Investigations of meltwater refreezing and density variations in the snowpack and firn within the percolation zone of the Greenland Ice Sheet

The mass balance of polythermal ice masses is critically dependent on the proportion of surface-generated meltwater that subsequently refreezes in the snowpack and firn. In order to quantify this effect and to characterize its spatial variability, we measured near-surface (26%, resulting in a 32% increase in net accumulation. This 'seasonal densification' increased at lower elevations, rising to 47% 10 km closer to the ice-sheet margin at 1860 m a. s. l. Density/depth profiles from nine sites within 1 km2 at ∼1945 m a.s.l. reveal complex stratigraphies that change over short spatial scales and seasonally. We conclude that estimates of mass-balance change cannot be calculated solely from observed changes in surface elevation, but that near-surface densification must also be considered. However, predicting spatial and temporal variations in densification may not be straightforward. Further, the development of complex firn-density profiles both masks discernible annual layers in the near-surface firn and ice stratigraphy and is likely to introduce error into radar-derived estimates of surface elevation

Possible geopotential improvement from satellite altimetry

Possible geopotential improvement from satellite altimetr

Findings from a pilot randomised trial of an asthma internet self-management intervention (RAISIN)

<b>Objective </b>To evaluate the feasibility of a phase 3 randomised controlled trial (RCT) of a website (Living Well with Asthma) to support self-management.<p></p> <b>Design and setting</b> Phase 2, parallel group, RCT, participants recruited from 20 general practices across Glasgow, UK. Randomisation through automated voice response, after baseline data collection, to website access for minimum 12 weeks or usual care.<p></p> <b>Participants </b>Adults (age≥16 years) with physician diagnosed, symptomatic asthma (Asthma Control Questionnaire (ACQ) score ≥1). People with unstable asthma or other lung disease were excluded.<p></p> <b>Intervention</b> Living Well with Asthma’ is a desktop/ laptop compatible interactive website designed with input from asthma/ behaviour change specialists, and adults with asthma. It aims to support optimal medication management, promote use of action plans, encourage attendance at asthma reviews and increase physical activity.<p></p> <b>Outcome measures</b> Primary outcomes were recruitment/retention, website use, ACQ and mini- Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes included patient activation, prescribing, adherence, spirometry, lung inflammation and health service contacts after 12 weeks. Blinding postrandomisation was not possible.<p></p> <b>Results </b>Recruitment target met. 51 participants randomised (25 intervention group). Age range 16–78 years; 75% female; 28% from most deprived quintile. 45/51 (88%; 20 intervention group) followed up. 19 (76% of the intervention group) used the website, for a mean of 18 min (range 0–49). 17 went beyond the 2 ‘core’ modules. Median number of logins was 1 (IQR 1–2, range 0–7). No significant difference in the prespecified primary efficacy measures of ACQ scores (−0.36; 95% CI −0.96 to 0.23; p=0.225), and mini-AQLQ scores (0.38; −0.13 to 0.89; p=0.136). No adverse events.<p></p> <b>Conclusions</b> Recruitment and retention confirmed feasibility; trends to improved outcomes suggest use of Living Well with Asthma may improve self-management in adults with asthma and merits further development followed by investigation in a phase 3 trial

Ultra-Rare BRD9 Loss-of-Function Variants Limit the Antiviral Action of Interferon

The human type I interferon (IFN) system is central to innate immune defense, and is essential to protect individuals against severe viral disease. Consequently, genetic disruption of IFN signaling or effector mechanisms is extremely rare, as affected individuals typically suffer life-threatening infections at an early age. While loss-of-function (LOF) mutations in canonical JAK-STAT signaling genes (such as IFNAR2, TYK2, STAT1, STAT2 and IRF9) have previously been characterized, little is known about the consequences of mutations in other human factors required for IFN signaling. Here, we studied the impact of rare human genetic variants in the recently identified contributor to IFN-stimulated gene expression and antiviral activity, bromodomain-containing protein 9 (BRD9). Using a cell-based BRD9 knock-out and reconstitution model system, we functionally assessed 12 rare human BRD9 missense variants predicted to impair protein function, as well as 3 ultra-rare human BRD9 LOF variants that lead to truncated versions of BRD9. As compared to wild-type BRD9, none of the 12 BRD9 missense variants affected the ability of exogenous IFN to limit virus replication. In contrast, all 3 truncated BRD9 LOF variants failed to allow exogenous IFN to function efficiently, as evidenced by exacerbated replication of an IFN-sensitive virus and diminished IFN-stimulated gene expression. Thus, while no homozygous BRD9 LOF carriers have yet been identified, our results predict that such extremely rare individuals would exhibit a compromised ability to mount a fully protective IFN-mediated antiviral response. Genetic variation in BRD9 could be considered in future studies to understand the infection susceptibility of some individuals

Empirical Studies of Evolving Systems

This paper describes the results of the working group investigating the issues of empirical studies for evolving systems. The groups found that there were many issues that were central to successful evolution and this concluded that this is a very important area within software engineering. Finally nine main areas were selected for consideration. For each of these areas the central issues were identified as well as success factors. In some cases success stories were also described and the critical factors accounting for the success analysed. In some cases it was later found that a number of areas were so tightly coupled that it was important to discuss them together

Considerations for monitoring of deep circular excavations

Understanding the magnitude and distribution of ground movements associated with deep shaft construction is a key factor in designing efficient damage prevention/mitigation measures. Therefore, a large-scale monitoring scheme was implemented at Thames Water's 68 m deep Abbey Mills Shaft F in East London, UK, constructed as part of the Lee Tunnel Project. The scheme comprised inclinometers and extensometers which were installed in the diaphragm walls and in boreholes around the shaft to measure deflections and ground movements. However, interpreting the measurements from inclinometers can be a challenging task, as it is often not feasible to extend the boreholes into ground unaffected by movements. The paper describes in detail how the data are corrected. The corrected data showed very small wall deflections of less than 4 mm at the final shaft excavation depth. Similarly, very small ground movements were measured around the shaft. Empirical ground settlement prediction methods derived from different shaft construction methods significantly overestimate settlements for a diaphragm wall shaft. The results of this study will help to inform future projects, such as the forthcoming 25 km long Thames Tideway Tunnel with its 18 deep shafts being constructed adjacent to existing infrastructure. Engineering and Physical Sciences Research CouncilThis is the author accepted manuscript. The final version is available from ICE Publishing via http://dx.doi.org/10.1680/jgeen.15.0006