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Brain network connectivity underlying neuropsychiatric symptoms in prodromal Lewy body dementia
No full textNeuropsychiatric symptoms (NPS) are prevalent, emerge early, and are associated with poorer outcomes in Lewy body dementia (LBD). Research suggests NPS may reflect LBD-related dysfunction in distributed neuronal networks. This study investigated NPS neural correlates in prodromal LBD using resting-state functional MRI. Fifty-seven participants were included with mild cognitive impairment (MCI) with Lewy bodies (MCI-LB, n = 28) or Parkinson's disease (PD-MCI, n = 29). Functional MRI assessed connectivity within five resting-state networks: primary visual, dorsal attention, salience, limbic, and default mode networks. NPS were measured using the Neuropsychiatric Inventory. Principal component analyses identified three neuropsychiatric factors: affective disorder (apathy, depression), psychosis (delusions, hallucinations) and anxiety. Seed-to-voxel connectivity maps were analysed to determine associations between NPS and network connectivity. In PD-MCI, affective symptoms and anxiety were associated with greater connectivity between limbic orbitofrontal cortex and default mode areas, including medial prefrontal cortex, subgenual cingulate and precuneus, and weaker connectivity between limbic orbitofrontal cortex and the brainstem and between the salience network and medial prefrontal cortex (all pFWE<0.001). Psychosis severity in PD-MCI correlated with connectivity across multiple networks (all pFWE<0.001). In MCI-LB, no significant correlations were found between NPS severity and network connectivity. However, participants with anxiety demonstrated a trend towards greater connectivity within medial prefrontal areas than those without (pFWE=0.046). Altered connectivity within and between networks associated with mood disorders may explain affective and anxiety symptoms in PD-MCI. Neural correlates of NPS in MCI-LB, however, remain unclear, highlighting the need for research in larger, more diverse LBD populations to identify symptomatic treatment targets
Association of Complement Proteins with C Reactive Protein in Non-Obese Women with and Without Polycystic Ovary Syndrome
Get PDFComplement proteins are increased in polycystic ovary syndrome (PCOS), as are markers of inflammation, such as the C-reactive protein (CRP); however, both may be increased in obesity. We hypothesised that body mass index (BMI)-driven CRP would comparably associate with an increase in complement proteins when obesity was accounted for in non-obese women with and without PCOS. In a non-obese, non-insulin-resistant population without inflammation (24 with PCOS and 24 control women), plasma CRP was measured by immunoassay. Slow Off-rate Modified Aptamer (SOMA)-scan plasma proteomic analysis of the classical, lectin, and alternative pathway complement proteins was undertaken. BMI, insulin resistance, and CRP did not differ (p 0.05). CRP correlated positively (p < 0.05) with C4 of the classical pathways in women with PCOS alone. Hyperandrogenemia did not correlate with CRP or complement in non-obese PCOS. BMI correlated positively with C3, C3adesArg, C3a, iC3b, Factor B, Factor H, and properdin: classical pathway proteins; C1q, C4, C5 and C5a in PCOS women; BMI only correlated negatively with C1q in non-PCOS women. Upregulation of complement proteins occur in non-obese PCOS, and CRP is positively associated with complement protein changes in both women with and without PCOS. This indicates that BMI induces changes in CRP that lead to changes in the complement pathways, particularly the alternate pathway, with increases in CRP (though still within the reference laboratory normal range) leading to upregulation of complement proteins in PCOS. This suggests an enhanced set point for CRP-induced complement protein dysregulation in PCOS
Our medieval murder maps reveal the surprising geography of violence in 14th-century English cities
Get PDF949 Exploring the Relationship Between Clinical Factors and Ex-Vivo Skin Wound Healing
