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PubMed1991

The influence of dosage time of midazolam on its pharmacokinetics and effects in humans.

The influence of dosage time of midazolam on its pharmacokinetics and effects on the central nervous system were investigated in six healthy volunteers, with pharmacokinetic-pharmacodynamic modeling. Each volunteer received single oral doses of 15 mg midazolam on four separate occasions: 8 AM, 2 PM, 8 PM, and 2 AM. An almost significant circadian variation was found in elimination half-life, shortest at 2 PM (1.26 +/- 0.47 hours, mean +/- SD) and longest at 2 AM (1.57 +/- 0.44 hours) (p = 0.05). Drug effects measured were alpha activity of the electroencepalograph and P100 latency of the visual-evoked response. The maximum drug effect (Emax) model described the concentration-effect relationship, extended with either a threshold drug concentration or a sigmoidicity parameter. A significant circadian variation was found in baseline alpha activity: highest at 8 AM (109% +/- 19% of the 24-hour mean) and lowest at 2 AM (80% +/- 12%). For alpha activity the drug concentration at half-maximum effect of both threshold Emax model and sigmoid Emax model showed lower values at 8 AM and 2 AM and higher values at 2 PM and 8 PM. However, these differences were either not significant (p = 0.10, threshold model) or on the verge of statistical significance (p = 0.05, sigmoid model). No circadian variation was found in the parameters describing the effect on the visual-evoked response. We conclude that the sensitivity of the central nervous system to midazolam, as reflected in alpha activity, possibly shows a circadian variation.

Administration, Oral↗
PubMed1990

In vivo tests of the concept of photodynamic threshold dose in normal rat liver photosensitized by aluminum chlorosulphonated phthalocyanine.

In its simplest form, the photodynamic therapy (PDT) threshold dose model states that tissue necrosis due to PDT will occur if the number of photons absorbed by the photosensitizer per unit volume of tissue exceeds a critical value. This threshold is given by the product of photon fluence, photosensitizer concentration and specific absorption coefficient. To test the validity of this concept for PDT of normal rat liver sensitized with aluminum chlorosulphonated phthalocyanine (AISPC), all three of these parameters were varied by changing the injected AISPC dose, the wavelength of excitation and the irradiation geometry. The extent of necrosis caused by the treatment was consistent with the threshold model, except when the concentration of AISPC in the liver exceeded 20 micrograms g-1. For this animal model, we estimate the threshold to be (3.8 +/- 0.2) x 10(19) photons cm-3.

Animals↗
PubMed2004

A risk-based model to establish threshold planning quantities of hazardous substances.

The Threshold Planning Quantity (TPQ) is the minimum quantity of any hazardous substance stored or processed at an industry that can pose a defined level of risk up to a certain distance from the industrial premises should an accidental release occur. These are recommended by the concerned government departments of the respective countries. Often, concerned regulatory authorities focus on simple screening tools to prescribe TPQs of hazardous chemicals rather than on more detailed technical aspects. This is illustrated with the help of TPQs presently administered in India, which are followed based on Control of Industrial Major Accident Hazard regulations of the United Kingdom. In this paper, the risk ranking matrix (RRM) approach is described to evaluate the recommended TPQs and prescribe these for some extremely hazardous chemicals (EHS) commonly used in industries. The RRM presented here is unique in the sense that various acceptable risk criteria are reviewed to appropriately rank the risk potential and provide suitability criteria in terms of individual risk factors and geosocietal risk factors (GSRF). Based on this concept, an attempt has been made to develop a risk-based model to determine the TPQs of various EHS (acrolein, ammonia, chlorine, hydrogen fluoride, and phosgene).

Air Pollutants↗
PubMed1987

A systems model approach to the ventilatory anaerobic threshold.

