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PubMed1993

Comparison of earphone and sound field methods for estimating noise attenuation of foam earplugs.

The Real Ear Attenuation at Threshold (REAT) of E-A-R (slow recovery) from earplugs was determined, using three methods of presentation of the test tones during a single fitting of the earplug. The three presentation methods were (a) sound-field listening; (b) TDH49 earphone mounted in the shell of a circumaural earmuff; and (c) TDH49 earphone in a Model 51 cushion. Thresholds were tested once under each condition. Test frequencies were .125, .25, .5, 1.0, 2.0, 3.0, 4.0, 6.0, and 8.0 kHz. Comparison of the REAT values measured by the three methods indicated that the mean REAT obtained by the reference (Sound Field) method could be reliably estimated by both earphone methods for frequencies up to and including 4.0 kHz. However, the Sound Field REAT values of individual subjects could not be predicted reliably from their REAT determined by either type of earphone presentation. It is concluded that TDH49 earphones in standard audiometric earcushions could be used to check the overall effectiveness of slow recovery foam earplugs in the workplace. Further research is necessary to ascertain whether the audiometric earphone/earcushion test could be modified to achieve satisfactory reliability in assessing earplug fitting in individual workers.

Adult↗

PubMedDate not supplied

Visible lesion thresholds with pulse duration, spot size dependency, and model predictions for 1.54-microm, near-infrared laser pulses penetrating porcine skin.

Er:glass lasers have been in operation with both long pulses (hundreds of microseconds) and Q-switched pulses (50 to 100 ns) for more than 35 yr. The ocular hazards of this laser were reported early, and it was determined that damage to the eye from the 1.54-microm wavelength occurred mainly in the cornea where light from this wavelength is highly absorbed. Research on skin hazards has been reported only in the past few years because of limited pulse energies from these lasers. Currently, however, with pulse energies in the hundreds of joules, these lasers may be hazardous to the skin in addition to being eye hazards. We report our minimum visible lesion (MVL) threshold measurements for two different pulse durations and three different spot sizes for the 1.54-microm wavelength using porcine skin as an in vivo model. We also compare our measurements to results from our model, based on the heat transfer equation and the rate process equation. Our MVL-ED50 thresholds for the long pulse (600 micros) at 24 h postexposure were measured to be 20, 8.1, and 7.4 J cm(-2) for spot diameters of 0.7, 1.0, and 5 mm, respectively. Q-switched laser pulses of 31 ns had lower ED50 (estimated dose for a 50% probability of laser-induced damage) thresholds of 6.1 J cm(-2) for a 5-mm-diam, top-hat spatial profile laser pulse.

Animals↗

PubMed1983

A theoretical basis for large coefficient of variation and bimodality in neuronal interspike interval distributions.

We consider the classic Stein (1965) model for stochastic neuronal firing under random synaptic input. Our treatment includes the additional effect of synaptic reversal potentials. We develop and employ two numerical methods (in addition to Monte Carlo simulations) to study the relation of the various parameters of the model to the shape of the theoretical interspike interval distribution. Contrary to the results of Tuckwell (1979) we are unable to account, on the basis of substantial synaptic inhibition and with parameter settings in the known physiologic range, for experimental interspike interval distributions which exhibit large coefficients of variation or bimodality. We therefore introduce a time varying threshold into the model, which readily allows for such distributions and which has physiological justification.

Action Potentials↗

PubMed2001

Neuromuscular neutral zones sensitivity to lumbar displacement rate.

OBJECTIVES: To determine the displacement and tension thresholds (developed during anterior lumbar flexion) which trigger reflexive muscular activity in the multifidus muscles; their variability with the velocity of flexion; and the pattern of threshold variability across the lumbar spine.Design. An in-vivo study of the feline during passive lumbar flexion applied via the L-4/5 supraspinous ligament. METHOD: EMG from six pairs of intramuscular electrodes inserted in the L-1/2 to L-6/7 multifidus muscles was recorded while the lumbar spine was passively flexed to 75% of the physiological strain of the supraspinous ligament at rates of 17-100%/s. Three-dimensional models of tension threshold, flexion rate and lumbar levels were developed from the experimental data. RESULTS: Displacement and tension thresholds were the lowest at the fastest flexion rate and gradually increased as flexion rates decreased. Electromyographic activity was detected at low thresholds at the center of the flexion and at gradually increasing thresholds at higher and lower lumbar segments. CONCLUSION: Multifidus reflexive muscular activity, which stabilize the spine, is triggered at a displacement and tension thresholds of 5-15% of the physiological range. Earlier activation of muscular activity occurs as the velocity of flexion increases. Earlier activation also occurs near the center of flexion. RELEVANCE: Sensory-motor neurological feedback maintains spine stability and is responsive to the velocity of lumbar motion. A neuromuscular silence exists in small lumbar movements in which spine stability is not protected by the musculature. Spine models constructed to predict risk factors could benefit from incorporating this new information.

