179566 research outputs found
Sort by
What We Can Learn About Mars from the Magnetism of Returned Samples
Get PDFThe Red Planet is a magnetic planet. The Martian crust contains strong magnetization from a core dynamo that likely was active during the Noachian period when the surface may have been habitable. The evolution of the dynamo may have played a central role in the evolution of the early atmosphere and the planet’s transition to the current cold and dry state. However, the nature and history of the dynamo and crustal magnetization are poorly understood given the lack of well-preserved, oriented, ancient samples with geologic context available for laboratory study. Here, we describe how magnetic measurements of returned samples could transform our understanding of six key unknowns about Mars’ planetary evolution and habitability. Such measurements could i) determine the history of the Martian dynamo field’s intensity; ii) determine the history of the Martian dynamo field’s direction; iii) test the hypothesis that Mars experienced plate tectonics or true polar wander; iv) constrain the thermal and aqueous alteration history of the samples; v) identify sources of Martian crustal magnetization and vi) characterize sedimentary and magmatic processes on Mars. We discuss how these goals can be achieved using future laboratory analyses of samples acquired by the Perseverance rover
A Digital Tool for Clinical Evidence-Driven Guideline Development:Studying Properties of Trial Eligible and Ineligible Populations
Get PDFBackground: Clinical guideline development preferentially relies on evidence from randomisedcontrolled trials (RCTs). RCTs are the gold-standard method to evaluate the efficacy of treatments with the highest internal validity but limited external validity, in the sense that their findings may not always be applicable to or generalisable to clinical populations/population characteristics. The external validity of RCTs for the clinical population is constrained by the lack of tailored epidemiological data analysis designed for this purpose due to data governance, consistency of disease/condition definitions, re-duplicated effort in analysis code, etc.Objective: To develop a digital tool that characterises the overall population and differences between clinical trial eligible and ineligible populations from the clinical populations of a disease/condition regarding demography (in terms of groupings for e.g., age, sex, ethnicity), comorbidity, co-prescription, hospitalisation and mortality. Currently, the process is complex, onerous, and time-consuming, whereas a real-time tool may be used to rapidly inform a guideline developer’s judgement about the applicability of evidence.Methods: The National Institute for Health and Care Excellence (NICE) – particularly the gout guideline development group - and the Scottish Intercollegiate Guidelines Network (SIGN) guideline developers were consulted to gather their requirements and evidential data needs when developing guidelines. An R shiny tool was designed and developed using electronic primary healthcare data linked with hospitalisation and mortality data built upon an optimised data architecture. Disclosure control mechanisms were built into the tool to ensure data confidentiality. The tool was deployed within the Trusted Research Environment (TRE), allowing only trusted pre-approved researchers to conduct analysis.Results: The tool supports 128 chronic health conditions as index conditions and 161 conditions as comorbidities (33 in addition to the 128 index conditions). It enables two types of analyses via the graphic interface: overall population and stratified by user-defined eligibility criteria. The analyses produce overview statistical tables(on, e.g., age, gender) of the index condition population and, within the overview groupings, produce details on e.g., electronic Frailty Index (eFI), comorbidities, and co-prescriptions. The disclosure control mechanism is integral to the tool, limiting tabular counts to meet local governance needs. An exemplary result for gout as an index condition is presented to demonstrate the tool's functionality. Guideline developers from NICE and SIGN provided positive feedback on the tool.Discussion: The tool is a proof-of-concept, and the user feedback has demonstrated that this is a step towards computer interpretable guideline development.Conclusions: Using the digital tool can potentially improve evidence-driven guideline development through the availability of real-world data in real time.Keywords: Multimorbidity, clinical practice guideline, gout, Trusted Research Environment (TRE), National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN
Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with Multiple Sclerosis
Get PDFMultiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterized. Here we focussed on neutrophils, which are innate immune cells and rapid responders to inflammation, and which have recently been linked to other chronic autoimmune conditions. Multiple strands of evidence in patients with MS and in mice with the experimental autoimmune encephalomyelitis MS model suggest neutrophils may play a role in driving MS inflammation. Here, we performed proteomic analysis on neutrophils from patients with MS and healthy donors, revealing striking differences. In particular, granule proteins were significantly more abundant in the MS neutrophils compared to the healthy controls, with a particular overabundance of proteins in primary and secondary granules. In addition, members of the MAVS signalling pathway were differently regulated compared to healthy donor cells. Finally, we find that MS neutrophils do not suppress T cell activation equivalently to healthy neutrophils, and in particular are unable to suppress expression of CD161 on the T cells, indicative of a suppression of Th17 differentiation. We propose that neutrophil dysregulation in MS may contribute to dysfunctional T cell responses.</p
Arab feminist cyber activism:Theorising indigenous knowledge production and decolonising feminism
Get PDFThere is a need to situate current iterations of Arabic feminist cyber activism within the long history of feminist activism in the region and to read them as initiatives in/from the margin that adopt an intersectional approach with an explicit focus on indigenous decolonial knowledge. Some Arab feminist collectives active today are producing and enabling the production of distinctly indigenous articulations of feminism situated in opposition to what can be termed hegemonic feminism, embodied in international and non-governmental women’s organizations. I analyse these collectives’ works on two levels: the level of feminist positioning and the level of mediated activism. This article argues that these collectives’ interventions are authentic and of the region, embody resistance from the margin, as well as the ethos and politics of solidarity, particularly considering their positioning on Palestine, and they resist digital colonialism through abstaining from extractive media practices and adopting a redistributive ethos
Humeral head-split fracture in two dogs
