324139 research outputs found
Sort by
The genome sequence of an orbweaving spider, <i>Gibbaranea gibbosa</i> (Walckenaer, 1802)
Get PDFWe present a genome assembly from a specimen of Gibbaranea gibbosa (orbweaving spider; Arthropoda; Arachnida; Araneae; Araneidae). The genome sequence has a total length of 2,816.88 megabases. Most of the assembly (98.61%) is scaffolded into 13 chromosomal pseudomolecules, including the X 1 and X 2 sex chromosomes. The mitochondrial genome has also been assembled and is 14.1 kilobases in length
Relationship between left ventricular shape and cardiovascular risk factors: comparison between the Multi-Ethnic Study of Atherosclerosis and UK Biobank
Get PDFBackground: Statistical shape atlases have been used in large-cohort studies to investigate relationships between heart shape and risk factors. The generalisability of these relationships between cohorts is unknown. The aims of this study were to compare left ventricular (LV) shapes in patients with differing cardiovascular risk factor profiles from two cohorts and to investigate whether LV shape scores generated with respect to a reference cohort can be directly used to study shape differences in another cohort. Methods: Two cardiac MRI cohorts were included: 2106 participants (median age: 65 years, 54% women) from the Multi-Ethnic Study of Atherosclerosis (MESA) and 2960 participants (median age: 64 years, 52% women) from the UK Biobank (UKB) study. LV shape atlases were constructed from 3D LV models derived from expert-drawn contours from separate core labs. Atlases were considered generalisable for a risk factor if the area under the receiver operating characteristic curves (AUC) were not significantly different (p>0.05) between internal (within-cohort) and external (cross-cohort) cases. Results: LV mass and volume indices were differed significantly between cohorts, even in age-matched and sex-matched cases without risk factors, partly reflecting different core lab analysis protocols. For the UKB atlas, internal and external discriminative performance were not significantly different for hypertension (AUC: 0.77 vs 0.76, p=0.37), diabetes (AUC: 0.79 vs 0.77, p=0.48), hypercholesterolaemia (AUC: 0.76 vs 0.79, p=0.38) and smoking (AUC: 0.69 vs 0.67, p=0.18). For the MESA atlas, diabetes (AUC: 0.79 vs 0.74, p=0.09) and hypercholesterolaemia (AUC: 0.75 vs 0.70, p=0.10) were not significantly different. Both atlases showed significant differences for obesity. Conclusions: The MESA and UKB atlases demonstrated good generalisability for diabetes and hypercholesterolaemia, without requiring corrections for differences in mass and volume. Significant differences in obesity may be due to different relationships between obesity and heart shapes between cohorts
From just transitions to just transformations; observations from Aotearoa New Zealand in addressing the human wellbeing impacts of climate change
Get PDFThis paper interrogates the utility of a just transition framework for climate change and human wellbeing in the context of Aotearoa New Zealand. Drawing on historical conceptualisations and applications of just transitions, their limitations and potential, we argue that an expansive and anti-reductionist conceptualisation of the just transition is best suited to address complex and inter-sectoral issues across time and space. Expansive just transitions are characterised by four features; relationality, systems-thinking, place-based and inter-generational approaches, where emancipation is held as the overarching objective. While we argue in favour of an expansive and anti-reductionist just transition framework being employed in the face of complex issues, such as the human wellbeing impacts of climate change, we introduce the concept of a just transformation: achieving true equity and justice in the face of climate change requires a transformative approach, situated outside of the confines of the hegemonic economic system and linear transitions. Transformations and not transitions are required for the health and wellbeing outcomes desired amidst threats of climate change
Family-focused intervention programme to foster adolescent mental health and well-being: protocol for a multicountry cluster randomised factorial trial (FLOURISH Phase 2)
