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PubMed2002

[Why should we research in bioethics?].

This article reviews the conceptual evolution of bioethics, conditioned by cultural changes. The discipline could be strengthened with new analytical methodologies and with an empirical approach. The dangers of a purely descriptive bioethics, solely linked to practical experience are also discussed. This may cause the loss of the regulatory frame, that allows bioethics to enrich medical practice from a humane and moral viewpoint. Therefore, there is a need to find the balance between the theoretical analysis and an empirical approach, to face the growing complexity of contemporary ethical problems.

Bioethics↗
PubMed2005

The circumplex model of affect: an integrative approach to affective neuroscience, cognitive development, and psychopathology.

The circumplex model of affect proposes that all affective states arise from cognitive interpretations of core neural sensations that are the product of two independent neurophysiological systems. This model stands in contrast to theories of basic emotions, which posit that a discrete and independent neural system subserves every emotion. We propose that basic emotion theories no longer explain adequately the vast number of empirical observations from studies in affective neuroscience, and we suggest that a conceptual shift is needed in the empirical approaches taken to the study of emotion and affective psychopathologies. The circumplex model of affect is more consistent with many recent findings from behavioral, cognitive neuroscience, neuroimaging, and developmental studies of affect. Moreover, the model offers new theoretical and empirical approaches to studying the development of affective disorders as well as the genetic and cognitive underpinnings of affective processing within the central nervous system.

Affect↗
PubMed2001

Compartmental model identification based on an empirical Bayesian approach: the case of thiamine kinetics in rats.

Compartmental models are a very popular tool for the analysis of experiments in living systems. There are three main aspects that have to be taken into account: the degree of detail of the model, its a priori identifiability and the a posteriori (numerical) identifiability. In some cases, where standard approaches are adopted, the models can be either a priori or a posteriori unidentifiable. The paper proposes model identification within a Bayesian framework, to solve a posteriori unidentifiability problems. In particular, a stochastic simulation algorithm is proposed to perform a Bayesian identification of compartmental models, and an empirical Bayesian technique is proposed to propagate information among multiple experiments. The power of this methodology was demonstrated by evaluating the kinetics of thiamine under several experimental conditions. The complexity of the existing model (nine parameters) and limited experimental data (8/12 for each model) caused a posteriori identifiability problems when standard approaches were adopted. The application of the methodology identifies all 28 models (four tissues under seven different conditions).

Animals↗
PubMed2004

An empirical Bayes approach to inferring large-scale gene association networks.

MOTIVATION: Genetic networks are often described statistically using graphical models (e.g. Bayesian networks). However, inferring the network structure offers a serious challenge in microarray analysis where the sample size is small compared to the number of considered genes. This renders many standard algorithms for graphical models inapplicable, and inferring genetic networks an 'ill-posed' inverse problem. METHODS: We introduce a novel framework for small-sample inference of graphical models from gene expression data. Specifically, we focus on the so-called graphical Gaussian models (GGMs) that are now frequently used to describe gene association networks and to detect conditionally dependent genes. Our new approach is based on (1) improved (regularized) small-sample point estimates of partial correlation, (2) an exact test of edge inclusion with adaptive estimation of the degree of freedom and (3) a heuristic network search based on false discovery rate multiple testing. Steps (2) and (3) correspond to an empirical Bayes estimate of the network topology. RESULTS: Using computer simulations, we investigate the sensitivity (power) and specificity (true negative rate) of the proposed framework to estimate GGMs from microarray data. This shows that it is possible to recover the true network topology with high accuracy even for small-sample datasets. Subsequently, we analyze gene expression data from a breast cancer tumor study and illustrate our approach by inferring a corresponding large-scale gene association network for 3883 genes.

Algorithms↗
PubMed1990

On the potential of various approaches in load analysis to reduce the frequency of sports injuries.

