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The potential synergy between cognitive models and modern psychometric models.

Analyses of cognitive aspects of survey methodology (CASM) and psychometric analysis are two methods that are able to complement each other. We use concrete examples to illustrate how psychometric analyses can test hypotheses from CASM. The psychometrics framework recognizes that survey responses are affected by other factors than the concept being assessed, for example by cognitive factors and processes. Such factors are subsumed under the concept of measurement error. Possible sources of measurement error can be tested, e.g. by randomized experiments. A standard way to reduce measurement error is to ask several questions about the same concept and combine the answers into a multi-item scale that is more precise than the individual items. Techniques like structural equation models use the item correlations to assess the magnitude of measurement error and to test the assumptions behind the multi-item scale, e.g. the effect of common response choices and item time frames. A central problem in modern psychometrics is how to model the mapping of the continuous latent variable onto the item response choice categories. This is achieved by threshold models (e.g. item response models and structural equation models for categorical data). These models can, for example, analyze the impact of mode of administration, test whether the items function in the same way for all people (measurement invariance/differential item functioning) and examine the consistency of responses from any single person. Such analyses provide new possibilities for combining psychometrics and cognitive methods.

Attitude to Health↗

Heritability for Alzheimer's disease: the study of dementia in Swedish twins.

BACKGROUND: Alzheimer's disease has been thought to have familial and sporadic forms, and several genetic defects have been identified that chiefly explain early-onset familial cases. In this study, our purpose was to detect all cases of dementia in an established twin registry and to estimate total extent of genetic contribution to liability to Alzheimer's disease. METHODS: At the first stage, members of the registry were screened for dementia, using in-person or telephone mental status testing. At the second stage, those who screened positively and their partners were referred for clinical work-ups, including neuropsychological assessment, physician examination, laboratory tests, and neuroimaging. Clinical diagnoses were assigned at a multidisciplinary consensus conference. Probandwise concordance rates were examined by zygosity, and structural modeling was applied to the data to estimate genetic and environmental influences, using both single- and multiple-threshold models. RESULTS: Sixty-five pairs were identified in which one or both was demented. The probandwise concordance rate for Alzheimer's disease among monozygotic pairs was 67%; the corresponding figure for dizygotic pairs was 22%. Heritability of liability to Alzheimer's disease was estimated to be .74; to any dementia, .43. The other variance is attributable to environmental influences. CONCLUSIONS: Findings indicate a substantial genetic effect for these predominantly late-onset Alzheimer's disease cases. At the same time, structural modeling results and large intra-pair differences in age of onset suggest that environmental factors are also important in determining whether and when an individual may develop dementia.

Age of Onset↗

Selective antagonism of calcium channel activators by fluspirilene.

1. Fluspirilene has been claimed to bind to a high affinity site in the calcium channel in skeletal muscle. We have investigated its calcium-antagonistic effects in smooth muscle and affinity for the channel in radioligand binding assays. 2. Fluspirilene was weakly active as an antagonist of Ca2(+)-induced contractions in K(+)-depolarized taenia preparations from the guinea-pig caecum, with threshold antagonism starting from concentrations of 30 nM. Nitrendipine, nicardipine and nimodipine were very potent antagonists in this model (threshold antagonism, greater than 1 nM). 3. In contrast, fluspirilene (10-1000 nM) was a potent non-competitive antagonist of the effects of Bay K 8644 (1-3000 nM) on Ca2(+)-induced contractions and, at 10 nM, selectively antagonised the effects of Bay K 8644, abolished the Ca2(+)-channel activator effects of CGP 28392, without changing the calcium antagonist effects of nitrendipine, or modifying the sensitivity of the tissues to Ca2+. In contrast, the dihydropyridines were more effective as antagonists of Ca2+ than of Bay K 8644. Fluspirilene therefore selectively antagonised the effects of dihydropyridine Ca2+ channel activators without affecting the antagonist potency. 4. In radioligand binding experiments, fluspirilene was a potent displacer of [3H]-PN-200-110 binding to rat cerebral cortical membranes (EC50 30 nM), albeit with a low Hill slope (0.66), and was more potent than other lipophilic diphenylalkylamines such as flunarizine and lidoflazine. Fluspirilene interacted non-competitively with [3H]-PN-200-110 and increased dissociation of the radioligand.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Stochastic resonance in a sinusoidally forced LIF model with noisy threshold.

