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PubMed2006

Computational tools for isotopically instationary 13C labeling experiments under metabolic steady state conditions.

(13)C metabolic flux analysis (MFA) has become an important and powerful tool for the quantitative analysis of metabolic networks in the framework of metabolic engineering. Isotopically instationary (13)C MFA under metabolic stationary conditions is a promising refinement of classical stationary MFA. It accounts for the experimental requirements of non-steady-state cultures as well as for the shortening of the experimental duration. This contribution extends all computational methods developed for classical stationary (13)C MFA to the instationary situation by using high-performance computing methods. The developed tools allow for the simulation of instationary carbon labeling experiments (CLEs), sensitivity calculation with respect to unknown parameters, fitting of the model to the measured data, statistical identifiability analysis and an optimal experimental design facility. To explore the potential of the new approach all these tools are applied to the central metabolism of Escherichia coli. The achieved results are compared to the outcome of the stationary counterpart, especially focusing on statistical properties. This demonstrates the specific strengths of the instationary method. A new ranking method is proposed making both an a priori and an a posteriori design of the sampling times available. It will be shown that although still not all fluxes are identifiable, the quality of flux estimates can be strongly improved in the instationary case. Moreover, statements about the size of some immeasurable pool sizes can be made.

Biomedical Engineering↗
PubMed2000

The information and communication society: how people will live and work in the new millennium.

This paper analyses information and communication technology (ICT) and its relation to work organizations, human communication, stress, allocation issues, knowledge transfer and global villages. An interdisciplinary research programme on 'Computer technology and work life' was initiated and led by the author at Stockholm University in 1974, followed by many programmes in Sweden in the field. A theoretical framework was developed including two theoretical models, one more general, the other where the concepts and their interrelationships were specified. The models were tested empirically in three large work organizations in Sweden, representing three main historical periods of computer technology. It was also used as a model in discussing what might be desirable goals in the information society. The present fourth period, the 'Network period', is characterized by a convergence of three main technologies: computer, telecommunication and media. ICT is used in almost every activity and is embedded in many things. The author proposes a superimposed theoretical model reflecting 'ICT and the psychosocial life environment', a revised model of her initial models. Finally, future research is discussed with reference to theoretical models revised, and conclusions address major psychosocial processes, psychosocial life environments and a call for synthesis.

Computer Communication Networks↗
PubMed2003

Fiswidgets: a graphical computing environment for neuroimaging analysis.

Current fMRI neuroimaging software programs offer the researcher a wealth of analysis methods and tools. However, the incompatibilities in user interface, data format, and computing environment in these tools make it difficult if not impossible for most researchers to take advantage of the full set of resources available for neuroimaging analyses. We describe a graphical computing environment, Functional Imaging Software Widgets (fiswidgets), which was developed to address these interoperability and usability problems. This environment provides a desktop style framework into which 100 subcomponents from a number of widely used fMRI analysis software packages (e.g., AFNI, AIR) are incorporated. It is an open-source, extensible environment available for reuse and modification by other software developers. A discussion of the design criteria (open architecture, modularity, wrapper technology, commercial utilities) that support such loosely integrative computing environments, and the problems entailed in maintaining them (development overhead, distribution logistics, format incompatibilities, graphics vs scripting tradeoffs, and appropriate acknowledgment of software developers) follows.

Computer Graphics↗
PubMed2001

Changing clinicians' laboratory test requesting behaviour: can the poacher turn gamekeeper?

A major reason for the dramatic increase in laboratory costs is the increased number of laboratory investigations, many of which are perceived to be a waste of time and money. In consequence, several strategies, reviewed below, for curtailing clinicians' laboratory usage have been proposed but none has been universally successful. It is clear, however, that a combination of several strategies is likely to be more successful than any single approach. There may be several reasons why no single strategy has been widely adopted in routine practice. We suggest that modern computers have the ability to overcome these obstacles. We propose, therefore, that expert systems at the clinical-laboratory interface utilising a multifactorial approach within a framework of commitment from clinicians and laboratorians offer the best prospect for reducing inappropriate laboratory usage.

