Interferon-free therapy for hepatitis C, how prepared is Australia for biosimilars?

The Hepatitis C virus (HCV) affects some 150 million people worldwide. However, unlike hepatitis A and B there is no vaccination for HCV and approximately 75% of people exposed to HCV develop chronic hepatitis. In Australia, around 226,700 people live with chronic HCV infection costing the government approximately $252 million per year. Historically, the standard approved/licenced treatment for HCV is pegylated interferon with ribavirin. There are major drawbacks with interferon-based therapy including side effects, long duration of therapy, limited access and affordability. Our previous survey of an at-risk population reported HCV treatment coverage of only 5%. Since April 2013, a new class of interferon-free treatments for chronic HCV is subsidised under the Pharmaceutical Benefits Scheme: boceprevir and telaprevir - estimated to cost the Australian Government in excess of $220 million over five years. Other biologic interferon-free therapeutic agents are scheduled to enter the Australian market. Use of small molecule generic pharmaceuticals has been advocated as a means of public cost savings. However, with the new biologic agents, generics (biosimilars) may not be feasible or straightforward, due to long patent life; marketing exclusivity; and regulatory complexity for these newer products.

Precedent-free fault isolation in a diesel engine EGR valve system

In this paper, a framework for isolating unprecedented faults for an EGR valve system is presented. Using normal behavior data generated by a high fidelity engine simulation, the recently introduced Growing Structure Multiple Model System (GSMMS) is used to construct models of normal behavior for an EGR valve system and its various subsystems. Using the GSMMS models as a foundation, anomalous behavior of the entire system is then detected as statistically significant departures of the most recent modeling residuals from the modeling residuals during normal behavior. By reconnecting anomaly detectors to the constituent subsystems, the anomaly can be isolated without the need for prior training using faulty data. Furthermore, faults that were previously encountered (and modeled) are recognized using the same approach as the anomaly detectors.

Precedent-free fault isolation in a diesel engine exhaust gas recirculation system

In this paper, a recently introduced model-based method for precedent-free fault detection and isolation (FDI) is modified to deal with multiple input, multiple output (MIMO) systems and is applied to an automotive engine with exhaust gas recirculation (EGR) system. Using normal behavior data generated by a high fidelity engine simulation, the growing structure multiple model system (GSMMS) approach is used to construct dynamic models of normal behavior for the EGR system and its constituent subsystems. Using the GSMMS models as a foundation, anomalous behavior is detected whenever statistically significant departures of the most recent modeling residuals away from the modeling residuals displayed during normal behavior are observed. By reconnecting the anomaly detectors (ADs) to the constituent subsystems, EGR valve, cooler, and valve controller faults are isolated without the need for prior training using data corresponding to particular faulty system behaviors.

Modeling the viability of the free-ranging cheetah population in Namibia : an object-oriented Bayesian network approach

Conservation of free-ranging cheetah (Acinonyx jubatus) populations is multi faceted and needs to be addressed from an ecological, biological and management perspective. There is a wealth of published research, each focusing on a particular aspect of cheetah conservation. Identifying the most important factors, making sense of various (and sometimes contrasting) findings, and taking decisions when little or no empirical data is available, are everyday challenges facing conservationists. Bayesian networks (BN) provide a statistical modeling framework that enables analysis and integration of information addressing different aspects of conservation. There has been an increased interest in the use of BNs to model conservation issues, however the development of more sophisticated BNs, utilizing object-oriented (OO) features, is still at the frontier of ecological research. We describe an integrated, parallel modeling process followed during a BN modeling workshop held in Namibia to combine expert knowledge and data about free-ranging cheetahs. The aim of the workshop was to obtain a more comprehensive view of the current viability of the free-ranging cheetah population in Namibia, and to predict the effect different scenarios may have on the future viability of this free-ranging cheetah population. Furthermore, a complementary aim was to identify influential parameters of the model to more effectively target those parameters having the greatest impact on population viability. The BN was developed by aggregating diverse perspectives from local and independent scientists, agents from the national ministry, conservation agency members and local fieldworkers. This integrated BN approach facilitates OO modeling in a multi-expert context which lends itself to a series of integrated, yet independent, subnetworks describing different scientific and management components. We created three subnetworks in parallel: a biological, ecological and human factors network, which were then combined to create a complete representation of free-ranging cheetah population viability. Such OOBNs have widespread relevance to the effective and targeted conservation management of vulnerable and endangered species.

