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PubMed1994

Duration comparison: relative stimulus differences stimulus age, and stimulus predictiveness.

Under a psychophysical trials procedure, pigeons were presented with a red light of one duration followed by a green light of a second duration. Eight geometrically spaced base durations were paired with one of four shorter and four longer durations as the alternate member of a duration pair, with different pairs randomly intermixed. One choice was reinforced if red had lasted longer than green, and a second choice was reinforced if green had lasted longer. Performance was compared when all the base durations and their pair members were included (entire-range condition) or when only the four longest base durations and their comparison durations (restricted-range condition) were used. Discrimination sensitivity decreased for longer duration pairs under both conditions, supporting a memory-based account. Sensitivity was lower under the restricted-range condition. Under both conditions, a bias to report "green as longer" increased as the second green duration increased. Bias changed as a matching function of the green-duration predictiveness of the correct choice. The results are related to a quantitative model of timing and remembering proposed by Staddon.

Animals↗
PubMed2002

Categorization, concept learning, and behavior analysis: an introduction.

Categorization and concept learning encompass some of the most important aspects of behavior, but historically they have not been central topics in the experimental analysis of behavior. To introduce this special issue of the Journal of the Experimental Analysis of Behavior (JEAB), we define key terms; distinguish between the study of concepts and the study of concept learning; describe three types of concept learning characterized by the stimulus classes they yield; and briefly identify several other themes (e.g., quantitative modeling and ties to language) that appear in the literature. As the special issue demonstrates, a surprising amount and diversity of work is being conducted that either represents a behavior-analytic perspective or can inform or constructively challenge this perspective.

Animals↗
PubMed2003

Quantitative analyses of matching-to-sample performance.

Six pigeons performed a simultaneous matching-to-sample (MTS) task involving patterns of dots on a liquid-crystal display. Two samples and two comparisons differed in terms of the density of pixels visible through pecking keys mounted in front of the display. Selections of Comparison 1 after Sample 1, and of Comparison 2 after Sample 2, produced intermittent access to food, and errors always produced a time-out. The disparity between the samples and between the comparisons varied across sets of conditions. The ratio of food deliveries for the two correct responses varied over a wide range within each set of conditions, and one condition arranged extinction for correct responses following Sample 1. The quantitative models proposed by Davison and Tustin (1978), Alsop (1991), and Davison (1991) failed to predict performance in some extreme reinforcer-ratio conditions because comparison choice approached indifference (and strong position biases emerged) when the sample clearly signaled a low (or zero) rate of reinforcement. An alternative conceptualization of the reinforcement contingencies operating in MTS tasks is advanced and was supported by further analyses of the data. This model relates the differential responding between the comparisons following each sample to the differential reinforcement for correct responses following that sample.

Animals↗
PubMed1991

The application of risk assessment methods in making veterinary public health and animal health decisions.

The newly emerging discipline of quantitative risk assessment has wide application in the field of veterinary public health and animal health. Regulatory authorities are increasingly faced with public policy decisions that must assess the risks of new technology or practices relative to the potential benefits, thereby establishing a level of acceptable risk. The elements of risk are a choice of action, a probability of loss and a magnitude of loss. Perceived risk and actual risk are seldom equivalent; adoption of the methodologies used in technological and human health risk assessments will allow veterinary regulators to make better decisions. Determination of levels of acceptable risk are increasingly dependent on quantitative models, and examples are presented for evaluation of different post-mortem meat inspection systems, estimating disease risks associated with animal embryo transfer and formulating national border protection strategies. All models have some degree of subjectivity, and the decisions made by regulators and risk managers should incorporate a wide knowledge of the risk assessment process, as well as the conditions of use that will occur in the real world.

Animals↗
PubMed1994

Tsetse flies and their control.

