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[Knowledge-based diagnosis and therapeutic recommendations with fuzzy-set theory methods in patients with acute lung failure (ARDS)].

OBJECTIVE: Since the treatment of patients with severe ARDS using the extracorporal lung assist (ECLA) methods remains a cost intensive and speculative procedure, a knowledge based computer system should be created and evaluated in order to support clinical decisions. METHODS: The model was based on the fuzzy set theory and therefore able to give decisions between yes and no, that means that a criterion could also be fulfilled to 35% or 80% for example. The development of this computer program consists of two steps: first, the entry criteria for the ECLA therapy were established within a framework of an international evaluation of clinical data from 3 centres (Berlin, Marburg, Vienna). Here, inherent vagueness, uncertainty of the occurrence and limited availability of medical data are to be considered to establish a useful tool. Secondly, this was done by grouping and weighting of parameters by the system and the status of each patient or patient group was assigned by the percentage of fulfillment of the criterion. RESULTS: By using a mixed sample of patients from these three centres, the fulfillment of entry criteria according either to definitions of Berlin or to definition of Marburg was different (68% versus 36%). Other differences (36% vs. 22% and 68% vs. 60%) were found between the fuzzy based score and the crisp score which represents the usually performed method. CONCLUSIONS: This now preevaluated minimal data set to describe severe ARDS patients based on the fuzzy set theory may be useful to evaluate patients for ECLA therapy or for another controlled ARDS-therapy.

Acute Disease↗

The importance of computer observation of postoperative complications in ophthalmology presented on the model of postoperative complications following cataract surgery.

Medical documentation is getting more extensive, it is not standardised and can hardly be used to provide the exact and proper feedback. The crisis of data storage, processing and uninterrupted flow of information is becoming concial in the medical institutions as well. An example of informatic model of observation of postoperative complications following cataract surgery is presented in this work. The model has a very flexible pattern, and can, therefore, with minor changes, be used in observation of all postoperative complications in ophthalmology. It is based on the use of personal computer with professional software support (data base III programme was used for creation of data base, while statistical graphic analysis was carried out by following programmes: MICROSTAT, ABSTAT, STATGRAPHIC and FRAMEWORK). It has to be pointed out that any doctor, after only a short (optional) education, could prepare such models for his own purposes, and could thus assist in overcoming the information in medicine. In conclusion, the authors state computer is simple to work with, fast, economical and precise. Computerisation of health service shall include it in one of the aspects of practical realisation of the third technological revolution.

Cataract Extraction↗

Tomographic image reconstruction based on a content-adaptive mesh model.

In this paper, we explore the use of a content-adaptive mesh model (CAMM) for tomographic image reconstruction. In the proposed framework, the image to be reconstructed is first represented by a mesh model, an efficient image description based on nonuniform sampling. In the CAMM, image samples (represented as mesh nodes) are placed most densely in image regions having fine detail. Tomographic image reconstruction in the mesh domain is performed by maximum-likelihood (ML) or maximum a posteriori (MAP) estimation of the nodal values from the measured data. A CAMM greatly reduces the number of unknown parameters to be determined, leading to improved image quality and reduced computation time. We demonstrated the method in our experiments using simulated gated single photon emission computed tomography (SPECT) cardiac-perfusion images. A channelized Hotelling observer (CHO) was used to evaluate the detectability of perfusion defects in the reconstructed images, a task-based measure of image quality. A minimum description length (MDL) criterion was also used to evaluate the effect of the representation size. In our application, both MDL and CHO suggested that the optimal number of mesh nodes is roughly five to seven times smaller than the number of projection bins. When compared to several commonly used methods for image reconstruction, the proposed approach achieved the best performance, in terms of defect detection and computation time. The research described in this paper establishes a foundation for future development of a (four-dimensional) space-time reconstruction framework for image sequences in which a built-in deformable mesh model is used to track the image motion.

Algorithms↗

Comparison of some control strategies for three-compartment PK/PD models.

