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PubMed2005

Genetic and environmental influences on conduct disorder: symptom, domain and full-scale analyses.

BACKGROUND: We used variable threshold models which accounted for age and gender differences to investigate the genetic and environmental influences on DSM-IV conduct disorder (CD) at the level of symptoms, aggressive versus non-aggressive domains, and full-scale. METHOD: A community sample of 1100 twin pairs (age 11-18) was interviewed using the Diagnostic Interview Schedule for Children. RESULTS: Behavior genetic model fitting suggested that genetic and environmental influences on individual symptoms varied by symptom. The best-fitting models for aggressive and non-aggressive domains, and full-scale CD included additive genetic effects and unique environmental effects only (AE models). These effects could be constrained across age cohorts and sex. The results suggest that using models that incorporate age- and gender-appropriate thresholds specific to each subject we can account for prevalence differences between cohorts. Heritability estimates were .49, .55 and .53 for the aggressive domain, non-aggressive domain, and full-scales, respectively. These results are in contrast to previous research on antisocial behavior measured with the CBCL reporting higher heritability for aggressive versus non-aggressive domains. CONCLUSIONS: Results suggest that individual symptoms of CD may be differentially heritable. Additionally, CD assessed using DSM-IV criteria may show differing patterns of heritability compared with estimates obtained for other measures of antisocial behavior such as the CBCL.

Adolescent↗

PubMedDate not supplied

Stochastic thresholds.

Thresholds have traditionally been represented by a single number; the optimal management of the patient depends on whether his probability of disease is above or below this number. The concept of a threshold as a single number, however, inadequately represents the treatment approach of a group of physicians who do not have all the same threshold or a single physician who is uncertain about the exact value of the threshold. An alternative to a single valued threshold is to consider the threshold as having a probability distribution: for every probability that the patient has the disease there is a probability that the threshold is exceeded. This "stochastic" threshold model contains information about the uncertainty of the threshold estimation. Stochastic thresholds can be useful for testing the sensitivity of a management decision to the patient's probability of disease. They can also be used for comparing the standards of practice of individual physicians or comparing the practice of an individual physician with that of a group.

Decision Making↗

PubMed2001

Twinning rates for North American Holstein sires.

Calving data of North American Holsteins were analyzed using a linear sire model and a threshold sire model to estimate fixed effects and sire predicted transmitting abilities (PTA) for twinning rate. The data were 1,324,678 births of 37,174 sires of cows from the National Association of Animal Breeders (NAAB) calving ease database. All twins were assumed to be dizygotic. Triplets were not included in the analysis. The twinning rate was 5.02%. The sire model included relationships among sires and fixed effects of herd-years, season, parity, and sire groups. Different estimates of heritability due to models and restrictions on data have been demonstrated. Heritability estimates for the sire of the cow effect were 2.10% by the linear model analysis and 8.71% by the threshold model analysis. Sire PTA for twinning rate ranged from 1.6 to 8.0%. Mean incidence of twins increased from first to fifth and later parities: 1.63, 5.22, 6.66, 7.19, and 7.19%, respectively. Some changes with season were also evident. The incidence of twins was highest in April to June, at 5.88%, and lowest in October to December, at 4.23%. Sire group effects showed that sires born after 1990 had a higher incidence of twins than sires born before 1990. The mean twinning rate for sires born before 1980 was 4.55% compared with a mean of 5.58% for sires born after 1991. Characteristics of individual sire evaluations are discussed. Ample opportunity exists to change the incidence of twins in the Holstein population. Sire selection can be used to reduce the incidence of twins and also the increased cost of production associated with twins. From a national perspective, a reduction in the incidence of twin births can result in a saving of as much as $55 million per year.

Animals↗

PubMed2005

Support for a continuous (single-process) model of recognition memory and source memory.

