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Preventive conservation of amber: some preliminary investigations. Pyrite Decay in Amber: Deterioration of Collections and Conservation Guidelines
Get PDFFossilised plant resin (amber) collections represent invaluable sources of information about the past. However, amber is particularly sensitive to exposure to light and oxygen, as well as changing temperature and humidity, rendering its preservation a major challenge. Here we reveal significant degradation of raw and carved amber specimens from part of the Early Cretaceous amber collection of Rábago-El Soplao (Cantabria, Spain), extracted more than a decade ago. These amber specimens, which originated from resin namely formed under subaerial conditions and so generally lack bioinclusions, are of remarkable importance from the palaeoecological, taphonomic, and physicochemical standpoint. Deterioration in amber pieces is due to pyrite decay resulting from the oxidation and hydration of iron sulphides in sedimentary rock remains intimately associated with the amber. We structurally, chemically and morphologically characterise hydrated-sulphate efflorescences found adhered on or included in amber as thin veins or nodules. Clays from sedimentary rock remains associated with the amber play a dual role: they react with acid derived from the dissolution of previous pyrite or sulphates to provide Al, Si, and K that are incorporated into the new sulphates, and they reinforce the alteration of pyrite by hygroscopically capturing water. We also provide guidelines for preventing and remedying pyrite disease in amber specimens, including treatment for new specimens entering collections, optimal physicochemical conditions for storage, and conservation for mildly-altered specimens. Our results urge putting measures in place to guarantee the integrity of the raw and polished amber pieces from the Rábago-El Soplao collection, and are more broadly relevant for the conservation of amber in palaeontological, mineralogical, gemological, and archaeological contexts
<i>BTN2A1</i> and <i>BTN3A1</i> as Novel Coeliac Disease Risk Loci: An In Silico Analysis
Get PDFCoeliac disease (CeD) is a gastrointestinal enteropathy triggered by the consumption of gluten in predisposed individuals. A recent study showed that individuals were at more than 10% risk of having CeD if a first-degree relative also had the disease. However, only around 50% of CeD genetic heritability is attributable to specific loci, with the majority of this heritable risk attributed to the HLA loci, while the remaining 50% of disease risk is currently unidentified. We investigated the butyrophilin family of immunomodulators as novel CeD risk loci. We sequenced the butyrophilin loci of 48 CeD and 46 control patients and carried out gene-based burden testing on the captured single-nucleotide polymorphisms (SNPs). We found a significantly increased BTN2A1 gene burden in CeD patients. To validate these results, the SNP data of 3094 CeD patients and 29,762 control participants from the UK Biobank database were subjected to single-variant analyses. Fourteen BTN2A1, ten BTN3A1, and thirteen BTN3A2 SNPs were significantly associated with CeD status. These results are interesting, as BTN2A1 and BTN3A2 have not been associated with CeD risk previously but are known to modulate the activation of Vγ9+ γδ T cells and NK cells. Twenty of the 37 SNPs above were associated with CeD status independent of the risk-associated HLA genotypes. All twenty of these SNPs, alongside a novel SNP not included in the above SNPs, were associated with CeD in HLA-DQ2.5-matched case-control groups. We reaffirm the association of the BTN3A2 locus with CeD risk and identify BTN2A1 and BTN3A1 as putative novel CeD risk loci
WONOEP XVII appraisal: The immunopathogenesis of epilepsy
Get PDFThere is a wealth of data indicating that the immune system plays an important role in seizure disorders. This includes autoimmune encephalitis, in which an immune response directed against neuronal antigens results in brain inflammation and subsequent seizure activity, as well as autoimmune‐associated epilepsy and neuroinflammatory changes detected in the tissues of patients with epilepsy, in which context it is often difficult to distinguish whether the inflammation is causal or a consequence of the seizures. Here, we summarize the discussion on this topic held during the XVII Workshop on Neurobiology of Epilepsy (WONOEP XVII), organized in 2023 by the Neurobiology Commission of the International League Against Epilepsy on the topic of the extracellular space in epilepsy. This critical appraisal explores the progress, emerging concepts, and discussion on the immunopathogenesis of epilepsy, with a particular focus on the interplay between the immune system and the central nervous system, highlighting the role of autoimmunity, neuroinflammation, and neuroimmunological processes in the etiology of various epileptic disorders and the prospects for new therapies