In this report, the LIF neural model driven by underthreshold sinusoidal signals but with a gaussian-distributed noise on the threshold, is approximated by suitably defining an instantaneous firing (or escape) rate, which depends only on the momentary value of the voltage variable. This allows us to obtain, by analytically solving the relevant equations, the main statistical functions describing the "firing activity"; namely, the probability density function of firing phases and that of interspike intervals. From these functions two quantities can be derived, whose dependence on the noise intensity allows the Stochastic Resonance (SR) to be demonstrated. Besides the "regular" SR, the analysed system was found to produce, either for low frequencies and large amplitudes of modulation or for high modulation frequencies, resonance curves displaying two peaks. This bimodal feature of the resonance curves is accounted for on the basis of phase locked firing patterns.

Electrophysiology↗

Genetic analysis of the cause of exencephaly in the SELH/Bc mouse stock.

A new mouse stock, SELH/Bc, having a high liability to exencephaly has been developed. About 17% of SELH fetuses are exencephalic. The genetic cause of this exencephaly was investigated in a cross to a normal related ICR/Bc strain and in subsequent classical genetic crosses (F2, first and second backcrosses). The data were compared with a number of genetic models, including that of a single recessive mutation with 17% penetrance. The data did not fit single-locus inheritance. The expectations from the multifactorial threshold model based on an underlying quantitative liability trait with additive inheritance were found to fit the data very well. The number of loci involved was estimated to be about two or three. About 70% of exencephalic SELH fetuses are female, and there is no overall deficiency of males. The relatively higher risk in females was constant across the genetic backgrounds in the experiment. In summary, the liability to exencephaly in SELH mice appears to be a multifactorial threshold trait, and it therefore resembles human neural tube defects in type of genetic etiology. SELH therefore may be a valuable animal model in the study of neural tube defects.

Animals↗

Reading a population code: a multi-scale neural model for representing binocular disparity.

Although binocular neurons in the primary visual cortex are sensitive to retinal disparity, their activity does not constitute an unambiguous disparity signal. A multi-spatial-scale neural model for disparity computation is developed to examine how population activity might be interpreted to overcome ambiguities at the single neuron level. The model incorporates a front end that encodes disparity by a family of complex cell-like energy units and a second stage that reads the population activity. Disparity is recovered by matching the population response to a set of canonical templates, derived from the mean response to white noise stimuli at a range of disparities. Model predictions are qualitatively consistent with a variety of psychophysical results in the literature, including the effects of spatial frequency on stereoacuity and bias in perceived depths, and the effect of standing disparity on increment thresholds. Model predictions are also consistent with data on qualitative appearance of complex stimuli, including depth averaging, transparency, and corrugation. The model also accounts for the non-linear interaction of disparities in compound grating stimuli. These results show that a template-match approach reduces ambiguities in individual and pooled neuronal responses, and allows for a broader range of percepts, consistent with psychophysics, than other models. Thus, the pattern of neural population activity across spatial scales is a better candidate for the neural correlate of depth perception than the activity of single neurons or the pooled activity of multiple neurons.

Depth Perception↗

The effect of saccades on threshold perception--a model study.

The effect of saccadic eye movements on threshold perception is investigated theoretically. The proposed model considers eye movements by taking into account the shifting of the stimulus pattern on the retina during the occurrence of an eye movement. Saccades are characterized by high velocity and short duration. These motions cause overshoots in the response of linear filters to certain stimulus patterns. Therefore, the model predicts facilitation effects of saccades in the perception of low spatial frequency patterns and patterns flickering with high temporal frequencies. These results agree with experimentally obtained data presented in a subsequent paper. A simple approach is formulated which approximates the complex shifting function of a saccade by a switching of the pattern.

Eye Movements↗

corneal epithelial injury thresholds for exposures to 1.54 microm radiation-dependence on beam diameter.

