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What happened after the epidemic? Equine influenza surveillance sheds light on sources and seasonal risk in the United Kingdom.
No full textBACKGROUND: The epidemiology of equine influenza (EI) in the United Kingdom has not been systematically described since the 2019 epidemic. OBJECTIVES: To summarise UK EI surveillance (2020-2024), quantify outbreak seasonality and assess movement-related sources. STUDY DESIGN: Retrospective observational analysis of national surveillance and horse importation data. METHODS: Epidemiological data for laboratory-confirmed EI cases in the United Kingdom were collated. Outbreaks (EI-infected premises) were defined as one or more laboratory-confirmed cases on the same premises within a 4-week period. Monthly outbreak counts were analysed using negative binomial regression with year, calendar-quarter and ordered quartiles of 1-month lagged Irish exports to the United Kingdom by equid commodity code. A subset of Q4-2022 sales-related EI outbreaks were mapped. RESULTS: Epidemiological data were available for 149 cases on 126 premises. Outbreaks displayed a repeatable late-year pattern: Q4 (October to December) accounted for 52% (65/126), with a 3.25-fold higher per-month rate than the rest of the year. Over 75% (95/126) of premises reported a new arrival within ≤2 weeks; 56% (28/50) of index new-arrival cases with recorded origin came from Ireland. Q4 incidence exceeded Q1 (incidence rate ratio [IRR] 6.9, p < 0.001) and years 2021-2024 incidence exceeded 2020 (IRRs 4.5-5.6, p < 0.001). Adding lagged Irish imports other than pure-bred breeding animals, improved fit, attenuated the Q4 effect (IRR = 3.9, p < 0.001) and identified higher import quartiles as predictors (quartile-3: IRR 4.5, p < 0.001; quartile-4: IRR 3.7, p < 0.001). MAIN LIMITATIONS: Under-ascertainment, UK-wide exposure data versus Great Britain-only outcomes, COVID-19 suppression of movements/testing in 2020. CONCLUSIONS: EI in the United Kingdom in 2020-2024 was characterised by a notable October to December risk window and strong links to horse movements. Trade in non-pure-bred horses aligns with outbreak timing and partly explains the seasonal excess. Control measures should prioritise vaccination of new arrivals, post-arrival quarantine and strengthened biosecurity during transport
The Climate Opportunities and Risks of Contrail Avoidance
No full textNavigational contrail avoidance presents an opportunity for rapid reduction in aviation-attributable warming. Here, we use the Aviation Climate and Air Quality Impacts model to evaluate the global temperature changes associated with contrail avoidance towards 2050. If no avoidance is adopted, aviation is projected to contribute 0.040 K of CO₂ warming and 0.054 K of contrail warming by 2050. The combined warming from aviation CO₂ and contrails is 19% of the difference between current temperatures and the +2 °C limit above pre-Industrial levels, i.e. 19% of our remaining temperature budget. An avoidance strategy phased in over 2035-2045 may recover 9% of this budget, but a 10-year delay may reduce this to 2%. The warming due to additional CO₂ emitted during avoidance is two orders of magnitude lower than the expected contrail warming reduction. For every year of delay, the world will be on average 0.003 K hotter in 2050. The most significant climate risk associated with contrail avoidance is therefore inaction
Learning from tobacco control to tackle gambling industry harms.
No full textThe use of tobacco industry tactics by the gambling and other health harming industries means governments must act to prevent large scale avoidable harm, argue May van Schalkwyk and colleague
A randomized, controlled proof-of-concept trial evaluating durable effects of memory flexibility training (MemFlex) on autobiographical memory distortions and on relapse of recurrent major depressive disorder over 12 months.
