Reconstructing boulder deposition histories: extreme wave signatures on a complex rocky shoreline of Malta

The Żonqor coastline, southeast Malta, displays an exceptional range of geomorphic signatures of extreme coastal events. This paper brings together evidence acquired from a field survey, analysis of time-sequential imagery, and hydrodynamic modelling to investigate the histories of boulder groups identified by their intrinsic and contextual characteristics. Clear differences are revealed between the distribution of boulders recently moved and those of considerable age. Tracking the movement of boulders since 1957 confirms that storms of surprisingly frequent interval are capable of complex boulder movements, including lifting of megaclasts. Scrutiny of the ancient boulders, including weathering features and fascinating landward-facing (reverse) imbrication, cautiously suggests tsunami as the agent for their emplacement. A novel method is developed for depicting the velocity decay profiles of hypothetical waves, which overcomes some of the limitations of the Nott approach. Applied here, the wave run-up context further sets the ancient movers apart from their recent mover companions. The combined evidence implies a palimpsestic landscape where storm waves are regular geomorphic agents that add to and rework the distribution of boulders close to the shoreline, but over long time periods the landscape becomes reset by tsunami—a concept that is of value to agencies in Malta responsible for coastal safety, planning and management

Towards targeted dietary support for shift workers with type 2 diabetes (Shift-Diabetes study): A mixed-methods case study protocol

BACKGROUND: Blood glucose is higher in people working night-shifts compared to day-workers. Changes to eating behaviour, activity, and sleep patterns in addition to circadian disruption are likely to impact glucose management in night-shift workers with Type 2 diabetes. AIM: To investigate current dietary intake and glucose variability during night work, including barriers and facilitators to dietary behavior in this context. METHODS: A mixed-methods case study will be conducted. Shift workers with Type 2 diabetes working in a hospital setting will be recruited to this two-part study. Part 1: 70 participants will complete a 10-day observational study collecting data on continuous glucose, diet (self-report diary), sleep and physical activity during a period covering night work, rest days and non-night workdays. Mean glucose concentration and variability, and the mean healthy diet index score, will be compared between days of night work, non-night work and rest, after adjusting for other individual factors (sleep/physical activity/demographics). Part 2: A sample (n~13) will complete semi-structured interviews based on behavioural science frameworks to explore barriers/enablers to dietary behaviour when working night shifts. This will inform a quantitative survey to explore the generalisability of interview findings. DISCUSSION: Findings from Part 1 and 2 will be triangulated to identify potential intervention strategies to address key barriers and enablers to healthier eating, and in turn improved glucose control, in shift workers with Type 2 diabetes. This will be facilitated through stakeholder consultation and application of behavioural science frameworks

The Case for RackOut: Scalable Data Serving Using Rack-Scale Systems

To provide low latency and high throughput guarantees, most large key-value stores keep the data in the memory of many servers. Despite the natural parallelism across lookups, the load imbalance, introduced by heavy skew in the popularity distribution of keys, limits performance. To avoid violating tail latency service-level objectives, systems tend to keep server utilization low and organize the data in micro-shards, which provides units of migration and replication for the purpose of load balancing. These techniques reduce the skew, but incur additional monitoring, data replication and consistency maintenance overheads. In this work, we introduce RackOut, a memory pooling technique that leverages the one-sided remote read primitive of emerging rack-scale systems to mitigate load imbalance while respecting service-level objectives. In RackOut, the data is aggregated at rack-scale granularity, with all of the participating servers in the rack jointly servicing all of the rack’s micro-shards. We develop a queuing model to evaluate the impact of RackOut at the datacenter scale. In addition, we implement a RackOut proof-of-concept key-value store, evaluate it on two experimental platforms based on RDMA and Scale-Out NUMA, and use these results to validate the model. Our results show that RackOut can increase throughput up to 6× for RDMA and 8.6× for Scale-Out NUMA compared to a scale-out deployment, while respecting tight tail latency service-level objectives

