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Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling.

In this paper, we address methods of multivariate regression. We discuss the value of regression compared to matched pairs analysis, methods of coding variables, basic concepts of the Cox model and interpretation of results of the Cox model. We present methods of handling variables whose effect changes with time. We present methods to check the assumptions of the Cox regression. Finally, and perhaps most importantly, we provide suggestions for presenting the results in clear and thorough tables and graphs.

Bone Marrow Transplantation↗

Corneal temperatures--a study of normal and laser-injured corneas in the Dutch belted rabbit.

Air Force laser safety standards are developed from laser-exposure data obtained in studies using experimental animals and from biomathematical modeling procedures. Interpretation of research data and predictive modeling calculations are enhanced by knowledge of the temperature values of the tissue absorption sites. Corneal temperature values for the normal, the anesthetized, and the laser-injured Dutch belted rabbit are presented and compared with values obtained in other studies. The corneal temperatures were measured by infrared radiometry.

Anesthesia, Intravenous↗

A computer-aided approach to the structural analysis and modification of a large circulatory system model.

The purpose of this study is to show an approach to making an intelligent support system for understanding and modifying a large circulatory system model using techniques of system analysis. Structural analysis makes it possible to visualize hierarchies of Coleman's circulatory model Human. Two techniques are successively applied for structural analysis, model reduction and graph analysis by interpretative structural modeling (ISM). First, the analysis for model reduction removes input-output relations with an input-output gain less than a given threshold, and second, the ISM technique applied to the reduced model of Human provides hierarchical directed graphs. The proposed approach: 1) enables visualization of a hierarchy graph of cause and effect relations of the large circulatory model, 2) suggests control and diagnostic information to the model by tracing back a path in the hierarchy, and 3) allows the user to modify the circulatory model. The efficiency and performance of the proposed approach demonstrates technical indications of success in analyzing and justifying experimental evidences with the online help of the system.

Algorithms↗

Are qualitative methods misunderstood?

Qualitative research methods are increasingly utilised by health researchers. Along with this the criteria for assessing the quality of qualitative research are changing from a natural science model to an interpretative social science model. This is a product of the realisation by health researchers that qualitative methods utilise a different epistemology to statistical methods. I demonstrate that a recent article in the Australian and New Zealand Journal of Public Health draws on a now outdated natural science methodology of assessing bias in focus groups. Drawing on interpretativist social science theory and recent work in the British Medical Joumal I argue for the importance of examining the social contexts through which qualitative data is produced.

Anecdotes as Topic↗

A stochastic model simulating the feeding-health-production complex in a dairy herd.

A dynamic, stochastic, and mechanistic Monte Carlo model, simulating a dairy herd with focus on the feeding-health-production complex is presented. By specifying biological parameters at cow level and a management strategy at herd level, the model can simulate the technical and economic consequences of scenarios at herd level. The representation of the feeding-health-production complex is aimed to be sufficiently detailed, to include relationships likely to cause significant herd effects, and to be sufficiently simple to enable a feasible parameterization of the model and interpretation of the results from the model. Consequently, diseases are defined as four disease types: two metabolic disease types, an udder disease type, and a reproductive disease type. Risk factors for the diseases were defined as parity, yield capacity, disease recurrence, disease interrelationships, lactation stage, and season. Direct effects of the diseases were defined according to milk yield, feed intake, feed utilization, conception, culling, involuntary removal, and death. Scenarios differing in base risks of milk fever and ketosis, heat detection rate, and culling strategy were simulated for describing the model behavior. Annual milk yield per cow was decreased by increased risk of ketosis and by increased risk of milk fever, even though no direct effect of milk fever on milk yield was modeled at the cow level. The indirect effect from milk fever is a consequence of increased replacement rate (relatively lower milk yield from younger cows). By ignoring the history of milk fever in insemination and replacement decisions, a significantly reduced net income per cow was found in some herds. We concluded that important benefits from using such a herd model are the capability of accounting for herd management factors and the advantage of avoiding to double count the indirect effects from disease, such as increased risk of other diseases, poorer reproduction results, and increased risk of culling and death.

