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At least 1,423 records · Page 79Linked to original sources
PubMed2004

Assessing lung cancer risk in railroad workers using a first hitting time regression model.

This article examines the application of a first hitting time (FHT) model, using an operational time scale, to assess mortality risk differentials of the work environment. A major case application is presented that applies the model to three job categories of railroad workers. The data set involves a study of more than 50 000 workers with mortality assessed from 1959 to 1996. Lung cancer mortality was assessed because of a suspected link to diesel exhaust exposure. Based on a model that stipulates that death occurs when the disease state of a subject first hits a threshold value, the FHT model provides insights into factors influencing disease progression. In this application, in particular, the findings suggest that a job category in 1959 alters the risk of death from lung cancer.

Journal Article↗
PubMed2006

Sinusoid = light bar + dark bar?

A sinusoidal grating can be viewed as a series of light and dark bars. Here we measure the contrast discrimination thresholds for light and dark bars individually, and find that the contrast discrimination thresholds for the whole sinusoid can be explained as ideal summation of the light and dark bar thresholds. We propose a model for light bar, dark bar, and sinusoidal contrast discrimination which involves local light adaptation and multiplicative noise. The model accounts for the data very well, and also accounts for contrast discrimination of light and dark edges.

Adaptation, Ocular↗
PubMed2004

Quantitative structure-activity relationship modeling of alcohol, ester, aldehyde, and ketone flavor thresholds in beer from molecular features.

Three quantitative structure-activity relationship approaches-principal components regression, partial least-squares regression, and alternating conditional expectations-were used to investigate relationships between the flavor thresholds of 38 alcohols, 40 esters, 45 aldehydes, and 43 ketones in beer and their structures. Strong nonlinear relationships between the logarithm of the flavor threshold and four or five structure descriptors were found for each class of compounds (R2 = 0.920, 0.937, 0.920, and 0.928 for alcohols, esters, aldehydes, and ketones, respectively). Simple nonlinear relationships between the alcohol, ester, and aldehyde thresholds and the numbers of hydrogen atoms in the molecules were also demonstrated.

Alcohols↗
PubMed2006

The mechanism for stochastic resonance enhancement of mammalian auditory information processing.

BACKGROUND: In a mammalian auditory system, when intrinsic noise is added to a subthreshold signal, not only can the resulting noisy signal be detected, but also the information carried by the signal can be completely recovered. Such a phenomenon is called stochastic resonance (SR). Current analysis of SR commonly employs the energies of the subthreshold signal and intrinsic noise. However, it is difficult to explain SR when the energy addition of the signal and noise is not enough to lift the subthreshold signal over the threshold. Therefore, information modulation has been hypothesized to play a role in some forms of SR in sensory systems. Information modulation, however, seems an unlikely mechanism for mammalian audition, since it requires significant a priori knowledge of the characteristics of the signal. RESULTS: We propose that the analysis of SR cannot rely solely on the energies of a subthreshold signal and intrinsic noise or on information modulation. We note that a mammalian auditory system expends energy in the processing of a noisy signal. A part of the expended energy may therefore deposit into the recovered signal, lifting it over threshold. We propose a model that in a rigorous mathematical manner expresses this new theoretical viewpoint on SR in the mammalian auditory system and provide a physiological rationale for the model. CONCLUSION: Our result indicates that the mammalian auditory system may be more active than previously described in the literature. As previously recognized, when intrinsic noise is used to generate a noisy signal, the energy carried by the noise is added to the original subthreshold signal. Furthermore, our model predicts that the system itself should deposit additional energy into the recovered signal. The additional energy is used in the processing of the noisy signal to recover the original subthreshold signal.

Algorithms↗
PubMed2002

Peeling model for cell detachment.