Corneal epithelial injury thresholds have been determined for exposures to 1.54 mum infrared radiation from an Erbium fiber laser. Thresholds were determined for beam diameters from 0.05 to 0.7 cm for exposures having durations from approximately 1 to 100 s and for a fixed beam diameter of 0.1 cm for exposures with durations between 0.036 and 0.26 s. Near-threshold damage appeared within 30 min post-exposure. There was no evidence of latent damage from lesser exposures appearing up to 24-48 h post-exposure. The dependence of the threshold radiant exposures on laser beam diameter for exposures >1 s provides strong evidence supporting a critical temperature damage model. However, the shorter exposures are not in accord with a critical temperature damage model. Thresholds for exposures longer than 1 s are greater than 10 times the maximum permissible exposure (MPE) in ANSI Z-136.5-2000; however, the safety factor decreases to less than 10 for exposures less than 0.1 s with a 0.1-cm-diameter beam.

Animals↗

The role of genetic diversity in nest cooling in a wild honey bee, Apis florea.

Simulation studies of the task threshold model for task allocation in social insect colonies suggest that nest temperature homeostasis is enhanced if workers have slightly different thresholds for engaging in tasks related to nest thermoregulation. Genetic variance in task thresholds is one way a distribution of task thresholds can be generated. Apis mellifera colonies with large genetic diversity are able to maintain more stable brood nest temperatures than colonies that are genetically uniform. If this phenomenon is generalizable to other species, we would predict that patrilines should vary in the threshold in which they engage in thermoregulatory tasks. We exposed A. florea colonies to different temperatures experimentally, and retrieved fanning workers at these different temperatures. In many cases we found statistically significant differences in the proportion of fanning workers of different patrilines at different experimental temperatures. This suggests that genetically different workers have different thresholds for performing the thermoregulatory task of fanning. We suggest, therefore, that genetically based variance in task threshold is a widespread phenomenon in the genus Apis.

Animals↗

Mathematical beta cell model for insulin secretion following IVGTT and OGTT.

Evaluation of beta cell function is conducted by a variety of glucose tolerance tests and evaluated by a number of different models with less than perfect consistency among results obtained from different tests. We formulated a new approximation of the distributed threshold model for insulin secretion in order to approach a model for quantifying beta cell function, not only for one, but for several different experiments. Data was obtained from 40 subjects that had both an oral glucose tolerance test (OGTT) and an intravenous tolerance test (IVGTT) performed. Parameter estimates from the two experimental protocols demonstrate similarity, reproducibility, and indications of prognostic relevance. Useful first phase indexes comprise the steady state amount of ready releasable insulin A0 and the rate of redistribution krd, where both yield a considerable correlation (both r=0.67) between IVGTT and OGTT estimates. For the IVGTT, A0 correlates well (r=0.96) with the 10 min area under the curve of insulin above baseline, whereas krd represents a new and possibly more fundamental first phase index. For the useful second phase index gamma, a correlation of 0.75 was found between IVGTT and OGTT estimates.

Adult↗

The genetic epidemiology of bulimia nervosa.

OBJECTIVE: The authors seek to clarify, from both an epidemiologic and genetic perspective, the major risk factors for bulimia nervosa and to understand the relationship between narrowly defined bulimia and bulimia-like syndromes. METHOD: Personal structured psychiatric interviews were conducted with 2,163 female twins from a population-based register. Psychiatric disorders were assessed using DSM-III-R criteria. RESULTS: Lifetime prevalence and risk for narrowly defined bulimia were 2.8% and 4.2%, respectively. Including bulimia-like syndromes increased these estimates to 5.7% and 8.0%, respectively. Risk factors for bulimia included 1) birth after 1960, 2) low paternal care, 3) a history of wide weight fluctuation, dieting, or frequent exercise, 4) a slim ideal body image, 5) low self-esteem, 6) an external locus of control, and 7) high levels of neuroticism. Significant comorbidity was found between bulimia and anorexia nervosa, alcoholism, panic disorder, generalized anxiety disorder, phobia, and major depression. Proband-wise concordance for narrowly defined bulimia was 22.9% in monozygotic and 8.7% in dizygotic twins. The best-fitting model indicated that familial aggregation was due solely to genetic factors with a heritability of liability of 55%. A multiple threshold model indicated that narrowly defined bulimia nervosa and bulimia-like syndromes represented different levels of severity on the same continuum of liability. CONCLUSIONS: The liability to fully syndromal bulimia nervosa, which affects around one in 25 women at some point in their lives, is substantially influenced by both epidemiologic and genetic risk factors. The same factors that influence the risk for narrowly defined bulimia also influence the risk for less severe bulimia-like syndromes.