Does memory retrieval occur in a continuous or an all-or-none manner? The shape of the receiver operating characteristic (ROC) has been used to answer this question, with curvilinear and linear memory ROCs indicating continuous and all-or-none retrieval processes, respectively. Signal detection models (e.g., the unequal variance model) correspond to a continuous retrieval process, whereas threshold models (including the multinomial model and the recollection component of the dual-process model) correspond to an all-or-none process. In studies of source memory, Slotnick et al. (2000) and others have observed curvilinear ROCs (supporting the unequal variance model), whereas Yonelinas (1999) observed linear ROCs (supporting the dual-process model). We resolve these seemingly inconsistent results, showing that source memory ROCs are naturally curvilinear but can appear linear when nondiagnostic source information is included in the analysis. Furthermore, the unequal variance model accounted for both recognition memory and source memory ROCs, supporting a continuous process of memory retrieval.

Humans↗

PubMed2004

[Risk of postirradiation induction of cancer of the modern methods of radiotherapy (3D CRT and IMRT) head and neck cancer].

Ionizing radiation is a known "universal carcinogen" for a wide variety of tumors in man. Human populations are exposed to radiation coming from natural and industrial environment, and from medical sources. However, these are radiotherapy patients who receive the highest doses. Radiation both mutates and sterilizes cells (lethal effect). The risk of cancer induction from cells that have received very high doses of radiation (therapeutic dose about 2 Gy) is lower then from the cells with low doses, since the majority of them will have been sterilized. The epidemiological studies based on the population of atomic bomb survivors have indicated that the most acceptable model of carcinogenesis is the linear non-threshold model. The evaluation of clinical risk related to a wide range of radiation doses, which range from 0.01 Gy to 2 Gy, is connected with many methodological problems such as: differences in treatment factors (dose range, irradiated volume, anatomical site), unknown epidemiological data (smoking abuse, comorbidity), shortening of the follow-up (short lifespan, migration), evaluation of small groups of patients. The most important difficulty is lack of the sufficient knowledge of genetic background which is probably most significant in carcinogenesis process. The introduction into clinical practice of a new sophisticated method of irradiation such as the three-dimensional conformal radiotherapy (3D CRT) or intensity modulated radiotherapy (IMRT) leads to the increase of low irradiation dose for very large volume of normal tissue. Thus, the evaluation of these new methods in the context of carcinogenesis is a very important objective in the future. Today, we can only introduce the most important questions concerned with the risk of carcinogenesis induction which await answers: what is the risk of induction of cancer due to the implementation of these new methods of treatment, and how important is this risk for clinical practice, especially in the case of combined radiochemotherapy? Despite a large body of experimental and clinical studies, radiation carcinogenesis is not fully understood yet. Additional problems related to the impact of irradiation of low dose on carcinogenesis are not resolved. For example, the bystander effect, the low dose hypersensitivity and the adaptive response could modulate the total response after irradiation, but the impact on the carciongenesis is unknown.

Bystander Effect↗

PubMed2006

Genetic parameters for calving rate and calf survival from linear, threshold, and logistic models in a multibreed beef cattle population.

Generalized mixed linear, threshold, and logistic sire models and Markov chain, Monte Carlo simulation procedures were used to estimate genetic parameters for calving rate and calf survival in a multibreed beef cattle population. Data were obtained from a 5-generation rotational crossbreeding study involving Angus, Brahman, Charolais, and Hereford (1969 to 1995). Gelbvieh and Simmental bulls sired terminal-cross calves from a sample of generation 5 cows. A total of 1,458 cows sired by 158 bulls had a mean calving rate of 78% based on 4,808 calving records. Ninety-one percent of 5,015 calves sired by 260 bulls survived to weaning. Mean heritability estimates and standard deviations for daughter calving rate from posterior distributions were 0.063 +/- 0.024, 0.150 +/- 0.049, and 0.130 +/- 0.047 for linear, threshold, and logistic models, respectively. For calf survival, mean heritability estimates and standard deviations from posterior distributions were 0.049 +/- 0.022, 0.160 +/- 0.058, and 0.190 +/- 0.078 from linear, threshold, and logistic models, respectively. When transformed to an underlying normal scale, linear sire, mixed model, heritability estimates were similar to threshold and logistic sire mixed model estimates. Posterior density distributions of estimated heritabilities from all models were normal. Spearman rank correlations between sire EPD across statistical models were greater than 0.97 for daughter calving rate and for calf survival. Sire EPD had similar ranges across statistical models for daughter calving rate and for calf survival.

