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PubMed1993

The effects of age and diabetes mellitus on nerve function.

OBJECTIVE: This project evaluated the association of age and vibratory thresholds (assessment modality of large sensory nerve fibers) in subjects with and without diabetes mellitus. DESIGN: Cross-sectional study. SETTING: Medical Research Institute of Delaware. PARTICIPANTS: Individuals with non-insulin-dependent diabetes mellitus and non-diabetic control subjects. MEASUREMENTS: Vibratory thresholds were examined in four age groups (ie, < 45 yrs, 45-54 yrs, 55-64 yrs, > or = 65 yrs). The independent association of age, duration of diabetes, height, gender, glycemic control, and smoking history were analyzed in terms of their relationship to vibratory thresholds. MAIN RESULTS: Vibratory thresholds increased with age for both control and diabetic subjects. Comparing controls with diabetic subjects in the same age categorizes revealed significant differences for vibratory thresholds only in the > or = 65 year old age group. Modeling with vibratory thresholds as the dependent variable showed that age and male gender were independently associated with vibratory thresholds for the controls and explained the majority of the variability (R2 = 0.79). Age, duration of diabetes, and height were independently associated with vibratory thresholds for the diabetic subjects but explained much less of the variability (R2 = 0.39). CONCLUSIONS: The results suggest an acceleration of the natural aging process for large sensory nerve fiber function in diabetic subjects. Thus, young diabetic subjects may be at a risk of lower extremity complications as a result of injuries similar to that older non-diabetic individuals.

Adult↗

PubMed1999

The relationship between the myocardial kinetics of meperidine and its effect on myocardial contractility: model-independent analysis and optimal regional model.

The myocardial kinetics of meperidine and the relationship between these kinetics and the effect of meperidine on myocardial contractility (maximum positive rate of change of left ventricular pressure) were examined by analysis of previously published data collected in sheep after the i.v. injection of 100 mg of meperidine over 1 s. There was significant hysteresis between reductions in myocardial contractility and the arterial concentrations of meperidine, but not the coronary sinus blood (effluent from the heart) or calculated myocardial concentrations. The peak reduction in contractility occurred after the peak arterial concentration, at the time of the peak myocardial concentration, but before the peak coronary sinus concentration, suggesting that the site of drug action in the heart was not in equilibrium with either arterial blood or effluent blood from the heart. The most appropriate form of a dynamic model (a linear model with a threshold) was determined, without the need to assume a kinetic model, by directly fitting the observed reductions in myocardial contractility to the calculated myocardial concentrations. To determine the optimal kinetic and combined kinetic-dynamic models, a variety of one-, two-, and three-compartment models of the myocardium were fitted to the coronary sinus concentrations by using hybrid modeling. These included "tank in series" models that accounted well for drug dispersion and "peripheral compartment" models that accounted well for deep distribution. The most appropriate model was a "compilation" model, which incorporated features of both these extremes and was a better fit to the observed data than either a traditional single flow-limited compartment or a traditional membrane-limited model.

Algorithms↗

PubMed1988

Pharmacokinetic-pharmacodynamic modeling of midazolam effects on the human central nervous system.

The effect of midazolam on alpha-activity of the EEG and latency of the P-100 of the visual evoked response (VER) was studied in six healthy subjects. Drug concentration was related to effect with the Emax model that was used with either a threshold drug concentration or a sigmoid exponent. An effect compartment was included in the pharmacokinetic-pharmacodynamic model. Four subjects showed hysteresis, and mean values of half-lives-k(eo) ranged from 0.26 to 0.60 hour. Mean values of EC50 ranged from 42.0 to 48.1 ng/ml. Goodness of fit did not differ significantly between the sigmoid Emax model and the threshold Emax model. The sigmoid exponent estimated was 3.7 +/- 1.8 (EEG, mean +/- SD) and 2.9 +/- 1.4 (VER); the threshold concentration was estimated at 15.7 +/- 11.1 ng/ml (EEG) and 11.3 +/- 7.0 ng/ml (VER). We conclude that the Emax model adequately describes the relationship between midazolam concentration and effect and that the sigmoid exponent can be substituted by a threshold drug concentration, with a comparable fit of the model to the data.