Clinical Laboratory Techniques↗
PubMed2000

Computer-based inpatient medical record in colorectal surgery: pilot study.

PURPOSE: Clinical guidelines and care maps are important tools for improving quality of care and reducing costs. However, problems of quantity, quality, and accessibility of data recorded in the inpatient medical record have not been solved by the implementation of clinical pathways. Variance or "charting by exception" improves legibility, in part. The aim of the present study was to design a computer-based medical record on a database platform to provide legible notes within a clinical guideline and variance charting framework. METHODS: A computerized database program was written, integrating pre-established clinical guidelines into a user-friendly interface according to modification of the charting by exception principles. Patient care guidelines were provided for each postoperative day. After an initial debugging process by entering data from old charts of patients, the software was installed and its function was evaluated on selected patients. The charting time was compared with the standard charting method. Functionality and user friendliness were assessed. RESULTS: After a brief introduction of ten minutes, all users were able to use the software without difficulties. It was found to be functional and user friendly. The charting time was shorter for the computer-based inpatient medical record compared with the charting time of the standard charts. Because all daily notes were printed on standardized forms on a laser printer, legibility was excellent. CONCLUSIONS: The results of this pilot study suggest that the idea of computer-based inpatient medical record integrating an on-line inpatient medical record in a database platform is feasible. Further development and integration with other hospital information systems and the other health-care providers is required.

Colectomy↗
PubMed2003

Efficiency of [(18)F]FDG PET in characterising renal cancer and detecting distant metastases: a comparison with CT.

The purpose of this study was to assess the efficiency of fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the characterisation and primary staging of suspicious renal masses, in comparison with computed tomography, the current standard imaging modality. Fifty-three FDG PET studies were performed within the framework of a prospective study: 35 for both characterisation and staging of a suspicious mass, and 18 for staging early after surgical removal of a renal cancer. In the characterisation of renal masses, a high rate of false negative results was observed, leading to a sensitivity, specificity and accuracy of 47%, 80% and 51% respectively, versus 97%, 0/5 and 83% respectively for CT. FDG PET detected all the sites of distant metastasis revealed by CT, as well as eight additional metastatic sites, leading to an accuracy of 94% versus 89% for CT. However, 36/53 patients (68%) did not have any distant metastasis on either CT or on PET. All but one of these patients had a low Fuhrman histological grade and a limited local stage (< or =pT2). We conclude that FDG PET does not offer any advantage over CT for the characterisation of renal masses but that it appears to be an efficient tool for the detection of distant metastasis in renal cancer. However, our data suggest that a selection process could be implemented to determine which patients should undergo PET. FDG PET could be performed in the event of a solitary metastasis or doubtful images on CT. Selection could also be based on adverse histological findings from nephrectomy specimens in order to perform staging early after nephrectomy.

Adult↗
PubMed1996

Basic framework for the economic evaluation of animal health control programmes.

The further integration of international markets means that co-ordinated policies against contagious animal infections have become increasingly important, and stricter demands for control and eradication should be expected in the future. To meet these demands, it would be desirable to create a computer simulation environment in which 'what if?' scenarios could be performed, in order to explore the epidemiological and economic effects of various infections and control strategies. The authors propose a flexible economic framework and illustrate this framework with an example. The framework has four elements: changes in the percentage of infectious herds, changes in product quantities, changes in product prices and economic integration. Each element is specifically defined and has its own input and output data, depending on the control strategy under consideration. In an illustration of the framework, probability distributions of the different control strategies are compared and the optimal strategy is chosen, according to the attitude of the decision-maker towards risk. Such a framework can be considered as a new standardised approach for comparing and selecting animal health control strategies, by integrating technical and economic data and principles.

Animal Diseases↗
PubMed2003

A Bayesian framework for combining heterogeneous data sources for gene function prediction (in Saccharomyces cerevisiae).

