PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “threshold model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed2006

Auditory-nerve first-spike latency and auditory absolute threshold: a computer model.

A computer model of the auditory periphery was used to address the question of what constitutes the physiological substrate of absolute auditory threshold. The model was first evaluated to show that it is consistent with experimental findings that auditory-nerve fiber spikes can be predicted to occur when the running integral of stimulus pressure reaches some critical value [P. Heil and H. Neubauer, J. Neurosci. 15, 7404-7415 (2001)]. It was then modified to examine two ways in which the accumulation and clearance of receptor presynaptic calcium might explain this effect. Both methods gave results that matched the animal data. It was also shown how the rate of clearance of presynaptic calcium could be used to explain the origin of differences between low and high spontaneous-rate fiber types. When spiking activity is aggregated across a number of similar high spontaneous-rate fibers and used as the input to a model of a cochlear nucleus coincidence neuron, its response can be used to judge whether or not a stimulus is present. A simulated psychophysical experiment then demonstrated that this simple decision procedure can reproduce measurements of absolute auditory threshold for tones in quiet where the threshold is a joint function of both time and level.

Acoustic Stimulation↗
PubMed1998

Nonallelic noncomplementation models in mice: the first arch and lidgap-Gates mutations.

We tested for complementation between two Mendelian mutations in mice, Far (first arch) and lgGa (lidgap-Gates). Each of these mutations gives greater than 70% risk of the birth defect, open eyelids, in homozygotes and gives little or no risk in heterozygotes. Far and lgGa are known to not be alleles; Far maps to Chr 2 and lgGa maps to Chr 13. However the cross between +/Far (on the BALB/cGaBc strain) and lgGa/lgGa (on the LGG/Bc strain) gave 32% (48/149) of progeny affected with open eyelids at birth: 63% (45/71) of the double heterozygote, +/Far, +/lgGa, compared with 4% (3/78) of the +/+, +/lgGa progeny. That is, the complementation test suggests that Far and lgGa are alleles, whereas the mapping data show that they are not. We interpret the result of the Far by lgGa test as an example of nonallelic noncomplementation (or "false allelism") in mammals, and suggest that this phenomenon might be expected because open eyelids at birth involves a developmental threshold. Our data also show that both the embryonic and the maternal background genotypes strongly influence the risk of open eyelids in the Far by lgGa crosses. The risk to the double heterozygote (+/Far, +/lgGa) is highest (77%) with Far from the BALB/cGaBc rather than the ICR/Bc (0%) strain and in a BALB/cGaBc (77%) rather than an LGG/Bc (50%) dam in the reciprocal cross. This effect of genetic context on risk is also predicted by the threshold model. Based on our data on open eyelids at birth, we suggest that false allelism may be common in mammalian birth defects that result from failure to meet developmental thresholds, even when the "causal" mutations are Mendelian.

Animals↗
PubMed2000

Parallels between timing of onset responses of single neurons in cat and of evoked magnetic fields in human auditory cortex.

Sound onsets constitute particularly salient transients and evoke strong responses from neurons of the auditory system, but in the past, such onset responses have often been analyzed with respect to steady-state features of sounds, like the sound pressure level. Recent electrophysiological studies of single neurons from the auditory cortex of anesthetized cats have revealed that the timing and strength of onset responses are shaped by dynamic stimulus properties at their very onsets. Here we demonstrate with magnetoencephalography that stimulus-response relationships very similar to those of the single neurons are observed in two onset components, N100m and P50m, of auditory evoked magnetic fields (AEFs) from the auditory cortex of awake humans. In response to tones shaped with cosine-squared rise functions, N100m and P50m peak latencies vary systematically with tone level and rise time but form a rather invariant function of the acceleration of the envelope at tone onset. Hence N100m and P50m peak latencies, as well as peak amplitudes, are determined by dynamic properties of the stimuli within the first few milliseconds, though not necessarily by acceleration. The changes of N100m and P50m peak latencies with rise time and level are incompatible with a fixed-amplitude threshold model. The direct comparison of the neuromagnetic and single-neuron data shows that, on average, the variance of the neuromagnetic data is larger by one to two orders of magnitude but that favorable measurements can yield variances as low as those derived from neurons with mediocre precision of response timing. The striking parallels between the response timing of single cortical neurons and of AEFs provides a stronger link between single neuron and population activity.

Acceleration↗
PubMed1994

Human evidence: lung cancer mortality risk from chrysotile exposure.

