Acropolis Educational Resources Repository
Not a member yet
31278 research outputs found
Sort by
Chronic multidimensional poverty in Europe
No full textIn 2021, interest in understanding and redressing the social exclusion of individuals and groups remains powerful and unabated. This chapter seeks to deepen understanding of potential measures of poverty and social exclusion in the EU. It uses the EU-SILC longitudinal data set to construct two types of multidimensional poverty indicators for 2014–2017 to study the individual persistence/volatility of multidimensional poverty over that period. The first indicator is based on the three AROPE dimensions. The second indicator is an extended measure that includes other salient dimensions of social exclusion: education, health and housing
The antibiotic darobactin mimics a β-strand to inhibit outer membrane insertase
No full textAntibiotics that target Gram-negative bacteria in new ways are needed to resolve the antimicrobial resistance crisis. Gram-negative bacteria are protected by an additional outer membrane, rendering proteins on the cell surface attractive drug targets. The natural compound darobactin targets the bacterial insertase BamA6—the central unit of the essential BAM complex, which facilitates the folding and insertion of outer membrane proteins. BamA lacks a typical catalytic centre, and it is not obvious how a small molecule such as darobactin might inhibit its function. Here we resolve the mode of action of darobactin at the atomic level using a combination of cryo-electron microscopy, X-ray crystallography, native mass spectrometry, in vivo experiments and molecular dynamics simulations. Two cyclizations pre-organize the darobactin peptide in a rigid β-strand conformation. This creates a mimic of the recognition signal of native substrates with a superior ability to bind to the lateral gate of BamA. Upon binding, darobactin replaces a lipid molecule from the lateral gate to use the membrane environment as an extended binding pocket. Because the interaction between darobactin and BamA is largely mediated by backbone contacts, it is particularly robust against potential resistance mutations. Our results identify the lateral gate as a functional hotspot in BamA and will allow the rational design of antibiotics that target this bacterial Achilles heel
Emergent supersymmetry on the edges
No full textThe WZW models describe the dynamics of the edge modes of Chern-Simons theories in three dimensions. We explore the WZW models which can be mapped to supersymmetric theories via the generalized Jordan-Wigner transformation. Some of such models have supersymmetric Ramond vacua, but the others break the supersymmetry spontaneously. We also make a comment on recent proposals that the Read-Rezayi states at filling fraction ν = 1/2, 2/3 are able to support supersymmetry
Drug discovery and development: technology in transition
No full textEssential insight into drug development and the pharmaceutical industry With unprecedented interest in the power that the modern therapeutic armamentarium has to combat disease, the new edition of Drug Discovery and Development is an essential resource for anyone interested in understanding how drugs and other therapeutic interventions are discovered and developed, through to clinical research, registration, and market access. The text has been thoroughly updated, with new information on biopharmaceuticals and vaccines as well as clinical development and target identification. Drug discovery and development continues to evolve rapidly and this new edition reflects important changes in the landscape. Edited by industry experts Raymond Hill and Duncan Richards, this market-leading text is suitable for undergraduates and graduates undertaking degrees in pharmacy, pharmacology, toxicology, and clinical development through to those embarking on a career in the pharmaceutical industry
Semi-Modular Inference: enhanced learning in multi-modular models by tempering the influence of components
No full textBayesian statistical inference loses predictive optimality when generative
models are misspecified.
Working within an existing coherent loss-based generalisation of Bayesian
inference, we show existing Modular/Cut-model inference is coherent, and write
down a new family of Semi-Modular Inference (SMI) schemes, indexed by an
influence parameter, with Bayesian inference and Cut-models as special cases.
We give a meta-learning criterion and estimation procedure to choose the
inference scheme. This returns Bayesian inference when there is no
misspecification.
The framework applies naturally to Multi-modular models. Cut-model inference
allows directed information flow from well-specified modules to misspecified
modules, but not vice versa. An existing alternative power posterior method
gives tunable but undirected control of information flow, improving prediction
in some settings. In contrast, SMI allows tunable and directed information flow
between modules.
