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PubMed1994

[Heuristic and empirical approaches in psychiatry].

Scientific investigations with their realistic orientation have brought about an increase in our knowledge about details in psychiatry. Despite these gains, their actual contribution to psychiatric cognition has been modest. They have been unable to conceptually grasp the role of personal components which are decisive for our discipline. They have also been unable to produce those connections which organize what is supposed to be the object of our concerns. The psychopathological reflections which are employed here rely on the heuristic approach. The example of idiopathic, and especially, the affective psychotic syndromes, makes clear the need to apply heuristic approaches.

Brain↗
PubMed1997

A semi-empirical approach to the evaluation of the relative biological effectiveness of therapeutic proton beams: the methodological framework.

We address the problem of the evaluation of the relative biological effectiveness (RBE) of therapeutic proton beams for cell inactivation. We consider a general approach to the evaluation of the lethal effect of protons which is applicable to different situations, including those in which an extended Bragg peak is obtained via a modulated beam. Our approach combines two kinds of information: (1) the experimental results available in the literature for the response of Chinese hamster V79 cells to monoenergetic beams and (2) the energy spectrum of the beam in the target volume, computed through a Monte Carlo algorithm. We have applied this method to a simple Bragg peak produced by a broad-field proton beam of about 70 MeV initial energy, such as those that, after attenuation, are typically used for treatment of ocular tumors. We have found that the RBE increases with depth, even beyond the Bragg peak, up to a value close to 2, when evaluated at the same surviving fraction as that resulting after exposure to 2 Gy of X rays.

Animals↗
PubMed1998

[Gerotranscendence as a life cycle perspective: an initial empirical approach among the elderly in The Netherlands].

Gerotranscendence has been defined as a shift in meta-perspective, from a materialistic and rationalistic perspective to a more cosmic and transcendent one that accompanies the process of aging. The present study describes scale characteristics of the Dutch translation of Tornstam's gerotranscendence scale, using data from a sample among adults aged 56-76 years (N = 556). Two subscales evolve from scale analysis, similar to those found by Tornstam: cosmic transcendence and egotranscendence. Scores on both subscales are higher for the older old, as well as for the unmarried; divorced or widowed respondents who suffer from physical impairments. Scale scores are also higher for respondents with depressive complaints. On the subscale cosmic transcendence Roman Catholics have higher scores than Protestants and non-church members. On the subscale ego-transcendence well educated respondents and those with few social contacts have higher scores than persons with less education and those with many contacts. The strength of the associations is modest and the variance explained is small. The findings warrant further research into the question whether gerotranscendence adds to competence in later life.

Aged↗
PubMed2005

Population pharmacokinetic studies in pediatrics: issues in design and analysis.

The current review addresses the following 3 frequently encountered challenges in the design and analysis of population pharmacokinetic studies in pediatrics: (1) body size adjustments during the development of pharmacostatistical models, (2) design and validation of limited sampling strategies, and (3) the integration of historical priors in data analysis and trial simulation. Size adjustments with empiric approaches based on body weight or body surface area have frequently proven as a pragmatic tool to overcome large size differences in a pediatric study population. Allometric size adjustments, however, provide a more mechanistic, physiologically based approach that, if used a priori, allows delineation of the effect of size from that of other covariates that show a high degree of collinearity. The frequent lack of dense data sets in pediatric clinical pharmacology because of ethical and logistic constraints in study design can be overcome with the application of D-optimality-based limited sampling schemes in combination with Bayesian and nonlinear mixed-effects modeling approaches. Empirically based dose selection and clinical trial designs for pediatric clinical pharmacology studies can be improved by applying clinical trial simulation techniques, especially if they integrate adult and pediatric in vitro and/or in vivo data as historic priors. Although integration of these concepts and techniques in population pharmacokinetic analyses is not only limited to pediatric research, their application allows researchers to overcome some major hurdles frequently encountered in pharmacokinetic studies in pediatrics and, thus, provides the basis for additional clinical pharmacology research in this previously insufficiently studied fraction of the general population.

Humans↗
PubMed1993

Empirical and rational approaches for development of inhibitors of the human immunodeficiency virus--HIV-1.

The human immunodeficiency virus, HIV-1, is generally accepted to be responsible for AIDS. It is imperative that all approaches, empirical and rational, be taken for development of a drug for therapy of this disease. These approaches are discussed, with emphasis on the direction being pursued in our laboratory. Empirically, we found 3'-deoxy-2',3'-didehydrothymidine, a compound first synthesized for potential anticancer activity by J. Horwitz in the 1960s, to be a potent inhibitor of HIV-1. It is now in Phase II/III clinical trials. We have also synthesized several 2,5'-anhydro pyrimidine nucleoside analogs, which have interesting chemical and biological properties. We have evaluated a natural product, gossypol and synthesized various derivatives for anti-HIV-1 activity, but none were appreciably more inhibitory than the parent compound. More recently, we have taken the rational approach and synthesized a boron-modified tetrapeptide, Ac-Thr-Leu-Asn-boro-Phe, which corresponds to the COOH-terminal of the Phe-Pro scissle bond of the gag/pol gene polyprotein product. Potent inhibition of the HIV-1 encoded protease was observed. These approaches and findings will be discussed.

