Role of the geosphere in deep nuclear waste disposal – An England and Wales perspective

To dispose permanently of its higher activity nuclear waste England and Wales have chosen deep geological disposal as the most appropriate solution currently available. The purpose of this paper is to describe the main geological features, events and processes relevant to England and Wales that will need to be considered to demonstrate that a site is suitable for a geological disposal facility (GDF). England and Wales are in the early stages of a GDF siting process in which areas of interest are being evaluated using mainly existing data from surface mapping and hydrocarbon exploration and production. Sites are evaluated consistently under six overarching headings, three of which are impacted by their geological setting – safety, engineering feasibility and value for money. “Suitable” geology is that which is safe during the operational and long-term post-closure period, which could have a GDF and its accessways constructed within it, and which delivers value for money. A GDF needs to fulfil dual safety functions wherever it is located: long-term containment of radionuclides, and isolation of the waste from human actions and from natural processes such as glaciations and earthquakes. The role of the geosphere in delivering these safety functions is to provide a low-flux groundwater environment with geochemical conditions that minimise degradation of the engineered components of the GDF, to promote retention of mobilised radionuclides, and to protect the waste from the impacts of humans and natural processes. The containment function of a GDF is provided by a combination of rock and engineering generally referred to as the multibarrier system. It comprises the engineered barriers – solid wasteforms, canisters, buffers, backfill materials, plugs and seals – that work together with the rock to ensure long-term containment. The GDF Programme in England and Wales seeks to identify suitable geological environments for which bespoke engineered barriers can be tailored to optimize the performance of the multibarrier system. The post-closure period over which independent regulators will require a safety case to demonstrate the long-term containment and isolation capabilities of a GDF is up to 1 million years. The long timescales make post-closure safety assessments a unique feature of deep geological disposal programmes. A comprehensive site characterization programme will use information mostly from seismic surveying and deep investigation boreholes to establish adequate rock availability (host rock depth, thickness, areal extent and compartmentalisation), suitable properties and behaviour of the deep geological environment, and the constructability and operability of a potential GDF site including its surface to subsurface access ways. Nuclear Waste Services, the organisation tasked with developing a GDF in England and Wales, is currently engaged with four Community Partnerships through a volunteer siting process: three in west Cumbria, and one on the English east coast in Theddlethorpe, Lincolnshire. In all of these areas Mesozoic claystones have been provisionally identified as potentially suitable GDF host rocks and are being investigated further, with a dedicated 3D seismic survey acquired off the coast of Cumbria in 2022. The main conclusion to be drawn from this paper is that a GDF could be sited in a large number of geological settings in England and Wales, and that the success of the current siting process will largely depend on engaging effectively with willing communities and building enduring relationships with them

Human rights and ethical reasoning : capabilities, conventions and spheres of public action

This interdisciplinary article argues that human rights must be understood in terms of opportunities for social participation and that social and economic rights are integral to any discussion of the subject. We offer both a social constructionist and a normative framework for a sociology of human rights which reaches beyond liberal individualism, combining insights from the work of Amartya Sen and from French convention theory. Following Sen, we argue that human rights are founded on the promotion of human capabilities as ethical demands shaped by public reasoning. Using French convention theory, we show how the terms of such deliberation are shaped by different constructions of collectively held values and the compromises reached between them. We conclude by demonstrating how our approach offers a new perspective on spheres of public action and the role these should play in promoting social cohesion, individual capabilities and human rights

Do topical repellents divert mosquitoes within a community? Health equity implications of topical repellents as a mosquito bite prevention tool.

