Characterising encapsulated nuclear waste using cosmic-ray muon tomography

Tomographic imaging techniques using the Coulomb scattering of cosmic-ray muons have been shown previously to successfully identify and characterise low- and high-Z materials within an air matrix using a prototype scintillating-fibre tracker system. Those studies were performed as the first in a series to assess the feasibility of this technology and image reconstruction techniques in characterising the potential high-Z contents of legacy nuclear waste containers for the UK Nuclear Industry. The present work continues the feasibility study and presents the first images reconstructed from experimental data collected using this small-scale prototype system of low- and high-Z materials encapsulated within a concrete-filled stainless-steel container. Clear discrimination is observed between the thick steel casing, the concrete matrix and the sample materials assayed. These reconstructed objects are presented and discussed in detail alongside the implications for future industrial scenarios.Comment: 6 pages, 4 figure

5-hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT₃ receptor resensitization due to Its subsequent release

The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT(3)) receptors. We report that recombinantly expressed 5-HT(3) receptor binding sites are reduced by chronic exposure to 5-HT (IC(50) of 154.0 ± 45.7 μm, t(½) = 28.6 min). This is confirmed for 5-HT(3) receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC(50) of 2.3 ± 1.0 μm, t(½) = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization

Presentism remains

Here I examine some recent attempts to provide a new way of thinking about the philosophy of time that question the central role of ‘presentness’ within the definition of presentism. The central concern raised by these critics turns on the intelligibility and theoretical usefulness of the term ‘is present’ (cf. Correia and Rosenkrantz in Thought 4:19–27, 2015; Deasy in Nous, 2017. https://doi.org/10.1111/nous.12109; Williamson in Modal logic as metaphysics, OUP, Oxford, 2013). My overarching aim is to at least challenge such concerns. I begin with arguments due to Deasy (Nous, 2017. https://doi.org/10.1111/nous.12109). Deasy develops a view that he calls ‘transientism’ and that he takes to be a well-motivated version of presentism. I show that both this way of thinking about presentism and the argument supposedly motivating it all fail. I then move to an argument due to Correia and Rosenkrantz (Thought 4:19–27, 2015). Correia and Rosenkrantz purport to show that presentism can be salvaged without making recourse to the term ‘is present’. I demonstrate that their arguments fail. I then move on to a view, proposed and defended by Merricks (Truth and ontology, OUP, Oxford, 2007), Tallant (Erkenntnis 79:479–501, 2014), and Zimmerman (Philos Pap 25:115–126, 1996), and show that it has the wherewithal to meet the challenges raised by Williamson (Modal logic as metaphysics, OUP, Oxford, 2013) who, as noted above, raises genuine concerns about our capacity to define presentism

Lifestyle, efficiency and limits: modelling transport energy and emissions using a socio-technical approach

It is well-known that societal energy consumption and pollutant emissions from transport are influenced not only by technical efficiency, mode choice and the carbon/pollutant content of energy but also by lifestyle choices and socio-cultural factors. However, only a few attempts have been made to integrate all of these insights into systems models of future transport energy demand or even scenario analysis. This paper addresses this gap in research and practice by presenting the development and use of quantitative scenarios using an integrated transport-energy-environment systems model to explore four contrasting futures for Scotland that compare transport-related ‘lifestyle’ changes and socio-cultural factors against a transition pathway focussing on transport electrification and the phasing out of conventionally fuelled vehicles using a socio-technical approach. We found that radical demand and supply strategies can have important synergies and trade-offs between reducing life cycle greenhouse gas and air quality emissions. Lifestyle change alone can have a comparable and earlier effect on transport carbon and air quality emissions than a transition to EVs with no lifestyle change. Yet, the detailed modelling of four contrasting futures suggests that both strategies have limits to meeting legislated carbon budgets, which may only be achieved with a combined strategy of radical change in travel patterns, mode and vehicle choice, vehicle occupancy and on-road driving behaviour with high electrification and phasing out of conventional petrol and diesel road vehicles. The newfound urgency of ‘cleaning up our act’ since the Paris Agreement and Dieselgate scandal suggests that we cannot just wait for the ‘technology fix’

Public health campaigns and obesity - a critique

<p>Abstract</p> <p>Background</p> <p>Controlling obesity has become one of the highest priorities for public health practitioners in developed countries. In the absence of safe, effective and widely accessible high-risk approaches (e.g. drugs and surgery) attention has focussed on community-based approaches and social marketing campaigns as the most appropriate form of intervention. However there is limited evidence in support of substantial effectiveness of such interventions.</p> <p>Discussion</p> <p>To date there is little evidence that community-based interventions and social marketing campaigns specifically targeting obesity provide substantial or lasting benefit. Concerns have been raised about potential negative effects created by a focus of these interventions on body shape and size, and of the associated media targeting of obesity.</p> <p>Summary</p> <p>A more appropriate strategy would be to enact high-level policy and legislative changes to alter the obesogenic environments in which we live by providing incentives for healthy eating and increased levels of physical activity. Research is also needed to improve treatments available for individuals already obese.</p

The genomic basis of adaptive evolution in threespine sticklebacks

Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine–freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine–freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.National Human Genome Research Institute (U.S.)National Human Genome Research Institute (U.S.) (NHGRI CEGS Grant P50-HG002568

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients