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A review of evidence of health benefit from artificial neural networks in medical intervention.

The purpose of this review is to assess the evidence of healthcare benefits involving the application of artificial neural networks to the clinical functions of diagnosis, prognosis and survival analysis, in the medical domains of oncology, critical care and cardiovascular medicine. The primary source of publications is PUBMED listings under Randomised Controlled Trials and Clinical Trials. The rĵle of neural networks is introduced within the context of advances in medical decision support arising from parallel developments in statistics and artificial intelligence. This is followed by a survey of published Randomised Controlled Trials and Clinical Trials, leading to recommendations for good practice in the design and evaluation of neural networks for use in medical intervention.

Decision Support Techniques↗

Neural networks in astronomy.

In the last decade, the use of neural networks (NN) and of other soft computing methods has begun to spread also in the astronomical community which, due to the required accuracy of the measurements, is usually reluctant to use automatic tools to perform even the most common tasks of data reduction and data mining. The federation of heterogeneous large astronomical databases which is foreseen in the framework of the astrophysical virtual observatory and national virtual observatory projects, is, however, posing unprecedented data mining and visualization problems which will find a rather natural and user friendly answer in artificial intelligence tools based on NNs, fuzzy sets or genetic algorithms. This review is aimed to both astronomers (who often have little knowledge of the methodological background) and computer scientists (who often know little about potentially interesting applications), and therefore will be structured as follows: after giving a short introduction to the subject, we shall summarize the methodological background and focus our attention on some of the most interesting fields of application, namely: object extraction and classification, time series analysis, noise identification, and data mining. Most of the original work described in the paper has been performed in the framework of the AstroNeural collaboration (Napoli-Salerno).

Astronomy↗

Three Centuries of Category Errors in Studies of the Neural Basis of Consciousness and Intentionality.

Recent interest in consciousness and the mind-brain problem has been fueled by technological advances in brain imaging and computer modeling in artificial intelligence: can machines be conscious? The machine metaphor originated in Cartesian "reflections" and culminated in 19th century reflexology modeled on Newtonian optics. It replaced the Aquinian view of mind, which was focused on the emergence of intentionality within the body, with control of output by input through brain dynamics. The state variables for neural activity were identified successively with animal spirits, élan vital, electricity, energy, information, and, most recently, Heisenbergian potentia. The source of dynamic structure in brains was conceived to lie outside brains in genetic and environmental determinism. An alternative view has grown in the 20th century from roots in American Pragmatists, particularly John Dewey, and European philosophers, particularly Heidegger and Piaget, by which brains are intrinsically unstable and continually create themselves. This view has new support from neurobiological studies in properties of self-organizing nonlinear dynamic systems. Intentional behavior can only be understood in relation to the chaotic patterns of neural activity that produce it. The machine metaphor remains, but the machine is seen as self-determining.

Journal Article↗

Template-based procedures for neural network interpretation.

Although neural networks often achieve impressive learning and generalization performance, their internal workings are typically all but impossible to decipher. This characteristic of the networks, their opacity, is one of the disadvantages of connectionism compared to more traditional, rule-oriented approaches to artificial intelligence. Without a thorough understanding of the network behavior, confidence in a system's results is lowered, and the transfer of learned knowledge to other processing systems - including humans - is precluded. Methods that address the opacity problem by casting network weights in symbolic terms are commonly referred to as rule extraction techniques. This work describes a principled approach to symbolic rule extraction from standard multilayer feedforward networks based on the notion of weight templates, parameterized regions of weight space corresponding to specific symbolic expressions. With an appropriate choice of representation, we show how template parameters may be efficiently identified and instantiated to yield the optimal match to the actual weights of a unit. Depending on the requirements of the application domain, the approach can accommodate n-ary disjunctions and conjunctions with O(k) complexity, simple n-of-m expressions with O(k(2)) complexity, or more general classes of recursive n-of-m expressions with O(k(L+2)) complexity, where k is the number of inputs to an unit and L the recursion level of the expression class. Compared to other approaches in the literature, our method of rule extraction offers benefits in simplicity, computational performance, and overall flexibility. Simulation results on a variety of problems demonstrate the application of our procedures as well as the strengths and the weaknesses of our general approach.

