Three-dimensional behaviour of a prototype radioactive waste repository in fractured granitic rock

An investigation of the three-dimensional coupled thermohydromechanical behaviour of a prototype repository in fractured granitic rock is presented. The pre-placement behaviour of the repository is first considered, making use of a full three-dimensional simulation of the problem. An effective continuum approach, augmented with discrete features with a high hydraulic conductivity, is employed. The method adopted is found to be able to simulate accurately the highly anisotropic flow regime observed at the pre-placement phase. The major features of the full repository experiment under applied heating conditions were then successfully simulated. The range of buffer hydration rates, the thermal response of the repository, and the associated mechanical response were successfully simulated. Approaches to capture both the transient microstructural behaviour of the compacted bentonite (MX-80 type) and a MX-80 pellet material are incorporated. The repository behaviour was shown to be strongly influenced by complex coupled processes, including interactions between the system components. The adoption of a three-dimensional modelling approach proved to be essential to realistically simulate the behaviour of a repository incorporating anisotropic flow behaviour. Finally, potential impacts of the processes considered on performance of the barrier system and in safety assessment are considered

A coupled compressible flow and geomechanics model for dynamic fracture aperture during carbon sequestration in coal

This paper presents the development of a discrete fracture model of fully coupled compressible fluid flow, adsorption and geomechanics to investigate the dynamic behaviour of fractures in coal. The model is applied in the study of geological carbon dioxide sequestration and differs from the dual porosity model developed in our previous work, with fractures now represented explicitly using lower‐dimensional interface elements. The model consists of the fracture‐matrix fluid transport model, the matrix deformation model and the stress‐strain model for fracture deformation. A sequential implicit numerical method based on Galerkin finite element is employed to numerically solve the coupled governing equations, and verification is completed using published solutions as benchmarks. To explore the dynamic behaviour of fractures for understanding the process of carbon sequestration in coal, the model is used to investigate the effects of gas injection pressure and composition, adsorption and matrix permeability on the dynamic behaviour of fractures. The numerical results indicate that injecting nonadsorbing gas causes a monotonic increase in fracture aperture; however, the evolution of fracture aperture due to gas adsorption is complex due to the swelling‐induced transition from local swelling to macro swelling. The change of fracture aperture is mainly controlled by the normal stress acting on the fracture surface. The fracture aperture initially increases for smaller matrix permeability and then declines after reaching a maximum value. When the local swelling becomes global, fracture aperture starts to rebound. However, when the matrix permeability is larger, the fracture aperture decreases before recovering to a higher value and remaining constant. Gas mixtures containing more carbon dioxide lead to larger closure of fracture aperture compared with those containing more nitrogen

Validation of treatment escalation as a definition of atopic eczema flares.

BACKGROUND: Atopic eczema (AE) is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured. OBJECTIVE: To validate two concepts of AE flares based on daily reports of topical medication use: (i) escalation of treatment and (ii) days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors). METHODS: Data from two published AE studies (studies A (n=336) and B (n=60)) were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10) as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC) curve for binary outcome measures. RESULTS: Good agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only). Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS) and the duration of AE flares occurring in the previous week - POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks). CONCLUSION: Both definitions were good proxy indicators of AE flares. We found no evidence that 'escalation of treatment' was a better measure of AE flares than 'use of topical anti-inflammatory medications'. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71423189 (Study A)

A numerical modelling study to support design of an in-situ CO2 injection test facility using horizontal injection well in a shallow-depth coal seam

Previous projects on CO2 storage in coal often reported the challenges associated with coal swelling and swelling-induced loss of gas injectivity. Since coal seams are typically thin, commonly used vertical wells only intersect a target reservoir over a small contact area, placing constraints on CO2 injectivity in addition to those resulting from coal swelling. This leaves the storage reservoirs largely under-utilized and, therefore, questions the viability of this technology. To address the challenges/limitations of the current practice, a novel in-situ CO2 injection test is planned using horizontal injection wells in Mikolow, Poland. This paper presents the pre-operational simulation studies conducted to assist the design and operation of the in-situ test. An existing dual-porosity model that is built on a coupled thermo-hydro-chemical-mechanical (THCM) modelling framework is employed in this study. Sensitivity of the model parameters and validity of the model are tested. Several simulation scenarios are developed in reference to the selected test site for various horizontal well configurations and gas injection conditions. From the results and analyses, it is evident that by varying the coal-CO2 contact area via the length of the horizontal injection well, as well as the operating conditions including fixed pressure, and fixed rate injection scenarios, the targeted amount (between 1 to 10 tonnes) of CO2 can be injected into the seam without significant loss of permeability or injectivity, yielding sustained gas injection. Moreover, the spread of CO2 is predicted to be contained within the model domain suggesting no significant concern of spread exceeding the test area