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells

Transient receptor potential (TRP) channels TRPC3 and TRPC6 are expressed in both sensory neurons and cochlear hair cells. Deletion of TRPC3 or TRPC6 in mice caused no behavioural phenotype, although loss of TRPC3 caused a shift of rapidly adapting (RA) mechanosensitive currents to intermediate-adapting currents in dorsal root ganglion sensory neurons. Deletion of both TRPC3 and TRPC6 caused deficits in light touch and silenced half of small-diameter sensory neurons expressing mechanically activated RA currents. Double TRPC3/TRPC6 knock-out mice also showed hearing impairment, vestibular deficits and defective auditory brain stem responses to high-frequency sounds. Basal, but not apical, cochlear outer hair cells lost more than 75 per cent of their responses to mechanical stimulation. FM1-43-sensitive mechanically gated currents were induced when TRPC3 and TRPC6 were co-expressed in sensory neuron cell lines. TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes

The Relative Importance of Clinical, Economic, Patient Values and Feasibility Criteria in Cancer Drug Reimbursement in Canada:A Revealed Preferences Analysis of Recommendations of the Pan-Canadian Oncology Drug Review 2011–2017

Background: Most Canadian provinces and territories rely on the pan-Canadian Oncology Drug Review (pCODR) to provide recommendations regarding public reimbursement of cancer drugs. The pCODR review process considers four dimensions of value—clinical benefit, economic evaluation, patient-based values and adoption feasibility—but they do not define weights for individual decision criteria or an acceptable threshold for any of the criteria. Given this implicit review process, it is of interest to understand which factors appear to carry the most weight in pCODR recommendations using a revealed preferences approach. Methods: Using publicly available decision summaries (n = 91) describing submissions and resulting recommendations 2011–2017, we extracted ten attributes that characterized each submission. Using logistic regression, we identified statistically significant attributes and estimated their relative impact in final recommendations. Results: Clinical aspects appear to carry the greatest weight in the decision to reject or not reject, along with aspects of patient value (treatments with no alternatives were less likely to be rejected). Cost effectiveness does not appear to play a role in the initial decision to reject or not reject but is critical in full versus conditional approvals. There is evidence of a maximum acceptable threshold of around $Can140,000 per quality-adjusted life-year (QALY) gained. Conclusion: A set of factors driving pCODR recommendations is identifiable, supporting the consistency of the review process. However, the implicit nature of the review process and the difficulty of extracting and interpreting some of the attribute levels used in the analysis suggests that the process may still lack full transparency

Depression chains in seafloor of contrasting morphology, Atacama Trench margin: a comment on Marsh et al. (2018)

This comment presents acoustic and visual data showing deep seafloor depression chains similar to those reported in Marsh et al. (R. Soc. open sci. 5: 180286), though from a different deep-sea setting. Marsh et al. present data collected during cruise JC120 from polymetallic nodule rich sites within the Clarion-Clipperton Fracture Zone (CCFZ), at water depths of between 3999 and 4258 m. Within this comment, we present data collected with equivalent acoustic and imaging devices on-board the RV Sonne (SO261—March/April 2018) from the Atacama Trench, approximately 4000 m depth, which shows comparable depression chains in the seafloor. In contrast with the CCFZ observations, our study area was wholly free of polymetallic nodules, an observation therefore weakening the ‘ballast collection’ by deep-sea diving mammals formation hypothesis discussed in their paper. We support their alternate hypothesis that if these features are indeed generated by deep-diving megafauna, then they are more likely the resultant traces of infauna feeding or marks made during opportunistic capture of benthic fish/cephalopods. We observed these potential prey fauna with lander and towed camera systems during the cruise, with example images of these presented here. Both the SO261 and JC120 cruises employed high-resolution sidescan systems at deployment altitudes seldom used routinely until the last few years during scientific deep-sea surveys. Given that both cruises found these depression chains in contrasting physical regions of the East Pacific, they may have a more ubiquitous distribution than at just these sites. Thus, the impacts of cetacean foraging behaviour on deep seafloor communities, and the potential relevance of these prey sources to deep-diving species, should be considered