Global analysis of serum microRNAs as potential biomarkers for lung adenocarcinoma

Early diagnosis and the ability to predict the most relevant treatment option for individuals is essential to improve clinical outcomes for non-small cell lung cancer (NSCLC) patients. Adenocarcinoma (ADC), a subtype of NSCLC, is the single biggest cancer killer and therefore an urgent need to identify minimally invasive biomarkers to enable early diagnosis. Recent studies, by ourselves and others, indicate that circulating miRNA s have potential as biomarkers. Here we applied global profiling approaches in serum from patients with ADC of the lung to explore if miRNA s have potential as diagnostic biomarkers. This study involved RNA isolation from 80 sera specimens including those from ADC patients (equal numbers of stages 1, 2, 3, and 4) and age- and gender-matched controls (n = 40 each). Six hundred and sixty-seven miRNA s were co-analyzed in these specimens using TaqMan low density arrays and qPCR validation using individual miRNA s. Overall, approximately 390 and 370 miRNA s were detected in ADC and control sera, respectively. A group of 6 miRNA s, miR-30c-1* (AU C = 0.74; P < 0.002), miR-616(AU C = 0.71; P = 0.001), miR-146b-3p (AU C = 0.82; P < 0.0001), miR-566 (AU C = 0.80; P < 0.0001), miR-550 (AU C = 0.72; P = 0.0006), and miR-939 (AU C = 0.82; P < 0.0001) was found to be present at substantially higher levels in ADC compared with control sera. Conversely, miR-339-5p and miR-656 were detected at substantially lower levels in ADC sera (co-analysis resulting in AU C = 0.6; P = 0.02). Differences in miRNA profile identified support circulating miRNA s having potential as diagnostic biomarkers for ADC. More extensive studies of ADC and control serum specimens are warranted to independently validate the potential clinical relevance of these miRNA s as minimally invasive biomarkers for ADC.

Exploring pedestrian accessibility and walkability : insight from public place observations in inner-urban higher density Brisbane, Australia

As planners work to create more sustainable and liveable urban environments, a priority is to transition away from prioritising the automobile and towards enhancing the pedestrian experience. Thus, this research explores the experience of pedestrian accessibility in inner-urban higher-density Brisbane in Australia, drawing on findings from semi-structured in-depth interviews with 24 residents and over 100 hours of public place observations in three case-study neighbourhoods. The interviews took place in residents homes and explored their experience of higher density living and their neighbourhood, whilst observations were recorded through a combination of methods including photographs, sketch maps, recordings and field journals. Observation locations included retail and commercial space, roads, parkland and open space, with multiple observations at each location. A thematic analysis identified common themes in both interviews and the observations, with this paper focusing on residents’ lived experience in urban built environments. This analysis revealed that pedestrian accessibility is linked to access to local amenities and direct routes, aesthetics, sense of community, ownership of space and safety. In particular, observations revealed how pedestrian accessibility and route-taking works with, against or in spite of the design features of urban environments, as well as the importance of the social use of the built environment. Residents spoke about although walking quick and preferred for local amenities, the decision to walk was moderated by factors such as time of day and perceived safety. Measures to ensure and improve the pedestrian accessibility of urban areas needs to take into account the propensity for people to prefer and improvise direct routes (often to the detriment of traffic safety considerations), the importance of ongoing maintenance and upgrading of walking infrastructure and the importance of aesthetically pleasing and safe walking environments. By combining interviews and observations, this research highlights the current dominance of the automobile culture in Brisbane and the layers of meaning, experiences and complexity hidden within the pedestrian experience.

New suburbs in the making? Locating master planned estates in a comparative analysis of suburbs in South-East Queensland

In urban scholarship Master Planned Estates (MPEs) are viewed as illustrative of broader changes to the urban environment and characterised as homogenous, affluent enclaves where community life is largely orchestrated by the developer. Yet no study has fully considered if, and to what extent, MPEs can be distinguished from other suburb types in terms of their residential composition and their levels of sociability and community attachment. In this article, we empirically test if MPEs are different from ‘conventional’ suburbs by examining them structurally in terms of their demographic and socio-economic characteristics, as well as in terms of their key community social processes. Using data from a 2008 study of 148 suburbs across Brisbane, Australia (which includes data from two MPEs), we undertake a comparative analysis of suburbs and examine the density of neighbour networks, residents' reports of place attachment and cohesion and neighbourly contact in MPEs compared to other residential suburbs. Our findings suggest that MPEs are not distinct in terms of their degree of homogeneity and socio-economic characteristics, but that connections among residents are lower than other suburbs despite—or perhaps because of—the active interventions of the developer.