Adolescent↗

Method for detection of intracellular pH threshold; comparison between subjective observation and regression analysis.

The aim of this study is to examine the objectivity and reproducibility of intracellular pH threshold (pHT) detected by eye (E), and by regression analysis on linear (L), semilog (SL) and log-log (LL) models. Threshold for inorganic phosphate-to-phosphocreatine ratio (PT) was also examined by three regression analysis. Fifteen males volunteered as subjects. They performed wrist flexion in a ramp protocol of 0.14W/min till exhaustion. Throughout the exercise, 31P-MRS was obtained continuously from wrist flexors. Intracellular pH and phosphate compound in the muscle tissue were monitored as minute-by-minute data. In E, three observers determined pHT subjectively as a work rate just before pH decrement. In three regression analysis, pHT was detected as an intersection of a pair of linear regression lines which was selected statistically or subjectively. pHT detected by four methods showed significant reproducibility between each other, although PT did not. These results provide one of the evidences of threshold behavior of change in pH, and a question of existence of PT in contrast to pHT.

Exercise↗

alpha2-Heremans-Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effect of single-nucleotide polymorphisms (SNPs) in the gene encoding the human alpha(2)-Heremans-Schmid glycoprotein (AHSG) on obesity and insulin action in adipocytes. METHODS: We screened 24 individuals for SNPs in AHSG. Six haplotype-tagging SNPs were genotyped in 188 lean and 176 obese otherwise healthy women for whom common blood chemistry phenotypes were also available. Adipocyte lipolysis and lipogenesis phenotypes were quantified in a subset of 117 lean and 174 obese women. RESULTS: The -469T>G SNP, which is located in the 5' region of AHSG, was associated with insulin-mediated inhibition of lipolysis and stimulation of lipogenesis, as well as basal and 8-bromocyclic AMP-stimulated lipolysis. Three AHSG SNPs were associated with circulating levels of cholesterol. None of the six genotyped SNPs or inferred haplotypes were associated with BMI, calculated percent body fat, waist circumference, circulating levels of glucose or insulin, or homeostasis model assessment of insulin resistance, which was used as an estimate of in vivo insulin sensitivity. CONCLUSIONS/INTERPRETATION: Our results are in agreement with a threshold model of susceptibility for insulin resistance and type 2 diabetes, in which specific genetic loci regulate intermediate molecular phenotypes. When an individual's set of susceptibility alleles at such loci exceeds a threshold, clinical disease occurs. Lipolysis in adipocytes appears to be a phenotype that is particularly sensitive to variation in AHSG.

8-Bromo Cyclic Adenosine Monophosphate↗

The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study.

BACKGROUND: The magnitude of heritability of schizophrenia remains controversial, due in part to limitations of estimates derived from index twin pairs exclusively. We applied structural equation modeling in a total population of twins to determine the significance and magnitudes of the genetic and environmental contributions to schizophrenia. METHODS: All monozygotic (1180 male and 1315 female pairs) and same-sex dizygotic (2765 male and 2613 female pairs) twins born from 1940 to 1957 in Finland were screened for nonorganic psychotic disorder diagnoses as recorded on an inpatient or outpatient basis or from an eligibility review for a disability pension. RESULTS: The lifetime prevalence of schizophrenia was 2.0%, with a marginally higher prevalence in men (2.2%) than women (1.8%). Model fitting indicated that 83% of the variance in liability was due to additive genetic factors, and the remaining 17% was due to unique environmental factors. Sex-limitation modeling revealed no evidence of sex-specific genetic effects and no sex difference in the magnitude of heritability. A multiple threshold model incorporating affective and other psychoses as a phenotype intermediate between schizophrenia and no diagnosis was rejected. CONCLUSIONS: In a population-based twin study of schizophrenia, heritability was estimated at 83%, with the remaining variance in liability attributed to environmental factors not shared in common among co-twins. Despite the notable limitation of using diagnoses ascertained through treatment contacts, the heritability estimate in this study is almost identical to those reported in recent studies of index pairs using standardized applications of DSM-III or later criteria.