No full textAimThis study aimed to evaluate the effects of comorbidities, neoadjuvant chemotherapy, haemoglobin levels, and nutritional status on a novel model of ex-vivo wound healing.MethodHuman skin samples were obtained from surgical waste of patients undergoing plastic and reconstructive procedures. Ex vivo wounds were created using punch biopsies, cultured over a 48-hour healing time course, and analysed for mean healed area (%). Patient records were reviewed for comorbidities, smoking status, preoperative chemoradiotherapy, and haemoglobin and albumin levels. Data analysis was conducted using univariate and multivariate regression analyses to identify predictors of wound healing outcomes.ResultsA total of 64 ex vivo donor skin samples were analysed, with a mean area healed at 48 hours of 69.3% ± 20.3% and a median of 71.7%. Smoking, obesity, nutrition, haemoglobin, neoadjuvant chemotherapy, diabetes, autoimmune disease, or preoperative immunosuppressant use were not significant predictors of mean area healed at 48 hours (all p values > 0.05). However, concurrent autoimmune disease and immunosuppressant use significantly reduced the mean area healed (p = 0.048; 95% CI: [-1.86, -0.01]).ConclusionsThe ex vivo model examined real patient samples, offering insights into wound healing variability. No significant effects of smoking, obesity, nutrition, haemoglobin, or neoadjuvant chemotherapy were observed on healing outcomes. However, autoimmune disease and immunosuppressant use significantly reduced healing. Larger, diverse cohorts with extended follow-up are needed to address subgroup limitations. This model highlights the complexity of wound healing and its potential to bridge laboratory findings with clinical practice, enabling personalised medicine
Patient Reported Outcome Measures for Mental Health: Development and Pragmatic Evaluation in the NHS
Get PDFBackground: Patient-reported outcome measures (PROMs) are standardised questionnaires or interviews that elicit subjective reports of health. They have growing potential for improving patient-centred care and decision making. The National Institute for Health and Care Excellence (NICE) recommends considering their use at regular points in the treatment pathway for common mental health conditions and physical problems such as cancer.Aims: To assess the feasibility, acceptability and usefulness of implementing four established PROMS: the Patient Health Questionnaire-9 (PHQ-9) for depression, Generalised Anxiety Disorder-7 scale (GAD-7), Short Warwick & Edinburgh Mental Wellbeing Scale (SWEMWBS) and Distress Thermometer (DT), and to pilot two novel ‘developed for purpose’ satisfaction tools: Carers’ & Users’ Expectations of Service (CUES) and Recovering Quality of Life (ReQoL).Setting: Mental health multidisciplinary teams within the UK National Health Service.Methods: Outcomes evaluated were mental/physical symptoms, emotional distress, life/service satisfaction and global quality of life. Designs were pragmatic, including quantitative and mixed methods, cross sectional and prospective before and after studies.Results: The thesis comprises five original research publications and three academic linked papers. Where assessed, PROM acceptability and completion rates were high (76-98%), leading to changes in care in 49% cases. Following therapeutic interventions, a large clinical effect size was observed: within community mental health teams PHQ-9, GAD-7 scores and functioning all improved (Cohen’s d = 0.52-0.77). In cancer psychology services, median distress (DT) scores decreased significantly (Wilcoxon’s z = -4.83, p<0.001, Cohen’s d =1.22). Sensitivity to change was greater for ReQoL, PHQ-9, GAD-7 and DT than for SWEMWBS.Conclusions: This body of research provides cumulative evidence that validated mental health PROMS can reliably assess meaningful changes at key stages in a patient’s journey, with apparent absence of significant harms. PROMS should be more widely integrated into frontline care, to inform individual treatment planning and contribute to service improvements
Book Review: The Hamas Intelligence War Against Israel Netanel Flamer. Cambridge University Press, Cambridge, 2025. pp. 207. Pb. £30.99. ISBN: 9781009499408
No full textOpening paragraph:This book is a decisive contribution to our previously partial and fragmented understanding of the trajectory and capabilities of the intelligence services of the Palestinian Islamic Resistance Movement (Hamas) since its inception in 1988. Flamer’s research extends beyond the relatively narrow subject of Hamas’s intelligence operation, offering insights into the broader literature on the intelligence of violent non-state actors (VNSA), such as the Provisional IRA in Northern Ireland, on which there is a more substantial existing body of work. A common thread among these VNSAs is their strong focus on counterintelligence and operationally oriented offensive intelligence
Comparative Performance Of Clinician And Computational Approaches In Forecasting Adverse Outcomes In Intermittent Claudication
