Lime stabilisation for earthworks: a UK perspective

Lime stabilisation is a versatile technique applied during earthworks operations. Modern soil recycling units are much more efficient at pulverising fill material and intermixing the added binder/water than machinery available 20 years ago. While supplier innovation adds flexibility to the site working method, specifications have not been sufficiently updated to permit optimal application. This review paper details the physico-chemical changes instigated through the lime-clay soil reaction, updating previous reviews. It aims to assist scientific debate, current practitioners and future specification changes. For example, the application of the minimum 24 h mellowing periods (mandatory to UK specifications) with high reactivity, quicklime powders is concluded to cause increased air voids in the compacted fill. Increased air voids are associated with reduced long-term strength and potential volume change from water ingress, which is of particular concern for sulfate swelling. Shorter mellowing periods and/or use of hydrated lime may lesson this issue; however, a 'one size fits all' approach is discouraged in preference to site-specific methodologies refined to suit the fill material and project requirements. The discussion also summarises working methods which may lower the risk of sulfate swell and defines areas requiring further practical research

The Impact of Moving from EQ-5D-3L to -5L in NICE Technology Appraisals

Background: The EuroQol-5 Dimension (EQ-5D) instrument is the National Institute for Health and Care Excellence (NICE)’s preferred measure of health-related quality of life (QoL) in adults. The three-level (3L) value set is currently recommended for use, but the five-level (5L) set is increasingly being used in practice. Objective: We aimed to explore the impact of moving from 3L to 5L in NICE appraisals. Methods: We adapted our existing mapping for use with health state utility values derived from a population where the original distribution of utilities was unknown. We used this mapping to estimate 5L utilities for 21 comparisons of interventions from models used in NICE technology appraisal decision making, covering a range of disease areas. Results: All utilities increased using 5L, and the differences between highest and lowest utilities decreased. In ten oncology comparisons, using 5L generally increased the incremental quality-adjusted life-years (QALYs) as the benefit from improving survival increased. In four non-oncology comparisons where the intervention improved QoL only, the incremental QALYs decreased as the benefit of improving QoL was reduced. In seven non-oncology comparisons where interventions improved survival and QoL, there was a trade-off between increasing the benefit from survival and decreasing the benefit from improving QoL. Conclusion: 3L and 5L lead to substantially different estimates of incremental QALYs and cost effectiveness. The direction and magnitude of the change is not consistent across case studies. Using 5L instead of 3L may lead to different reimbursement decisions. NICE will face inconsistencies in decision making if it uses 3L and 5L concurrently

Generating inner ear organoids containing putative cochlear hair cells from human pluripotent stem cells

In view of the prevalence of sensorineural hearing defects in an ageing population, the development of protocols to generate cochlear hair cells and their associated sensory neurons as tools to further our understanding of inner ear development are highly desirable. We report herein a robust protocol for the generation of both vestibular and cochlear hair cells from human pluripotent stem cells which represents an advance over currently available methods that have been reported to generate vestibular hair cells only. Generating otic organoids from human pluripotent stem cells using a three-dimensional culture system, we show formation of both types of sensory hair cells bearing stereociliary bundles with active mechano-sensory ion channels. These cells share many morphological characteristics with their in vivo counterparts during embryonic development of the cochlear and vestibular organs and moreover demonstrate electrophysiological activity detected through single-cell patch clamping. Collectively these data represent an advance in our ability to generate cells of an otic lineage and will be useful for building models of the sensory regions of the cochlea and vestibule

The MAPS reporting statement for studies mapping onto generic preference-based outcome measures: Explanation and elaboration

Background: The process of “mapping” is increasingly being used to predict health utilities, for application within health economic evaluations, using data on other indicators or measures of health. Guidance for the reporting of mapping studies is currently lacking. Objective: The overall objective of this research was to develop a checklist of essential items, which authors should consider when reporting mapping studies. The MAPS (MApping onto Preference-based measures reporting Standards) statement is a checklist, which aims to promote complete and transparent reporting by researchers. This paper provides a detailed explanation and elaboration of the items contained within the MAPS statement. Methods: In the absence of previously published reporting checklists or reporting guidance documents, a de novo list of reporting items and accompanying explanations was created. A two-round, modified Delphi survey, with representatives from academia, consultancy, health technology assessment agencies and the biomedical journal editorial community, was used to identify a list of essential reporting items from this larger list. Results: From the initial de novo list of 29 candidate items, a set of 23 essential reporting items was developed. The items are presented numerically and categorised within six sections, namely, (i) title and abstract, (ii) introduction, (iii) methods, (iv) results, (v) discussion and (vi) other. For each item, we summarise the recommendation, illustrate it using an exemplar of good reporting practice identified from the published literature, and provide a detailed explanation to accompany the recommendation. Conclusions: It is anticipated that the MAPS statement will promote clarity, transparency and completeness of reporting of mapping studies. It is targeted at researchers developing mapping algorithms, peer reviewers and editors involved in the manuscript review process for mapping studies, and the funders of the research. The MAPS working group plans to assess the need for an update of the reporting checklist in 5 years’ time

Meridional overturning circulation: stability and ocean feedbacks in a box model

A box model of the inter-hemispheric Atlantic meridional overturning circulation is developed, including a variable pycnocline depth for the tropical and subtropical regions. The circulation is forced by winds over a periodic channel in the south and by freshwater forcing at the surface. The model is aimed at investigating the ocean feedbacks related to perturbations in freshwater forcing from the atmosphere, and to changes in freshwater transport in the ocean. These feedbacks are closely connected with the stability properties of the meridional overturning circulation, in particular in response to freshwater perturbations. A separate box is used for representing the region north of the Antarctic circumpolar current in the Atlantic sector. The density difference between this region and the north of the basin is then used for scaling the downwelling in the north. These choices are essential for reproducing the sensitivity of the meridional overturning circulation observed in general circulation models, and therefore suggest that the southernmost part of the Atlantic Ocean north of the Drake Passage is of fundamental importance for the stability of the meridional overturning circulation. With this configuration, the magnitude of the freshwater transport by the southern subtropical gyre strongly affects the response of the meridional overturning circulation to external forcing. The role of the freshwater transport by the overturning circulation (M ov ) as a stability indicator is discussed. It is investigated under which conditions its sign at the latitude of the southern tip of Africa can provide information on the existence of a second, permanently shut down, state of the overturning circulation in the box model. M ov will be an adequate indicator of the existence of multiple equilibria only if salt-advection feedback dominates over other processes in determining the response of the circulation to freshwater anomalies. M ov is a perfect indicator if feedbacks other than salt-advection are negligible