Is Australia positioned to take advantage of biosimilars?

Australia currently has a small generic and biosimilar industry despite having a good track record in biomedical research and a sound reputation in producing high quality but small volume biological pharmaceuticals. In recent times, Australia has made incremental changes to its regulation of biosimilars – in patent registration, in the use of commercial confidential information, and in remuneration. These improvements, together with Australia’s geographical proximity and strong trade relationship with the Asian biocluster have positioned Australia to take advantage of potential public cost savings from the increased use of biosimilars.

Memory and Epileptogenesis in Complex Biological and Simulated Systems

Oscillations of neural activity may bind widespread cortical areas into a neural representation that encodes disparate aspects of an event. In order to test this theory we have turned to data collected from complex partial epilepsy (CPE) patients with chronically implanted depth electrodes. Data from regions critical to word and face information processing was analyzed using spectral coherence measurements. Similar analyses of intracranial EEG (iEEG) during seizure episodes display HippoCampal Formation (HCF)—NeoCortical (NC) spectral coherence patterns that are characteristic of specific seizure stages (Klopp et al. 1996). We are now building a computational memory model to examine whether spatio-temporal patterns of human iEEG spectral coherence emerge in a computer simulation of HCF cellular distribution, membrane physiology and synaptic connectivity. Once the model is reasonably scaled it will be used as a tool to explore neural parameters that are critical to memory formation and epileptogenesis.

Further development of discrete computational techniques for calculation of restricted diffusion propagators in porous media

Magnetic resonance is a well-established tool for structural characterisation of porous media. Features of pore-space morphology can be inferred from NMR diffusion-diffraction plots or the time-dependence of the apparent diffusion coefficient. Diffusion NMR signal attenuation can be computed from the restricted diffusion propagator, which describes the distribution of diffusing particles for a given starting position and diffusion time. We present two techniques for efficient evaluation of restricted diffusion propagators for use in NMR porous-media characterisation. The first is the Lattice Path Count (LPC). Its physical essence is that the restricted diffusion propagator connecting points A and B in time t is proportional to the number of distinct length-t paths from A to B. By using a discrete lattice, the number of such paths can be counted exactly. The second technique is the Markov transition matrix (MTM). The matrix represents the probabilities of jumps between every pair of lattice nodes within a single timestep. The propagator for an arbitrary diffusion time can be calculated as the appropriate matrix power. For periodic geometries, the transition matrix needs to be defined only for a single unit cell. This makes MTM ideally suited for periodic systems. Both LPC and MTM are closely related to existing computational techniques: LPC, to combinatorial techniques; and MTM, to the Fokker-Planck master equation. The relationship between LPC, MTM and other computational techniques is briefly discussed in the paper. Both LPC and MTM perform favourably compared to Monte Carlo sampling, yielding highly accurate and almost noiseless restricted diffusion propagators. Initial tests indicate that their computational performance is comparable to that of finite element methods. Both LPC and MTM can be applied to complicated pore-space geometries with no analytic solution. We discuss the new methods in the context of diffusion propagator calculation in porous materials and model biological tissues.

Facilitating lifestyle changes to manage menopausal symptoms in women with breast cancer: A randomized controlled pilot trial of The Pink Women’s Wellness Program

OBJECTIVE Women diagnosed as having breast cancer may experience difficulties with posttreatment effects such as menopausal symptoms. The aims of this pilot study were to (1) evaluate the impact of a multimodal lifestyle program on reducing menopausal symptoms in women with breast cancer and (2) examine the impact of the program on health-related quality of life (HRQoL) and adherence to lifestyle recommendations. METHODS Overall, 55 women aged 45 to 60 years with one moderate to severe menopausal symptom and a history of breast cancer were randomized into an intervention group (n = 26) or a control group (n = 29). Women in the intervention group received a lifestyle intervention (The Pink Women’s Wellness Program) that included clinical consultations and a tailored health education program. Measurements of menopausal symptoms (Greene Climacteric Scale), HRQoL (SF-12 and Functional Assessment of Cancer Therapy—Breast), and modifiable lifestyle factors (food intake, physical activity, smoking and alcohol use, and sleep disturbance) were taken at baseline and 12 weeks. RESULTS Women in the intervention group reported clinically significant reductions in many menopausal symptoms, specifically somatic symptoms (d = 0.52), vasomotor symptoms (d = 0.55), sexual dysfunction (d = .65), and overall menopausal symptoms (d = 0.54), at 12 weeks compared with the control group (d = 0.03, d = 0.24, d = 0.18, and d = 0.05, respectively). Women in the intervention group reported improvements in Functional Assessment of Cancer Therapy—Breast subscale scores, physical well-being and functional well-being, and Functional Assessment of Cancer Therapy—General total scores (intervention group: d = 0.54, d = 0.50, and d = 0.48, respectively; control group: d = 0.22, d = 0.11, and d = 0.05, respectively). CONCLUSIONS The Pink Women’s Wellness Program is effective in decreasing menopausal symptoms, thus improving HRQoL. This being a pilot study, further research is recommended to investigate the benefits of combining nonpharmacological interventions for women with breast cancer to reduce their treatment-related menopausal symptoms.

