SEARCH · PubMed Health

Results for “Model interpretability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources

PubMed2004

Random dynamics of the Morris-Lecar neural model.

Determining the response characteristics of neurons to fluctuating noise-like inputs similar to realistic stimuli is essential for understanding neuronal coding. This study addresses this issue by providing a random dynamical system analysis of the Morris-Lecar neural model driven by a white Gaussian noise current. Depending on parameter selections, the deterministic Morris-Lecar model can be considered as a canonical prototype for widely encountered classes of neuronal membranes, referred to as class I and class II membranes. In both the transitions from excitable to oscillating regimes are associated with different bifurcation scenarios. This work examines how random perturbations affect these two bifurcation scenarios. It is first numerically shown that the Morris-Lecar model driven by white Gaussian noise current tends to have a unique stationary distribution in the phase space. Numerical evaluations also reveal quantitative and qualitative changes in this distribution in the vicinity of the bifurcations of the deterministic system. However, these changes notwithstanding, our numerical simulations show that the Lyapunov exponents of the system remain negative in these parameter regions, indicating that no dynamical stochastic bifurcations take place. Moreover, our numerical simulations confirm that, regardless of the asymptotic dynamics of the deterministic system, the random Morris-Lecar model stabilizes at a unique stationary stochastic process. In terms of random dynamical system theory, our analysis shows that additive noise destroys the above-mentioned bifurcation sequences that characterize class I and class II regimes in the Morris-Lecar model. The interpretation of this result in terms of neuronal coding is that, despite the differences in the deterministic dynamics of class I and class II membranes, their responses to noise-like stimuli present a reliable feature.

Animals↗

PubMed2004

Calorimetric determination of thermodynamic parameters of 2'-dUMP binding to Leishmania major dUTPase.

We have investigated the binding of 2'-deoxyuridine 5'-monophosphate (2'-dUMP) to Leishmania major deoxyuridine 5'-triphosphate nucleotide hydrolase (dUTPase) by isothermal titration microcalorimetry under different experimental conditions. Binding to dimeric L. major dUTPase is a non-cooperative process, with a stoichiometry of 1 molecule of 2'-dUMP per subunit. The utilization of buffers with different ionization enthalpies has allowed us to conclude that the formation of the 2'-dUMP-dUTPase complex, at pH 7.5 and 30 degrees C, is accompanied by the uptake of 0.33 +/- 0.05 protons per dUTPase subunit from the buffer media. Moreover, 2'-dUMP shows a moderate affinity for the enzyme, and binding is enthalpically driven across the temperature range studied. Besides, whereas DeltaG degrees remains practically invariant as a function of temperature, both DeltaH and DeltaS degrees decrease with increasing temperature. The TS and TH were 23.4 and 13.6 degrees C, respectively. The temperature dependence of the enthalpy change yields a heat capacity change of DeltaCp degrees = -618.1 +/- 126.4 cal x mol(-1) x K(-1), a value low enough to discard major conformational changes, in agreement with the fitting model. An interpretation of this value in terms of solvent-accessible surface areas is provided.

Animals↗

PubMed2006

Quantitative time-resolved fluorescence spectra of the cortical sarcoma and the adjacent normal tissue determined with an in vivo experimental method and theoretical model.

In this paper, a time-resolved fluorescence spectrum method is proposed to study the difference between the cortical sarcoma and the adjacent normal tissue. This is a fluorescence-light-intensity-independent method, which makes it more reliable in the presence of interference light emitted by nonfluorescent light absorbers and scatterers. In the implementation, a model of the tumor tissue and a model of light transport in turbid media using improved Monte Carlo simulations are proposed. In this method, the time-resolved fluorescence is collected in vivo. The improved theoretical model can interpret the fluorescence lifetime measurement. The simulation results show that the decay constant of the tumor tissue spectrum is larger than that of the adjacent normal tissue because of hypoxia and hyperplasia, which fits the theoretical analysis very well.

Animals↗

PubMed2026

Genomic signatures associated with epidemiologically defined high-risk pathogenic Escherichia coli isolates identified by interpretable machine learning.