The purpose of this paper is to discuss various approaches used in load analysis with special consideration of whether there is some evidence that these approaches have actually contributed to a reduction of sport injuries and whether these approaches have the theoretical potential to reduce the frequency of injuries at all. Two possible approaches are compared. The 'cause-effect approach' uses the estimation of internal stress. It is proposed that a comparison of the internal stress with the critical stress limits for an anatomical structure of interest may not help to reduce the frequency of injuries for two reasons. Firstly, the estimation of the critical stress limits and the internal stress may have significant errors which inhibit possible conclusions. Secondly, the information provided by the comparison of internal stress and critical stress limits was implicitly available in the injury frequencies and no new knowledge has been added. It is proposed that stresses estimated from model calculations can successfully be used to reduce the frequency of injuries if they are compared (comparison technique) with stresses estimated for comparable situations (e.g. shoes with and without orthotics). The 'empirical approach' is based on the assumption that the knowledge of the mechanisms of an injury is not a prerequisite for the reduction of the frequency of injuries. The approach establishes statistical correlations between factors related to injuries on one side and specific injuries or groups of injuries on the other side. This approach has frequently been used in the development of sport shoes. It is speculated that studies using an empirical approach have the potential to actually reduce the frequency of injuries. The conclusive evidence that biomechanical research in load analysis has in fact contributed to a reduction of the frequency of injuries is still missing for both discussed approaches.

Athletic Injuries↗
PubMed1994

Empirical therapy of community-acquired pneumonia.

An empiric approach to the therapy of community-acquired pneumonia (CAP) is needed because of the limitations of traditional approaches to antibiotic selection. The use of sputum Gram's stain and culture tests to guide initial therapy is potentially inaccurate and of limited use. Clinical syndromes cannot be reliably used to predict microbial pathogens, primarily because host, as well as bacterial factors, contribute to the presence of specific clinical signs and symptoms. The routine use of extensive diagnostic testing on all patients with CAP is expensive and of limited clinical usefulness. An empirical approach is presented that is based on an assessment of three factors that can help to predict the likely etiologic pathogens and thus guide initial therapy. These factors are the place of therapy, the presence of advanced age and/or comorbidity, and the severity of illness on initial clinical presentation. When these factors are used to guide empirical therapy, it is important to recognize and appropriately evaluate the nonresponding patient, and it is in this setting that an extensive diagnostic evaluation may be most useful.

Age Factors↗
PubMed1999

Treat or investigate?

Although upper gastrointestinal endoscopy provides very useful information about organic diseases, such as ulcers or cancer, there are still some questions about the most cost-effective strategy to apply in gastroesophageal reflux disease (GERD). In other words, is it mandatory to perform endoscopy in all patients before starting anti-reflux therapy, or is it better to treat empirically with an antisecretory drug? There are several factors in support of an empirical approach for the management of GERD in clinical practice. Indeed, typical symptoms like heartburn or regurgitation are very specific for the diagnosis of GERD when they are dominant. However, heartburn and regurgitation are so frequent in the primary care setting that it is not practical or even feasible to investigate all patients. In contrast, the prevalence of esophagitis in the community is very low. At least half of the patients referred to an open-access endoscopy unit are 'endoscopy-negative' or show irrelevant findings. In fact, most patients with esophagitis have mild lesions at endoscopy, and severe complications (such as stenosis or ulcer) are very rare. Moreover, there is no evidence that mild-to-moderate esophagitis worsens with time. Last but not least, symptoms are what matter to the patient. They can adversely impact the quality of life, whether or not esophagitis is present at endoscopy. On the other hand, empirical therapy should not result in the masking of organic diseases or delaying the investigation of conditions in which late diagnosis and treatment could have an impact. The risk of masking malignancy is age, context and geographically dependent. However, there is a quite good consensus that an empirical approach for the management of GERD is acceptable if symptoms are typical, the patient is young (< 45 years old) and there are no alarm symptoms. Other concerns about empirical therapy in GERD include: (a) inappropriate prolonged use of drug therapy, (b) weakening of subsequent investigation, (c) side effects, and (d) a great likelihood of symptom recurrence, possibly resulting in postponement of endoscopy and increased direct and indirect costs (sick-leave days). Indeed, the long-term expense for different strategies depends on the cost of endoscopy (with or without sedation), the cost of physician visits and the symptom recurrence rate. If GERD is associated with a high rate of recurrences, savings may be relatively modest with an empirical strategy. On the contrary, reducing the cost of endoscopy and developing open-access endoscopy units without long waiting lists may be more cost-effective than promoting empirical treatment. In conclusion, a symptom-based strategy is certainly practical and feasible for the majority of GERD patients seen by general practitioners in the primary care setting. In these patients, a proton pump inhibitor (PPI) can be safely prescribed in empirical conditions, provided simple guidelines are followed. Symptom relief can also be used as an indication of healing in patients with mild or moderate esophagitis at initial endoscopy. In contrast, endoscopy is still indicated in patients with persistent or recurrent symptoms of GERD. The role of the PPI test for diagnosis of GERD should be further validated before being widely recommended.