An analogue systems model of whole-body human bioenergetics predicts a change in kinetics of VO2 time series values as a result of exercise levels above an anaerobic threshold. Plotted VO2 results from exercising subjects appear to confirm this change. The purpose of this study is to describe the background to the systems model analogue of the anaerobic threshold and a test procedure devised to estimate this threshold. The estimate so obtained has the dual advantages of being based on model theory and of not being subject to the sort of ambient variations inherent in a single-test determination. A non-homogeneous group of eight subjects comprising a full replicate of a 2(3) factorial experimental design, with factors age, sex and training status, took part in the study. On one hand the results indicate acceptance of the systems model theory. On the other, the analogue threshold measure possesses corresponding properties to the conventional anaerobic threshold. It is higher for trained (155-214 W) than for untrained subjects (108-158 W), higher for males (149-214 W) than for females (108-170 W), and displays no evident interaction effects. Results for the VO2 time constant and for the work efficiency, display similar effects except for an interaction in the latter between age and training status. These experimental findings are regarded as confirmatory of the nature of the analogue threshold measure.

Adult↗
PubMed2000

Heating and pain sensation produced in human skin by millimeter waves: comparison to a simple thermal model.

Cutaneous thresholds for thermal pain were measured in 10 human subjects during 3-s exposures at 94 GHz continuous wave microwave energy at intensities up to approximately 1.8 W cm(-2). During each exposure, the temperature increase at the skin's surface was measured by infrared thermography. The mean (+/- s.e.m.) baseline temperature of the skin was 34.0+/-0.2 degrees C. The threshold for pricking pain was 43.9+/-0.7 degrees C, which corresponded to an increase in surface temperature of approximately 9.9 degrees C (from 34.0 degrees C to 43.9 degrees C). The measured increases in surface temperature were in good agreement with a simple thermal model that accounted for heat conduction and for the penetration depth of the microwave energy into tissue. Taken together, these results support the use of the model for predicting thresholds of thermal pain at other millimeter wave (length) frequencies.

Adult↗
PubMed2006

Stages of change for moderate-intensity physical activity in deprived neighborhoods.

BACKGROUND: This article describes the association of external and psychosocial factors with the stages of change for moderate-intensity physical activity among individuals with generally low socioeconomic positions. METHODS: A self-administered questionnaire among individuals aged 18-65 years (response rate 60%, n = 2781) in deprived neighborhoods in Eindhoven, The Netherlands, was conducted in September 2000. To identify factors associated with stages of change an ordinal logistic regression model, the "Threshold of Change model (TCM)", was used to analyze the data. RESULTS: Thirty-six percent of the respondents were in the pre-action stages, 15% was in action and 49% in maintenance. Individuals who were, older, lower educated, had low health locus of control, had less knowledge of physical activity issues, and presented other risky health behaviors, were more likely to be in a lower stage of change category. A positive attitude, high self-efficacy expectations, perceiving the physical activity level of others as high, and much social support were associated with the higher stages of change categories. CONCLUSION: The distribution across the stages of change supports the need to improve physical activity behavior in these deprived neighborhoods. Interventions need to be tailored to the psychosocial, and the external factors that are likely to play a role in the behavioral change process.

Adolescent↗
PubMed1996

[3-D visualization of thoracic tumors from MR images].

AIM: In cooperation with the thoracic surgery department 3-D visualizations of tumors were generated to support the surgeons in preoperative planning. As opposed to 3-D reconstructions of CT data, those representations based on MRI images remain an exception. In this paper different methods of three dimensional visualization of lung tumors are presented and compared to each other. DESIGN: These methods are 1. contour based surface models, 2. threshold based surface models and 3. rendered scenes of segmented volume data with transparent, color-coded display. RESULTS: Combinations of all three methods in one single image are possible as well with the software we developed. Furthermore, cut planes through the original data can be integrated into the 3-D scene. The segmentation of anatomical objects is performed either manually or automatically with various procedures. CONCLUSIONS: Adequate possibilities of manipulation and archiving allow a fast handling and processing even of large data sets. The calculated volumes of the anatomical objects can be used for quantitative studies. Arbitrary views of the three dimensional reconstructions can be generated within a few seconds. Even animation can easily be calculated and displayed with 30 frames/second.

Adult↗
PubMed2004

Stages of change for fruit and vegetable consumption in deprived neighborhoods.