Adult↗

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.

The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation.

Aminolevulinic Acid↗

Torus palatinus and torus mandibularis: a review of the literature.

The torus has been mentioned in the literature for about 180 years. However, little has been revealed about it until the last two decades when great advances were made in the field of genetics. Its occurrence in various ethnic groups ranges from 9 to 66 per cent. Even between similar ethnic groups living in different environments, different figures have been reported. It has been statistically proven that differences do occur between various ethnic groups and the sexes. In current thinking, the occurrence of tori is considered to be an interplay of genetic and environmental factors. The quasi-continuous genetic or threshold model seems to hold the answers to their formation. This theory proposes that the environmental factors responsible must first reach a threshold level before the genetic factors can express themselves in the individual. Hence, both genetic and environmental factors determine liability, making the system multifactorial.

Adult↗

Statistical models for low dose exposure.

Extrapolation of health risks from high to low doses has received a considerable amount of attention in carcinogenic risk assessment over decades. Fitting statistical dose-response models to experimental data collected at high doses and use of the fitted model for estimating effects at low doses lead to quite different risk predictions. Dissatisfaction with this procedure was formulated both by toxicologists who saw a deficit of biological knowledge in the models as well as by risk modelers who saw the need of mechanistically-based stochastic modeling. This contribution summarizes the present status of low dose modeling and the determination of the shape of dose-response curves. We will address the controversial issues of the appropriateness of threshold models, the estimation of no observed adverse effect levels (NOAEL), and their relevance for low dose modeling. We will distinguish between quantal dose-response models for tumor incidence and models of the more informative age/time dependent tumor incidence. The multistage model and the two-stage model of clonal expansion are considered as dose-response models accounting for biological mechanisms. Problems of the identifiability of mechanisms are addressed, the relation between administered dose and effective target dose is illustrated by examples, and the recently proposed Benchmark Dose concept for risk assessment is presented with its consequences for mechanistic modeling and statistical estimation.

Age Factors↗

[Influences on the occurrence of abomasal displacements in German Holstein cows].

The objectives of this study were to analyse risk factors for the prevalence of abomasal displacement in German Holstein cows. In the period from 02/01/1999 to 01/31/2000 five veterinary surgeons in Northern Lower Saxony registered all cases of abomasal displacement in German Holstein cows being under the official milk recording scheme. In total, the investigation included 160 farms and 9315 cows. An abomasal displacement was registered in 151 German Holstein cows, corresponding to a frequency of 1.6%. More than 75% of the abomasal displacements appeared during the first 30 days after calving. The left abomasal displacement (74.8%) was recorded more often than the right abomasal displacement (25.2%). Milk recording and pedigree data were supplied by the VIT (Vereinigte Informationssystem Tierhaltung), Verden, and merged with the own recordings. The influences of the calving month, the lactation number, the age at calving, the inbreeding coefficient, calving performance, duration of pregnancy, breed of calf sire, calf sire and the breeding values for the milk performance did not explain a significant part of the variation of the frequency of the abomasal displacement. Significant effects of the sire, birth of twins or even more calves and the herd were obtained for the leftsided abomasal displacement. For the rightsided abomasal displacement and for all abomasal displacements the herd effect was not significant. Heritability estimates using bivariate linear REML models were h2 = 0.043 +/- 0.012 for the leftsided abomasal displacement, and h2 = 0.007 +/- 0.004 for the rightsided abomasal displacement, respectively. Using the threshold model the heritabilities yielded estimates of h2 = 0.51 for the left abomasal displacement, and for the right abomasal displacement of h2 = 0.19, respectively.

Abomasum↗