Final-year student nurses were offered aspirant nurse roles to support busy clinical teams within district nursing services as part of the response to the COVID-19 pandemic. Student nurses in their final year of training had the opportunity to work as an aspirant nurse (paid band 4 position) for a 12-week period, as per the emergency education standards delivered by the Nursing and Midwifery Council in an effort to help out during the pandemic. This gave the students additional responsibilities to allow them to work autonomously but still under the supervision of the registered nurse. This role was separate to their student nurse role, becoming part of the clinical team where they were placed. Building on this concept, a collaboration between higher education institutions and the Essex Partnership University Trust resulted in the development of a structured pilot student autonomous visit programme, at the time referred to as non-direct supervision students. This initiative aimed at improving student learning and enhancing professional identity and confidence, while addressing challenges in recruitment and retention in community nursing roles. This article outlines the development and implementation of the pilot programme, evaluates its impact and discusses its implications for nurse education and workforce planning. Results indicate enhanced student preparedness and improved staff retention in district nursing, strengthening interprofessional collaboration between universities and NHS teams.
Displaced intra-articular calcaneal fractures (DIACFs) managed with open reduction internal fixation through extensile lateral or sinus tarsi approaches are associated with a high rate of soft tissue complications. We present the technique of minimally invasive percutaneous fixation of DIACFs and the early outcomes from a major trauma centre. This was a retrospective case series from a single major trauma centre between 2021 and 2024. Seventeen DIACFs in 13 patients were followed up for a mean of 14 months (range, 12-16 months). The mean age was 41 years (range, 18-60 years). Two out of 17 fractures were open injuries. There were seven Sanders type 2 and ten Sanders type 3 fractures. Simple tongue-type fractures were excluded. Fracture reduction was performed using a Schanz pin, combined with the 'Essex-Lopresti manoeuvre' and manual correction of varus and shortening. Fixation was with at least three 6.5 mm partially-threaded cancellous screws. Patients were immobilised in a below knee backslab for 6-weeks post-operatively. Radiological parameters (Böhler's angle, calcaneal height and width), the Kerr-Atkins score, VAS pain score, and any re-operations or complications were recorded. At final follow-up, the mean Kerr-Atkins score was 67 and the mean VAS pain score was 3.4. The average time from injury to surgery was 6.9 days (range, 3-21). All patients were mobilising unaided, and only 2 patients required orthotic footwear. One patient had a re-operation due to a late-declaring necrotic eschar. Mean Böhler's angle increased from 14.9° to 26.8° (p < 0.0001). The mean calcaneal height increased from 38.7 mm to 45.4 mm (p < 0.0001). No patients had developed clinical or radiological subtalar arthritis during the study period. In our case series, we have demonstrated that minimally invasive percutaneous fixation of DIACFs is a safe procedure, with a very low complication rate. Early functional and radiological outcomes are excellent, with all patients mobilising unaided, and most were able to wear normal footwear with a plantigrade, shoeable foot.
Psychiatric diagnoses can significantly inform identity and self-understanding but hold different meanings to different people. This research takes a symbolic interactionist approach and addresses these matters in relation to anorexia nervosa. Drawing on data collected through in-depth interviews with 13 participants diagnosed with anorexia, I examine the extent to which participants dis/identify with the diagnosis and how it informs their self-understanding. Findings suggest that participants first came to identify with anorexia via self-labelling or being labelled by others, and that an (increasing) identification with anorexia was learned through diagnostic framing in treatment and ongoing identity work. However, participants reflexively engaged with diagnostic definitions and explanations of their struggles resulting in anorexia identities that were differentially 'clinically' and 'critically' informed and were sometimes ambivalent. I conclude with a discussion of the implications of the research findings for therapeutic approaches to anorexia that seek to address identity.
Eunicid polychaetes are often found in association with Cold Water Corals (CWCs), even establishing symbiotic relationships, such as those described between Desmophyllum pertusum and Eunice norvegica. While genetic connectivity of CWCs across the North Atlantic has been widely studied, little is known about their associated fauna in this regard. Here, we present a study combining a focused analysis of the genetic connectivity of E. norvegica with a regional assessment of the distribution and evolutionary relationships of three CWC-associated eunicid species from the Cantabrian Sea and the North of the United Kingdom (190-1,230 m depth). An integrative approach using genetic (16S, COI and 18S), morphological and ecological data allowed the identification of the eunicids studied, with new records of Eunice cf. nicidioformis and Eunice cf. antarctica in the Cantabrian Sea, as well as previously undocumented associations with CWC species. In addition, RADseq data contributed to the delimitation of the closely related species E. norvegica and Eunice philocorallia. Moreover, the genetic connectivity of E. norvegica was studied trough a RADseq (1,067 neutral SNPs) approach. Our results indicate a single panmictic population across approximately 2,000 km, suggesting that oceanographic currents facilitate passive dispersal of E. norvegica lecithotrophic larvae, aided by coral host stepping-stones. The connectivity patterns observed for E. norvegica mirror those of D. pertusum, on which the worm is ecologically dependent. Our study highlights the importance of using integrated genetic, morphological and ecological data to characterise and delineate understudied CWC-associated species and improve our understanding of their dispersal capabilities and genetic connectivity to inform future conservation recommendations.
We present a review of a pro bono legal service provided to patients treated at a regional burns centre in the United Kingdom for the period between October 2012 and October 2019. A solicitor, supported by a paralegal, was available to give pro bono advice to any patient attending the burns service. The legal team provided assistance to patients and their relatives with advice pertaining to their personal and financial affairs as impacted by the injury. This was provided independently from, but in addition to, existing support from the hospital legal and ethical departments. The pro bono legal service has advised on 108 patient cases since this service began in October 2012 and has provided more than 2100 h of solicitors' time. 777 h were spent on non-compensation advice given on welfare benefits and insurance. Advice on welfare and/or financial matters was requested by all patients, and although potential claims for compensation against a third party were found in 83 cases, of these, the law firm operating the legal service was known to have been instructed to pursue recourse in only 16 cases. However, of the 16 cases instructed to make a compensation claim so far, 6 cases have settled, recovering a total of over £ 3.7 million. This review shows a likely benefit to patients from pro bono legal advice available in a burns unit setting. It also showed the significant financial gain to the government and potentially the NHS when a compensation claim was made by a patient.
We report an unusual mortality event affecting the isolated Egyptian fruit bat (Rousettus aegyptiacus) population in northern Cyprus, combining clinical admissions, microbiological findings, and roost surveys to assess magnitude and potential drivers. From January to June 2025, the Cyprus Wildlife Research Institute (CWRI) Wildlife Hospital received an unprecedented surge in admissions with 12 individuals (compared with a total of 16 admissions from 2017 to 2024), with high acute mortality: most bats arrived moribund and died within 12-24 h. Clinical records noted localized purulent lesions and abscesses in 58% of cases. Bacteriological culture and PCR assays recovered Staphylococcus aureus from abscesses and skin swab samples in multiple individuals; isolates exhibited susceptibility to tested antibiotics. Necropsy sampling confirmed viable S. aureus in several specimens despite prolonged storage. Concurrent targeted surveys of 10 known roosts in Feb-Mar 2026 documented marked declines at multiple historical sites, including reductions from hundreds to single-digit counts at formerly large colonies and the complete absence of bats at multiple roosts. No clear evidence of recent human disturbance, extreme weather anomalies, or reduced food availability was found; shotgun cartridges from historical hunting were present, but no direct anthropogenic cause was apparent. Although S. aureus infections-seasonally concentrated in winter-are consistent with observed lesions and may have contributed to morbidity and mortality, causality for the population-level declines remains unknown, and other factors (toxins, unassessed pathogens, and multifactor stressors) cannot be excluded. Given the genetic isolation and conservation significance of the Cyprus Egyptian fruit bat population, these findings are concerning. We recommend urgent, coordinated longitudinal population monitoring, expanded pathogen surveillance including whole-genome sequencing of S. aureus isolates, toxicological screening, and development of a species recovery plan incorporating emergency response, habitat protection, and public outreach.