Genomic sequencing is no longer a novelty, but gene function annotation remains a key challenge in modern biology. A variety of functional genomics experimental techniques are available, from classic methods such as affinity precipitation to advanced high-throughput techniques such as gene expression microarrays. In the future, more disparate methods will be developed, further increasing the need for integrated computational analysis of data generated by these studies. We address this problem with MAGIC (Multisource Association of Genes by Integration of Clusters), a general framework that uses formal Bayesian reasoning to integrate heterogeneous types of high-throughput biological data (such as large-scale two-hybrid screens and multiple microarray analyses) for accurate gene function prediction. The system formally incorporates expert knowledge about relative accuracies of data sources to combine them within a normative framework. MAGIC provides a belief level with its output that allows the user to vary the stringency of predictions. We applied MAGIC to Saccharomyces cerevisiae genetic and physical interactions, microarray, and transcription factor binding sites data and assessed the biological relevance of gene groupings using Gene Ontology annotations produced by the Saccharomyces Genome Database. We found that by creating functional groupings based on heterogeneous data types, MAGIC improved accuracy of the groupings compared with microarray analysis alone. We describe several of the biological gene groupings identified.

Algorithms↗
PubMed1979

A computer program for testing average partial association in three-way contingency tables (PARCAT).

PARCAT is a computer program which implements alternative tests for average partial association in three-way contingency tables within the framework of the product multiple hypergeometric probability model. Primary attention is directed at the relationship between two of the variables, controlling for the effects of a covariable. This approach is essentially a multivariate extension of the Cochran/Mantel-Haenszel test to sets of (s x r) tables. A set of scores such as uniform, ridits, or probits can be assigned to categories which are ordinally scaled. In particular, if ridit scores with midranks assigned for ties are utilized, this procedure is equivalent to a partial Kruskal-Wallis test when one variable is ordinally scaled, and is equivalent to a partial Spearman rank correlation test when both variables are ordinally scaled.

Age Factors↗
PubMed2006

Finding function: evaluation methods for functional genomic data.

BACKGROUND: Accurate evaluation of the quality of genomic or proteomic data and computational methods is vital to our ability to use them for formulating novel biological hypotheses and directing further experiments. There is currently no standard approach to evaluation in functional genomics. Our analysis of existing approaches shows that they are inconsistent and contain substantial functional biases that render the resulting evaluations misleading both quantitatively and qualitatively. These problems make it essentially impossible to compare computational methods or large-scale experimental datasets and also result in conclusions that generalize poorly in most biological applications. RESULTS: We reveal issues with current evaluation methods here and suggest new approaches to evaluation that facilitate accurate and representative characterization of genomic methods and data. Specifically, we describe a functional genomics gold standard based on curation by expert biologists and demonstrate its use as an effective means of evaluation of genomic approaches. Our evaluation framework and gold standard are freely available to the community through our website. CONCLUSION: Proper methods for evaluating genomic data and computational approaches will determine how much we, as a community, are able to learn from the wealth of available data. We propose one possible solution to this problem here but emphasize that this topic warrants broader community discussion.

Algorithms↗
PubMed1993

[Sleep analysis computer in diagnosis of sleep-related respiratory disorders].

Sleep related breathing disorders influence the structure of sleep by considerably modifying the ratios of the individual sleep stages. The sleep analyses carried out by polysomnography in the diagnosis of sleep related breathing disorders have so far been evaluated manually according to the criteria of Rechtschaffen and Kales, since automatic systems do not permit standardised evaluation as yet. Automatic sleep analyses via SAC, however, has been developed further in recent years and has widened its scope and efficiency. It is now possible to perform a comprehensive sleep analysis via SAC by means of modified criteria after Rechtschaffen and Kales. The SAC determines individual curves in the EEG and EOG and includes in addition to the EEG parameters an automatic apnoea detection as well as detailed breathing and oxygen saturation analyses. The Sleep Analysis Computer (SAC) records 15 parameters (2 EEG, 2 EOG, 2 EMG, ECG, NAF, thoracic and abdominal breathing curves, oxygen saturation, body posture, optionally blood pressure = RR, CPAP etc.). This means that all the parameters required for diagnosing sleep related breathing disorders as well as their differential diagnosis can be determined. Within the framework of a blood pressure study, 16 patients (average 45.5 SD 4.6 years) were subjected to SAC measurement in addition to conventional PSG. The computer recordings were evaluated according to apnoea index, the form of the apnoea and the oxygen saturation desaturations. The evaluation yielded the following pattern: 4 patients with AI < 10, 8 patients with AI between 10 and 20, 4 patients with AI > 20. Obstructive apnoeas were seen in 6 patients, mixed apnoeas in 8 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Cortex↗
PubMed2002

