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Epilepsy in the Aging Brain: Time to Rethink the Narrative
Get PDFThis article reflects key themes and discussions from the American Epilepsy Society Annual Meeting 2025, Epilepsy and Aging Special Interest Group (SIG) session entitled "Multimodal Biomarkers of Epilepsy in Older Adults." The perspectives presented here are intended to highlight emerging priorities for the field. Epilepsy in older adults is the fastest-growing segment of the epilepsy population worldwide. Despite rising incidence, prevalence, and substantial morbidity, care for late-onset epilepsy (LOE) remains anchored to a seizure-centric framework that inadequately addresses the broader consequences of seizures in later life. Older adults with LOE face markedly increased risks of dementia, mortality, and stroke, yet are frequently excluded from epilepsy and Alzheimer's disease (AD) clinical trials. Patient-centered outcomes, including cognition, sleep, function, and quality of life, remain underprioritized. In this article, we argue that LOE requires multimodal biomarkers and multidisciplinary care. We contend that LOE should be reframed as a biologically meaningful warning signal of network vulnerability and overlapping brain pathology, rather than a late-life complication to be managed pragmatically. Cognitive dysfunction is common, heterogeneous, and often precedes overt neurodegenerative diagnoses, positioning cognition as an early clinical signal. Neuroimaging and electrophysiological evidence further place LOE along a continuum intersecting cardiovascular risk factors, sleep disruption, and AD biology, challenging traditional silos between epilepsy and dementia care. We argue for greater inclusion of older adults in antiseizure medication trials and for the inclusion of individuals with epilepsy in AD clinical trials. We propose a brain-health-centered framework for LOE that integrates longitudinal electroencephalography, particularly sleep-inclusive strategies, routine cognitive screening with targeted neuropsychological assessment, neuroimaging, vascular and sleep risk evaluation, and selective use of neurodegenerative biomarkers when clinically actionable. Together, these shifts move care beyond seizure counting toward a comprehensive brain-health model aligned with the realities of aging epilepsy
Comorbidities, medication use, and overall survival in eight cancers: a multinational cohort study of 1.7 million patients across Europe
Get PDFBackgroundReal-world evidence provides valuable insights into cancer burden, presentation, and care variations. Through a large-scale federated approach, this study aims to explore patient characteristics and overall survival for eight cancers using data from 11 electronic health records and cancer registries from eight European countries, mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM).MethodsPatients aged 18 years or older with a primary cancer diagnosis between 2000 and 2019 were included. Patients were followed from cancer diagnosis until death, database exit, or study end. Mortality data was sourced from linked national or subnational death registries for most databases. Patient characteristics, including comorbidities, and medication use, were summarised. Age-standardised overall survival (OS) at one, five, and ten years were calculated using the Kaplan-Meier method and stratified by cancer type, age group and sex.FindingsThere were 1,796,278 eligible cancer patients included with most diagnoses in individuals aged 60-79 years. Top comorbidities and medications were relatively consistent across databases, with certain variations observed by cancer type, possibly indicative of early cancer signs and risk factors. For instance, anaemia was frequent in colorectal (9% [HUS]-23% [IMASIS]; 791/8395-730/3141 individuals) and stomach cancers (10% [HUS]-34% [IMASIS]; 130/1277-225/670), while chronic obstructive pulmonary disease (18% [SIDIAP]-34% [HUVM], 5310/29,009-1039/3063) and pneumonia (5% [CPRD GOLD]-33% [UTARTU], 1904/34,990-1001/3063) were common in lung cancer patients. Breast and prostate cancers had the highest one, five and ten-year overall survival, with 5-year OS ranging from 76% [ECi]-85% [IMASIS] and 75% [HUVM]-83% [SIDIAP], respectively. Pancreatic cancer showed the lowest survival ranging from 3% [NCR]-25% [IMASIS] 5-year OS. Variations in cancer survival estimates were observed across data sources and countries.InterpretationFederated analysis of diverse European real-world databases, standardised to OMOP-CDM, offer a valuable benchmark for future cancer research, particularly in understanding prodromes and risk factors, often recorded in routinely collected healthcare data prior to cancer onset.FundingThe European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union's Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations partners