The linear, no-threshold model is commonly used for estimating lifetime lung cancer risk from asbestos exposures. Studies of chrysotile workers have observed shallow slopes for the exposure-response relationship for miners/millers, friction products manufacturing workers and asbestos-cement (primarily chrysotile) workers but a steeper slope (approximately 16 times higher) for textile workers. For chrysotile exposures in buildings, where short fibres constitute the great majority of the fibres, the shallow slope is judged more appropriate. Using this slope the data regarding exposure levels to building occupants and maintenance workers, the annualized risks of lung cancer would be approximately 0.01 and 0.6 per million for these groups, respectively. Using the higher slope would result in risks 16 times higher, still considerably lower than those commonly accepted. Contrary to the model's assumption of increased risk for any amount of exposure, a number of studies have demonstrated evidence that lung cancer risk is not associated with years exposed to low exposure levels. Moreover, the accumulating evidence that asbestos-induced lung cancer may require lung fibrosis suggests a practical threshold since detectable lung fibrosis will not result from environmental exposure levels. Evidence suggests that the relative risk to non-smokers bay be slightly higher than to smokers (by a factor of 1.8). However, if this is true, this has little effect on risk assessment due to the low absolute risk in non-smokers. Tremolite has been associated with an increased risk of lung cancer in a study of vermiculite miners; the slope of the exposure-response relationship was similar to that for crocidolite miners and much higher than that of chrysotile miners. In spite of a recent report indicating that asbestos-associated lung cancer risk may be limited only to adenocarcinomas, the bulk of the evidence fails to confirm this.

Adolescent↗
PubMed1996

Dose-response relationship for rat liver DNA damage caused by 1,2-dimethylhydrazine.

An experimental approach was taken to the question of dose-response curves for chemical carcinogenesis, using DNA damage as a biomarker. Female rats were give 13 different doses of 1,2-dimethylhydrazine (from 1.4 to 135,000 micrograms/kg) and the subsequent hepatic DNA damage was determined by the alkaline elution technique. DMH doses below 450 micrograms/kg did not significantly damage DNA; all DMH doses of 1000 micrograms/kg or higher damaged rat hepatic DNA (P < 0.05). In this study the x values (dose) ranged over five orders of magnitude and the y values (DNA damage) ranged 30-fold. Ten different regression models (linear, quadratic, cubic, power, and six nonlinear transition models) were compared in their ability to fit the experimental data. With respect to log transformed dose, the six nonlinear transition equations fit the data considerably better than the four power type of equations. A sigmoid model fit to the log transformed dose of 1,2-dimethylhydrazine had an r2 of 0.9979, a degree of freedom adjusted r2 of 0.9969, a F-statistic of 1,457, and a fit standard error of 0.50. With respect to untransformed dose, only three equations (sigmoid, cascade and gaussian cumulative) could creditably fit the DMH data. The experimental results are interpreted with respect to hormesis, use of log transformed dose, sigmoid dose-response models, thresholds of biological response and cancer risk assessment.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Impact of a psychoeducational intervention on caregiver response to behavioral problems.

BACKGROUND: Eighty percent of persons with Alzheimer's disease and related disorders are cared for by family members who often lack adequate support and training for this all-consuming job. OBJECTIVE: To evaluate the efficacy of a longitudinal, multisite, community-based intervention designed to teach home caregivers to manage behavioral problems in persons with Alzheimer's disease. METHODS: Usable data were analyzed from 237 caregiver/care recipient dyads (n = 132 Experimental; n = 105 Comparison). The experimental group received a psychoeducational nursing intervention that was conceptually grounded in the Progressively Lowered Stress Threshold model (Hall & Buckwalter, 1987). The comparison group received routine information and referrals for case management, community-based services, and support groups. Although a variety of psychosocial outcomes were compared between caregivers in the two groups, this article focuses on frequency and response to behavioral problems and functional decline. RESULTS: The Progressively Lowered Stress Threshold intervention had a statistically significant effect on spousal response to memory/behavioral problems (p <.01) for all caregivers and on response to activities of daily living problems (p <.01) for spousal caregivers. In addition, nonspouses in the experimental group reported a reduction in the frequency of memory/behavioral problems (p <.01). No intervention effect on reports of activities of daily living frequencies was found for either spouses or nonspouses. CONCLUSIONS: This Progressively Lowered Stress Threshold-based intervention had a positive impact on both the frequency of and response to problem behaviors among spousal caregivers.

Activities of Daily Living↗
PubMed2004

Assessment of reliability of microarray data and estimation of signal thresholds using mixture modeling.