Nonlinear analysis of plastic ball grid array solder joints

A nonlinear finite element analysis was carried out to investigate the viscoplastic deformation of solder joints in a ball grid array (BGA) package under temperature cycle. The effects of constraint on print circuit board (PCB) and stiffness of substrate on the deformation behaviour of the solder joints were also studied. A relative damage stress was adopted to analyze the potential failure sites in the solder joints. The results indicated that high inelastic strain and strain energy density were developed in the joints close to the package center. On the other hand, high constraint and high relative damage stress were associated with the joint closest to the edge of the silicon chip. The joint closest to the edge of the silicon chip was regarded as the most susceptible failure site if cavitation instability is the dominant failure mechanism. Increase the external constraint on the print circuit board (PCB) causes a slight increase in stress triaxiality (m/eq) and relative damage stress in the joint closest to the edge of silicon die. The relative damage stress is not sensitive to the Young’s modulus of the substrate.

Recursive pathways to marginal likelihood estimation with prior-sensitivity analysis

We investigate the utility to computational Bayesian analyses of a particular family of recursive marginal likelihood estimators characterized by the (equivalent) algorithms known as "biased sampling" or "reverse logistic regression" in the statistics literature and "the density of states" in physics. Through a pair of numerical examples (including mixture modeling of the well-known galaxy dataset) we highlight the remarkable diversity of sampling schemes amenable to such recursive normalization, as well as the notable efficiency of the resulting pseudo-mixture distributions for gauging prior-sensitivity in the Bayesian model selection context. Our key theoretical contributions are to introduce a novel heuristic ("thermodynamic integration via importance sampling") for qualifying the role of the bridging sequence in this procedure, and to reveal various connections between these recursive estimators and the nested sampling technique.

Personal media and wireless cities : towards an urban spatial analysis

For the past decade, at least, varieties of small, hand held networked instruments have appeared on the global scene, selling in record numbers, and being utilized by all manner of persons from the old to the young; children, women, men, the wealthy and the poor and in all countries. Their presences bespeak a radical shift in telecommunications infrastructure and the future of communications. They are particularly visible in urban areas where mobile transmission network infrastructure (3G, 4G, cellular and Wi-Fi) is more established and substantial, options more plentiful, and density of populations more dramatic. These end user products—I phones, cell phones, Blackberries, DSi, DS, IPads, Zooms, and others – of the mobile communications industry are the latest, hottest globalized commodities. At the same time, wirelessness, or the state of being wireless, and therefore capable of taking along one's networks, communicating from unlikely spaces, and navigating with GPS, is a complex social, political and economic communications phenomenon of early 21st century life. This thesis examines the specter of being wireless in cities. It lends the entire idea an experimentally envisioned, historical and planned context wherein personalization of media tools is seen both as a design development of corporate, artistic, and military imagination, as well as a profound social phenomenon enabling new forms of sharing, belonging, and urban community. In doing that it asserts the parameters of a new mobile space which, aside from clear benefits to humankind by way of mobility, has reinscribed numerous categories including gender. Moreover, it posits the recognition of other, more nuanced theoretical spaces for complex readings of gender and gendered use, including some instantiation of the notion of 'network' itself as a cyborgian and gendered social form. Additionally, cities are studied as places where technology is not only quickly popularized, but is connected to larger political interests, such as the reading of data, tracking of information, and the new security culture. In so doing the work has been undertaken as an urban spatial analysis and experimental ethnography, utilizing architectural, feminist, techno-utopian, industrial and theoretical literatures as discursive underpinnings from whence understandings and interpretations of mobile space, the mobile office, networked mobility, and personal media have come, linking the space of cities to specific, pioneering urban public art projects in which voice, texting and MMS have been utilized in expressions of ubiquitous networks and urban history. Through numerous examples of techno art, the thesis discusses the 'wireless city' as an emerging cultural, socially constructed economic and spatial entity, both conceived and formed through historic processes of urbanization.

