A Gas Leak Rate Measurement System for the ATLAS MUON BIS-Monitored Drift Tubes

A low-cost, reliable and precise system developed for the gas leak rate measurement of the BIS-Monitored Drift Tubes (MDTs) for the ATLAS Muon Spectrometer is presented. In order to meet the BIS-MDT mass production rate, a total number of 100 tubes are tested simultaneously in this setup. The pressure drop of each one of the MDT is measured, within a typical time interval of 48 hours, via a differential manometer comparing with the pressure of a gas tight reference tube. The precision of the method implemented is based on the system temperature homogeneity, with accuracy of ÄT = 0.3 oC. For this reason, two thermally isolated boxes are used testing 50 tubes each of them, to achieve high degree of temperature uniformity and stability. After measuring several thousands of the MDTs, the developed system is confirmed to be appropriate within the specifications for testing the MDTs during the mass production

Structural insights into Clostridium perfringens delta toxin pore formation

Clostridium perfringens Delta toxin is one of the three hemolysin-like proteins produced by C. perfringens type C and possibly type B strains. One of the others, NetB, has been shown to be the major cause of Avian Nectrotic Enteritis, which following the reduction in use of antibiotics as growth promoters, has become an emerging disease of industrial poultry. Delta toxin itself is cytotoxic to the wide range of human and animal macrophages and platelets that present GM2 ganglioside on their membranes. It has sequence similarity with Staphylococcus aureus β-pore forming toxins and is expected to heptamerize and form pores in the lipid bilayer of host cell membranes. Nevertheless, its exact mode of action remains undetermined. Here we report the 2.4 Å crystal structure of monomeric Delta toxin. The superposition of this structure with the structure of the phospholipid-bound F component of S. aureus leucocidin (LukF) revealed that the glycerol molecules bound to Delta toxin and the phospholipids in LukF are accommodated in the same hydrophobic clefts, corresponding to where the toxin is expected to latch onto the membrane, though the binding sites show significant differences. From structure-based sequence alignment with the known structure of staphylococcal α-hemolysin, a model of the Delta toxin pore form has been built. Using electron microscopy, we have validated our model and characterized the Delta toxin pore on liposomes. These results highlight both similarities and differences in the mechanism of Delta toxin (and by extension NetB) cytotoxicity from that of the staphylococcal pore-forming toxins

The Biomarker Toolkit - an evidence-based guideline to predict cancer biomarker success and guide development

BACKGROUND: An increased number of resources are allocated on cancer biomarker discovery, but very few of these biomarkers are clinically adopted. To bridge the gap between Biomarker discovery and clinical use, we aim to generate the Biomarker Toolkit, a tool designed to identify clinically promising biomarkers and promote successful biomarker translation. METHODS: All features associated with a clinically useful biomarker were identified using mixed-methodology, including systematic literature search, semi-structured interviews, and an online two-stage Delphi-Survey. Validation of the checklist was achieved by independent systematic literature searches using keywords/subheadings related to clinically and non-clinically utilised breast and colorectal cancer biomarkers. Composite aggregated scores were generated for each selected publication based on the presence/absence of an attribute listed in the Biomarker Toolkit checklist. RESULTS: Systematic literature search identified 129 attributes associated with a clinically useful biomarker. These were grouped in four main categories including: rationale, clinical utility, analytical validity, and clinical validity. This checklist was subsequently developed using semi-structured interviews with biomarker experts (n=34); and 88.23% agreement was achieved regarding the identified attributes, via the Delphi survey (consensus level:75%, n=51). Quantitative validation was completed using clinically and non-clinically implemented breast and colorectal cancer biomarkers. Cox-regression analysis suggested that total score is a significant driver of biomarker success in both cancer types (BC: p>0.0001, 95.0% CI: 0.869-0.935, CRC: p>0.0001, 95.0% CI: 0.918-0.954). CONCLUSIONS: This novel study generated a validated checklist with literature-reported attributes linked with successful biomarker implementation. Ultimately, the application of this toolkit can be used to detect biomarkers with the highest clinical potential and shape how biomarker studies are designed/performed

CRC COVID: Colorectal cancer services during COVID-19 pandemic. Study protocol for service evaluation

COVID-19 has had an impact on the provision of colorectal cancer care. The aim of the CRC COVID study is to describe the changes in colorectal cancer services in the UK and USA in response to the pandemic and to understand the long-term impact

Managing big, linked, and open earth-observation data: Using the TELEIOS/LEO software stack

Big Earth-observation (EO) data that are made freely available by space agencies come from various archives. Therefore, users trying to develop an application need to search within these archives, discover the needed data, and integrate them into their application. In this article, we argue that if EO data are published using the linked data paradigm, then the data discovery, data integration, and development of applications becomes easier. We present the life cycle of big, linked, and open EO data and show how to support their various stages using the software stack developed by the European Union (EU) research projects TELEIOS and the Linked Open EO Data for Precision Farming (LEO). We also show how this stack of tools can be used to implement an operational wildfire-monitoring service

Behavioural and psychological symptoms in the older population without dementia - relationship with socio-demographics, health and cognition

<p>Abstract</p> <p>Background</p> <p>Behavioural and psychological symptoms are associated with dementia, but are also present in a significant number of the older population without dementia. Here we explore the distribution of behavioural and psychological symptoms in the population without dementia, and their relationship with domains and severity of health and cognitive impairment.</p> <p>Methods</p> <p>The Medical Research Council Cognitive Function and Ageing Study is a two-phase longitudinal study of ageing representative of the population aged 65 and over of England and Wales. A subsample of 1781 participants without a study diagnosis of dementia was included in this study. Information on symptoms including depression, apathy, anxiety, feelings of persecution, hallucination, agitated behaviour, elation, irritability, sleep problems, wandering, confabulation and misidentification, cognitive function, health related factors and socio-demographic information was extracted from interviews with participants and knowledgeable informants. Participants were classified according to the Mini-Mental State Examination and by criteria for subtypes of mild cognitive impairment (MCI). The prevalence of behavioural and psychological symptoms and associations with cognitive function, health and socio-demographics was examined. Co-occurrence of symptoms was tested using factor analysis.</p> <p>Results</p> <p>Most symptoms were reported more frequently in those with more severe cognitive impairment. Subjective memory complaints were the strongest independent predictor of reported symptoms, and most were reported more often in those classified as having MCI than in those with cognitive impairments that did not meet the MCI criteria. The pattern of co-occurrence of symptoms is similar to that seen in dementia.</p> <p>Conclusions</p> <p>Our results highlight that behavioural and psychological symptoms are prevalent in the cognitively impaired older population, and partly explain the variation observed in previous cohorts of individuals with MCI. Behavioural and psychological symptoms offer a target for intervention and so are an important consideration in the assessment of cognitively impaired older people.</p

Soil surface temperatures reveal moderation of the urban heat island effect by trees and shrubs

Urban areas are major contributors to air pollution and climate change, causing impacts on human health that are amplified by the microclimatological effects of buildings and grey infrastructure through the urban heat island (UHI) effect. Urban greenspaces may be important in reducing surface temperature extremes, but their effects have not been investigated at a city-wide scale. Across a midsized UK city we buried temperature loggers at the surface of greenspace soils at 100 sites, stratified by proximity to city centre, vegetation cover and land-use. Mean daily soil surface temperature over 11 months increased by 0.6 °C over the 5 km from the city outskirts to the centre. Trees and shrubs in non-domestic greenspace reduced mean maximum daily soil surface temperatures in the summer by 5.7 °C compared to herbaceous vegetation, but tended to maintain slightly higher temperatures in winter. Trees in domestic gardens, which tend to be smaller, were less effective at reducing summer soil surface temperatures. Our findings reveal that the UHI effects soil temperatures at a city-wide scale, and that in their moderating urban soil surface temperature extremes, trees and shrubs may help to reduce the adverse impacts of urbanization on microclimate, soil processes and human health