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT geneenvironment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT1A receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration. Appeared originally in Mol Psychiatry 2023; 28:3243-3256.
The 18th GCC Closed Forum was held in New Orleans, LA, USA, on 11 April 2025. Representatives from international bioanalytical Contract Research Organizations were in attendance to discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at the meeting included: Compliance with US FDA Guidance for Biomarkers; Emerging Technologies; Sample Reconciliation Efforts; Chicken anti-Human IgG antibody; Post-extraction Sample Stability; Singlicate for LBA; Discrepancies of ELISpot data; Regulatory Inspection Experiences; Cross-validation Harmonization in Regulated Bioanalysis; and ELN/LIMS. Conclusions and consensus from discussions of these topics are included in this article.
High-intensity interval training (HIIT) and strength exercise (SE) induce corticospinal plasticity in exercised and non-exercised muscles. While HIIT's systemic neuromodulatory effects are well-established, SE's comparable remote responses remain unclear. This study investigated changes in corticospinal, intracortical, and spinal excitability, as well as motor performance, in non-exercised flexor carpi radialis following single-session HIIT and plantar flexion SE. Using a randomised crossover design, eighteen participants completed: (1) 20-minute high-intensity interval cycling, (2) high-intensity resistive plantar flexion, and (3) control. Corticospinal responses were assessed using transcranial magnetic stimulation and peripheral nerve stimulation; motor performance through reaction time tasks and maximum voluntary force at baseline and post-exercise. Only HIIT significantly increased motor-evoked potential amplitude (p = 0.002) and reduced short-interval intracortical inhibition (p = 0.04). HIIT reduced silent period duration compared to baseline and control (p <0.001), while SE showed reduction only versus control (p <0.001). Both HIIT and SE improved reaction time compared to baseline and control (p <0.05). These findings highlight differential corticospinal responses in a remote, non-exercised muscle, with HIIT inducing distributed excitability enhancements compared to SE. Unilateral, small-muscle SE may be insufficient to induce widespread corticospinal excitability changes, with implications for neurorehabilitation strategies targeting remote muscle groups.
The aim of this project was to design, develop and evaluate co-produced, evidence-based patient resources for adults with blunt chest injuries following hospital discharge. The project comprised two stages. 1) Face to face co-production workshop in which adults with lived experience of chest injuries and healthcare professionals developed the content for new patient resources. This was followed by an online workshop to design the format and finalise the patient resources. 2) Online surveys to evaluate the co-production process and the project outputs. Data analysis of surveys was completed using descriptive statistics and content analysis. 18 participants attended the face to face workshop, 14 continued to participate in the online workshop. Two resources were developed and designed; an advice sheet (also an easy read and screen reader/digital Braille software version) and an online animation providing additional information, with voiceover and subtitles. Feedback of the co-production process and final outputs was positive, with useful suggestions for future development. Recovery from blunt chest injuries following hospital is challenging. This co-production project has developed and designed two new patient resources accessible in a number of formats, that can support the patient through the recovery process. Recovery from blunt chest injuries is a challenging process, often resulting in negative outcomes including chronic pain and poor health-related quality of life.Advice and educational resources for patients with blunt chest injuries are reportedly unhelpful and highly variable in quality.New patient resources in a variety of accessible formats have been co-produced by adults with lived experience of chest injuries, their family members and healthcare professionals.These resources can guide patients through the recovery process following hospital discharge.