We illustrate our methods on two standard test cases from the literature and
a motivating archaeological data set
Images of emperor and emirs in early Islamic Egypt
No full textAt some point in the seventh century, an artist in Egypt sat down to decorate a Sahidic Coptic manuscript containing books of the Old Testament. At the conclusion to the Book of Job, on the blank half page beneath, and under the bold Coptic title ‘Job the Just’ (written in the same hand as the preceding text), this artist decided to depict the eponymous hero alongside his three daughters – Hemera, Kasia, and Amalthaias. The subsequent sketches, all frontal and standing in a row, are striking. On the left Job himself, tall and nimbate, appears with a short, circular beard, and with curled hair protruding beneath an ornate diadem topped with a cross; he wears a paludamentum fastened at his shoulder with a brooch, a knee-length belted tunic beneath a cuirass, and short boots; and he bears in his right hand a staff or sceptre, and in his left a globe. To the right, the three daughters all wear full-length tunics with ornate girdles, all have earrings, and the two older, central, women have their hair in a snood; the other wears a crown
A bespoke reagent free amperometric chloride sensor for drinking water
No full textChloride quantification is important in drinking water quality control. A bespoke, rapid and reagent free electrochemical method is reported for a simple and accurate chloride sensor specifically for mineral water without the need for added electrolyte. The voltammetry used embraces first the reduction of oxygen to clean and activate the electrode surface and ensure reproducibility without the requirement for any mechanical polishing, followed by silver chloride formation and stripping. A linear correlation was found with silver chloride stripping peak currents and chloride concentrations within the range of 0.4 mM to 3.2 mM on a silver macro disc electrode. The chloride concentrations in two different mineral water samples were measured giving excellent agreement with independent analysis
Phase I trial evaluating the safety and immunogenicity of candidate TB vaccine MVA85A, delivered by aerosol to healthy M.tb-infected adults
No full textThe immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogenicity of MVA85A delivered by aerosol in UK adults with LTBI (NCT02532036). Two volunteers were recruited, and the vaccine was well-tolerated with no safety concerns. Aerosolised vaccination with MVA85A induced mycobacterium- and vector-specific IFN-γ in blood and mycobacterium-specific Th1 cytokines in bronchoalveolar lavage. We identified several important barriers that could hamper recruitment into clinical trials in this patient population. The trial did not show any safety concerns in the aerosol delivery of a candidate viral-vectored TB vaccine to two UK adults with Mycobacterium tuberculosis (M.tb) infection. It also systemically and mucosally demonstrated inducible immune responses following aerosol vaccination. A further trial in a country with higher incidence of LTBI would confirm these findings
Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: a systematic review and meta-analysis
No full textBackground and Aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), two-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) are proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).
Methods: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model.
Results: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and four 2DSWE studies, and for diagnosing NASH in four MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs.
Conclusions: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking
COVID-19 hospital admissions and deaths after BNT162b2 and ChAdOx1 nCoV-19 vaccinations in 2·57 million people in Scotland (EAVE II): a prospective cohort study
No full textBackground
The UK COVID-19 vaccination programme has prioritised vaccination of those at the highest risk of COVID-19 mortality and hospitalisation. The programme was rolled out in Scotland during winter 2020–21, when SARS-CoV-2 infection rates were at their highest since the pandemic started, despite social distancing measures being in place. We aimed to estimate the frequency of COVID-19 hospitalisation or death in people who received at least one vaccine dose and characterise these individuals.
Methods
We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) national surveillance platform, which contained linked vaccination, primary care, RT-PCR testing, hospitalisation, and mortality records for 5·4 million people (around 99% of the population) in Scotland. Individuals were followed up from receiving their first dose of the BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines until admission to hospital for COVID-19, death, or the end of the study period on April 18, 2021. We used a time-dependent Poisson regression model to estimate rate ratios (RRs) for demographic and clinical factors associated with COVID-19 hospitalisation or death 14 days or more after the first vaccine dose, stratified by vaccine type.
Findings
Between Dec 8, 2020, and April 18, 2021, 2 572 008 individuals received their first dose of vaccine—841 090 (32·7%) received BNT162b2 and 1 730 918 (67·3%) received ChAdOx1. 1196 (<0·1%) individuals were admitted to hospital or died due to COVID-19 illness (883 hospitalised, of whom 228 died, and 313 who died due to COVID-19 without hospitalisation) 14 days or more after their first vaccine dose. These severe COVID-19 outcomes were associated with older age (≥80 years vs 18–64 years adjusted RR 4·75, 95% CI 3·85–5·87), comorbidities (five or more risk groups vs less than five risk groups 4·24, 3·34–5·39), hospitalisation in the previous 4 weeks (3·00, 2·47–3·65), high-risk occupations (ten or more previous COVID-19 tests vs less than ten previous COVID-19 tests 2·14, 1·62–2·81), care home residence (1·63, 1·32–2·02), socioeconomic deprivation (most deprived quintile vs least deprived quintile 1·57, 1·30–1·90), being male (1·27, 1·13–1·43), and being an ex-smoker (ex-smoker vs non-smoker 1·18, 1·01–1·38). A history of COVID-19 before vaccination was protective (0·40, 0·29–0·54).
Interpretation
COVID-19 hospitalisations and deaths were uncommon 14 days or more after the first vaccine dose in this national analysis in the context of a high background incidence of SARS-CoV-2 infection and with extensive social distancing measures in place. Sociodemographic and clinical features known to increase the risk of severe disease in unvaccinated populations were also associated with severe outcomes in people receiving their first dose of vaccine and could help inform case management and future vaccine policy formulation