Molecular approaches to diagnosis and management of ovarian cancer

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.

Angiogenesis as a biomarker and target in cancer chemoprevention

Angiogenesis, the formation of new blood vessels from existing vasculature, is essential to the late stages of carcinogenesis, allowing tumours to grow beyond 1-2 mm in diameter, invade surrounding tissue, and metastasise. However, more than two decades ago, angiogenesis that preceded neoplastic transformation was seen. Indeed, it can be detected in inflammatory and infectious diseases that increase the risk of developing cancer. Recent advances in fluorescence endoscopy and histological assessment suggest that, for certain cancers, the degree of new blood-vessel formation may differ between the early and late stages of carcinogenic progression. The association between angiogenesis and cancer occurrence, and ease of detection of this process in accessible tissues early in carcinogenesis, mean that angiogenesis fulfils the criteria for a biomarker of the effectiveness of chemopreventive intervention. There is also some evidence that biochemical assays of angiogenic growth factors may after similar potential as surrogate biomarkers. Many natural and synthetic chemopreventive agents in development or in clinical use inhibit new vessel formation in vivo. Validation of angiogenesis as a biomarker for the effectiveness of chemoprevention should further the advancement of some chemopreventive agents.

Improving PLDA speaker verification with limited development data

This paper analyses the probabilistic linear discriminant analysis (PLDA) speaker verification approach with limited development data. This paper investigates the use of the median as the central tendency of a speaker’s i-vector representation, and the effectiveness of weighted discriminative techniques on the performance of state-of-the-art length-normalised Gaussian PLDA (GPLDA) speaker verification systems. The analysis within shows that the median (using a median fisher discriminator (MFD)) provides a better representation of a speaker when the number of representative i-vectors available during development is reduced, and that further, usage of the pair-wise weighting approach in weighted LDA and weighted MFD provides further improvement in limited development conditions. Best performance is obtained using a weighted MFD approach, which shows over 10% improvement in EER over the baseline GPLDA system on mismatched and interview-interview conditions.

Video analytics for the detection of near-miss incidents on approach to railway level crossings

Recent modelling of socio-economic costs by the Australian railway industry in 2010 has estimated the cost of level crossing accidents to exceed AU$116 million annually. To better understand causal factors that contribute to these accidents, the Cooperative Research Centre for Rail Innovation is running a project entitled Baseline Level Crossing Video. The project aims to improve the recording of level crossing safety data by developing an intelligent system capable of detecting near-miss incidents and capturing quantitative data around these incidents. To detect near-miss events at railway level crossings a video analytics module is being developed to analyse video footage obtained from forward-facing cameras installed on trains. This paper presents a vision base approach for the detection of these near-miss events. The video analytics module is comprised of object detectors and a rail detection algorithm, allowing the distance between a detected object and the rail to be determined. An existing publicly available Histograms of Oriented Gradients (HOG) based object detector algorithm is used to detect various types of vehicles in each video frame. As vehicles are usually seen from a sideway view from the cabin’s perspective, the results of the vehicle detector are verified using an algorithm that can detect the wheels of each detected vehicle. Rail detection is facilitated using a projective transformation of the video, such that the forward-facing view becomes a bird’s eye view. Line Segment Detector is employed as the feature extractor and a sliding window approach is developed to track a pair of rails. Localisation of the vehicles is done by projecting the results of the vehicle and rail detectors on the ground plane allowing the distance between the vehicle and rail to be calculated. The resultant vehicle positions and distance are logged to a database for further analysis. We present preliminary results regarding the performance of a prototype video analytics module on a data set of videos containing more than 30 different railway level crossings. The video data is captured from a journey of a train that has passed through these level crossings.