Amino Acid Sequence↗
PubMed1992

Defining patterns of drinking in adolescence: a cluster analytic approach.

Most empirical approaches to defining patterns of adolescent alcohol consumption focus on frequency of drunkenness. In an attempt to define patterns of drinking in a more comprehensive way, the present study used measures of social context in addition to frequency and quantity of alcohol use. Subjects' scores on frequency, quantity and five social context variables were cluster analyzed separately for males and females. Results yielded four socially appropriate drinking patterns and three problem drinking patterns (two for males and one for females). Socially appropriate patterns for both sexes were light drinkers, light party drinkers, family drinkers and dating drinkers. Problem drinking patterns included school drinkers and solitary/stranger drinkers for males, and solitary/school drinkers for females. These groups of subjects showed significant differences on reasons for drinking and on drinking consequences even after differences due to frequency and quantity were statistically controlled. Effects of drinking primarily attributable to frequency and quantity appeared to be limited to differences concerning the physiological effects of alcohol.

Adolescent↗
PubMedDate not supplied

Dynamic use of tumor markers, rationale-clinical applications and pitfalls.

The dynamic evaluation of tumor markers is a promising area of investigation which is expected to provide clinical information when serial samples are available from the same patient. This is feasible in the post-operatory evaluation, during the follow-up after the treatment for to the primary tumor and in the monitoring of the treatment for metastatic disease. Variations among serial samples may be assessed using both empirical and mathematical approaches. Empirical approaches rely on overcoming a given percentage usually chosen on the base of arbitrary decisions. Mathematical approaches include the actual half-life, the doubling time, a dose/time regression analysis and the calculation of the critical difference. The two former are currently used in clinical practice whereas the two latter are still matter of investigation. As concerns the assessment of the radicality of the surgery for the primary tumor, the serum markers are used in germ cell tumors and in prostate cancer. The half-life of the markers is the decision criteria used in germ cell cancers, while in prostate cancer PSA is expected to be undetectable more than 30 days after the radical prostatectomy. Tumor markers are currently used during the follow-up of several malignancies after the treatment for primary tumor. Although several samples are available, decision criteria are still based on positive/negative cut-off values in several instances. Promising dynamic approaches are under investigation and are expected to lead to earlier and probably more accurate information concerning the disease progression. A critical point still under debate is the actual impact of tumor markers on patients' survival in malignancies incurable when metastatic, such as colorectal cancer and breast cancer. This matter urgently demands perspective clinical studies. Finally, the dynamic use of tumor markers is now commonly applied in the monitoring of the therapy for metastatic malignancies. In this clinical setting mathematical criteria are used for ovarian and and germ cell tumors with promising results. Nevertheless, the use of empirical criteria, namely the percentage of variation between two consecutive samples, is successfully used for the monitoring of the therapy of metastatic breast cancer. In conclusion, when several samples are available from an individual patient they may be evaluated according to dynamic criteria instead of referring to a conventional positive/negative cut-off point. Although mathematical decision criteria are expected to provide more reliable data, empirical approaches are used as well and provide useful information in decision making.

Biomarkers, Tumor↗
PubMed2006

Genetic profiling as a marker for risk of sudden cardiac death.

PURPOSE OF REVIEW: Clinical trials provide evidence that an empirical approach of implantable cardioverter-defibrillator implantation in all heart failure patients (ejection fraction </= 35%) with mild to moderate symptoms effectively reduces mortality rate as compared to the best available medical therapy. At least 50% of patients, however, will succumb to a non-arrhythmic demise and over half of all patients will not require device therapy over long-term follow-up. Thus, the approach of empiric implantable cardioverter-defibrillator implantation is costly in light of the considerable expense of device cost, implantation, and patient follow-up. This review discusses the prospect of genomic medicine as an approach to assess genetic susceptibility to sudden arrhythmic death in at-risk populations. RECENT FINDINGS: Through the past 10 years of primary prevention implantable cardioverter-defibrillator trials, the number of patients needed to treat to prevent a sudden death has risen from one in four patients to one in 14. Although numerous clinical tests exist for stratification, they are of low positive predictive value in assessing arrhythmic risk, and have not been prospectively validated as effective strategies in identifying arrhythmia-prone patients. Recent data from genetic studies identifying genes responsible for sudden cardiac death have compiled a list of relatively common genetic variations (polymorphisms). These polymorphisms, encoding for proteins known to be involved in cardiac electrophysiology, may contribute to arrhythmic risk in the milieu of heart failure. SUMMARY: Current clinical indications for implantable cardioverter-defibrillator implantation in primary prophylaxis of sudden cardiac death necessarily include a significant number of patients who may not benefit. The identification of common genetic variations causing an increased risk of vulnerability to ventricular arrhythmia in heart failure patients may optimize the use of medical resources through rapid identification of sub-populations at highest risk.