Endoscopy, Gastrointestinal↗
PubMed1989

Prediction of beta-turns in proteins using neural networks.

The use of neural networks to improve empirical secondary structure prediction is explored with regard to the identification of the position and conformational class of beta-turns, a four-residue chain reversal. Recently an algorithm was developed for beta-turn predictions based on the empirical approach of Chou and Fasman using different parameters for three classes (I, II and non-specific) of beta-turns. In this paper, using the same data, an alternative approach to derive an empirical prediction method is used based on neural networks which is a general learning algorithm extensively used in artificial intelligence. Thus the results of the two approaches can be compared. The most severe test of prediction accuracy is the percentage of turn predictions that are correct and the neural network gives an overall improvement from 20.6% to 26.0%. The proportion of correctly predicted residues is 71%, compared to a chance level of about 58%. Thus neural networks provide a method of obtaining more accurate predictions from empirical data than a simpler method of deriving propensities.

Algorithms↗
PubMed2000

Empirical Bayes approach to estimating the number of HIV-infected individuals in hidden and elusive populations.

In this paper we estimate the numbers of intravenous drug users (IVDUs) and commercial sex workers (CSWs) in Thailand infected with human immunodeficiency virus (HIV) who have not developed acquired immunodeficiency syndrome (AIDS) directly from the semi-annual HIV serosurveillance data of Thailand from June 1993 to June 1995. We propose a 'generalized removal model for open populations' for estimating HIV-infected population size within a hidden, elusive, and perhaps high-risk population group, for all sampling time when capture probabilities vary with time. We apply empirical Bayes methodology to the generalized removal model for open populations by using the Gibbs sampler, a Markov chain Monte Carlo method. No assumption on the size of the hidden population in question is needed to implement this procedure. The statistical method proposed here requires very little computing and only a minimum of two sets of serosurvey data to obtain an estimate, thereby providing a simple and viable option in epidemiological studies when either powerful computing facilities or abundant sampling data are lacking.

Bayes Theorem↗
PubMed2006

[Personality disorder traits in childhood and adolescence: concepts, methodological approaches and empirical results].

OBJECTIVE: The practical and theoretical advantages of the diagnosis and classification of personality disorder traits in childhood and adolescence remain controversial topics, the investigation of which is particularly neglected in German-speaking countries. METHOD: This review reports in detail research findings on the diagnostic validity and on the stability of personality disorder dimensions from childhood and adolescence to adulthood. RESULTS: On the one hand, the latest research findings refer to the validity of diagnoses of personality disorder in adolescence, and on the other, to the stability of personality traits over the course of development. Evidence of the continuity of personality disorder traits from adolescence to adulthood, however, is still lacking. Dimensional approaches are considered superior with regard to the assessment of personality disorder traits, particularly since they reflect development aspects, and also due to their higher sensitivity in this respect. CONCLUSIONS: Longitudinal studies during both childhood and adolescence are required in order to assess the continuity, or the instability, respectively, of dimensionally assessed personality profiles and the influence of infant personality factors on the development of psychopathology.

Adolescent↗
PubMed1995

Appropriate utilization and cost control of the hospital laboratory: panel testing and repeat orders.