The evaluation of a clinical scar scale for porcine burn scars

This study describes the evaluation of a clinical scar scale for our porcine burn scars, which includes scar cosmetic outcome, colour, height and hair, supplemented with reference porcine scar photographs representing each scar outcome and scar colour scores. A total of 72 porcine burn scars at week 6 after burn were rated in vivo and/or on photographs. Good agreements were achieved for both intra-rater reliability (correlation is 0.86-0.98) and inter-rater reliability (ICC=80-85%). The results showed statistically significant correlations for each pair in this clinical scar scale (p<0.01), with the best correlation found between scar cosmetic outcome and scar colour. A multivariate principle components analysis revealed that this clinical scar assessment was highly correlated with scar histology, wound size, and re-epithelialisation data (p<0.001). More severe scars are clinically characterised by darker purple colouration, more elevation, no presence of hair, histologically by thicker scar tissue, thinner remaining normal dermis, are more likely to have worse contraction, and slower re-epithelialisation. This study demonstrates that our clinical scar scale is a reliable, independent and valuable tool for assessing porcine burn outcome and truthfully reflects scar appearance and function. To our knowledge, this is the first study demonstrating a high correlation between clinical scar assessment and scar histology, wound contraction and re-epithelialisation data on porcine burn scars. We believe that the successful use of porcine scar scales is invaluable for assessing potential human burn treatments.

Burn healing is dependent on burn site : a quantitative analysis from a porcine burn model

This retrospective review examines healing in different sites on a porcine burn model; 24 pairs of burns on 18 pigs from other animal trials were selected for analysis. Each pair of burns was located on the either the cranial or the caudal part of the thoracic ribs region, on the same side of the animal. The burns were 40-50 cm(2) in size and of uniform deep-dermal partial thickness. Caudal burns healed significantly better than cranial burns, demonstrated by earlier closure of wounds, less scar formation and better cosmesis. To our knowledge, this is the first detailed study reporting that burn healing is affected by location on a porcine burn model. We recommend that similar symmetrical burns should be used for future comparative assessments of burn healing.

Assessment of freestanding membranes prepared from Antheraea pernyi silk fibroin as a potential vehicle for corneal epithelial cell transplantation

Freestanding membranes created from Bombyx mori silk fibroin (BMSF) offer a potential vehicle for corneal cell transplantation since they are transparent and support the growth of human corneal epithelial cells (HCE). Fibroin derived from the wild silkworm Antheraea pernyi (APSF) might provide a superior material by virtue of containing putative cell- attachment sites that are absent from BMSF. Thus we have investigated the feasibility of producing transparent, freestanding membranes from APSF and have analysed the behaviour of HCE cells on this material. No significant differences in cell numbers or phenotype were observed in short term HCE cell cultures established on either fibroin. Production of transparent freestanding APSF membranes, however, proved to be problematic as cast solutions of APSF were more prone to becoming opaque, displayed significantly lower permeability and were more brittle than BMSF-membranes. Cultures of HCE cells established on either membrane developed a normal stratified morphology with cytokeratin pair 3/12 being immuno-localized to the superficial layers. We conclude that while it is feasible to produce transparent freestanding membranes from APSF, the technical difficulties associated with this biomaterial, along with an absence of enhanced cell growth, currently favours the continued development of BMSF as a preferred vehicle for corneal cell transplantation. Nevertheless, it remains possible that refinement of techniques for processing APSF might yet lead to improvements in the handling properties and performance of this material.

Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark) : study design and baseline characteristics

Aims Corneal nerve morphology and corneal sensation threshold have recently been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of the ‘Longitudinal Assessment of Neuropathy in type 1 Diabetes using novel ophthalmic Markers’(LANDMark) study. Methods The LANDMark study is a 4-year, two-site, natural history study of three participant groups: type 1 diabetes with neuropathy (T1W), type 1 diabetes without neuropathy (T1WO) and control participants without diabetes or neuropathy. All participants undergo a detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal aesthesiometry. Results 76 T1W, 166 T1WO and 154 control participants were enrolled into the study. Corneal sensation threshold (mbars) was significantly higher (i.e. sensitivity was lower) in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (p < 0.001), with no difference between T1WO and controls. Corneal nerve fibre length was lower in T1W (14.0 ± 6.4 mm/mm2) compared to T1WO (19.1 ± 5.8 mm/mm2) and controls (23.2 ± 6.3 mm/mm2) (p < 0.001). Corneal nerve fibre length was lower in T1WO compared to controls. Conclusions The LANDMark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy. However, corneal nerve fibre length is reduced even in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy.