Global gene expression profiling in Escherichia coli K12. The effects of leucine-responsive regulatory protein.

Leucine-responsive regulatory protein (Lrp) is a global regulatory protein that affects the expression of multiple genes and operons in bacteria. Although the physiological purpose of Lrp-mediated gene regulation remains unclear, it has been suggested that it functions to coordinate cellular metabolism with the nutritional state of the environment. The results of gene expression profiles between otherwise isogenic lrp(+) and lrp(-) strains of Escherichia coli support this suggestion. The newly discovered Lrp-regulated genes reported here are involved either in small molecule or macromolecule synthesis or degradation, or in small molecule transport and environmental stress responses. Although many of these regulatory effects are direct, others are indirect consequences of Lrp-mediated changes in the expression levels of other global regulatory proteins. Because computational methods to analyze and interpret high dimensional DNA microarray data are still an early stage, much of the emphasis of this work is directed toward the development of methods to identify differentially expressed genes with a high level of confidence. In particular, we describe a Bayesian statistical framework for a posterior estimate of the standard deviation of gene measurements based on a limited number of replications. We also describe an algorithm to compute a posterior estimate of differential expression for each gene based on the experiment-wide global false positive and false negative level for a DNA microarray data set. This allows the experimenter to compute posterior probabilities of differential expression for each individual differential gene expression measurement.

Base Sequence↗
PubMed1999

Fonetix: building virtual speech therapy practicum over the Internet.

The purpose of this project is to create an advanced interactive speech therapy site that can be used over the World Wide Web (WWW). This multimedia site, which we have named Fonetix, includes animation of articulation, audio, and video display and capture. The main function of Fonetix is to augment the role a speech language pathologist can play while interacting with patients remotely over the Internet. High quality consultative services via the Internet means that all individuals, regardless of their locale, can have access to best possible service. Fonetix could allow a patient, no matter how remote they are, to have access to the services often only available in major centres. The basic research work into Fonetix has been completed and a functional model has been constructed that will run on any type of personal computer with standard audio and video cards, therefore avoiding expensive equipment requirements. The ultimate goal of the Fonetix system is to create a multi-functional framework that will allow meaningful interactions via the Internet in a variety of circumstances--including clinical, educational and social functions.

Diagnosis, Computer-Assisted↗
PubMed2005

On the design of computer-based models for integrated environmental science.

The current research agenda in environmental science is dominated by calls to integrate science and policy to better understand and manage links between social (human) and natural (nonhuman) processes. Freshwater resource management is one area where such calls can be heard. Designing computer-based models for integrated environmental science poses special challenges to the research community. At present it is not clear whether such tools, or their outputs, receive much practical policy or planning application. It is argued that this is a result of (1) a lack of appreciation within the research modeling community of the characteristics of different decision-making processes including policy, planning, and (2) participation, (3) a lack of appreciation of the characteristics of different decision-making contexts, (4) the technical difficulties in implementing the necessary support tool functionality, and (5) the socio-technical demands of designing tools to be of practical use. This article presents a critical synthesis of ideas from each of these areas and interprets them in terms of design requirements for computer-based models being developed to provide scientific information support for policy and planning. Illustrative examples are given from the field of freshwater resources management. Although computer-based diagramming and modeling tools can facilitate processes of dialogue, they lack adequate simulation capabilities. Component-based models and modeling frameworks provide such functionality and may be suited to supporting problematic or messy decision contexts. However, significant technical (implementation) and socio-technical (use) challenges need to be addressed before such ambition can be realized.