Central Nervous System↗

PubMed1994

Perspectives: a vital biomechanical model of synovial joint design.

Making a durable joint requires adapting the one present at birth to its subsequent mechanical usage and then maintaining it. The total loads on a joint's momentarily loaded area plus the size of that area determine the unit loads on its articular cartilage and subchondral bone. Given those facts, this model suggests the following. For adaptation: As is true for bone, a threshold range of unit loads that could turn cartilage modeling ON would lie below this tissue's microdamage threshold. When a joint's unit loads rose to that modeling threshold, chondral modeling would begin enlarging the momentarily loaded area to reduce and keep the unit loads on it below the microdamage thresholds of the bone and cartilage supporting that area. For maintenance: Maintenance activities would control the stiffness of cartilage and bone, which would also affect a joint's momentarily loaded area. These activities would usually repair whatever microdamage normally arises in those tissues, and could modify their microdamage thresholds too. In children, modeling and maintenance in bone and cartilage would function effectively. In adults chondral modeling becomes ineffective, but maintenance activities in bone and cartilage would remain effective, and likewise for modeling in the subchondral bone. This model assigns special importance in joint design to the stiffness of bone, cartilage, and ligament (as distinguished from their strength), to the typical largest unit loads applied to them by a subject's usual weekly physical activities, and to their microdamage.

Age Factors↗

PubMed1991

Image invariance with changes in size: the role of peripheral contrast thresholds.

The appearance of objects generally does not change with changes in the size of their retinal image that occur as the distance from the observer increases or decreases. Contrast constancy ensures this invariance for suprathreshold image features, but fully robust size invariance also requires invariance at threshold, so that near-threshold image features do not appear or disappear with distance changes. Since the angular size and the eccentricity of image features covary with distance changes, the threshold requirement for invariance could be satisfied approximately if contrast thresholds were to vary as the product of the spatial frequency and the eccentricity from the fovea. This model fits contrast thresholds for orientation identification over spatial frequencies of 1-16 cycles/deg and for retinal eccentricities of as much as 23 deg. Contrast detection thresholds from six different studies conform to this model over an even wider range of spatial frequencies and retinal eccentricities. The fitting variable, the fundamental eccentricity constant, was similar for all three studies that measured detection along the horizontal meridian and was higher for the orientation identification contrast thresholds along the same meridian. The eccentricity constant from studies that measured detection along the vertical meridian was higher than the constant calculated for the horizontal meridian and lower than the eccentricity constant for chromatic isoluminance gratings. Our model and these results provide new tools for analyzing the visibility of displays and for designing equal-visibility or variable-visibility displays.

Contrast Sensitivity↗

PubMed1995

Heart muscle contraction oscillation.

van der Pol developed a mathematical model for self-sustained radio oscillations described by his non-linear differential equation D2X + epsilon(X2-1)DX + X = 0 in which X is a function of time T and D/DT the differential operator to T. For epsilon = 0, this is the differential equation for the harmonic oscillator which has sinusoidal solutions. For epsilon not equal to 0 the equation is non-linear. If epsilon > 1 van der Pol coined the name relaxation oscillations for its solutions. These are non-linear and quite different from simple sinusoidal oscillations. They are mathematical models for many physical and biological phenomena. van der Pol suggested that his equation is also a model for the heartbeat. However, biomedical oscillations, including the heartbeat, have a threshold which the mathematical model described by van der Pol's equation does not possess. It has, in addition to an unstable origin, only a stable limit cycle of Poincaré. In this paper, van der Pol's equation is extended in such a way that it has in addition to a stable origin and a stable limit cycle, an unstable limit cycle. Because it possesses such an unstable limit cycle, the extension obtained is a mathematical model for a threshold oscillation. It is also shown that an asymmetric analogy of the extended equation is a mathematical model for an isometric contraction of the mammalian cardiac muscle.

Algorithms↗

PubMed2002

Meridional ray backscattering enhancements for empty truncated tilted cylindrical shells: measurements, ray model, and effects of a mode threshold.