In drug therapy, effective dosage strategies are needed to maintain target drug effects. The relationship between drug dose and drug effect is often described by pharmacokinetic/pharmacodynamic (PK/PD) models where typically the PK model has a multicompartment form and the PD model is the sigmoidal Emax model. The parameters in the PK/PD model are generally unknown in the individual patient, although prior knowledge may be available and can be updated after measurements of drug effect are taken during the therapy. This fact, together with the complexity of the PK/PD model, makes the control problem complex. This paper investigates several control strategies in the framework of a three-compartment PK model plus an effect site with a PD model. Using computer simulations under different assumptions, we show that a MAP (maximum a posteriori) Bayesian type of strategy is effective, nevertheless in high-risk situations a stochastic control strategy hedging against estimation errors provides better performance at computational cost.

Bayes Theorem↗

Uniform system for the evaluation of substances. I. Principles and structure.

In April 1994, the first version of the Uniform System for the Evaluation of Substances (USES 1.0) was launched to comply with an action point of the Netherlands National Environmental Policy Plan. USES is a tool for the rapid, quantitative assessment of the hazards and risks of chemical substances, including new substances, existing substances, agricultural pesticides and biocides. It was developed to be applied as a decision-support system by the central government, by industry and institutes in the private sector and by international fora. Since hazard and risk assessment must be transparent to all users and easy to perform, USES 1.0 is well documented and available as a computer program. An overview of this system will be presented including its objectives, the national and international framework, the general principles involved, as well as the structure and the content of the models used.

Animals↗

Introducing spatio-temporal reasoning into the inverse problem in electroencephalography.

Studying the Brain's Electrical and Magnetic Signals (BEMS) requires the contribution of many area of research that include anatomy, neurophysiology and electromagnetic theory. NEUROLAB is a framework dedicated to the study of brain disorders. Upon completion, it should provide users with an intelligent computational environment that incorporates qualitative and quantitative models of the brain and head, and a model for representing and reasoning about time and space. Spatio-temporal knowledge of a given problem is represented as a constraint network where to each node of the network are attached temporal and spatial variables that must satisfy the constraints defined by the arch labels connecting the nodes. In this paper, we show how temporal reasoning can be combined with spatial descriptions to produce different scenarios of possible seizure spread. These scenarios can provide a priori information for the inverse problem the role of which is to localise the sources of the observed BEMS.

Artificial Intelligence↗

Early mortality among triplets in the United States: black-white disparity.

OBJECTIVE: In this study, we sought to estimate the black-white gap in early mortality among triplets. STUDY DESIGN: This was a retrospective cohort study on triplets delivered in the United States from 1995 to 1997. We computed relative risks for early mortality among triplets born to black mothers using the generalized estimating equation framework. RESULTS: There were 1317 black and 14,364 white triplets analyzed. Black triplets were twice as likely to have neonatal and infant mortality compared with whites (Odds ratio [OR], 2.00, 95% CI, 1.38-2.77; and OR, 2.20, 95% CI, 1.59-3.00, respectively). The widest disparity was observed postneonatally, with black triplets sustaining a level of risk almost 4-fold that of whites (OR, 3.60, 95% CI, 2.10-6.10). Stillbirth and perinatal mortality were comparable for both races. CONCLUSION: Black-white disparity for early mortality among triplets was widest postneonatally. This finding bears important clinical and public health implications.

Adult↗

Single-channel autocorrelation functions: the effects of time interval omission.

We present a general mathematical framework for analyzing the dynamic aspects of single channel kinetics incorporating time interval omission. An algorithm for computing model autocorrelation functions, incorporating time interval omission, is described. We show, under quite general conditions, that the form of these autocorrelations is identical to that which would be obtained if time interval omission was absent. We also show, again under quite general conditions, that zero correlations are necessarily a consequence of the underlying gating mechanism and not an artefact of time interval omission. The theory is illustrated by a numerical study of an allosteric model for the gating mechanism of the locust muscle glutamate receptor-channel.

Computer Simulation↗

Surface dyslexia in a Japanese patient with semantic dementia: evidence for similarity-based orthography-to-phonology translation.