Animals↗

PubMed1993

Comment on 'ventilation and blood lactate increase exponentially during incremental exercise'.

A recent paper in this journal has examined the ventilatory compensation for metabolic acidosis with increasing oxygen uptake, making extensive use of mathematical and statistical techniques. The authors conclude that '...respiratory compensation for metabolic acidosis during incremental exercise is a continuous process...'. While this may indeed be so, the following major aspects of the paper render the evidence at best dubious, surely inconclusive and perhaps even worthless: (1) The mathematical and statistical methodology is sloppy, incomplete and, at times, flawed. (2) No discontinuous model is presented for comparative purposes, only three continuous ones. (3) The authors ignore the fact that some threshold models produce smooth continuous data, and as a consequence, a good fit of a smooth continuous model cannot exclude the presence of a threshold. (4) The data in Table 5 show the amplitude parameter A of the preferred model to be not significantly different from zero. This paper draws these matters to the attention of readers of this journal, reviewers of manuscripts and other researchers, with comment and suggestion. This is done in the hope that all those concerned with mathematical and statistical methodologies will become more aware of their proper use.

Anaerobic Threshold↗

PubMed1993

Dobutamine infusions in stable, critically ill children: pharmacokinetics and hemodynamic actions.

OBJECTIVE: To delineate dobutamine pharmacokinetics and hemodynamic responses in children. DESIGN: Prospective, pharmacokinetic study using sequential, graded dosing of drug. INTERVENTIONS: Graded intravenous dobutamine infusions of 0.5, 2.5, 5, 10, and 20 micrograms/kg/min were sequentially administered for 25 mins each. Plasma dobutamine concentrations and echocardiographically determined hemodynamic data were obtained at baseline and at 15 and 25 mins during each infusion rate. Hemodynamic responses were evaluated by paired t-test and by computerized evaluation of individual dose-response curves. SETTING: Pediatric intensive care unit in a university setting. PATIENTS: Eleven stable, critically ill children previously requiring inotropic support with dobutamine. Seven patients were postcardiac surgical patients; four patients had acute cardiac dysfunction with septic shock and/or adult respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: Mean cardiac index increased from 3.8 to 5.2 L/min/m2 (p < .05). Increasing the infusion rate from 10 to 20 micrograms/kg/min increased cardiac index by 16% (p < .05). Cardiac index increased by > 10% in four of seven patients at a dobutamine infusion rate of 0.5 microgram/kg/min (mean 21%). The relationship of plasma dobutamine concentration to cardiac index, systolic blood pressure, and heart rate fit a threshold model with a log-linear relationship after the threshold in seven of nine, seven of 11, and eight of 11 patients, respectively. As anticipated, in the patients who responded, there were linear increases in hemodynamic responses with exponential increases in plasma dobutamine concentrations. Mean plasma clearance rate was 82 +/- 3 mL/min/kg. First-order kinetics were demonstrated by the direct linear relationship of plasma dobutamine concentration to infusion rate (mean r2 = .95; p < .01 for each patient) and by independence of clearance from dose and duration of each infusion. CONCLUSIONS: Dobutamine effectively improves systolic function in critically ill children. Hemodynamic responses to dobutamine generally follow a predicted log-linear dose-response model. Dobutamine clearance in this study was consistent with first-order kinetics. The wide variability in hemodynamic responses and clearance kinetics indicate that dobutamine infusions must be titrated individually.

Adolescent↗

PubMed1982

Chromosome interactions in Drosophila melanogaster. II. Total fitness.