Donation after circulatory death (DCD) liver transplantation is currently limited by inferior outcomes compared with donation after brain death (DBD), predominantly due to ischaemia-reperfusion injury and biliary complications. Abdominal normothermic regional perfusion (aNRP) is an emerging graft-preservation technique that aims to improve graft viability, patient outcomes and reduce rate of complications in DCD liver transplantation. The aim of this review is to appraise the current literature on the utility of aNRP in liver transplantation surgery. The PRISMA guidelines for systematic reviews were followed and relevant databases searched. Primary outcomes were graft and patient survival rates. Secondary outcomes were primary non-function, early allograft dysfunction, biliary complications including ischaemic cholangiopathy (IC)/ischaemic type biliary lesions (ITBL) and retransplantation rates. Risk-of-bias analysis was conducted. Narrative synthesis was performed due to marked heterogeneity in the included studies. Fourteen studies (2014-2026) encompassing 1,278 transplanted aNRP liver grafts were included in this review. aNRP was associated with a reduction in IC/ITBL rates, lower rates of primary non-function and lower early allograft dysfunction compared with conventional retrieval (super rapid recovery followed by static cold storage). Graft loss and retransplantation rates were also lower in aNRP cohorts. Compared with DBD transplantation, aNRP outcomes were similar with near-zero rates of IC in both groups. No significant differences were also observed between aNRP and ex situ normothermic machine perfusion (NMP). aNRP is associated with reductions in biliary complications, graft loss and retransplantation compared with conventional DCD retrieval, with outcomes comparable to DBD and ex situ NMP and offers a solution to expand the donor pool.
Retinitis pigmentosa (RP) is a hereditary retinal degeneration disorder often caused by mutations in the rhodopsin gene, leading to photoreceptor death and vision loss. While structural misfolding of rhodopsin is a known contributor to disease pathology, the mechanisms of its cellular and in particular metabolic consequences are poorly understood. To study the direct effects of rhodopsin misfolding and structural rescue on cellular metabolism, we used the P23A mutant and its N2C/D282C stabilized counterpart as a structural tool to assess how differences in folding stability relate to measurable changes at the metabolite level. The engineered cysteine pair allows the formation of a disulfide bond restoring structural integrity and reinforcing the stable seven-transmembrane bundle. We used untargeted Gas Chromatography-Mass Spectrometry (GC-MS) metabolomics analysis conducted in inducible rhodopsin-expressing cell lines, providing a broad and general profiling of metabolic pathway alterations in response to the expression of RP mutants and their structurally rescued counterparts. Principal component analysis, hierarchical clustering, and K-means clustering revealed distinct metabolic signatures associated with each rhodopsin-expressing cell line, demonstrating a highly significant effect of genotype on global metabolite composition (F = 71.679; R2 = 0.93724; p = 0.001). Pairwise comparisons and background-subtracted analyses identified consistent alterations in arginine and proline metabolism, glutathione metabolism, and the TCA cycle, nucleotide, amino acid metabolism, redox regulation, and mitochondrial function in cells expressing misfolded P23A. Pathway enrichment highlighted key metabolites in the respective pathways as candidate biomarkers for the rhodopsin P23A mutation. As this study employs a non-retinal cell system, the observed metabolic changes reflect conserved responses to rhodopsin misfolding and proteostatic stress in the ER rather than a direct model of rod cell degeneration. Our findings support the hypothesis that there is a biochemical link, most likely the UPR, between rhodopsin folding/misfolding status and metabolic homeostasis and suggest that targeted metabolic modulation may offer a complementary therapeutic avenue for treating RP.
