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Goal-Oriented Adaptive Modeling: Oden’s Legacy, Recent Results, and Future Trends
Get PDFThis article is meant to be not only a tribute to the many contributions by J. Tinsley Oden to the field of goal-oriented error estimation and adaptivity, but also a laudation for being a visionary leader in computational mechanics, sciences, and engineering. Oden was a kind and generous person, making him an effective mentor for many young scholars, always willing to share his knowledge and foster new collaborations. He was also recognized as a very effective speaker, whose lectures have inspired generations of research scientists over his long career
Bioelectrochemical detection of viable but non-culturable bacterial cells on screen-printed carbon electrodes
Get PDFBacterial cells in a viable but non-culturable (VBNC) state are metabolically active, but cannot be cultivated using a routine growth medium, which poses a challenge to identifying VBNC contamination in food and the health sector. Non-growth assays for VBNC identification based on membrane integrity and metabolic monitoring are either costly or lead to ambiguous results. Nucleic acid (DNA and RNA) amplification techniques are effective, but their higher cost and complexity prevent routine applications. Bioelectrochemical assays might be a viable alternative for VBNC detection, due to their low cost and rapid analysis time. However, conventional bioelectrochemical methods, in which electrodes are polarized at constant electrochemical potential, are not suitable for monitoring planktonic non-growing cells like VBNC.To circumvent this issue, culturable and VBNC Pseudomonas aeruginosa cells were embedded in hydroxyethyl cellulose (HEC) coating and exposed to alternated cathodic and anodic potentials for a short-time. The resulting current output was interpreted in terms of charge/discharge of the bacterial membrane at the polarized electrode, which is a proxy for bacterial viability. P. aeruginosa cells were induced into the VBNC state by either UV-C or NaOCl. In the presence of 5 mM K3[Fe(CN)6] and 20 mM glucose, the current output correlates inversely with the VBNC cells concentration. For cells inactivated by heat or 4% paraformaldehyde, the current output was not significantly different from the blank electrode, indicating the ability of the proposed bioelectrochemical method to detect changes in cellular viability before the loss of culturability
Baseline characteristics of patients recruited to the mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH) trial
Get PDFBackground Mannitol, an osmotic diuretic and free radical scavenger might decrease cerebral oedema after acute intracerebral haemorrhage. Aims The Mannitol for cerebral oedema after acute intracerebral haemorrhage trial is testing the feasibility of performing a phase II trial to define the optimal approach for a phase III trial of testing mannitol in patients with cerebral oedema or at risk of it to improve outcome. Methods MACE-ICH is a multicentre, prospective, randomised, open-label, blinded-endpoint outcome assessment trial. Participants presenting within 72 h of ictus were randomised to one of three groups: 1:1 g/kg 10 % single dose mannitol infusion at 10 ml/min, in addition to standard care; 1 g/kg 10 % mannitol at 10 ml/min followed by a second dose 1 g/kg repeated 24 h later (providing serum osmolality '320 mOsm/Kg and sodium'160 mmol/L), in addition to standard care or standard care alone. The trial was registered prospectively: ISRCTN15383301. Results 46 (of planned 45) participants were recruited from 8 sites between February 2024-April 2025. Baseline characteristics: mean age 74.7 years (standard deviation 12.0); male 69 %; onset-to-randomisation 22.9 h; severity (National Institutes of Health Stroke Scale) 12.1 (8.3); blood pressure 155.3 (29.0)/78.9 (16.5) mmHg. Haematoma characteristics: lobar 58 %, mass effect 58.7 %, midline shift (34.8 %). The mean maximum haemorrhage diameter was 4.3 cm. Conclusion MACE-ICH successfully enroled patients with cerebral oedema after acute intracerebral haemorrhage to assess the feasibility and safety of intravenous mannitol. The trial is novel with a dose-comparative approach with assessment of single and repeated mannitol dosing regimens, addressing an important gap in clinical practice
Dual end-functionalisation of poly(beta-amino ester) gene delivery vectors using multicomponent chemistry
Get PDFThe use of RNA therapeutics provides a potent tool to enhance patient outcomes, but successful RNA delivery requires efficient and safe vectors. Cationic polymers provide one technology platform for this delivery and among these materials, poly(beta-amino esters) (PBAEs) have emerged as efficient and well tolerated vectors. Changing the end group of these materials can have a profound impact on their physical and biological properties, and the development of new pathways for end-group functionalisation can provide access to untapped material libraries for further development. We therefore developed a synthetic pathway that exploits the Passerini 3-component reaction as a means to incorporate aldehyde and isocyanide materials into the end-groups of an acid terminated PBAE. Polyplexes were then prepared and studied for encapsulation efficiencies, formulation properties and gene transfectability in vitro. Select polymers demonstrated high mRNA transfection efficiency in HEK293T cells. Our findings indicate that this synthetic pathway provides a versatile and adaptable pathway for the further modification of PBAEs and that this modification serves to provide new materials with enhanced nucleic acid delivery properties
fMRI responses to horizontal and vertical symmetry axes in ascending visual hierarchy
Get PDFVisual regularities such as reflection and translation are known to engage extrastriate visual cortex, but how regularity type, axis orientation, and task demand jointly shape these responses remains unclear. We used functional Magnetic Resonance Imaging (fMRI) to measure univariate and multivariate responses to reflection and translation patterns with vertical or horizontal axis of orientation while participants (n = 24, 6 male) performed either a regularity discrimination task or an orientation discrimination task.Univariate analysis showed that stimulus-evoked responses increased from V3 onwards, with minimal responses in V1-V2. Contrary to classical salience accounts, early dorsal regions (V3, V3a, V3b) responded more strongly to translation than reflection. Orientation effects dissociated across regions: V3a and V3b showed stronger responses to horizontal than vertical axes, whereas LO2 showed the opposite preference. Task effects were limited, with no overall enhancement of responses during regularity discrimination.Multivariate (searchlight MVPA) analysis revealed reliable decoding of regularity in extrastriate regions and decoding of axis orientation in early visual cortex. Orientation information was reduced in extrastriate regions during regularity discrimination relative to orientation discrimination.These findings show that responses to visual regularities in human visual cortex depend on regularity type, axis orientation, and task demands, with dorsal and ventral regions showing distinct response profiles