Journal Article↗

Confidentiality issues for medical data miners.

The first task in any medical data mining effort is ensuring patient confidentiality. In the past, most data mining efforts ensured confidentiality by the dubious policy of withholding their raw data from colleagues and the public. A cursory review of medical informatics literature in the past decade reveals that much of what we have "learned" consists of assertions derived from confidential datasets unavailable for anyone's review. Without access to the original data, it is impossible to validate or improve upon a researcher's conclusions. Without access to research data, we are asked to accept findings as an act of faith, rather than as a scientific conclusion. This special issue of Artificial Intelligence in Medicine is devoted to medical data mining. The medical data miner has an obligation to conduct valid research in a way that protects human subjects. Today, data miners have the technical tools to merge large data collections and to distribute queries over disparate databases. In order to include patient-related data in shared databases, data miners will need methods to anonymize and deidentify data. This article reviews the human subject risks associated with medical data mining. This article also describes some of the innovative computational remedies that will permit researchers to conduct research AND share their data without risk to patient or institution.

Computer Security↗

Lightweight fuzzy processes in clinical computing.

In spite of advances in computing hardware, many hospitals still have a hard time finding extra capacity in their production clinical information system to run artificial intelligence (AI) modules, for example: to support real-time drug-drug or drug-lab interactions; to track infection trends; to monitor compliance with case specific clinical guidelines; or to monitor/ control biomedical devices like an intelligent ventilator. Historically, adding AI functionality was not a major design concern when a typical clinical system is originally specified. AI technology is usually retrofitted 'on top of the old system' or 'run off line' in tandem with the old system to ensure that the routine work load would still get done (with as little impact from the AI side as possible). To compound the burden on system performance, most institutions have witnessed a long and increasing trend for intramural and extramural reporting, (e.g. the collection of data for a quality-control report in microbiology, or a meta-analysis of a suite of coronary artery bypass grafts techniques, etc.) and these place an ever-growing burden on typical the computer system's performance. We discuss a promising approach to adding extra AI processing power to a heavily-used system based on the notion 'lightweight fuzzy processing (LFP)', that is, fuzzy modules designed from the outset to impose a small computational load. A formal model for a useful subclass of fuzzy systems is defined below and is used as a framework for the automated generation of LFPs. By seeking to reduce the arithmetic complexity of the model (a hand-crafted process) and the data complexity of the model (an automated process), we show how LFPs can be generated for three sample datasets of clinical relevance.

Biopsy, Needle↗

Advances in fuzzy theory.

Recent advances in the foundations of fuzzy theory facilitated by Bart Kosko's discovery of the fuzzy hypercube are of high relevance to artificial intelligence in medicine research. The new concepts of set inclusion, equality, and similarity are therefore reported in this paper. A unifying notion of a Lotfi Zadeh space is also introduced to show that Bart Kosko's fuzzy hypercube is a Zadeh space.

Fuzzy Logic↗

Planning treatment of ischemic heart disease with partially observable Markov decision processes.

Diagnosis of a disease and its treatment are not separate, one-shot activities. Instead, they are very often dependent and interleaved over time. This is mostly due to uncertainty about the underlying disease, uncertainty associated with the response of a patient to the treatment and varying cost of different diagnostic (investigative) and treatment procedures. The framework of partially observable Markov decision processes (POMDPs) developed and used in the operations research, control theory and artificial intelligence communities is particularly suitable for modeling such a complex decision process. In this paper, we show how the POMDP framework can be used to model and solve the problem of the management of patients with ischemic heart disease (IHD), and demonstrate the modeling advantages of the framework over standard decision formalisms.

