Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer

Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97, LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC = 0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC, C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins. Copyright © 2011 UICC.

Receptor tyrosine kinases and their activation in melanoma

Receptor tyrosine kinases (RTKs) and their downstream signalling pathways have long been hypothesized to play key roles in melanoma development. A decade ago, evidence was derived largely from animal models, RTK expression studies and detection of activated RAS isoforms in a small fraction of melanomas. Predictions that overexpression of specific RTKs implied increased kinase activity and that some RTKs would show activating mutations in melanoma were largely untested. However, technological advances including rapid gene sequencing, siRNA methods and phospho-RTK arrays now give a more complete picture. Mutated forms of RTK genes including KIT, ERBB4, the EPH and FGFR families and others are known in melanoma. Additional over- or underexpressed RTKs and also protein tyrosine phosphatases (PTPs) have been reported, and activities measured. Complex interactions between RTKs and PTPs are implicated in the abnormal signalling driving aberrant growth and survival in malignant melanocytes, and indeed in normal melanocytic signalling including the response to ultraviolet radiation. Kinases are considered druggable targets, so characterization of global RTK activity in melanoma should assist the rational development of tyrosine kinase inhibitors for clinical use. © 2011 John Wiley & Sons A/S.

Block models for improved earthwork allocation planning in linear infrastructure construction

Earthwork planning has been considered in this article and a generic block partitioning and modelling approach has been devised to provide strategic plans of various levels of detail. Conceptually this approach is more accurate and comprehensive than others, for instance those that are section based. In response to environmental concerns the metric for decision making was fuel consumption and emissions. Haulage distance and gradient are also included as they are important components of these metrics. Advantageously the fuel consumption metric is generic and captures the physical difficulties of travelling over inclines of different gradients, that is consistent across all hauling vehicles. For validation, the proposed models and techniques have been applied to a real world road project. The numerical investigations have demonstrated that the models can be solved with relatively little CPU time. The proposed block models also result in solutions of superior quality, i.e. they have reduced fuel consumption and cost. Furthermore the plans differ considerably from those based solely upon a distance based metric thus demonstrating a need for industry to reflect upon their current practices.

Emergency Health Services (EHS) : demand and service delivery models. monograph 3 : patients’ reasons and perceptions

Executive Summary Emergency health is a critical component of Australia’s health system and emergency departments (EDs) are increasingly congested from growing demand and blocked access to inpatient beds. The Emergency Health Services Queensland (EHSQ) study aims to identify the factors driving increased demand for emergency health and to evaluate strategies which may safely reduce the future demand growth. This monograph addresses the perspectives of users of both ambulance services and EDs. The research reported here aimed to identify the perspectives of users of emergency health services, both ambulance services and public hospital Emergency Departments and to identify the factors that they took into consideration when exercising their choice of location for acute health care. A cross-sectional survey design was used involving a survey of patients or their carers presenting to the EDs of a stratified sample of eight hospitals. A specific purpose questionnaire was developed based on a novel theoretical model which had been derived from analysis of the literature (Monograph 1). Two survey versions were developed: one for adult patients (self-complete); and one for children (to be completed by parents/guardians). The questionnaires measured perceptions of social support, health status, illness severity, self-efficacy; beliefs and attitudes towards ED and ambulance services; reasons for using these services, and actions taken prior to the service request. The survey was conducted at a stratified sample of eight hospitals representing major cities (four), inner regional (two) and outer regional and remote (two). Due to practical limitations, data were collected for ambulance and ED users within hospital EDs, while patients were waiting for or under treatment. A sample size quota was determined for each ED based on their 2009/10 presentation volumes. The data collection was conducted by four members of the research team and a group of eight interviewers between March and May 2011 (corresponding to autumn season). Of the total of 1608 patients in all eight emergency departments the interviewers were able to approach 1361 (85%) patients and seek their consent to participate in the study. In total, 911 valid surveys were available for analysis (response rate= 67%). These studies demonstrate that patients elected to attend hospital EDs in a considered fashion after weighing up alternatives and there is no evidence of deliberate or ill-informed misuse. • Patients attending ED have high levels of social support and self-efficacy that speak to the considered and purposeful nature of the exercise of choice. • About one third of patients have new conditions while two thirds have chronic illnesses • More than half the attendees (53.1%) had consulted a healthcare professional prior to making the decision. • The decision to seek urgent care at an ED was mostly constructed around the patient’s perception of the urgency and severity of their illness, reinforced by a strong perception that the hospital ED was the correct location for them (better specialised staff, better care for my condition, other options not as suitable). • 33% of the respondent held private hospital insurance but nevertheless attended a public hospital ED. Similarly patients exercised considered and rational judgements in their choice to seek help from the ambulance service. • The decision to call for ambulance assistance was based on a strong perception about the severity of the illness (too severe to use other means of transport) and that other options were not considered appropriate. • The decision also appeared influenced by a perception that the ambulance provided appropriate access to the ED which was considered most appropriate for their particular condition (too severe to go elsewhere, all facilities in one spot, better specialised and better care). • In 43.8% of cases a health care professional advised use of the ambulance. • Only a small number of people perceived that ambulance should be freely available regardless of severity or appropriateness. These findings confirm a growing understanding that the choice of professional emergency health care services is not made lightly but rather made by reasonable people exercising a judgement which is influenced by public awareness of the risks of acute health and which is most often informed by health professionals. It is also made on the basis of a rational weighing up of alternatives and a deliberate and considered choice to seek assistance from a service which the patient perceived was most appropriate to their needs at that time. These findings add weight to dispensing with public perceptions that ED and ambulance congestion is a result of inappropriate choice by patients. The challenge for health services is to better understand the patient’s needs and to design and validate services that meet those needs. The failure of our health system to do so should not be grounds for blaming the patient, claiming inappropriate patient choices.

