Across the dividing range - bridging the divides: Pharmacy opportunities across the hospital/community and inter-professional divides in rural and remote Australia

Rural and remote areas of Australia offer many opportunities for innovation in healthcare services. Some true healthcare 'network' models based around rural pharmacy can be established and evaluated. The lines between community and hospital pharmacy are often blurred and communication between health professionals enhanced. The blurring divide between hospital and community pharmacy in rural and remote areas has provided significant advances in practice. Projects have been set up to investigate the feasibility of community pharmacists integrating care for patients. These projects take advantage of the dual roles and the enhanced interaction between pharmacists and other health professionals in the bush. Opportunities for provision of clinical services beyond the traditional supply role have been taken in a number of remote communities

Validation and refinement of survival models for liver retransplantation

Orthotopic liver retransplantation (re-OLT) is highly controversial. The objectives of this study were to determine the validity of a recently developed United Network for Organ Sharing (UNOS) multivariate model using an independent cohort of patients undergoing re-OLT outside the United States, to determine whether incorporation of other variables that were incomplete in the UNOS registry would provide additional prognostic information, to develop new models combining data sets from both cohorts, and to evaluate the validity of the model for end-stage liver disease (MELD) in patients undergoing re-OLT. Two hundred eighty-one adult patients undergoing re-OLT (between 1986 and 1999) at 6 foreign transplant centers comprised the validation cohort. We found good agreement between actual survival and predicted survival in the validation cohort; 1-year patient survival rates in the low-, intermediate-, and high-risk groups (as assigned by the original UNOS model) were 72%, 68%, and 36%, respectively (P < .0001). In the patients for whom the international normalized ratio (INR) of prothrombin time was available, MELD correlated with outcome following re-OLT; the median MELD scores for patients surviving at least 90 days compared with those dying within 90 days were 20.75 versus 25.9, respectively (P = .004). Utilizing both patient cohorts (n = 979), a new model, based on recipient age, total serum bilirubin, creatinine, and interval to re-OLT, was constructed (whole model χ(2) = 105, P < .0001). Using the c-statistic with 30-day, 90-day, 1-year, and 3-year mortality as the end points, the area under the receiver operating characteristic (ROC) curves for 4 different models were compared. In conclusion, prospective validation and use of these models as adjuncts to clinical decision making in the management of patients being considered for re-OLT are warranted.

Typing mineral deposits using their grades and tonnages in an artificial neural network

A test of the ability of a probabilistic neural network to classify deposits into types on the basis of deposit tonnage and average Cu, Mo, Ag, Au, Zn, and Pb grades is conducted. The purpose is to examine whether this type of system might serve as a basis for integrating geoscience information available in large mineral databases to classify sites by deposit type. Benefits of proper classification of many sites in large regions are relatively rapid identification of terranes permissive for deposit types and recognition of specific sites perhaps worthy of exploring further. Total tonnages and average grades of 1,137 well-explored deposits identified in published grade and tonnage models representing 13 deposit types were used to train and test the network. Tonnages were transformed by logarithms and grades by square roots to reduce effects of skewness. All values were scaled by subtracting the variable's mean and dividing by its standard deviation. Half of the deposits were selected randomly to be used in training the probabilistic neural network and the other half were used for independent testing. Tests were performed with a probabilistic neural network employing a Gaussian kernel and separate sigma weights for each class (type) and each variable (grade or tonnage). Deposit types were selected to challenge the neural network. For many types, tonnages or average grades are significantly different from other types, but individual deposits may plot in the grade and tonnage space of more than one type. Porphyry Cu, porphyry Cu-Au, and porphyry Cu-Mo types have similar tonnages and relatively small differences in grades. Redbed Cu deposits typically have tonnages that could be confused with porphyry Cu deposits, also contain Cu and, in some situations, Ag. Cyprus and kuroko massive sulfide types have about the same tonnages. Cu, Zn, Ag, and Au grades. Polymetallic vein, sedimentary exhalative Zn-Pb, and Zn-Pb skarn types contain many of the same metals. Sediment-hosted Au, Comstock Au-Ag, and low-sulfide Au-quartz vein types are principally Au deposits with differing amounts of Ag. Given the intent to test the neural network under the most difficult conditions, an overall 75% agreement between the experts and the neural network is considered excellent. Among the largestclassification errors are skarn Zn-Pb and Cyprus massive sulfide deposits classed by the neuralnetwork as kuroko massive sulfides—24 and 63% error respectively. Other large errors are the classification of 92% of porphyry Cu-Mo as porphyry Cu deposits. Most of the larger classification errors involve 25 or fewer training deposits, suggesting that some errors might be the result of small sample size. About 91% of the gold deposit types were classed properly and 98% of porphyry Cu deposits were classes as some type of porphyry Cu deposit. An experienced economic geologist would not make many of the classification errors that were made by the neural network because the geologic settings of deposits would be used to reduce errors. In a separate test, the probabilistic neural network correctly classed 93% of 336 deposits in eight deposit types when trained with presence or absence of 58 minerals and six generalized rock types. The overall success rate of the probabilistic neural network when trained on tonnage and average grades would probably be more than 90% with additional information on the presence of a few rock types.