Get PDFTwo skeletally immature female dogs were each investigated for chronic weight-bearing thoracic limb lameness. The first patient was lame for 2 months following a tumble whilst playing, and the second patient had been intermittently lame since 3 weeks of age. In both cases, radiographic examination of the shoulder revealed fissuring of the caudal humeral head consistent with an incomplete proximal humeral Salter-Harris type IV fracture with an Enoki-mushroom-like appearance of the caudal fragment, where two heads rise from a common stem. There was secondary neoarthrosis of the caudal humeral head fragment with the glenoid rim of the scapula. Humeral head-split fracture is an unusual fracture pattern that rarely occurs in skeletally immature patients, and conservative management appears to result in reasonable short-term outcomes. The role of early detection and surgical intervention remains unknown.</p
On the scalability of truss geometry and topology optimization with global stability constraints via chordal decomposition
Get PDFGeometry optimization was recently introduced to existing truss topology optimization with global stability constraints. The resulting problems are formulated as highly nonlinear semidefinite programming problems that demand extensive computational effort to solve and have been solved only for small problem instances. The main challenge for effective computation is the positive semidefinite constraints which involve large sparse matrices. In this paper, we apply several techniques to tackle the challenge. First, we use the well-known chordal decomposition approach to replace each positive semidefinite constraint on a large sparse matrix by several positive semidefinite constraints on smaller submatrices together with suitable linking constraints. Moreover, we further improve the efficiency of the decomposition by applying a graph-based clique merging strategy to combine submatrices with significant overlap. Next, we couple these techniques with an optimization algorithm that fully exploits the structure of the smaller submatrices. As a result, we can solve much larger problems, which allows us to extend the existing single-load case to the multiple-load case, and to provide a computationally tractable approach for the latter case. Finally, we employ adaptive strategies from previous studies to solve successive problem instances, enabling the joints to navigate larger regions, and ultimately obtain further improved designs. The efficiency of the overall approach is demonstrated via computational experiments on large problem instances
On the importance of considering concurrent effects in random-intercept cross-lagged panel modelling:Example analysis of bullying and internalising problems
Get PDFRandom-intercept cross-lagged panel models (RI-CLPMs) are increasingly used to investigate research questions focusing on how one variable at one time point affects another variable at the subsequent time point. Due to the implied temporal sequence of events in such research designs, interpretations of RI-CLPMs primarily focus on longitudinal cross-lagged paths while disregarding concurrent associations and modeling these only as residual covariances. However, this may cause biased cross-lagged effects. This may be especially so when data collected at the same time point refers to different reference timeframes, creating a temporal sequence of events for constructs measured concurrently. To examine this issue, we conducted a series of empirical analyses in which the impact of modeling or not modeling of directional within-time point associations may impact inferences drawn from RI-CLPMs using data from the longitudinal z-proso study. Results highlight that not considering directional concurrent effects may lead to biased cross-lagged effects. Thus, it is essential to carefully consider potential directional concurrent effects when choosing models to analyze directional associations between variables over time. If temporal sequences of concurrent effects cannot be clearly established, testing multiple models and drawing conclusions based on the robustness of effects across all models is recommended
Continuous colonisation of the Atlantic Coastal Rain Forests of South America from Amazônia
No full textThe two main extensions of rain forest in South America are the Amazon (Amazônia) and the Atlantic rain forest (Mata Atlântica), which are separated by a wide ‘dry diagonal’ of seasonal vegetation. We used the species-rich tree genus Inga to test if Amazônia - Mata Atlântica dispersals have been clustered during specific time periods corresponding to past, humid climates. We performed hybrid capture DNA sequencing of 810 nuclear loci for 453 accessions representing 164 species that included 62% of Mata Atlântica species and estimated a dated phylogeny for all accessions using maximum likelihood, and a species-level tree using coalescent methods. There have been 16 to 20 dispersal events to the Mata Atlântica from Amazônia with only one or two dispersals in the reverse direction. These events have occurred over the evolutionary history of Inga, with no evidence for temporal clustering, and model comparisons of alternative biogeographic histories and null simulations showing the timing of dispersal events matches a random expectation. Time-specific biogeographic corridors are not required to explain dispersal between Amazônia and the Mata Atlântica for rain forest trees such as Inga, which are likely to have used a dendritic net of gallery forests to cross the dry diagonal
Cognitive rationality is heritable and lies under general cognitive ability
Get PDFIntelligence and rationality both predict optimal decision making. However, whether cognitive rationality (CR) and general cognitive ability (CA) are identical or reflect fundamentally distinct processes is hotly debated. Here, we report a twin study aimed at distinguishing the cognitive mechanisms involved in CR and CA. CR and CA tests were administered to a large twin sample. Univariate analyses indicated that both CA and CR were strongly heritable. Multivariate modelling of CA scales and CR indicated that CR was accounted for by a latent g-factor, which itself was strongly heritable. We conclude that CR is not a distinct disposition from CA, but instead that the reflexive and reflective aspects of cognitive ability make making CR a robust and efficient test of general cognitive ability
Financing smart local energy systems:A conceptual framework and research agenda
Get PDFSmart local energy systems (SLES) are expected to contribute to meeting net zero carbon emission targets, as well as enabling energy decentralisation, democratisation and digitalisation. There are, however, unresolved questions about finance. We extend the existing corporate governance and risk management model CLASS to a new CCLLASS model. The model is used to explore pathways to SLES investment through securitising future cash flows. Case study evidence is used to explore governance and risk management practices suited to building investor confidence in securitisation. Several governance and risk management measures already in place support implementation and operation of securitisation, and should strengthen investor confidence. There is however scope for improvement in several elements, including final market architecture and explicit characterisation of benefits to localities. Further research is needed to test feasibility of a SLES future cash flow securitisation mechanism, including quantitative asset aggregation and systematic comparison of securitisation and other financial instruments
Access Repository Dashboard
Do you manage Edinburgh Research Explorer? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!