Sectional analysis of stormwater treatment performance of a constructed wetland

Constructed wetlands are among the most common Water Sensitive Urban Design (WSUD) measures for stormwater treatment. These systems have been extensively studied to understand their performance and influential treatment processes. Unfortunately, most past studies have been undertaken considering a wetland system as a lumped system with a primary focus on the reduction of the event mean concentration (EMC) values of specific pollutant species or total pollutant load removal. This research study adopted an innovative approach by partitioning the inflow runoff hydrograph and then investigating treatment performance in each partition and their relationships with a range of hydraulic factors. The study outcomes confirmed that influenced by rainfall characteristics, the constructed wetland displays different treatment characteristics for the initial and later sectors of the runoff hydrograph. The treatment of small rainfall events (<15 mm) is comparatively better at the beginning of runoff events while the trends in pollutant load reductions for large rainfall events (>15 mm) are generally lower at the beginning and gradually increase towards the end of rainfall events. This highlights the importance of ensuring that the inflow into a constructed wetland has low turbulence in order to achieve consistent treatment performance for both, small and large rainfall events.

Sources and transport pathways of common heavy metals to urban road surfaces

Heavy metals that are built-up on urban impervious surfaces such as roads are transported to urban water resources through stormwater runoff. Therefore, it is essential to understand the predominant pathways of heavy metals to the build-up on roads in order to develop suitable pollution mitigation strategies to protect the receiving water environment. The study presented in this paper investigated the sources and transport pathways of manganese, lead, copper, zinc and chromium, which are heavy metals commonly present in urban road build-up. It was found that manganese and lead are contributed to road build-up primarily by direct deposition due to the re-suspension of roadside soil by wind turbulence, while traffic is the predominant source of copper, zinc and chromium to the atmosphere and road build-up. Atmospheric deposition is also the major transport pathway for copper and zinc, and for chromium, direct deposition by traffic sources is the predominant pathway.

Major changes to property law in Queensland

From 1 December 2014 a number of major changes were made to property law in Queensland with the simultaneous commencement of the Land Sales and Other Legislation Amendment Act 2014 (Qld) and the Property Occupations Act 2014 (Qld). This article examines these changes, their rationale and their implications for practice.

Enhancing the auditor's report : to what extent is there support for the IAASB's proposed changes?

This article outlines proposed reforms to auditor reporting currently being considered by the International Auditing and Assurance Standards Board (IAASB), and other key national and transnational standard-setters and regulatory bodies. It adds to recent academic contributions on reforming the auditor’s report by analyzing the 165 stakeholder responses to the IAASB’s 2012 Invitation to Comment: Improving the Auditor’s Report to determine levels of support for the IAASB’s proposed reforms, and the differences, if any, between the views of various respondents based on stakeholder groups (e.g. audit and assurance firms, users, preparers, regulators, etc.) and regional classifications. Guided by insights from communication theory, our results show the levels of stakeholder support for the IAASB’s proposed reforms addressing auditors’ expectations, information and communication gaps are mixed. The strongest overall support was for enhanced auditor reporting on other information attached to, or intended to be read with, the financial statements, and the least supported initiative was including additional information in the auditor’s report about the auditor’s judgements and processes. Whilst overall there is generally consensus across both stakeholder groups and regions concerning the various questions investigated, we highlight where statistically significant differences between groups do exist. Notably, North American respondents were less likely to support a number of the IAASB’s proposed reforms than their counterparts from other regions.