Contralateral symmetrising mastectomy (CSM) may be a good alternative to breast reconstruction for some women following a single mastectomy for breast cancer, but women report challenges accessing care. We explored the current practice and provision of CSM as an alternative to breast reconstruction in the UK. An online survey was developed to explore current pathways for women seeking CSM and the information and support provided. The survey was circulated via social media and the UK professional associations, July 2023-May 2024. One survey was completed per unit. Descriptive statistics were used to summarise the results. Content analysis was used for free text. 51 units participated in the survey. Of these, only 28% (n = 14) reported having a formalised pathway for women seeking CSM. Pathways varied in their requirements for multidisciplinary team discussions, psychology and/or plastic surgery referral and/or inclusion of a 'cooling off' period, but most had been developed exclusively by breast surgeons with little multidisciplinary involvement. None of the pathways had been developed with patients. Units without pathways reported managing patients on a case-by-case basis. Most units did not have a formal 'cooling off' period between index mastectomy and CSM but two-thirds would not perform the procedures at the same time as the therapeutic mastectomy. Over 70% (n = 36) only discussed CSM if this was specifically raised by the patient. There is significant variation in the practice and provision of CSM in the UK. Consensus-based guidelines are needed to support equitable and appropriate access to care.
Emergency department (ED) triage systems are essential for prioritizing patients based on clinical urgency, yet traditional methods are subject to inter-observer variability and limited predictive accuracy. Artificial intelligence (AI) and machine learning (ML) have emerged as promising tools to enhance triage decision-making. This systematic review synthesizes existing evidence on AI/ML-based triage systems in EDs, focusing on predictive performance and reported clinical outcomes, while critically appraising methodological quality and gaps affecting clinical applicability. A comprehensive search was conducted across PubMed, Scopus, CINAHL, IEEE Xplore, and Web of Science (2021-2026), supplemented by citation tracking. Studies developing or validating AI/ML models for ED triage and reporting quantitative performance metrics were included. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used for quality assessment. A narrative synthesis was performed due to substantial heterogeneity. Fourteen retrospective observational studies (2021-2026) from eight countries met the inclusion criteria (sample sizes: 657 to >2.6 million visits). Models included gradient-boosted trees, random forest, logistic regression, neural networks, natural language processing, and large language models. AUC-ROC ranged from 0.642 to 0.991 (highest for mortality (0.874-0.933) and pediatric critical illness (0.991)). However, calibration was reported in only three studies, external validation in only five, and only one study demonstrated direct clinical process improvement (reduced missed ECGs). No prospective or randomized controlled trials were identified. PROBAST rated 11 studies as low risk of bias, two as high, and two as unclear. AI/ML models show moderate to excellent retrospective predictive performance for ED triage outcomes, particularly ensemble tree-based and NLP-enhanced approaches. However, the evidence base is severely limited by overreliance on heterogeneous retrospective designs, insufficient calibration reporting, and lack of prospective or external validation. Consequently, the strength of conclusions regarding clinical applicability remains weak. Future research must prioritize rigorous prospective validation, calibration reporting, and randomized trials measuring patient-centered outcomes before clinical implementation is considered.