Lattice-free descriptions of collective motion with crowding and adhesion

Cell-to-cell adhesion is an important aspect of malignant spreading that is often observed in images from the experimental cell biology literature. Since cell-to-cell adhesion plays an important role in controlling the movement of individual malignant cells, it is likely that cell-to-cell adhesion also influences the spatial spreading of populations of such cells. Therefore, it is important for us to develop biologically realistic simulation tools that can mimic the key features of such collective spreading processes to improve our understanding of how cell-to-cell adhesion influences the spreading of cell populations. Previous models of collective cell spreading with adhesion have used lattice-based random walk frameworks which may lead to unrealistic results, since the agents in the random walk simulations always move across an artificial underlying lattice structure. This is particularly problematic in high-density regions where it is clear that agents in the random walk align along the underlying lattice, whereas no such regular alignment is ever observed experimentally. To address these limitations, we present a lattice-free model of collective cell migration that explicitly incorporates crowding and adhesion. We derive a partial differential equation description of the discrete process and show that averaged simulation results compare very well with numerical solutions of the partial differential equation.

Training-free probability models for whole-image based place recognition

Whole-image descriptors such as GIST have been used successfully for persistent place recognition when combined with temporal filtering or sequential filtering techniques. However, whole-image descriptor localization systems often apply a heuristic rather than a probabilistic approach to place recognition, requiring substantial environmental-specific tuning prior to deployment. In this paper we present a novel online solution that uses statistical approaches to calculate place recognition likelihoods for whole-image descriptors, without requiring either environmental tuning or pre-training. Using a real world benchmark dataset, we show that this method creates distributions appropriate to a specific environment in an online manner. Our method performs comparably to FAB-MAP in raw place recognition performance, and integrates into a state of the art probabilistic mapping system to provide superior performance to whole-image methods that are not based on true probability distributions. The method provides a principled means for combining the powerful change-invariant properties of whole-image descriptors with probabilistic back-end mapping systems without the need for prior training or system tuning.

Mesoporous titania microspheres composed of exposed active faceted nanosheets and their catalytic activities for solvent-free synthesis of azoxybenzenes

Mesoporous titania microspheres composed of nanosheets with exposed active facets were prepared by hydrothermal synthesis in the presence of hexafluorosilicic acid. They exhibited superior catalytic activity in the solvent-free synthesis of azoxybenzene by oxidation of aniline and could be used for 7 cycles with slight loss of activity.

Architecture for a free subjectivity

In October 2012, Simone presented her book Architecture for a Free Subjectivity to the University of Michigan, Taubman College of Architecture and Urban Planning. This book explores the architectural significance of Deleuze’s philosophy of subjectivization, and Guattari’s overlooked dialogue on architecture and subjectivity. In doing so, it proposes that subjectivity is no longer the exclusive provenance of human beings, but extends to the architectural, the cinematic, the erotic, and the political. It defines a new position within the literature on Deleuze and architecture, while highlighting the neglected issue of subjectivity in contemporary discussion.

Towards training-free appearance-based localization : probabilistic models for whole-image descriptors

Whole image descriptors have recently been shown to be remarkably robust to perceptual change especially compared to local features. However, whole-image-based localization systems typically rely on heuristic methods for determining appropriate matching thresholds in a particular environment. These environment-specific tuning requirements and the lack of a meaningful interpretation of these arbitrary thresholds limits the general applicability of these systems. In this paper we present a Bayesian model of probability for whole-image descriptors that can be seamlessly integrated into localization systems designed for probabilistic visual input. We demonstrate this method using CAT-Graph, an appearance-based visual localization system originally designed for a FAB-MAP-style probabilistic input. We show that using whole-image descriptors as visual input extends CAT-Graph’s functionality to environments that experience a greater amount of perceptual change. We also present a method of estimating whole-image probability models in an online manner, removing the need for a prior training phase. We show that this online, automated training method can perform comparably to pre-trained, manually tuned local descriptor methods.

Rapid quantification of free cholesterol in tears using direct insertion/electron ionization-Mass spectrometry

Purpose. To establish a simple and rapid analytical method, based on direct insertion/electron ionization-mass spectrometry (DI/EI-MS), for measuring free cholesterol in tears from humans and rabbits. Methods. A stable-isotope dilution protocol employing DI/EI-MS in selected ion monitoring mode was developed and validated. It was used to quantify the free cholesterol content in human and rabbit tear extracts. Tears were collected from adult humans (n = 15) and rabbits (n = 10) and lipids extracted. Results. Screening, full-scan (m/z 40-600) DI/EI-MS analysis of crude tear extracts showed that diagnostic ions located in the mass range m/z 350 to 400 were those derived from free cholesterol, with no contribution from cholesterol esters. DI/EI-MS data acquired using selected ion monitoring (SIM) were analyzed for the abundance ratios of diagnostic ions with their stable isotope-labeled analogues arising from the D6-cholesterol internal standard. Standard curves of good linearity were produced and an on-probe limit of detection of 3 ng (at 3:1 signal to noise) and limit of quantification of 8 ng (at 10:1 signal to noise). The concentration of free cholesterol in human tears was 15 ± 6 μg/g, which was higher than in rabbit tears (10 ± 5 μg/g). Conclusions. A stable-isotope dilution DI/EI-SIM method for free cholesterol quantification without prior chromatographic separation was established. Using this method demonstrated that humans have higher free cholesterol levels in their tears than rabbits. This is in agreement with previous reports. This paper provides a rapid and reliable method to measure free cholesterol in small-volume clinical samples. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Jacobian-free Newton-Krylov methods with GPU acceleration for computing nonlinear ship wave patterns

