Familiar drugs may prevent cancer

Despite positive results in large scale chemoprevention trials, many physicians are unaware of the potential cancer preventive properties of drugs in common usage. The antioestrogen tamoxifen and the selective cyclo-oxygenase-2 inhibitor celecoxib have been licensed in the USA for the chemoprevention of breast and colorectal cancers respectively in selected high risk individuals. Similarly, folate and retinol have been shown to decrease the incidence of colorectal cancer and squamous cell carcinoma of the skin respectively in large scale intervention trials. Other retinoids have proved efficacious in the tertiary chemoprevention of cancers of the breast and head/neck. Epidemiological evidence also exists in favour of aspirin, nonsteroidal anti-inflammatory drugs, and angiotensin converting enzyme inhibitors preventing certain cancers. Phytochemicals may represent less toxic alternatives to these agents. Although some of these drugs are available without prescription and most are not yet licensed for use in cancer chemoprevention, physicians and students of medicine should be aware of this accumulating evidence base. Practitioners should be amenable to patient referral to discuss complex issues such as risk estimation or potential benefit from intervention.

Agents as intermediaries : when do they compete with their suppliers?

In cases involving allegations of price fixing under the former s 45A of the Trade Practices Act 1974 (Cth), it was necessary to prove that at least two parties to the arrangement or understanding at issue were “in competition with each other”. The same requirement is contained in the cartel provisions of the Competition and Consumer Act 2010 (Cth) (CCA) that replaced s 45A. The so-called “competition condition” is set out in s 44ZZRD (4) of the CCA. Where a supplier enters into vertical supply arrangements with agents or brokers, problems can arise if the supplier also has a downstream presence. At that functional level there may be a horizontal and therefore competitive dimension, and the competition condition may be satisfied. In such circumstances, great care will need to be taken in any discussions between the supplier and its downstream agents or distributors about the prices, discounts, allowances, rebates or credits that the agent or distributor may charge. Whether agents or brokers competed with their suppliers in vertical supply arrangements arose for consideration in two decisions handed down by the Federal Court in Brisbane...

Cytotoxicity of topical antimicrobial agents used in burn wounds in Australasia

BACKGROUND: Burn sepsis is a leading cause of mortality and morbidity in patients with major burns. The use of topical antimicrobial agents has helped improve the survival of these patients. Silvazine (Sigma Pharmaceuticals, Melbourne, Australia) (1% silver sulphadiazine and 0.2% chlorhexidine digluconate) is used exclusively in Australasia, and there is no published study on its cytotoxicity. This study compared the relative cytotoxicity of Silvazine with 1% silver sulphadiazine (Flamazine (Smith & Nephew Healthcare, Hull, UK)) and a silver-based dressing (Acticoat (Smith & Nephew Healthcare, Hull, UK)). METHODS: Dressings were applied to the centre of culture plates that were then seeded with keratinocytes at an estimated 25% confluence. The plates were incubated for 72 h and culture medium and dressings then removed. Toluidine blue was added to stain the remaining keratinocytes. Following removal of the dye, the plates were photographed under standard conditions and these digital images were analysed using image analysis software. Data was analysed using Student's t-test. RESULTS: In the present study, Silvazine is the most cytotoxic agent. Seventy-two hour exposure to Silvazine in the present study results in almost no keratinocyte survival at all and a highly statistically significant reduction in cell survival relative to control, Acticoat and Flamazine (P<0.001, P<0.01, P<0.01, respectively). Flamazine is associated with a statistically significant reduction in cell numbers relative to control (P<0.05), but is much less cytotoxic than Silvazine (P<0.005). CONCLUSION: In this in-vitro study comparing Acticoat, Silvazine and Flamazine, Silvazine shows an increased cytotoxic effect, relative to control, Flamazine and Acticoat. An in-vivo study is required to determine whether this effect is carried into the clinical setting.