We studied the reading performance of a Japanese-speaking patient, TI, with bilateral but asymmetrical (left more than right) temporal-lobe atrophy, severe anomia, and poor word comprehension. Most Japanese kanji characters correspond to several different legitimate pronunciations in different contexts, with varying degrees of correspondence consistency. TI made many errors in reading aloud words that violate statistically typical character-sound correspondences, especially for less common words, but had relatively preserved ability to read aloud strings in which the assignment of the typical pronunciation for each component character yields the correct pronunciation for the whole word. The degree of consistency of character-sound correspondences affected his performance on both words and nonwords in a graded manner. One interpretation is that TI's surface dyslexic reading reflects intact direct computation of phonology from orthography, but without the additional constraint from word meaning that is, in this framework, considered critical for correct pronunciation of lower-frequency words with atypical character-sound correspondences. Another interpretation is that TI's performance reflects partially damaged lexical knowledge of whole-word orthography and phonology, coupled with spared sublexcal knowledge of character-sound correspondence rules. Whichever of these interpretations is preferred, this study offers the most detailed information yet available on the characteristics of surface dyslexia in Japanese.

Dementia↗

Abstract temporal diagnosis in medical domains.

Most current model-based diagnosis formalisms and algorithms are defined only for static systems, which is often inadequate for medical reasoning. In this paper we describe a model-based framework plus algorithms for diagnosing time-dependent systems where we can define qualitative temporal scenarios. Complex temporal behavior is described within a logical framework extended by qualitative temporal constraints. Abstract observations aggregate from observations at time points to assumptions over time intervals. These concepts provide a very natural representation and make diagnosis independent of the number of actual observations and the temporal resolution. The concept of abstract temporal diagnosis captures in a natural way the kind of indefinite temporal knowledge which is frequently available in medical diagnoses. We use viral hepatitis B (including a set of real hepatitis B data) to illustrate and evaluate our framework. The comparison of our results with the results of HEPAXPERT-I is promising. The diagnosis computed in our system is often more precise than the diagnosis in HEPAXPERT-I and we detect inconsistent data sequences which cannot be detected in the latter system.

Algorithms↗

Transmission dynamics and control options for Echinococcus granulosus.

Cystic echinococcosis, caused by the larval stage of Echinococcus granulosus, is a global public health problem. Whilst in a few localities, such as New Zealand, the parasite has been effectively controlled or even eradicated, in most endemic regions it remains a persistent problem. In some areas, such as the former Soviet Union, the disease incidence in humans has increased rapidly in recent years. It is important to have an understanding of the transmission dynamics, both between dogs and domestic livestock where the parasite maintains itself and from dogs to people. It is from this knowledge that effective control measures can be devised to reduce the prevalence of the parasite in animals and hence reduce the incidence of human disease. Mathematical models to describe the transmission of the parasite and the effects of different control strategies were first proposed over twenty years ago. Since then further information has been acquired, new technology has been developed and better computing technology has become available. In this review, we summarise these developments and put together a theoretical framework on the interpretation of surveillance information, how this affects transmission and how this information can be exploited to develop new intervention strategies for the control of the parasite. In particular, the parasite remains a persistent or re-emerging problem in countries of low economic output where resources for an intensive control programme, that has been successful in rich countries, are not available. By understanding of the transmission biology, including mathematical modelling, alternative and cost-effective means of control can be developed.

Animals↗

Direct observation of host-guest hydrogen bonding in the zeolite NaY/chloroform system by neutron scattering.

The differential H pair distribution function obtained from neutron scattering contrast measurements on hydrogenous and deuterated chloroform adsorbed into zeolite NaY (two molecules per supercage) reveals direct evidence for hydrogen bonding between hydrogen atoms on the sorbate molecule and oxygen atoms of the zeolite framework. A vector between the hydrogen and framework Si/Al atoms is also observed. The results confirm the conclusions drawn from previous vibrational spectroscopy and computer modeling studies.

Journal Article↗

An alternative interpretation of the C-H bond strengths of alkanes.

