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At least 1,225 records · Page 68Linked to original sources
PubMed2000

A Hodgkin-Huxley model exhibiting bursting oscillations.

We investigate bursting behaviour generated in an electrophysiological model of pituitary corticotrophs. The active and silent phases of this mode of bursting are generated by moving between two stable oscillatory solutions. The bursting is indirectly driven by slow modulation of the endoplasmic reticulum Ca2+ concentration. The model exhibits different modes of bursting, and we investigate mode transitions and similar modes of bursting in other Hodgkin-Huxley models. Bifurcation analysis and the use of null-surfaces facilitate a geometric interpretation of the model bursting modes and action potential generation, respectively.

Action Potentials↗
PubMed1990

Perceptual-learning systems as conservative structures: is economy an attractor?

It is discussed whether information-processing or connectionist models might explain the law of Prägnanz under constraints resulting from a physical interpretation of these models. An information-processing approach is contrasted with thermodynamics and, finally, an alternative approach more directly inspired by Gestalt is discussed. It is argued that this model could be physically realized with relatively moderate requirements on the substrate in terms of information-processing resources.

Animals↗
PubMed2026

Swimming Upstream to Understand Congenital Anomalies of the Kidney and Urinary Tract: Zebrafish Models for Developmental Biology, Disease Mechanisms, and Functional Interpretation of Genetic Variation.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of pediatric chronic kidney disease (CKD) and comprise a heterogeneous group of developmental disorders with a substantial genetic contribution. Advances in next-generation sequencing have facilitated the identification of numerous candidate genes and rare variants associated with CAKUT. However, establishing causality and defining the biological functions of implicated genes remain major challenges. Functional validation is therefore essential to bridge the gap between gene discovery and mechanistic understanding, enabling the interpretation of genetic variation within the context of kidney development and disease. The zebrafish (Danio rerio) has emerged as a powerful in vivo model for studying renal development and interrogating the function of CAKUT-associated genes. Its utility stems from a high degree of genetic and developmental conservation with humans, conserved nephrogenic pathways, optical transparency during embryogenesis, and the relative ease of genetic manipulation. In this review, we provide an overview of zebrafish kidney development within the broader context of vertebrate nephrogenesis, highlighting the key genetic programs governing intermediate mesoderm specification, nephron segmentation, and pronephric morphogenesis. We then systematically examine CAKUT-associated genes that have been modeled in zebrafish, focusing on studies that have linked genetic perturbations to renal development and structural phenotypes. Finally, we discuss the strengths and limitations of zebrafish models for functional genomics and variant interpretation and consider their emerging role in bridging genetic discovery with mechanistic insights into CAKUT pathogenesis.

Animals↗
PubMed2004

Relations between Lagrangian models and synthetic random velocity fields.

The authors propose an alternative interpretation of Markovian transport models based on the well-mixed condition, in terms of the properties of a random velocity field with second order structure functions scaling linearly in the space-time increments. This interpretation allows direct association of the drift and noise terms entering the model, with the geometry of the turbulent fluctuations. In particular, the well-known nonuniqueness problem in the well-mixed approach is solved in terms of the antisymmetric part of the velocity correlations; its relation with the presence of nonzero mean helicity and other geometrical properties of the flow is elucidated. The well-mixed condition appears to be a special case of the relation between conditional velocity increments of the random field and the one-point Eulerian velocity distribution, allowing generalization of the approach to the transport of nontracer quantities. Application to solid particle transport leads to a model satisfying, in the homogeneous isotropic turbulence case, all the conditions on the behavior of the correlation times for the fluid velocity sampled by the particles. In particular, correlation times in the gravity and in the inertia dominated case, respectively, longer and shorter than in the passive tracer case; in the gravity dominated case, correlation times longer for velocity components along gravity, than for the perpendicular ones. The model produces, in channel flow geometry, particle deposition rates in agreement with experiments.

Journal Article↗
PubMed1994

The analysis of binary and categorical data from crossover trials.

A review is presented of methods for the analysis of discrete data from crossover trials. The definition and interpretation of the model for the data is used as a central theme. Distinctions are drawn between different types of model, particularly marginal and subject specific. It is seen how much recent methodology for analysing correlated categorical data can be applied successfully to the crossover setting. The current accessibility of each method is considered and the different approaches are illustrated and compared using two examples.