Wernicke's aphasia is a challenging communication disability to live with, characterised by fluent speech, impaired auditory comprehension and reduced self-monitoring. There is little literature addressing functional therapy approaches. For example, there is limited evidence for communication partner training (CPT) for this client group, despite research on its effectiveness more generally. It is not known how speech and language therapists (SLTs) understand and apply this limited and disparate evidence to their practice. To explore how SLTs assess and treat people with Wernicke's aphasia (PwWA), specifically how SLTs engage with PwWA; work with the multi-disciplinary team to support PwWA; support significant others of PwWA, including through the provision of CPT. In this qualitative interview study, SLTs were recruited through social media and professional newsletters. Interviews via videoconferencing followed a topic guide and were transcribed and analysed using Framework Analysis. Fifteen SLTs participated, with 1.5-34 years of experience, working in England and Wales across a range of inpatient and community settings. SLTs described a range of issues when working with PwWA. Building a therapeutic alliance was considered important, but could take longer than in other types of aphasia. Informal assessment was required for many PwWA, with published language assessments deemed unsuitable by many. It was perceived that available outcome measures did not capture change. SLTs took differing views on which theoretical models they should use to guide impairment-based therapy. Treatment choices were sometimes driven by trial and error. SLTs offered CPT throughout the stroke pathway, reporting it to be clinically useful; however, there was uncertainty around which communication strategies to recommend. Many SLTs viewed working with PwWA negatively. They wanted to help but felt unsure about how to do so, and commented that the evidence base for treatment was limited. SLTs worked most closely with occupational therapists to manage Wernicke's aphasia. SLTs expressed concerns around the quality of decision-making capacity assessments completed by other members of the multidisciplinary team and access to psychological support for PwWA. SLTs want evidence to guide their practice when working with Wernicke's aphasia. Further research is needed to inform CPT and outcome measures for PwWA. CPT should be supported by empirical research into interactions involving PwWA. There needs to be improved access to mental health support and high-quality decision-making capacity assessment for PwWA. What is already known on this subject Impairment-based treatments for Wernicke's aphasia from varied theoretical perspectives are reported in the literature. There is little literature reporting on functional approaches and communication partner training for Wernicke's aphasia. It is not known how practising speech and language therapists (SLTs) assess and treat people with Wernicke's aphasia (PwWA). What this paper adds to existing knowledge SLTs found PwWA difficult to work with; they wanted to help but felt unsure about what to offer. SLTs are offering communication partner training for Wernicke's aphasia throughout the stroke pathway; however, they expressed differing opinions on which communication strategies to recommend. What are the potential or actual clinical implications of this work? SLTs would like more research evidence to guide them when managing Wernicke's aphasia. There is a need for assessments, treatments, outcome measures and psychological support that meet the unique needs of PwWA.
Oropharyngeal dysphagia is common and often results in aspiration. Thickeners are widely used to thicken liquids to slow the liquid bolus and prevent aspiration and aspiration pneumonia, despite multiple concerns about their use. To date, there is little data on prescribing/dispensing practices. This study aims to provide the first overview of thickener dispensing practices, serve as foundational material for parties interested in research, practice and policy making, and guide further work in this area. We explored English general practitioner thickener dispensing practices for the five-year period 2019-2024 via the NHS Business Services Authority ePACT2 database and using descriptive statistics and linear regression to analyse the data. We hypothesized that with a large data set, it would be possible to detect trends in dispensing. Between 2019 and 2024, nearly three million thickening items were dispensed in primary care in England at a cost of nearly 90 million sterling. Thickened liquids is primarily an intervention for older people although there was a significant decreasing trend in dispensed thickener items in adult populations. Thickener dispensing has increased in the youngest age group (0-1-years-old). The cost of thickeners to the NHS has risen in the last year under study despite the significant decline in use observed for most age groups. Of dispensed items over the five-year period, the vast majority were gum-based. While the data provided in this study is limited to GP dispensed thickeners in England, it provides researchers, clinicians and policy makers with initial information on dispensing practices. From the available data, a decreasing dispensing trend is seen in the context of rising costs, older people comprise the population who primarily receive thickeners and gum-based products dominate the market. This study raises a number of questions regarding the use of thickeners for people with swallowing problems.