The authors use a quantitative modelling framework to describe and explore the features of the biology of tsetse flies (Glossina spp.) which are important in determining the rate of transmission of the African trypanosomiases between hosts. Examples are presented of the contribution of previous research on tsetse to quantified epidemiological and epizootiological understanding, and areas of current ignorance are identified for future study. Spatial and temporal variations in risk are important (but rarely-studied) determinants of the impact of trypanosomiasis on humans, domestic animals and agricultural activities. Recent grid-based sampling surveys to Togo provide valuable data sets on tsetse, cattle and trypanosomiasis throughout the country. A combination of ground-based meterological and remotely-sensed satellite data, within linear discriminant analytical models, enables description of the observed distributions of the five species of tsetse occurring in Togo, with accuracies of between 72% (Glossina palpalis and G. tachinoides) and 98% (G. fusca). Abundance classes of the two most widespread species, G. palpalis and G. tachinoides, are described with accuracies of between 47% and 83%. This is especially remarkable given the relatively small differences between the average values of the predictor variables in areas of differing fly abundance. Similar analyses could be used to predict the occurrence and abundance of flies in other areas, which have not been surveyed to date, in order to plan tsetse control campaigns or explore development options. Finally, some recent tsetse control campaigns are briefly reviewed. The shift of emphasis from fly eradication to fly control is associated with a devolution of responsibility for control activities from central government to local areas, communities or even individuals. The future role of central governments will remain crucial, however, in determining the areas in which different control options are practised, in facilitating control by local communities and in protecting controlled areas from re-invasion by flies from other areas.

Animals↗
PubMed1994

Using census and mortality data to target small areas for breast, colorectal, and cervical cancer screening.

OBJECTIVES: The goal of this study was to develop and validate quantitative models for estimating cancer incidence in small areas. METHODS: The outcome for each cancer site was the incidence of disease that had reached a late stage at the time of diagnosis. Two sets of predictors were used: (1) census-based demographic variables and (2) census-based demographic variables together with the cancer-specific mortality rate. RESULTS: The best models accounted for a substantial percentage of between area variability in late-stage rates for cancer of the breast (46%), cervix (61%), and colon/rectum (58%). A validation procedure indicated that correct identification of small areas with high rates of late-stage disease was two to three times more likely when model-based estimates were used than when areas were selected at random. CONCLUSIONS: Additional testing is needed to establish the generality of the geographic targeting methodology developed in this paper. However, there are strong indications that small-area estimation models will be useful in many regions where planners wish to target cancer screening programs on a geographic basis.

Breast Neoplasms↗
PubMed2001

Quantitative pharmacogenetics of nortriptyline: a novel approach.

OBJECTIVE: To quantitatively model nortriptyline clearance as a function of the cytochrome P450 (CYP) 2D6 genotype and to estimate the contribution of genotype to the interindividual variability in steady-state plasma concentration and metabolic clearance. DESIGN: Modelling study using data from two previously published studies. PARTICIPANTS: 20 healthy volunteers receiving single oral doses of nortriptyline and 20 patients with depression on steady-state oral treatment. METHODS: A total of 275 nortriptyline plasma concentrations were analysed by standard nonlinear regression and nonlinear mixed effect models. The pharmacokinetic model was a 1-compartment model with first order absorption and elimination. All participants had previously been genotyped with respect to the CYP2D6 polymorphism. RESULTS: A model in which the intrinsic clearance is a linear function of the number of functional CYP2D6 genes and hepatic blood flow is fixed to 60 L/h gave the closest fit of the pharmacokinetic model to the data. Stable estimates were obtained for population pharmacokinetic parameters and interindividual variances. Assuming 100% absorption, the model allows systemic clearance and bioavailability to be estimated. Bioavailability was found to vary between 0.17 and 0.71, depending on the genotype. Using the frequency distribution of CYP2D6 genotype with the above results we estimate that, in compliant Swedish individuals on nortriptyline monotherapy, the number of functional CYP2D6 genes could explain 21% of the total interindividual variance in oral clearance of nortriptyline and 34% of that in steady-state plasma concentrations. CONCLUSION: Nonlinear mixed-effects modelling can be used to quantify the influence of the number of functional CYP2D6 genes on the metabolic clearance and plasma concentration of drugs metabolised by this enzyme. Gene dose has a significant impact on drug pharmacokinetics and prior knowledge of it may aid in predicting plasma concentration of the drug and thus tailoring patient-specific dosage regimens.

Adolescent↗
PubMed2004

Design of a compound screening collection for use in high throughput screening.

In this paper we introduce a quantitative model that relates chemical structural similarity to biological activity, and in particular to the activity of lead series of compounds in high-throughput assays. From this model we derive the optimal screening collection make up for a given fixed size of screening collection, and identify the conditions under which a diverse collection of compounds or a collection focusing on particular regions of chemical space are appropriate strategies. We derive from the model a diversity function that may be used to assess compounds for acquisition or libraries for combinatorial synthesis by their ability to complement an existing screening collection. The diversity function is linked directly through the model to the goal of more frequent discovery of lead series from high-throughput screening. We show how the model may also be used to derive relationships between collection size and probabilities of lead discovery in high-throughput screening, and to guide the judicious application of structural filters.

