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Intraoperative drug delivery to hindbrain tumours via an injectable hydrogel is well tolerated and confers survival benefit against atypical teratoid/rhabdoid xenografts
No full textIntraoperatively applied local drug delivery systems (LDDS) offer a means of overcoming blood–brain barrier (BBB) impermeability. However, there is a paucity of LDDS development for paediatric tumours arising in the posterior fossa. Here we demonstrate applicability of an LDDS against medulloblastoma group 3 (G3 MB) and atypical teratoid/rhabdoid tumours (AT/RT), neoplasms associated with poor prognoses. A poly(ethyleneglycol)-poly(caprolactone)-poly(ethyleneglycol) (PECE) hydrogel loaded with chemotherapeutics identified as effective against primary G3 MB and AT/RTin vitro, was prepared as an injectable, biodegradable formulation. CHIR99021 (glycogen synthase kinase-3 inhibitor), ribavirin (guanosine analogue) and PG545 (heparanase inhibitor) were chosen based upon an inability to traverse the BBB. The hydrogel alone was well-tolerated, and drug-loaded hydrogel achieved > 1-month therapeutic release.Orthotopic xenograft studies against G3 MB and AT/RT indicated good tolerability to combined CHIR99021 and PG545 or combined CHIR99021 and ribavirin loaded loaded LDDS respectively. Median survival of AT/RT arms receiving XRT alone was comparable to CHIR99021- and ribavirin-loaded LDDS, with long-term survivors observed only in the latter arm, demonstrating a significant survival benefit. LDDS against cerebellar tumours using PECE offers a promising therapeutic alternative and the possibility of circumventing radiation-induced adverse effects for children impacted by these diseases
Online Remote Behavioural Intervention for Tics (ORBIT-UK): protocol of a single cohort usability study
No full textIntroduction Tourette syndrome is a common, disabling childhood-onset condition. Exposure and response prevention (ERP) is an effective treatment for tics, yet access remains limited due to a shortage of trained therapists and uneven geographical distribution of services. The ORBIT trial demonstrated that internet-delivered ERP is both clinically and cost-effective, but was developed on a university research platform, not suitable for widescale roll-out. To enable adoption by the National Health Service (NHS) in England, ORBIT has been redeveloped on an NHS compliant platform. This study will evaluate the usability, acceptability and preliminary outcomes of ORBIT on the new platform within an NHS tic disorder service.Methods and analysis This single-cohort usability study will recruit 20 children and young people (aged 9–17) with tics and their chosen supporters (parents/carers). Participants will receive a 10-week online ERP intervention supported by trained coaches. Outcomes include uptake, adherence, system usability, satisfaction and clinical measures such as the Yale Global Tic Severity Scale, Parent Tic Questionnaire and Goal-Based Outcomes. Qualitative feedback will be collected via semi-structured exit interviews. Usability metrics and adverse events will be monitored throughout.Ethics and dissemination The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref: 25/NW/0107). The findings from the study will inform future NHS adoption. The results will be submitted for publication in peer-reviewed journals.Trial registration number ISRCTN82718960. Registered 10 July 2025. https://doi.org/10.1186/ISRCTN8271896
Validation and Preference-Based Scoring of the York Binaural Hearing-Related Quality of Life Questionnaire for Young People
Get PDFObjectives: The York Binaural Hearing-Related Quality of Life questionnaire for Young People (YBHRQL-Y) is a 3-item measure of hearing-related quality of life devised specifically for use with young people (children aged 8 to 16 years old) with hearing loss. This research had three objectives: (1) to assign numerical values where a higher value corresponds to better perceived overall health status (“health utility weights”) to each of 27 unique combinations of difficulties with speech understanding, sound localization, and listening effort (“hearing health states”); (2) to assess its validity and reproducibility when used with young people with hearing loss; (3) to assess the feasibility of a proxy version designed to be completed by the parents/guardians of young people with hearing loss.Design: Health utility weights were obtained by conducting time trade-off interviews with a cross-sectional sample of 155 young adults, aged 18 to 24 years old, recruited from social media and UK universities. To assess validity and reproducibility, the YBHRQL-Y and other established instruments measuring functional hearing and hearing-related quality of life in children were administered to young people with hearing loss at two time points, 2 wk apart. In total, 71 children aged 8 to 16 yr old with at least a severe hearing loss took part and were recruited from social media, relevant charities, and support groups in the United Kingdom. The feasibility of obtaining information about the binaural hearing-related quality of life of young people with hearing loss indirectly was assessed by administering a proxy version of the YBHRQL-Y to the parents or guardians of the young people who participated in the research. A total of 71 parents or guardians were recruited from social media, relevant charities, and support groups in the United Kingdom.Results: The health utility weights elicited from young adults varied monotonically with the level of hearing-related impact described on each of the three dimensions of the YBHRQL-Y, such that the greater the degree of hearing-related impact, the poorer the corresponding health state was judged to be by the respondents. Convergent validity analyses suggested that the domains of the YBHRQL-Y