Competencies for advanced clinical practice (ACP) hand therapists in first-line management of closed hand fractures: Results of a United-Kingdom (UK) stakeholder consensus study
Get PDFIntroductionIn the United Kingdom [UK], Advanced Clinical Practice (ACP) roles are being developed to improve access to high-quality patient care, where healthcare services are struggling to meet steadily increasing service demands. Increasingly, ACP hand therapists are assessing and treating acute closed hand fractures. However, the knowledge and skills required of these roles has not been identified or standardised.MethodsConsensus recommendations were developed from an expert panel of medical doctors and hand therapists using an electronic Delphi process. Participants were recruited from purposive and snowball sampling. Delphi questions were developed from a literature review and clinician survey and included rating of items open text responses. Consensus was defined as ≥75% agreement. Summary feedback was provided after each round.ResultsThere were 20 panellists (12 medical doctors and 8 hand therapists), of which 18 (90%) completed all rounds. 23 competencies were consistently identified as very important; there was less agreement on how to evidence these competencies.ConclusionThese findings can be used to develop ACP hand therapist roles and provide a framework to guide individual therapists to base their own learning and development. They underpin safe, efficient and costeffective patient care
A mixed methods investigation into GP attitudes and experiences of using social prescribing in their practice
Get PDFAimSocial prescribing (SP) enables clinicians to signpost patients to non-medical services in the community in order to support their psycho-social needs. SP has been promoted as a positive service delivery model for primary and community care; however, there are few data on the views of doctors working in this area on the effectiveness of SP and its implementation.Subject and methodsThis study used a mixed methods approach to examine attitudes and experiences of general practitioners (GPs) on their use of SP. GPs completed an online survey (n = 102), provided narrative written responses (n = 55) and took part in semi-structured interviews on the topic (n = 8).ResultsPrincipal component analysis (PCA) showed that 90% of respondents use SP in their practice, with significant factor loadings on six separate components. Thematic analysis revealed three main themes, which were then combined with the PCA components to derive overarching themes that underpin effective implementation of SP: (1) perceptions of effectiveness and efficacy of SP, (2) training and awareness, and (3) structure and operational delivery.ConclusionThis study is one of the first to explore attitudes of doctors to SP. Whilst data shows that most respondents are supportive of SP in principle, the analysis also reveals that there are specific barriers that need to be overcome to enable effective implementation
Responsible Generative AI for SMEs in UK and Africa (RAISE): A Financial Investment AI Case Study
Get PDFThis report presents a series of case studies developed under the Responsible Generative AI for SMEs in the UK and Africa (RAISE) project, examining how small and medium-sized enterprises (SMEs) understand, adopt, and operationalise generative AI in practice. Drawing on in-depth qualitative engagement with participating organisations across diverse sectors, the case studies explore anticipated benefits, technical and organisational challenges, and the ethical, legal, and social considerations shaping AI integration. The RAISE case studies demonstrate how responsible AI principles are interpreted pragmatically by SMEs and illustrate the value of context-sensitive, actionable guidance in supporting responsible adoption. Collectively, the cases provide empirical insight into the realities of generative AI use in resource-constrained environments and inform the development of practical frameworks for responsible AI implementation in SMEs
Mapping undergraduate pharmacy curricula in Saudi Arabia against a national competency framework: A case study of two PharmD programmes
Get PDFIntroduction: Pharmacy education in Saudi Arabia has expanded rapidly, with most colleges transitioning to the PharmD as the entry-level degree. A proposed national competency framework for foundation-level pharmacists was recently developed to support curricular reform and improve graduate preparedness. However, the extent to which current PharmD programmes align with this framework appears to be variable. Methods: Curriculum mapping was employed to evaluate two undergraduate PharmD programmes as a case study. Intended curricular content, including course descriptions and learning outcomes, was analysed against behavioural statements from the proposed national competency framework using qualitative content analysis. Competency coverage, subject domain weighting, and curricular emphasis were visualised through heat maps, radar charts, and descriptive statistics. Results: Both programmes incorporated most of the proposed competencies, with greater emphasis on technical areas such as medicines information, compounding, and communication skills, and less coverage of organisational management and public health competencies. One programme exhibited a physical science-focused orientation, while the other was more practice-oriented. Gaps were identified in leadership, continuing professional development, and patient consultation competencies. Although both programmes were PharmD degrees, the findings revealed differences in curricular structure and content, suggesting limited differentiation from traditional BPharm models. Conclusion: This study presents a replicable method for assessing curriculum alignment with national competencies. The findings highlight the need for more balanced competency-based curricula to better prepare graduates for expanded professional roles aligned with national healthcare priorities
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