Animals↗

Risk models for rebleeding and postoperative mortality in bleeding gastric ulcer.

In order to better define management policies we attempted to construct risk models for rebleeding on initial conservative management and mortality after emergency surgery for failure of medical therapy in 387 patients with bleeding gastric ulcer. Several different models were constructed using logistic regression analysis with validation by the 'leaving-one-out' method. However, despite large patient numbers, modelling in this way is difficult because of inherent wide variation between patients. Suitable models for rebleeding were regarded as rather unsatisfactory, for although overall accuracy was 86%, sensitivity was only 54%. More promising was a model for mortality after emergency surgery which had an accuracy of 93% and a sensitivity of 80%. Such mortality models incorporating age, history of previous malignant disease or dyspepsia, the presence or absence of ascites and total transfusion requirements may well prove to be of value in surgical practice. This paper seeks to examine the process of modelling rebleeding and mortality and of interpreting the models produced.

Aged↗

Dynamic selection of models for a ventilator-management advisor.

A ventilator-management advisor (VMA) is a computer program that monitors patients who are treated with a mechanical ventilator. A VMA implements a patient-specific physiologic model to interpret patient data and to predict the effects of alternative control settings for the ventilator. Because a VMA evaluates its physiologic model repeatedly during each cycle of data interpretation, highly complex models may require more computation time than is available in this time-critical application. On the other hand, less complex models may be inaccurate if they are unable to represent a patient's physiologic abnormalities. For each patient, a VMA should select a model that balances the tradeoff of prediction accuracy and computation-time complexity. I present a method to select models that are at an appropriate level of detail for time-constrained decision tasks. The method is based on a local search in a graph of models (GoM) for a model that maximizes the tradeoff of computation-time complexity and prediction accuracy. For each model under consideration, a belief network computes a probability of model adequacy given the qualitative prior information, and the goodness of fit of the model to the data provides a measure of the conditional probability of adequacy given the quantitative observations. I apply this method to the problem of model selection for a VMA. I describe an implementation of a graph of physiologic models that range in complexity from VentPlan, a simple model with 3 compartments, to VentSim, a multicompartment model with detailed airway, circulation and mechanical ventilator components.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗

A case study on the choice, interpretation and checking of multilevel models for longitudinal binary outcomes.

Recent advances in statistical software have led to the rapid diffusion of new methods for modelling longitudinal data. Multilevel (also known as hierarchical or random effects) models for binary outcomes have generally been based on a logistic-normal specification, by analogy with earlier work for normally distributed data. The appropriate application and interpretation of these models remains somewhat unclear, especially when compared with the computationally more straightforward semiparametric or 'marginal' modelling (GEE) approaches. In this paper we pose two interrelated questions. First, what limits should be placed on the interpretation of the coefficients and inferences derived from random-effect models involving binary outcomes? Second, what diagnostic checks are appropriate for evaluating whether such random-effect models provide adequate fits to the data? We address these questions by means of an extended case study using data on adolescent smoking from a large cohort study. Bayesian estimation methods are used to fit a discrete-mixture alternative to the standard logistic-normal model, and posterior predictive checking is used to assess model fit. Surprising parallels in the parameter estimates from the logistic-normal and mixture models are described and used to question the interpretability of the so-called 'subject-specific' regression coefficients from the standard multilevel approach. Posterior predictive checks suggest a serious lack of fit of both multilevel models. The results do not provide final answers to the two questions posed, but we expect that lessons learned from the case study will provide general guidance for further investigation of these important issues.

Journal Article↗

Beyond the decoupling approximation in the model free approach for the interpretation of NMR relaxation of macromolecules in solution.

