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On tori periods of Weil representations of unitary groups
Get PDFWe determine the restriction of Weil representations of unitary groups to maximal tori. In the local case, we show that the Weil representation contains a pair of compatible characters if and only if a root number condition holds. In the global case, we show that a torus period corresponding to a maximal anisotropic torus of the global theta lift of a character does not vanish if and only if the local condition is satisfied everywhere and a central value of an L-function does not vanish. Our proof makes use of the seesaw argument and of the well-known theta lifting results from
to U(1) to U(1). Our results are used in [1, 2] to construct Arthur packets for G2
Impact of young people's admissions to adult mental health wards in England:national qualitative study
Get PDFBACKGROUND: National policy in England recommends that young people be admitted to mental health wards that are age-appropriate. Despite this, young people continue to be admitted to adult wards. AIMS: To explore the impact of young people's admissions to adult wards, from the perspectives of young people, parents/carers and mental health professionals working in adult services. METHOD: Semi-structured interviews were conducted with 29 participants to explore experiences of receiving and delivering care in adult mental health wards. Participants were four young people (aged 16-17 years), four parents/carers and 21 mental health professionals from adult mental health services in England. Data were analysed using framework analysis. RESULTS: Young people's admissions to adult wards tend to occur out of hours, at a time of crisis and when no suitable adolescent bed is available. Admissions were conceptualised as a short-term safety measure rather than for any therapeutic input. Concerns were raised about safeguarding, limited treatment options and a lack of education provision for young people on adult wards. However, exceptionally, for older adolescents, an adult ward might be clinically or socially appropriate. Recommendations to reduce adult ward admissions included better integration of adolescent and adult services, having more flexible policies and increasing community provision. CONCLUSIONS: Our findings emphasise the importance of young people being admitted to age-appropriate in-patient facilities. Earlier intervention and increased provision of specialist care in the community could prevent young people's admissions to adult wards
Exposing socialization and systemic exclusion barriers in UK universities
No full textThis chapter examines the systemic barriers Neurodivergent students face in United Kingdom higher education, with a focus on international students from China, who often lack autism diagnoses, and female students, who are frequently underdiagnosed or misdiagnosed. It explores how financial structures, cultural expectations, and institutional policies create an environment that fosters disengagement and learned helplessness among Neurodivergent students. Drawing on Seligman's Learned Helplessness Theory, Bandura's Social Learning Theory, and Vygotsky's Sociocultural Theory, the chapter analyzes how repeated institutional failures discourage self-advocacy and reinforce disadvantage. The chapter advocates for Universal Design for Learning (UDL) as a solution to reduce the burden of self-advocacy and create more inclusive academic environments. There are recommendations for systemic reform, including culturally competent disability support, proactive outreach, and structural changes to enhance accessibility for neurodivergent students in higher education
Risk of stroke associated with risperidone in dementia with and without comorbid cardiovascular disease: population-based matched cohort study
Get PDFBackground
Agitation and aggression occur in up to half of people living with dementia over the course of the disease. Although non-pharmacological interventions are used as first-line treatment strategies, antipsychotics may be indicated in severe cases. A major adverse effect of antipsychotics in dementia is stroke; the mechanism of action of atypical antipsychotic risperidone has been linked to cardiovascular disease (CVD) biological pathways in preclinical studies.
Aims
To evaluate the risk of stroke associated with risperidone across different patient subgroups defined by stroke and CVD history.
Method
Anonymised primary care data from the UK-based Clinical Practice Research Datalink were used to identify individuals diagnosed with dementia after the age of 65 years between 2004 and 2023. Risk of stroke over 1 year was compared between individuals initiating risperidone and propensity-score-matched controls across subgroups with and without history of stroke and any CVD.
Results
In the overall cohort (28 403 risperidone users and 136 324 mtatched controls), risperidone was associated with increased risk of stroke (adjusted hazard ratio: 1.28; 95% CI: 1.20–1.37). In the risperidone user group, the incidence rate of stroke was substantially higher in those with a prior history of stroke (incidence rate: 222 per 1000 person-years) and CVD (incidence rate: 94.1 per 1000 person-years) than in the overall cohort (incidence rate: 53.3 per 1000 person-years). Relative risks related to risperidone were similar across all CVD and stroke subgroup comparisons (hazard ratios between 1.23 and 1.44).