measure the intended constructs and the overall measure relates to the respondent’s health-related quality of life. Test-retest analyses suggested it was reliable and showed good agreement between administrations. Pairwise analysis of responses from the young person with hearing loss and those of their parent/guardian suggested that the proxy measure had poor reliability and poor agreement with the measure administered directly to the young person with hearing loss.Conclusions: The YBHRQL-Y is a valid and reliable measure of hearing-related quality of life when administered directly to a young person aged 8 to 16 with at least a severe hearing loss. An individual’s preference-based score, derived from the preferences of young adults, successfully integrates information about binaural-related hearing across the domains of speech understanding, sound localization, and listening effort. The combination of brief age-appropriate questions, good psychometric performance across time, and a preference-based scoring method makes the YBHRQL-Y a straightforward means to assess hearing-related quality of life in young people with hearing loss
The Role of Processed Electroencephalography in the Detection and Management of Acute Cerebral Ischemia: A Scoping Review
Get PDFProcessed electroencephalography (pEEG) is increasingly used to titrate the depth of anesthesia. Whether such intra-procedural pEEG monitoring can offer additional information on cerebral perfusion or acute focal or global cerebral ischemia is unknown. This scoping review aimed to provide a narrative analysis of the current literature reporting the potential role of pEEG in adults with acute cerebral ischemia. In keeping with the scoping review methodology, a broad search strategy was defined, including descriptions of encephalography in acute ischemic stroke, carotid endarterectomy, cardiac surgery, and cardiac arrest. Additional screening of citations was conducted by 2 independent assessors. From 310 records, 28 full-text articles met inclusion criteria. Most identified studies were observational in design, and described the diagnostic ability of pEEG to identify cerebral hypoperfusion or its prognostic sensitivity after stroke or carotid surgery. No studies were identified that evaluated pEEG in the specific setting of endovascular therapy for acute ischemic stroke. Low sensitivity associations between pEEG indices and cerebral blood flow were highlighted, which may be influenced by cerebral autoregulatory thresholds. Despite the associations reported in observational studies, this review identified significant uncertainty in the role of pEEG during cerebral ischemia. There is a paucity of high-level observational (cohort or case-control) or randomized trial research examining the possible role of pEEG for the detection and management of cerebral ischemia during acute stroke, including during endovascular therapy, or in other common scenarios of acute cerebral ischemia
A Multimodal Adaptive Framework for Social Interaction with the MiRo-E Robot
Get PDFHighlights: This study explores how robots can interact with people in a more engaging way. By combining real-time user engagement estimation with advanced language models, the system allows robots to respond consistently through both speech and body language. Tests show that this approach makes interactions feel more natural while improving user engagement and task success. What are the main findings? Adapting the interaction based on user engagement significantly enhances user experience. The MiRo-E social HRI platform lends itself well to integrating verbal and nonverbal HRI. What are the implications of the main findings? Enhancing perceived naturalness is an important goal in social human–robot interaction. Generative AI and multimodality offer a credible pathway to achieving this goal. Adaptivity is a key component of social human–robot interaction (HRI) towards achieving more natural and human-like interactions. Current interactive systems tend to rely on preset and repetitive verbal communication and isolated nonverbal interactions, which results in unappealing engagement. This study proposes an integrated framework that combines a coordinated nonverbal interaction system based on real-time emotion expression with a fine-tuned large language model-based verbal communication system, resulting in more engaging and context-aware interaction. The design utilises the MiRo-E as the zoomorphic social interaction platform, with the aim of enhancing the consistency across verbal and nonverbal modalities and improving user engagement through adaptive and emotionally aligned responses. To evaluate the effectiveness of the approach, a user study was conducted with tasks designed to assess user engagement, task performance, and the perceived naturalness of interaction. Task performance metrics and subjective questionnaire responses indicate that the framework significantly enhances user experience, improving task completion rates, engagement, and perceived naturalness
A dynamic modelling framework to assess the impact of manual emergency responses on nuclear power plant resilience
Get PDFThe escalating frequency of extreme natural disasters due to climate change poses unprecedented risks to nuclear power plants (NPPs), underscoring the need to quantify the efficacy of manual emergency responses in enhancing resilience. However, quantifying the effectiveness of these measures remains a significant challenge. This paper develops a Petri Net-based resilience assessment framework to model multi-phase accident progression in an NPP subjected to extreme events, including loss of coolant accidents and station blackout scenarios. The PN models integrate stochastic system degradation processes, automated safety responses, manual recovery processes, and offsite resource mobilisations. The simulation results show that the developed model can successfully assess the impact of the efficiency of human responses on NPP resilience. This work provides actionable insights for optimising NPP emergency procedures and resource allocation strategies. The findings underscore the importance of timely manual interventions during emergency scenarios, offering a quantitative basis for enhancing nuclear safety management policies