In a large experiment, using nearly 200 population cages, we have measured the fitness of Drosophila melanogaster homozygous (1) for the second chromosome, (2) for the third chromosome, and (3) for both chromosomes. Twenty-four second chromosomes and 24 third chromosomes sampled from a natural population were tested. The mean fitness of the homozygous flies is 0.081 +/- 0.014 for the second chromosome, 0.080 +/- 0.017 for the third chromosome, and 0.079 +/- 0.024 for both chromosomes simultaneously. Assuming that fitnesses are multiplicative (the additive fitness model makes no sense in the present case because of the large selection coefficients involved), the expected mean fitness of the homozygotes for both chromosomes is 0.0066; their observed fitness is more than ten times greater. Thus, it appears that synergistic interactions between loci are considerable; and that, consequently, the fitness function substantially departs from linearity. Two models are tentatively suggested for the fitness function: a "threshold" model and a "synergistic" model.--The experiments reported here confirm previous results showing that the concealed genetic load present in natural populations of Drosophila is sufficient to account for the selective maintenance of numerous polymorphisms (of the order of 1000).

Animals↗

PubMed2005

Is inferential reasoning just probabilistic reasoning in disguise?

Oaksford, Chater, and Larkin (2000) have suggested that people actually use everyday probabilistic reasoning when making deductive inferences. In two studies, we explicitly compared probabilistic and deductive reasoning with identical if-then conditional premises with concrete content. In the first, adults were given causal premises with one strongly associated antecedent and were asked to make standard deductive inferences or to judge the probabilities of conclusions. In the second, reasoners were given scenarios presenting a causal relation with zero to three potential alternative antecedents. The participants responded to each set of problems under both deductive and probabilistic instructions. The results show that deductive and probabilistic inferences are not isomorphic. Probabilistic inferences can model deductive responses only using a limited, very high threshold model, which is equivalent to a simple retrieval model. These results provide a clearer understanding of the relations between probabilistic and deductive inferences and the limitations of trying to consider these two forms of inference as having a single underlying process.

Humans↗

PubMed2002

Metapopulation models for extinction threshold in spatially correlated landscapes.

Simple analytical models assuming homogeneous space have been used to examine the effects of habitat loss and fragmentation on metapopulation size. The models predict an extinction threshold, a critical amount of suitable habitat below which the metapopulation goes deterministically extinct. The consequences of non-random loss of habitat for species with localized dispersal have been studied mainly numerically. In this paper, we present two analytical approaches to the study of habitat loss and its metapopulation dynamic consequences incorporating spatial correlation in both metapopulation dynamics as well as in the pattern of habitat destruction. One approach is based on a measure called metapopulation capacity, given by the dominant eigenvalue of a "landscape" matrix, which encapsulates the effects of landscape structure on population extinctions and colonizations. The other approach is based on pair approximation. These models allow us to examine analytically the effects of spatial structure in habitat loss on the equilibrium metapopulation size and the threshold condition for persistence. In contrast to the pair approximation based approaches, the metapopulation capacity based approach allows us to consider species with long as well as short dispersal range and landscapes with spatial correlation at different scales. The two methods make dissimilar assumptions, but the broad conclusions concerning the consequences of spatial correlation in the landscape structure are the same. Our results show that increasing correlation in the spatial arrangement of the remaining habitat increases patch occupancy, that this increase is more evident for species with short-range than long-range dispersal, and that to be most beneficial for metapopulation size, the range of spatial correlation in landscape structure should be at least a few times greater than the dispersal range of the species.

Algorithms↗

PubMedDate not supplied

Clinical guidelines for using two dichotomous tests.

Building on the threshold model developed by Pauker and Kassirer for a single test, the authors describe a decision analytic model for two tests with dichotomous outcomes. The model includes ten decision strategies that differ depending on which tests are performed, whether the tests are performed together or in sequence, and the definition of a positivity criterion used to make the treatment decision when the test results disagree. Formulas derived from the model are used to compute the preferred option as a function of disease probability and to calculate test and test-treatment thresholds. General guidelines developed from the model can be used without calculation to identify relative preferences for alternative options and to predict threshold effects.

Diagnosis↗

PubMed2006

Neoplastic transformation in vitro by low doses of ionizing radiation: role of adaptive response and bystander effects.