OBJECTIVES: Repellents do not kill mosquitoes--they simply reduce human-vector contact. Thus it is possible that individuals who do not use repellents but dwell close to repellent users experience more bites than otherwise. The objective of this study was to measure if diversion occurs from households that use repellents to those that do not use repellents. METHODS: The study was performed in three Tanzanian villages using 15%-DEET and placebo lotions. All households were given LLINs. Three coverage scenarios were investigated: complete coverage (all households were given 15%-DEET), incomplete coverage (80% of households were given 15%-DEET and 20% placebo) and no coverage (all households were given placebo). A crossover study design was used and coverage scenarios were rotated weekly over a period of ten weeks. The placebo lotion was randomly allocated to households in the incomplete coverage scenario. The level of compliance was reported to be close to 100%. Mosquito densities were measured through aspiration of resting mosquitoes. Data were analysed using negative binomial regression models. FINDINGS: Repellent-users had consistently fewer mosquitoes in their dwellings. In villages where everybody had been given 15%-DEET, resting mosquito densities were fewer than half that of households in the no coverage scenario (Incidence Rate Ratio [IRR]=0.39 (95% confidence interval [CI]: 0.25-0.60); p<0.001). Placebo-users living in a village where 80% of the households used 15%-DEET were likely to have over four-times more mosquitoes (IRR=4.17; 95% CI: 3.08-5.65; p<0.001) resting in their dwellings in comparison to households in a village where nobody uses repellent. CONCLUSIONS: There is evidence that high coverage of repellent use could significantly reduce man-vector contact but with incomplete coverage evidence suggests that mosquitoes are diverted from households that use repellent to those that do not. Therefore, if repellents are to be considered for vector control, strategies to maximise coverage are required

<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

Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats

Rationale Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Objectives Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. Methods The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. Results We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. Conclusions These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

Background: Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings: Male balb/c mice were assigned randomly to either sham burn (control) or 30 % total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression

Gravitational Waves from Gravitational Collapse

Gravitational wave emission from the gravitational collapse of massive stars has been studied for more than three decades. Current state of the art numerical investigations of collapse include those that use progenitors with realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non--axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Increased Asymmetric Dimethylarginine in Severe Falciparum Malaria: Association with Impaired Nitric Oxide Bioavailability and Fatal Outcome

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is a predictor of mortality in critical illness. Severe malaria (SM) is associated with decreased NO bioavailability, but the contribution of ADMA to the pathogenesis of impaired NO bioavailability and adverse outcomes in malaria is unknown. In adults with and without falciparum malaria, we tested the hypotheses that plasma ADMA would be: 1) increased in proportion to disease severity, 2) associated with impaired vascular and pulmonary NO bioavailability and 3) independently associated with increased mortality. We assessed plasma dimethylarginines, exhaled NO concentrations and endothelial function in 49 patients with SM, 78 with moderately severe malaria (MSM) and 19 healthy controls (HC). Repeat ADMA and endothelial function measurements were performed in patients with SM. Multivariable regression was used to assess the effect of ADMA on mortality and NO bioavailability. Plasma ADMA was increased in SM patients (0.85 µM; 95% CI 0.74–0.96) compared to those with MSM (0.54 µM; 95%CI 0.5–0.56) and HCs (0.64 µM; 95%CI 0.58–0.70; p<0.001). ADMA was an independent predictor of mortality in SM patients with each micromolar elevation increasing the odds of death 18 fold (95% CI 2.0–181; p = 0.01). ADMA was independently associated with decreased exhaled NO (rs = −0.31) and endothelial function (rs = −0.32) in all malaria patients, and with reduced exhaled NO (rs = −0.72) in those with SM. ADMA is increased in SM and associated with decreased vascular and pulmonary NO bioavailability. Inhibition of NOS by ADMA may contribute to increased mortality in severe malaria

At work and play; business events as entrepreneurial spaces

There is inadequate literature examining, and illustrating, the integration of play and business events and how this facilitates entrepreneurial opportunities. Business events are distinct from the patterns of ordinary life and increasingly offer participants an ‘invitation to play’, encouraging socialization and trust. This article examines the role of play in the design of business events and how this can enable entrepreneurial outcomes. Through examination of diverse, but related, literature and three contrasting, empirically based, case studies, this article illustrates how event creators take an increasingly entrepreneurial approach. These cases range from a charity event with participants sleeping with the homeless on a city’s streets, a major flooring manufacturer designing events to outsource innovation and an imaginative event activity termed ‘coffee and papers’. Designing events that fuse, rather than polarize, play and work enables business event settings, and activities, which trigger entrepreneurial outcomes. This article adds to the embryonic literature and concludes by identifying four principles that underlie the effectual facilitation of play in a business event setting