Comparing methods for modelling spreading cell fronts

Spreading cell fronts play an essential role in many physiological processes. Classically, models of this process are based on the Fisher-Kolmogorov equation; however, such continuum representations are not always suitable as they do not explicitly represent behaviour at the level of individual cells. Additionally, many models examine only the large time asymptotic behaviour, where a travelling wave front with a constant speed has been established. Many experiments, such as a scratch assay, never display this asymptotic behaviour, and in these cases the transient behaviour must be taken into account. We examine the transient and asymptotic behaviour of moving cell fronts using techniques that go beyond the continuum approximation via a volume-excluding birth-migration process on a regular one-dimensional lattice. We approximate the averaged discrete results using three methods: (i) mean-field, (ii) pair-wise, and (iii) one-hole approximations. We discuss the performace of these methods, in comparison to the averaged discrete results, for a range of parameter space, examining both the transient and asymptotic behaviours. The one-hole approximation, based on techniques from statistical physics, is not capable of predicting transient behaviour but provides excellent agreement with the asymptotic behaviour of the averaged discrete results, provided that cells are proliferating fast enough relative to their rate of migration. The mean-field and pair-wise approximations give indistinguishable asymptotic results, which agree with the averaged discrete results when cells are migrating much more rapidly than they are proliferating. The pair-wise approximation performs better in the transient region than does the mean-field, despite having the same asymptotic behaviour. Our results show that each approximation only works in specific situations, thus we must be careful to use a suitable approximation for a given system, otherwise inaccurate predictions could be made.

Laser-camera data discrepancies and reliable perception in outdoor robotics

This work aims to promote integrity in autonomous perceptual systems, with a focus on outdoor unmanned ground vehicles equipped with a camera and a 2D laser range finder. A method to check for inconsistencies between the data provided by these two heterogeneous sensors is proposed and discussed. First, uncertainties in the estimated transformation between the laser and camera frames are evaluated and propagated up to the projection of the laser points onto the image. Then, for each pair of laser scan-camera image acquired, the information at corners of the laser scan is compared with the content of the image, resulting in a likelihood of correspondence. The result of this process is then used to validate segments of the laser scan that are found to be consistent with the image, while inconsistent segments are rejected. Experimental results illustrate how this technique can improve the reliability of perception in challenging environmental conditions, such as in the presence of airborne dust.

Longitudinal assessment of neuropathy in diabetes using novel ophthalmic markers (LANDMark) : baseline findings

Purpose Over the past decade, corneal nerve morphology and corneal sensation threshold have been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of a Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic Markers (LANDMark). Methods The LANDMark Study is a 5-year, two-site, natural history (observational) study of individuals with Type 1 diabetes stratified into those with (T1W) and without (T1WO) neuropathy according to the Toronto criteria, and control subjects. All study participants undergo detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal esthesiometry. Results 396 eligible individuals (208 in Brisbane and 188 in Manchester) were assessed: 76 T1W, 166 T1WO and 154 controls. Corneal sensation threshold (mbars) was significantly higher in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (P=0.002); post-hoc analysis (PHA) revealed no difference between T1WO and controls (Tukey HSD, P=0.502). Corneal nerve fiber length (mm/mm2) (CNFL) was lower in T1W (13.8 ± 6.4) than T1WO (19.1 ± 5.8) and controls (23.2 ± 6.3) (P<0.001); PHA revealed CNFL to be lower in T1W than T1WO, and lower in both of these groups than controls (P<0.001). Corneal nerve branch density (branches/mm2) (CNBD) was significantly lower in T1W (40 ± 32) than T1WO (62 ± 37) and controls (83 ± 46) (P<0.001); PHA showed CNBD was lower in T1W than T1WO, and lower in both groups than controls (P<0.001). Alcohol and cigarette consumption did not differ between groups, although age, BMI, BP, waist circumference, HbA1c, albumin-creatinine ratio, and cholesterol were slightly greater in T1W than T1WO (p<0.05). Some site differences were observed. Conclusions The LANDMark baseline findings confirm that corneal sensitivity and corneal nerve morphometry can detect differences in neuropathy status in individuals with Type 1 diabetes and healthy controls. Corneal nerve morphology is significantly abnormal even in diabetic patients ‘without neuropathy’ compared to control participants. Results of the longitudinal trial will assess the capability of these tests for monitoring change in these parameters over time as potential surrogate markers for neuropathy.