Bias↗
PubMed2026

Performance of AI-Based Screening Tools for Obstructive Sleep Apnea Across Apnea-Hypopnea Index Thresholds: Systematic Review and Meta-Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent but remains substantially underdiagnosed. Polysomnography (PSG) is the reference standard, but its cost and limited availability constrain large-scale case identification. AI-based screening tools may support risk stratification and referral prioritization, but their diagnostic accuracy across apnea-hypopnea index (AHI) thresholds remains uncertain. OBJECTIVE: This review aimed to systematically evaluate the diagnostic accuracy of AI-based OSA screening tools at AHI thresholds of ≥5, ≥15, and ≥30 events/hour, with emphasis on models using non-PSG-derived inputs. METHODS: PubMed, Embase, Scopus, and Web of Science were searched for studies published from January 1, 2016, to May 3, 2026. Eligible studies included adults evaluated for suspected OSA or recruited from population-based cohorts, assessed AI-based models intended or interpretable for OSA screening, risk prediction, or screening-oriented severity classification, used PSG as the reference standard, and reported sufficient data to construct or reconstruct 2×2 contingency tables. Diagnostic accuracy was synthesized separately by AHI threshold and input source using bivariate random-effects models, with 95% CIs and prediction intervals (PIs). Risk of bias and certainty of evidence were assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation), respectively. RESULTS: A total of 60 studies were included, of which 47 contributed data to the meta-analysis. At AHI thresholds of ≥5, ≥15, and ≥30 events/hour, pooled sensitivities were 0.94 (95% CI 0.92-0.96; 95% PI 0.71-0.99), 0.87 (95% CI 0.84-0.89; 95% PI 0.66-0.96), and 0.83 (95% CI 0.79-0.87; 95% PI 0.61-0.94), respectively; the corresponding specificities were 0.77 (95% CI 0.69-0.84; 95% PI 0.30-0.96), 0.81 (95% CI 0.75-0.85; 95% PI 0.39-0.96), and 0.91 (95% CI 0.87-0.94; 95% PI 0.55-0.99), respectively. The corresponding areas under the summary receiver operating characteristic curves were 0.943, 0.907, and 0.920. For non-PSG-derived tools, sensitivities were 0.92, 0.85, and 0.81, and specificities were 0.70, 0.74, and 0.85 at the 3 thresholds, respectively. For PSG-derived models, sensitivities were 0.96, 0.90, and 0.85, and specificities were 0.82, 0.88, and 0.96, respectively. Exploratory subgroup analyses suggested performance variation across selected study and model characteristics, including region, algorithmic framework, data source, and validation method. CONCLUSIONS: AI-based tools showed generally favorable screening performance for OSA across clinically relevant AHI thresholds, although wide PIs suggest variable performance across future comparable populations and settings. By synthesizing diagnostic accuracy across 3 AHI thresholds and distinguishing non-PSG-derived from PSG-derived models, this review extends previous broad or modality-specific reviews and offers a clinically interpretable, pathway-specific basis for linking model performance to intended use. The findings may clarify potential roles for non-PSG-derived tools in front-end screening and referral prioritization and for PSG-derived models in reduced-channel assessment and sleep-laboratory workflow support. Given substantial heterogeneity, limited external validation, and low or very low certainty of evidence, prospective validation is needed before routine implementation.

Humans↗
PubMed2006

Theoretical model for a tetrad of hydrogen bonds and its application to interpretation of infrared spectra of salicylic acid.

Theoretical model of vibrational interactions in hydrogen-bonded salicylic acid dimer is presented which takes into account the adiabatic couplings between high- and low-frequency O-H and O...O stretching vibrations, resonance interactions between both intermolecular hydrogen bonds and between inter- and intramolecular hydrogen bonds, and Fermi resonance between the O-H stretching fundamental and the first overtone of the O-H in-plane bending vibrations. The model is used for theoretical simulation of the nu(s) stretching bands of salicylic acid and its OD derivative at 300 K. The effect of deuteration is successfully reproduced by our model. Infrared, far infrared, Raman, and low-frequency Raman spectra of the polycrystalline salicylic acid and its deuterated derivative have been measured. The geometry and experimental frequencies are compared with the results of density-functional theory calculations performed at the B3LYP6-31 ++ G**, B3LYP/cc-pVTZ, B3PW916-31 ++ G**, and B3PW91/cc-pVTZ levels. O-H, O-D, and O...O stretching frequencies are used in theoretical simulation of the nu(s) stretching bands.

Journal Article↗
PubMed2006

1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms.