Animals↗

PubMed2000

Controlling activity fluctuations in large, sparsely connected random networks.

Controlling activity in recurrent neural network models of brain regions is essential both to enable effective learning and to reproduce the low activities that exist in some cortical regions such as hippocampal region CA3. Previous studies of sparse, random, recurrent networks constructed with McCulloch-Pitts neurons used probabilistic arguments to set the parameters that control activity. Here, we extend this work by adding an additional, biologically appropriate, parameter to control the magnitude and stability of activity oscillations. The new constant can be considered to be the rest conductance in a shunting model or the threshold when subtractive inhibition is used. This new parameter is critical for large networks run at low activity levels. Importantly, extreme activity fluctuations that act to turn large networks totally on or totally off can now be avoided. We also show how the size of external input activity interacts with this parameter to affect network activity. Then the model based on fixed weights is extended to estimate activities in networks with distributed weights. Because the theory provides accurate control of activity fluctuations, the approach can be used to design a predictable amount of pseudorandomness into deterministic networks. Such nonminimal fluctuations improve learning in simulations trained on the transitive inference problem.

Computer Simulation↗

PubMed2004

Signal propagation and failure in discrete autocrine relays.

A mechanistic model of discrete one-dimensional arrays of autocrine cells interacting via diffusible signals is investigated. Under physiologically relevant assumptions, the model is reduced to a system of ordinary differential equations for the intracellular variables, with a particular, biophysically derived type of long-range coupling between cells. Exact discrete traveling wave and static kink solutions are obtained in the model with sharp threshold nonlinearity. It is argued that the considered mechanism may be used extensively for transmission of information in tissues during homeostasis and development.

Autocrine Communication↗

PubMed2000

A qualitative comparison of some diffusion models for neural activity via stochastic ordering.

A number of diffusion processes have been proposed as a continuous analog of Stein's model for the subthreshold membrane potential of a neuron. Interspike intervals are then described as the first-passage-time of the corresponding diffusion model through a suitable threshold. Various biological considerations suggest the use of more sophisticated models in lieu of the Ornstein-Uhlenbeck model. However, the advantages of the additional complexity are not always clear. Comparisons among different models generally use numerical methods in specific examples without a general sensitivity analysis on the role of the model parameters. Here, we compare the distribution of interspike intervals from different models using the method of stochastic ordering. The qualitative comparison of the role of each parameter extends the results obtained from numerical simulations. One result on neurons with high positive net excitation is that the reversal potential models considered do not greatly differ from the Ornstein-Uhlenbeck model. For neurons with increased inhibition, the models give greater differences among the interspike interval distributions. In particular, when the mean trajectories are matched, the Feller model gives shorter times than the Ornstein-Uhlenbeck model but longer times than our double reversal potential model.

Action Potentials↗

PubMed2004

Novel moment closure approximations in stochastic epidemics.

Moment closure approximations are used to provide analytic approximations to non-linear stochastic population models. They often provide insights into model behaviour and help validate simulation results. However, existing closure schemes typically fail in situations where the population distribution is highly skewed or extinctions occur. In this study we address these problems by introducing novel second- and third-order moment closure approximations which we apply to the stochastic SI and SIS epidemic models. In the case of the SI model, which has a highly skewed distribution of infection, we develop a second-order approximation based on the beta-binomial distribution. In addition, a closure approximation based on mixture distribution is developed in order to capture the behaviour of the stochastic SIS model around the threshold between persistence and extinction. This mixture approximation comprises a probability distribution designed to capture the quasi-equilibrium probabilities of the system and a probability mass at 0 which represents the probability of extinction. Two third-order versions of this mixture approximation are considered in which the log-normal and the beta-binomial are used to model the quasi-equilibrium distribution. Comparison with simulation results shows: (1) the beta-binomial approximation is flexible in shape and matches the skewness predicted by simulation as shown by the stochastic SI model and (2) mixture approximations are able to predict transient and extinction behaviour as shown by the stochastic SIS model, in marked contrast with existing approaches. We also apply our mixture approximation to approximate a likelihood function and carry out point and interval parameter estimation.