In many experimental situations, the adhesion of cells to solid substrates is due to non-covalent chemical bonds. It is the thesis of this paper that many phenomena occurring in cell detachment experiments, such as in I (E. Decavé, G. Garriver, Y. Brechet, B. Fourcade, F. Bruckert, Biophys. J. 82, 2383 (2002)), result from the static and dynamic properties of the adhesive bridges at the extreme margin of the cell. This region defines the adhesive belt where the distribution of connected bonds crosses over to zero where the membrane leaves the substrate. The theoretical model we introduce in this paper discusses the threshold force together with the peeling velocity in the same theoretical framework. In this one-dimensional model, the threshold force results from a non-homogeneous distribution of anchor proteins along the membrane so that the adhesive belt increases its capacity to resist motion with increasing the external force. Analyzing the kinetics of the the contact line motion, we derive the characteristic relationship speed versus external force and we describe the non-equilibrium state of the adhesive belt as a function of the speed. We discuss our model in view of the experimental results obtained with D. discoideum for hydrodynamic shear experiments. Our results could be also confronted to single-cell observations.

Journal Article↗
PubMed1986

Pain threshold changes in adjuvant-induced inflammation: a possible model of chronic pain in the mouse.

A chronic hyperalgesic condition was induced in mice by the injection of Freund's complete adjuvant (FCA) into the lower lumbar region or directly into the hind footpads. Although little or no visible inflammation was observed after a single intradermal injection of FCA into the lower lumbar area of rats or mice, significant alterations in nociceptive thresholds occurred in each species as determined by decreases in response latency in tail-flick and hot-plate assays. Unilateral intraplantar administration of FCA in mice resulted in visible inflammation in the area of the tibiotarsal (ankle) joint. Changes in the response latency to a noxious stimulus in the areas surrounding the inflamed joint were similar to those observed in non-inflamed limbs, suggesting that changes in sensitivity to noxious stimuli were not merely the result of local hypersensitivity of the inflamed tissue, but may also be due to alterations in nociception at the level of the central nervous system (CNS). When the chronic inflammatory condition induced in the mouse tibiotarsal joint was evaluated by histological and morphological techniques, it was found to have the same characteristics as described in the early stages of FCA-induced arthritis in rats. The similarities between the response to FCA in rat and mouse suggest that injection of FCA in mice may prove to be a useful model for the study of chronic pain in mice as well as in rats.

Adjuvants, Immunologic↗
PubMed2004

L-selectin-mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding events.

L-selectin-mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments, which supports the interpretation that L-selectin-mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin-mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the time scale of 10(-1) seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of 10(4) Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first-order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin, and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.

Cell Movement↗
PubMedDate not supplied

Application of treatment thresholds to diagnostic-test evaluation: an alternative to the comparison of areas under receiver operating characteristic curves.

Diagnostic tests are often evaluated by comparison of the areas under receiver operating characteristic (ROC) curves. In this study the authors compared this approach with a more direct method that takes into account consequences of a diagnosis. Data from a prospective study of diagnosis of pulmonary embolism were used for a motivating example. Using multivariable logistic regression analysis, three diagnostic models were built and compared based on their ROC curves. Although model 1 (0.706) and model 2 (0.702) had the same ROC-curve area, they performed differently when risks and benefits of subsequent decisions were considered by applying the treatment probability threshold. Models 1 and 3 (0.611) had substantially different ROC-curve areas but performed similarly taking into account the therapeutic consequences. This demonstrates that comparison of diagnostic tests using the areas under the ROC curves may lead to erroneous conclusions about therapeutic usefulness. To correspond to daily practice, it would be more appropriate to also consider the clinical implications in evaluating diagnostic tests. This is made feasible by explicit definition and application of a treatment threshold.

Decision Support Techniques↗
PubMed2001

A comparison between human magnetostimulation thresholds in whole-body and head/neck gradient coils.