The most recent refinement of the crystallographic structure of oxyhaemoglobin (oxyHb) was completed in 1983, and differences between this real-space refined model and later R state models have been interpreted as evidence of crystallisation artefacts, or numerous sub-states. We have refined models of deoxy, oxy and carbonmonoxy Hb to 1.25 A resolution each, and compare them with other Hb structures. It is shown that the older structures reflect the software used in refinement, and many differences with newer structures are unlikely to be physiologically relevant. The improved accuracy of our models clarifies the disagreement between NMR and X-ray studies of oxyHb, the NMR experiments suggesting a hydrogen bond to exist between the distal histidine and oxygen ligand of both the alpha and beta-subunits. The high-resolution crystal structure also reveals a hydrogen bond in both subunit types, but with subtly different geometry which may explain the very different behaviour when this residue is mutated to glycine in alpha or beta globin. We also propose a new set of relatively fixed residues to act as a frame of reference; this set contains a similar number of atoms to the well-known "BGH" frame yet shows a much smaller rmsd value between R and T state models of HbA.

Amino Acid Sequence↗
PubMed2001

Mathematical modeling of the aging processes and the mechanisms of mortality: paramount role of heterogeneity.

Main problems of modeling the link between aging processes and mechanisms of mortality are addressed. Various applications of Gompertz's law, which allowed to formulate some fruitful hypotheses on the field, are reviewed. Some pitfalls occurring in its applications are also discussed using a model built on purpose to overcome these difficulties. The role played by heterogeneity emerges as the common cause of some relevant failure in using Gompertz's law and the necessary key ingredient of any model aimed to interpret the link between aging and mortality correctly. Though a number of problems are related to inter-individual variability, the search for their solution can lead to an intriguing approach to the study of aging and mortality. Living beings can be considered as complex systems and their age-related changes can be described at the light of complex system theory.

Aging↗
PubMed2004

On-clock non-paralyzable count-loss model.

This paper proposes a new count-loss model that is applicable to radiation detection systems in the field of nuclear medicine. The proposed model, represented by n = (1 - exp(-tau(n)0))/tau(n)0: input rate, n: output rate,tau: system clock duration), gives higher count rates than the well-known standard nonparalyzable (non-extensible) model represented by n = n0/(1 + tau(n)0) does, being equally simple. This model assumes that a part of the data processing is performed on a fixed system clock, requiring a data buffering function (latch) to retain digital event information temporarily, and that input timing is random. The model's simple interpretation and expression also offers an advantage over various other advanced count-loss models proposed so far. This model was found to be a better fit to a data-acquisition system for a positron emission tomography scanner.

Algorithms↗
PubMed2003

A survey of the Predictive Toxicology Challenge 2000-2001.

MOTIVATION: The Predictive Toxicology Challenge (PTC) was initiated to stimulate the development of advanced techniques for predictive toxicology models. The goal of this challenge was to compare different approaches for the prediction of rodent carcinogenicity, based on the experimental results of the US National Toxicology Program (NTP). RESULTS: 111 sets of predictions for 185 compounds have been evaluated on quantitative and qualitative scales to select the most predictive models and those with the highest toxicological relevance. The accuracy of the submitted predictions was between 25 and 79 %. An evaluation of the most accurate models by toxicological experts showed, that it is still hard for domain experts to interpret the submitted models and to put them into relation with toxicological knowledge. AVAILABILITY: PTC details and data can be found at: http://www.predictive-toxicology.org/ptc/.

Animals↗
PubMed2006

Thematic review series: patient-oriented research. Design and analysis of lipoprotein tracer kinetics studies in humans.

Lipoprotein tracer kinetics studies have for many years provided new and important knowledge of the metabolism of lipoproteins. Our understanding of kinetics defects in lipoprotein metabolism has resulted from the use of tracer kinetics studies and mathematical modeling. This review discusses all aspects of the performance of kinetics studies, including the development of hypotheses, experimental design, statistical considerations, tracer administration and sampling schedule, and the development of compartmental models for the interpretation of tracer data. In addition to providing insight into new metabolic pathways, such models provide quantitative information on the effect of interventions on lipoprotein metabolism. Compartment models are useful tools to describe experimental data but can also be used to aid in experimental design and hypothesis generation. The SAAM II program provides an easy-to-use interface with which to develop and test compartmental models against experimental models. The development of a model requires that certain checks be performed to ensure that the model describes the experimental data and that the model parameters can be estimated with precision. In addition to methodologic aspects, several compartment models of apoprotein and lipid metabolism are reviewed.

Computer Simulation↗
PubMedDate not supplied

Ordinal logistic regression in medical research.