Building adaptable agent-based models – application to the electricity distribution network

Agent-based modelling (ABM), like other modelling techniques, is used to answer specific questions from real world systems that could otherwise be expensive or impractical. Its recent gain in popularity can be attributed to some degree to its capacity to use information at a fine level of detail of the system, both geographically and temporally, and generate information at a higher level, where emerging patterns can be observed. This technique is data-intensive, as explicit data at a fine level of detail is used and it is computer-intensive as many interactions between agents, which can learn and have a goal, are required. With the growing availability of data and the increase in computer power, these concerns are however fading. Nonetheless, being able to update or extend the model as more information becomes available can become problematic, because of the tight coupling of the agents and their dependence on the data, especially when modelling very large systems. One large system to which ABM is currently applied is the electricity distribution where thousands of agents representing the network and the consumers’ behaviours are interacting with one another. A framework that aims at answering a range of questions regarding the potential evolution of the grid has been developed and is presented here. It uses agent-based modelling to represent the engineering infrastructure of the distribution network and has been built with flexibility and extensibility in mind. What distinguishes the method presented here from the usual ABMs is that this ABM has been developed in a compositional manner. This encompasses not only the software tool, which core is named MODAM (MODular Agent-based Model) but the model itself. Using such approach enables the model to be extended as more information becomes available or modified as the electricity system evolves, leading to an adaptable model. Two well-known modularity principles in the software engineering domain are information hiding and separation of concerns. These principles were used to develop the agent-based model on top of OSGi and Eclipse plugins which have good support for modularity. Information regarding the model entities was separated into a) assets which describe the entities’ physical characteristics, and b) agents which describe their behaviour according to their goal and previous learning experiences. This approach diverges from the traditional approach where both aspects are often conflated. It has many advantages in terms of reusability of one or the other aspect for different purposes as well as composability when building simulations. For example, the way an asset is used on a network can greatly vary while its physical characteristics are the same – this is the case for two identical battery systems which usage will vary depending on the purpose of their installation. While any battery can be described by its physical properties (e.g. capacity, lifetime, and depth of discharge), its behaviour will vary depending on who is using it and what their aim is. The model is populated using data describing both aspects (physical characteristics and behaviour) and can be updated as required depending on what simulation is to be run. For example, data can be used to describe the environment to which the agents respond to – e.g. weather for solar panels, or to describe the assets and their relation to one another – e.g. the network assets. Finally, when running a simulation, MODAM calls on its module manager that coordinates the different plugins, automates the creation of the assets and agents using factories, and schedules their execution which can be done sequentially or in parallel for faster execution. Building agent-based models in this way has proven fast when adding new complex behaviours, as well as new types of assets. Simulations have been run to understand the potential impact of changes on the network in terms of assets (e.g. installation of decentralised generators) or behaviours (e.g. response to different management aims). While this platform has been developed within the context of a project focussing on the electricity domain, the core of the software, MODAM, can be extended to other domains such as transport which is part of future work with the addition of electric vehicles.

"Candidatus Similichlamydia laticola", a novel Chlamydia-like agent of epitheliocystis in seven consecutive cohorts of farmed Australian barramundi, lates calcarifer (Bloch)

Six consecutively hatched cohorts and one cohort of pre-hatch eggs of farmed barramundi (Lates calcarifer) from south Australia were examined for Chlamydia-like organisms associated with epitheliocystis. To identify and characterise the bacteria, 59 gill samples and three pre-hatch egg samples were processed for histology, in situ hybridisation and 16S rRNA amplification, sequencing and comprehensive phylogenetic analysis. Cases of epitheliocystis were observed microscopically and characterised by membrane-enclosed basophilic cysts filled with a granular material that caused hypertrophy of the epithelial cells. In situ hybridisation with a Chlamydiales-specific probe lead to specific labelling of the epitheliocystis inclusions within the gill epithelium. Two distinct but closely related 16S rRNA chlamydial sequences were amplified from gill DNA across the seven cohorts, including from pre-hatch eggs. These genotype sequences were found to be novel, sharing 97.1 - 97.5% similarity to the next closest 16S rRNA sequence, Ca. Similichlamydia latridicola, from Australian striped trumpeter. Comprehensive phylogenetic analysis of these genotype sequences against representative members of the Chlamydiales order and against other epitheliocystis agents revealed these Chlamydia-like organisms to be novel and taxonomically placed them within the recently proposed genus Ca. Similichlamydia. Following Fredricks and Relman's molecular postulates and based on these observations, we propose the epitheliocystis agents of barramundi to be known as "Candidatus Similichlamydia laticola" (sp. nov.).

Molecular characterization of "Candidatus Parilichlamydia carangidicola," a novel Chlamydia-like epitheliocystis agent in yellowtail kingfish, Seriola lalandi (Valenciennes), and the proposal of a new family, "Candidatus Parilichlamydiaceae" fam. nov. (order Chlamydiales).