The model free (MF) approach allows straightforward extraction of generalized order parameters and correlation times for internal and overall bond vector reorientational fluctuations from NMR spin relaxation measurements for macromolecules in solution. The drawback of this approach is the use of a decoupling approximation that neglects correlations between internal and overall molecular motions. These correlations are significant when fluctuation amplitudes are less than the size of the "cage" that restricts the bond vector. In this regime, motion of the bond vector is only indirectly affected by molecule fluctuations through the orienting potential for the local director axis. By separating the regimes of large and small amplitude molecular fluctuations, an expression for the spectral density function is derived that does not invoke the decoupling approximation, but that relies on the same macroscopic level of description as the original MF approach. The parameters of the spectral density function provide insight into the effects on the MF parameters that result from violation of the decoupling approximation.

Computer Simulation↗

GT-Mamba: a Topology-Aware Graph-State space model for robust and interpretable epigenetic age prediction.

MOTIVATION: Current epigenetic clocks face a trade-off between predictive accuracy and biological interpretability, often relying on dataset-specific correction to generalize across cohorts. We propose GT-Mamba, a novel architecture that integrates a Structure-Aware Graph Transformer with the Mamba state space model. This design captures CpG topological correlations and genome-wide long-range dependencies. RESULTS: GT-Mamba demonstrates strong out-of-the-box robustness across heterogeneous independent validation cohorts, achieving a weighted average MAE of 4.43 years. Notably, it effectively generalizes to EPIC 850k arrays despite partial feature missingness, and maintains consistent performance across homologous age distribution shifts (MAE 2.94 years in a young cohort). Ablation studies confirm that graph topology contributes to improved robustness against noise. Mechanistic analysis suggests that the model captures methylation patterns associated with both developmental and functional processes. AVAILABILITY: Source code and pre-trained models are freely available at https://github.com/NENUBioCompute/GT-Mamba and archived on Zenodo (DOI: 10.5281/zenodo.19703155).

Epigenesis, Genetic↗

Identification of antibody epitopes within the CB-11 peptide of type II collagen. II. Computer modelling studies of peptides and the interpretation of epitope scanning results.

Computer modelling techniques were used to investigate the structure of 8-mers from the CB-11 peptide of bovine type II collagen which were recognised by sera from rats which had previously been injected with bovine type II collage. It was discovered that all the hydrophobic peptides recognised by the rat sera were predicted to have collagenous-like secondary structures. The primary structure of the 8-mers which were recognised was also compared against the sequences in the OWL protein sequence database. The combined results of the computer modelling and sequence analysis suggested that the sequence Gly-Pro-Gly-Phe-Pro is a minimal B cell epitope of the CB-11 fragment of bovine type II collagen.

Amino Acid Sequence↗

A plausible molecular interpretation of the polar coordinate model with a centripetal degeneracy of distinctive field values.

I have attempted to interpret, in molecular terms, the polar coordinate model for epimorphic regulation, revised to accommodate the rigorously-held constraints of the polar coordinate system (Sibatani, 1981). If the angular coordinate of the field value is represented by a physical variable in the form of a proportion function, R, to be defined as the intensity ratio of two morphogen curves then R can stay unchanged along any radius mapped on the actual space, while the intensity of the two morphogens together approaches zero towards the field centre, satisfying the requirement of the centripetal degeneracy of the distinctive angular field values. Implications of this idea are discussed in theoretical and molecular terms as well as in respect of interpretations of some experimental data.

Animals↗

Validation of a model of left ventricular segmentation for interpretation of SPET myocardial perfusion images.

