Diagnostic utility of thyroglobulin measurement in the fine needle aspirates from cervical lymph nodes: a case report

Fine needle aspiration cytology (FNAC) is the more accurate diagnostic method for cervical lymph node (CLN) metastasis from differentiated thyroid cancers (DTC). However, FNAC diagnosis of cystic CLN is, in most cases, uninformative due to inadequate cellularity. Recently, thyroglobulin (Tg) detection in FNAC needle washout fluid has been shown to improve the diagnostic accuracy of FNAC, and its routine association with cytology is recommended. We here describe the case of a 20 yr old girl complaining of the recent appearance of palpable non-painful laterocervical nodes in the neck. Ultrasound examination revealed the presence of 3 cystic CLNs and 2 mixed thyroid nodules, with the larger one showing irregular margins. On the latter, and on 2 larger CLNs, FNAC was performed, and both Tg protein and mRNA were determined in the needle washout. The cytological analysis was not diagnostic for the two CLNs, while that of the thyroid nodule reported the presence of colloid and groups of thyrocytes with normal morphology. Both CLNs showed, however, high levels of Tg protein and were positive for Tg mRNA, suggestive of metastatic DTC. Based on these findings, the FNAC analysis was performed on the second smaller thyroid nodule suggesting (Tir4) the presence of PTC. The patient was then subjected to total thyroidectomy with lymph nodes resection of the central and homolateral compartments. The histological diagnosis confirmed the presence of a PTC in the small nodule and metastatic lymph nodes. In conclusion, this case confirms that the cytological diagnosis of cystic lymph nodes is challenging, and that the measurement of Tg protein and/or mRNA in the needle washout may overcome this limitation.

Security and Trust in Distributed Computation

We propose three research problems to explore the relations between trust and security in the setting of distributed computation. In the first problem, we study trust-based adversary detection in distributed consensus computation. The adversaries we consider behave arbitrarily disobeying the consensus protocol. We propose a trust-based consensus algorithm with local and global trust evaluations. The algorithm can be abstracted using a two-layer structure with the top layer running a trust-based consensus algorithm and the bottom layer as a subroutine executing a global trust update scheme. We utilize a set of pre-trusted nodes, headers, to propagate local trust opinions throughout the network. This two-layer framework is flexible in that it can be easily extensible to contain more complicated decision rules, and global trust schemes. The first problem assumes that normal nodes are homogeneous, i.e. it is guaranteed that a normal node always behaves as it is programmed. In the second and third problems however, we assume that nodes are heterogeneous, i.e, given a task, the probability that a node generates a correct answer varies from node to node. The adversaries considered in these two problems are workers from the open crowd who are either investing little efforts in the tasks assigned to them or intentionally give wrong answers to questions. In the second part of the thesis, we consider a typical crowdsourcing task that aggregates input from multiple workers as a problem in information fusion. To cope with the issue of noisy and sometimes malicious input from workers, trust is used to model workers' expertise. In a multi-domain knowledge learning task, however, using scalar-valued trust to model a worker's performance is not sufficient to reflect the worker's trustworthiness in each of the domains. To address this issue, we propose a probabilistic model to jointly infer multi-dimensional trust of workers, multi-domain properties of questions, and true labels of questions. Our model is very flexible and extensible to incorporate metadata associated with questions. To show that, we further propose two extended models, one of which handles input tasks with real-valued features and the other handles tasks with text features by incorporating topic models. Our models can effectively recover trust vectors of workers, which can be very useful in task assignment adaptive to workers' trust in the future. These results can be applied for fusion of information from multiple data sources like sensors, human input, machine learning results, or a hybrid of them. In the second subproblem, we address crowdsourcing with adversaries under logical constraints. We observe that questions are often not independent in real life applications. Instead, there are logical relations between them. Similarly, workers that provide answers are not independent of each other either. Answers given by workers with similar attributes tend to be correlated. Therefore, we propose a novel unified graphical model consisting of two layers. The top layer encodes domain knowledge which allows users to express logical relations using first-order logic rules and the bottom layer encodes a traditional crowdsourcing graphical model. Our model can be seen as a generalized probabilistic soft logic framework that encodes both logical relations and probabilistic dependencies. To solve the collective inference problem efficiently, we have devised a scalable joint inference algorithm based on the alternating direction method of multipliers. The third part of the thesis considers the problem of optimal assignment under budget constraints when workers are unreliable and sometimes malicious. In a real crowdsourcing market, each answer obtained from a worker incurs cost. The cost is associated with both the level of trustworthiness of workers and the difficulty of tasks. Typically, access to expert-level (more trustworthy) workers is more expensive than to average crowd and completion of a challenging task is more costly than a click-away question. In this problem, we address the problem of optimal assignment of heterogeneous tasks to workers of varying trust levels with budget constraints. Specifically, we design a trust-aware task allocation algorithm that takes as inputs the estimated trust of workers and pre-set budget, and outputs the optimal assignment of tasks to workers. We derive the bound of total error probability that relates to budget, trustworthiness of crowds, and costs of obtaining labels from crowds naturally. Higher budget, more trustworthy crowds, and less costly jobs result in a lower theoretical bound. Our allocation scheme does not depend on the specific design of the trust evaluation component. Therefore, it can be combined with generic trust evaluation algorithms.