The shape of the dose-response curve for cancer induction by low doses of ionizing radiation is of critical importance to the assessment of cancer risk at such doses. Epidemiologic analyses are limited by sensitivity to doses typically greater than 50-100 mGy for low LET radiation. Laboratory studies allow for the examination of lower doses using cancer-relevant endpoints. One such endpoint is neoplastic transformation in vitro. It is known that this endpoint is responsive to both adaptive response and bystander effects. The relative balance of these processes is likely to play an important role in determining the shape of the dose-response curve at low doses. A factor that may influence this balance is cell density at time of irradiation. The findings reported in this paper indicate that the transformation suppressive effect of low doses previously seen following irradiation of sub-confluent cultures, and attributed to an adaptive response, is reduced for irradiated confluent cultures. However, even under these conditions designed to optimize the role of bystander effects the data do not fit a linear no-threshold model and are still consistent with the notion of a threshold dose for neoplastic transformation in vitro by low LET radiation.

Cell Communication↗

PubMed2000

Sensoristasis and imbalance in persons with dementia.

PURPOSE: To present a model of sensoristasis and imbalance for use by health care professionals to deliver care to older adults with irreversible dementing illness. ORGANIZING CONSTRUCTS: The Sensoristasis Model shows the need of people with dementia to experience a balance between sensory-stimulating and sensory-calming activity. This model builds on Lawton's environmental docility hypothesis and on Hall and Buckwalter's Progressively Lowered Stress Threshold Model. METHODS: The model was derived from empirical evidence, theory, and clinical experience. Levels of agitation of three acute care patients experiencing sensoristasis and imbalances in sensoristasis indicate tenets of the model. FINDINGS: Older adults with dementia experience intrapsychic discomfort because of imbalances in the pacing of sensory-stimulating or sensory-calming activity. Consequences of intrapsychic discomfort include agitated behaviors and episodic or premature decline in instrumental and social function. CONCLUSIONS: Pacing of activity must be guided by interventions that facilitate optimum sensoristasis and often need to be adjusted during stress, environmental change, and progression of the illness. Interventions can ameliorate some of the negative consequences of imbalances in sensoristasis when optimal pacing is not attained.

Aged↗

PubMed1998

Patterns of alcohol, cigarette and illicit drug use in English adolescents.

AIMS: The aim of this study was to describe associations between alcohol, tobacco and illicit drug use in adolescents and demographic factors associated with substance use. DESIGN, SETTING, SUBJECTS: The study was a classroom survey of the total population of pupils (n = 5383, ages 11-16) in six schools selected from different locations around England. MEASURES: Respondents were asked confidentially about their use and extent of use of alcohol, cigarettes and illegal drugs. FINDINGS: The prevalence of regular substance use within the sample rose from 30.4% at age 11 to 83.9% at age 16. The prevalence of alcohol use did not differ between girls and boys, but smoking was more prevalent in girls and illegal drug use was more prevalent in boys. Alcohol was used more frequently than any other substance, or combination of substances, and alcohol use almost invariably accompanied the use of other substances: exclusive use of cigarettes or illegal drugs was negligible. In addition, high levels of alcohol intoxication were associated with increased use of both illegal drugs and cigarettes. Overall, around half the drinkers (46.8%) preferred alcopops to other types of alcoholic drink; this figure was greater in girls (56.4%) than in boys (37.1%), but fell sharply with age (62.9% at age 11; 37.7% at age 16), particularly in boys. Preference for spirits increased with age, and was particularly marked in girls (28.4% in girls vs. 18.5% in boys at age 16). Spirits drinkers were more likely to use cigarettes and drugs, and had been more frequently drunk, than either beer/wine or alcopops drinkers; these measures also tended to be higher in alcopop drinkers than in beer/wine drinkers, particularly among 11-13-year-old girls. CONCLUSION: The use of both tobacco and illicit drugs appears to be strongly associated with alcohol use, which is more prevalent, and the risk of smoking and illicit drug use is particularly high in adolescents who report high levels of drunkenness. Our results are consistent with a simple threshold model of substance abuse in which alcohol occupies a low threshold position relative to the higher threshold of cigarettes and illegal drugs. Smoking, drug use and drunkenness were lowest in beer/wine drinkers, intermediate in alcopop drinkers, and highest in spirits drinkers.