High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers

Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

Pattern analysis of the diversity of morphological plant attributes and herbage yield in a world collection of white clover (Trifolium repens L.) germplasm characterised in a summer moisture stress environment of Australia

Information on the variation available for different plant attributes has enabled germplasm collections to be effectively utilised in plant breeding. A world sourced collection of white clover germplasm has been developed at the White Clover Resource Centre at Glen Innes, New South Wales. This collection of 439 accessions was characterised under field conditions as a preliminary study of the genotypic variation for morphological attributes; stolon density, stolon branching, number of nodes. number of rooted nodes, stolon thickness, internode length, leaf length, plant height and plant spread, together with seasonal herbage yield. Characterisation was conducted on different batches of germplasm (subsets of accessions taken from the complete collection) over a period of five years. Inclusion of two check cultivars, Haifa and Huia, in each batch enabled adjustment of the characterisation data for year effects and attribute-by-year interaction effects. The component of variance for seasonal herbage yield among batches was large relative to that for accessions. Accession-by-experiment and accession-by-season interactions for herbage yield were not detected. Accession mean repeatability for herbage yield across seasons was intermediate (0.453). The components of genotypic variance among accessions for all attributes, except plant height, were larger than their respective standard errors. The estimates of accession mean repeatability for the attributes ranged from low (0.277 for plant height) to intermediate (0.544 for internode length). Multivariate techniques of clustering and ordination were used to investigate the diversity present among the accessions in the collection. Both cluster analysis and principal component analysis suggested that seven groups of accessions existed. It was also proposed from the pattern analysis results that accessions from a group characterised by large leaves, tall plants and thick stolons could be crossed with accessions from a group that had above average stolon density and stolon branching. This material could produce breeding populations to be used in recurrent selection for the development of white clover cultivars for dryland summer moisture stress environments in Australia. The germplasm collection was also found to be deficient in genotypes with high stolon density, high number of branches high number of rooted nodes and large leaves. This warrants addition of new germplasm accessions possessing these characteristics to the present germplasm collection.

Thoracoscopic scoliosis surgery – a cheaper option? A cost analysis of 189 consecutive cases

INTRODUCTION: Increasing health care costs, limited resources and increased demand makes cost effective and cost-efficient delivery of Adolescent Idiopathic Scoliosis (AIS) management paramount. Rising implant costs in deformity correction surgery have prompted analysis of whether high implant densities are justified. The objective of this study was to analyse the costs of thoracoscopic scoliosis surgery, comparing initial learning curve costs with those of the established technique and to the costs involved in posterior instrumented fusion from the literature. METHODS: 189 consecutive cases from April 2000 to July 2011 were assessed with a minimum of 2 years follow-up. Information was gathered from a prospective database covering perioperative factors, clinical and radiological outcomes, complications and patient reported outcomes. The patients were divided into three groups to allow comparison; 1. A learning curve cohort, 2. An intermediate cohort and 3. A third cohort of patients, using our established technique. Hospital finance records and implant manufacturer figures were corrected to 2013 costs. A literature review of AIS management costs and implant density in similar curve types was performed. RESULTS: The mean pre-op Cobb angle was 53°(95%CI 0.4) and was corrected postop to mean 22.9°(CI 0.4). The overall complication rate was 20.6%, primarily in the first cohort, with a rate of 5.6% in the third cohort. The average total costs were $46,732, operating room costs of $10,301 (22.0%) and ICU costs of $4620 (9.8%). The mean number of screws placed was 7.1 (CI 0.04) with a single rod used for each case giving average implant costs of $14,004 (29.9%). Comparison of the three groups revealed higher implant costs as the technique evolved to that in use today, from $13,049 in Group 1 to $14577 in Group 3 (P<0.001). Conversely operating room costs reduced from $10,621 in Group 1 to $7573 (P<0.001) in Group 3. ICU stay was reduced from an average of 1.2 to 0 days. In-patient stay was significantly (P=0.006) lower in Groups 2 and 3 (5.4 days) than Group 1 (5.9 days) (i.e. a reduction in cost of approximately $6,140). CONCLUSIONS: The evolution of our thoracoscopic anterior scoliosis correction has resulted in an increase in the number of levels fused and reduction in complication rate. Implant costs have risen as a result, however, there has been a concurrent decrease in those costs generated by operating room use, ICU and in-patient stay with increasing experience. Literature review of equivalent curve types treated posteriorly shows similar perioperative factors but higher implant density, 69-83% compared to the 50% in this study. Thoracoscopic Scoliosis surgery presents a low density, reliable, efficient and effective option for selected curves. A cost analysis of Thoracoscopic Scoliosis Surgery using financial records and a prospectively collected database of all patients since 2000, demonstrating a clear cost advantage compared to equivalent posterior instrumentation and fusion.

