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The hardening soil (HS) model is an advanced soil plasticity model, which incorporates many features including stiffness stress dependency, hardening from initial loading and soil dilatancy. In this paper, the HS model is explored in depth and two improvements are proposed. The first is a new shear yield surface and hardening rule that have been reformulated to remove singularities. The second is a robust implicit return mapping scheme. Options for improving the global convergence of finite-element analyses are also explored. Single-elements tests replicate results from experimental triaxial data and previous versions of the HS model very closely, and at excellent convergence rates. In addition, a slope stability analysis is performed using the φ − c strength reduction method in two-dimensional plane strain. The results from the slope analysis showed good agreement with analytical and graphical slope stability methods. A three-dimensional (3D) slope stability analysis was also conducted with modified boundary conditions, in order to demonstrate the 3D capabilities of the model.

The enormous expansion of information, which is assembled from various design tools, has caused challenges in data exchange and compelled companies to find various solutions to improve collaboration. Data exchange within Building Information Modelling (BIM) context has been mainly focused on individual disciplines. Even though several attempts have been made to develop data exchange requirements for BIM models, there is still a lack of homogeneity since no method for classifying and sharing those requirements is clearly outlined. A clearly defined “single truth of information” is still not acknowledged yet. Software tools require unambiguous clarity of the semantics, which can help various stakeholders to proceed with their design tasks. However, there is still a lack of multi-dimensional knowledgebase for holistic decision-making within a BIM workflow. Therefore, this paper presents a common data analysis (CDA) referencing various concepts such as the standardised Information Delivery Manual (IDM) method, model view definition (MVD) and the concept of semantic intersection to conclude “single truth of information” and “partial truth of information” data sets that form the basis for a theoretical holistic decision-making framework to support collaborative design. The information defined in this research was validated based on existing resources and literature. Following the concluded data sets, a model can be transformed automatically at the minimum commonality level, creating a starting point for other professions. Following the analysis, a theoretical holistic decision-making framework was proposed. The innovation of the proposed framework lies in providing a holistic decision-making system that combines both data extraction using the concluded data sets and semantic web technology to eliminate inefficiencies in data sharing and improve the decision-making process in the early design stage by providing the stakeholders with rational solutions with less effort and time. This paper provides the essential requirement for a holistic decision framework from a data processing perspective.

BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19, in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

Background: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. Methods: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 10 10 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT 50]; a microneutralisation assay [MNA 50, MNA 80, and MNA 90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Findings: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p80 and in 35 (100%) participants when measured in PRNT 50. After a booster dose, all participants had neutralising activity (nine of nine in MNA 80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R 2=0·67 by Marburg VN; p

Purpose Choroidal thickness (ChT) and choroidal vascularity index (CVI) represent two important metrics in health-, disease-, and myopia-related studies. Wide-field swept-source optical coherence tomography (OCT) provides improved and extended imaging and extraction of choroidal variables. This study characterizes the topography and repeatability of these parameters in healthy eyes. Methods Swept-source OCT volume scans were obtained on 14 young adult patients on three separate days. ChT and CVI were automatically corrected for image magnification and extracted for different enface regions within an extended ETDRS grid of 10 mm diameter. Topographical distribution, correlation to ocular length, and intersession repeatability of both choroidal parameters were assessed. Results CVI showed little fluctuation between subfields, unlike ChT, which demonstrated thinning toward the peripheral choroid (coefficients of variation 5.92 vs. 0.89). ChT showed a consistent negative correlation with axial length (ρ = −0.05 to −0.61), although this was only statistically significant in the inner superior subfield (P = 0.02). There was no consistent or significant relationship between CVI and axial length or between CVI and ChT. The repeatability of CVI measurements (3.90%–5.51%) was more consistent between scan regions than ChT measurements (10.37–20.33 µm). Conclusions CVI values were consistent across the central 10 mm of the retina, while ChT reduced with eccentricity. The repeatability of both parameters is similar to the effect size reported in many studies using the choroid as a biomarker, which should be considered in the interpretation of findings. Translational Relevance This study provided normative as well as metrological information for the clinical interpretation of ChT and CVI in health and disease.

Research into dust deposition rates on the wall paintings in the State Apartments at the Palace of Westminster, London, UK, began during the restoration of the encaustic floor tiles. The study has ...