The main burden of non-invasive pneumococcal diseases in adults is largely due to community-acquired pneumonia (CAP). This study aimed to investigate the distribution and dynamics of pneumococcal vaccine serotypes and to determine the proportion of CAP cases attributable to serotypes covered by 13-valent conjugate vaccine (PCV13), the 20-valent conjugate vaccine (PCV20), and the 23-valent polysaccharide vaccine (PPV23) among adults in Germany from 2020 to 2023. In this prospective multicenter cohort study, we analyzed all adult patients with CAP enrolled between January 1, 2020, and December 31, 2023, at 26 centers in Germany who provided urine samples for serotype-specific urine antigen detection (SSUAD) testing. Annual trends of pneumococcal vaccine serotypes from 2020 to 2023 were calculated for all patients and patient groups at risk using cluster-robust generalized linear models with heteroscedasticity-consistent standard errors. Of the 2,028 patients with all-cause CAP, 1,504 (1,008 patients aged ≥ 60 years, 373 younger patients with at least one comorbidity) had urine samples analyzed with SSUAD tests. Overall proportion of vaccine-type pneumococcal pneumonia among all-cause CAP for PCV13, PCV20, and PPV23 serotypes was 5.41% (95% CI 4.12-7.06%), 8.11% (95% CI 6.35-10.31%), and 8.31% (95% CI 6.27-10.93%), and serotype 3 was the most prevalent serotype (52 cases). Among patients aged ≥ 60 years, an increasing annual trend was observed for serotype 3 (OR 1.84, 95% CI 1.01-2.67), PCV13 (OR 1.89, 95% CI 0.89-2.89), PCV20 (OR 1.57, 95% CI 0.99-2.14), and PPV23 serotypes (OR 1.47, 1.04-1.91). The findings demonstrate that vaccine serotypes, particularly serotype 3, continued to circulate and reemerged among older adults with CAP in Germany.
Excessive foraging of colonic mucin glycans by gut bacteria is associated with diseases such as inflammatory bowel disease. Although Akkermansia muciniphila is an important mucin degrader, the role of carbohydrate sulfatases that facilitate digestion of these heavily sulfated glycans remains unclear. Combining in vitro digestion assays, proteomics and structural biology, we show that A. muciniphila sulfatases, such as Amuc1755 and Amuc0953, have rare adaptations targeted towards known sulfated mucin structures. They show larger degrees of modularity, including a previously unknown mucin-binding domain. When grown on colonic mucin substrates, glycoproteins of reduced size were important for the growth of A. muciniphila. Further mutational analysis and localization studies revealed that desulfation of N-acetyl-D-glucosamine was periplasmic, while desulfation of D-galactose occurred extracellularly and in the periplasm. These data improve our understanding of contexts for the positive health correlations of A. muciniphila while metabolizing colonic mucin as its sole carbon source.
Children who start school at a younger age are more likely to receive pharmacological treatment for attention deficit hyperactivity disorder (ADHD). This pattern is widely attributed to peer-comparison biases, but the relative importance of different underlying mechanisms remains debated. We use administrative data from England to study how school starting age affects ADHD prescription rates from ages 5 to 15. Exploiting a sharp school-entry cutoff and comparing children born just before and after September 1, we estimate both age- and grade-specific effects of early school entry. We find that early starters are 40-50% more likely to be treated for ADHD by age 15. This long-term gap is entirely driven by first-time prescriptions among children aged 5 to 8. Using a novel decomposition strategy, we isolate the roles of relative age, absolute age, the length of school exposure, and age at school entry. We find that relative age is the primary long-term driver, aligning with previous evidence on peer-comparison bias, while absolute age and the length of school exposure have only short-lived effects. Our findings suggest that early starters are more likely to receive marginal diagnoses due to their relative immaturity, and we recommend refining diagnostic guidelines and classroom grouping practices to reduce diagnostic gaps. The online version contains supplementary material available at 10.1007/s00148-026-01190-y.
A model of the generation of collective safety in social connection is proposed. This model posits that not being able to make sense of the behavior of others functions as an alert that motivates people who feel more vulnerable to the actions of societal collectives to find compensatory reason to trust in others. In two separate studies, participants in the United Kingdom and participants in the United States completed surveys the day before, and after, the 2024 general/federal elections. Preregistered moderated mediation analyses revealed that when family/friends behaved more (vs. less) inexplicably, participants who felt more (vs. less) vulnerable to the political party in power trusted sociopolitical relationships more rather than less. Such compensatory affirmations predicted renewed trust in personal relationships and strengthened feelings of connection post-election, suggesting that inexplicable behavior can motivate vulnerable people to generate the safety they need to see during societal transitions.