DNA microarray is an important tool for the study of gene activities but the resultant data consisting of thousands of points are error-prone. A serious limitation in microarray analysis is the unreliability of the data generated from low signal intensities. Such data may produce erroneous gene expression ratios and cause unnecessary validation or post-analysis follow-up tasks. In this study, we describe an approach based on normal mixture modeling for determining optimal signal intensity thresholds to identify reliable measurements of the microarray elements and subsequently eliminate false expression ratios. We used univariate and bivariate mixture modeling to segregate the microarray data into two classes, low signal intensity and reliable signal intensity populations, and applied Bayesian decision theory to find the optimal signal thresholds. The bivariate analysis approach was found to be more accurate than the univariate approach; both approaches were superior to a conventional method when validated against a reference set of biological data that consisted of true and false gene expression data. Elimination of unreliable signal intensities in microarray data should contribute to the quality of microarray data including reproducibility and reliability of gene expression ratios.

Algorithms↗
PubMed2001

Colour thresholds and receptor noise: behaviour and physiology compared.

Photoreceptor noise sets an absolute limit for the accuracy of colour discrimination. We compared colour thresholds in the honeybee (Apis mellifera) with this limit. Bees were trained to discriminate an achromatic stimulus from monochromatic lights of various wavelengths as a function of their intensity. Signal-to-noise ratios were measured by intracellular recordings in the three spectral types of photoreceptor cells. To model thresholds we assumed that discrimination was mediated by opponent mechanisms whose performance was limited by receptor noise. Most of the behavioural thresholds were close to those predicted from receptor signal-to-noise ratios, suggesting that colour discrimination in honeybees is affected by photoreceptor noise. Some of the thresholds were lower than this theoretical limit, which indicates summation of photoreceptor cell signals.

Animals↗
PubMed1993

Effect of divergent selection for immune responsiveness and of major histocompatibility complex on resistance to Marek's disease in chickens.

Lines of chickens selected for nine generations for high (H) or low (L) antibody response to SRBC, a randombred control (C) line, and an F1 cross between H and L lines were challenged for resistance to Marek's disease (MD). Hens only were challenged at day-old by contact with virulent MD Strain K. Birds were serologically typed for MHC erythrocyte antigens. Chicks from the L and H lines died earlier and later, respectively, than the C chicks, whereas time of death did not differ between F1 birds and the L chicks. Mortality in the L line (70.1%) was higher than in the C line (42.8%), but mortality in the H line (40.9%) was not lower than in the C line or the F1 cross (47.5%). Effects of MHC genotypes and haplotypes on mortality from MD were estimated within lines with a logistic regression model. Effect of MHC was moderate in the H line (P < .10) and highly significant in the C line (P < .005). Effects of MHC genotypes were similar in the H and C line but differed in the L and F1. Heritability of mortality from MD estimated with a threshold model including relationships between individuals was .40 when all lines were grouped together, whereas heritability estimated for each line separately was .45, .51, and .78 in the H, C, and L lines, respectively. Correlations between estimated breeding values for antibody response to SRBC and mortality from MD varied between lines and sexes. Correlations also were affected by whether or not the MHC effect was taken into account.

Animals↗
PubMed1992

Dobutamine pharmacokinetics and pharmacodynamics in pediatric intensive care patients.

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of dobutamine in critically ill children. DESIGN: A prospective study of pediatric patients receiving continuous infusions of dobutamine in a stepwise format from 2.5 to 10.0 micrograms/kg/min. SETTING: A pediatric critical care unit. PATIENTS: Twelve children ranging in age from 1 month to 17 yrs with primary medical conditions. MEASUREMENTS: Plasma dobutamine concentrations and hemodynamic responses were measured at each infusion rate at steady state. Dose response data were analyzed to determine the threshold or minimum plasma dobutamine concentration necessary for discernible hemodynamic effects. MAIN RESULTS: Dobutamine plasma clearance rates ranged from 40 to 130 mL/kg/min. Each patient presented a linear increase in the plasma dobutamine concentration at each infusion rate (r2 = .97, p less than .001). Plasma clearance rate vs. actual dobutamine concentration did not vary. Cardiac output, BP, and heart rate increased 30%, 17%, and 7%, respectively, at maximal dose. The dobutamine concentration thresholds for changes in cardiac output, BP, and heart rate were 13 +/- 6, 23 +/- 14, and 65 +/- 30 ng/mL, respectively. CONCLUSIONS: There was no effect of plasma dobutamine concentration or infusion rate on plasma clearance rate. For this group of patients, over the range of the intravenous doses studied, dobutamine pharmacokinetics followed a first-order kinetic model. Threshold values for dobutamine usually show increases in cardiac output before changes in heart rate. These data demonstrate that dobutamine is an effective inotropic agent in critically ill pediatric patients and has minimal chronotropic action.

