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Results for “Model interpretability”

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At least 271 records · Page 15Linked to original sources

PubMed1997

Anatomical variability and functional ability of vascular trees modeled by constrained constructive optimization.

The aim of this study was to investigate the extent that functional capability of vascular trees is related to anatomical variability. To these ends we used the method of Constrained Constructive Optimization (CCO) to generate optimized computer models of coronary arterial trees. All these model trees were optimized according to the same principle under equal boundary conditions of pressures and flows. However, by stochastically casting the locations of the terminal segments, different tree structures were generated, each of which conformed to the same boundary conditions. The structural variability of these models was interpreted as the correlate of the anatomical variability found in real arterial trees. The advantage that computer model trees are known in numerical detail was exploited to perform comprehensive and exact classifications of all segments into bifurcation levels, STRAHLER orders and composite vessels, and to compute the area expansion ratio. The unexpected result was that, despite striking visual differences in anatomical structure, the model trees were almost identical with regard to functional performance. We conclude that models optimized on the computer for a given perfusion task show little differences in their morphometric parameters even if they differ considerably regarding the course of the large vessels.

Computer Simulation↗

PubMed1990

Comments on a time-dependent version of the linear-quadratic model.

The accuracy and interpretation of the "LQ + time" model (E = D(alpha + beta d) - gamma T) are discussed. Evidence is presented, based on data in the literature, that this model does not accurately describe the changes in isoeffect dose occurring with protraction of the overall treatment time during fractionated irradiation of the lung. This lack of fit of the model explains, in part, the surprisingly large values of gamma/alpha that have been derived from experimental lung data. The large apparent time factors for lung suggested by the model are also partly explained by the fact that gamma T/alpha, despite having units of dose, actually measures the influence of treatment time on the effect scale, not the dose scale, and is shown to consistently overestimate the change in total dose. The unusually high values of alpha/beta that have been derived for lung using the model (approximately 5 Gy) are shown to be influenced by the method by which the model was fitted to data. Reanalyses of the data using a more statistically valid regression procedure produce estimates of alpha/beta more typical of those usually cited for lung (approximately 3 Gy). Most importantly, published isoeffect data from lung indicate that the true deviation from the linear-quadratic (LQ) model is nonlinear in time, instead of linear, and also depends on other factors such as the effect level and the size of dose per fraction. Thus, we do not advocate the use of the "LQ + time" expression as a general isoeffect model.

Animals↗

PubMedDate not supplied

Multiplicative and additive models with external controls in a cohort study of cancer mortality.

The use of additive and multiplicative hazard models is examined for a cohort study of 2696 women followed up for 12 years. The multiplicative model implied that women with a haemoglobin level less than 12 g/dl were at higher risk from cancer, and the additive model showed that this risk was confined to women after the menopause. Despite difficulties in fitting and in interpretation, additive model can be useful in the analysis of cohort studies.

Adult↗

PubMed1995

Some limitations of spatio temporal source models.

The spatio temporal source model (STSM) interprets the successive scalp topographies of an electrophysiological event as the summed activity of a few fixed generators. This modeling methodology is expected to provide a unique solution for a fixed number of sources. Because in general there is no "a priori" available physiological information, independent criteria need to be applied for determining the correct number of sources (Ns). This study illustrates theoretically as well as in simulations, that the existence of a unique solution can only be claimed when Ns is known a priori. Since most of the methods proposed for estimate Ns are not accurate as illustrated here, STSM may result in unpredictable non-physiological solutions. Basic modeling aspects and additional factors affecting reliability of STSM such as those related to the optimization process associated to the source parameter search are discussed. Some of the possible inverse solutions are illustrated in our simulations. Our main conclusion is the need to improve STSM before claims about neural generator localization can be accepted. We will also discuss, how attempts to apply STSM to clinical data, apparently supporting their reliability, are plagued with incorrect assumptions and do not justify the expectancy aroused about such models. We discuss some ways for improving STSM and the need to develop measures to evaluate their reliability, independent of the physiological plausibility of the solutions obtained. Finally we propose two mathematical measures that can be incorporated to the optimization process to contribute to the evaluation of its performance.