Computer Simulation↗

PubMed2001

[Role of the GABA-ergic and adrenergic system in transmission and modulation of pain and possibilities of pharmacologic control].

The dorsal horn of the spinal cord contains many transmitters and receptors involving in pain transmission and modulation. Monoamines and gamma-aminobutyric acid (GABA) play a key role in the modulation at level of dorsal horn (DH) of the spinal cord, the site of primary processing of afferent nociceptive information. Agents that enhance the action of GABA at the GABAA receptors can produce antinociception. For example intrathecal administration of benzodiazepines increases pain threshold in various models of pain. There is also substantial evidence for robust antinociceptive properties of spinal administration of clonidine and other alpha 2-agonists.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1989

The General Health Questionnaire: a psychometric analysis using latent trait theory.

This study examines the Likert-style successive integer scoring of Goldberg's (1972, 1978) General Health Questionnaire (GHQ) with a psychometric model in which the thresholds between successive categories within each item can be estimated. The model is particularly appropriate because the scoring of the successive categories, which are not named in the same way across items, by successive integers has received substantial discussion in the literature. Results from 1967 teachers in Western Australia who completed the 30-item form of the GHQ show that the items conform reasonably well to the model at a general or macro-level of analysis. In particular, the original ordering of categories is supported. However, as expected, there are systematic differences between distances among threshold within items and systematic differences among thresholds between items. The differences between positively and negatively orientated items confirm a suggestion in the literature that these two classes of items form sufficiently different scales so that they could be treated as separate, though reasonably correlated, scales.

Adaptation, Psychological↗

PubMed1999

Threshold dose response for tumor induction by genotoxic carcinogens modeled via cell-cycle delay.

Dose-response relationships for tumor induction in animal bioassays for carcinogenicity are often postulated to include thresholds, particularly for nongenotoxic chemicals that increase the rate of cell proliferation at high doses. In this report, thresholds are postulated also for genotoxic carcinogens. The hypothesis is based on the idea of a delay of the cell cycle induced by low-level DNA damage and an acceleration at cytotoxic dose levels, thus resulting in a J-shaped (or U-shaped) dose response for cell turnover. Calculations were based on the 2-stage clonal expansion model of carcinogenesis. The background values chosen for the model parameters resulted in a 10.5% "spontaneous" 2-year cumulative tumor incidence. Using this as a starting point, a decrease by 3, 10, and 30% in the rates of cell turnover resulted in a decrease in the spontaneous tumor incidence to 9.4, 7.1 and 3.0%, respectively. Dose-responses with J-shaped curves for the rates of cell birth and death were modeled by shifted quadratic functions reaching the minimum at dose 1. Combinations with linearly increasing mutation rates also generated, under certain conditions, J-shaped dose-response curves for tumor incidence. As an example, for a 30% increase in mutation rates and a 10% decrease in cell turnover rates (both at dose 1), the dose-response curve showed an initial decrease of tumor incidence below the spontaneous rate, a reversion to the background value at 0.8 dose units, and an increase thereafter. The 0.8 dose could be considered to represent the "threshold dose." The approach presented might reconcile opposing views on thresholds on a biologically plausible mechanistic basis, and show a way for the quantitative estimation of threshold doses.

Animals↗

PubMed2004

DNA elements important for CAG*CTG repeat thresholds in Saccharomyces cerevisiae.

Trinucleotide repeat (TNR) instability is of interest because of its central role in human diseases such as Huntington's and its unique genetic features. One distinctive characteristic of TNR instability is a threshold, defined as a minimal repeat length that confers frequent mutations. While thresholds are well established, important risk determinants for disease-causing mutations, their mechanistic analysis has been delayed by the lack of suitably tractable experimental systems. In this study, we directly compared for the first time three DNA elements-TNR sequence, purity and flanking sequence-all of which are suggested in the literature to contribute to thresholds. In a yeast model system, we find that CAG repeats require a substantially longer threshold to contract than CTG tracts, indicating that the lagging template repeat sequence helps determine the threshold. In contrast, ATG interruptions within a CTG run do not inhibit contractions via a threshold mechanism, but by altering the likelihood of forming a hairpin intermediate. The presence of a GC-rich flanking sequence, similar to a haplotype found in some Huntington's patients, does not detectably alter expansions of Okazaki fragment CTG tracts, suggesting no role for this flanking sequence on thresholds. Together these results help better define TNR thresholds by delineating sequence elements that modulate instability.

