Effect of solid waste landfill organic pollutants on groundwater in three areas of Sicily (Italy) characterized by different vulnerability

The aim of this study was to obtain information on the presence and levels of hazardous organic pollutants in groundwater located close to solid waste landfills. Eighty-two environmental contaminants, including 16 polycyclic aromatic hydrocarbons (PAHs), 20 volatile organic compounds (VOCs), 29 polychlorinated biphenyls (PCBs), 7 dioxins (polychlorinated dibenzo-p-dioxins, PCDDs) and 10 furans (polychlorinated dibenzofurans, PCDFs) were monitored in areas characterised by different geological environments surrounding three municipal solid waste landfills (Palermo, Siculiana and Ragusa) in Sicily (Italy) in three sampling campaigns. The total concentrations of the 16 PAHs were always below the legal threshold. Overall, the Fl/Fl + Py diagnostic ratio revealed that PAHs had a petrogenic origin. VOC levels, except for two notable exceptions near Palermo landfill, were always below the legal limit. As concerns PCB levels, several samples were found positive with levels exceeding the legal limits. It is worth noting that the % PCB distribution differs from that of commercial compositions. In parallel, some samples of groundwater containing PCDDs and PCDFs exceeding the legal threshold were also found. Among the 17 congeners monitored, the most abundant were the highest molecular weight ones

SPARC 2017 retrospect & prospects : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2017 SPARC conference. This year we not only celebrate the work of our PGRs but also the 50th anniversary of Salford as a University, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 130 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to exploit this great opportunity to engage with researchers working in different subject areas to your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers

Graphene-based quantum Hall arrays in cross–square recursion configurations

In electrical metrology, the quantum Hall effect is accessed at the Landau level filling factor i = 2 plateau to define and disseminate the unit of electrical resistance (ohm). The robustness of the plateau is only exhibited at this Landau level filling factor and thus places a constraint on the quantized resistances that are accessible when constructing quantized Hall array resistance standards (QHARSs) using epitaxial graphene on SiC. To overcome device constraints by using Hall elements in series or in parallel, this work approaches the fabrication of a cross-square network configuration, which is similar to but departs slightly from conventional wye-delta designs and achieves significantly higher effective quantized resistance outputs. Furthermore, the use of pseudofractal-like recursion amplifies the ability to reach high resistances. QHARS devices designed as the ones here are shown to achieve an effective resistance of 55.81 Mohm in one configuration and 27.61 Gohm in another, with a hypothetically projected 317.95 Tohm that could be accessed with more specialized equipment. Teraohmmeter measurements reveal the limits of conventional wet cryogenic systems due to resistance leakage. Ultimately, this work builds on the capability of realizing exceptionally high-value quantum resistance standards

Widespread West Nile virus activity, eastern United States, 2000.

In 1999, the U.S. West Nile (WN) virus epidemic was preceded by widespread reports of avian deaths. In 2000, ArboNET, a cooperative WN virus surveillance system, was implemented to monitor the sentinel epizootic that precedes human infection. This report summarizes 2000 surveillance data, documents widespread virus activity in 2000, and demonstrates the utility of monitoring virus activity in animals to identify human risk for infection

Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Background Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19.Methods For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes.Findings Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2middot97 [95% CI 1middot43-6middot27], p=0middot0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1middot89 [95% CI 1middot17-3middot20] per SD, p=0middot012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [>= 6middot99] vs low [<6middot99] C19-RS; hazard ratio [HR] 3middot31 [95% CI 1middot49-7middot33], p=0middot0033; and 2middot58 [1middot10-6middot05], p=0middot028), adjusted for clinical factors, biochemical biomarkers of inflammation and myocardial injury, and technical parameters. The adjusted HR for in-hospital mortality was 8middot24 (95% CI 2middot16-31middot36, p=0middot0019) in patients who received no dexamethasone treatment, but 2middot27 (0middot69-7middot55, p=0middot18) in those who received dexamethasone after the scan, suggesting that vascular inflammation might have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0middot61, p=0middot00031) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways.Interpretation Radiotranscriptomic analysis of CT angiography scans introduces a potentially powerful new platform for the development of non-invasive imaging biomarkers. Application of this platform in routine CT pulmonary angiography scans done in patients with COVID-19 produced the radiotranscriptomic signature C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation and responsible for adverse clinical outcomes, which predicts in-hospital mortality and might allow targeted therapy. Funding Engineering and Physical Sciences Research Council, British Heart Foundation, Oxford BHF Centre of Research Excellence, Innovate UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, Onassis Foundation.Copyright (c) 2022 The Author(s). Published by Elsevier Ltd.This is an Open Access article under the CC BY 4.0 license

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in Covid-19.

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome