Prototyping and load testing of thin-shell concrete floors

Buildings are being constructed at ever faster rates, fuelled by population growth and urbanisation. The total worldwide floor area of buildings is expected to almost double over the next 40 years, the equivalent of constructing Paris every five days. The majority of the mass and embodied energy (60% to 70%) in a typical multi-storey building structure exists within the floors, making these a primary target for sustainable structural design. In a typical reinforced concrete slab, much of the concrete is assumed to be cracked and therefore not structurally utilised, but nevertheless adds significant weight. This project proposes a radical re-design of concrete floors, using precast textile-reinforced concrete shells with an in-situ foamed concrete fill. By harnessing membrane action, self-weight savings of 62% have been demonstrated for typical spans (compared to traditional flat slabs). This paper discusses the design, optimisation, construction, measurement, analysis and structural testing of two prototype shells, one with and one without foamed concrete fill. The construction accuracy was quantified using digital scanner measurements which were then used as a geometry input for the analysis model. Each shell was loaded both uniformly and asymmetrically to beyond the design loading before failure. The foamed concrete was found to provide only a small increase in strength and stiffness. A design methodology for full-scale, practical application is currently under development.Building Research Establishment (BRE) Trust Cambridge University Department of Engineerin

Exoplanet Catalogues

One of the most exciting developments in the field of exoplanets has been the progression from 'stamp-collecting' to demography, from discovery to characterisation, from exoplanets to comparative exoplanetology. There is an exhilaration when a prediction is confirmed, a trend is observed, or a new population appears. This transition has been driven by the rise in the sheer number of known exoplanets, which has been rising exponentially for two decades (Mamajek 2016). However, the careful collection, scrutiny and organisation of these exoplanets is necessary for drawing robust, scientific conclusions that are sensitive to the biases and caveats that have gone into their discovery. The purpose of this chapter is to discuss and demonstrate important considerations to keep in mind when examining or constructing a catalogue of exoplanets. First, we introduce the value of exoplanetary catalogues. There are a handful of large, online databases that aggregate the available exoplanet literature and render it digestible and navigable - an ever more complex task with the growing number and diversity of exoplanet discoveries. We compare and contrast three of the most up-to-date general catalogues, including the data and tools that are available. We then describe exoplanet catalogues that were constructed to address specific science questions or exoplanet discovery space. Although we do not attempt to list or summarise all the published lists of exoplanets in the literature in this chapter, we explore the case study of the NASA Kepler mission planet catalogues in some detail. Finally, we lay out some of the best practices to adopt when constructing or utilising an exoplanet catalogue.Comment: 14 pages, 6 figures. Invited review chapter, to appear in "Handbook of Exoplanets", edited by H.J. Deeg and J.A. Belmonte, section editor N. Batalh

Building an Open Dissemination System

COPIM's Work package 5 (WP5) is developing technical protocols and infrastructure to better integrate OA books into institutional library, digital learning, and repository systems. This will support wider discovery and dissemination of OA books. Existing print and ebook distribution channels are difficult for new or OA publishers to engage with, requiring submission of metadata in multiple different formats (e.g. MARC, ONIX, KBART), and many platforms requiring multiple different metadata submissions; In addition, existing distribution channels are not well suited to OA content, while entirely new discovery and dissemination platforms are emerging (e.g. Google Books/Scholar). Guided by the perspective of new and emerging not-for-profit OA presses that have not yet been sufficiently integrated into existing discovery systems, knowledge bases, and supply routes, the aim of WP5 is to develop methods and systems to better integrate the catalogues of OA publishers into curated research records. The implementation of “best practices” workflows for OA book publishers will allow their catalogues to be better integrated into the scholarly record (discoverability, reach, persistence), increasing the impact of OA books. WP5 will build an Open Dissemination System (ODS) for OA books and a shared “best practices” digital catalogue. The ODS will be built as a decentralised system, using open source code, open protocols and standards and distributed databases—all under collective control. Doing so will ensure the system cannot be operated for the benefit of a single entity (either commercial or not). The ODS is currently under development under the project name Thoth. It consists of a metadata management system and a suite of exporting functions to allow publication metadata to be exported to all main metadata formats and data transfer with all relevant major platforms in the library and book selling supply chain. This scoping report is a key deliverable of WP5, in order to support the creation of the ODS. The report itself will discuss the distribution of books via the traditional library supply and new forms of digital dissemination before looking at metadata in depth. Metadata creation and types will be investigated in order to form a number of key recommendations for WP5. These recommendations are noted throughout the report before being grouped and discussed further in the recommendation section (see 9.0). Rather than publishing this report at the outset of the work package, it was decided to publish a time-stamped version, while simultaneously continuing to develop the report as the project progressed over time, and to encourage comment from the community. Version 1.0 of this report is available here and on Zenodo as a PDF (https://doi.org/10.5281/zenodo.3961564), and on the COPIM documentation site as a living document

<i>Trypanosoma brucei rhodesiense</i> transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis

Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies. To understand better how infection with this parasite leads to disease, we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys. One infected tsetse fly was allowed to feed on each host individual, and in all cases infections were successful. The characteristics of infection and disease were similar in all hosts, but the rate of progression varied considerably. Parasites were first detected in the blood 4-10 days after infection, showing that migration of parasites from the site of fly bite was very rapid. Anaemia was a key feature of disease, with a reduction in the numbers and average size of red blood cells and associated decline in numbers of platelets and white blood cells. One to six weeks after infection, parasites were observed in the cerebrospinal fluid (CSF), indicating that they had moved from the blood into the brain; this was associated with a white cell infiltration. This study shows that fly-transmitted infection in vervets accurately mimics human disease and provides a robust model to understand better how sleeping sickness develops

Vedolizumab for Treating Moderately to Severely Active Crohn’s Disease After Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe, active Crohn’s disease. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned as the Evidence Review Group (ERG) and produced a critical review of the evidence of the clinical effectiveness and cost effectiveness of the technology, based upon the company’s submission to NICE. The GEMINI II and III trials formed the main supporting evidence for the intervention. Both studies were phase III, randomised, double-blind, placebo-controlled, multicentre trials designed to evaluate the efficacy and safety of vedolizumab. They included patients who were naïve to tumour necrosis factor alpha antagonist (anti-TNF-α) therapy and patients who had an inadequate response to, loss of response to or intolerance of immunomodulators or anti-TNF-α agents. GEMINI II was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment (dosing at weeks 0 and 2, with assessment at week 6) and maintenance treatment (during weeks 6–52). In contrast, GEMINI III was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment only, with doses at weeks 0, 2 and 6, and assessment at weeks 6 and 10. In the absence of any direct head-to-head, randomised, controlled trials comparing vedolizumab with other relevant biologic therapies (adalimumab and infliximab) for the treatment of moderate-to-severe Crohn’s disease, the company conducted a network meta-analysis, which compared vedolizumab, adalimumab, infliximab and placebo for the outcomes of clinical response, enhanced clinical response, clinical remission and discontinuation due to adverse events. The company model estimated the incremental cost-effectiveness ratio (ICER) for vedolizumab compared with the standard of care (consisting of 5-aminosalicylic acids, corticosteroids and immunosuppressants) to be £21,620 per quality-adjusted life-year (QALY) gained within the anti-TNF-α-failure population (which included a confidential patient access scheme for vedolizumab). The ICERs were above £30,000 per QALY gained for the mixed intention-to-treat population (including both anti-TNF-α-naïve and anti-TNF-α-failure populations) and in patients who were anti-TNF-α naïve only. The ERG identified a number of limitations that were believed to limit the robustness of the results presented by the company. These limitations could not be addressed by the ERG without major restructuring of the economic model. Therefore, the ERG concluded that the results from the company’s model needed to be interpreted with caution and that it was unclear whether the ICERs would increase or decrease following amendment of the identified structural issues