Get PDFIntroduction: Adolescent mental health problems represent a significant global health issue, particularly in low- and middle-income countries, such as the Republic of North Macedonia and the Republic of Moldova. Effective and scalable interventions are urgently needed to address these challenges. Methods and analysis: This protocol outlines a multicountry cluster randomised factorial trial, implemented according to the multiphase optimisation strategy (Phase 2), which evaluates the effectiveness and costs of three add-on components for the Parenting for Lifelong Health for Parents and Teens programme: adolescent mental health tools based on UNICEFs Helping Adolescents Thrive comics, adolescent peer support based on UNICEFs ‘I Support My Friends’ intervention and engagement booster designed to enhance attendance and programme completion through incentives. The study will recruit 720 families and involve 64 clusters in North Macedonia and Moldova. Primary outcomes will include adolescent internalising problems and social support, family functioning and attendance during the programme. Secondary outcomes will assess broader aspects of mental health among caregivers and adolescents, as well as implementation and cost outcomes. Data will be collected at baseline and postintervention, approximately, 8 weeks later. Statistical analyses will include regression models to assess the main and interaction effects of the intervention components and cost analyses. Ethics and dissemination: The study received ethical approval from the University of Klagenfurt in Austria (approval number: 2023–013), the Medical Faculty at St. Cyril and Methodius University in North Macedonia (approval number: 03-2144/4) and the National Committee of Ethical Expertise for Clinical Trials in Moldova (approval number: 1476). The results will be disseminated through peer-reviewed journals, conferences, webinars in multiple languages, regional forums, stakeholder meetings with policymakers and practitioners, public communication through media engagement and open access platforms, including data sharing and early release of findings. Trial registration details: Trial registration: NCT06562244; Project page: https://www.flourish-study.org/about.htm
Improving structural plausibility in diffusion-based 3D molecule generation via property-conditioned training with distorted molecules
Get PDFTraditional drug design methods are costly and time-consuming due to their reliance on trial-and-error processes. As a result, computational methods, including diffusion models, designed for molecule generation tasks have gained significant traction. Despite their potential, they have faced criticism for producing physically implausible outputs. As a solution to this problem, we propose a conditional training framework resulting in a model capable of generating molecules of varying and controllable levels of structural plausibility. This framework consists of adding distorted molecules to training datasets, and then annotating each molecule with a label representing the extent of its distortion, and hence its quality. By training the model to distinguish between favourable and unfavourable molecular conformations alongside the standard molecule generation training process, we can selectively sample molecules from the high-quality region of learned space, resulting in improvements in the validity of generated molecules. In addition to the standard two datasets used by molecule generation methods (QM9 and GEOM), we also test our method on a druglike dataset derived from ZINC. We use our conditional method with EDM, the first E(3) equivariant diffusion model for molecule generation, as well as two further models—a more recent diffusion model and a flow matching model—which were built off EDM. We demonstrate improvements in validity as assessed by RDKit parsability and the PoseBusters test suite; more broadly, though, our findings highlight the effectiveness of conditioning methods on low-quality data to improve the sampling of high-quality data
The Galaxy Activity, Torus, and Outflow Survey (GATOS). VII. The 20–214 μ m Imaging Atlas of Active Galactic Nuclei Using SOFIA
Get PDFWe present a 19.7–214 μm imaging atlas of local (4–181 Mpc; median 43 Mpc) active galactic nuclei (AGN) observed with FORCAST and HAWC+ on board the SOFIA telescope with angular resolutions ~3″–20″. This atlas comprises 22 Seyferts (17 Type 2 and five Type 1) with a total of 69 images, 41 of which have not been previously published. The AGN span a range of luminosities of log10(Lbol[ergs-1])=[42, 46] with a median of log10(Lbol[ergs−1])=44.1±1.0 . We provide the total fluxes of our sample using aperture photometry for point-source objects and a 2D Gaussian fitting for objects with extended host galaxy emission, which was used to estimate the unresolved nuclear component. Most galaxies in our sample are pointlike sources; however, four sources (Centaurus A, Circinus, NGC 1068, and NGC 4388) show extended emission in all wavelengths. The 30–40 μm extended emission in NGC 4388 is coincident with the narrow-line region at PA ~ 50°, while the dusty extension at longer wavelengths arises from the host galaxy at PA ~ 90°. Our new observations allow us to construct the best-sampled parsec-scales (spectral energy distributions, SEDs) available between 30 and 500 μm for a sample of nearby AGN. We estimate that the average peak wavelength of the nuclear SEDs is ~40 μm in νFν, which we associate with an unresolved extended dusty region heated by the AGN