Blood Pressure↗
PubMed1998

Photodynamic therapy of intracranial tissues: a preclinical comparative study of four different photosensitizers.

OBJECTIVE: The effectiveness of four different photosensitizers for intracranial photodynamic therapy (PDT) of normal brain tissues and an intracranial tumor was investigated in rabbits, using the photodynamic threshold model. SUMMARY: PDT is currently being investigated as an adjuvant treatment to surgical resection and/or radio chemotherapy of intracranial neoplasms. While possible neurotoxic side effects of the treatment have been noted, only limited preclinical data quantifying the response of intracranial normal and tumor tissues following PDT are available. MATERIALS AND METHODS: The photodynamic threshold dose values for the four photosensitizers, Photofrin, 5-aminolevulinic acid (ALA)-induced Protoporphyrin IX (PpIX), Tin Ethyl Etiopurpurin (SnET2), and chloroaluminum phthalocyanine (AlClPc), were determined using measured light fluence distributions, photosensitizer concentration in tissue, and histologically-determined extent of necrosis following PDT. These measurements were made in normal rabbit brain and in an intracranially-implanted carcinoma (VX2). RESULTS: For Photofrin, AlClPc, and SnET2 (in an emulsion delivery vehicle) normal grey and white matter were very sensitive to PDT, showing a significantly lower threshold dose value than VX2-tumor. For ALA-induced PpIX and SnET2 (in liposome) very little or no white matter damage was observed. Additionally, ALA-PpIX showed significantly lower concentration in white matter than in cortex and tumor. Normal brain structures lacking a blood-brain barrier showed high uptake of all photosensitizers and, hence, are at risk of collateral damage during PDT. CONCLUSIONS: For clinical PDT of most adult intracranial neoplasms ALA-induced PpIX appears to be promising, and SnET2 (liposomal) has potential for selective tumor destruction with relative sparing of white matter. Other normal brain structures and, for the other photosensitizers, also white matter are at risk of collateral damage, if exposed to light during PDT.

Animals↗
PubMed2003

Low fluence.

The question of the appropriate extrapolation to low dose has long been a subject of controversy. A linear no-threshold model is favored by regulatory bodies as the basis of RBE assignments and estimates of radiation hazards to the general population. This model is largely supported by extensive application of the linear-quadratic survival formula "fitted" statistically to a wide variety of experimental data obtained at doses typically exceeding 1 Gy, and then extrapolated to mGy for practical applications, and even to the prediction of hazards from single electrons. Such extrapolations are questionable at best, and may even prove hazardous for risk evaluations. Fluence and geometry rather than dose based data are proposed as a basis for a limiting "threshold" for a "low dose" extrapolation. The proposed threshold is one where the fluence of particles is one per square micron, where on average only 2/3 of the 1 micrometers2 pixels covering an irradiated area are traversed by one or more particles. The corresponding dose threshold is determined by the LET of the bombarding radiation. For relativistic electrons this dose is about 0.032 Gy.

Cell Physiological Phenomena↗
PubMed2003

Population pharmacokinetic modelling of unbound and total plasma concentrations of paclitaxel in cancer patients.

The aim of this study was to validate and further develop a mechanism-based population pharmacokinetic model for paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ, USA) based on the knowledge of Cremophor EL (CrEL) micelle entrapment and to evaluate the exposure/toxicity relationships. Paclitaxel (total and unbound) and CrEL concentrations were obtained according to a sparse sampling scheme with on average only 3.5 samples per course from 45 patients with solid tumours who received 3-hour infusions of paclitaxel (final dose range 112-233 mg/m(2)). The present data were predicted well by the mechanism-based model. In addition, bilirubin and body size were found to be significant as covariates. A change in body surface area (BSA) of 0.1 m(2) typically caused a change in clearance (CL) of 22.3 l/h and an increase in bilirubin of 10 microM typically caused a decrease in CL of 41 l/h. Toxicity was best described by a threshold model. In conclusion, even with a sparse sampling scheme, the same mechanism-based binding components as in the previously developed model could be identified. Once the CrEL and total paclitaxel plasma concentrations are known, the unbound concentrations, which are more closely related to the haematological toxicity, can be predicted.

Adult↗
PubMed1997

Modelling for precision weed management.