Three cohorts of farmed yellowtail kingfish (Seriola lalandi) from South Australia were examined for Chlamydia-like organisms associated with epitheliocystis. To characterize the bacteria, 38 gill samples were processed for histopathology, electron microscopy, and 16S rRNA amplification, sequencing, and phylogenetic analysis. Microscopically, the presence of membrane-enclosed cysts was observed within the gill lamellae. Also observed was hyperplasia of the epithelial cells with cytoplasmic vacuolization and fusion of the gill lamellae. Transmission electron microscopy revealed morphological features of the reticulate and intermediate bodies typical of members of the order Chlamydiales. A novel 1,393-bp 16S chlamydial rRNA sequence was amplified from gill DNA extracted from fish in all cohorts over a 3-year period that corresponded to the 16S rRNA sequence amplified directly from laser-dissected cysts. This sequence was only 87% similar to the reported "Candidatus Piscichlamydia salmonis" (AY462244) from Atlantic salmon and Arctic charr. Phylogenetic analysis of this sequence against 35 Chlamydia and Chlamydia-like bacteria revealed that this novel bacterium belongs to an undescribed family lineage in the order Chlamydiales. Based on these observations, we propose this bacterium of yellowtail kingfish be known as "Candidatus Parilichlamydia carangidicola" and that the new family be known as "Candidatus Parilichlamydiaceae."

Molecular characterization of "Candidatus Similichlamydia latridicola" gen. nov., sp. nov. (Chlamydiales: "Candidatus Parilichlamydiaceae"), a novel Chlamydia-like epitheliocystis agent in the striped trumpeter, Latris lineata (Forster)

Histological analysis of gill samples taken from individuals of Latris lineata reared in aquaculture in Tasmania, Australia, and those sampled from the wild revealed the presence of epitheliocystis-like basophilic inclusions. Subsequent morphological, in situ hybridization, and molecular analyses were performed to confirm the presence of this disease and discovered a Chlamydia-like organism associated with this condition, and the criteria set by Fredericks and Relman's postulates were used to establish disease causation. Three distinct 16S rRNA genotypes were sequenced from 16 fish, and phylogenetic analyses of the nearly full-length 16S rRNA sequences generated for this bacterial agent indicated that they were nearly identical novel members of the order Chlamydiales. This new taxon formed a well-supported clade with "Candidatus Parilichlamydia carangidicola" from the yellowtail kingfish (Seriola lalandi). On the basis of sequence divergence over the 16S rRNA region relative to all other members of the order Chlamydiales, a new genus and species are proposed here for the Chlamydia-like bacterium from L. lineata, i.e., "Candidatus Similichlamydia latridicola" gen. nov., sp. nov.

Impact of passenger group dynamics on an airport evacuation process using an agent-based model

The safety of passengers is a major concern to airports. In the event of crises, having an effective and efficient evacuation process in place can significantly aid in enhancing passenger safety. Hence, it is necessary for airport operators to have an in-depth understanding of the evacuation process of their airport terminal. Although evacuation models have been used in studying pedestrian behaviour for decades, little research has been done in considering the evacuees’ group dynamics and the complexity of the environment. In this paper, an agent-based model is presented to simulate passenger evacuation process. Different exits were allocated to passengers based on their location and security level. The simulation results show that the evacuation time can be influenced by passenger group dynamics. This model also provides a convenient way to design airport evacuation strategy and examine its efficiency. The model was created using AnyLogic software and its parameters were initialised using recent research data published in the literature.

A Lagrangian approach to nonlinear modeling of anti-roll tanks

This paper presents two novel nonlinear models of u-shaped anti-roll tanks for ships, and their linearizations. In addition, a third simplified nonlinear model is presented. The models are derived using Lagrangian mechanics. This formulation not only simplifies the modeling process, but also allows one to obtain models that satisfy energy-related physical properties. The proposed nonlinear models and their linearizations are validated using model-scale experimental data. Unlike other models in the literature, the nonlinear models in this paper are valid for large roll amplitudes. Even at moderate roll angles, the nonlinear models have three orders of magnitude lower mean square error relative to experimental data than the linear models.

Intermittent Fugu parathyroid hormone 1 (1–34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats

Human parathyroid hormone (hPTH) is currently the only treatment for osteoporosis that forms new bone. Previously we described a fish equivalent, Fugu parathyroid hormone 1 (fPth1) which has hPTH-like biological activity in vitro despite fPth1(1–34) sharing only 53% identity with hPTH(1–34). Here we demonstrate the in vivo actions of fPth1(1–34) on bone. In study 1, young male rats were injected intermittently for 30 days with fPth1 [30 μg–1000 μg/kg body weight (b.w.), (30fPth1–1000fPth1)] or hPTH [30 μg–100 μg/kg b.w. (30hPTH–100hPTH)]. In proximal tibiae at low doses, the fPth1 was positively correlated with trabecular bone volume/total volume (TbBV/TV) while hPTH increased TbBV/TV, trabecular thickness (TbTh) and trabecular number (TbN). 500fPth1 and 1000fPth1 increased TbBV/TV, TbTh, TbN, mineral apposition rate (MAR) and bone formation rate/bone surface (BFR/BS) with a concomitant decrease in osteoclast surface and number. In study 2 ovariectomized (OVX), osteopenic rats and sham operated (SHAM) rats were injected intermittently with 500 μg/kg b.w. of fPth1 (500fPth1) for 11 weeks. 500fPth1 treatment resulted in increased TbBV/TV (151%) and TbTh (96%) in the proximal tibiae due to increased bone formation as assessed by BFR/BS (490%) and MAR (131%). The effect was restoration of TbBV/TV to SHAM levels without any effect on bone resorption. 500fPth1 also increased TbBV/TV and TbTh in the vertebrae (L6) and cortical thickness in the mid-femora increasing bone strength at these sites. fPth1 was similarly effective in SHAM rats. Notwithstanding the low amino acid sequence homology with hPTH (1–34), we have clearly established the efficacy of fPth1 (1–34) as an anabolic bone agent.

Anti-wind-up designs for dynamic positioning of marine vehicles with control allocation

This paper presents a framework for the design of a joint motion controller and a control allocation strategy for dynamic positioning of marine vehicles. The key aspects of the proposed designs are a systematic approach to deal with actuator saturation and to inform the motion controller about saturation. The proposed system uses a mapping that translates the actuator constraint sets into constraint sets at the motion controller level. Hence, while the motion controller addresses the constraints, the control allocation algorithm can solve an unconstrained optimisation problem. The constrained control design is approached using a multivariable anti-wind-up strategy for strictly proper controllers. This is applicable to the implementation of PI and PID type of motion controllers.

Agent-based modelling simulation case study : assessment of airport check-in and evacuation process by considering group travel behaviour of air passengers

Passenger experience has become a major factor that influences the success of an airport. In this context, passenger flow simulation has been used in designing and managing airports. However, most passenger flow simulations failed to consider the group dynamics when developing passenger flow models. In this paper, an agent-based model is presented to simulate passenger behaviour at the airport check-in and evacuation process. The simulation results show that the passenger behaviour can have significant influences on the performance and utilisation of services in airport terminals. The model was created using AnyLogic software and its parameters were initialised using recent research data published in the literature.

Agent-based application on different boarding strategies

In this paper we implemented six different boarding strategies (Wilma, Steffen, Reverse Pyramid, Random, Blocks and By letter) in order to minimize boarding time and turnaround time for Boeing 777 and Airbus 380 aircrafts by using Agent-based modelling approach. In the simulation, we divided passengers into six different categories which are group size more than 5 people, passengers with child, gold members, first class passengers, business class passengers and economy class passengers. Results from the simulation demonstrates Reverse Pyramid method is the best boarding method for Boeing 777 and Steffen method is the best boarding method for Airbus 380.

Modelling airport passenger group dynamics using an agent-based method

This thesis investigates the influence of passenger group dynamics on passengers' behaviour in an international airport. A simulation model is built to analyse passengers' behaviour during airport departure processes and during an emergency event. Results from the model showed that passengers' group dynamics have significant influences on the performance and utilisation of airport services. The agent-based model also provides a convenient way to investigate the effectiveness of space design and service allocations, which may contribute to the enhancement of passenger airport experiences.

Broadcast anti-jamming systems

In a traditional anti-jamming system a transmitter who wants to send a signal to a single receiver spreads the signal power over a wide frequency spectrum with the aim of stopping a jammer from blocking the transmission. In this paper, we consider the case that there are multiple receivers and the transmitter wants to broadcast a message to all receivers such that colluding groups of receivers cannot jam the reception of any other receiver. We propose efficient coding methods that achieve this goal and link this problem to well-known problems in combinatorics. We also link a generalisation of this problem to the Key Distribution Pattern problem studied in combinatorial cryptography.