Pathological validation and significance of micrometastasis in sentinel nodes in primary breast cancer

In embracing a multidisciplinary approach to the management of patients with sentinel node biopsy in breast cancer, the pathologist task is to screen sentinel nodes for possible metastasis. The consequences of missing sentinel node micrometastasis can directly influence treatment strategies, and this screening therefore has to be performed with more attention than usual. There is presently great diversity in the histopathological work-up of sentinel nodes, with many centres employing additional techniques such as immunohistochemistry, reverse transcription polymerase chain reaction or flow cytometry in addition to routine haematoxylin and eosin staining. In this review, we address the pathological validation and significance of micrometastasis in sentinel node biopsy in primary breast cancer

'Malicious Code Execution Detection and Response Immune System inspired by the Danger Theory'

The analysis of system calls is one method employed by anomaly detection systems to recognise malicious code execution. Similarities can be drawn between this process and the behaviour of certain cells belonging to the human immune system, and can be applied to construct an artificial immune system. A recently developed hypothesis in immunology, the Danger Theory, states that our immune system responds to the presence of intruders through sensing molecules belonging to those invaders, plus signals generated by the host indicating danger and damage. We propose the incorporation of this concept into a responsive intrusion detection system, where behavioural information of the system and running processes is combined with information regarding individual system calls.

Analysis and modelling of immune cell behaviour in lymph nodes based on multi-photon imaging

This thesis presents quantitative studies of T cell and dendritic cell (DC) behaviour in mouse lymph nodes (LNs) in the naive state and following immunisation. These processes are of importance and interest in basic immunology, and better understanding could improve both diagnostic capacity and therapeutic manipulations, potentially helping in producing more effective vaccines or developing treatments for autoimmune diseases. The problem is also interesting conceptually as it is relevant to other fields where 3D movement of objects is tracked with a discrete scanning interval. A general immunology introduction is presented in chapter 1. In chapter 2, I apply quantitative methods to multi-photon imaging data to measure how T cells and DCs are spatially arranged in LNs. This has been previously studied to describe differences between the naive and immunised state and as an indicator of the magnitude of the immune response in LNs, but previous analyses have been generally descriptive. The quantitative analysis shows that some of the previous conclusions may have been premature. In chapter 3, I use Bayesian state-space models to test some hypotheses about the mode of T cell search for DCs. A two-state mode of movement where T cells can be classified as either interacting to a DC or freely migrating is supported over a model where T cells would home in on DCs at distance through for example the action of chemokines. In chapter 4, I study whether T cell migration is linked to the geometric structure of the fibroblast reticular network (FRC). I find support for the hypothesis that the movement is constrained to the fibroblast reticular cell (FRC) network over an alternative 'random walk with persistence time' model where cells would move randomly, with a short-term persistence driven by a hypothetical T cell intrinsic 'clock'. I also present unexpected results on the FRC network geometry. Finally, a quantitative method is presented for addressing some measurement biases inherent to multi-photon imaging. In all three chapters, novel findings are made, and the methods developed have the potential for further use to address important problems in the field. In chapter 5, I present a summary and synthesis of results from chapters 3-4 and a more speculative discussion of these results and potential future directions.

Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice

International audience

'Malicious Code Execution Detection and Response Immune System inspired by the Danger Theory'

The analysis of system calls is one method employed by anomaly detection systems to recognise malicious code execution. Similarities can be drawn between this process and the behaviour of certain cells belonging to the human immune system, and can be applied to construct an artificial immune system. A recently developed hypothesis in immunology, the Danger Theory, states that our immune system responds to the presence of intruders through sensing molecules belonging to those invaders, plus signals generated by the host indicating danger and damage. We propose the incorporation of this concept into a responsive intrusion detection system, where behavioural information of the system and running processes is combined with information regarding individual system calls.