Narrow-band backscattering experiments are used to characterize a meridional ray enhancement on a tilted, finite empty cylindrical shell having a blunt truncation. The meridional ray of the lowest order flexural leaky Lamb wave is examined, which has previously been shown to lead to large backscattering enhancements for excitation frequencies near and above the shell's coincidence frequency. The measurements are used to validate a convolution formulation ray theory describing the far-field backscattered amplitudes. Comparisons are also made with an approximate partial wave series solution for the finite cylindrical shell. The amplitude of the meridional ray enhancement is dependent on the nature of the reflection of the leaky wave from the shell truncation. While the peak measured amplitude agrees with predictions at low frequencies, experiments indicate the enhancement is degraded at high frequencies and exhibits an abrupt drop near the frequency of the mode threshold (cutoff) for the next-highest flexural mode. The nature of the leaky wave end reflection is examined using an approximate calculation of the energy reflection coefficient for leaky waves on a semi-infinite free plate. Results suggest the observed degradation is the result of mode conversion effects.

Acoustics↗

PubMed2006

[The effects of EPHPH on acoustic brainstem response threshold and its relative factors of senile model rats].

OBJECTIVE: The effect of EPHPH on aged deafness and its mechanism was explored by observing the effects of EPHPH on acoustic brainstem response threshold (ABRT), malondialdehyde (MDA), superoxide dismutase (SOD), total-nitrogen monoxide (NOS) and typing-nitrogen monoxide (iNOS) in cochleae tissues of senile model rats. METHOD: ABRT value was measured by induced potentiometer, MDA was measured by TBA colorimetry, SOD was determined by nitrite method, NOS and iNOS was determined by spectrophotometry in cochleae tissues of senile model rats that separately administered by gavage the alcoholic extract from 2.16, 4.32 or 8.64 g x kg(-1) x d(-1) PHPH once a day for 6 months. RESULT: ABRT value and MDA content notably increased, activities) of SOD, NOS and iNOS notably decreased in cochlear tissues of senile model rats from control. It indicated on relative analysis that relativity between ABRT value ascent and MDA ascent showed positive, relaxivities between ABRT value ascent and activity descents of SOD, NOS and iNOS showed all negative. It differently resisted ABRT value ascent and MDA ascent in cochlear tissues that senile model rats separately administered the alcoholic extract from 2.16, 4.32 or 8.64 g x kg(-1) x d(-1) PHPH whose relaxivities between quantity and efficiency showed all negative. It differently inhibited activity descents of SOD, NOS and iNOS in cochlear tissues that senile model rats separately administered various doses of EPHPH whose relaxivities between quantity and efficiency showed all positive. CONCLUSION: EPHPH may relieve the degree of aged deafness and its mechanism may be connected with eliminating oxygen free radicals and increasing the activities of SOD, NOS and iNOS in cochleae of natural senile rats.

Aging↗

PubMed1995

Threshold fluctuations in an N sodium channel model of the node of Ranvier.

Computer simulations of stochastic single-channel open-close kinetics are applied to an N sodium channel model of a node of Ranvier. Up to 32,000 voltage-gated sodium channels have been simulated with modified amphibian sodium channel kinetics. Poststimulus time histograms are obtained with 1000 monophasic pulse stimuli, and measurements are made of changes in the relative spread of threshold (RS) with changes in the model parameters. RS is found to be invariant with pulse durations from 100 microseconds to 3 ms. RS is approximately of inverse proportion to square-root of N. It decreases with increasing temperature and is dependent on passive electrical properties of the membrane as well as the single-channel conductance. The simulated RS and its independence of pulse duration is consistent with experimental results from the literature. Thus, the microscopic fluctuations of single, voltage-sensitive sodium channels in the amphibian peripheral node of Ranvier are sufficient to account for the macroscopic fluctuation if threshold to electrical stimulation.

Action Potentials↗

PubMed1998

Preultimate 4th/5th instar Trichoplusia ni naturally-injected with venom/calyx fluid from Chelonus curvimaculatus precociously metamorphose, rather than obey the metamorphic size threshold that would normally compel molting to a 5th/6th instar.