No full textIntroduction and ObjectivesMachine learning (ML) based prediction modelling has demonstrated superior abilities in analysing non-linear data with complex relationships. Pilot work in this work-stream has shown that ML techniques can accurately forecast adverse cardiovascular and limb events in patients with intermittent claudication. This is the first study to compare the predictive performance of ML approaches, traditional regression, and clinician prediction
Identifying haemochromatosis patients with C282Y homozygosity from inpatient electronic patient records in England using a novel algorithm: a retrospective observational study
Get PDFINTRODUCTION: Hereditary haemochromatosis (HH) is the most common genetic condition among populations of northern European ancestry, but it does not have a specific International Classification of Diseases 10th revision (ICD-10) diagnosis code. HH is commonly assigned the ICD-10 code E83.1 defined as 'disorders of iron metabolism'. However, the E83.1 diagnosis code is also applied to patients with transfusion-related iron overload and hyperferritinaemia from non-iron loading conditions. Venesection is the main treatment option for patients with HH and is assigned the Office of Population, Census and Surveys Classification of Interventions and Procedures, 4th revision (OPCS-4) code X36.2. We aimed to develop a novel algorithm to identify haemochromatosis patients with C282Y homozygosity from electronic patient records (EPR) using ICD-10 and OPCS-4 codes. METHODS: The Hospital Episode Statistics Admitted Patient Care (APC) database was used to identify all patients with the ICD-10 code E83.1 from 1 April 2018 to 31 March 2023 in our NHS Trust. Case notes were reviewed to evaluate the presence of HH, genotype, medical history and associated procedures. Algorithms were generated using Stata MP V.18 by applying a combination of ICD-10 and OPCS-4 codes to all patients with the diagnosis code E83.1 including those without HH gene mutations. RESULTS: A total of 9264 patient episodes were identified from the HES APC database corresponding to 787 unique patients: 479 (60.9%) C282Y homozygous, 107 (13.6%) C282Y/H63D compound heterozygotes, 42 (5.3%) other HH genetic mutations and 159 (20.2%) without any HH gene mutations. Six algorithms were developed to identify patients with HH within inpatient EPR, all of which showed improved positive predictive value (PPV) compared with the baseline cohort. The application of the OPCS-4 code for venesection (X36.2) in five of the algorithms resulted in large improvements in specificity and increased all their PPVs to >70%. Algorithms 4 and 6 had the best PPV at 74.3% and 74.4%, respectively, and included the removal of patients with ICD-10 codes associated with transfusion-related iron overload and other conditions treated with venesection. CONCLUSION: These novel algorithms represent a more reliable method to detect haemochromatosis patients with C282Y homozygosity from EPR than the single ICD-10 code E83.1. It may be applied to large administrative datasets for investigation of HH in population studies
The Seaward Migration of European Eel at a Continental Scale: A Europe-Wide Biotelemetry Meta-Analysis
Get PDFThe European eel (Anguilla anguilla L.) has a catadromous life cycle, with a single panmictic population that colonises continental Europe and northern Africa yet migrates 5000 to 9000 km to spawn in the Atlantic Ocean. It is unknown how this continental migration is organised so individual eels arrive in time for spawning with conspecifics. This meta-analysis combined tracking data from 18 water bodies in freshwater and transitional systems distributed along the southwest-northeast axis of Europe, resulting in a dataset of 2306 eels, making it the most comprehensive in terms of geographical coverage and number of eels tagged. The eels were tracked using acoustic telemetry and the Nedap Trail System and allowed us to study the eel's migration phenology at a continental scale. The findings reveal that the day when eels arrive at sea varies significantly with latitude, with northern eels arriving earlier. Migration speed differs between tidal and non-tidal habitats, suggesting that tidal currents facilitate faster movement. However, despite these patterns, we observed substantial variability in arrival at sea time and migration speed within water bodies, suggesting that the eel's migration phenology is considerably plastic. The presence of water regulating structures such as weirs, pumping stations and hydropower plants can impact migration timing and speed, potentially delaying eels, but is likely dependent on local hydrological conditions which can be water body specific