Chemistry, Pharmaceutical↗
PubMed1994

Retirement as a psychosocial transition: process of adaptation to change.

This study seeks to verify if the work-to-retirement process meets the requirements inherent to the Psychosocial Transitions Model. Quantitative and qualitative evaluations are used to verify if pre-, intra-, and post-retirement periods are different from one another when the individual's internal organization is examined. The experimental group (n = 17, age = 65) takes IPAT, LSI-A, and clinical interviews evaluations at pre-, intra-, and post-retirement measurement times. The control group (n = 22, age = 65), used to verify the test-retest effect, takes these evaluations only at the post-retirement session. Variance analysis (ANOVA) show, at a quantitative level that the retirement transition triggers observable changes in anxiety levels. A posteriori analysis (HELMERT) shows that these operate significantly between the pre- and intra-retirement times. The content analysis of interviews shows, at a qualitative level, observable changes in pre-post-retirement preoccupations. These include death thoughts.

Adaptation, Psychological↗
PubMed2003

Dynamics of calcium clearance in mouse pancreatic beta-cells.

Pancreatic beta-cells maintain glucose homeostasis by their regulated Ca(2+)-dependent secretion of insulin. Several cellular mechanisms control intracellular Ca(2+) levels, but their relative significance in mouse beta-cells is not fully known. We used photometry to measure the dynamics of cytosolic Ca(2+) ([Ca(2+)](i)) clearance after brief, depolarization-induced Ca(2+) entry. Treatment with thapsigargin or cyclopiazonic acid, inhibitors of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) pumps, nearly doubled the peak and slowed the decay of the depolarization-induced Ca(2+) transients. The remaining thapsigargin-insensitive decay was slowed further by inhibition of the plasma membrane Ca(2+)-ATPase (PMCA) and plasma membrane Na(+)/Ca(2+) exchanger (NCX) via alkalization of the bath solution, by adding lanthanum, or by substitution of Na(+) with Li(+). Mitochondrial Ca(2+) uptake contributed little to clearance in thapsigargin-pretreated cells. Together, the SERCA, PMCA, and NCX transport mechanisms accounted for 89 to 97% of clearance in normal solutions. We developed a quantitative model for the dynamic role of removal mechanisms over a wide range of [Ca(2+)](i). According to our model, 50 to 64% of initial Ca(2+) removal is via the SERCA pump, whereas the NCX contributes 21-30% of the extrusion at high [Ca(2+)](i), and the PMCA contributes 21-27% at low [Ca(2+)](i).

Animals↗
PubMed1999

Dysphoric mood and preference for immediate versus delayed monetary reinforcement.

It has been proposed that depression is the product of deficits in self-management skills: self-monitoring, self-evaluation, and self-reinforcement. While interventions based on this theory have shown promise, some of the basic tenets upon which the theory is based lack empirical support. The present experiment tested one such tenet--the claim that depressed individuals select smaller more immediate reinforcers (an impulsive choice) at the expense of larger more delayed reinforcers (a self-control choice). Currently, empirical support for this notion is sparse and contradictory. This study addressed several methodological problems in earlier studies by creating divergent groups based on Beck Depression Inventory scores, employing a task requiring multiple responses and applying a quantitative model to determine reinforcer value. Analyses indicated no systematic difference between participants in the dysphoric and nondysphoric groups in ability to delay reinforcement. Thus, the current results provide no support for the hypothesis that the 36 dysphoric individuals were unable to delay reinforcement relative to the 21 nondysphoric individuals. Because respondents across the sample as a whole showed a self-control preference, however, the data are consistent with findings in the experimental study of choice responding with adult human subjects. Interpretations in terms of sensitivity and pseudosensitivity to the experimental contingencies are explored.

Adolescent↗
PubMed1996

Assessment of the severity of asthma in a family practice.

