
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