No full textLow-intensity psychological interventions that target cognitive risk factors for depressive relapse may improve access to relapse prevention programs and thereby reduce subsequent risk. This study provides the first evaluation of an autobiographical memory-based intervention for relapse prevention, to establish whether memory-training programs that are efficacious for acute depression may also aid those currently in remission. We also provide the longest follow-up to-date of the effects of autobiographical memory training on autobiographical memory processes themselves. This pre-registered randomized-controlled proof-of-concept trial (N = 74) compared an autobiographical Memory Flexibility (MemFlex) intervention to Psychoeducation about cognitive-behavioral mechanisms which maintain depression. Both interventions were primarily self-guided, and delivered via paper workbooks completed over four weeks. The key cognitive outcome was ability to retrieve and alternate between specific and general autobiographical memories. Co-primary clinical outcomes were time until depressive relapse and depression-free days in the twelve-months following intervention. Results indicated a small-moderate effect size (d = 0.35) in favor of MemFlex for the cognitive outcome. A small Hazard Ratio (1.08) was observed for time until depressive relapse, along with a negligible effect size for depression-free days (d = 0.11). Although MemFlex produced long-term improvement in memory retrieval skills, there was little support for MemFlex as a relapse prevention program for depression
Combining protection and restoration strategies enables cost-effective compensation with ecological equivalence in Brazil
No full textEcological compensation and offsets have been used worldwide to repair the residual impacts caused by human activities. Achieving ecological equivalence in them has been challenging, and conflicts between development and environmental sectors commonly arise. We addressed this issue by testing an approach that is cost-effective and includes equivalence in compensation. We used the Brazilian Native Vegetation Protection Law's Legal Reserve (a native vegetation percentage of every rural property that must be conserved) compensation scheme as a study case. We created scenarios to test the law's three main compensation strategies (vegetation protection, restoration, and regularization of private lands inside public protected areas) separately and combined. We used a recently developed framework to assess ecological equivalence, including biodiversity, landscape, and ecosystem attributes measured and exchanged in a disaggregated manner. Cost-effectiveness was evaluated regarding deficit resolution (deficit in Legal Reserve needing compensation), economic costs, and native vegetation gained (additionality). The most effective strategy for deficit resolution was restoration (98.99 % of resolution), followed by protection (40.22 %) and regularization (0.15 %). Restoration was the most expensive strategy, but it also had the highest additionality. Combined scenarios resulted in balanced cost-effectiveness. The combination of protection followed by restoration was the best strategy, since its deficit resolution was high (99.47 %), with an intermediate cost and additionality. It is thus possible to make cost-effective compensation exchanges accounting for ecological equivalence adequately. We also used simple calculations in a new spatial optimization automated deficit and compensation prioritization path to generate spatially explicit results. Considering ecological equivalence guarantees additionality and more equitable spatial distribution of ecological benefits. These findings underscore the importance of incorporating equivalence in compensation, offering a promising avenue for bolstering efforts in compensation and offset schemes to address the ongoing climate and environmental global crisis by proposing a new approach to achieve this
Wnt/β-catenin signalling modulates the timing of cell fate decision making in the early mouse embryo.
No full textCell fate choice is a key event happening during preimplantation mouse development. From embryonic day 3.5 (E3.5) to E4.5, the inner cell mass (ICM) differentiates into epiblast (Epi, NANOG expressing cells) and primitive endoderm (PrE, GATA6, SOX17 and/or GATA4 expressing cells). The mechanism by which ICM cells differentiate into Epi cells and PrE cells remains partially unknown. FGF/ERK has been proposed as the main signalling pathway for this event, but it does not explain co-expression of NANOG and GATA6 or how the cell fate choice is initiated. In this study, we investigate whether Wnt/β-catenin signalling also plays a role. To this end, we use two in vitro models based on inducible GATA6 expression: one in 2D (flat cultured cells), and another in 3D, namely ICM organoids. By combining these in vitro models with in vivo mouse embryos, chemical and classical genetics, and quantitative 3D immunofluorescence analyses, we propose a dual role for Wnt/β-catenin signalling. We find that β-catenin, acting alongside FGF/ERK signalling, helps to guide the cell fate choice towards PrE. Additionally, by regulating GATA6 and GATA4 stability, Wnt/β-catenin signalling further facilitates this choice. To summarise, we observe that Wnt/β-catenin signalling pathway activation promotes PrE differentiation, while its inhibition delays it
Strong constitutive NF-κB signaling in B cells drives SLL/CLL-like lymphomagenesis and overcomes microenvironmental dependencies.
No full textAberrant activation of NF-κB transcription factors is a hallmark of human lymphomas. Most lymphoma-intrinsic as well as microenvironment-induced NF-κB activation occurs upstream of the key kinase IKK2, therefore affecting additional pathways. Here, we show that canonical NF-κB signaling in mouse B cells, induced through the expression of one or two copies of a constitutively active IKK2 variant, dose-dependently drives lymphomagenesis. The observed phenotype and stereotypic B cell receptor clonality resemble human small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL). Stronger IKK2 signaling drives early B1a cell expansion and uniform SLL/CLL-like lymphomagenesis, while intermediate signals cause more heterogeneous malignancies. Mechanistically, constitutive IKK2 signals provide a profound cell-intrinsic competitive advantage to B1a cells and dose-dependently synergize with TCL1 overexpression in driving aggressive CLL. Further, strong constitutive NF-κB activation overcomes critical microenvironmental dependencies of TCL1-driven lymphomas. Our findings establish canonical NF-κB as an oncogenic driver in lymphoma and reveal reduced microenvironment dependency as a key NF-κB-mediated mechanism, thus highlighting its therapeutic relevance
Statistical agnostic regression: A machine learning method to validate regression models.