Dynamic shocks powered by a wide, relativistic, super-Eddington outflow launched by an accreting neutron star in the mid-20th century
Get PDFAccreting systems can launch powerful outflows which interact with the surrounding medium. We combine new radio observations of the accreting neutron star X-ray binary (XRB) Circinus X-1 (Cir X−1) with archival radio observations going back 24 yr. The pc scale wide-angle radio and X-ray emitting caps found around Cir X−1 are identified as synchrotron emitting shocks with significant proper motion and morphological evolution on decade time-scales. Proper motion measurements of the shocks reveal they are mildly relativistic and decelerating, with apparent velocity of at a propagation distance of 2 pc. We demonstrate that these shocks are likely powered by a hidden relativistic () wide-angle conical outflow launched in , in stark contrast to known structures around other XRBs formed by collimated jets over 1000s of years. The minimum time-averaged power of the outflow required to produce the observed synchrotron emission is , while the time-averaged power required for the kinetic energy of the shocks is , where n is the average ambient medium number density. This reveals the outflow powering the shocks is likely significantly super-Eddington. We measure significant linear polarisation up to in the shocks demonstrating the presence of an ordered magnetic field of strength . We show that the shocks are potential PeVatrons, capable of accelerating electrons to and protons to , and we estimate the injection and energetic efficiencies of electron acceleration in the shocks. Finally, we predict that next generation gamma-ray facilities may be able to detect hadronic signatures from the shocks
Freedom as perfect, rounded and lustrous as a pearl: fugitive subjectivity in The Golden Bowl
No full textAn ice sheet‐to‐ocean analysis of carbon stores and fluxes in Earth's polar regions (RECCAP2, polar ice sheets)
Get PDFThe polar ice sheets, their surrounding land fringes and oceans (68 × 106 km2; 13% of Earth's surface) are hot spots for carbon cycle perturbation under future climate change due to glacier retreat, rising meltwater fluxes, reduced sea ice, thawing permafrost, warming land-surfaces and increased precipitation. Here we assess carbon stored and exchanged with the atmosphere (as carbon dioxide and methane) across an expansive bipolar ice-to-ocean domain. We show that the polar regions harbor large reserves of carbon stored in sediments, rocks and the ocean, which differ in their reactivity and turnover times: 5,300–22,200 PgC of organic carbon and 5,600–8,600 PgC of inorganic carbon. These carbon reservoirs include potential reserves of marine and subglacial methane hydrate (80–570 PgC), which could become destabilized under future warming scenarios. Oceans (270–360 PgC) and ice sheets (14–96 PgC Greenland, 5,000–21,000 PgC Antarctica) dominate organic carbon stores, with smaller (but regionally important) stocks found in ice sheet land fringes (13–58 PgC). Estimates of natural CO2 and CH4 fluxes from these polar regions to the atmosphere present high uncertainty but highlight oceanic CO2 sinks in Greenland (−110 to −49 TgC-CO2 a−1) and in the ICE and SPSS biomes of the Southern Ocean (−480 to 55 TgC-CO2 a−1), with potential CH4 sources associated with the Greenland Ice Sheet. Such high uncertainty in polar carbon reservoirs and fluxes is important to resolve if future feedbacks between the polar regions, Earth's carbon cycle and climate are to be conclusively determined
Ancestral neuronal receptors are bacterial accessory toxins
Get PDFHorizontal gene transfer events were crucial in the emergence of multicellular life. A striking example is the acquisition of Teneurins, putative surface-exposed toxins in bacteria that function as cell adhesion receptors in metazoan neuronal development. Here, we demonstrate the evolutionary relationships between metazoan and bacterial Teneurins. We use cryogenic electron microscopy and bioinformatic analysis to show that bacterial Teneurins harbour a toxic protein in a proteinaceous shell. They are rare but widely distributed across bacterial taxa and are predominantly seen in species with complex social behaviours, suggesting roles in cell-to-cell interaction. This work confirms that metazoan Teneurins are repurposed bacterial toxins that have evolved to be essential mediators of intercellular communication in all advanced nervous systems. Their acquisition was a key event in the evolution of metazoans
M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress
Get PDFMethionine-1 (M1)-linked ubiquitin chains, assembled by the linear ubiquitin chain assembly complex (LUBAC) and disassembled by the deubiquitinase OTULIN, are critical regulators of inflammation and immune homoeostasis. Genetic loss or mutation of the LUBAC subunits HOIP and HOIL-1 or of OTULIN causes autoinflammatory syndromes accompanied by metabolic defects, including amylopectinosis, lipodystrophy, and fatty liver disease. Yet, it remains unclear how LUBAC and OTULIN control metabolic signalling. Here, we demonstrate that LUBAC and OTULIN dynamically regulate the energy-sensing kinase AMPK, a central sensor and switch for cellular and organismal energy balance. LUBAC's activity through the catalytic subunit HOIP is required for full AMPK activation in response to energetic stress, whereas OTULIN antagonises this response. LUBAC and OTULIN form a complex with AMPK, and LUBAC can directly ubiquitinate AMPKα and β subunits in cells and in vitro, establishing AMPK as a bona fide M1-linked ubiquitin substrate. Loss of LUBAC blunts AMPK activation, reduces bioenergetic adaptability, impairs autophagy, and sensitises cells to starvation-induced death, while Drosophila lacking Lubel - the fly orthologue of LUBAC - exhibit defective AMPK activation and reduced survival during starvation. Our findings identify M1-linked ubiquitination as a previously unrecognised regulatory layer controlling AMPK activation, metabolic adaptability, and the cellular response to energetic stress
Bullying in special schools: Types, frequency and school staff's self‐efficacy
Get PDFBullying is an education and health priority. The existing evidence has primarily focused on mainstream schools, with few studies conducted in special education schools. The present study aimed to quantify school staff's observations of bullying in special schools, also presenting by school specialism. The second part measured school staff self‐efficacy when dealing with bullying. A total of 72 school staff sampled from special schools in England participated in an anonymous survey with closed‐ and open‐ended questions. Results indicated that physical, verbal, and relational bullying were all evident in special schools, yet the observed frequency pattern changed when schools were split by specialism. Moreover, t‐test showed no significant difference between classroom and non‐classroom staff, gender or years of experience regarding self‐efficacy when dealing with bullying, but significant differences were found showing higher self‐efficacy for those who had received training on dealing with bullying. An understanding of bullying from the special school staff perspective provides insight for the development of anti‐bullying programmes or training on dealing with bullying, specifically designed for learners or school staff in special schools
Unpacking the complex mechanisms of teacher-to-student emotion transmission in foreign language classrooms: a mixed-methods study
No full textDrawing on emotion contagion and social appraisal theories of interpersonal emotion transmission and the control-value theory of achievement emotions, this mixed-method study explored how foreign language students’ perceptions of teacher emotions transferred to their own emotions in classroom settings. We collected data using self-report questionnaires completed by 408 middle school students, along with semi-structured interviews of 12 additional participants. Quantitative results revealed that students’ perceptions of teacher enjoyment and anxiety were positively associated with their own corresponding emotions. Appraisals of control and value collectively and partially mediated the association between perceived teacher enjoyment and student enjoyment whereas only control appraisal mediated the association between perceived teacher anxiety and student anxiety. Qualitative findings supported quantitative results and further illuminated the role of emotion contagion and social appraisal in teacher-to-student emotion transfer. However, interview data also revealed instances where students responded to teacher emotions with non-congruent emotions. Implications for innovative foreign language pedagogy are also discussed
100 m climate and heat stress data up to 2100 for 142 cities around the globe
Get PDFCities worldwide are increasingly facing the challenges of heat stress, a problem expected to worsen with ongoing climate change. The lack of detailed, city-specific data hinders effective response measures and limits the adaptive capacity of urban populations. In this data descriptor, we introduce a comprehensive database providing climate and heat stress information for 142 cities globally, covering the present and extending projections up to 2100 across three distinct climate scenarios, including two overshoot scenarios. This dataset includes 34 heat stress indicators at a spatial resolution of 100 meters, offering a unique database to identify vulnerable areas and deepen the understanding of urban heat risks. The data is presented through an accessible, user-friendly dashboard, enabling policymakers, researchers, and city planners, as well as non-experts, to easily visualise and interpret the findings, supporting more informed decision-making and urban adaptation strategies