Indexing and efficient instance-based retrieval of process models using untanglings

Process-Aware Information Systems (PAISs) support executions of operational processes that involve people, resources, and software applications on the basis of process models. Process models describe vast, often infinite, amounts of process instances, i.e., workflows supported by the systems. With the increasing adoption of PAISs, large process model repositories emerged in companies and public organizations. These repositories constitute significant information resources. Accurate and efficient retrieval of process models and/or process instances from such repositories is interesting for multiple reasons, e.g., searching for similar models/instances, filtering, reuse, standardization, process compliance checking, verification of formal properties, etc. This paper proposes a technique for indexing process models that relies on their alternative representations, called untanglings. We show the use of untanglings for retrieval of process models based on process instances that they specify via a solution to the total executability problem. Experiments with industrial process models testify that the proposed retrieval approach is up to three orders of magnitude faster than the state of the art.

Examining workload models in online and blended teaching

Over the past decade, most Australian universities have moved increasingly towards online course delivery for both undergraduate and graduate programs. In almost all cases, elements of online teaching are part of routine teaching loads. Yet detailed and accurate workload data are not readily available. As a result, institutional policies on academic staff workload are often guided more by untested assumptions about reduction of costs per student unit, rather than being evidence-based, with the result that implementation of new technologies for online teaching has resulted in poorly defined workload expectations. While the academics in this study often revealed a limited understanding of their institutional workload formulas, which in Australia are negotiated between management and the national union through their local branches, the costs of various types of teaching delivery have become a critical issue in a time of increasing student numbers, declining funding, pressures to increase quality and introduce minimum standards of teaching and curriculum, and substantial expenditure on technologies to support e-learning. There have been relatively few studies on the costs associated with workload for online teaching, and even fewer on the more ubiquitous ‘blended’, ‘hybrid’ or ‘flexible’ modes, in which face-to-face teaching is supplemented by online resources and activities. With this in mind the research reported here has attempted to answer the following question: What insights currently inform Australian universities about staff workload when teaching online?

Data requirements of hedonic models in determining the impact of infrastructure charges on new housing costs

The use of hedonic models to estimate the effects of various factors on house prices is well established. This paper examines a number of international hedonic house price models that seek to quantify the effect of infrastructure charges on new house prices. This work is an important factor in the housing affordability debate, with many governments in high growth areas having user-pays infrastructure charging policies operating in tandem with housing affordability objectives, with no empirical evidence on the impact of one on the other. This research finds there is little consistency between existing models and the data sets utilised. Specification appears dependent upon data availability rather than sound theoretical grounding. This may lead to a lack of external validity with model specification dependent upon data availability rather than sound theoretical grounding.

Skin cancer detection by one click - are we any closer?

To the editor...

The detection of incipient faults in small multi-cylinder diesel engines using multiple acoustic emission sensors

This thesis investigates condition monitoring (CM) of diesel engines using acoustic emission (AE) techniques. The AE signals recorded from a small size diesel engine are mixtures of multiple sources from multiple cylinders. Thus, it is difficult to interpret the information conveyed in the signals for CM purposes. This thesis develops a series of practical signal processing techniques to overcome this problem. Various experimental studies conducted to assess the CM capabilities of AE analysis for diesel engines. A series of modified signal processing techniques were proposed. These techniques showed promising results of capability for CM of multiple cylinders diesel engine using multiple AE sensors.