Passive and specific targeting of lymph nodes: the influence of the administration route

Numéro spécial: Translational Nanomedicine

Integrating science through Bayesian Belief Networks : case study of Lyngbya in Moreton Bay

Bayesian Belief Networks (BBNs) are emerging as valuable tools for investigating complex ecological problems. In a BBN, the important variables in a problem are identified and causal relationships are represented graphically. Underpinning this is the probabilistic framework in which variables can take on a finite range of mutually exclusive states. Associated with each variable is a conditional probability table (CPT), showing the probability of a variable attaining each of its possible states conditioned on all possible combinations of it parents. Whilst the variables (nodes) are connected, the CPT attached to each node can be quantified independently. This allows each variable to be populated with the best data available, including expert opinion, simulation results or observed data. It also allows the information to be easily updated as better data become available ----- ----- This paper reports on the process of developing a BBN to better understand the initial rapid growth phase (initiation) of a marine cyanobacterium, Lyngbya majuscula, in Moreton Bay, Queensland. Anecdotal evidence suggests that Lyngbya blooms in this region have increased in severity and extent over the past decade. Lyngbya has been associated with acute dermatitis and a range of other health problems in humans. Blooms have been linked to ecosystem degradation and have also damaged commercial and recreational fisheries. However, the causes of blooms are as yet poorly understood.

SKMA - A Key Management Architecture for SCADA Systems

Supervisory Control And Data Acquisition (SCADA) systems are widely used in the management of critical infrastructure such as electricity and water distrubution systems. Currently there is little understanding of how to best protect SCADA systems from malicious attacks. We review the constraints and requirements for SCADA security and propose a suitable architecture (SKMA) for secure SCADA communications. The architecture includes a proposed key management protocol (SKMP). We compare the architecture with a previous proposal from Sandia Labs.

Access all

Access All was performance produced following a three-month mentorship in web-based performance that I was commissioned to conduct for the performance company Igneous. This live, triple-site performance event for three performers in three remote venues was specifically designed for presentation at Access Grid Nodes - conference rooms located around the globe equipped with a high end, open source computer teleconferencing technology that allowed multiple nodes to cross-connect with each other. Whilst each room was setup somewhat differently they all deployed the same basic infrastructre of multiple projectors, cameras, and sound as well as a reconfigurable floorspace. At that time these relatively formal setups imposed a clear series of limitations in terms of software capabilities and basic infrastructure and so there was much interest in understanding how far its capabilities might be pushed.----- Numerous performance experiments were undertaken between three Access Grid nodes in QUT Brisbane, VISLAB Sydney and Manchester Supercomputing Centre, England, culminating in the public performance staged simultaneously between the sites with local audiences at each venue and others online. Access All was devised in collaboration with interdisciplinary performance company Bonemap, Kelli Dipple (Interarts curator, Tate Modern London) and Mike Stubbs British curator and Director of FACT (Liverpool).----- This period of research and development was instigated and shaped by a public lecture I had earlier delivered in Sydney for the ‘Global Access Grid Network, Super Computing Global Conference’ entitled 'Performance Practice across Electronic Networks'. The findings of this work went on to inform numerous future networked and performative works produced from 2002 onwards.

Universally composable contributory group key exchange

We treat the security of group key exchange (GKE) in the universal composability (UC) framework. Analyzing GKE protocols in the UC framework naturally addresses attacks by malicious insiders. We define an ideal functionality for GKE that captures contributiveness in addition to other desired security goals. We show that an efficient two-round protocol securely realizes the proposed functionality in the random oracle model. As a result, we obtain the most efficient UC-secure contributory GKE protocol known.

Protocol engineering for protection against denial-of-service attacks

Denial-of-service attacks (DoS) and distributed denial-of-service attacks (DDoS) attempt to temporarily disrupt users or computer resources to cause service un- availability to legitimate users in the internetworking system. The most common type of DoS attack occurs when adversaries °ood a large amount of bogus data to interfere or disrupt the service on the server. The attack can be either a single-source attack, which originates at only one host, or a multi-source attack, in which multiple hosts coordinate to °ood a large number of packets to the server. Cryptographic mechanisms in authentication schemes are an example ap- proach to help the server to validate malicious tra±c. Since authentication in key establishment protocols requires the veri¯er to spend some resources before successfully detecting the bogus messages, adversaries might be able to exploit this °aw to mount an attack to overwhelm the server resources. The attacker is able to perform this kind of attack because many key establishment protocols incorporate strong authentication at the beginning phase before they can iden- tify the attacks. This is an example of DoS threats in most key establishment protocols because they have been implemented to support con¯dentiality and data integrity, but do not carefully consider other security objectives, such as availability. The main objective of this research is to design denial-of-service resistant mechanisms in key establishment protocols. In particular, we focus on the design of cryptographic protocols related to key establishment protocols that implement client puzzles to protect the server against resource exhaustion attacks. Another objective is to extend formal analysis techniques to include DoS- resistance. Basically, the formal analysis approach is used not only to analyse and verify the security of a cryptographic scheme carefully but also to help in the design stage of new protocols with a high level of security guarantee. In this research, we focus on an analysis technique of Meadows' cost-based framework, and we implement DoS-resistant model using Coloured Petri Nets. Meadows' cost-based framework is directly proposed to assess denial-of-service vulnerabil- ities in the cryptographic protocols using mathematical proof, while Coloured Petri Nets is used to model and verify the communication protocols using inter- active simulations. In addition, Coloured Petri Nets are able to help the protocol designer to clarify and reduce some inconsistency of the protocol speci¯cation. Therefore, the second objective of this research is to explore vulnerabilities in existing DoS-resistant protocols, as well as extend a formal analysis approach to our new framework for improving DoS-resistance and evaluating the performance of the new proposed mechanism. In summary, the speci¯c outcomes of this research include following results; 1. A taxonomy of denial-of-service resistant strategies and techniques used in key establishment protocols; 2. A critical analysis of existing DoS-resistant key exchange and key estab- lishment protocols; 3. An implementation of Meadows's cost-based framework using Coloured Petri Nets for modelling and evaluating DoS-resistant protocols; and 4. A development of new e±cient and practical DoS-resistant mechanisms to improve the resistance to denial-of-service attacks in key establishment protocols.

