Monte Carlo evaluation of collapsed-cone convolution calculations in head and neck radiotherapy treatment plans

The presence of air and bone interfaces makes the dose distribution for head and neck cancer treatments difficult to accurately predict. This study compared planning system dose calculations using the collapsed-cone convolution algorithm with EGSnrcMonte Carlo simulation results obtained using the Monte Carlo DICOMToolKit software, for one oropharynx, two paranasal sinus and three nodal treatment plans. The difference between median doses obtained from the treatment planning and Monte Carlo calculations was found to be greatest in two bilateral treatments: 4.8%for a retropharyngeal node irradiation and 6.7% for an ethmoid paranasal sinus treatment. These deviations in median dose were smaller for two unilateral treatments: 0.8% for an infraclavicular node irradiation and 2.8% for a cervical node treatment. Examination of isodose distributions indicated that the largest deviations between Monte Carlo simulation and collapsed-cone convolution calculations were seen in the bilateral treatments, where the increase in calculated dose beyond air cavities was most significant.

Assessment of “change in flexibility method” in structural health monitoring systems

The modern structural diagnosis process is rely on vibration characteristics to assess safer serviceability level of the structure. This paper examines the potential of change in flexibility method to use in damage detection process and two main practical constraints associated with it. The first constraint addressed in this paper is reduction in number of data acquisition points due to limited number of sensors. Results conclude that accuracy of the change in flexibility method is influenced by the number of data acquisition points/sensor locations in real structures. Secondly, the effect of higher modes on damage detection process has been studied. This addresses the difficulty of extracting higher order modal data with available sensors. Four damage indices have been presented to identify their potential of damage detection with respect to different locations and severity of damage. A simply supported beam with two degrees of freedom at each node is considered only for a single damage cases throughout the paper.

The identification of therapeutic targets in metastatic melanoma

Metastatic melanoma, a cancer historically refractory to chemotherapeutic strategies, has a poor prognosis and accounts for the majority of skin cancer related mortality. Although the recent approval of two new drugs combating this disease, Ipilimumab and Vemurafenib (PLX4032), has demonstrated for the first time in decades an improvement in overall survival; the clinical efficacy of these drugs has been marred by severe adverse immune reactions and acquired drug resistance in patients, respectively. Thus, understanding the etiology of metastatic melanoma will contribute to the improvement of current therapeutic strategies while leading to the development of novel drug approaches. In order to identify recurrently mutated genes of therapeutic relevance in metastatic melanoma, a panel of stage III local lymph node melanomas were extensively characterised using high-throughput genomic technologies. This led to the identification of mutations in TFG in 5% of melanomas from a candidate gene sequencing approach using SNP array analysis, 24% of melanomas with mutations in MAP3K5 or MAP3K9 though unbiased whole-exome sequencing strategies, and inactivating mutations in NF1 in BRAF/NRAS wild type tumours though pathway analysis. Lastly, this thesis describes the development of a melanoma specific mutation panel that can rapidly identify clinically relevant mutation profiles that could guide effective treatment strategies through a personalised therapeutic approach. These findings are discussed in respect to a number of important issues raised by this study including the current limitation of next-generation sequencing technology, the difficulty in identifying ‘driver’ mutations critical to the development of melanoma due to high carcinogenic exposure by UV radiation, and the ultimate application of mutation screening in a personalised therapeutic setting. In summary, a number novel genes involved in metastatic melanoma have been identified that may have relevance for current therapeutic strategies in treating this disease.

Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients

Breast cancer is a leading contributor to the burden of disease in Australia. Fortunately, the recent introduction of diverse therapeutic strategies have improved the survival outcome for many women. Despite this, the clinical management of breast cancer remains problematic as not all approaches are sufficiently sophisticated to take into account the heterogeneity of this disease and are unable to predict disease progression, in particular, metastasis. As such, women with good prognostic outcomes are exposed to the side effects of therapies without added benefit. Furthermore, women with aggressive disease for whom these advanced treatments would deliver benefit cannot be distinguished and opportunities for more intensive or novel treatment are lost. This study is designed to identify novel factors associated with disease progression, and the potential to inform disease prognosis. Frequently overlooked, yet common mediators of disease are the interactions that take place between the insulin-like growth factor (IGF) system and the extracellular matrix (ECM). Our laboratory has previously demonstrated that multiprotein insulin-like growth factor-I (IGF-I): insulin-like growth factor binding protein (IGFBP): vitronectin (VN) complexes stimulate migration of breast cancer cells in vitro, via the cooperative involvement of the insulin-like growth factor type I receptor (IGF-IR) and VN-binding integrins. However, the effects of IGF and ECM protein interactions on the dissemination and progression of breast cancer in vivo are unknown. It was hypothesised that interactions between proteins required for IGF induced signalling events and those within the ECM contribute to breast cancer metastasis and are prognostic and predictive indicators of patient outcome. To address this hypothesis, semiquantitative immunohistochemistry (IHC) analyses were performed to compare the extracellular and subcellular distribution of IGF and ECM induced signalling proteins between matched normal, primary cancer, and metastatic cancer among archival formalin-fixed paraffin-embedded (FFPE) breast tissue samples collected from women attending the Princess Alexandra Hospital, Brisbane. Multivariate Cox proportional hazards (PH) regression survival models in conjunction with a modified „purposeful selection of covariates. method were applied to determine the prognostic potential of these proteins. This study provides the first in-depth, compartmentalised analysis of the distribution of IGF and ECM induced signalling proteins. As protein function and protein localisation are closely correlated, these findings provide novel insights into IGF signalling and ECM protein function during breast cancer development and progression. Distinct IGF signalling and ECM protein immunoreactivity was observed in the stroma and/or in subcellular locations in normal breast, primary cancer and metastatic cancer tissues. Analysis of the presence and location of stratifin (SFN) suggested a causal relationship in ECM remodelling events during breast cancer development and progression. The results of this study have also suggested that fibronectin (FN) and ¥â1 integrin are important for the formation of invadopodia and epithelial-to-mesenchymal transition (EMT) events. Our data also highlighted the importance of the temporal and spatial distribution of IGF induced signalling proteins in breast cancer metastasis; in particular, SFN, enhancer-of-split and hairy-related protein 2 (SHARP-2), total-akt/protein kinase B 1 (Total-AKT1), phosphorylated-akt/protein kinase B (P-AKT), extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (ERK1/2) and phosphorylated-extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (P-ERK1/2). Multivariate survival models were created from the immunohistochemical data. These models were found to fit well with these data with very high statistical confidence. Numerous prognostic confounding effects and effect modifications were identified among elements of the ECM and IGF signalling cascade and corroborate the survival models. This finding provides further evidence for the prognostic potential of IGF and ECM induced signalling proteins. In addition, the adjusted measures of associations obtained in this study have strengthened the validity and utility of the resulting models. The findings from this study provide insights into the biological interactions that occur during the development of breast tissue and contribute to disease progression. Importantly, these multivariate survival models could provide important prognostic and predictive indicators that assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy. The outcomes of this study further inform the development of new therapeutics to aid patient recovery. The findings from this study have widespread clinical application in the diagnosis of disease and prognosis of disease progression, and inform the most appropriate clinical management of individuals with breast cancer.

The utility of serum CA-125 in predicting extra-uterine disease in apparent early stage endometrial cancer

Objectives: To evaluate the clinical value of pre-operative serum CA125 in predicting the presence of extra-uterine disease in patients with apparent early stage endometrial cancer. Methods: Between October 6, 2005 and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. This study is based on data from 657 patients with endometrial adenocarcinoma who had a pre-operative serum CA125 value, and was undertaken to correlate pre-operative serum CA125 with final stage. Results: Using a pre-operative CA-125 cutpoint of 30U/ml was associated with the smallest misclassification error (14.5%) using a multiple cross-validation method. Median pre-operative serum CA-125 was 14U/ml, and using a cutpoint of 30U/ml, 14.9% of patients had elevated CA-125 levels. Of 98 patients with elevated CA-125 level, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had elevated CA-125 level. In univariate and multivariate logistic regression analysis, only pre-operative CA-125 level was found to be associated with extra-uterine spread of disease. Utilising a cutpoint of 30U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0%, 88.5%, 36.7% and 85.7% respectively. Overall, 326/657 (49.6%) of patients had full surgical staging involving lymph node dissection. When analysis was limited to patients that had undergone full surgical staging, the outcomes remained essentially unchanged. Conclusions: Elevated CA-125 above 30U/ml in patients with apparent early stage disease is associated with a sensitivity of 31.0% and specificity of 88.5% in detecting extra-uterine disease. Pre-operative identification of this risk factor may assist to triage patients to tertiary centres and comprehensive surgical staging.

Old-fashioned and forward looking : Neoliberalism and nostalgia in the Daring Books for Girls

This paper interogates the international bestselling series, The Daring Books for Girls (Buchanan & Peskowitz, 2007, 2008), asking what kinds of girls are produced through these texts.

CCI-CCI Creative City Index 2012

The CCI-Creative City Index was commissioned in 2010 by the Beijing Academy of Science & Technology's Beijing Research Center for the Science of Science. John Hartley was asked to develop a new creative global city index. The brief was to improve on the existing indexes with a specific focus on creative industries and the sources of creative development. This report, by John Hartley, Jason Potts, Trent MacDonald, with Chris Erkunt and Carl Kufleitner, sets out the new model we have developed, which we call the CCI Creative City Index (CCI-CCI). It presents the results of a pilot application of the index to six cities: London, Cardiff, Berlin, Bremen, Melbourne and Brisbane. The index incorporates many elements from other global and creative city indexes, but also adds several new dimensions relating to creative industries scope, micro-productivity, and the economy of attention. The report and Excel spreadsheets of index calculations can be found on this site.