Eye rubbing-induced changes in intraocular pressure and corneal thickness measured at five locations, in subjects with ocular allergy

AIM To assess the effects of eye rubbing on corneal thickness (CT) and intraocular pressure (IOP) measurements obtained 0-30min after habitual eye rubbing in symptomatic patients. METHODS Measurements of IOP and CT were obtained at five locations (central, temporal, superior, nasal and inferior) before, and every 5min for 30min interval after 30s of eye rubbing, for 25 randomly selected eyes of 14 subjects with ocular allergy and 11 age-matched normals. Differences in measurements were calculated in each group [Baseline measurements minus measurements recorded at each time interval after eye rubbing (for IOP), and for each corneal location (for CT)] and comparison were then made between groups (allergic versus control) for differences in any observed effects. RESULTS Within groups, baseline mean IOPs in the allergic patient-group (14.2±3.0 mm Hg) and in the control group (13.1±1.9 mm Hg) were similar at all times, after eye rubbing (P >0.05, for all). The maximum reduction in IOP was 0.8 mm Hg in the control subjects and the maximum increase was also 0.8 mm Hg in the allergic subjects. Between groups (allergic versus control), the changes in IOP remained under 1 mm Hg at all times (P=0.2) after 30min of eye rubbing. Between 0 and 30min of CT measurements after eye rubbing, the mean central CT (CCT), inferior CT (ICT), superior CT (SCT), temporal CT (TCT) and nasal CT (NCT) did not vary significantly from baseline values in the control and allergic-subject groups (P>0.05, for both). Between both groups, changes in CT were similar at all locations (P>0.05) except for the TC which was minimally thinner by about 4.4 µm (P=0.001) in the allergic subjects than in the control subjects, 30min following 30s of eye rubbing. CONCLUSION IOP measured in allergic subjects after 30s of habitual eye rubbing was comparable with that obtained in normal subjects at all times between 0 and 30min. Although, CT in the allergic subjects were similar to those of the control subjects at all times, it varied between +10 and -7.5 µm following eye rubbing, with the temporal cornea showing consistent reductions in thickness in the subjects with allergy. However, this reduction was minimal and was considered to not be clinically relevant.

Age-related changes to adenosine in rat coronary resistance vessels

1. The vasodilator effects of adenosine receptor agonists, isoprenaline and histamine were examined in perfused heart preparations from young (4–6 weeks) and mature (12–20 weeks) rats. 2. Adenosine induced a biphasic concentration-dependent decrease in KCl (35 mM) raised coronary perfusion pressure in hearts from young and mature rats, suggesting the presence of both high- and low-affinity sites for adenosine receptors in the two age groups tested. In heart preparations from mature rats, vasodilator responses to adenosine were significantly reduced compared with responses observed in young rats. 3. Responses to 5′-N-ethylcarboxamidoadenosine (NECA) and 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680) were reduced in preparations from mature rats, whereas the vasodilator actions of N6-cyclopentyladenosine (CPA) and N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not change with age. 4. The results presented in this study suggest that several adenosine receptor subtypes mediate vasodilator responses in the coronary circulation of the rat and that a reduction in response to adenosine with age may be due to changes in the high-affinity receptor site.

Locally weighted learning methods for non-rigid robot control

This thesis develops a novel approach to robot control that learns to account for a robot's dynamic complexities while executing various control tasks using inspiration from biological sensorimotor control and machine learning. A robot that can learn its own control system can account for complex situations and adapt to changes in control conditions to maximise its performance and reliability in the real world. This research has developed two novel learning methods, with the aim of solving issues with learning control of non-rigid robots that incorporate additional dynamic complexities. The new learning control system was evaluated on a real three degree-of-freedom elastic joint robot arm with a number of experiments: initially validating the learning method and testing its ability to generalise to new tasks, then evaluating the system during a learning control task requiring continuous online model adaptation.

Accounting for management costs in sensitivity analyses of matrix population models

Traditional sensitivity and elasticity analyses of matrix population models have been used to inform management decisions, but they ignore the economic costs of manipulating vital rates. For example, the growth rate of a population is often most sensitive to changes in adult survival rate, but this does not mean that increasing that rate is the best option for managing the population because it may be much more expensive than other options. To explore how managers should optimize their manipulation of vital rates, we incorporated the cost of changing those rates into matrix population models. We derived analytic expressions for locations in parameter space where managers should shift between management of fecundity and survival, for the balance between fecundity and survival management at those boundaries, and for the allocation of management resources to sustain that optimal balance. For simple matrices, the optimal budget allocation can often be expressed as simple functions of vital rates and the relative costs of changing them. We applied our method to management of the Helmeted Honeyeater (Lichenostomus melanops cassidix; an endangered Australian bird) and the koala (Phascolarctos cinereus) as examples. Our method showed that cost-efficient management of the Helmeted Honeyeater should focus on increasing fecundity via nest protection, whereas optimal koala management should focus on manipulating both fecundity and survival simultaneously. These findings are contrary to the cost-negligent recommendations of elasticity analysis, which would suggest focusing on managing survival in both cases. A further investigation of Helmeted Honeyeater management options, based on an individual-based model incorporating density dependence, spatial structure, and environmental stochasticity, confirmed that fecundity management was the most cost-effective strategy. Our results demonstrate that decisions that ignore economic factors will reduce management efficiency. ©2006 Society for Conservation Biology.