DNA↗

PubMed1997

Same-different texture discrimination in pigeons: testing competing models of discrimination and stimulus integration.

The choice behavior of 6 pigeons performing a mulltidimensional same-different texture discrimination was examined. On each trial, they had to choose among 2 choice hoppers depending on whether a color, shape, or redundant (color and shape) target signal was present or not in a textured stimulus. Receiver operating characteristic (ROC) curves were produced by variations in the priori signal presentation probabilities across conditions. Quantitative analyses of these ROC curves were used to evaluate different competing theories of discrimination (signal detection vs. high-threshold-default response models) and information integration (independent observations, additive integration, unidimensional models). The results suggested the structure of the pigeons' choice behavior in this same-different discrimination was best described by an unequal variance signal detection model involving a unidimensional evidence variable (e.g., degree of difference).

Animals↗

PubMed2007

Full modelling of the MOSAIC animal PET system based on the GATE Monte Carlo simulation code.

Positron emission tomography (PET) systems dedicated to animal imaging are now widely used for biological studies. The scanner performance strongly depends on the design and the characteristics of the system. Many parameters must be optimized like the dimensions and type of crystals, geometry and field-of-view (FOV), sampling, electronics, lightguide, shielding, etc. Monte Carlo modelling is a powerful tool to study the effect of each of these parameters on the basis of realistic simulated data. Performance assessment in terms of spatial resolution, count rates, scatter fraction and sensitivity is an important prerequisite before the model can be used instead of real data for a reliable description of the system response function or for optimization of reconstruction algorithms. The aim of this study is to model the performance of the Philips Mosaic animal PET system using a comprehensive PET simulation code in order to understand and describe the origin of important factors that influence image quality. We use GATE, a Monte Carlo simulation toolkit for a realistic description of the ring PET model, the detectors, shielding, cap, electronic processing and dead times. We incorporate new features to adjust signal processing to the Anger logic underlying the Mosaic system. Special attention was paid to dead time and energy spectra descriptions. Sorting of simulated events in a list mode format similar to the system outputs was developed to compare experimental and simulated sensitivity and scatter fractions for different energy thresholds using various models of phantoms describing rat and mouse geometries. Count rates were compared for both cylindrical homogeneous phantoms. Simulated spatial resolution was fitted to experimental data for (18)F point sources at different locations within the FOV with an analytical blurring function for electronic processing effects. Simulated and measured sensitivities differed by less than 3%, while scatter fractions agreed within 9%. For a 410-665 keV energy window, the measured sensitivity for a centred point source was 1.53% and mouse and rat scatter fractions were respectively 12.0% and 18.3%. The scattered photons produced outside the rat and mouse phantoms contributed to 24% and 36% of total simulated scattered coincidences. Simulated and measured single and prompt count rates agreed well for activities up to the electronic saturation at 110 MBq for the mouse and rat phantoms. Volumetric spatial resolution was 17.6 microL at the centre of the FOV with differences less than 6% between experimental and simulated spatial resolution values. The comprehensive evaluation of the Monte Carlo modelling of the Mosaic system demonstrates that the GATE package is adequately versatile and appropriate to accurately describe the response of an Anger logic based animal PET system.

Animals↗

PubMed2006

Assessing the predictive accuracy of hMLH1 and hMSH2 mutation probability models.