Bistability and switching in the lysis/lysogeny genetic regulatory network of bacteriophage lambda

Bistability and switching are two important aspects of the genetic regulatory network of phage. Positive and negative feedbacks are key regulatory mechanisms in this network. By the introduction of threshold values, the developmental pathway of A phage is divided into different stages. If the protein level reaches a threshold value, positive or negative feedback will be effective and regulate the process of development. Using this regulatory mechanism, we present a quantitative model to realize bistability and switching of phage based on experimental data. This model gives descriptions of decisive mechanisms for different pathways in induction. A stochastic model is also introduced for describing statistical properties of switching in induction. A stochastic degradation rate is used to represent intrinsic noise in induction for switching the system from the lysogenic pathway to the lysis pathway. The approach in this paper represents an attempt to describe the regulatory mechanism in genetic regulatory network under the influence of intrinsic noise in the framework of continuous models. (C) 2003 Elsevier Ltd. All rights reserved.

The cross-entropy method for network reliability estimation

Consider a network of unreliable links, modelling for example a communication network. Estimating the reliability of the network-expressed as the probability that certain nodes in the network are connected-is a computationally difficult task. In this paper we study how the Cross-Entropy method can be used to obtain more efficient network reliability estimation procedures. Three techniques of estimation are considered: Crude Monte Carlo and the more sophisticated Permutation Monte Carlo and Merge Process. We show that the Cross-Entropy method yields a speed-up over all three techniques.

GPNN: Power studies and applications of a neural network method for detecting gene-gene interactions in studies of human disease

Background The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease. Results We show that GPNN has high power to detect even relatively small genetic effects (2–3% heritability) in simulated data models involving two and three locus interactions. The limits of detection were reached under conditions with very small heritability (

Classical simulation of quantum many-body systems with a tree tensor network

We show how to efficiently simulate a quantum many-body system with tree structure when its entanglement (Schmidt number) is small for any bipartite split along an edge of the tree. As an application, we show that any one-way quantum computation on a tree graph can be efficiently simulated with a classical computer.

Stochastic models for regulatory networks of the genetic toggle switch

Bistability arises within a wide range of biological systems from the A phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. in this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

GPNN: Power studies and applications of a neural network method for detecting gene-gene interactions in studies of human disease

Background: The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease. Results: We show that GPNN has high power to detect even relatively small genetic effects (2-3% heritability) in simulated data models involving two and three locus interactions. The limits of detection were reached under conditions with very small heritability (

A bayesian artificial neural network method to characterise laminar defects using dynamic measurements

This paper reports on the development of an artificial neural network (ANN) method to detect laminar defects following the pattern matching approach utilizing dynamic measurement. Although structural health monitoring (SHM) using ANN has attracted much attention in the last decade, the problem of how to select the optimal class of ANN models has not been investigated in great depth. It turns out that the lack of a rigorous ANN design methodology is one of the main reasons for the delay in the successful application of the promising technique in SHM. In this paper, a Bayesian method is applied in the selection of the optimal class of ANN models for a given set of input/target training data. The ANN design method is demonstrated for the case of the detection and characterisation of laminar defects in carbon fibre-reinforced beams using flexural vibration data for beams with and without non-symmetric delamination damage.

Robustness of mathematical models for biological systems

The robustness of mathematical models for biological systems is studied by sensitivity analysis and stochastic simulations. Using a neural network model with three genes as the test problem, we study robustness properties of synthesis and degradation processes. For single parameter robustness, sensitivity analysis techniques are applied for studying parameter variations and stochastic simulations are used for investigating the impact of external noise. Results of sensitivity analysis are consistent with those obtained by stochastic simulations. Stochastic models with external noise can be used for studying the robustness not only to external noise but also to parameter variations. For external noise we also use stochastic models to study the robustness of the function of each gene and that of the system.

A Reactive Agent-based Neural Network Car Following Model

This paper presented a novel approach to develop car following models using reactive agent techniques for mapping perceptions to actions. The results showed that the model outperformed the Gipps and Psychophysical family of car following models. The standing of this work is highlighted by its acceptance and publication in the proceedings of the International IEEE Conference on Intelligent Transportation Systems (ITS), which is now recognised as the premier international conference on ITS. The paper acceptance rate to this conference was 67 percent. The standing of this paper is also evidenced by its listing in international databases like Ei Inspec and IEEE Xplore. The paper is also listed in Google Scholar. Dr Dia co-authored this paper with his PhD student Sakda Panwai.

Actor-network theory as a theoretical lens and research strategy for investigating firm internationalisation

Totally generalisable theories of firm internationalisation in the post-industrial era of international business, where national barriers are becoming less significant and technology becoming more influential, appear to be illusory. Stepwise or evolutionary models that predict gradual internationalisation are under challenge from empirical evidence of rapid internationalisation such as the phenomenon of the “born global” firm. Similarly, equilibrium models such as the eclectic paradigm have been criticised for being static and unable to account for process and path dependency. In this paper, the information and knowledge assumptions implied in theories of firm internationalisation are outlined and discussed. From this discussion, we suggest that actor-network theory, with its balance between description and explanation, may be a useful theoretical and empirical tool for investigating the complex and heterogeneous process of firm internationalisation whilst creating opportunities for further theory building.

Structure and dynamics of a gene network model incorporating small RNAs

As advances in molecular biology continue to reveal additional layers of complexity in gene regulation, computational models need to incorporate additional features to explore the implications of new theories and hypotheses. It has recently been suggested that eukaryotic organisms owe their phenotypic complexity and diversity to the exploitation of small RNAs as signalling molecules. Previous models of genetic systems are, for several reasons, inadequate to investigate this theory. In this study, we present an artificial genome model of genetic regulatory networks based upon previous work by Torsten Reil, and demonstrate how this model generates networks with biologically plausible structural and dynamic properties. We also extend the model to explore the implications of incorporating regulation by small RNA molecules in a gene network. We demonstrate how, using these signals, highly connected networks can display dynamics that are more stable than expected given their level of connectivity.