In normally regulated larval metamorphosis of Trichoplusia ni, a 4th, 5th or other numbered instar is a 'preultimate' instar, and will normally continue larval molting, if the larva has not yet surpassed the critical (minimal) size threshold corresponding to attainment of the 'ultimate' (metamorphic) instar. Natural injection of T. ni embryos with venom/calyx fluid of female Chelonus sp. near curvimaculatus caused 'penultimate' 4th or 5th instar larvae that would normally molt at least once more, to a 5th/6th instar, to instead precociously metamorphose without another larval molt. These effects were observed in naturally-injected insects that never contained either a parasite larva, a viable parasite embryo, or a parasite egg. These data demonstrate that this effect of venom/calyx fluid of this wasp to induce precocious metamorphosis, at an instar earlier than would otherwise have typically occurred under normal growth conditions, does not require the presence of a parasite larva. Other data did indicate the parasite larva contributes an additional effect that causes a 4th instar host (that from its size would normally require not just one, but at least two more larval molts to reach the metamorphic instar) to not grow to the size metamorphic threshold, but to instead, precociously metamorphose at an even smaller size than occurs with the venom/calyx fluid alone. Additionally, arylphorin was precociously highly expressed in parasitized hosts in a manner independent of a decline in the host JH titer. Therefore, the main target of the venom/calyx fluid activity to induce precocious metamorphosis appears to be an event upstream of the decline in JH production by the corpora allata. Pseudoparasitized hosts become developmentally arrested as precocious prepupae and express a 2.7kb polydnavirus transcript. The larger (but still subthreshold size) larvae showed less suppressed prepupal ecdysteroid titers, less developmental suppression, and a much weaker expression of that transcript. A general model for mechanisms of action of chelonine venom/calyx fluid, and larvae, to cause precocious host metamorphosis and suppressed prepupal development is presented that is based on the current 'size threshold' model of normal lepidopteran development, rather than the older, displaced 'instar count' model. By basing the model for chelonine regulation of host development on the current 'size threshold' model for normal development, the proposed model for chelonine action both accounts for observations reported on various species of that subfamily and makes useful, testable predictions.

Journal Article↗

PubMed2004

Reliability and validity of a short form household food security scale in a Caribbean community.

BACKGROUND: We evaluated the reliability and validity of the short form household food security scale in a different setting from the one in which it was developed. METHODS: The scale was interview administered to 531 subjects from 286 households in north central Trinidad in Trinidad and Tobago, West Indies. We evaluated the six items by fitting item response theory models to estimate item thresholds, estimating agreement among respondents in the same households and estimating the slope index of income-related inequality (SII) after adjusting for age, sex and ethnicity. RESULTS: Item-score correlations ranged from 0.52 to 0.79 and Cronbach's alpha was 0.87. Item responses gave within-household correlation coefficients ranging from 0.70 to 0.78. Estimated item thresholds (standard errors) from the Rasch model ranged from -2.027 (0.063) for the 'balanced meal' item to 2.251 (0.116) for the 'hungry' item. The 'balanced meal' item had the lowest threshold in each ethnic group even though there was evidence of differential functioning for this item by ethnicity. Relative thresholds of other items were generally consistent with US data. Estimation of the SII, comparing those at the bottom with those at the top of the income scale, gave relative odds for an affirmative response of 3.77 (95% confidence interval 1.40 to 10.2) for the lowest severity item, and 20.8 (2.67 to 162.5) for highest severity item. Food insecurity was associated with reduced consumption of green vegetables after additionally adjusting for income and education (0.52, 0.28 to 0.96). CONCLUSIONS: The household food security scale gives reliable and valid responses in this setting. Differing relative item thresholds compared with US data do not require alteration to the cut-points for classification of 'food insecurity without hunger' or 'food insecurity with hunger'. The data provide further evidence that re-evaluation of the 'balanced meal' item is required.

Adult↗

PubMed2002

How noise contributes to contrast invariance of orientation tuning in cat visual cortex.