Three-dimensional off-design numerical analysis of an organic Rankine cycle radial-inflow turbine

Optimisation of organic Rankine cycles(ORCs for binary cycle applications could play a major role in determining the competitiveness of low to moderate renewable sources. An important aspect of the optimisation is to maximise the turbine output power for a given resource. This requires careful attention to the turbine design notably through numerical simulations. Challenges in the numerical modelling of radial-inflow turbines using high-density working fluids still need to be addressed in order to improve the turbine design and better optimise ORCs. Thispaper presents preliminary 3D numerical simulations of a high-density radial-inflow ORC turbine in sensible geothermal conditions. Following extensive investigation of the operating conditions and thermodynamic cycle analysis, therefrigerant R143a is chosen as the high-density working fluid. The 1D design of the candidate radial-inflow turbine is presented in details. Furthermore, commercially-available software Ansys-CFX is used to perform preliminary steady-state 3D CFD simulations of the candidate R143a radial-inflow turbine for a number of operating conditions including off-design conditions. The real-gas properties are obtained using the Peng–Robinson equations of state.The thermodynamic ORC cycle is presented. The preliminary design created using dedicated radial-inflow turbine software Concepts-Rital is discussed and the 3D CFD results are presented and compared against the meanline analysis.

Simulation-based density estimation for time series using covariate data

This paper proposes a simulation-based density estimation technique for time series that exploits information found in covariate data. The method can be paired with a large range of parametric models used in time series estimation. We derive asymptotic properties of the estimator and illustrate attractive finite sample properties for a range of well-known econometric and financial applications.

Analysis of resource efficiency : a production frontier approach

This article integrates the material/energy flow analysis into a production frontier framework to quantify resource efficiency (RE). The emergy content of natural resources instead of their mass content is used to construct aggregate inputs. Using the production frontier approach, aggregate inputs will be optimised relative to given output quantities to derive RE measures. This framework is superior to existing RE indicators currently used in the literature. Using the exergy/emergy content in constructing aggregate material or energy flows overcomes a criticism that mass content cannot be used to capture different quality of differing types of resources. Derived RE measures are both ‘qualitative’ and ‘quantitative’, whereas existing RE indicators are only qualitative. An empirical examination into the RE of 116 economies was undertaken to illustrate the practical applicability of the new framework. The results showed that economies, on average, could reduce the consumption of resources by more than 30% without any reduction in per capita gross domestic product (GDP). This calculation occurred after adjustments for differences in the purchasing power of national currencies. The existence of high variations in RE across economies was found to be positively correlated with participation of people in labour force, population density, urbanisation, and GDP growth over the past five years. The results also showed that economies of a higher income group achieved higher RE, and those economies that are more dependent on imports and primary industries would have lower RE performance.

The application of social network analysis in the construction industry of Hong Kong

The Hong Kong construction industry is currently facing ageing problem and labour shortage. There are opportunities for employing ethnic minority construction workers to join this hazardous industry. These ethnic minority workers are prone to accidents due to communication barriers. Safety communication is playing an important role for avoiding the accidents on construction sites. However, the ethnic minority workers are not very fluent in the local language and facing safety communication problems while working with local workers. Social network analysis (SNA), being an effective tool to identify the safety communication flow on the construction site, is used to attain the measures of safety communication like centrality, density and betweenness within the ethnic minorities and local workers, and to generate sociograms that visually represent communication pattern within the effective and ineffective safety networks. The aim of this paper is to present the application of SNA for improving the safety communication of ethnic minorities in the construction industry of Hong Kong. The paper provides the theoretical background of SNA approaches for the data collection and analysis using the software UCINET and NetDraw, to determine the predominant safety communication network structure and pattern of ethnic minorities on site.

The global burden attributable to low bone mineral density

Introduction The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. Objectives To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. Methods A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm2) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. Results Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. Conclusions Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.