Optimal planning of electric-vehicle charging stations in distribution systems

With the progressive exhaustion of fossil energy and the enhanced awareness of environmental protection, more attention is being paid to electric vehicles (EVs). Inappropriate siting and sizing of EV charging stations could have negative effects on the development of EVs, the layout of the city traffic network, and the convenience of EVs' drivers, and lead to an increase in network losses and a degradation in voltage profiles at some nodes. Given this background, the optimal sites of EV charging stations are first identified by a two-step screening method with environmental factors and service radius of EV charging stations considered. Then, a mathematical model for the optimal sizing of EV charging stations is developed with the minimization of total cost associated with EV charging stations to be planned as the objective function and solved by a modified primal-dual interior point algorithm (MPDIPA). Finally, simulation results of the IEEE 123-node test feeder have demonstrated that the developed model and method cannot only attain the reasonable planning scheme of EV charging stations, but also reduce the network loss and improve the voltage profile.

Collective equipments of power: The road and the city

A year ago, I became aware of the historical existence of the group CERFI— Le centre d’etudes, de recherches, et de formation institutionelles, or The Study Center for Institutional Research and Formation. CERFI emerged in 1967 under the hand of Lacanian psychiatrist and Trotskyite activist Félix Guattari, whose antonymous journal Recherches chronicled the group’s subversive experiences, experiments, and government-sponsored urban projects. It was a singularly bizarre meeting of the French bureaucracy with militant activist groups, the French intelligentsia, and architectural and planning practitioners at the close of the ‘60s. Nevertheless, CERFI’s analysis of the problems of society was undertaken precisely from the perspective of the state, and the Institute acknowledged a “deep complicity between the intellectual and statesman ... because the first critics of the State, are officials themselves!”1 CERFI developed out of FGERI (The Federation of Groups for Institutional Study and Research), started by Guattari two years earlier. While FGERI was created for the analysis of mental institutions stemming from Guattari’s work at La Borde, an experimental psychiatric clinic, CERFI marks the group’s shift toward urbanism—to the interrogation of the city itself. Not only a platform for radical debate on architecture and the city, CERFI was a direct agent in the development of urban planning schemata for new towns in France. 2 CERFI’s founding members were Guattari, the economist and urban theorist François Fourquet, feminist philosopher Liane Mozère, and urban planner and editor of Multitides Anne Querrien—Guattari’s close friend and collaborator. The architects Antoine Grumback, Alain Fabre, Macary, and Janine Joutel were also members, as well as urbanists Bruno Fortier, Rainier Hoddé, and Christian de Portzamparc. 3 CERFI was the quintessential social project of post-‘68 French urbanism. Located on the Far Left and openly opposed to the Communist Party, this Trotskyist cooperative was able to achieve what other institutions, according to Fourquet, with their “customary devices—the politburo, central committee, and the basic cells—had failed to do.”4 The decentralized institute recognized that any formal integration of the group was to “sign its own death warrant; so it embraced a skein of directors, entangled, forming knots, liquidating all at once, and spinning in an unknown direction, stopping short and returning back to another node.” Allergic to the very idea of “party,” CERFI was a creative project of free, hybrid-aesthetic blocs talking and acting together, whose goal was none other than the “transformation of the libidinal economy of the militant revolutionary.” The group believed that by recognizing and affirming a “group unconscious,” as well as their individual unconscious desires, they would be able to avoid the political stalemates and splinter groups of the traditional Left. CERFI thus situated itself “on the side of psychosis”—its confessed goal was to serve rather than repress the utter madness of the urban malaise, because it was only from this mad perspective on the ground that a properly social discourse on the city could be forged.

Pulse dynamics in a three-component system : existence analysis

In this article, we analyze the three-component reaction-diffusion system originally developed by Schenk et al. (PRL 78:3781–3784, 1997). The system consists of bistable activator-inhibitor equations with an additional inhibitor that diffuses more rapidly than the standard inhibitor (or recovery variable). It has been used by several authors as a prototype three-component system that generates rich pulse dynamics and interactions, and this richness is the main motivation for the analysis we present. We demonstrate the existence of stationary one-pulse and two-pulse solutions, and travelling one-pulse solutions, on the real line, and we determine the parameter regimes in which they exist. Also, for one-pulse solutions, we analyze various bifurcations, including the saddle-node bifurcation in which they are created, as well as the bifurcation from a stationary to a travelling pulse, which we show can be either subcritical or supercritical. For two-pulse solutions, we show that the third component is essential, since the reduced bistable two-component system does not support them. We also analyze the saddle-node bifurcation in which two-pulse solutions are created. The analytical method used to construct all of these pulse solutions is geometric singular perturbation theory, which allows us to show that these solutions lie in the transverse intersections of invariant manifolds in the phase space of the associated six-dimensional travelling wave system. Finally, as we illustrate with numerical simulations, these solutions form the backbone of the rich pulse dynamics this system exhibits, including pulse replication, pulse annihilation, breathing pulses, and pulse scattering, among others.