Pathogenic Escherichia coli is a major cause of foodborne illness worldwide and includes strains capable of causing severe disease. To establish a genome-informed framework for foodborne outbreak surveillance, we analyzed 1,029 E. coli isolates from clinical, food, livestock, and environmental sources using whole-genome sequencing. Pathogenic isolates obtained from human clinical cases or linked to documented outbreaks were classified as epidemiologically defined high-risk (EpiHR), whereas the remaining pathogenic isolates were classified as non-EpiHR. Virulence-associated genomic features were extracted using a bioinformatics pipeline, and four machine learning (ML) algorithms, including gradient boosting machine, random forest (RF), and support vector machines with linear and radial basis function kernels, were evaluated. Among them, the RF model showed the best performance, achieving an area under the curve (AUC) of 0.98 and accuracy of 0.93 in 10-fold cross-validation. Additional leave-one-group-out validation showed retained discrimination across held-out sequence types and serotypes, although performance was reduced when isolates were grouped by isolation source. Evaluation using an independent test dataset of 1,908 publicly available pathogenic E. coli genomes showed an AUC of 0.97 and a sensitivity of 0.98. Feature importance analysis using Shapley additive explanations identified influential predictive features, including traT, etpB, and enterotoxin-associated genes. A reduced 10-feature model achieved an AUC of 0.79 in the independent test dataset, supporting its exploratory use for future simplified screening approaches. These results indicate that genome-based ML provides a sensitive framework for surveillance-oriented prioritization of EpiHR pathogenic E. coli isolates, with model predictions interpreted together with epidemiological information.

Escherichia coli↗

PubMed2002

A review of multilevel theory for ecologic analyses.

This paper reviews multilevel and conventional models for the analysis of ecologic (group, aggregate) data. It emphasizes the non-separability of contextual (group-level) effects and individual-level effects that arises from the multilevel structure of the underlying effects. Contrary to common misperceptions, this problem afflicts ecologic studies in which the sole objective is to estimate contextual effects, as well as studies in which the objective is to estimate individual effects. Multilevel effects also severely complicate causal interpretations of model coefficients.

Bias↗

PubMed2001

Binding and oxidation of alkyl 4-nitrophenyl ethers by rabbit cytochrome P450 1A2: evidence for two binding sites.

Although most cytochrome P450 (P450) reactions demonstrate saturation kinetics that fit to the standard Michaelis-Menten equation, there are important exceptions where sigmoidal or nonhyperbolic behavior is observed and have been fit instead to kinetic models involving two binding sites. To assess these models, we demonstrate the consistency of a two binding site model to interpret both steady-state kinetics and binding events. Rates of 4-nitrophenol and formaldehyde production from the O-demethylation of 1-methoxy-4-nitrobenzene by P450 1A2 isolated from rabbit liver produced biphasic plots, when plotted against substrate concentration. Experiments confirmed the absence of the further oxidation of the products. Recombinant rabbit P450 1A2 yielded the same maximal velocity and more marked biphasicity. Overall, these steady-state data fit well to kinetic models involving two binding sites. Steady-state studies of substrates with bulkier O-ethyl or O-isopropoxy groups indicated decreased affinity for the second site. Based on binding studies, the affinity of P450 1A2 for these substrates increased 200-fold with the larger alkyl groups. To analyze the single binding site model, competition studies were conducted with 1,4-phenyldiisocyanide and the alkyl 4-nitrophenyl ethers. Although the observed dissociation constants and the competing titrant demonstrated a linear dependence, the affinity for the competing titrant depended on the presence of the other titrant, which violates the single binding site model. Alternatively, we applied a two binding site model to these data to obtain dissociation constants for the binary and ternary complexes. The agreement between the dissociation constants for the heterogeneous complexes supports the appropriateness of the two binding site model. This novel finding for P450 1A2 may be more common than originally perceived for P450s.

Animals↗

PubMed2005

Disclosing disease mechanisms with a spatio-temporal summation paradigm.