Adolescent↗

PubMed1999

A stochastic model of the electrically stimulated auditory nerve: single-pulse response.

Most models of neural response to electrical stimulation, such as the Hodgkin-Huxley equations, are deterministic, despite significant physiological evidence for the existence of stochastic activity. For instance, the range of discharge probabilities measured in response to single electrical pulses cannot be explained at all by deterministic models. Furthermore, there is growing evidence that the stochastic component of auditory nerve response to electrical stimulation may be fundamental to functionally significant physiological and psychophysical phenomena. In this paper we present a simple and computationally efficient stochastic model of single-fiber response to single biphasic electrical pulses, based on a deterministic threshold model of action potential generation. Comparisons with physiological data from cat auditory nerve fibers are made, and it is shown that the stochastic model predicts discharge probabilities measured in response to single biphasic pulses more accurately than does the equivalent deterministic model. In addition, physiological data show an increase in stochastic activity with increasing pulse width of anodic/cathodic biphasic pulses, a phenomenon not present for monophasic stimuli. These and other data from the auditory nerve are then used to develop a population model of the total auditory nerve, where each fiber is described by the single-fiber model.

Action Potentials↗

PubMed1997

Relationship between blood pressure and body mass index in lean populations.

Associations between body mass index (BMI) and blood pressure (BP) have been consistently observed, but remain poorly understood. One unresolved question is whether there is a linear relationship across the entire BMI range. We investigated this question among 11,235 adult men and women from seven low-BMI populations in Africa and the Caribbean. We used kernel smoothing and multivariate linear and spline regression modeling to examine gender differences in the relationship and to test for a threshold. Age-adjusted slopes of BP on BMI were uniformly higher in men than women, with pooled slope ratios of 2.00 and 2.20 for systolic and diastolic BPs, respectively. Men displayed no evidence of age modification or nonlinearity in the relationship, and the age-adjusted slope of systolic BP on BMI was 0.90 (95% confidence interval [CI], 0.76 to 1.04). Women demonstrated both age modification and nonlinearity. For both younger (<45 years) and older (45+ years) women, the optimal change point for a single threshold model was found to be 21 kg/m2. Slopes of systolic BP on BMI above this threshold were positive and significant: 0.68 (95% CI, 0.54 to 0.81) and 0.53 (95% CI, 0.29 to 0.76) for younger and older women, respectively. Slopes below the threshold were essentially zero for both groups of women, and the difference between the slopes above and below the threshold was significant for younger women (P=.019). In summary, we observed a threshold at 21 kg/m2 in the relationship between BMI and BP for women but not for men. This contributes to the effort to identify the mechanisms that underlie this relationship and how they differ by gender.

Adult↗

PubMed2001

An application of the thresholds of change model to the analysis of mental health data.

The threshold of change model (TCM) is a statistical technique for analyzing ordered stages of change variables. TCM focuses on the thresholds that separate the ordered stages, and the effects of explanatory variables are evaluated in terms of raising or lowering the thresholds. TCM also allows the explanatory variables to exert differential influence on each threshold. In this paper, we use TCM to analyze the data from a clinical trial that compared assertive community treatment (ACT) with standard case management (SCM) for patients with co-occurring severe mental illness and substance use disorder. Endpoint data (36-month follow up) were used for this analysis. The response variable is the recoded Substance Abuse Treatment Scale with three ordered levels (engagement/persuasion, active treatment, and recovery/relapse prevention), and hence two thresholds. The explanatory variables are gender and group (ACT vs. SCM). The results indicate that gender exerts constant and significant effects on both thresholds. The group effect is somewhat mixed: ACT lowers the first threshold (active treatment), but raises the second threshold (recovery/relapse prevention).

Adolescent↗