This article describes the association of external and psychosocial factors on the stages of change for fruit and vegetable consumption, among 2,781 inhabitants, aged 18 to 65 years, in deprived neighborhoods (response rate 60%). To identify correlates of forward stage transition, an ordinal logistic regression model, the Threshold of Change Model (TCM), was used to analyze the data. The results indicate that men, those from Dutch origin, those with (rather) low health locus of control, those displaying risk behaviors, and those without knowledge of dietary guidelines were less likely to move from one stage to another and therefore were more likely to be in a lower stage-of-change category. The results make it possible to distinguish target groups, which should receive more attention in future health promotion campaigns, and to identify factors to be addressed in those programs.

Adolescent↗
PubMed2005

A Bayesian threshold-normal mixture model for analysis of a continuous mastitis-related trait.

Mastitis is associated with elevated somatic cell count in milk, inducing a positive correlation between milk somatic cell score (SCS) and the absence or presence of the disease. In most countries, selection against mastitis has focused on selecting parents with genetic evaluations that have low SCS. Univariate or multivariate mixed linear models have been used for statistical description of SCS. However, an observation of SCS can be regarded as drawn from a 2- (or more) component mixture defined by the (usually) unknown health status of a cow at the test-day on which SCS is recorded. A hierarchical 2-component mixture model was developed, assuming that the health status affecting the recorded test-day SCS is completely specified by an underlying liability variable. Based on the observed SCS, inferences can be drawn about disease status and parameters of both SCS and liability to mastitis. The prior probability of putative mastitis was allowed to vary between subgroups (e.g., herds, families), by specifying fixed and random effects affecting both SCS and liability. Using simulation, it was found that a Bayesian model fitted to the data yielded parameter estimates close to their true values. The model provides selection criteria that are more appealing than selection for lower SCS. The proposed model can be extended to handle a wide range of problems related to genetic analyses of mixture traits.

Animals↗
PubMed2000

[Circadian rhythm of the ventricular fibrillation threshold in a model of hypoventilation-reoxygenation in female Wistar rats].

Hypoxia, similarly as myocardial ischemia, decreases the electric stability of the heart and thus produces the conditions for the genesis of ventricular arrhythmias within the 24 h period however a prompt restoration of oxygen supply or blood flow within myocardium causes serious ventricular arrhythmias. Therefore the aim of our study was to evaluate the reoxygenation impact on myocardium after hypoventilation in circadian dependence. The experiments were performed in female Wistar rats (pentobarbital anesthesia 40 mg/1 kg i.p., open chest experiments). The animals were adapted to the light regimen 12:12 hours, with the dark phase from 18.00 h to 06.00 h. Normal ventilation was used in the control group (n = 17) and in the second one (n = 4), 20 min reoxygenation followed 20 min of hypoventilation. The heart rate (HR) had been recorded just before the ventricular arrhythmias rose. Hypoventilation decreased significantly (p < 0.001) the VFT and HR when compared with the control group and changed the 24-hour rhythm of VFT to moderate bi-phase one. Reoxygenation counter changed this rhythm to inverse in the comparison with the control group. The lowest VFT values occurred when the top of VFT circadian rhythm was detected during normal ventilation. No dependence was detected between VFT and HR in both ventilation types. It is concluded that reoxygenation alternates the myocardial vulnerability to ventricular arrhythmias in dependence on alternation of light and dark and without the evident dependence on HR in the course of the whole 24-hour period. (Tab. 2, Fig. 2, Ref. 43.)

Animals↗
PubMed1991

Complex segregation analysis of nonsyndromic cleft lip and palate.

This study was undertaken to examine the inheritance pattern of nonsyndromic cleft lip with or without cleft palate (CL/P). Complex segregation analysis using the unified model as in POINTER and the regressive model as in REGD programs were applied to analyze a midwestern U.S. Caucasian population of 79 families ascertained through a proband with CL/F. In REGD, the dominant or codominant Mendelian major locus models of inheritance were the most parsimonious fit. In POINTER, besides the Mendelian major locus model, the multifactorial threshold (MF/T) model and the mixed model were also consistent with the observed data. However, the high heritability parameter of .93 (SD .063) in the MF/T model suggests that any random exogenous factors are unlikely to be the underlying mechanisms, and the mixed model indicates that this high heritability is accounted for by a major dominant locus component. These findings indicate that the best explanation for the etiology of CL/P in this study population is a putative major locus associated with markedly decreased penetrance. Molecular studies may provide further insight into the genetic mechanism underlying CL/P.