No full textINTRODUCTION: Regression analysis is a central topic in statistical modeling, aimed at estimating the relationships between a dependent variable, commonly referred to as the response variable, and one or more independent variables, i.e., explanatory variables. Linear regression is by far the most popular method for performing this task in various fields of research, such as data integration and predictive modeling when combining information from multiple sources. OBJECTIVES: Classical methods for solving linear regression problems, such as Ordinary Least Squares (OLS), Ridge, or Lasso regressions, often form the foundation for more advanced machine learning (ML) techniques, which have been successfully applied, though without a formal definition of statistical significance. At most, permutation or analyses based on empirical measures (e.g., residuals or accuracy) have been conducted, leveraging the greater sensitivity of ML estimations for detection. METHODS: In this paper, we introduce Statistical Agnostic Regression (SAR) for evaluating the statistical significance of ML-based linear regression models. This is achieved by analyzing concentration inequalities of the actual risk (expected loss) and considering the worst-case scenario. To this end, we define a threshold that ensures there is sufficient evidence, with a probability of at least 1-η, to conclude the existence of a linear relationship in the population between the explanatory (feature) and the response (label) variables. CONCLUSIONS: Simulations demonstrate that the proposed agnostic (non-parametric) test can perform an analysis of variance comparable to the classical multivariate F-test for the slope parameter, without relying on the underlying assumptions of classical methods. A power analysis on a putative regression task revealed an overinflated false positive rate in standard ML methods, whereas the SAR test exhibited excellent control. Moreover, the residuals computed using this method represent a trade-off between those obtained from ML approaches and classical OLS
A Visual Method to Compare the Quality and Complexity of Archaeological Textiles: The Cotton Mantas of Pre-Hispanic Colombia
No full textConcepts such as cost, value, skill, complexity, and quality are central to archaeological interpretations of material culture, yet often they remain undefined, resulting in subjective and inconsistent analyses. This is particularly true in archaeological textile studies, where technological complexity, cost, and craftsmanship are frequently underexplored or assessed informally. This paper proposes a formal method for evaluating and comparing the production of archaeological textiles, using complexity and quality as proxies for skill and cost. Drawing on sociology, economics, and material culture studies, we argue that value is context-dependent, shaped by both intrinsic properties of objects and cultural frameworks. Skill involves embodied knowledge and culturally informed standards of what constitutes a ‘well-made’ artefact. To operationalise these concepts, we integrate the chaîne opératoire with a colour-coded matrix and comparative diagrams inspired by Kuijpers’ work on metallurgical skill (2018b, 2018c). These visual tools enhance transparency, interpretation, and reproducibility across case studies. We apply this method to five types of pre-Hispanic cotton mantas woven by the Muisca and Guane of Colombia’s Eastern Highlands, and a further comparative set from the southern Nariño department. The analysis identifies both shared and variable features that reflect differences in complexity, quality, and labour investment. Correlations among variables reveal forms of labour organisation and social constraints. Our visualisation tools highlight patterns within and across textile assemblages. By making the technical aspects explicit, this formal approach enables better comparison, reduces bias, and fosters more nuanced understandings of craft organisation, skilled labour and complexity in past technologies. (For an extended summary of this paper in Spanish, see Supplementary Materials)
The locomotor behaviour of subfossil Malagasy sloth-lemurs (Strepsirrhini: Indriidae) and koala-lemurs (Strepsirrhini: Megaladapidae): new insights from limb trabecular bone
No full textThe locomotion of Malagasy Quaternary subfossil lemurs, including palaeopropithecines (‘sloth-lemurs’) and megaladapids (‘koala-lemurs’), has been investigated on abundant postcranial remains. Proposed strategies include some that lack living primate parallels, such as sloth-like suspensory arboreality in palaeopropithecines, although the degree of suspensory behaviour in palaeopropithecines or locomotor diversity in koala-lemurs is poorly understood. Unlike the external morphology, internal bone structure in these taxa is largely unexplored. We compared the humeral and femoral trabecular architecture of sloth- and koala-lemurs with several extant mammals, studying spherical/hemispherical trabecular samples extracted from high-resolution scans. After defining locomotor categories from quantitative data, we tested links between trabecular parameters and locomotor modes through exploratory and multivariate analyses, accounting for body size and phylogeny. In extant mammals, only femoral trabecular traits, particularly the degree of anisotropy and bone volume fraction, were significantly associated with locomotion, distinguishing suspensory and bridging arboreal taxa from others. Using this model, we inferred suspensory adaptations in palaeopropithecines, especially Palaeopropithecus, confirming earlier reconstructions, but also in Megaladapis edwardsi, a striking result that would place it alongside extant orangutans as the largest mammals known to adopt such habits. This work highlights the potential of internal bone structure for reconstructing primate locomotor evolution