A new model based on 1,3 repulsive steric interactions (geminal repulsion) is proposed for explaining the variation in the C-H bond strengths of the alkanes. The model builds from the assumption that 1,3 repulsive interactions are the major factor in determining the stability of a C-C or C-H bond in an alkane. From this simple premise, the model successfully reproduces the effect of branching on the stability of alkanes, alkyl radicals, and alkenes. The results suggest that geminal repulsion can provide a simple, unified explanation for these fundamental stability trends. Although previous explanations have been widely accepted, it is shown that the theoretical support for them is relatively shallow and that the current hyperconjugative stabilization model is inconsistent with several experimental and computational results concerning alkyl radicals. In contrast, an explanation based on geminal repulsion provides a general conceptual framework for rationalizing each of these stability trends and is based on a physical effect that is known to play a role in the stability of alkanes and related species.

Journal Article↗

A humanized antibody that binds to the interleukin 2 receptor.

The anti-Tac monoclonal antibody is known to bind to the p55 chain of the human interleukin 2 receptor and to inhibit proliferation of T cells by blocking interleukin 2 binding. However, use of anti-Tac as an immunosuppressant drug would be impaired by the human immune response against this murine antibody. We have therefore constructed a "humanized" antibody by combining the complementarity-determining regions (CDRs) of the anti-Tac antibody with human framework and constant regions. The human framework regions were chosen to maximize homology with the anti-Tac antibody sequence. In addition, a computer model of murine anti-Tac was used to identify several amino acids which, while outside the CDRs, are likely to interact with the CDRs or antigen. These mouse amino acids were also retained in the humanized antibody. The humanized anti-Tac antibody has an affinity for p55 of 3 x 10(9) M-1, about 1/3 that of murine anti-Tac.

Amino Acid Sequence↗

An anatomical model of the gastric system for producing bioelectric and biomagnetic fields.

Between 60 and 70 million people in the United States are affected by gastrointestinal disorders. Many of these conditions are difficult to assess without surgical intervention and accurate noninvasive techniques to aid in clinical assessment are needed. Through the use of a superconducting quantum interference device (SQUID) gradiometer, the weak magnetic field generated as a result of muscular activity in the digestive system can be measured. However, the interpretation of these magnetic recordings remains a significant challenge. We have created an anatomically realistic biophysically based mathematical model of the human digestive system and using this model normal gastric electrical control activity (ECA) has been simulated. The external magnetic fields associated with this gastric ECA have also been computed and are shown to be in qualitative agreement with recordings taken from normal individuals. The model framework thus provides a rational basis from which to begin interpreting magnetic recordings from normal and diseased individuals.

Digestive System Physiological Phenomena↗

Genomic scale sub-family assignment of protein domains.

Many classification schemes for proteins and domains are either hierarchical or semi-hierarchical yet most databases, especially those offering genome-wide analysis, only provide assignments to sequences at one level of their hierarchy. Given an established hierarchy, the problem of assigning new sequences to lower levels of that existing hierarchy is less hard (but no less important) than the initial top level assignment which requires the detection of the most distant relationships. A solution to this problem is described here in the form of a new procedure which can be thought of as a hybrid between pairwise and profile methods. The hybrid method is a general procedure that can be applied to any pre-defined hierarchy, at any level, including in principle multiple sub-levels. It has been tested on the SCOP classification via the SUPERFAMILY database and performs significantly better than either pairwise or profile methods alone. Perhaps the greatest advantage of the hybrid method over other possible approaches to the problem is that within the framework of an existing profile library, the assignments are fully automatic and come at almost no additional computational cost. Hence it has already been applied at the SCOP family level to all genomes in the SUPERFAMILY database, providing a wealth of new data to the biological and bioinformatics communities.

Computational Biology↗

Kink nucleation in the two-dimensional Frenkel-Kontorova model.

A computer simulation of thermofluctuation nucleation of kinks on dislocations and their dynamics is carried out in the framework of the two-dimensional Frenkel-Kontorova model. It is shown that at relatively low temperatures and applied stresses the kinks can appear as a result of developing instability of phonon modes localized in the vicinity of the dislocation. The transition from this mechanism to the ordinary thermofluctuation kink nucleation with temperature increase can reveal itself in the peculiarities of yield stress temperature dependence.

Journal Article↗