Medical research workers are making increasing use of logistic regression analysis for binary and ordinal data. The purpose of this paper is to give a non-technical introduction to logistic regression models for ordinal response variables. We address issues such as the global concept and interpretation of logistic models, the model building procedure from a practical point of view, and the assessment of the model adequacy. For illustrative purposes we apply these methods to real data of a study investigating the association between glycosylated haemoglobin and retinopathy. We give some recommendations for the use and assessment of ordinal logistic regression models in medical research.

Analysis of Variance↗
PubMed1997

Interpreting the chi-square statistics reported in the many-faceted Rasch model.

The different chi-square statistics reported in the many-faceted Rasch model analysis are presented and interpreted. In addition, other chi-square summary values are computed and presented for interpretation of facets. The chi-square values are useful for determining: (1) the significance of a facet in the Rasch model; (2) the significant contribution of facet main and interaction effects; (3) differences among facet elements; and (4) identifying the specific facet interaction adjustments to the subjects' calibrated logit ability measure.

Chi-Square Distribution↗
PubMedDate not supplied

[Ethics of care and new profiles of the woman].

INTRODUCTION: In health professions listening represents an essential condition for any cure relation. Learning to listen is thus neither easy nor granted. It requires the ability to put oneself in somebody else's place, maintaining self-possession of judgement and the ability of evaluating events. PROBLEM ANALYSIS: In health professions women have always occupied a privileged position for their sensitiveness and their ability of giving meaning even to everyday life. Empathy is the privileged way women have of getting to know, understand and take care of people. They follow a feminine style which accepts and welcomes other people even if they are not able to explain their intimate contradictions, their anxieties, their difficulties, their pain and weakness. Women know how to be near people, even if they understand they are not up to the situation, not expecting to solve pain: neither personal nor other people's. They act in a different way from men who instead are attached to a reductionism that assumes a theoretical scheme to understand the issue. Man's need to dominate the problem with knowledge makes him sacrifice the complexity of reality in which he lives. Men's simplicity, their tendency to generalize processes and easily find guidelines to proceed with no useless wastes, often sacrifices elements which find no place into the chosen standards. For women this way of behaving, apparently reassuring, is not possible because they are aware that such aspects while escaping their understanding express the personality of the people involved in this process, their uniqueness which does not accept generalisations. Behind interpretative schemes, behind apparently definitive diagnosis, women perceive vagueness and interpretative inadequacy. CONCLUSIONS: Female rationality is inclined to live with one's own and other's contradictions just because it is strongly attached to a reality which avoids simplification of understanding. It refuses interpretative schemes, theories which try to offer themselves as exhaustive models which can explain all events, lessening the value or even denying elements which do not fall within the interpretation model assumed. Women appear contradictory because they do not refuse confrontation with life contradictions and its perennial changes.

Attitude of Health Personnel↗
PubMed1998

Longitudinal models for AIDS marker data.

Over the past decade, researchers have put a great amount of effort into developing suitable models for the analysis of longitudinal CD4 data and other markers of AIDS progression. These models must be general enough to allow for different patterns of change in the marker data. In this paper, we review the existing literature including our preferred models which involve mixed effects, stochastic terms and independent measurement error. Adding stochastic terms to standard mixed effects models gives an interpretable and parsimonious method for generalizing the covariance structure of the measurement error and short-term variability. We focus on univariate and bivariate models with integrated Ornstein-Uhlenbeck (IOU) stochastic terms. The IOU process allows for a range of biologically plausible derivative tracking that encompasses both random trajectory and Brownian motion behaviour. We illustrate these modelling techniques on longitudinal CD4 and viral RNA data.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Kinetic analysis and modelling of the allosteric behaviour of liver and muscle glycogen phosphorylases.

Allosteric enzymes have very complex kinetic behaviours which are primarily interpreted through simplified models. To describe the functional properties of liver and muscle glycogen phosphorylase isozymes we have developed an experimental strategy based on the measurements of initial reaction rates in the presence of different concentrations of the effectors glucose-1-phosphate and methyl-xanthines. Using the extensive structural information available for the two glycogen phosphorylase conformers T (inactive) and R (active) with different ligands, we have applied the Monod-Wyman-Changeux model and analysed the results in the context of the exclusive binding of the inhibitors to the T state, meanwhile the substrate glucose-1-phosphate binds to both, the R and T states. The kinetic analysis shows a good agreement between our model and the results obtained from the glycogen phosphorylases and inhibitors included in this study, which demonstrates the validity of the approach described here.

Allosteric Regulation↗