The nonlinear problem of steady free-surface flow past a submerged source is considered as a case study for three-dimensional ship wave problems. Of particular interest is the distinctive wedge-shaped wave pattern that forms on the surface of the fluid. By reformulating the governing equations with a standard boundary-integral method, we derive a system of nonlinear algebraic equations that enforce a singular integro-differential equation at each midpoint on a two-dimensional mesh. Our contribution is to solve the system of equations with a Jacobian-free Newton-Krylov method together with a banded preconditioner that is carefully constructed with entries taken from the Jacobian of the linearised problem. Further, we are able to utilise graphics processing unit acceleration to significantly increase the grid refinement and decrease the run-time of our solutions in comparison to schemes that are presently employed in the literature. Our approach provides opportunities to explore the nonlinear features of three-dimensional ship wave patterns, such as the shape of steep waves close to their limiting configuration, in a manner that has been possible in the two-dimensional analogue for some time.

Building sensitising terms to understand free-play in open-ended interactive art environments

In this paper we introduce and discuss the nature of free-play in the context of three open-ended interactive art installation works. We observe the interaction work of situated free-play of the participants in these environments and, building on precedent work, devise a set of sensitising terms derived both from the literature and from what we observe from participants interacting there. These sensitising terms act as guides and are designed to be used by those who experience, evaluate or report on open-ended interactive art. That is, we propose these terms as a common-ground language to be used by participants communicating while in the art work to describe their experience, by researchers in the various stages of research process (observation, coding activity, analysis, reporting, and publication), and by inter-disciplinary researchers working across the fields of HCI and art. This work builds a foundation for understanding the relationship between free-play, open-ended environments, and interactive installations and contributes sensitising terms useful for the HCI community for discussion and analysis of open-ended interactive art works.

Clinician-driven automated classification of limb fractures from free-text radiology reports

The aim of this research is to report initial experimental results and evaluation of a clinician-driven automated method that can address the issue of misdiagnosis from unstructured radiology reports. Timely diagnosis and reporting of patient symptoms in hospital emergency departments (ED) is a critical component of health services delivery. However, due to disperse information resources and vast amounts of manual processing of unstructured information, a point-of-care accurate diagnosis is often difficult. A rule-based method that considers the occurrence of clinician specified keywords related to radiological findings was developed to identify limb abnormalities, such as fractures. A dataset containing 99 narrative reports of radiological findings was sourced from a tertiary hospital. The rule-based method achieved an F-measure of 0.80 and an accuracy of 0.80. While our method achieves promising performance, a number of avenues for improvement were identified using advanced natural language processing (NLP) techniques.

Automatic classification of free-text radiology reports to identify limb fractures using machine learning and the SNOMED CT ontology

Objective To develop and evaluate machine learning techniques that identify limb fractures and other abnormalities (e.g. dislocations) from radiology reports. Materials and Methods 99 free-text reports of limb radiology examinations were acquired from an Australian public hospital. Two clinicians were employed to identify fractures and abnormalities from the reports; a third senior clinician resolved disagreements. These assessors found that, of the 99 reports, 48 referred to fractures or abnormalities of limb structures. Automated methods were then used to extract features from these reports that could be useful for their automatic classification. The Naive Bayes classification algorithm and two implementations of the support vector machine algorithm were formally evaluated using cross-fold validation over the 99 reports. Result Results show that the Naive Bayes classifier accurately identifies fractures and other abnormalities from the radiology reports. These results were achieved when extracting stemmed token bigram and negation features, as well as using these features in combination with SNOMED CT concepts related to abnormalities and disorders. The latter feature has not been used in previous works that attempted classifying free-text radiology reports. Discussion Automated classification methods have proven effective at identifying fractures and other abnormalities from radiology reports (F-Measure up to 92.31%). Key to the success of these techniques are features such as stemmed token bigrams, negations, and SNOMED CT concepts associated with morphologic abnormalities and disorders. Conclusion This investigation shows early promising results and future work will further validate and strengthen the proposed approaches.