Pulse dynamics in a three-component system : stability and bifurcations

In this article, we analyze the stability and the associated bifurcations of several types of pulse solutions in a singularly perturbed three-component reaction-diffusion equation that has its origin as a model for gas discharge dynamics. Due to the richness and complexity of the dynamics generated by this model, it has in recent years become a paradigm model for the study of pulse interactions. A mathematical analysis of pulse interactions is based on detailed information on the existence and stability of isolated pulse solutions. The existence of these isolated pulse solutions is established in previous work. Here, the pulse solutions are studied by an Evans function associated to the linearized stability problem. Evans functions for stability problems in singularly perturbed reaction-diffusion models can be decomposed into a fast and a slow component, and their zeroes can be determined explicitly by the NLEP method. In the context of the present model, we have extended the NLEP method so that it can be applied to multi-pulse and multi-front solutions of singularly perturbed reaction-diffusion equations with more than one slow component. The brunt of this article is devoted to the analysis of the stability characteristics and the bifurcations of the pulse solutions. Our methods enable us to obtain explicit, analytical information on the various types of bifurcations, such as saddle-node bifurcations, Hopf bifurcations in which breathing pulse solutions are created, and bifurcations into travelling pulse solutions, which can be both subcritical and supercritical.

Slotted distributed space-time coding

Distributed space-time coding (DSTC) exploits the concept of cooperative diversity and space-time coding to offer a powerful bandwidth efficient solution with improved diversity. In this paper, we evaluate the performance of DSTC with slotted amplify-and-forward protocol (SAF). Relay nodes between the source and the destination nodes are grouped into two relay clusters based on their respective locations and these relay clusters cooperate to transmit the space-time coded signal to the destination node in different time frames. We further extend the proposed Slotted-DSTC to Slotted DSTC with redundant code (Slotted-DSTC-R) protocol where the relay nodes in both relay clusters forward the same space-time coded signal to the destination node to achieve a higher diversity order.

Combinatorial design of key distribution mechanisms for wireless sensor networks

Secure communications in wireless sensor networks operating under adversarial conditions require providing pairwise (symmetric) keys to sensor nodes. In large scale deployment scenarios, there is no prior knowledge of post deployment network configuration since nodes may be randomly scattered over a hostile territory. Thus, shared keys must be distributed before deployment to provide each node a key-chain. For large sensor networks it is infeasible to store a unique key for all other nodes in the key-chain of a sensor node. Consequently, for secure communication either two nodes have a key in common in their key-chains and they have a wireless link between them, or there is a path, called key-path, among these two nodes where each pair of neighboring nodes on this path have a key in common. Length of the key-path is the key factor for efficiency of the design. This paper presents novel deterministic and hybrid approaches based on Combinatorial Design for deciding how many and which keys to assign to each key-chain before the sensor network deployment. In particular, Balanced Incomplete Block Designs (BIBD) and Generalized Quadrangles (GQ) are mapped to obtain efficient key distribution schemes. Performance and security properties of the proposed schemes are studied both analytically and computationally. Comparison to related work shows that the combinatorial approach produces better connectivity with smaller key-chain sizes.

Establishing initial trust in autonomous delay tolerant networks without centralised PKI

A Delay Tolerant Network (DTN) is one where nodes can be highly mobile, with long message delay times forming dynamic and fragmented networks. Traditional centralised network security is difficult to implement in such a network, therefore distributed security solutions are more desirable in DTN implementations. Establishing effective trust in distributed systems with no centralised Public Key Infrastructure (PKI) such as the Pretty Good Privacy (PGP) scheme usually requires human intervention. Our aim is to build and compare different de- centralised trust systems for implementation in autonomous DTN systems. In this paper, we utilise a key distribution model based on the Web of Trust principle, and employ a simple leverage of common friends trust system to establish initial trust in autonomous DTN’s. We compare this system with two other methods of autonomously establishing initial trust by introducing a malicious node and measuring the distribution of malicious and fake keys. Our results show that the new trust system not only mitigates the distribution of fake malicious keys by 40% at the end of the simulation, but it also improved key distribution between nodes. This paper contributes a comparison of three de-centralised trust systems that can be employed in autonomous DTN systems.