Gradient coil magnetostimulation thresholds were measured in a group of 20 volunteers in both a whole-body gradient coil and a head/neck gradient coil. Both coils were operated using both x and y axes simultaneously (xy oblique mode). The waveform applied was a 64-lobe trapezoidal train with 1-ms flat-tops and varying rise times. Thresholds were based on the subjects' perception of stimulation, and painful sensations were not elicited. Thresholds were expressed in terms of the total gradient excursion required to cause stimulation as a function of the duration of the excursion. Thresholds for each subject were fit to a linear model, and values for the threshold curve slope (SR(min)) and vertical axis intercept (DeltaG(min)) were extracted. For the body coil, the mean values were: SR(min) = 62.2 mT/m/ms, DeltaG(min) = 44.4 mT/m. For the head/neck coil, the mean values were: SR(min) = 87.3 mT/m/ms, DeltaG(min) = 78.9 mT/m. These curve parameters were combined with calculated values for the induced electric field as a function of position within the coil to yield the tissue specific parameters E(r) (electric field rheobase) and tau(c) (chronaxie). For tissue stimulated within the body coil, the mean values were: E(r) = 1.8 V/m, tau(c) = 770 micros. For tissue stimulated within the head/neck coil, the mean values were: E(r) = 1.3 V/m, tau(c) = 1100 micros. Scalar potential contributions were not included in the calculation of induced electric fields. The mean threshold curves were combined with the gradient system performance curves to produce operational limit curves. The operational limit curves for the head/neck coil system were verified to be higher than those of the whole-body coil; however, the head/neck system was also found to be physiologically limited over a greater range of its operation than was the body coil. Subject thresholds between the two coils were not well correlated.

Female↗
PubMed1998

Hematopoietic model with moving boundary condition and state dependent delay: applications in erythropoiesis.

An age-structured model for erythropoiesis is extended to include the active destruction of the oldest mature cells and possible control by apoptosis. The former condition, which is applicable to other population models where the predator satiates, becomes a constant flux boundary condition and results in a moving boundary condition. The method of characteristics reduces the age-structured model to a system of threshold type differential delay equations. Under certain assumptions, this model can be reduced to a system of delay differential equations with a state dependent delay in an uncoupled differential equation for the moving boundary condition. Analysis of the characteristic equation for the linearized model demonstrates the existence of a Hopf bifurcation when the destruction rate of erythrocytes is modified. The parameters in the system are estimated from experimental data, and the model is simulated for a normal human subject following a loss of blood typical of a blood donation. Numerical studies for a rabbit with an induced auto-immune hemolytic anemia are performed and compared with experimental data.

Anemia, Hemolytic, Autoimmune↗
PubMed1987

Correlative development of cochlear action potential sensitivity, latency, and frequency selectivity.

The present study was undertaken in order to study the rate of maturation of the cochlear action potential sensitivity, latency, and tuning curves for various stimulus frequencies and to correlate the development of latency and frequency selectivity with threshold development. This study showed a two-stage model of maturation in which thresholds and latencies declined rapidly and linearly during the first stage, and slowly and exponentially during the last stage. These results suggest that latencies and thresholds are influenced by similar maturational processes. The correlative study of frequency selectivity and thresholds showed a linear relationship during the period of rapid maturation, and conversely, a dissociation between the development of tuning and threshold during the late period of slow acquisition of adult sensitivity. This dissociation was particularly marked at 8 kHz where Q10 values continued to increase even when thresholds were adultlike. These results were discussed in relation to anatomical and functional data available from the rat cochlea.

Age Factors↗
PubMed2005

Application of stochastic measurement models to visual function rating scale questionnaires.

PURPOSE: To test hypotheses that low vision patient responses to visual function rating scale questionnaires conform to an additive conjoint structure and that the Likert score is a sufficient statistic for the latent patient trait; to compare results for two competing stochastic measurement models; and to determine if different questionnaires measure the same construct in low vision patients. METHODS: Visual function rating scale questionnaires were administered to 284 low vision subjects by telephone. Each subject was administered two of four questionnaires: ADVS, NEI VFQ-25 plus supplement, expanded VAQ, and VF-14. RESULTS: Data were analyzed with the Muraki item response model and the Andrich measurement model. The estimates of latent person, item, and response threshold measures from the two models are linearly related. The Muraki model produced a better overall fit to the item response data, the Andrich model produced a better fit to the average ratings for each person and item. Fit statistics for the Andrich model were proportional to the item-dependent discrimination parameter in the Muraki model. The ADVS was the most accurate measure and the NEI VFQ was the least. Reliability was similar for all four instruments. Person measures for each pair of instruments were linearly related indicating that all four instruments measured the same construct. The person measure estimate from the Andrich model is monotonic with the average rating. That relationship suggests a transformation of the Likert score that can correct the floor and ceiling effects in rating scale data. CONCLUSIONS: Patient responses to all four questionnaires conform to varying degrees to an additive conjoint structure. The Likert score is a sufficient statistic for the ADVS and the VAQ, but not for the NEI VFQ or VF-14. All four instruments measure the same construct in the low vision population, but they differ in measurement accuracy and precision.