Algorithms↗

PubMed1970

Conduction mechanisms in Lillie's iron-wire model of nerve.

Based on theory and experiment, we found that the conduction through the oxide film in Lillie's iron-wire model is dominated by Schottky emission at low fields (below 10(6) v/cm), by electron tunneling from trap to trap at intermediate fields and by direct tunneling (Fowler-Nordheim type) at higher fields (above 3 x 10(6) v/cm). The trap-to-trap tunneling is considered to give rise to the negative resistance and the fixed position of the current maximum as observed. Some of the nervelike properties of the Lillie's model are interpreted on this tunneling mechanism.

Electrophysiology↗

PubMed1996

Design and analysis of lipid tracer kinetic studies.

A fundamental problem in lipid metabolism is designing experiments to quantitate the kinetics of the plasma lipids and lipoproteins in the body. Tracers have been used extensively. In this review, we will combine our knowledge of the theory and application of tracer kinetic studies to discuss current state of the art methodologies for lipid metabolism. We will review the use of stable and radioactive isotopes pointing out the importance of the measurement variables, and the theory and application of noncompartmental and compartmental models to interpret the data.

Humans↗

PubMed1978

General theory of critical periods and development of obesity.

The general systems theory (GST), the general theory of organization (GTO), and the general theory of critical periods (GTCP) have been applied to some nutritional problems. This theoretical approach seems to be in good agreement with most of the data of the literature and with the personal experience, pointing at the possibility to use a simple general model to interpret the complex problem of obesity.

Critical Period, Psychological↗

PubMed1991

A framework for the interpretation of first-order interaction in logit modeling.

Several suggestions have been tendered for interpreting first-order interaction in log-linear analysis. Occasionally these methods result either in a loss of information or in results that are difficult to grasp on an intuitive level. It is argued that interpreting effect parameters in terms of odds ratios provides an elegant and intuitively appealing conceptual framework that has great generality across models. The interaction term then resembles a cross-product term in linear regression. In both forms of analysis, the partial effect of a given predictor on the response is composed of a constant and a correction that is a function of the other predictor involved in the interaction. This framework is especially appealing for models in which the logit is based on a bifurcation of the dependent variable. Although odds ratios are still useful for summarizing effects on polytomous dependent variables, greater caution must be exercised to avoid misleading interpretations.

Humans↗

PubMed1994

Young children's ability to understand a model as a spatial representation.

Children's ability to understand that a real environment can be represented in a symbolic form (i.e., by a model) is an important developmental achievement. Researchers have claimed that children who are just 3 years of age appreciate models as representations. This research was based on tasks that involved having young children use a model to locate a hiding place in an actual room. In this article, however, we point out the difficulties in interpreting previous model tasks, and we describe two studies that showed that young 3-year-olds could perform model tasks successfully when the hiding place they were looking for was a unique place in the model (and room). When the hiding place was unique, the children had to note only that place and they needed no further knowledge about the relationship between the model and the room. When the hiding place was one of two identical places, however, the children needed to take spatial relationships into account to distinguish the correct place, and young 3-year-olds were unable to do this. Four-year-olds were able to use spatial relationships to distinguish identical places when the model was aligned with the space it represented, but they had difficulty when the model was not aligned. Five-year-olds could use spatial relationships effectively between one model space and another whether or not the model was aligned.

Child↗

PubMed1994

Application of 3-dimensional homology modeling of cytochrome P450 2B1 for interpretation of site-directed mutagenesis results.