Effective web service discovery using a combination of a semantic model and a data mining technique

With the advent of Service Oriented Architecture, Web Services have gained tremendous popularity. Due to the availability of a large number of Web services, finding an appropriate Web service according to the requirement of the user is a challenge. This warrants the need to establish an effective and reliable process of Web service discovery. A considerable body of research has emerged to develop methods to improve the accuracy of Web service discovery to match the best service. The process of Web service discovery results in suggesting many individual services that partially fulfil the user’s interest. By considering the semantic relationships of words used in describing the services as well as the use of input and output parameters can lead to accurate Web service discovery. Appropriate linking of individual matched services should fully satisfy the requirements which the user is looking for. This research proposes to integrate a semantic model and a data mining technique to enhance the accuracy of Web service discovery. A novel three-phase Web service discovery methodology has been proposed. The first phase performs match-making to find semantically similar Web services for a user query. In order to perform semantic analysis on the content present in the Web service description language document, the support-based latent semantic kernel is constructed using an innovative concept of binning and merging on the large quantity of text documents covering diverse areas of domain of knowledge. The use of a generic latent semantic kernel constructed with a large number of terms helps to find the hidden meaning of the query terms which otherwise could not be found. Sometimes a single Web service is unable to fully satisfy the requirement of the user. In such cases, a composition of multiple inter-related Web services is presented to the user. The task of checking the possibility of linking multiple Web services is done in the second phase. Once the feasibility of linking Web services is checked, the objective is to provide the user with the best composition of Web services. In the link analysis phase, the Web services are modelled as nodes of a graph and an allpair shortest-path algorithm is applied to find the optimum path at the minimum cost for traversal. The third phase which is the system integration, integrates the results from the preceding two phases by using an original fusion algorithm in the fusion engine. Finally, the recommendation engine which is an integral part of the system integration phase makes the final recommendations including individual and composite Web services to the user. In order to evaluate the performance of the proposed method, extensive experimentation has been performed. Results of the proposed support-based semantic kernel method of Web service discovery are compared with the results of the standard keyword-based information-retrieval method and a clustering-based machine-learning method of Web service discovery. The proposed method outperforms both information-retrieval and machine-learning based methods. Experimental results and statistical analysis also show that the best Web services compositions are obtained by considering 10 to 15 Web services that are found in phase-I for linking. Empirical results also ascertain that the fusion engine boosts the accuracy of Web service discovery by combining the inputs from both the semantic analysis (phase-I) and the link analysis (phase-II) in a systematic fashion. Overall, the accuracy of Web service discovery with the proposed method shows a significant improvement over traditional discovery methods.

A bridging transition technique for the combination of meshfree method with finite element method in 2D solids and structures

For certain continuum problems, it is desirable and beneficial to combine two different methods together in order to exploit their advantages while evading their disadvantages. In this paper, a bridging transition algorithm is developed for the combination of the meshfree method (MM) with the finite element method (FEM). In this coupled method, the meshfree method is used in the sub-domain where the MM is required to obtain high accuracy, and the finite element method is employed in other sub-domains where FEM is required to improve the computational efficiency. The MM domain and the FEM domain are connected by a transition (bridging) region. A modified variational formulation and the Lagrange multiplier method are used to ensure the compatibility of displacements and their gradients. To improve the computational efficiency and reduce the meshing cost in the transition region, regularly distributed transition particles, which are independent of either the meshfree nodes or the FE nodes, can be inserted into the transition region. The newly developed coupled method is applied to the stress analysis of 2D solids and structures in order to investigate its’ performance and study parameters. Numerical results show that the present coupled method is convergent, accurate and stable. The coupled method has a promising potential for practical applications, because it can take advantages of both the meshfree method and FEM when overcome their shortcomings.