Cleft Lip↗
PubMed1994

Caring for people with Alzheimer's disease using the conceptual model of progressively lowered stress threshold in the clinical setting.

Care of the people with Alzheimer's disease and related disorders (ADRD) has been fraught with controversy, often resulting in competing philosophies about what constitutes the "correct" approach. Whether developing an individualized plan of care or specialized programming, it is helpful to use a conceptual framework. The Progressively Lowered Stress Threshold (PLST) conceptual model has been used extensively for planning individualized care for patients with ADRD, developing specialized environments and programming, evaluating outcomes of interventions, and serving as the theoretical framework for nursing research. This article describes use of the PLST model in a clinical setting.

Adaptation, Psychological↗
PubMed1996

Optimization principles for the neural code.

Recent experiments show that the neural codes at work in a wide range of creatures share some common features. At first sight, these observations seem unrelated. However, we show that these features arise naturally in a linear filtered threshold crossing model when we set the threshold to maximize the transmitted information. This maximization process requires neural adaptation to not only the DC signal level, as in conventional light and dark adaptation, but also to the statistical structure of the signal and noise distributions. We also present a new approach for calculating the mutual information between a neuron's output spike train and any aspect of its input signal which does not require reconstruction of the input signal. This formulation is valid provided the correlations in the spike train are small, and we provide a procedure for checking this assumption. This paper is based on joint work (DeWeese M 1995 Optimization principles for the neural code, Dissertation, Princeton University). Preliminary results from the linear filtered threshold crossing model appeared in a previous proceedings (DeWeese M and Bialek W 1995 Information flow in sensory neurons, Nuovo Cimento D 17 733-8), and the conclusions we reached at that time have been reaffirmed by further analysis of the model.

Journal Article↗
PubMed1986

When is a diagnostic test result positive? Decision tree models based on net utility and threshold.

The question "When is a diagnostic test result positive?" can be addressed by clinical decision analysis. We developed two simple decision tree models for selecting appropriate cutoff levels: a net utility model and a threshold model. These models have been incorporated in a software program for desktop computers. We believe it is important for investigators to provide raw data on test performance, for three reasons. First, these data can be used in simple decision tree models to identify "appropriate" cutoff levels. Second, they can be used to evaluate empiric cutoff levels or decision rules. Third, they can be used to evaluate optimal cutoff levels for detailed decision trees depicting specific clinical problems.

Cost-Benefit Analysis↗
PubMedDate not supplied

Skin sensitization thresholds: determination in predictive models.

For many years, test methods for the prospective identification of skin sensitizing chemicals have been widely available. However, although these techniques have permitted the identification of the great majority of skin sensitizers, their use in assessing the relative potency of a particular chemical as a human contact allergen has not been well described. A primary reason for this is the inherent difficulty of such an exercise. A complex phenomenon involving interactions between the vehicle, the allergen, the skin and its inflammatory responses takes place during the induction and elicitation of sensitization. All these factors can have a profound effect on the threshold values determined for a skin sensitizer. Consequently, whether the assessment is conducted in humans or in animal models, a threshold concentration is always a function of the method of measurement as much as the potency of the allergen. Although an exhaustive review has not been carried out, this paper considers the attempts that have been made to assess relative potency by the measurement of dose-response relationships and the determination of induction and elicitation thresholds in both animal models and in humans. The latter has special relevance for regulatory toxicology and this matter is given particular attention in this article. Finally, recommendations are made: (a) that threshold concentrations for skin sensitizers should be determined on a case by case basis in relation to the likely mode of skin contact; (b) where the data are used in comparisons of skin sensitization potency, then there should be standardization of the method used for the determinations.

Animals↗