Recently, the need for the development of weed management systems with a reduced dependency on herbicides has increased because of concern about environmental side-effects and cost. The development of such systems requires new strategies based on improvements with respect to (1) prevention, (2) decision making and (3) weed control technology. For the development of improvements in all three aspects, quantitative understanding of weed population dynamics and crop-weed interactions is needed. Models that integrate the available quantitative knowledge can be used to design preventive measures, to develop long-term and short-term strategies for weed management, to assist in decision making to determine if, when, where and how weeds should be controlled and to identify new opportunities for weed control. Ecophysiological simulation models for crop-weed competition simulate growth and production of species in mixtures, based on ecophysiological processes in plants and their response to the environment. Such models help improve insight into the crop-weed system and can be used for purposes such as the development of simple predictive yield-loss models, threshold levels or the design of competitive crop plant types. For strategic weed management decisions, preventive measures and the identification of new opportunities for weed control, quantitative insight into the dynamics and spatial patterns of weed populations is also required. The complexity of the process and the long-term character of weed population dynamics make the use of models necessary. Different modelling approaches have been developed and are described briefly. Opportunities to use the available knowledge and models to improve weed management are discussed. Weeds occur in patches and their sensitivity to herbicides changes strongly with developmental stage, making precision techniques for herbicide application in time and space an option for reducing herbicide use. Limitations related to insight in biological processes as well as the state of technological development are discussed.

Agriculture↗
PubMedDate not supplied

Economical designs for detecting and characterizing departure from additivity in mixtures of many chemicals.

A well-chosen experimental design can result in efficient estimation of model parameters and often savings of resources. When the interaction of components in a mixture is under study, a useful experimental layout is a factorial design-where all combinations of the levels of each component are observed together. However, as the number of components in the mixture becomes large, these types of designs become infeasible. Using the definition of additivity as proposed by Berenbaum, some authors have instead used an experimental design necessary to estimate coefficients in an additivity model where only dose-response (concentration-effect) information of single compounds is required. Two approaches for using an additivity model are described. Both compare what is observed with what is predicted under the assumption of additivity. One is based on a comparison of responses to a mixture of interest; the other is based on a comparison of locations of mixtures that yield the same predicted response when the components are at a fixed proportion. An example using a threshold model for the dose-response relationship is provided.

Animals↗
PubMed2005

Sex inheritance in gynodioecious species: a polygenic view.

Gynodioecy is defined as the coexistence of two different sexual morphs in a population: females and hermaphrodites. This breeding system is found among many different families of angiosperms and is usually under nucleo-cytoplasmic inheritance, with maternally inherited genes causing male sterility and nuclear factors restoring male fertility. Numerous theoretical models have investigated the conditions for the stable coexistence of females and hermaphrodites. To date, all models rest on the assumption that restoration of a given male sterile genotype is controlled by a single Mendelian factor. Here, we review data bearing on the genetic determinism of sex inheritance in three gynodiecious plant species. We suggest that restoration of male fertility is probably best viewed as a quantitative trait controlled by many loci. We develop a threshold model that accommodates an underlying polygenic trait, which is resolved at the phenotypic level in discrete sexual morphs. We use this model to reanalyse data in Thymus vulgaris, Silene vulgaris and Plantago coronopus. A simple Mendelian inheritance of sex determinism is unlikely in all three species. We discuss how our model can shed additional light on the genetics of restoration and point towards future efforts in the modelling of gynodioecy.

Genotype↗
PubMed1999

Fears and phobias: reliability and heritability.

BACKGROUND: Familial factors, which are partly genetic, influence risk for phobias. Prior family and twin studies, however, were based on a single lifetime assessment, which may be only moderately reliable. METHODS: We obtained, 8 years apart, two assessments of lifetime history of five unreasonable fears and phobias (agoraphobia and social, situational, animal and blood-injury phobia) from face-to-face and telephone interviews from 1708 individual female twins from a population-based registry. We also obtained, 1 month apart, test retest reliability on 192 twins. We fitted, using the program Mx, a measurement model that estimates the role of genetic and environmental risk factors correcting for measurement error. RESULTS: Short-term reliability of the five phobias was modest (mean kappa = 0.46), but higher than long-term stability (mean kappa = 0.30). Unreliability occurred both for subject recall of unreasonable fears and for interviewer assessment of which fears constituted phobias. Examining fears and phobias together, in a multiple threshold model, results suggested that twin resemblance was due solely to genetic factors, with estimated total heritabilities, corrected for unreliability, of: any 43%, agoraphobia 67%, animal 47%, blood/injury 59%, situational 46% and social 51%. With the exception of animal phobia, similar results were obtained analysing phobias alone. CONCLUSIONS: Lifetime histories of unreasonable fears and phobias assessed at personal interview have substantial unreliability. Correcting for unreliability, the liability to fears and their associated phobias is moderately heritable. Individual-specific environmental experiences play an important role in the development of phobias, while familial-environmental factors appear to be of little aetiological significance.

Adult↗