The width of the orientation tuning curves of the spike response of neurons in V1 is invariant to contrast. This property constrains the possible mechanisms underlying orientation selectivity. It has been suggested that noise circumvents the iceberg effect that would prevent contrast invariance in the purely feedforward mechanism. Here we investigate systematically how noise contributes to the contrast invariance of orientation tuning curves in V1. We study three models of increasing complexity: a simple threshold-linear firing rate model, a leaky integrate-and-fire model, and a conductance-based model. We show that the noise transmutes the threshold nonlinearity of the input-output relationships into an approximate power law without a threshold within some firing rate range. This implies that, under certain conditions which are derived here, the tuning of the neuron output is approximately contrast invariant. In particular we show that this mechanism for contrast invariance requires that the neuron firing rate must not be too large and that increasing or lowering the contrast too much destroys this invariance. We also show that if this mechanism operates in V1, the spike response, R, and average voltage response V of the neurons in V1 should vary with the contrast, C, according to R(C)gamma proportional to V(C)gamma. The exponent gamma can be estimated from the amount by which the spike tuning curve is sharpened with respect to the voltage tuning curves of the neurons. This prediction does not depend on the specifics of the model and can be tested experimentally.

Animals↗

PubMedDate not supplied

Porcine skin visible lesion thresholds for near-infrared lasers including modeling at two pulse durations and spot sizes.

With the advent of such systems as the airborne laser and advanced tactical laser, high-energy lasers that use 1315-nm wavelengths in the near-infrared band will soon present a new laser safety challenge to armed forces and civilian populations. Experiments in nonhuman primates using this wavelength have demonstrated a range of ocular injuries, including corneal, lenticular, and retinal lesions as a function of pulse duration. American National Standards Institute (ANSI) laser safety standards have traditionally been based on experimental data, and there is scant data for this wavelength. We are reporting minimum visible lesion (MVL) threshold measurements using a porcine skin model for two different pulse durations and spot sizes for this wavelength. We also compare our measurements to results from our model based on the heat transfer equation and rate process equation, together with actual temperature measurements on the skin surface using a high-speed infrared camera. Our MVL-ED50 thresholds for long pulses (350 micros) at 24-h postexposure are measured to be 99 and 83 J cm(-2) for spot sizes of 0.7 and 1.3 mm diam, respectively. Q-switched laser pulses of 50 ns have a lower threshold of 11 J cm(-2) for a 5-mm-diam top-hat laser pulse.

Animals↗

PubMed2006

Localized activity profiles and storage capacity of rate-based autoassociative networks.

We study analytically the effect of metrically structured connectivity on the behavior of autoassociative networks. The steady state equations are derived for a generic input-output function, and then we focus on their solutions in the case of networks composed of three alternative simple rate-based model neurons: threshold-linear, binary or smoothly saturating units. For a connectivity which is short range enough the threshold-linear network shows localized retrieval states. The saturating and binary models also exhibit spatially modulated retrieval states if the highest activity level that they can achieve is above the maximum activity of the units in the stored patterns. We show that this saturation level together with the linear gain of the transfer function are important parameters that determine the possibility of localized retrieval. If the ratio of the number of stored patterns to the number of connections per unit goes to zero, while the latter goes to infinity, it is possible to derive an analytical formula for the critical value of the connectivity width, below which one observes spatially nonuniform retrieval states. The formula is also shown to offer a good first approximation for higher storage loads. We show that even in the case of localized retrieval the storage capacity remains proportional to the number of connections per neurons, with the proportionality constant lower by a factor of 3-4 compared to uniform retrieval. The approach that we present here is generic in the sense that there are no specific assumptions on the single unit input-output function nor on the exact connectivity structure.

Algorithms↗

PubMed2004

An integrated comprehensive workbench for inferring genetic networks: voyagene.

We propose an integrated, comprehensive network-inferring system for genetic interactions, named VoyaGene, which can analyze experimentally observed expression profiles by using and combining the following five independent inferring models: Clustering, Threshold-Test, Bayesian, multi-level digraph and S-system models. Since VoyaGene also has effective tools for visualizing the inferred results, researchers may evaluate the combination of appropriate inferring models, and can construct a genetic network to an accuracy that is beyond the reach of a single inferring model. Through the use of VoyaGene, the present study demonstrates the effectiveness of combining different inferring models.

Algorithms↗

PubMed2026

MultiDMPcaller: a one-stop software for detection and visualization of differentially methylated positions and regions.