Adult↗
PubMed1989

Age-associated change in pain threshold measured by transcutaneous neuronal electrical stimulation.

The measurement of cutaneous pain threshold using the Neuromod Selectra Model 7750 Transcutaneous Neuronal Electrical Stimulator is described. Pain threshold, measured in 520 healthy volunteers aged 5-105 years, increased with age. Consistent values were obtained in 22 healthy volunteers on three successive days. Pain threshold may be rapidly measured by this method which is potentially of value in the assessment of patients with neurological deficits.

Adolescent↗
PubMed2004

Males lose hearing earlier in mouse models of late-onset age-related hearing loss; females lose hearing earlier in mouse models of early-onset hearing loss.

Gender-related differences in human hearing have been attributed to genetic, environmental, and/or genetic x environmental interactive factors. These differences tend to increase with age, with males showing greater high frequency threshold elevations. An appropriate animal model could aid in prediction, treatment, and prevention of some of these losses. This paper examines inbred strains of mice that are widely used as models of late- (CBA/J and CBA/CaJ) and early- (C57BL/6J) onset age-related hearing loss. In the former two genotypes, the thresholds to high frequency stimuli of the auditory brainstem response (ABR) are higher in the male than in the female. This gender difference was less pronounced in thresholds to the cochlear nerve envelope response of the CBA/CaJ, although this response was more sensitive to the influence of age than was the ABR. In contrast, the male C57BL/6J had more sensitive thresholds than the female, with both measures showing massive loss of sensitivity with increasing age. The data are discussed in terms of the applicability of these animals as tools for examining factors that degrade cochlear function.

Aging↗
PubMed1985

Retinitis-pigmentosa-like tapetoretinal degeneration in a rabbit breed.

By chance, we found a rabbit strain with retinal dystrophy. The eyes of these rabbits were examined by ophthalmoscopy, electroretinography, histology, and cytology--the latter after retina dissociation with papaine. The results suggest this rabbit strain to be a possible animal model for human retinitis pigmentosa.

Animals↗
PubMed1998

The economics of febrile neutropenia: implications for the use of colony-stimulating factors.

The occurrence of fever and neutropenia following cancer chemotherapy generally prompts hospitalisation for evaluation and treatment. Colony-stimulating factors (CSFs) have been shown to reduce the risk of febrile neutropenia (FN) and the need for hospitalisation in such patients. This study was undertaken to obtain estimates of the actual institutional costs associated with FN and the impact of these costs on threshold estimates for the appropriate use of CSFs. Total hospital expenditures for patients admitted with FN over a 2 year period were studied. A cost allocation function was utilised to allocate all direct costs for non-revenue-generating support centres to revenue-generating service centres as indirect costs. A cost accounting function was then utilised to allocate direct and indirect costs for each service centre to the charge code level. Two groups of patients were defined based on diagnostic codes to represent the spectrum of patients with FN. Total hospital costs were estimated and incorporated into a cost model for the use of CSFs. Variation in the total cost of hospitalisation for FN relates primarily to differences in the average length of stay. The daily cost of hospitalisation was comparable in the groups studied, averaging between US$1675 and US$1892. Incorporation of these cost estimates into the cost model yielded FN risk threshold projections for CSF use in the range of 20-25%. Preliminary studies suggest that incorporation of non-medical, indirect and intangible costs into the CSF decision models will further decrease FN risk threshold projections. Total hospitalisation cost estimates for managing patients with FN are greater than those previously reported, reducing projected FN risk thresholds for CSF use.

Adult↗