Prospects for dark matter observations in dwarf spheroidal galaxies with the Cherenkov Telescope Array Observatory
Get PDFThe dwarf spheroidal galaxies (dSphs) orbiting the Milky Way are widely regarded as systems supported by velocity dispersion against self-gravity, and as prime targets for the search for indirect dark matter (DM) signatures in the GeV-to-TeV -ray range owing to their lack of astrophysical -ray background. We present forecasts of the sensitivity of the forthcoming Cherenkov Telescope Array Observatory (CTAO) to annihilating or decaying DM signals in these targets. An original selection of candidates is performed from the current catalogue of known objects, including both classical and ultrafaint dSphs. For each, the expected DM content is derived using the most comprehensive photometric and spectroscopic data available, within a consistent framework of analysis. This approach enables the derivation of novel astrophysical factor profiles for indirect DM searches, which are compared with results from the literature. From an initial sample of 64 dSphs, eight promising targets are identified – Draco I, Coma Berenices, Ursa Major II, Ursa Minor, and Willman 1 in the North, Reticulum II, Sculptor, and Sagittarius II in the South – for which different DM density models yield consistent expectations, leading to robust predictions. CTAO is expected to provide the strongest limits above 10 TeV, reaching velocity-averaged annihilation cross sections of cm s and decay lifetimes up to s for combined limits. The dominant uncertainties arise from the imprecise determination of the DM content, particularly for ultrafaint dSphs. Observation strategies are proposed that optimize either deep exposures of the best candidates or diversified target selections
Identification of conserved immune-related adverse event risk factors and clinical outcomes in a pan-immunotherapy data mart
Get PDFBackgroundCancer immunotherapy (CIT) often triggers immune-related adverse events (irAEs). Analysis of irAEs in large checkpoint inhibitor (CPI) trials has enhanced their management and demonstrated their prognostic value for treatment outcome. However, data on irAEs in non-standard CITs are limited, and systematic exploration is lacking. Identifying predictive biomarkers for irAEs in these therapies is still emerging and essential for improving patient care.MethodsWe established a harmonized data mart from 27 early-phase CIT trials, encompassing 14 molecules with diverse mechanisms across various cancer indications. This dataset includes 3,608 patients, both CPI-naïve and CPI-experienced, with detailed information on clinical data, tumor characteristics, soluble biomarkers, and genome-wide genotyping. We examined the occurrence of different irAEs and CIT molecules concerning incidence, severity, and onset. A meta-analysis was conducted to assess the association between risk factors and the time to onset of irAEs. Finally, we explored the predictive value of irAEs for clinical outcomes, specifically measured by progression-free survival (PFS).ResultsOur analysis reveals significant variation in irAE incidence and kinetics across CIT molecules. Common irAEs include hepatitis, rash, acute kidney injuries, and hypothyroidism, with hepatitis often severe and others mild. Hepatitis is frequently associated with immunocytokine treatment, while T-cell bispecifics are linked to organ-specific toxicities. Hepatic metastases correlate with hepatitis but inversely with rash; elevated liver enzymes are associated with hepatitis, and high ferritin levels with acute kidney injury risk. Higher myeloid cell counts are associated with reduced rash likelihood. No tumor microenvironment associations were found, and polygenic risk scores show limited utility in our setting. Rash correlates with improved outcomes, whereas hepatitis is associated with a poorer prognosis, independent of baseline prognostic state assessed by the Real World Prognostic score.ConclusionsThese findings highlight the complexity of immune toxicities in early-phase trials, emphasizing the importance of the CIT class, as well as the roles of tumor burden, metastasis sites, and systemic immune state in the development of irAEs. Additionally, the observed association between skin toxicities and improved PFS suggests that skin toxicity could serve as a marker of systemic immune activation across immunotherapy contexts
Smoking, nicotine and pregnancy 3 (SNAP3) trial: protocol for a randomised controlled trial of enhanced support and nicotine replacement therapy (NRT) offered for preloading, lapse recovery and smoking reduction in pregnancy