Cost-Benefit Analysis↗

Predictive non-linear modeling of complex data by artificial neural networks.

An artificial neural network (ANN) is an artificial intelligence tool that identifies arbitrary nonlinear multiparametric discriminant functions directly from experimental data. The use of ANNs has gained increasing popularity for applications where a mechanistic description of the dependency between dependent and independent variables is either unknown or very complex. This machine learning technique can be roughly described as a universal algebraic function that will distinguish signal from noise directly from experimental data. The application of ANNs to complex relationships makes them highly attractive for the study of biological systems. Recent applications include the analysis of expression profiles and genomic and proteomic sequences.

Biochemical Phenomena↗

Calculations of nucleic acid conformations.

The present computational power and sophistication of theoretical approaches to nucleic acid structural investigation are sufficient for the realization of static and dynamic models that correlate accurately with current crystallographic, NMR and solution-probing structural data, and consequently are able to provide valuable insights and predictions for a variety of nucleic acid conformational families. In molecular dynamics simulations, the year 1995 was marked by the foray of fast Ewald methods, an accomplishment resulting from several years' work in the search for an adequate treatment of the electrostatic long-range forces so primordial in nucleic acid behavior. In very large systems, and particularly in the RNA-folding field, techniques originating from artificial intelligence research, like constraint satisfaction programming or genetic algorithms, have established their utility and potential.

DNA↗

High-throughput protein crystallization.

High-throughput structural biology is a focus of a number of academic and pharmaceutical laboratories around the world. The use of X-ray crystallography in these efforts is critically dependent on high-throughput protein crystallization. The application of current protocols yields crystal leads for approximately 30% of the input proteins and well-diffracting crystals for a smaller fraction. Increasing the success rate will require a multidisciplinary approach that must invoke techniques from molecular biology, protein biochemistry, biophysics, artificial intelligence, and automation.

Automation↗

Computer expert system for the histopathologic diagnosis of salivary gland neoplasms.

The design, development, and testing of a prototype interactive histopathologic expert system capable of diagnosing 15 types of primary salivary gland neoplasms is described. The system incorporates a multiple subprogram modular design and makes use of multiple reasoning methods including: data-driven and goal-directed rule-based reasoning, linear pattern recognition, and Bayesian classification. Its user interface incorporates both a "hypertext" context-sensitive information assistance facility and the video display of stored and digitized photomicrographic images. The system can report a differential diagnosis of its findings with assessment of its confidence in its diagnosis. The system's performance was evaluated in a series of tests. The results of a weighted kappa analysis of the system's diagnoses versus those of four oral pathologists for 20 salivary gland neoplasms indicated no statistical difference in diagnostic performance between the system and the human experts and each of the experts in relationship to the others (Wilcoxon rank sums test). A modified version of Turing's test of artificial intelligence demonstrated no statistically significant difference in the system's diagnoses versus the diagnosis of four human expert pathologists (Fisher's exact test). The knowledge and experience gained in the development and testing of the expert system described in this study have demonstrated the validity of histopathologic diagnostic expert systems in a selected area of oral pathology.

Bayes Theorem↗

Computer model for recognition of functional transcription start sites in RNA polymerase II promoters of vertebrates.

This paper introduces a new computer system for recognition of functional transcription start sites (TSSs) in RNA polymerase II promoter regions of vertebrates. This system allows scanning complete vertebrate genomes for promoters with significantly reduced number of false positive predictions. It can be used in the context of gene finding through its recognition of the 5' end of genes. The implemented recognition model uses a composite-hierarchical approach, artificial intelligence, statistics, and signal processing techniques. It also exploits the separation of promoter sequences into those that are C+G-rich or C+G-poor. The system was evaluated on a large and diverse human sequence-set and exhibited several times higher accuracy than several publicly available TSS-finding programs. Results obtained using human chromosome 22 data showed even greater specificity than the evaluation set results. The system has been implemented in the Dragon Promoter Finder package, which can be accessed at http://sdmc.krdl.org.sg:8080/promoter/.