Arrhythmias, Cardiac↗
PubMed1992

Empirical Bayes approach to the estimation of "unsafety": the multivariate regression method.

There are two kinds of clues to the unsafety of an entity: its traits (such as traffic, geometry, age, or gender) and its historical accident record. The Empirical Bayes approach to unsafety estimation makes use of both kinds of clues. It requires information about the mean and the variance of the unsafety in a "reference population" of similar entities. The method now in use for this purpose suffers from several shortcomings. First, a very large reference population is required. Second, the choice of reference population is to some extent arbitrary. Third, entities in the reference population usually cannot match the traits of the entity the unsafety of which is estimated. To alleviate these shortcomings the multivariate regression method for estimating the mean and variance of unsafety in reference populations is offered. Its logical foundations are described and its soundness is demonstrated. The use of the multivariate method makes the Empirical Bayes approach to unsafety estimation applicable to a wider range of circumstances and yields better estimates of unsafety. The application of the method to the tasks of identifying deviant entities and of estimating the effect of interventions on unsafety are discussed and illustrated by numerical examples.

Accidents↗
PubMed1990

An application of the empirical Bayes approach to directly adjusted rates: a note on suicide mapping in California.

A simple, reliable, and comparable measure for suicide mapping and other health problems is needed. Because standardized mortality ratios (SMRs) may not indicate the relative meaning of their magnitudes when compared with one another, and statistical significance levels of tests for SMRs overlook the areas that have small populations, neither of these approaches provides a satisfactory index. The results using directly adjusted rates can be ordered directly according to their magnitudes. However, because of the lack of reliable estimates of local age-specific rates, the usefulness of directly adjusted rates in mapping suicide is also limited. To extend the usefulness of directly adjusted rates, an empirical Bayes approach whereby information from other areas is borrowed to improve the precision of the estimates of local age-specific rates in calculating directly adjusted rates--especially in the areas with small population sizes--is proposed. When an empirical Bayes approach was applied to the 1983 suicide data for California counties, a more reasonable conclusion than could be obtained by using directly adjusted rates was reached.

Adolescent↗
PubMed2002

Hierarchical modeling of sequential behavioral data: an empirical Bayesian approach.

The authors review the common methods for measuring strength of contingency between 2 behaviors in a behavioral sequence, the binomial z score and the adjusted cell residual, and point out a number of limitations of these approaches. They present a new approach using log odds ratios and empirical Bayes estimation in the context of hierarchical modeling, an approach not constrained by these limitations. A series of hierarchical models is presented to test the stationarity of behavioral sequences, the homogeneity of sequences across a sample of episodes, and whether covariates can account for variation in sequences across the sample. These models are applied to observational data taken from a study of the behavioral interactions of 254 couples to illustrate their use.

Bayes Theorem↗
PubMed2007

Violence and mental illness: a new analytic approach.

Empirical studies of violence and mental illness have used many different methods. Current state-of-the-art methods gather information from both subject and collateral interviews as well as official records. Typically these sources are treated as additive. Any report of a violent incident from any source is treated as true and all reported incidents are added to generate estimates of frequency. This paper presents a new statistical technique that uses the level of agreement between the sources of data to adjust those estimates. The evidence suggests that, although the additive technique for using multiple sources correctly estimates how many people are involved, it substantially underestimates the number of incidents. The new technique substantially reduces both false negatives and false positives.

Humans↗
PubMed2000

Forecasting summertime surface-level ozone concentrations in the Lower Fraser Valley of British Columbia: an ensemble neural network approach.

Empirical models for predicting daily maximum hourly average ozone concentrations were developed for 10 monitoring stations in the Lower Fraser Valley (LFV) of British Columbia. According to data from 1991 to 1996, ensemble neural network models increased explained variance an average of 7% over multiple linear regression models using the same input variables. Without modification, all models performed poorly on days when the observed peak ozone concentration exceeded 82 parts per billion, the National Ambient Air Quality Objective. When numbers of extreme events in training data were increased using a histogram equalization process, models were able to forecast exceedances with improved accuracy. Modified generalized additive model (GAM) plots and associated measures of input variable importance and interaction were generated for a subset of the trained models and used to investigate relationships between input variables and ozone levels. The neural network models displayed a high degree of interaction among inputs, and it is likely the ability of these model types to account for interactions, rather than the nonlinearity of individual input variables, that explains their improved forecast skill. Inspection of GAM-style plots indicated that the relative importance of input variables in the ensemble neural network models varied with geographic location within the LFV. Four distinct groups of stations were identified, and rankings of inputs within the groups were generally consistent with physical intuition and results of prior studies.

Algorithms↗