Get PDFIntroductionNicotine replacement therapy (NRT) helps pregnant women quit smoking. Usual National Health Service (NHS) cessation care in pregnancy starts only after women stop smoking and comprises behavioural support and NRT. NRT is stopped if women restart smoking. We hypothesised that NRT would have a bigger effect on cessation in pregnancy if used: (1) to reduce smoking before quitting ('preloading'), (2) during brief smoking lapses after quitting and (3) to help those who cannot stop smoking, to reduce instead.Methods and analysisA two-arm parallel group, open-label, multicentre, assessor-blind randomised controlled trial. Participants are recruited at hospital antenatal clinics and other NHS settings throughout England and Wales or via social media advertising. Those enrolled are in antenatal care, Ethics and disseminationEthics approval was granted by the West Midlands-Coventry & Warwickshire Research Ethics Committee (REC reference: 21/WM/0172; Protocol number 21001; IRAS Project ID: 291236). Written informed consent will be obtained from all participants. Findings will be disseminated to the public, funders, relevant practice and policy representatives and other researchers.Trial registration numberISRCTN84798566
A scoping review of nature-based programmes in schools for mental health and wellbeing in young people
Get PDFBackground: Adolescent mental health difficulties are rising in the UK, yet school-based provision is limited. Nature-based Programmes (NbPs) are increasingly promoted as alternative or supplementary interventions for Mental Health and Wellbeing (MHWB), but evidence in secondary schools is under-explored. Aim: In this scoping review, we map existing NbPs in secondary school contexts; identify reported outcomes for mental health, wellbeing, and learning; and assess evidence quality for NbPs in secondary-school provision. Methods: We followed PRISMA-ScR guidelines (protocol: https://osf.io/qczas), searching five databases and the grey literature. Eligible studies reported school-based NbPs for students aged 10–18. The review process included screening, data extraction, and appraisal (using MMAT), and was co-produced with policymakers, educators, and young people. Results: From 17,723 records, 22 studies were included. NbPs encompassed school gardening, outdoor education, conservation, forest pedagogy, recreation in nature, and passive nature engagements. Most NbPs were delivered weekly on school grounds or in local greenspaces. Reported MHWB outcomes included reduced anxiety and stress, improved selfesteem and resilience, enhanced prosocial behaviour and school connectedness, and enhanced nature connectedness. Evidence for academic outcomes was mixed, with modest gains in science engagement and arithmetic but little evidence of broader academic performance benefits. Overall study quality was moderate, with small samples, limited use of control groups, and heterogeneity in outcome metrics. Conclusion: NbPs show promise for supporting adolescent MHWB in secondary schools, with school and nature connectedness emerging as potential mediators. However, evidence for cognitive and academic gains remains limited. In future, robust, UK-based Randomized Control Trials (RCTs) with standardised outcome measures are needed to assess efficacy of NbPs
Towards label-free biological reasoning synthetic dataset creation via uncertainty filtering
No full textSynthetic chain-of-thought (CoT) traces are widely used to train large reasoning models (LRMs), improving generalization by providing step-level supervision. Yet most approaches require ground-truth labels to seed or filter these traces—an expensive bottleneck in domains like biology where wet-lab data are scarce. We propose a label-free alternative: uncertainty-based filtering, which uses a model’s own confidence—quantified through established uncertainty metrics like self-consistency and predictive perplexity—as a substitute for external labels. We sample multiple reasoning traces and retain only low-uncertainty subsets. Applied to biological perturbation prediction, a domain where wet-lab labels are especially costly, we show that the filtered subset has higher accuracy, and that supervised fine-tuning (SFT) on uncertainty-filtered data outperforms unfiltered synthetic data, narrows the gap to ground-truth training, and surpasses strong LRM baselines. Ablations show that per-class filtering corrects for class-specific uncertainty scales and that hybrid uncertainty metrics yield higher-quality datasets. Our results suggest that modelinternal confidence is a powerful signal for efficient reasoning dataset creation, enabling LRMs in domains where supervision is expensive
The role of symbolic number knowledge in early arithmetic skills
No full textBasic numerical skills are fundamental for everyday activities and predict a wide range of educational, health, economic and social outcomes. While a wealth of evidence shows robust associations between symbolic number knowledge and arithmetic skills, there is limited research that examines these relationships in finer-grained detail. Further, there remain gaps in what is known about numerical ordinality, a distinct property of symbolic number, especially in young children.