Three-dimensional structures of cytochrome P450 2B1 were modeled based on the crystallographic structure of P450cam. The effect of the alignment, loop choice, and minimization with or without water was assessed. Although final models were similar in overall structure, the identity of active site residues depended upon the alignment. An example is Phe-206, which may or may not form part of the active site. The choice of the loop conformation had a lesser effect, while including water in the final minimization step was essential for preserving the shape and size of the active site. The best model (model 2) was in good agreement with the data from site-directed mutagenesis studies, and correctly predicted the effect of substitutions at 9 out of 10 amino acid positions. Thus, residues important for P450 2B1 activity, such as Ile-114, Phe-206, Ile-290, Thr-302, Val-363, and Gly-478, constitute part of the active site and are able to interact with the substrate androstenedione through hydrophobic interactions. On the other hand, Ser-303, Ser-360 and Lys-473 are far from the active site and/or cannot interact with the substrate, in agreement with experimental data. The model indicates other residues likely to be important for enzyme function, such as Tyr-111, Leu-209, Ile-477, and Ile-480, which can be tested experimentally. The substrate may assume numerous binding orientations consistent with observed patterns of hydroxylation at C15 and C16. The replacement in the model of certain amino acid residues to mimic residue substitutions from site-directed mutagenesis studies and docking of the substrate into the modified active site allowed a plausible explanation for alterations in regio- and stereospecificities of some mutants of P450 2B1, such as Gly-478-->Ala or Val-363-->Ala.

Amino Acid Sequence↗

PubMed1991

Combining physiologic models and symbolic methods to interpret time-varying patient data.

This paper describes a methodology for representing and using medical knowledge about temporal relationships to infer the presence of clinical events that evolve over time. The methodology consists of three steps: (1) the incorporation of patient observations into a generic physiologic model, (2) the conversion of model states and predictions into domain-specific temporal abstractions, and (3) the transformation of temporal abstractions into clinically meaningful descriptive text. The first step converts raw observations to underlying model concepts, the second step identifies temporal features of the fitted model that have clinical interest, and the third step replaces features represented by model parameters and predictions into concepts expressed in clinical language. We describe a program, called TOPAZ, that uses this three-step methodology. TOPAZ generates a narrative summary of the temporal events found in the electronic medical record of patients receiving cancer chemotherapy. A unique feature of TOPAZ is its use of numeric and symbolic techniques to perform different temporal reasoning tasks. Time is represented both as a continuous process and as a set of temporal intervals. These two temporal models differ in the temporal ontology they assume and in the temporal concepts they encode. Without multiple temporal models, this diversity of temporal knowledge could not be represented.

Adult↗

PubMed1975

Intrauterine pressure wave form characteristics in hypocontractile labor before and after oxytocin administration.

The data demonstrate that the contractions of hypocontractile active labor and normal spontaneous labor are different in several measures in addition to maximal amplitude. Furthermore, when the pathophysiology is corrected by the use of oxytocin, the contractions resemble those of normal spontaneous labor except in the maximal rate of tension development. Our data tend to support the subcellular model of uterine contractility, although the incompleteness of these models limits interpretation.

Adrenocorticotropic Hormone↗

PubMed2026

Prediction of antimicrobial minimum inhibitory concentration from bacterial genomes using a scalable and interpretable machine learning approach.

Although machine learning models can predict antimicrobial susceptibility from bacterial whole genome sequencing (WGS), state-of-the-art approaches are computationally demanding or dependent on knowledge of genetic resistance determinants. Here, we describe an efficient data-driven approach to predicting minimum inhibitory concentration (MIC) by progressively extending and refining predictive genome segments, independent of prior knowledge of resistance determinants. Resultant models had high interpretability - known and potentially novel resistance determinants were captured. Using 762 clinical E. coli strains, 71.6% of predictions were within one dilution of the measured MIC. Models trained with this algorithm generalised better onto external data (F1 score = 0.85) compared with alternative models trained on annotated resistance determinants (F1 = 0.82) or k-mer counts (F1 = 0.74). Computational demands were low (RAM usage 23.6GB vs 38.8GB for k-mer model). These advantages represent an important advance in predicting antimicrobial susceptibility from WGS, with potential applications for clinical diagnostics, drug development, and surveillance.

Journal Article↗

PubMed1996

Cell cycle time of murine neopallial cells in vitro.

