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On manifolds with almost non-negative Ricci curvature and integrally-positive k th -scalar curvature: On manifolds with almost non-negative Ricci curvature..
Get PDFWe consider manifolds with almost non-negative Ricci curvature and strictly positive integral lower bounds on the sum of the lowest k eigenvalues of the Ricci tensor. If (Mn, g) is a Riemannian manifold satisfying such curvature bounds for k=2, then we show that M is contained in a neighbourhood of controlled width of an isometrically embedded 1-dimensional sub-manifold. From this, we deduce several metric and topological consequences: M has at most linear volume growth and at most two ends, it has bounded 1-Urysohn width, the first Betti number of M is bounded above by 1, and there is precise information on elements of infinite order in π1(M). If (Mn, g) is a Riemannian manifold satisfying such bounds for k≥2, then we show that M has at most (k-1)-dimensional behavior at large scales. If k=n=dim(M), so that the integral lower bound is on the scalar curvature, assuming in addition that the (n-2)-Ricci curvature is non-negative, we prove that the dimension drop at large scales improves to n-2. From the above results we deduce topological restrictions, such as upper bounds on the first Betti number
Developments and challenges in hit progression within fragment-based drug discovery
Get PDFFragment-based Drug Discovery (FBDD) is a proven methodology for the discovery of new therapeutics. After the identification of small molecular fragments, subsequent steps are guided by the "Design, Make, Test" (DMT) cycle. During the "Design" phase, chemical modifications are proposed that generate Structure-Activity Relationship information, improve interaction profiles and physicochemical properties. In the "Make" phase, designs are synthesised into viable compounds, with an emphasis on feasibility, scalability and the incorporation of novel chemistries enabling broad chemical space sampling. Finally, the "Test" phase evaluates these compounds through a series of assays, identifying binders and enabling Structure-Activity Relationship models that guide subsequent designs. Within DMT cycles, fragment progression - the process of converting initial hits into more potent follow-up lead compounds - is an essential component, but has many challenges associated with it. Here, we review such challenges along with recent developments designed to mitigate them
Towards Integrating Clinical and Non-Clinical Associates of Suicidality to Inform Potential Intervention Points among Youth in Nairobi Metropolitan, Kenya
Get PDFLiving in the Aftermath: Narratives on the impact of exposure to community and school violence in childhood on mental health and adjustment outcomes in later life
Get PDFObjectives: To understand the impact of and subsequent reactions to exposure to extreme violence in young adults in South Africa exposed during school years. In particular, to get an in‐depth understanding of its immediate consequences and factors that ameliorate or exacerbate it. Design: An exploratory qualitative research design was used, using purposive sampling. Methods: Semi‐structured interviews with 21 young South African adults aged 19–31 were conducted online. Transcripts were analysed using thematic analysis. Results: Violence exposure was found to result in trauma reactions with themes of a continued sense of being unsafe, feeling damaged and defective because of having these reactions, and mistrust towards others. In terms of coping reactions, a theme of avoidance and/or reacting with aggressive behaviour was identified, which likely exacerbated the challenges they experienced. By contrast, a more positive theme was identified in some, focused on having a sense of community and connectedness, which was experienced as ameliorating these challenges. Conclusions: Exposure to community and school violence in childhood has a lasting impact on mental health and adjustment in later life. The impact is likely worsened by mistrust of others, a continued sense of feeling unsafe and counterproductive coping mechanisms, while connectedness and community seem to lessen the impact. Further research can refine these findings to build an understanding of these mechanisms to inform secondary prevention and treatment interventions in low‐ and middle‐income countries
Visualizing electronic structure of twisted bilayer MoTe 2 in devices
Get PDFThe pursuit of emergent quantum phenomena lies at the forefront of modern condensed matter physics. A recent breakthrough in this arena is the discovery of the fractional quantum anomalous Hall effect (FQAHE) in twisted bilayer MoTe₂ (tbMoTe₂), marking a paradigm shift and establishing a versatile platform for exploring the intricate interplay among topology, magnetism, and electron correlations. While significant progress has been made through both optical and electrical transport measurements, direct experimental insights into the electronic structure – crucial for understanding and modeling this system – have remained elusive. Here, using spatially and angle-resolved photoemission spectroscopy (μ-ARPES), we directly map the electronic band structure of tbMoTe₂. We identify the valence band maximum, whose partial filling underlies the FQAHE, at the K points, situated approximately 150 meV above the Γ valley. By fine-tuning the doping level via in-situ alkali metal deposition, we also resolve the conduction band minimum at the K point, providing direct evidence that tbMoTe₂ exhibits a direct band gap – distinct from all previously known moiré bilayer transition metal dichalcogenide systems. These results offer critical insights for theoretical modeling and advance our understanding of fractionalized excitations and correlated topological phases in this emergent quantum material
Epidemiological Shifts in Visceral Leishmaniasis Incidence, Relapse, and Mortality in Brazil, 2007–2023: Analysis Using the National Notifiable Diseases Information System