Computer Simulation↗
PubMedDate not supplied

The tracking of boundaries in multidimensional medical images.

We became interested in the problems associated with boundary tracking in multidimensional spaces due to our involvement in medical imaging. We give as background our motivation from medicine. We define objects and their surfaces in discrete three-dimensional space and the state of the art in three-dimensional boundary tracking. Discussed are generalizations, conjectures, and open problems. Finally, we discuss what seems to us a suitable mathematical framework for future research in this area.

Algorithms↗
PubMed2005

Systems Biology-an interdisciplinary approach.

System-level approaches in biology are not new but foundations of "Systems Biology" are achieved only now at the beginning of the 21st century [Kitano, H., 2001. Foundations of Systems Biology. MIT Press, Cambridge, MA]. The renewed interest for a system-level approach is linked to the progress in collecting experimental data and to the limits of the "reductionist" approach. System-level understanding of native biological and pathological systems is needed to provide potential therapeutic targets. Examples of interdisciplinary approach in Systems Biology are described in U.S., Japan and Europe. Robustness in biology, metabolic engineering and idiotypic networks are discussed in the framework of Systems Biology.

Cell Physiological Phenomena↗
PubMed2006

Simulating the 'other-race' effect with autoassociative neural networks: further evidence in favor of the face-space model.

Other-race (OR) faces are less accurately recognized than same-race (SR) faces, but faster classified by race. This phenomenon has often been reported as the 'other-race' effect (ORE). Valentine (1991 Quarterly Journal of Experimental Psychology A: Human Experimental Psychology 43 161-204) proposed a theoretical multidimensional face-space model that explained both of these results, in terms of variations in exemplar density between races. According to this model, SR faces are more widely distributed across the dimensions of the space than OR faces. However, this model does not quantify nor state the dimensions coded within this face space. The aim of the present study was to test the face-space explanation of the ORE with neural network simulations by quantifying its dimensions. We found the predicted density properties of Valentine's framework in the face-projection spaces of the autoassociative memories. This was supported by an interaction for exemplar density between the race of the learned face set and the race of the faces. In addition, the elaborated face representations showed optimal responses for SR but not for OR faces within SR face spaces when explored at the individual level, as gender errors occurred significantly more often in OR than in SR face-space representations. Altogether, our results add further evidence in favor of a statistical exemplar density explanation of the ORE as suggested by Valentine, and question the plausibility of such coding for faces in the framework of recent neuroimaging studies.

Asian People↗
PubMed2003

Internal dosimetry of uranium isotopes using Bayesian inference methods.

A group of personnel at Los Alamos National Laboratory is routinely monitored for the presence of uranium isotopes by urine bioassay. Samples are analysed by alpha spectroscopy, and the results are examined for evidence of an intake of uranium. Because the measurement uncertainties are often comparable to the quantities of material we wish to detect, statistical considerations are crucial for the proper interpretation of the data. The problem is further complicated by the significant, but highly non-uniform, presence of uranium in local drinking water and, in some cases, food supply. Software originally developed for internal dosimetry of plutonium has been adapted to the problem of uranium dosimetry. The software uses an unfolding algorithm to calculate an approximate Bayesian solution to the problem of characterising any intakes which may have occurred, given the history of urine bioassay results for each individual in the monitored population. The program uses biokinetic models from ICRP Publications 68 and later, and a prior probability distribution derived empirically from the body of uranium bioassay data collected at Los Alamos over the operating history of the laboratory. For each individual, the software creates a posterior probability distribution of intake quantity and solubility type as a function of time. From this distribution, estimates are made of the cumulative committed dose (CEDE) to each individual. Results of the method are compared with those obtained using an earlier classical (non-Bayesian) algorithm for uranium dosimetry. We also discuss the problem of distinguishing occupational intakes from intake of environmental uranium, within a Bayesian framework.

Algorithms↗