Insights into the thermal performance of underground high voltage electricity transmission lines through thermo-hydraulic modelling

In this paper, a flexible numerical framework to provide thermal performance assessment for the underground buried cables, considering different geological and meteorological conditions, has been presented. Underground cables tend to retain the heat produced in the conductor, so complex coupled thermo-hydraulic response of the porous medium surrounding the cables needs to be assessed to prevent cable overheating and the associated reduction in cable capacity for carrying current. Applying a coupled thermo-hydraulic model within the developed numerical framework to conduct a health assessment on a subset of National Grid Electricity Transmission’s underground cables, this study provides novel insights into the thermal behaviour of buried circuits. The results indicate that backfill and surrounding native soil have the dominant effect on the thermal behaviour of cables, while the amount of precipitation and ambient temperature were found to have less impact on cable’s thermal behaviour. The findings strongly infer that the nature of the overloading which is undertaken in practice would have no ongoing negative impact, suggesting that more frequent or longer duration overloading regimes could be tolerated. Overall, this study demonstrates how the developed numerical framework could be harnessed to allow safe rating adjustments of buried transmission circuits

Safety of topical corticosteroids in atopic eczema:an umbrella review

Objective: An umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema .Methods: Embase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews searched until 7th November 2018 and Epistemonikos until 2nd March 2021. Reviews were included if they assessed safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality assessed using AMSTAR-2. PROSPERO registration: CRD42018079409. Results: 38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up usually short (2-4 weeks). Key findings: TCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4%-5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased. TCS versus topical calcineurin inhibitors (TCIs): Meta-analysis showed higher relative risk of skin-thinning with TCS (RR 4.86, 95% CI 1.06-22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares (‘weekend therapy’) versus vehicle: No meta-analyses identified. No evidence of skin-thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).Conclusions: We found no evidence of harm when TCS used intermittently “as required” to treat flares or “weekend therapy” to prevent flares. However, long-term safety data was limited

Emollient bath additives for the treatment of childhood eczema (BATHE): multi-centre pragmatic parallel group randomised controlled trial of clinical and cost-effectiveness

Objectives: To determine the clinical and cost-effectiveness of including emollient bath additives in the management of childhood eczema. Trial design: Pragmatic randomised open-label superiority trial with two parallel groups. Setting and recruitment: 96 general practices in Wales, West of England and Southern England. Invitation by personal letter or opportunistically by usual clinical team. Participants: Children were eligible to participate if aged over 12 months and less than 12 years, fulfilling UK Diagnostic Criteria for Atopic Dermatitis. Children with inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once a week, or whose carers were not willing to accept randomisation. 483 were randomised and one withdrew, leaving 482 children in the trial: 51% female, 84% white, mean age 5 years. Interventions: The intervention group were prescribed emollient bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued with standard eczema management and were given standardised advice on how to wash. Primary outcome: Eczema control measured by Patient Oriented Eczema Measure (POEM, range 0-28) weekly for 16 weeks. Secondary outcomes: Eczema severity over 1 year (4-weekly POEM from baseline to 52 weeks); number of eczema exacerbations resulting in primary healthcare consultation; disease-specific quality of life (QOL) (Dermatitis Family Impact); generic QoL (Child Health Utility-9D); resource utilisation; type and quantity of topical corticosteroid/calcineurin inhibitors prescribed. Randomisation: 483 children were randomised (1:1) using online software, stratified by recruiting centre. Results: 95.6% (461/482) of participants completed at least one post-baseline POEM, so were included in the analysis, and 76.8% (370/482) of participants completed questionnaires for more than 80% of the time points for the primary outcome (12/16 weekly questionnaires to 16 weeks). The mean Baseline POEM was 9.5 (s.d. 5.7) in the bath additives group and 10.1 (s.d. 5.8) in the no bath additives group. The mean POEM over the 16-week period was 7.5 (s.d. 6.0) in the bath additives group and 8.4 (6.0) in the no bath additives group. There was no statistically significant difference in weekly POEM scores between groups over 16 weeks. After controlling for baseline severity and confounders (ethnicity, topical corticosteroid use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% CI -0.27 to 1.10), below the published minimal clinically important difference for POEM of 3 points. There was no difference between groups in secondary outcomes, economic outcomes or in adverse effects. Conclusions: This trial found no evidence of clinical benefit from including emollient bath additives in the standard management of childhood eczema. Further research is needed into optimal regimens for leave-on emollient and use of soap substitutes for children with eczema