Does maternal migration affect spousal labour market decisions? Evidence from Sri Lanka
Get PDFThis paper examines Sri Lankan men's labor market outcomes when their wives emigrate to work, leaving the husbands and their children at home in Sri Lanka - the effects of maternal migration on the husbands' labor market decisions. We used nationally representative cross-sectional data and historical migration rates at the community level as an instrument for maternal migration in two-stage least squares estimations. We find that maternal migration reduces the husbands' labor supply. Husbands are more likely to exit the labor market and become unemployed; the employed are less likely to moonlight and have lower wages, and those that exit the labor market are more likely to become stay-at-home dads. Using a second instrument, an indicator of whether a community has foreign-employment agencies, we also confirmed our main results. Our findings indicate that policies that aim to promote female migration as an exogenous income source may fall short if they do not address the effects of the husbands' labor market decisions
Attention Utility: Evidence from Individual Investors
No full textWe study attention utility, the hedonic pleasure or pain derived purely from paying attention to information, which differs from the news utility that arises from gaining new information. The main, field, study examines brokerage account login data to show that investors pay disproportionate attention to already-known positive information on their stocks. Through its effect on logins, this selective attention affects their trading activity. Three experimental studies then show that (1) investors are more likely to engage in a paid task that will involve attention to a prior investment if that investment has gained value; (2) paying attention to a winning stock is more motivating than a doubling of monetary incentives; and that (3) attention has value independent of information acquisitio
Losing touch: class, social capital, and out of area housing
Get PDFWhilst the conceptualization of a housing crisis has become a common narrative within politics, research, and the media, its nebulous nature can risk failing to recognize the breadth of experiences or its exact relationship to inequality. By looking at out of area housing placements as one aspect of the ‘housing crisis’, this paper explores the way by which experiences of housing can be a disbenefit to people’s wellbeing through fracturing important social networks and connections. Using primary evidence from households placed out of area by their local authority, the paper recognizes the importance of class as a way to understood market power, which is increasingly salient as housing becomes increasingly commodified. However, in seeking to broaden this position, the concept of social capital is introduced as a way of counterbalancing economic understandings of inequality with social vulnerabilities. The paper is based on 10 households placed out of area following the use of freedom of information requests to English local authorities to ascertain the extent of the practice. The paper argues that out of area housing diminishes social capital, which as a component of total capital, can be seen as further impoverishing vulnerable households
A realist review of acute pain management in children and young people attended by ambulance
Get PDFAcute pain management in children and young people (CYP) attended by ambulance services is a significant challenge due to the complex nature of pain, the variation of approach needed across the age range, and the unpredictability of the environment. We aimed to understand how ambulance clinicians can provide improved prehospital acute pain management for CYP. A realist review was conducted and reported in accordance with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidance. We developed an initial programme theory (PT) using key stakeholder input, searched the major bibliographic databases MEDLINE, CINAHL Complete and PsycINFO, and other sources from January 2000 to February 2024, screened and assessed relevance and rigour in duplicate, and performed synthesis and programme theory refinement. We developed an initial PT that focussed on the preparedness of staff and the expectations of CYP and parents/carers, along with key outcomes such as pain score severity, fear and anxiety. The subsequent search strategy yielded 1503 documents, of which 95 were included, representing empirical research articles, reviews, theses, book chapters and clinical guidelines. The initial PT was tested and refined throughout the synthesis to produce a PT underpinned by 34 context-mechanism-outcome configurations. The PT portrayed positive (e.g. presence of parents, focussed education and training, building trust) and negative (e.g. misinformation, fear and anxiety, long-term consequences) effects on prehospital acute pain management for CYP. This PT was mapped to the Behaviour Change Wheel to provide a clinically relevant behaviour change model for improvement. This realist review has provided a clinically focussed model to guide the improvement of prehospital acute pain management in children and young people attended by ambulance. The programme theory lays a foundation on which future empirical testing can be conducted to effect behaviour change in practice
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