The objective of this study was to evaluate clinical history and self-perception of severity as predictors of asthma severity. A short-term longitudinal study was conducted in a family practice in Melbourne, Australia, utilizing peak flow monitoring, medication diary, and self-administered asthma severity questionnaire. Seventy-two asthmatic subjects with a positive bronchodilator or exercise test, aged between 6 and 79 years, were studied. Symptom and treatment items were correlated with peak flow variability and minimal peak expiratory flow rate (PEFR). An asthma severity scale was generated using the partial credit version of Item Response Theory and the participants' severity scores were validated against lung function tests and medication usage. Quantitative modeling procedures were used to investigate the interrelationships of factors associated with peak flow variability. Severity scores demonstrated significant relationships with peak flow variability (partial r = 0.34) and treatment items. Self-perceived severity of asthma in the preceding 2 weeks showed significant association with peak flow variability (partial rho = 0.46) and minimal PEFR (rho = -0.41). The severity module of the Monash Respiratory Questionnaire is a valid and reliable instrument. The most important symptoms appear to be the frequency of use of bronchodilator and frequency of nocturnal attacks. A carefully structured clinical history in conjunction with the peak flow criteria of variability and minimal peak flow rate would be appropriate in the evaluation of asthma severity. Patients' self-perception of the severity of their asthma needs further evaluation.

Adolescent↗
PubMedDate not supplied

Quantitative structure-activity relationships in a set of thiazolidin -4-ones acting as H1-histamine antagonists.

A series of 2-(3- and 4-substituted phenyl)-3-[3-(N, N-dimethyl-amino)propyl]-1,3-thiazolidin-4-ones acting as H1-antihistaminics was investigated with a combined Hansch-CoMFA approach. The substituents at the 3- and 4-positions of the phenyl ring have been described through steric, electronic and hydrophobic parameters and correlated with pA2 values. The obtained quantitative models suggest that affinity to the receptor is promoted by hydrophobic and small 4-substituents and by 3- and 4-substituents generating a positive electrostatic potential towards a complementary receptor region.

Animals↗
PubMed1993

Critical aspects of initiation, promotion, and progression in multistage epidermal carcinogenesis.

Carcinogenesis in mouse skin can be divided into three distinct stages: initiation, promotion, and progression (malignant conversion). Initiation, induced by a single exposure to a genotoxic carcinogen, can result from a mutation in a single critical gene (e.g., rasHa), apparently in only a few epidermal cells. The change is irreversible. Promotion, resulting in the development of numerous benign tumors (papillomas), is accomplished by the repeated application of a nonmutagenic tumor promoter. The effects of single applications of tumor promoters are reversible since papillomas do not develop after insufficient exposure of initiated skin to promoters or when the interval between individual promoter applications is increased sufficiently. The reversibility of promotion suggests an epigenetic mechanism. Promoter treatment provides an environment that allows the selective clonal expansion of foci of initiated cells. The conversion of squamous papillomas to carcinomas (termed progression or malignant conversion) occurs spontaneously at a low frequency. The rate of progression to malignancy can be significantly increased by treatment of papilloma-bearing mice with certain genotoxic agents. These progressor agents or converting agents are likely to act via a second genetic change in papillomas already bearing the initiating mutation. Progression in the skin is characterized by genetic changes that result in several distinct changes in the levels or activity of structural proteins, growth factors, and proteases. The mechanisms involved in progression are being studied in epidermal cell culture. In order to determine the in vivo phenotype of cultured cells, a grafting system was developed in which the cells were transferred from culture to a prepared skin bed in athymic mice. Introduction of an activated v-fos oncogene into initiated cells bearing an activated rasHa gene produced cells with a carcinoma phenotype, i.e., carcinomas formed when the cells were grafted as part of reconstituted skin. Grafted keratinocytes containing the rasHa gene alone produced papillomas; with v-fos alone, normal skin formed when grafted. The rasHa/fos carcinomas showed changes in differentiation markers characteristic of chemically induced carcinomas. A cell culture assay utilizing cells initiated by the introduction of an activated rasHa oncogene was developed to study progression. After exposure of initiated cells to progressor agents under conditions in which the proliferation of the rasHa-initiated cells was suppressed, proliferating foci developed, with a good correlation of activity in the assay with activity in the progression stage in vivo. The cell culture assay provides a quantitative model to study chemically induced neoplastic progression and may be useful to identify potential progressor agents.

Animals↗
PubMed2004

Not all maps are equal: GIS and spatial analysis in epidemiology.

Recently, Geographical Information System (GIS) has emerged as an innovative and important component of many projects in public health and epidemiology. One of the most useful functions of GIS in epidemiology continues to be its utility in basic mapping. GIS may also involve more sophisticated spatial analysis of disease occurrence and contributing environmental factors. Depending on the quantity and quality of data and the methodology used in analysis, a given map may be either useful or misleading. Although visual analyses (mapped evidence) strengthened by exploratory analyses are mostly sufficient for epidemiologists, the formal testing of certain hypotheses or the estimation of relationships between measures of disease incidence and, for example, environmental covariates require quantitative modelling of disease distribution. It is a promising prospect that spatial statistics and GIS technology have slowly started to merge. However, whether GIS will be useful in the model-based approach and the prediction in, for example, epidemiology remains to be seen. The desired future development of GIS requires a switch of emphasis from data and information to knowledge.