MOTIVATION: Whole-genome bisulfite sequencing (WGBS/BS-Seq) is the gold standard for single-base resolution DNA methylome profiling. However, the diverse statistical models of existing computational methods lead to limited overlap between their results, highlighting the need for novel methods to detect differentially methylated positions (DMPs) and differentially methylated regions (DMRs). RESULTS: We developed MultiDMPcaller, an automated downstream methylome analysis software. It processes upstream outputs to profile DMPs, non-DMPs, DMRs, and context-specific (CpG/CHG/CHH) methylation status, alongside visualizing their chromosomal distribution and enrichment. The software features two key innovations: (i) an adaptive two-step P-value adjustment strategy based on organism-specific methylation patterns, with raw P-value ≤0.05 pre-filtering followed by false discovery rate (FDR) correction, to recover potential DMPs usually missed by standard FDR correction in plant CHG/CHH and animal CpG contexts; and (ii) a multiple pairwise comparison approach, which performs m × n pairwise comparisons for m control and n experimental replicates, followed by a voting system supporting both user-defined majority thresholds and model-based adaptive thresholds, to identify robust and reliable DMPs (with a stricter voting threshold exclusively for loci with low methylation differences) and DMRs. On real datasets from Arabidopsis, apple, and mouse, as well as simulated human datasets, MultiDMPcaller's results showed good agreement with those of other software, exhibiting high conservativeness and superior precision, which suggested a low false discovery proportion. AVAILABILITY AND IMPLEMENTATION: MultiDMPcaller is available at GitHub (https://github.com/jiantaoyuNWAFU/MultiDMPcaller) and via a web server (https://ciebioinfo.nwafu.edu.cn).

Software↗

PubMed1997

Scoring hidden Markov models.

MOTIVATION: Statistical sequence comparison techniques, such as hidden Markov models and generalized profiles, calculate the probability that a sequence was generated by a given model. Log-odds scoring is a means of evaluating this probability by comparing it to a null hypothesis, usually a simpler statistical model intended to represent the universe of sequences as a whole, rather than the group of interest. Such scoring leads to two immediate questions: what should the null model be, and what threshold of log-odds score should be deemed a match to the model. RESULTS: This paper analyses these two issues experimentally. Within the context of the Sequence Alignment and Modeling software suite (SAM), we consider a variety of null models and suitable thresholds. Additionally, we consider HMMer's log-odds scoring and SAM's original Z-scoring method. Among the null model choices, a simple looping null model that emits characters according to the geometric mean of the character probabilities in the columns modeled by the hidden Markov model (HMM) performs well or best across all four discrimination experiments.

Algorithms↗

PubMed1998

A human cadaver model for determination of pathologic fracture threshold resulting from tumorous destruction of the vertebral body.

STUDY DESIGN: Thoracic vertebrae were subjected to compressive loads after drilling of the centrum to simulate destruction from metastatic tumorous involvement. OBJECTIVE: To determine whether a threshold exists that is predictive of fractures to establish a correlation between significant variables and vertebral strength. SUMMARY OF BACKGROUND DATA: The mechanical effects of metastatic destruction of thoracic vertebral bodies and their correlation to pathologic fractures has been analyzed in few studies. In additional studies on intact vertebral strength, investigators have determined that bone mineral density and geometric factors are important. METHOD: Fifty-four cadaveric thoracic vertebrae were studied. All were examined by quantitative computed tomography. T4 and T10 served as mechanical controls to predict the intact strength of T7. The test vertebrae were drilled from the anterior cortex through to the posterior cortex before they were loaded. RESULTS: Linear correlation between the strength of T4 and T10 in each spine supported the predicted strengths of T7. Because of variation from other factors, no threshold defect size was noted beyond which failure consistently occurred. Results of linear correlation analyses showed that the best combination of parameters for predicting vertebral strength was the product of bone mineral density and the remaining intact vertebral body cross-sectional area. This vertebral strength index correlated linearly with the strength of intact and compromised T7 vertebrae (r2 = 0.52). CONCLUSIONS: The vertebral strength index can be used to predict the strength of any thoracic vertebra. When compared with an idealized vertebral strength index based on the intact vertebral cross-sectional area and normal bone mineral density, a patient's actual vertebral strength index can be used as one of the criteria for prophylactic stabilization.

Aged↗