Get PDFBackground: Brazil accounts for >90% of visceral leishmaniasis (VL) cases reported in South America. VL is a notifiable disease in Brazil and patient records are captured in the Sistema de Informação de Agravos de Notificação (SINAN) database. Methods: We reviewed 55 723 patient records from the SINAN system (2007–2023) to present temporal trends in patient demographics, drug regimens administered, and treatment outcomes. Disease incidence was modeled using a negative binomial regression, and predictors of mortality were assessed using logistic regression. Results: The VL incidence declined 6% annually (incidence rate ratio, 0.94 [95% confidence interval {CI}, 0.92–0.97]), primarily during 2019–2023. The median age at presentation was 10 years (interquartile range [IQR], 2–33 years) in 2007 and 32 years (IQR, 7–48 years) in 2023. The proportion of relapse at presentation also increased over time; compared to 2007–2009, the odds of relapse during 2019–2023 were 2.10-fold higher (95% CI, 1.87–2.37) adjusted for human immunodeficiency virus status. The use of liposomal amphotericin B increased markedly from 6.1% during 2007–2009 to 38.1% during 2019–2023, while antimony use declined from 68.0% to 32.7% over the same period. Following treatment, death from VL was highest among infants (50 years of age (1471/7615 [19.3%]), compared to the other age groups (3.5%, 2.2%, and 8.0% among ages ≥1 to <5, ≥5 to <15, and ≥15 to ≤50 years, respectively). Conclusions: The shift toward older patients and increased relapse at presentation indicates a major change in disease epidemiology in Brazil. These findings highlight the need for prioritizing interventions for older and relapsing patients
Harnessing iEcology data to uncover invasive species behaviour
Get PDFInvasive animal species threaten ecosystems, biodiversity and human livelihoods. Behavioural traits such as boldness, exploratory tendencies, learning ability and social interactions are known to influence invasion success. Yet these behavioural traits remain underexplored due to challenges in observing behaviour across large spatial and temporal scales. The emerging field of iEcology—studying ecology using digital data such as online photos, videos, sounds and text, generated for other purposes—offers a novel and scalable approach for investigating invasive species behaviour. Here, we demonstrate the application of iEcology to uncover novel insights into the behaviour of invasive species, such as dominance over the native species, interactions with native species or increased tolerance to humans, all critical for assessing species' invasion potential and management. We also discuss challenges of applying iEcology to studying the behaviour of invasive animals and highlight the need for careful validation and complementary methods. Finally, we highlight ways and provide a workflow to maximise the potential of iEcology for advancing the study of invasive species behaviour. We advocate for integrating iEcology into invasion science to advance our understanding of animal behaviours accompanying invasion success and ultimately to support the monitoring, management and mitigation strategies of biological invasions. We argue that iEcology is best viewed as a complementary tool that enriches traditional behavioural ecology and invasion biology, enabling rapid, accessible insights into one of the most urgent ecological issues of our time
Detection of Bartonella schoenbuchensis and a novel sigmavirus within the microbiome of deer keds ( Lipoptena cervi ) from the United Kingdom
Get PDFBackground: Lipoptena cervi is a member of the Hippoboscidae family of insects and is a hematophagous ectoparasite of cervid species, commonly referred to as the deer ked. Lipoptena cervi has a wide geographical distribution and can be found from North America through Europe into East Asia. Deer keds occasionally bite humans and domestic animals and might act as disease vectors. The microbiome associated with this species of biting insect has not been investigated. Methods: Mass sequencing of both DNA and RNA extracted from L. cervi specimens collected from two locations in southern England was conducted to characterise the complete microbiome consisting of bacterial, viral and eukaryotic species. Three specimens were collected after landing on humans in Somerset, and three specimens were collected from European roe deer (Capreolus capreolus) in Oxfordshire. Bioinformatic analysis investigated the host and microbial composition of each specimen. Results: Near-complete mitochondrial genomes were assembled from all six specimens confirming morphological speciation as L. cervi. Bacterial endosymbionts were the most dominant organisms identified with Candidatus Arsenophonus lipoptenae being most abundant. In specimens that had fed on deer, the pathogen Bartonella schoenbuchensis was detected. A novel sigmavirus was also detected in five samples, four of which yielded near-complete genomes. The closest relative of this virus was a sigmavirus found in a sheep ked (Melophagus ovinus) sampled in the Russian Federation. Conclusions: The data from this study will allow for a better baseline understanding of the microbiome of L. cervi and provide evidence for their role as vectors of zoonotic pathogens. Graphical Abstract
OxWell 2025: summary report
Get PDFThe OxWell Student Survey 2025 is a large-scale, repeated, non-identifiable school-based survey designed to examine the wellbeing, mental health, and educational experiences of children and adolescents aged 9–18 years in England. In 2025, over 35,000 students from 95 primary, secondary, and further education institutions participated. The survey was co-developed with young people and administered online during the school day. No directly identifiable data were collected to promote accurate reporting. The survey included measures of school belonging, bullying, safety, loneliness, neurodiversity, physical health indicators (e.g. sleep and activity), symptoms of anxiety and depression (RCADS-25), self-harm, and patterns of access to informal, semi-formal, formal, and digital mental health support. Optional modules explored additional domains including body-focused repetitive behaviours, substance use, chronic pain, and adverse experiences. This report for stakeholder partners gives some preliminary findings from the survey from a range of the questions asked. Findings highlight the central role of belonging. Informal support networks (parents and friends) remain the most frequently accessed sources of help, while school-based staff are commonly approached across year groups. Approximately one in five students self-identified as neurodivergent, and overlapping vulnerabilities—including loneliness, school absence, and self-harm—were frequently observed. Results are returned to participating schools and local authorities through a secure data platform (OxHub) to support evidence-informed planning. OxWell aims to integrate population-level research with local implementation to inform mental health policy and practice