Several models of left ventricular segmentation have been developed that assume a standard coronary artery distribution, and are currently used for interpretation of single-photon emission tomography (SPET) myocardial perfusion imaging. This approach has the potential for incorrect assignment of myocardial segments to vascular territories, possibly over- or underestimating the number of vessels with significant coronary artery disease (CAD). We therefore sought to validate a 17-segment model of myocardial perfusion by comparing the predefined coronary territory assignment with the actual angiographically derived coronary distribution. We examined 135 patients who underwent both coronary angiography and stress SPET imaging within 30 days. Individualized coronary distribution was determined by review of the coronary angiograms and used to identify the coronary artery supplying each of the 17 myocardial segments of the model. The actual coronary distribution was used to assess the accuracy of the assumed coronary distribution of the model. The sensitivities and specificities of stress SPET for detection of CAD in individual coronary arteries and the classification regarding perceived number of diseased coronary arteries were also compared between the two coronary distributions (actual and assumed). The assumed coronary distribution corresponded to the actual coronary anatomy in all but one segment (#3). The majority of patients (80%) had 14 or more concordant segments. Sensitivities and specificities of stress SPET for detection of CAD in the coronary territories were similar, with the exception of the RCA territory, for which specificity for detection of CAD was better for the angiographically derived coronary artery distribution than for the model. There was 95% agreement between assumed and angiographically derived coronary distributions in classification to single- versus multi-vessel CAD. Reassignment of a single segment (segment #3) from the LCX to the LAD territory further improved the model's fit with the anatomic data. It is concluded that left ventricular segmentation using a model with assumed coronary artery distribution is valid for interpretation of SPET myocardial perfusion imaging.

Coronary Angiography↗

Electrical properties of frog skeletal muscle fibers interpreted with a mesh model of the tubular system.

This paper presents the construction, derivation, and test of a mesh model for the electrical properties of the transverse tubular system (T-system) in skeletal muscle. We model the irregular system of tubules as a random network of miniature transmission lines, using differential equations to describe the potential between the nodes and difference equations to describe the potential at the nodes. The solution to the equations can be accurately represented in several approximate forms with simple physical and graphical interpretations. All the parameters of the solution are specified by impedance and morphometric measurements. The effect of wide circumferential spacing between T-system openings is analyzed and the resulting restricted mesh model is shown to be approximated by a mesh with an access resistance. The continuous limit of the mesh model is shown to have the same form as the disk model of the T-system, but with a different expression for the tortuosity factor. The physical meaning of the tortuosity factor is examined, and a short derivation of the disk model is presented that gives results identical to the continuous limit of the mesh model. Both the mesh and restricted mesh models are compared with experimental data on the impedance of muscle fibers of the frog sartorius. The derived value for the resistivity of the lumen of the tubules is not too different from that of the bathing solution, the difference probably arising from the sensitivity of this value to errors in the morphometric measurements.

Animals↗

Mental models change rapidly with implicitly acquired information about the local environment: a two-tone image study.

The projection of 3-D objects to 2-D images necessitates a loss of information, thus the shape of volumetric objects depicted in images is inherently ambiguous. The results of 3 experiments suggest observers use mental models of the local visual environment to constrain image interpretation. These models change quickly and dramatically to accommodate implicitly acquired information. Observers viewed very high-contrast (2-tone) images of novel volumetric objects. Before priming, novel 2-tone images appeared 2-D. After incidental exposure to similar objects in grayscale or familiar objects in 2-tone, the test images appeared volumetric. Incidental leaming appears to alter observers' mental models, thus causing an alteration in image interpretation in the absence of any image change. Highlights were interpreted more accurately than shadows, suggesting shadows play a secondary role in shape recovery.

Adolescent↗

A mathematical high bar-human body model for analysing and interpreting mechanical-energetic processes on the high bar.