Eco-pilgrimages: Linking humans, heritage, and hydrology
Get PDFOver the last century, the health of aquatic ecosystems around the world has reached critical levels. In the UK, waterways are severely polluted, and yet many wells and springs are still venerated as ‘sacred’. This article presents ‘eco-pilgrimages’ as a sustainability strategy to connect key heritage sites through ecological corridors. This aims, simultaneously, to strengthen biodiversity; to enable immersive historical and ecological education; to contribute to human well-being; and to provide more effective flood amelioration in river catchment areas
Cognitive testing and the hazards of cut-offs
Get PDFThe article reviews some basic statistical concepts used in medicine, including the mean, standard deviation, sensitivity and specificity. Using this background the authors describe how these can be applied to cognitive tests, taking the Montreal Cognitive Assessment (MoCA) as an example. Two different approaches to using the MoCA in diagnosing dementia are considered: one using a fixed cut-off score, the other taking account of normative data about the effects of age and educational level on MoCA scores. It is recommended that clinicians assessing cognitive function should not rely on a fixed cut-off score, but where possible compare the patient's result with those of people of comparable age and educational background, although normative data of this kind are not always available
SGLT2 inhibition, acylcarnitines and heart failure: a Mendelian randomization study
Get PDFObjective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are guideline-recommended agents for treating heart failure (HF), but the role of metabolomic biomarkers in underlying mechanisms, particularly acylcarnitines, remains unclear. This study examined the associations of acylcarnitines with SGLT2 inhibition and incident HF. Methods: This subcohort study included 2178 participants from the prospective China Kadoorie Biobank without cardiovascular disease, diabetes or cancer at baseline. Plasma levels of 40 acylcarnitines were quantified using targeted mass spectrometry-based platforms. The impact of genetically predicted random plasma glucose (RPG) via SGLT2 inhibition on acylcarnitines was assessed with Mendelian randomization (MR). The associations of acylcarnitines with HF risk were assessed using Cox proportional hazards models. Acylcarnitines were classified into short-, medium- and long-chain groups and analysed individually or summed as scores. Results: Of the 2178 participants, the mean (SD) age was 53.2 (9.8) years. 13 incident HF cases occurred during a median follow-up of 10.5 years. SGLT2 inhibition was associated with higher levels of acylcarnitines, while higher levels of acylcarnitines were associated with reduced HF risk. An unweighted acylcarnitines score was associated with SGLT2 inhibition (β, 2.04 (0.29, 3.79) SD increase per 1 mmol/L lower genetic RPG via SGLT2 inhibition) and HF risk (HR, 0.97 (0.93, 0.99) per 1-SD higher of the score). Glucokinase activation, another antidiabetic agent used for comparison, showed weaker associations with acylcarnitines. Conclusion: MR analysis indicated SGLT2 inhibition showed associations with acylcarnitines, which are also associated with HF risk. Our findings highlighted the potential involvement of acylcarnitines in the mechanisms between SGLT2 inhibitors and HF
Insights of SEDRIC, the Surveillance and Epidemiology of Drug-Resistant Infections Consortium
Get PDFThe increasing threat from infection with drug-resistant pathogens is among the most serious public health challenges of our time. Formed by Wellcome in 2018, the Surveillance and Epidemiology of Drug-Resistant Infections Consortium (SEDRIC) is an international think tank whose aim is to inform policy and change the way countries track, share, and analyse data relating to drug-resistant infections, by defining knowledge gaps and identifying barriers to the delivery of global surveillance. SEDRIC delivers its aims through discussions and analyses by world-leading scientists that result in recommendations and advocacy to Wellcome and others. As a result, SEDRIC has made key contributions in furthering global and national actions. Here, we look back at the work of the consortium between 2018-2024, highlighting notable successes. We provide specific examples where technical analyses and recommendations have helped to inform policy and funding priorities that will have real-world impact on the surveillance and epidemiology of infections with drug-resistant pathogens