Enabling aircraft emergency landings using active visual site detection

The ability to automate forced landings in an emergency such as engine failure is an essential ability to improve the safety of Unmanned Aerial Vehicles operating in General Aviation airspace. By using active vision to detect safe landing zones below the aircraft, the reliability and safety of such systems is vastly improved by gathering up-to-the-minute information about the ground environment. This paper presents the Site Detection System, a methodology utilising a downward facing camera to analyse the ground environment in both 2D and 3D, detect safe landing sites and characterise them according to size, shape, slope and nearby obstacles. A methodology is presented showing the fusion of landing site detection from 2D imagery with a coarse Digital Elevation Map and dense 3D reconstructions using INS-aided Structure-from-Motion to improve accuracy. Results are presented from an experimental flight showing the precision/recall of landing sites in comparison to a hand-classified ground truth, and improved performance with the integration of 3D analysis from visual Structure-from-Motion.

Complete genomic sequence of a Rubus yellow net virus isolate and detection of genome-wide pararetrovirus-derived small RNAs

Rubus yellow net virus (RYNV) was cloned and sequenced from a red raspberry (Rubus idaeus L.) plant exhibiting symptoms of mosaic and mottling in the leaves. Its genomic sequence indicates that it is a distinct member of the genus Badnavirus, with 7932. bp and seven ORFs, the first three corresponding in size and location to the ORFs found in the type member Commelina yellow mottle virus. Bioinformatic analysis of the genomic sequence detected several features including nucleic acid binding motifs, multiple zinc finger-like sequences and domains associated with cellular signaling. Subsequent sequencing of the small RNAs (sRNAs) from RYNV-infected R. idaeus leaf tissue was used to determine any RYNV sequences targeted by RNA silencing and identified abundant virus-derived small RNAs (vsRNAs). The majority of the vsRNAs were 22-nt in length. We observed a highly uneven genome-wide distribution of vsRNAs with strong clustering to small defined regions distributed over both strands of the RYNV genome. Together, our data show that sequences of the aphid-transmitted pararetrovirus RYNV are targeted in red raspberry by the interfering RNA pathway, a predominant antiviral defense mechanism in plants. © 2013.

HMM relative entropy rate concepts for vision-based aircraft manoeuvre detection

Machine vision is emerging as a viable sensing approach for mid-air collision avoidance (particularly for small to medium aircraft such as unmanned aerial vehicles). In this paper, using relative entropy rate concepts, we propose and investigate a new change detection approach that uses hidden Markov model filters to sequentially detect aircraft manoeuvres from morphologically processed image sequences. Experiments using simulated and airborne image sequences illustrate the performance of our proposed algorithm in comparison to other sequential change detection approaches applied to this application.

Practical Modbus flooding attack and detection

The Modicon Communication Bus (Modbus) protocol is one of the most commonly used protocols in industrial control systems. Modbus was not designed to provide security. This paper confirms that the Modbus protocol is vulnerable to flooding attacks. These attacks involve injection of commands that result in disrupting the normal operation of the control system. This paper describes a set of experiments that shows that an anomaly-based change detection algorithm and signature-based Snort threshold module are capable of detecting Modbus flooding attacks. In comparing these intrusion detection techniques, we find that the signature-based detection requires a carefully selected threshold value, and that the anomaly-based change detection algorithm may have a short delay before detecting the attacks depending on the parameters used. In addition, we also generate a network traffic dataset of flooding attacks on the Modbus control system protocol.

Hydraulic instability onset detection in Kaplan turbines by monitoring shaft vibrations

Design of hydraulic turbines has often to deal with hydraulic instability. It is well-known that Francis and Kaplan types present hydraulic instability in their design power range. Even if modern CFD tools may help to define these dangerous operating conditions and optimize runner design, hydraulic instabilities may fortuitously arise during the turbine life and should be timely detected in order to assure a long-lasting operating life. In a previous paper, the authors have considered the phenomenon of helical vortex rope, which happens at low flow rates when a swirling flow, in the draft tube conical inlet, occupies a large portion of the inlet. In this condition, a strong helical vortex rope appears. The vortex rope causes mechanical effects on the runner, on the whole turbine and on the draft tube, which may eventually produce severe damages on the turbine unit and whose most evident symptoms are vibrations. The authors have already shown that vibration analysis is suitable for detecting vortex rope onset, thanks to an experimental test campaign performed during the commissioning of a 23 MW Kaplan hydraulic turbine unit. In this paper, the authors propose a sophisticated data driven approach to detect vortex rope onset at different power load, based on the analysis of the vibration signals in the order domain and introducing the so-called "residual order spectrogram", i.e. an order-rotation representation of the vibration signal. Some experimental test runs are presented and the possibility to detect instability onset, especially in real-time, is discussed.