The aims of this study were: 1. To study the transfer of energy between the high bar and the gymnast. 2. To develop criteria from the utilisation of high bar elasticity and the utilisation of muscle capacity to assess the effectiveness of a movement solution. 3. To study the influence of varying segment movement upon release parameters. For these purposes a model of the human body attached to the high bar (high bar-human body model) was developed. The human body was modelled using a 15-segment body system. The joint-beam element method (superelement) was employed for modelling the high bar. A superelement consists of four rigid segments connected by joints (two Cardan joints and one rotational-translational joint) and springs (seven rotation springs and one tension-compression spring). The high bar was modelled using three superelements. The input data required for the high bar human body model were collected with video-kinematographic (50 Hz) and dynamometric (500 Hz) techniques. Masses and moments of inertia of the 15 segments were calculated using the data from the Zatsiorsky et al. (1984) model. There are two major phases characteristic of the giant swing prior to dismounts from the high bar. In the first phase the gymnast attempts to supply energy to the high bar-humanbody system through muscle activity and to store this energy in the high bar. The difference between the energy transferred to the high bar and the reduction in the total energy of the body could be adopted as a criterion for the utilisation of high bar elasticity. The energy previously transferred into the high bar is returned to the body during the second phase. An advantageous increase in total body energy at the end of the exercise could only be obtained through muscle energy supply. An index characterising the utilisation of muscle capacity was developed out of the difference between the increase in total body energy and the energy returned from the high bar. A delayed and initially slow but even reduction of hip and shoulder angles provided more advantageous release conditions. The total body energy could be improved by up to 15%, the vertical CM release velocity by up to 10% and the angular momentum by up to 35%.

Algorithms↗

Vestibular adaptation: how models can affect data interpretations.

Vestibular adaptation can be induced optically or by chemical or physical injury to the vestibular apparatus or the brain stem. In searching for the sites or mechanisms of vestibular adaptation, neurophysiologists often rely on comparing central resting (background) activities and central modulations (sensitivity) during vestibular stimulation, before and after motor learning or vestibular compensation. It is assumed that adapted central sites must exhibit modulation changes that parallel vestibulo-ocular reflex changes. Using model simulations and analysis, we will show that such presumptions may be misleading. First, using a simple schematic of interconnected cells or nuclei, one can show that modulation depth and background "tone" can be modified (or fixed) independently, using weightings on direct or indirect afferent projections. That is, if synaptic weights along all stimulus pathways are altered, one may fix or strongly modify central premotor characteristics in a manner apparently unrelated to global reflex changes. In the vestibulo-ocular reflex, the dominant premotor pathways contain position-vestibular-pause cells and eye-head-velocity cells (which are behaviorally similar to floccular-target neurons). Several experiments have reported negligible changes in the velocity sensitivity of position-vestibular-pause cells, despite large gain changes in the vestibulo-ocular reflex induced by training with visual-vestibular conflict. On the other hand, the modulation changes on floccular-target neurons (position-vestibular-pause) can be much larger than the changes in reflex gain. Using a bilateral vestibulo-ocular reflex model, we show that overall increases or decreases in reflex gain can be expressed (even overexpressed) in one particular subgroup of premotor neurons. Nevertheless, such observations are theoretically compatible with synaptic changes on all primary projections in a widely interconnected central network. Hence, stable neural responses during reflex adaptation are not sufficient to exclude a potential site of sensory-motor adaptation. Similarly, modified neural responses (as in cerebellum) need not necessarily imply a direct role in supporting the adapted state. Model predictions should help to design additional experimental protocols, to test hypotheses, and to refine diagnostic measures of recovery after vestibular lesions.

Adaptation, Physiological↗

An anatomical, histochemical, and autoradiographic study of the ever-growing molar dentition of Microtus with comments on the role of structure in growth and eruption.

An analysis of the microanatomy of the molar dentition of Microtus utilizing histological, histochemical and autoradiographic techniques reveals a complex architecture with distinctive morphogenic mechanisms which respond to the functional requirements of the organism. These mechanisms include; the maintenance of continued growth and eruption of the molars to compensate for continued hard tissue loss from wear at the occlusal surface of the crown throughout the entire lifespan of the orgainism and a positive feedback repair mechanism to protect the growth systems from the potential destruction this normal occlusal wear could initiate. An awareness and understanding of these phenomena is of significant value for interpreting palentological specimens and formulating a theoretical model for interpreting the evolution of Microtine molar dentitions.

Alveolar Process↗