Monitoring of a novel FlexiArchTM bridge system to investigate soil-structure interaction

Masonry arch bridges are one of the oldest forms of bridge construction and have been around for thousands of years. Brick and stone arch bridges have proven to be highly durable as most of them have remained serviceable after hundreds of years. In contrast, many bridges built of modern materials have required extensive repair and strengthening after being in service for a relatively short part of their design life. This paper describes the structural monitoring of a novel flexible concrete arch known as: FlexiArchTM. This is a bridge system that can be transported as a flat-pack system to form an arch in-situ by the use of a flexible polymeric membrane. The system has been developed under a Knowledge Transfer Partnership between Queen’s University Belfast (QUB) and Macrete Ltd. Tievenameena Bridge in Northern Ireland was a replacement bridge for the Northern Ireland Roads Service and was monitored under different axle loadings using a range of sensors including discrete fiber optic Bragg gratings to measure the change in strain in the arch ring under live loading. This paper discusses the results of a laboratory model study carried out at QUB. A scaled arch system was loaded with a simulated moving axle. Various techniques were used to monitor the arch under the moving axle load with particular emphasis on the interaction of the arch ring and engineered backfill.

An invasive-native mammalian species replacement process captured by camera trap survey random encounter models

Camera traps are used to estimate densities or abundances using capture-recapture and, more recently, random encounter models (REMs). We deploy REMs to describe an invasive-native species replacement process, and to demonstrate their wider application beyond abundance estimation. The Irish hare Lepus timidus hibernicus is a high priority endemic of conservation concern. It is threatened by an expanding population of non-native, European hares L. europaeus, an invasive species of global importance. Camera traps were deployed in thirteen 1 km squares, wherein the ratio of invader to native densities were corroborated by night-driven line transect distance sampling throughout the study area of 1652 km2. Spatial patterns of invasive and native densities between the invader’s core and peripheral ranges, and native allopatry, were comparable between methods. Native densities in the peripheral range were comparable to those in native allopatry using REM, or marginally depressed using Distance Sampling. Numbers of the invader were substantially higher than the native in the core range, irrespective of method, with a 5:1 invader-to-native ratio indicating species replacement. We also describe a post hoc optimization protocol for REM which will inform subsequent (re-)surveys, allowing survey effort (camera hours) to be reduced by up to 57% without compromising the width of confidence intervals associated with density estimates. This approach will form the basis of a more cost-effective means of surveillance and monitoring for both the endemic and invasive species. The European hare undoubtedly represents a significant threat to the endemic Irish hare.

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the prostate-specific antigen level or a confirmed reduction in the circulating tumor-cell count from 5 or more cells per 7.5 ml of blood to less than 5 cells per 7.5 ml. Targeted next-generation sequencing, exome and transcriptome analysis, and digital polymerase-chain-reaction testing were performed on samples from mandated tumor biopsies.

RESULTS: Overall, 50 patients were enrolled; all had received prior treatment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received cabazitaxel. Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib.

CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. (Funded by Cancer Research UK and others; ClinicalTrials.gov number, NCT01682772; Cancer Research UK number, CRUK/11/029.).

Tooth replacement for partially dentate elders: a willingness-to-pay analysis

Objectives: The primary aim of this study was to investigate partially dentate elders’ willingness-to-pay (WTP) for two different tooth replacement strategies: using Removable Partial Dentures (RPDs) and, functionally orientated treatment (SDA). The secondary aim was to measure the same patient group’s WTP for dental implants.Methods: Patients who had completed a previous RCT comparing two tooth replacement strategies (RPDs and SDA) were recruited. 59 patients were asked to indicate their WTP for treatment to replace missing teeth in a number of hypothetical scenarios using the payment card method of contingency evaluation coupled to different costs. Data were collected on patients’ social class, longest held occupation, income levels and social circumstances.Results: The median age for the patient sample was 72.0 years (IQR: 71-75 years). Patients who had previously been provided with RPDs indicated that their WTP for this treatment strategy was significantly higher than those patients who had received SDA treatment (Mann-Whitney U Test: p<0.001). This group were also WTP a higher price for SDA treatment than those patients who had previously been treated according to this modality (Mann-Whitney U Test: p=0.005). The results indicated that patients’ age was not correlated with WTP but both social class and current income levels were significantly correlated (Spearman’s rank correlation: p<0.05).Patients in both treatment groups exhibited llittle WTP for dental implant treatment with a median price recorded which was lower than either RPD or SDA treatment.Conclusions: Amongst this patient cohort previous treatment experience had a strong influence on WTP as did social class and current income levels. The patients’ WTP indicated that they did not value dental implants over simpler forms of tooth replacement such as RPDs or a SDA approach.

Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis

Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells in vitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate in vivo and to repair defects in the monolayer. We further propose that the conventionally accepted 'postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells.

Institutional Hybridity in Public Sector Reform: Replacement, Blending, or Layering of Administrative Paradigms

Despite an abundance of studies on hybridization and hybrid forms of organizing, scholarly work has failed to distinguish consistently between specific types of hybridity. As a consequence, the analytical category has become blurred and lacks conceptual clarity. Our paper discusses hybridity as the simultaneous appearance of institutional logics in organizational contexts, and differentiates the parallel co-existence of logics from transitional combinations (eventually leading to the replacement of a logic) and more robust combinations in the form of layering and blending. While blending refers to hybridity as an ‘amalgamate’ with original components that are no longer discernible, the notion of layering conceptualizes hybridity in a way that the various elements, or clusters thereof, are added on top of, or alongside, each other, similar to sediment layers in geology. We illustrate and substantiate such conceptual differentiation with an empirical study of the dynamics of public sector reform. In more detail, we examine the parliamentary discourse around two major reforms of the Austrian Federal Budget Law in 1986 and in 2007/2009 in order to trace administrative (reform) paradigms. Each of the three identified paradigms manifests a specific field-level logic with implications for the state and its administration: bureaucracy in Weberian-style Public Administration, market-capitalism in New Public Management, and democracy in New Public Governance. We find no indication of a parallel co-existence or transitional combination of logics, but hybridity in the form of robust combinations. We explore how new ideas fundamentally build on – and are made resonant with – the central bureaucratic logic in a way that suggests layering rather than blending. The conceptual findings presented in our article have implications for the literature on institutional analysis and institutional hybridity.

Climate drives temporal replacement and nested‐resultant richness patterns of Scottish coastal vegetation

Beta diversity quantifies spatial and/or temporal variation in species composition. It is comprised of two distinct components, species replacement and nestedness, which derive from opposing ecological processes. Using Scotland as a case study and a β-diversity partitioning framework, we investigate temporal replacement and nestedness patterns of coastal grassland species over a 34-yr time period. We aim to 1) understand the influence of two potentially pivotal processes (climate and land-use changes) on landscape-scale (5 × 5 km) temporal replacement and nestedness patterns, and 2) investigate whether patterns from one β-diversity component can mask observable patterns in the other.

We summarised key aspects of climate driven macro-ecological variation as measures of variance, long-term trends, between-year similarity and extremes, for three important climatic predictors (minimum temperature, water-balance and growing degree-days). Shifts in landscape-scale heterogeneity, a proxy of land-use change, was summarised as a spatial multiple-site dissimilarity measure. Together, these climatic and spatial predictors were used in a multi-model inference framework to gauge the relative contribution of each on temporal replacement and nestedness patterns.

Temporal β-diversity patterns were reasonably well explained by climate change but weakly explained by changes in landscape-scale heterogeneity. Climate was shown to have a greater influence on temporal nestedness than replacement patterns over our study period, linking nestedness patterns, as a result of imbalanced gains and losses, to climatic warming and extremes respectively. Important climatic predictors (i.e. growing degree-days) of temporal β-diversity were also identified, and contrasting patterns between the two β-diversity components revealed.

Results suggest climate influences plant species recruitment and establishment processes of Scotland's coastal grasslands, and while species extinctions take time, they are likely to be facilitated by climatic perturbations. Our findings also highlight the importance of distinguishing between different components of β-diversity, disentangling contrasting patterns than can mask one another.