Conclusions
People with dementia with a prior history of CVD are at a significant increased risk of stroke, and risperidone further exacerbates this risk. Moreover, risperidone increases risk of stroke in patients without a prior history of CVD. This quantification of stroke risk across subgroups with and without history of CVD may help with communication of risk and aid more judicious prescribing
Platelet Reactive Oxygen Species, Oxidised Lipid Stress, Current Perspectives, and an Update on Future Directions
Get PDFBlood platelets are anucleate cells that play a vital role in haemostasis, innate immunity, angiogenesis, and wound healing. However, the inappropriate activation of platelets also contributes to vascular inflammation, atherogenesis, and thrombosis. Platelet activation is a highly complex receptor-mediated process that involves a multitude of signalling intermediates in which Reactive Oxygen Species (ROS) are proposed to play an important role. However, like for many cells, changes in the balance of ROS generation and/or scavenging in disease states may lead to the adoption of maladaptive platelet phenotypes. Here, we review the diverse roles of ROS in platelet function and how ROS are linked to specific platelet activation pathways. We also examine how changes in disease, particularly the plasma oxidised low-density lipoprotein (oxLDL), affect platelet ROS generation and platelet function
Missed opportunities of feedback for emergency ambulance staff: a mixed-methods diary study
Get PDFIntroduction: Providing feedback to emergency ambulance staff on performance or patient outcomes may improve care quality and professional development. Current feedback provision in ambulance services is limited and staff desire more feedback; however, we do not know what feedback would be most useful. This study aimed to determine the quality of feedback received by emergency ambulance staff, describe self-directed learning activities performed after receiving feedback (e.g. ‘reflected on what exactly I did right/wrong’) and identify situations where ambulance staff desired enhanced feedback.
Methods: An observational mixed-methods study was used. Emergency ambulance staff delivering face-to-face patient care in the United Kingdom’s National Health Service completed a baseline survey and diary entries between March and August 2022. Diary entries were event contingent and were collected when a participant identified that they had received feedback or desired feedback but had not received it. Free-text qualitative responses were categorised using content analysis before being included in the quantitative analyses. Quantitative data were analysed using descriptive and inferential statistics.
Results: Baseline surveys were completed by 299 participants; 100 participants submitted 374 feedback-desired diary entries and 105 participants submitted 538 feedback-received diary entries. Ambulance staff expressed a statistically significant preference for patient-outcome feedback (77.8% [95% CI 74.0, 82.1]), provided by non-ambulance healthcare professionals (70.7% [66.2, 75.3]) and delivered electronically (54.0% [48.9, 59.4]). Feedback was particularly desired for cases involving neurological (17.1%) and cardiovascular (16.6%) conditions and non-conveyed patients (11.5%). Self-directed learning activities post feedback included reflection (61.5%), considering alignment with own judgement (41.1%) and discussions with colleagues (37.0%).
Conclusion: The study identifies critical gaps in current feedback practices within ambulance services and provides directions for feedback designs that would enhance existing systems and approaches. Training programmes should educate ambulance staff on effective feedback utilisation and management of both positive and negative feedback. Cultivating a supportive feedback culture within ambulance services is crucial for fostering continuous professional growth and improving patient care outcomes
Changes in neurotransmitter-related functional connectivity along the Alzheimer’s disease continuum
Get PDFAlzheimer’s disease may be associated with early dopamine dysfunction. However, its effects on neurofunctional alterations in the neurotransmission pathways remain elusive. In this study, positron emission tomography atlases and functional MRI data for 86 older adults with mild cognitive impairment Alzheimer's disease (MCI), 58 with mild Alzheimer's disease-dementia and 76 cognitively unimpaired were combined to investigate connectivity alterations associated with the dopaminergic and cholinergic systems. A cross-sectional design was used to compare neurotransmitter-related functional connectivity across groups and associations between functional connectivity and cognitive performance. The findings show that the Alzheimer's disease dementia group showed a decline in mesocorticolimbic dopamine-related connectivity in the precuneus but heightened connectivity in the thalamus, whereas the Alzheimer's disease-MCI group showed a decline in nigrostriatal connectivity in the left temporal areas. Acetylcholine-related connectivity decline was observed in both Alzheimer's disease-MCI and Alzheimer's disease-dementia primarily in the temporo-parietal areas. Episodic memory scores correlated positively with acetylcholine- and dopamine-related connectivity in the temporo-parietal cortex and negatively with dopamine-related functional connectivity in the fronto-thalamic areas. This study shows that connectivity alterations in acetylcholine and dopamine functional pathways parallel cognitive decline in Alzheimer's disease and might be a clinically relevant marker in early Alzheimer's disease
Gene editing for collagen disorders: current advances and future perspectives
Get PDFCollagen disorders encompass a wide range of genetic conditions caused by pathogenic variants in collagen genes for which there is an unmet need for treatments. They present various clinical features, ranging from localised tissue abnormalities to severe systemic complications. Symptoms differ significantly and depend on the pathogenic variant, which can affect various systems, including the musculoskeletal, cardiovascular, and respiratory systems, highlighting the complex implications of collagen gene pathogenic variants and the wide range of expression patterns among different collagen types. Gene-editing technologies, particularly Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-Cas systems, have emerged as promising therapeutic options for these disorders, representing a putative one-for-all treatment strategy. This review provides an overview of current gene-editing strategies aimed at collagen-related diseases, including osteogenesis imperfecta, Alport syndrome, and dystrophic epidermolysis bullosa. We explore the application of CRISPR-Cas9, which facilitates targeted DNA modifications, base editing (BE), and prime editing (PE), enabling precise single-nucleotide alterations without double-strand breaks (DSB). Preclinical and clinical studies have shown the potential of gene therapy to enhance collagen production, restore tissue integrity, and alleviate symptoms. However, challenges persist, including the lack of recurring mutations, the need for improved delivery methods, the reduction of off-target effects, and the development of novel therapies. Despite these challenges, advancements in gene editing techniques appear promising in enhancing editing efficiency while minimising unintended mutations, paving the way for more precise and safer genetic interventions for collagen disorders. Gene editing is fundamentally transforming medicine and biotechnology. Its applications encompass advanced diagnostics, tailored therapeutic strategies, and solutions for rare genetic disorders. By enabling precise genetic modifications, gene editing is paving the way for treatments of previously untreatable diseases, including those linked to collagen pathogenic variants. This review discusses the latest advancements in gene therapy techniques targeting collagen-related disorders. It explores innovative approaches like CRISPR-Cas9-mediated gene editing and highlights emerging strategies, such as allele-specific inactivation and base editing (BE). By examining these cutting-edge therapies and their potential clinical applications, this review highlights the transformative impact of gene editing in treating collagen-related conditions, while also identifying critical challenges and future directions for research
Procalcitonin to guide antibiotic use during the first wave of COVID-19 in English and Welsh hospitals: integration and triangulation of findings from quantitative and qualitative sources
Get PDFAim
To integrate the quantitative and qualitative data collected as part of the PEACH (Procalcitonin: Evaluation of Antibiotic use in COVID-19 Hospitalised patients) study, which evaluated whether procalcitonin (PCT) testing should be used to guide antibiotic prescribing and safely reduce antibiotic use among patients admitted to acute UK National Health Service (NHS) hospitals.
Design
Triangulation to integrate quantitative and qualitative data.
Setting and participants
Four data sources in 148 NHS hospitals in England and Wales including data from 6089 patients.
Method
A triangulation protocol was used to integrate three quantitative data sources (survey, organisation-level data and patient-level data: data sources 1, 2 and 3) and one qualitative data source (clinician interviews: data source 4) collected as part of the PEACH study. Analysis of data sources initially took place independently, and then, key findings for each data source were added to a matrix. A series of interactive discussion meetings took place with quantitative, qualitative and clinical researchers, together with patient and public involvement (PPI) representatives, to group the key findings and produce seven statements relating to the study objectives. Each statement and the key findings related to that statement were considered alongside an assessment of whether there was agreement, partial agreement, dissonance or silence across all four data sources (convergence coding). The matrix was then interpreted to produce a narrative for each statement.
Objective
To explore whether PCT testing safely reduced antibiotic use during the first wave of the COVID-19 pandemic.
Results
Seven statements were produced relating to the PEACH study objective. There was agreement across all four data sources for our first key statement, ‘During the first wave of the pandemic (01/02/2020-30/06/2020), PCT testing reduced antibiotic prescribing’. The second statement was related to this key statement, ‘During the first wave of the pandemic (01/02/2020-30/06/2020), PCT testing safely reduced antibiotic prescribing’. Partial agreement was found between data sources 3 (quantitative patient-level data) and 4 (qualitative clinician interviews). There were no data regarding safety from data sources 1 or 2 (quantitative survey and organisational-level data) to contribute to this statement. For statements three and four, ‘PCT was not used as a central factor influencing antibiotic prescribing’, and ‘PCT testing reduced antibiotic prescribing in the emergency department (ED)/acute medical unit (AMU),’ there was agreement between data source 2 (organisational-level data) and data source 4 (interviews with clinicians). The remaining two data sources (survey and patient-level data) contributed no data on this statement. For statement five, ‘PCT testing reduced antibiotic prescribing in the intensive care unit (ICU)’, there was disagreement between data sources 2 and 3 (organisational-level data and patient-level data) and data source 4 (clinician interviews). Data source 1 (survey) did not provide data on this statement. We therefore assigned dissonance to this statement. For statement six, ‘There were many barriers to implementing PCT testing during the first wave of COVID-19’, there was partial agreement between data source 1 (survey) and data source 4 (clinician interviews) and no data provided by the two remaining data sources (organisational-level data and patient-level data). For statement seven, ‘Local PCT guidelines/protocols were perceived to be valuable’, only data source 4 (clinician interviews) provided data. The clinicians expressed that guidelines were valuable, but as there was no data from the other three data sources, we assigned silence to this statement.
Conclusion
There was agreement between all four data sources on our key finding ‘during the first wave of the pandemic (01/02/2020-30/06/2020), PCT testing reduced antibiotic prescribing’. Data, methodological and investigator triangulation, and a transparent triangulation protocol give validity to this finding
Data sources:
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