Graveyards on the Move: The Spatio-Temporal Distribution of Dead Ophiocordyceps-Infected Ants

Parasites are likely to play an important role in structuring host populations. Many adaptively manipulate host behaviour, so that the extended phenotypes of these parasites and their distributions in space and time are potentially important ecological variables. The fungus Ophiocordyceps unilateralis, which is pan-tropical in distribution, causes infected worker ants to leave their nest and die under leaves in the understory of tropical rainforests. Working in a forest dynamic plot in Southern Thailand we mapped the occurrence of these dead ants by examining every leaf in 1,360 m2 of primary rainforest. We established that high density aggregations exist (up to 26 dead ants/m2), which we coined graveyards. We further established that graveyards are patchily distributed in a landscape with no or very few O. unilateralis-killed ants. At some, but not all, spatial scales of analysis the density of dead ants correlated with temperature, humidity and vegetation cover. Remarkably, having found 2243 dead ants inside graveyards we only found 2 live ants of the principal host, ant Camponotus leonardi, suggesting that foraging host ants actively avoid graveyards. We discovered that the principal host ant builds nests in high canopy and its trails only occasionally descend to the forest floor where infection occurs. We advance the hypothesis that rare descents may be a function of limited canopy access to tree crowns and that resource profitability of such trees is potentially traded off against the risk of losing workers due to infection when forest floor trails are the only access routes. Our work underscores the need for an integrative approach that recognises multiple facets of parasitism, such as their extended phenotypes

Best emollients for eczema (BEE) – comparing four types of emollients in children with eczema: protocol for randomised trial and nested qualitative study

Introduction Atopic dermatitis/eczema affects around 20% of children and is characterised by inflamed, dry, itchy skin. Guidelines recommend ‘leave-on’ emollients that are applied directly to the skin to add or trap moisture and used regularly, they can soothe, enhance the skin barrier and may prevent disease ‘flares’. However, the suitability of the many different emollients varies between people and there is little evidence to help prescribers and parents and carers decide which type to try first.Methods and analysis Design: pragmatic, multicentre, individually randomised, parallel group superiority trial of four types of emollient (lotions, creams, gel or ointments).Setting: general practitioner surgeries in England.Participants: children aged over 6 months and less than 12 years with mild-to-severe eczema and no known sensitivity to study emollients.Interventions: study-approved lotion, cream, gel or ointment as the only leave-on emollient for 16 weeks, with directions to apply twice daily and as required. Other treatments, such as topical corticosteroids, used as standard care.Follow-up: 52 weeks.Primary outcome: validated patient-orientated eczema measure measured weekly for 16 weeks.Secondary outcomes: eczema signs (Eczema Area Severity Index) by masked researcher, treatment use, parent satisfaction, adverse events, child and family quality of life (Atopic Dermatitis Quality of Life, Child Health Utility 9D and Dermatitis Family Impact).Sample size: 520 participants (130 per group).Analysis: intention-to-treat using linear mixed models for repeated measures.Nested qualitative study: audio-recording of sample of baseline appointments and up to 60 interviews with participants at 4 and 16 weeks, interviews to be transcribed and analysed thematically.Ethics and dissemination Ethics approval granted by the NHS REC (South West - Central Bristol Research Ethics Committee 17/SW/0089). Findings will be presented at conferences, published in open-access peer-reviewed journals and the study website; and summaries shared with key stakeholders

Different strategies for using topical corticosteroids in people with eczema

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To establish the effectiveness and safety of different ways of using topical corticosteroids in people with eczema