Disaggregated glial cells from newborn CD1 mouse neopallia were cultured in low concentration (4.2 x 10(3) cells/cm2) for 72 hr and then either pulse labeled with BrdU by one 2-hr pulse at various times of culturing or continuously labeled for various lengths of time. At the end of incubation, the cells were fixed and immunoreacted with BrdU. All BrdU+ and BrdU- cell nuclei were counted in an area of 4.84 cm2. A three-compartment model for interpretation of the experimental data was developed consisting of active proliferating cells, non-active cells with proliferating potential, and nonproliferating cells. The model is based on assumptions of time invariance of culture conditions, random re-entry of cells into cell cycle and random exit from the proliferating pool. Furthermore, it is assumed that average values are representative for describing the numbers of cells in specific compartments as functions of time. A set of relationships representing the numbers of labeled cells for pulse labeling and continuous labeling assays is derived from these assumptions and the generally accepted representation of cell progress through the cell cycle, i.e., a genetically predetermined sequence of post-mitosis rest phase, S-phase, pre-mitosis rest phase, and mitosis. These relationships are used to evaluate the S-phase time tau s and cell cycle time tau c of proliferating cells. Under our particular conditions, we obtain approximately tau s = 8 hr and tau c = 16 hr, respectively. The applicability of the model and possible distorting factors are discussed.

Animals↗

PubMed1991

Domain of validity of classical models of leucine metabolism assessed by compartmental modeling.

Whole-body modeling of in vivo leucine (an essential amino acid) metabolism is fundamentally difficult due to the complexity of the system. This has favored the use of two simple kinetic models, the so-called primary and reciprocal pool models, to interpret tracer data, but their domain of validity is uncertain. We define here the error of these two approaches by using comprehensive compartmental models of leucine metabolism as true representations of the leucine system. Of particular interest is the comparison of the two simple models with an 11-compartment model characterized by a rich intracellular compartmentation that has recently been proposed as a sound physiological description of the system. Formulas are derived that define in structural terms the error of the primary and reciprocal pool models.

Humans↗

PubMed1995

Nonlinear autoregressive analysis of the 3/s ictal electroencephalogram: implications for underlying dynamics.

In a previous study, nonlinear autoregressive (NLAR) models applied to ictal electroencephalogram (EEG) recordings in six patients revealed nonlinear signal interactions that correlated with seizure type and clinical diagnosis. Here we interpret these models from a theoretical viewpoint. Extended models with multiple nonlinear terms are employed to demonstrate the independence of nonlinear dynamical interactions identified in the 'NLAR fingerprint' of patients with 3/s seizure discharges. Analysis of the role of periodicity in the EEG signal reveals that the fingerprints reflect the dynamics not only of the periodic discharge itself, but also of the fluctuations of each cycle about an average waveform. A stability analysis is used to make qualitative inferences concerning the network properties of the ictal generators. Finally, the NLAR fingerprint is analyzed in the context of Volterra-Weiner theory.

Electroencephalography↗

PubMed1985

Model-independent electron spin resonance for measuring order of immobile components in a biological assembly.

A model-independent description of the angular orientation distribution of elements in an ordered biological assembly is applied to the electron spin resonance (ESR) technique. As in a previous model-independent treatment of fluorescence polarization (Burghardt, T.P., 1984, Biopolymers, 23:2383-2406) the elemental order is described by an angular distribution of molecular frames with one frame fixed in each element of the assembly. The distribution is expanded in a complete orthonormal set of functions. The coefficients of the series expansion (the order parameters) describe the orientation distribution of the elements in the assembly without reference to a model and can be obtained from the observed spectrum. The method establishes the limitations of ESR in detecting order in the assembly by determining which distribution coefficients the technique can detect. A method of determining the order parameters from an ESR spectra, using a set of ESR basis spectra, is developed. We also describe a treatment that incorporates the actual line shape measured from randomly oriented, immobile elements. In this treatment, no model-dependent assumptions about the line shape are required. We have applied the model-independent analysis to ESR spectra from spin-labeled myosin cross-bridges in muscle fibers. The results contain detailed information on the spin-probe angular distribution and differ in interesting ways from previous model-dependent interpretations of the spectra.

Animals↗

PubMed1987

[The results of research on the biological effects of neutrons].

A study was made of the peculiarities of the biological effect of neutrons as compared to gamma-radiation. A number of biological models were proposed for interpretation of the phenomenon: a biophysical model of mutations and cell inactivation, a model for interpretation of the formation of a radioresistant and radiosensitive fraction.

Animals↗