Switching from natalizumab to alemtuzumab in patients with relapsing multiple sclerosis

Natalizumab is a disease-modifying therapy (DMT) used in relapsing-remitting multiple sclerosis (RRMS), licenced for use in patients with highly-active disease. It is an α4-integrin receptor antagonist that decreases activated T cell migration across the blood-brain barrier. Natalizumab carries a risk of progressive multifocal leucoencephalopathy (PML)—a risk that increases with duration of treatment; John Cunningham Virus (JCV) seropositivity and higher index values; prior use of immunosuppression. Patients may choose to withdraw from natalizumab to mitigate PML risk, or less commonly when natalizumab fails to control disease activity, or is poorly tolerated. Fingolimod has been commonly used as an option in those making the switch from natalizumab, but is associated with high rates of breakthrough clinical and/or radiological disease activity, although the risks may be lower with shorter washout periods. Rituximab has been suggested as an alternative to fingolimod in patients discontinuing natalizumab due to high PML risk, however, rituximab is not licenced for the treatment of RRMS and is not available in some countries for this indication. Alemtuzumab is a monoclonal antibody that binds to the CD52 surface protein on T and B lymphocytes, resulting in their depletion with subsequent repopulation, with comparable efficacy to natalizumab. Switching to alemtuzumab might be an alternative to fingolimod in patients stopping natalizumab but there is a paucity of clinical and safety data to guide this transition. Here, we present a single-centre experience in switching from natalizumab to alemtuzumab in RRMS

Biohydrogenation of 22:6n-3 by Butyrivibrio proteoclasticus P18

Background: Rumen microbes metabolize 22:6n-3. However, pathways of 22:6n-3 biohydrogenation and ruminal microbes involved in this process are not known. In this study, we examine the ability of the well-known rumen biohydrogenating bacteria, Butyrivibrio fibrisolvens D1 and Butyrivibrio proteoclasticus P18, to hydrogenate 22:6n-3. Results: Butyrivibrio fibrisolvens D1 failed to hydrogenate 22:6n-3 (0.5 to 32 mu g/mL) in growth medium containing autoclaved ruminal fluid that either had or had not been centrifuged. Growth of B. fibrisolvens was delayed at the higher 22:6n-3 concentrations; however, total volatile fatty acid production was not affected. Butyrivibrio proteoclasticus P18 hydrogenated 22:6n-3 in growth medium containing autoclaved ruminal fluid that either had or had not been centrifuged. Biohydrogenation only started when volatile fatty acid production or growth of B. proteoclasticus P18 had been initiated, which might suggest that growth or metabolic activity is a prerequisite for the metabolism of 22:6n-3. The amount of 22:6n-3 hydrogenated was quantitatively recovered in several intermediate products eluting on the gas chromatogram between 22:6n-3 and 22:0. Formation of neither 22:0 nor 22:6 conjugated fatty acids was observed during 22:6n-3 metabolism. Extensive metabolism was observed at lower initial concentrations of 22:6n-3 (5, 10 and 20 mu g/mL) whereas increasing concentrations of 22:6n-3 (40 and 80 mu g/mL) inhibited its metabolism. Stearic acid formation (18:0) from 18:2n-6 by B. proteoclasticus P18 was retarded, but not completely inhibited, in the presence of 22:6n-3 and this effect was dependent on 22:6n-3 concentration. Conclusions: For the first time, our study identified ruminal bacteria with the ability to hydrogenate 22:6n-3. The gradual appearance of intermediates indicates that biohydrogenation of 22:6n-3 by B. proteoclasticus P18 occurs by pathways of isomerization and hydrogenation resulting in a variety of unsaturated 22 carbon fatty acids. During the simultaneous presence of 18:2n-6 and 22:6n-3, B. proteoclasticus P18 initiated 22:6n-3 metabolism before converting 18:1 isomers into 18:0