Animals↗

Clinical decision-support systems for intensive care units using case-based reasoning.

The artificial intelligence approach used in this work focusses on case-based reasoning techniques for the estimation of medical outcomes and resource utilization. The systems were designed with a view to help medical and nursing personnel to assess patient status, assist in making a diagnosis, and facilitate the selection of a course of therapy. The initial prototype provided information on the closest-matching patient cases to the newest patient admission in an adult intensive care unit (ICU). The system was subsequently re-designed for use in a neonatal ICU. The results of a short clinical pilot evaluation performed in both adult and neonatal units are reported and have led to substantial improvement of the prototype. Future work will include longer-term clinical trials for both adult and neonatal ICUs, once all the software changes have been made to both prototypes in response to the comments of the users made during the preliminary evaluations. To date, the results are very encouraging and physician interest in the potential clinical usefulness of these two systems remains high, and particularly so in the new testing environment in Ottawa.

Adult↗

Crosstalk in plant cell signaling: structure and function of the genetic network.

Cell signaling integrates independent stimuli using connections between biochemical pathways. The sensory apparatus can be represented as a network, and the connections between pathways are termed crosstalk. Here, we describe several examples of crosstalk in plant biology. To formalize the network of signal transduction we evaluated the relevance of mechanistic models used in artificial intelligence. Although the perceptron model of neural networking provides a good description of the process, we suggest that Boolean networks should be used as a starting framework. The Boolean network model allows genetic data to be integrated into the logical network of connections deduced from DNA microarray data.

Journal Article↗

Is imitation learning the route to humanoid robots?

This review investigates two recent developments in artificial intelligence and neural computation: learning from imitation and the development of humanoid robots. It is postulated that the study of imitation learning offers a promising route to gain new insights into mechanisms of perceptual motor control that could ultimately lead to the creation of autonomous humanoid robots. Imitation learning focuses on three important issues: efficient motor learning, the connection between action and perception, and modular motor control in the form of movement primitives. It is reviewed here how research on representations of, and functional connections between, action and perception have contributed to our understanding of motor acts of other beings. The recent discovery that some areas in the primate brain are active during both movement perception and execution has provided a hypothetical neural basis of imitation. Computational approaches to imitation learning are also described, initially from the perspective of traditional AI and robotics, but also from the perspective of neural network models and statistical-learning research. Parallels and differences between biological and computational approaches to imitation are highlighted and an overview of current projects that actually employ imitation learning for humanoid robots is given.

Journal Article↗

A methodology for incorporating web technologies into a computer-based patient record, with contributions from cognitive science.

Cognitive science is a rich source of insight for creative use of new Web technologies by medical informatics workers. I outline a project to Web-enable an existing computer-based patient record (CPR) in the context of ideas from philosophy, linguistics, artificial intelligence, and cognitive psychology. Web prototypes play an important role (a) because Web technology lends itself to rapid prototype development, and (b) because prototypes help team members bridge among disparate medical, computing, and business ontologies. Six Web-enabled CPR prototypes were created and ranked. User scenarios were generated using a user communication matrix. Resulting prototypes were compared according to the degree to which they satisfied medical, computing, and business constraints. In a different organization, or at different time, candidate prototypes and their ranking might have been different. However, prototype generation and comparison are fundamentally influenced by factors usefully understood in a cognitive science framework.

Cognitive Science↗

Protocols and guides, tools.

The author describes in the first part of the review the definitions and relations of the occurring concepts. In the second part a short history of the topic is overviewed. The third part is dealing with the electronic patient record based development of guidelines in addition what are the relations among guidelines, protocols, tools, knowledge-based systems, diagnosis supporting systems, expert systems, outcome analysis and artificial intelligence. A short review of what was presented in the MIE '97 in this area is finally described and the Session Chairman's conclusion.

Computer Communication Networks↗