This thesis centres on early numeracy skills in children 4–5 years old, focusing on the contribution that subcomponents of symbolic number knowledge, particularly ordinality, make to arithmetic skills. The aim of the work was twofold: to address gaps in the literature concerning the critical role of symbolic number in children’s developing arithmetic; and to explore the topic of ordinality in detail, including its measurement in young children. This was tackled through three connected studies.
The first was correlational, examining a set of cognitive factors and how they relate to arithmetic in a large sample of UK children. It established patterns of association that align with the literature; in this case, the strongest concurrent predictors were number knowledge and ordering (along with phoneme awareness). The second investigated the possible causal relationship between these aspects of symbolic number knowledge and arithmetic skill by experimentally testing the effects of a digital game in which children practised numeral recognition and counting. Compared with an active control, findings indicated improvements on number ordering, while effects on arithmetic were positive but not significant.
Study 3 reports the development of a new digital measure of number ordering. Initial reliability and validity testing demonstrated promise for assessment in young children. The new measure was administered to 4–5-year-olds and revealed a ‘reverse distance effect’, the youngest age found for this effect to date.
The findings contribute theoretical and practical insights to our understanding of early numeracy development. They help establish whether causal relations are present and offer clear steps for further research. The development of a novel measure that reliably and effectively captures young children’s ordinal number knowledge adds to the measurement literature. There are potential implications for teaching, identification, and intervention for children at risk of falling behind
From locked down to shut out: school exclusion patterns pre- and post-COVID-19 England
Get PDFThis article explores patterns of disciplinary school exclusion before and after the COVID-19 pandemic. It reviews current concerns about formal and informal disciplinary school exclusion and school attendance in England after COVID-19 and develops a cultural historical theoretical understanding of the reasons for rising rates of exclusion. Permanent and temporary school exclusion rates in England were much higher pre-COVID than in the rest of the United Kingdom, and this pattern has increased since the pandemic. School exclusion disproportionately affects students with special needs, in foster care and similar situations, living in poverty, and from some ethnic backgrounds. This paper argues that looking at the issue of school exclusion is another way of looking at issues of inclusion and diversity in schools and raises issues of equity for children and young people who are marginalized in education and society. The paper illustrates this argument by reporting on some of the findings from the Economic and Social Research Council funded project The Political Economies of School Exclusion Across the UK (2019–2024) that has revealed that in England, conflicting policies around educational attainment and inclusion have led to perverse incentives to not meet the needs of some young people by excluding them from school. In this article on exclusion patterns in England, we draw on data from documentary policy analysis, discussions and interviews with professionals from education and other welfare agencies during the lockdown period of COVID-19, as well as interviews with headteachers and other senior school leaders in England. The article problematizes and theorizes questions of the categorization of children after the pandemic in order to understand the motives that drive school professionals in practices of permanent and fixed period exclusions from school