BACKGROUND: We develop the logic for a stimulus that can evaluate cone-dependent spatial summation and detail the modelling and interpretation of thresholds obtained with this stimulus. METHODS: Fifteen observers participated, including two young normals tested extensively in control experiments, and a clinical trial based on four observers with age-related macular degeneration (AMD), four age-similar controls and five young observers. Monocular spatial summation functions were measured with contrast-modulated Gabor targets that approximated the optimal visual contrast detector. Thresholds were returned from a yes/no adaptive psychophysical algorithm. By fine titration along the size domain it was demonstrated that the spatial summation of normal observers can be adequately described by a two-component model. A reduced set of variables are proposed for clinical applications and the model was applied to data derived using these variables in persons with AMD and age-similar controls. RESULTS: We do not find a significant age-related loss of contrast sensitivity in our normal group. On the other hand, persons with early AMD exhibited a 0.41 log unit loss of sensitivity (P=0.04) from age-similar controls, without any change in their maximum summation area (A(max)). CONCLUSIONS: The nature of the spatial summation is consistent with the interpretation that early AMD produces a decrease in cone input to post-receptoral mechanisms in the absence of neural remodelling.

Adult↗

PubMed1986

Determinants of perceived mental health status and help-seeking behavior: preliminary testing of a conceptual model.

This paper presents a preliminary test of the conceptual model of cognitive determinants of the perception of mental health status. Path analysis was used to examine the causal relationships between education, awareness of higher level needs, one's definition of mental health, and self-rating of mental health status. Discriminant analyses was used to evaluate these variables and others as predictors of help-seeking behavior. Results indicate the importance of cognitive factors in the perception of mental health status and support a direct causal interpretation of model variables. Symptom checklist scores and path variables were found to be the best predictors of help-seeking behavior.

Adult↗

PubMed2004

Simulation of a radiotracer experiment by flow and detection-chain modelling: a first step towards better interpretation.

The injection of a gamma-emitting tracer in backward-facing step flow was modelled. Flow and concentration fields were calculated by CFD and detector responses by a Monte-Carlo code. The objective was to show the influence of the radiotracer energy on the detector response, so as to interpret better data from radiotracer experiments. The radiotracer selection is important in obtaining reliable results, each specific case requiring careful analysis of the experimental data. However, more work is still required to achieve the prescribed goal aimed at.

Journal Article↗

PubMed2005

Nanoscale mechanical and dynamical properties of DNA single molecules.

Experimental evidence suggests DNA mechanical properties, in particular intrinsic curvature and flexibility, have a role in many relevant biological processes. Systematic investigations about the origin of DNA curvature and flexibility have been carried out; however, most of the applied experimental techniques need simplifying models to interpret the data, which can affect the results. Progress in the direct visualization of macromolecules allows the analysis of morphological properties and structural changes of DNAs directly from the digitised micrographs of single molecules. In addition, the statistical analysis of a large number of molecules gives information both on the local intrinsic curvature and the flexibility of DNA tracts at nanometric scale in relatively long sequences. However, it is necessary to extend the classical worm-like chain model (WLC) for describing conformations of intrinsically straight homogeneous polymers to DNA. This review describes the various methodologies proposed by different authors.

Cations, Divalent↗

PubMedDate not supplied

Toward theory-based diagnostic categories.

As a social institution, nursing has a responsibility to society for the development of knowledge in the areas described by nursing diagnoses. This article focuses on the need for developing the theoretical basis of each diagnostic category. Diagnoses are viewed as summarizations of underlying conceptual models for interpreting observations, and as such, they provide a perspective for understanding and thinking about a set of clinical observations. At present many diagnostic concepts do not meet this standard and suggest primitive, pretheoretical ideas with a minimal knowledge base. The importance of having valid and reliable diagnostic categories for use in making clinical judgements and as a focus for care planning is discussed. A cycle of development is outlined in three phases: diagnostic concept identification, concept analysis-model development, and construction/reconstruction of diagnostic categories. It is suggested that a useful category captures the conceptual understanding and state of knowledge development about a phenomena in its (a) name, (b) definition, and (c) cluster of defining characteristics.

Concept Formation↗

PubMed1992

Interpretation of the X-ray scattering profiles of chromatin at various NaCl concentrations by a simple chain model.