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by a susceptibility to colorectal and extra-colonic cancers. Several guidelines exist for the identification of families suspected of having HNPCC, however these guidelines lack adequate sensitivity and specificity. In an attempt to improve accuracy for the detection of individuals with HNPCC, the Wijnen pre-test probability model (1998) and Myriad Genetics Laboratory prevalence table (2004) were developed. Here we evaluate the Wijnen model and Myriad table at predicting the presence of a mutation in individuals undergoing genetic testing for HNPCC. Forty-nine patients who had undergone genetic testing for germline mutations in hMLH1 and/or hMSH2 were part of our analysis. Our results revealed that the revised Bethesda guidelines performed with the highest sensitivity for germline mutations (94.4%), however the specificity was low (12.9%). Using a 10.0% mutation probability threshold, the Wijnen model and Myriad table had sensitivities of 55.6 and 60.0%, respectively and specificities of 54.8 and 23.8%, respectively. The Wijnen model and Myriad table were poor predictors of mutation prevalence, which is shown by the areas underneath their corresponding receiver operator characteristic curves (0.616 and 0.400, respectively). The results of this study demonsrate that neither the Wijnen model nor the Myriad table are sensitive or specific enough to be used as the only indication when to offer genetic testing for HNPCC.

Adaptor Proteins, Signal Transducing↗

PubMed1987

Nd:YAG laser irradiation of an eye model: experimental analysis.

This work reviews a series of experiments performed on an eye model to study physical effect relevant for a safe and effective use of the Q-switched Nd:YAG laser in ophthalmic microsurgery. The breakdown probability per laser pulse has been found to depend exponentially on the reciprocal laser field. This indicates that, as in transparent solids, electron avalanche ionization is likely the main mechanism for optical breakdown in liquids. Shielding of the retina, by the laser-induced plasma, is not very effective, but an appreciable degree of shielding is present, in burst operation, even after membrane disruption. A backscattered beam, which presents the typical properties of stimulated Brillouin scattering, has been observed in the eye model, with a threshold of approximately 5 X 10(9) W/cm2. This beam, which presents an irregular spatial structure with peaks of irradiance well above the average value, may produce damage of the internal wall of the cornea.

Eye↗

PubMed2000

Models of schedule dependent haematological toxicity of 2'-deoxy-2'-methylidenecytidine (DMDC).

OBJECTIVE: DMDC (2'-deoxy-2'-methylidenecytidine) is-a potential antitumour deoxycytidine analogue of cytosine arabinoside. The major dose-limiting toxicity of DMDC is haematological depression, particularly neutropenia, and therefore quantitative exposure-toxicity relationships for DMDC are warranted. METHODS: Data on the survival fraction at nadir of leukocytes, neutrophils and platelets from 66 patients receiving a once-daily regimen and 85 patients receiving a twice-daily regimen of DMDC were related to DMDC concentration-time profiles using area under the plasma concentration-time curve (AUC), threshold and general models. A semiphysiological model of neutrophils versus time after DMDC administration included transient compartments to imitate the differentiation stages in the bone marrow. RESULTS: The relationship between plasma DMDC concentration-time profiles and the haematological toxicity at nadir was best described using an AUC-dependent model with separate functions for once- and twice-daily dosing, indicating schedule dependence of DMDC effects, even if differences in treatment duration had a similar explanatory value. Twice-daily dosing was associated with greater toxic effects than once-daily dosing. The AUC required for a 70% reduction in the neutrophils was 16 mg.h/l and 4.2 mg.h/l for the once- and twice-daily regimens, respectively. The semiphysiological model included nine proliferating transient compartments that were sensitive to DMDC in a schedule-dependent manner, five non-mitotic, non-sensitive compartments and one compartment for circulating neutrophils. CONCLUSIONS: The haematological toxicity of DMDC is schedule dependent. The survival fractions of leukocytes, neutrophils and platelets are predicted to be lower when given on a twice-daily regimen than on a once-daily regimen. A semiphysiological model with transient compartments successfully described the entire time course of neutropenia after DMDC administration.

Antineoplastic Agents↗

PubMed1991

Relation between hearing threshold level and its component parts.

A model is presented showing how different components of threshold shift combine. It has long been evident that simple arithmetical addition cannot apply, but it is only recently that experimental data have been shown to validate a simple interaction between age- and noise-related components. The combination formula extends to sensory loss from other causes. Used in conjunction with growth functions for the age and noise components, it facilitates both the prediction of future hearing loss and the 'retrodiction' of past hearing threshold levels at any point in the life of the average person, given the present age and the noise exposure history. By reconstructing the hearing thresholds for a notional 'life' in which an episode of noise exposure is eliminated, the formula enables the specific effect of that episode to be evaluated at later times. As with any such system, uncertainties arise in the application to individuals. Possible ways forward are discussed.

Auditory Threshold↗