Acropolis Educational Resources Repository
Not a member yet
31278 research outputs found
Sort by
Trends in health workers' compliance with outpatient malaria case-management guidelines across malaria epidemiological zones in Kenya, 2010-2016
No full textBACKGROUND:Health workers' compliance with outpatient malaria case-management guidelines has been improving, specifically regarding the universal testing of suspected cases and the use of artemisinin-based combination therapy (ACT) only for positive results (i.e., 'test and treat'). Whether the improvements in compliance with 'test and treat' guidelines are consistent across different malaria endemicity areas has not been examined. METHODS:Data from 11 national, cross-sectional, outpatient malaria case-management surveys undertaken in Kenya from 2010 to 2016 were analysed. Four primary indicators (i.e., 'test and treat') and eight secondary indicators of artemether-lumefantrine (AL) dosing, dispensing, and counselling were measured. Mixed logistic regression models were used to analyse the annual trends in compliance with the indicators across the different malaria endemicity areas (i.e., from highest to lowest risk being lake endemic, coast endemic, highland epidemic, semi-arid seasonal transmission, and low risk). RESULTS:Compliance with all four 'test and treat' indicators significantly increased in the area with the highest malaria risk (i.e., lake endemic) as follows: testing of febrile patients (OR = 1.71 annually; 95% CI = 1.51-1.93), AL treatment for test-positive patients (OR = 1.56; 95% CI = 1.26-1.92), no anti-malarial for test-negative patients (OR = 2.04; 95% CI = 1.65-2.54), and composite 'test and treat' compliance (OR = 1.80; 95% CI = 1.61-2.01). In the low risk areas, only compliance with test-negative results significantly increased (OR = 2.27; 95% CI = 1.61-3.19) while testing of febrile patients showed declining trends (OR = 0.89; 95% CI = 0.79-1.01). Administration of the first AL dose at the facility significantly increased in the areas of lake endemic (OR = 2.33; 95% CI = 1.76-3.10), coast endemic (OR = 5.02; 95% CI = 2.77-9.09) and semi-arid seasonal transmission (OR = 1.44; 95% CI = 1.02-2.04). In areas of the lowest risk of transmission and highland epidemic zone, none of the AL dosing, dispensing, and counselling tasks significantly changed over time. CONCLUSIONS:There is variability in health workers' compliance with outpatient malaria case-management guidelines across different malaria-risk areas in Kenya. Major improvements in areas of the highest risk have not been seen in low-risk areas. Interventions to improve practices should be targeted geographically
Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance
No full textOBJECTIVE: Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.
DESIGN: We performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.
RESULTS: We characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.
CONCLUSION: Our work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn's disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23
An undivided mind: John Habgood on science and religion
No full textThis study considers John Habgood’s understanding of the relation of science and religion, particularly his core notion that an ‘undivided mind’ engages different aspects of reality using disciplines of study appropriate to their specific subject matter. Particular attention is paid to the emergence of those views during his time as a research scientist at Cambridge, their location within the Anglican tradition, their expression in Habgood’s 1992 debate with Richard Dawkins, and their impact on his public ministry as Bishop of Durham and Archbishop of York, especially in public debates concerning bioethics
Core outcomes set for trials in people with coronavirus disease 2019
No full textObjectives:
The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019.
Design:
Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set.
Setting:
International.
Subjects:
Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers).
Interventions:
None.
Measurements:
None.
Main Results:
Six themes were identified. “Responding to the critical and acute health crisis” reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. “Capturing different settings of care” highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. “Encompassing the full trajectory and severity of disease” was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). “Distinguishing overlap, correlation and collinearity” meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). “Recognizing adverse events” refers to the potential harms of new and evolving interventions. “Being cognizant of family and psychosocial wellbeing” reflected the pervasive impacts of coronavirus disease 2019.
Conclusions:
Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials
VectorNet data series 3: Culicoides abundance distribution models for Europe and surrounding regions
No full textThis is the third in a planned series of data papers presenting modelled vector distributions produced during the ECDC and EFSA funded VectorNet project. The data package presented here includes those Culicoides vectors species first modelled in 2015 as part of the VectorNet gap analysis work namely C. imicola, C. obsoletus, C. scoticus, C. dewulfi, C. chiopterus, C. pulicaris, C. lupicaris, C. punctatus, and C. newsteadi. The known distributions of these species within the Project area (Europe, the Mediterranean Basin, North Africa, and Eurasia) are currently incomplete to a greater or lesser degree. The models are designed to fill the gaps with predicted distributions, to provide a) first indication of vector species distributions across the project geographical extent, and b) assistance in targeting surveys to collect distribution data for those areas with no field validated information. The models are based on input data from light trap surveillance of adult Culicoides across continental Europe and surrounding regions (71.8°N –33.5°S, – 11.2°W – 62°E), concentrated in Western countries, supplemented by transect samples in eastern and northern Europe. Data from central EU are relatively sparse
Learning models over relational data using sparse tensors and functional dependencies
No full textIntegrated solutions for analytics over relational databases are of great practical importance as they avoid the costly repeated loop data scientists have to deal with on a daily basis: select features from data residing in relational databases using feature extraction queries involving joins, projections, and aggregations; export the training dataset defined by such queries; convert this dataset into the format of an external learning tool; and train the desired model using this tool. These integrated solutions are also a fertile ground of theoretically fundamental and challenging problems at the intersection of relational and statistical data models.