In order to interpret the change in the X-ray scattering profiles from rat thymus chromatin, extensive model calculation was carried out. Chromatin is modelled as a string of subunits (nucleosomes) in which disorder is introduced into the positions of adjacent subunits. Disposition parameters characterizing the arrangement of subunits were estimated for various states of chromatin, so that the main feature of the scattering profiles is described. The result indicated that the structure of chromatin changes, as the NaCl concentration increases, from the extended "beads-on-a string" structure to the condensed helical structure. The latter has an outer diameter of about 26 nm with 3-4 nucleosomes per turn. In the intermediate state, it has a loose helical structure. The estimation of disorder suggested that the arrangement of subunits is appreciably disordered even in the condensed helical filament at 50 mM NaCl. Our model for chromatin condensation seems to support models of the "crossed linker" type.

Animals↗

PubMed1980

Kinetic isotope effects in cytochrome P-450-catalyzed oxidation reactions. Intermolecular and intramolecular deuterium isotope effects during the N-demethylation of N,N-dimethylphentermine.

Two N,N-dimethylphentermine (N,N-dimethyl-2-amino-2-methyl-3-phenylpropane) substrates differing in deuterium substitution have been used to determine the intermolecular and intramolecular isotope effects associated with the cytochrome P-450-dependent N-demethylation of this substrate. No intermolecular isotope effect was observed in Vmax or Vmax/Km when the reaction rates for this substrate were compared to those for the substrate in which both N-methyl groups contained deuterium. In contrast, identical isotope effects of 1.6 to 2.0 were observed in both Vmax and Vmax/Km when this reaction was studied with a substrate in which only one of the two N-methyl groups was substituted with deuterium. Furthermore, both the intermolecular and intramolecular isotope effects were independent of the cytochrome P-450/NADPH-cytochrome P-450 reductase mole ratio. From these data, it is concluded that: 1) the carbon-hydrogen bond cleavage step does not contribute significantly to Vmax; 2) the contribution of the carbon-hydrogen bond cleavage step to Vmax is not detectably increased through changes in the cytochrome P-450/NADPH-cytochrome P-450 reductase mole ratio; 3) the N-methyl groups are free to exchange at the enzyme active site. The basis for these conclusions is the proposal of a new kinetic model for interpretation of intramolecular isotope effects which shows that intramolecular isotope effects are not necessarily equal to intrinsic isotope effects and, in fact, may be much smaller.

Animals↗

PubMed2006

Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial.

BACKGROUND: The MRC Multicentre trial for Early Epilepsy and Single Seizures (MESS) showed a reduced risk of further seizures in patients, for whom treatment with antiepileptic drugs was uncertain, who were randomly assigned immediate treatment compared with delayed treatment. However, there was no evidence of an effect on [corrected] long-term remission rates. This study was undertaken to assess the role of patient characteristics and treatment in the prediction of seizure recurrence. This will enable decision-making on the basis of the perceived risk of treatment compared with the benefit of reducing the risk of further seizures in the initial years after diagnosis. METHODS: A prognostic model was developed based on individual patient data from MESS to enable identification of patients at low, medium, or high risk of seizure recurrence. A split-sample approach was used in which the model was developed on a subsample of the full data and validated on the remainder of the sample. Distinction of the prognostic groups and predictive accuracy of the model were assessed. FINDINGS: Number of seizures of all types at presentation, presence of a neurological disorder, and an abnormal electroencephalogram (EEG) were significant factors in indicating future seizures. Individuals with two or three seizures, a neurological disorder, or an abnormal EEG were identified as the medium-risk group, those with two of these features or more than three seizures as the high-risk group, and those with a single seizure only as the low-risk group. INTERPRETATION: The model shows that there is little benefit to immediate treatment in patients at low risk of seizure recurrence, but potentially worthwhile benefits are seen in those at medium and high risk.

Adolescent↗

PubMed2003

Effects of the local mechanical environment on vertebrate tissue differentiation during repair: does repair recapitulate development?