Modelling after-the-fact leakage for key exchange

Security models for two-party authenticated key exchange (AKE) protocols have developed over time to prove the security of AKE protocols even when the adversary learns certain secret values. In this work, we address more granular leakage: partial leakage of long-term secrets of protocol principals, even after the session key is established. We introduce a generic key exchange security model, which can be instantiated allowing bounded or continuous leakage, even when the adversary learns certain ephemeral secrets or session keys. Our model is the strongest known partial-leakage-based security model for key exchange protocols. We propose a generic construction of a two-pass leakage-resilient key exchange protocol that is secure in the proposed model, by introducing a new concept: the leakage-resilient NAXOS trick. We identify a special property for public-key cryptosystems: pair generation indistinguishability, and show how to obtain the leakage-resilient NAXOS trick from a pair generation indistinguishable leakage-resilient public-key cryptosystem.

One tune, three dances : using a traumatic stress framework to understand trauma survivors as networked news sources

Newman and Nelson (2012) describe three ‘dances’ to explain the vacillating psychological states of trauma survivors: the dance of approach and avoidance; the dance of fragmentation and integration; and the dance of resilience and vulnerability. The first pair of seemingly opposite responses describes how survivors at times cope by ‘approaching’ the trauma, for example by gathering information about what happened; whilst at other times, the same person will cope by ‘avoiding’ the trauma by engaging in activities which distract them from the memory of the trauma or having to deal with the consequences of it. The ‘dance’ of fragmentation and integration describes the opposing individual or group experiences encountered after traumas or disasters. Individuals may experience fragmentation, or emotional disconnection, from the trauma as an adaptive means of survival. The ‘dance’ of resilience and vulnerability refers to an individual’s ability to ‘process’ trauma and return to a resilient state in which they re-learn to trust people and the world around them and ‘bounce back’ to a state of being resilient again. This paper will illustrate how an understanding of the three dances can be used to enable survivors of child sexual assault to engage with the media to tell their stories. I will give current examples from six months of journalism research, collaboration and writing of a series of news stories and features which broke an exclusive story simultaneously in The Australian and The Times in London during 2013.

Structural characterization of glycerophospholipids by combinations of ozone- and collision-induced dissociation mass spectrometry: The next step towards "top-down" lipidomics

The complete structural elucidation of complex lipids, including glycerophospholipids, using only mass spectrometry represents a major challenge to contemporary analytical technologies. Here, we demonstrate that product ions arising from the collision-induced dissociation (CID) of the [M + Na] + adduct ions of phospholipids can be isolated and subjected to subsequent gas-phase ozonolysis-known as ozone-induced dissociation (OzID)-in a linear ion-trap mass spectrometer. The resulting CID/OzID experiment yields abundant product ions that are characteristic of the acyl substitution on the glycerol backbone (i.e., sn-position). This approach is shown to differentiate sn-positional isomers, such as the regioisomeric phosphatidylcholine pair of PC 16:0/18:1 and PC 18:1/16:0. Importantly, CID/OzID provides a sensitive diagnostic for the existence of an isomeric mixture in a given sample. This is of very high value for the analysis of tissue extracts since CID/OzID analyses can reveal changes in the relative abundance of isomeric constituents even within different tissues from the same animal. Finally, we demonstrate the ability to assign carbon-carbon double bond positions to individual acyl chains at specific backbone positions by adding subsequent CID and/or OzID steps to the workflow and that this can be achieved in a single step using a hybrid triple quadrupole-linear ion trap mass spectrometer. This unique approach represents the most complete and specific structural analysis of lipids by mass spectrometry demonstrated to date and is a significant step towards comprehensive top-down lipidomics. This journal is © The Royal Society of Chemistry 2014. Grant Number ARC/DP0986628, ARC/FT110100249, ARC/LP110200648

Quantum direct secret sharing with efficient eavesdropping-check and authentication based on distributed fountain codes

We propose to use a simple and effective way to achieve secure quantum direct secret sharing. The proposed scheme uses the properties of fountain codes to allow a realization of the physical conditions necessary for the implementation of no-cloning principle for eavesdropping-check and authentication. In our scheme, to achieve a variety of security purposes, nonorthogonal state particles are inserted in the transmitted sequence carrying the secret shares to disorder it. However, the positions of the inserted nonorthogonal state particles are not announced directly, but are obtained by sending degrees and positions of a sequence that are pre-shared between Alice and each Bob. Moreover, they can confirm that whether there exists an eavesdropper without exchanging classical messages. Most importantly, without knowing the positions of the inserted nonorthogonal state particles and the sequence constituted by the first particles from every EPR pair, the proposed scheme is shown to be secure.