This article introduces a unified framework for training and evaluating a class of statistical learning models over relational databases. This class includes ridge linear regression, polynomial regression, factorization machines, and principal component analysis. We show that, by synergizing key tools from database theory such as schema information, query structure, functional dependencies, recent advances in query evaluation algorithms, and from linear algebra such as tensor and matrix operations, one can formulate relational analytics problems and design efficient (query and data) structure-aware algorithms to solve them.
This theoretical development informed the design and implementation of the AC/DC system for structure- aware learning. We benchmark the performance of AC/DC against R, MADlib, libFM, and TensorFlow. For typical retail forecasting and advertisement planning applications, AC/DC can learn polynomial regression models and factorization machines with at least the same accuracy as its competitors and up to three orders of magnitude faster than its competitors whenever they do not run out of memory, exceed 24-hour timeout, or encounter internal design limitations
A duality theoretic view on limits of finite structures
No full textA systematic theory of structural limits for finite models has been developed by Nešetřil and Ossona de Mendez. It is based on the insight that the collection of finite structures can be embedded, via a map they call the Stone pairing, in a space of measures, where the desired limits can be computed. We show that a closely related but finer grained space of measures arises — via Stone-Priestley duality and the notion of types from model theory — by enriching the expressive power of first-order logic with certain “probabilistic operators”. We provide a sound and complete calculus for this extended logic and expose the functorial nature of this construction.
The consequences are two-fold. On the one hand, we identify the logical gist of the theory of structural limits. On the other hand, our construction shows that the duality-theoretic variant of the Stone pairing captures the adding of a layer of quantifiers, thus making a strong link to recent work on semiring quantifiers in logic on words. In the process, we identify the model theoretic notion of types as the unifying concept behind this link. These results contribute to bridging the strands of logic in computer science which focus on semantics and on more algorithmic and complexity related areas, respectively
Diverse vertebrate assemblage of the Kilmaluag Formation (Bathonian, Middle Jurassic) of Skye, Scotland
No full textThe Kilmaluag Formation on the Isle of Skye, Scotland, provides one of the richest Mesozoic vertebrate fossil assemblages in the UK, and is among the richest globally for Middle Jurassic tetrapods. Since its discovery in 1971, this assemblage has predominantly yielded small-bodied tetrapods, including salamanders, choristoderes, lepidosaurs, turtles, crocodylomorphs, pterosaurs, dinosaurs, non-mammalian cynodonts and mammals, alongside abundant fish and invertebrates. It is protected as a Site of Special Scientific Interest and by Nature Conservancy Order. Unlike contemporaneous localities from England, this assemblage yields associated partial skeletons, providing unprecedented new data. We present a comprehensive updated overview of the Kilmaluag Formation, including its geology and the fossil collections made to date, with evidence of several species occurrences presented here for the first time. We place the vertebrate faunal assemblage in an international context through comparisons with relevant contemporaneous localities from the UK, Europe, Africa, Asia and the US. This wealth of material reveals the Kilmaluag Formation as a vertebrate fossil assemblage of global significance, both in terms of understanding Middle Jurassic faunal composition and the completeness of specimens, with implications for the early evolutionary histories of mammals, squamates and amphibians
Macroevolutionary convergence connects morphological form to ecological function in birds
No full textAnimals have diversified into a bewildering variety of morphological forms exploiting a complex configuration of trophic niches. Their morphological diversity is widely used as an index of ecosystem function, but the extent to which animal traits predict trophic niches and associated ecological processes is unclear. Here we use the measurements of nine key morphological traits for >99% bird species to show that avian trophic diversity is described by a trait space with four dimensions. The position of species within this space maps with 70–85% accuracy onto major niche axes, including trophic level, dietary resource type and finer-scale variation in foraging behaviour. Phylogenetic analyses reveal that these form–function associations reflect convergence towards predictable trait combinations, indicating that morphological variation is organized into a limited set of dimensions by evolutionary adaptation. Our results establish the minimum dimensionality required for avian functional traits to predict subtle variation in trophic niches and provide a global framework for exploring the origin, function and conservation of bird diversity