The local mechanical environment is a crucial factor in determining cell and tissue differentiation during vertebrate skeletal development and repair. Unlike the basic response of bone to mechanical load, as described in Wolff's law, the mechanobiological relationship between the local mechanical environment and tissue differentiation influences everything from tissue type and molecular architecture to the formation of complex joints. This study tests the hypothesis that precisely controlled mechanical loading can regulate gene expression, tissue differentiation and tissue architecture in the adult skeleton and that precise manipulation of the defect's local mechanical environment can initiate a limited recapitulation of joint tissue development. We generated tissue type predictions using finite element models (FEMs) interpreted by published mechanobiological fate maps of tissue differentiation. The experiment included a custom-designed external fixator capable of introducing daily bending, shear or a combination of bending and shear load regimens to induce precisely controlled mechanical conditions within healing femoral defects. Tissue types and ratios were characterized using histomorphometrics and molecular markers. Tissue molecular architecture was quantified using polarized light and Fourier transforms, while immunological staining and in situ hybridization were used to characterize gene expression. The finite element models predicted the differentiation of cartilage within the defects and that substantial fibrous tissues would develop along the extreme excursion peripheries in the bending group. The three experimentally induced loading regimens produced contiguous cartilage bands across all experimental defects, inhibiting bony healing. Histomorphometric analysis of the ratios of cartilage to bone in the experimental groups were not significantly different from those for the knee joint, and Fourier transform analysis determined significantly different collagen fibril angle specializations within superficial, intermediate and deep layers of all experimental cartilages (P<0.0001), approximating those for articular cartilage. All stimulations resulted in the expression of collagen type II, while the bending stimulation also resulted in the expression of the joint-determining gene GDF-5. These findings indicate that the local mechanical environment is an important regulator of gene expression, tissue differentiation and tissue architecture.

Animals↗

PubMed2002

The Buproridae Thorell, 1859, a family of ascidicolous copepods (Copepoda: Cyclopoida).

The adult female of Buprorus loveni Thorell, 1859, a cyclopoid copepod inhabiting the branchial cavities of solitary ascidians, is redescribed in detail from new material collected in Scandinavian waters and from the southern part of the North Atlantic off Mauritania. The antennal segmentation pattern exhibited by all seven subfamilies of the family Ascidicolidae Thorell, 1860 is compared. The segmentation of the Buprorinae is different from that of all other subfamilies within the ascidicolid series. It is concluded that the antenna of Buprorus is not an appropriate model for interpreting the segmentation of other ascidicolids because the Buprorinae is the only subfamily in which the first and second endopodal segments are primitively fused and the third is distinct. The Buproridae Thorell, 1859 is here treated as a separate family within the Cyclopoida.

Animals↗

PubMed1987

Staff resistance to interpretive psychotherapy in the in-patient community meeting.

The authors propose using the in-patient psychiatry unit community meeting for large-group interpretive psychotherapy, employing the model of Winer & Lewis (1984). This model rests heavily on interpretation of group transferences in the here and now. The staff has the task of discovering patients' veiled references to them and interpreting the patients' resistance to direct expression of their experience of the staff. The authors discuss the impact of introducing the technique upon staff members. Staff members resist this new model in order to defend against self-esteem injury, loss and regression, staff-staff conflict, and the recognition of their own disavowed internal motives. Staff self-esteem can be endangered by any programme change, by the loss of accustomed roles, by the patients' hostility and direct criticism, and by the staff's own sense of failure to realize therapeutic ambitions. Some of the resistance specific to interpretive group psychotherapy arises from the threat of group silence or alienation. The group leader, in addition, faces the difficult task of understanding the dynamics of a large group with only minimal support.

Humans↗

PubMed2003

GESDOR - a generic execution model for sharing of computer-interpretable clinical practice guidelines.

We developed the Guideline Execution by Semantic Decomposition of Representation (GESDOR) model to share guidelines encoded in different formats at the execution level. For this purpose, we extracted a set of generalized guideline execution tasks from the existing guideline representation models. We then created the mappings between specific guideline representation models and the set of the common guideline execution tasks. Finally, we developed a generic task-scheduling model to harmonize the existing approaches to guideline task scheduling. The evaluation has shown that the GESDOR model can be used for the effective execution of guidelines encoded in different formats, and thus realizes guideline sharing at the execution level.

Decision Making, Computer-Assisted↗