Arctic Regions↗
PubMed1991

Predicting the shape of distance functions in curve tracing: evidence for a zoom lens operator.

Jolicoeur, Ullman, and MacKay (1986) showed that the time to confirm that two dots are on the same curve increases monotonically, but nonlinearly, as the curve distance between the two dots increases. These displays contained two curves and two dots. On same trials, the two dots were on the same curve (target curve), while the other curve served as a foil (distractor curve). The monotonically increasing effects of curve distance on response times for same trials suggested that the intervening curve segment was traced. In the present investigation of the source of the nonlinearity in these distance functions, it was hypothesized that differences in the distractor curves may have allowed a curve tracing operator with zoom lens properties to widen its receptive field while tracing parts of certain target curves. The wider receptive field may have allowed faster tracing over certain segments, owing to a reduced number of shifts required by the operator to scan the curve. The consequence of training certain segments of the curve more quickly than other segments of the curve would be a nonlinear effect of distance. A new set of stimuli was created for testing this hypothesis directly. Fairly linear distance effects were found for stimuli that contained a distractor curve that constrained the breadth of the postulated curve tracing operator, whereas stimuli that contained a distractor curve that could allow for a larger receptive field yielded nonlinear distance functions. The results are compared with the predictions of three quantitative models: pixel-by-pixel tracing; Jolicoeur, Ullman, and MacKay's (1991) bipartite operator; and a new zoom lens model, analogous to the zoom lens model of visual attention. The results were fit best by the latter model, in which tracing is accomplished by tracking the curve with a variably sized local operator.

Adult↗
PubMed1993

Additivity of loudness across critical bands: a critical test.

The use of magnitude estimation as well as axiomatic measurement theory has led to the suggestion that loudness adds across critical bands. In the present paper, we challenge this postulate by applying a more sensitive methodology, based on Falmagne's (1976) random conjoint measurement procedure. A necessary condition for additivity of loudness was investigated in tone complexes consisting of 2-kHz and 5-kHz (resp. 3-kHz) components; the results showed systematic deviations from additivity. We argue that these deviations are due to asymmetric masking of the higher component by the lower one, and we propose a tentative quantitative model to account for the data. Such a model is in line with results from tone-on-tone masking, which show masking to be effective over a range of several critical bands.

Auditory Threshold↗
PubMedDate not supplied

Multiple regression and vector analyses of laser in situ keratomileusis for myopia and astigmatism.

PURPOSE: To construct a quantitative model relating refractive results to laser settings and other factors. METHODS: A prospective clinical trial was performed, including 14 surgeons and 523 eyes of 278 patients who desired correction of myopia from -1.00 to -16.00 D (mean, -6.20 D) and astigmatism up to 6.00 D (mean, 1.10 D). Myopia and astigmatism were corrected by laser in situ keratomileusis (LASIK) with sequential spherical and cylindrical ablations using a 5.5-mm ablation zone and a transition zone to 7.0 mm. The Nidek EC-5000 excimer laser and the Chiron Automated Corneal Shaper were used. RESULTS: Surgically induced refractive changes 3 months after surgery were measured. Spherical ablation by LASIK produced a 19% greater refractive change than that predicted by the Nidek PRK algorithm. The laser setting needed to achieve each 1.00 D of cylinder correction induced 1.30 D change in spherical equivalent refraction (0.80 D more than expected). Patient age and nonlinear effects had small but statistically significant influences on refractive outcome. Sex, left/right eye, and surgeon were not significant factors. Residual variations in spherical equivalent refraction included a 0.50-D constant plus 9% of the predicted spherical equivlanet change. Residual variations in the parallel and orthogonal components of cylinder correction were, respectively, 28% and 13% of the predicted cylinder change plus a 0.30-D constant component. The standard deviation of axis alignment error for cylinder ablation was 3.7 degrees. CONCLUSIONS: Cylindrical ablation produced a spherical change that was larger than expected. To compensate for this, spherical ablation should be reduced in eyes with astigmatism. Variability in the correction of astigmatism was proportionally larger than that for spherical correction and was primarily due to magnitude rather than axis error.

Adult↗