Development and parameterization of a rain- and fire-driven model for exploring elephant effects in African savannas

We describe the development and parameterization of a grid-based model of African savanna vegetation processes. The model was developed with the objective of exploring elephant effects on the diversity of savanna species and structure, and in this formulation concentrates on the relative cover of grass and woody plants, the vertical structure of the woody plant community, and the distribution of these over space. Grid cells are linked by seed dispersal and fire, and environmental variability is included in the form of stochastic rainfall and fire events. The model was parameterized from an extensive review of the African savanna literature; when available, parameter values varied widely. The most plausible set of parameters produced long-term coexistence between woody plants and grass, with the tree-grass balance being more sensitive to changes in parameters influencing demographic processes and drought incidence and response, while less sensitive to fire regime. There was considerable diversity in the woody structure of savanna systems within the range of uncertainty in tree growth rate parameters. Thus, given the paucity of height growth data regarding woody plant species in southern African savannas, managers of natural areas should be cognizant of different tree species growth and damage response attributes when considering whether to act on perceived elephant threats to vegetation. © 2007 Springer Science+Business Media B.V.

A model-framed evaluation of elephant effects on tree and fire dynamics in African savannas

There is a concern that high densities of elephants in southern Africa could lead to the overall reduction of other forms of biodiversity. We present a grid-based model of elephant-savanna dynamics, which differs from previous elephant-vegetation models by accounting for woody plant demographics, tree-grass interactions, stochastic environmental variables (fire and rainfall), and spatial contagion of fire and tree recruitment. The model projects changes in height structure and spatial pattern of trees over periods of centuries. The vegetation component of the model produces long-term tree-grass coexistence, and the emergent fire frequencies match those reported for southern African savannas. Including elephants in the savanna model had the expected effect of reducing woody plant cover, mainly via increased adult tree mortality, although at an elephant density of 1.0 elephant/km2, woody plants still persisted for over a century. We tested three different scenarios in addition to our default assumptions. (1) Reducing mortality of adult trees after elephant use, mimicking a more browsing-tolerant tree species, mitigated the detrimental effect of elephants on the woody population. (2) Coupling germination success (increased seedling recruitment) to elephant browsing further increased tree persistence, and (3) a faster growing woody component allowed some woody plant persistence for at least a century at a density of 3 elephants/km2. Quantitative models of the kind presented here provide a valuable tool for exploring the consequences of management decisions involving the manipulation of elephant population densities. © 2005 by the Ecological Society of America.

Paying the extinction debt: Woodland birds in the Mount Lofty Ranges, South Australia

Approximately 90% of the original woodlands of the Mount Lofty Ranges of South Australia has been cleared, modified or fragmented, most severely in the last 60 years, and affecting the avifauna dependent on native vegetation. This study identifies which woodland-dependent species are still declining in two different habitats, Pink GumBlue Gum woodland and Stringybark woodland. We analyse the Mount Lofty Ranges Woodland Bird Long-Term Monitoring Dataset for 1999-2007, to look for changes in abundance of 59 species. We use logistic regression of prevalence on lists in a Bayesian framework, and List Length Analysis to control for variation in detectability. Compared with Reporting Rate Analysis, a more traditional approach, List Length Analysis provides tighter confidence intervals by accounting for changing detectability. Several common species were declining significantly. Increasers were generally large-bodied generalists. Many birds have already disappeared from this modified and naturally isolated woodland island, and our results suggest that more specialist insectivores are likely to follow. The Mount Lofty Ranges can be regarded as a 'canary landscape' for temperate woodlands elsewhere in Australia without immediate action their bird communities are likely to follow the trajectory of the Mount Lofty Ranges avifauna. Alternatively, with extensive habitat restoration and management, we could avoid paying the extinction debt. © Royal Australasian Ornithologists Union 2011.