Analysis of hospital laboratory utilization shows a bi-exponential relationship between the many different test combinations ordered and their frequency of use. This suggests two opposite strategies to reduce test volume. Policy could discourage use of the most popular request combinations to reduce volume, or policy could discourage use of the least popular request combinations to reduce order variety. Analysis of biochemical test orders further suggests that the largest part of test requests is associated with a small number of pathophysiological issues, namely those involving electrolytes, fluid balance, blood lipids, heart, liver, kidney or bone disease. Therefore, efficiency results when a limited number of standard test panels addressing these issues reduce order variety by discouraging infrequently used test combinations. Standard panels can be developed from an analysis of the most popular existing orders, accepting some degree of discrepancy among otherwise overlapping requests. This empiric approach avoids sterile debate about the composition of ideal panels. Since the resources of the laboratory, the mix of patients served and local medical tradition affect test orders, each institution providing health care must develop the standard panels best suited to its needs. Analysis of standing repeat orders suggests they are often used to anticipate potential pathology in stable patients. Therefore, economy results when test volume is reduced by discouraging series of futile repeat tests with unchanging normal results. Unfortunately, an empiric approach to regulate repeat orders is not available and only a more cumbersome process to build a locally agreed upon consensus between providers and users of laboratory services offers itself as a promising solution.

Alabama↗
PubMed2000

Resolution optimisation in micellar electrokinetic chromatography using empirical models.

Theoretical and empirical models can be used to model the migration or separation characteristics in micellar electrokinetic chromatography in order to optimise the resolution. In this paper only empirical models were used, because it is easier and more straightforward to obtain these models. Several empirical approaches for the optimisation of the resolution were compared in order to determine which response should be modelled preferably. The use of models of the effective mobility in combination with average plate numbers proved to be the most suitable approach to optimisation of the resolution, because the relative prediction errors of the models of the effective mobility were a factor of 2-4 smaller than the relative prediction errors of the models of the apparent mobility. Moreover for the least separated peak pair the resolutions based on the models of the apparent and effective mobility showed relative prediction errors that were approximately a factor of 2 smaller than the relative prediction errors of the resolutions based on the models of the resolution and separation factor. The predictions of the separation factor based on the different models generally showed lower prediction errors than the predictions of the corresponding resolutions. Although the relative prediction errors were large, particularly for closely migrating compounds, the empirical approach will probably lead to the optimum separation buffer composition.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2001

An empirical Bayes approach to estimating the relation of mortality to exposure to particulate matter.

As part of its assessment of the health risks associated with exposure to particulate matter (PM), the U.S. Environmental Protection Agency analyzed the risks associated with current levels, and the risk reductions that might be achieved by attainment of alternative PM standards, in two locations in the United States, Philadelphia, and Los Angeles. The concentration-response function describing the relation between a health endpoint and ambient PM concentrations is an important component, and a source of substantial uncertainty, in such risk analyses. In the absence of location-specific estimates, the concentration-response functions necessary for risk assessments in Philadelphia and Los Angeles must be inferred from the available information in other locations. Although the functional form of the concentration-response relations is assumed to be the same everywhere, the value of the PM coefficient in that function may vary from one location to another. Under this model, a distribution describes the probability that the PM coefficient in a randomly selected location will lie in any range of interest. An empirical Bayes estimation technique was used to improve the estimation of location-specific concentration-response functions relating mortality to short-term exposure to particles of aerodynamic diameter less than or equal to 2.5 microm (PM-2.5), for which functions have previously been estimated in several locations. The empirical Bayes-adjusted parameter values and their SEs were used to derive an estimate of the distribution of PM-2.5 coefficients for mortality associated with short-term exposures. From this distribution, distributions of relative risks corresponding to different specified changes in PM-2.5 concentrations could be derived.

Air Pollutants↗
PubMed1993

Empirical selection of psychosocial treatment targets for children and adolescents with diabetes.

Used an empirical approach to determine psychosocial variables related to optimal metabolic control of diabetes in two samples (total n = 56) of children and their families. Children and adolescents classified as either in optimal or nonoptimal control of diabetes (based on glycosylated hemoglobin results) completed self-report measures on variables of anxiety, coping, family environment and health locus of control, and a structured interview. Parents completed parallel self-report measures and a child behavior checklist. Children in optimal control of diabetes had more structured and controlling family environments, and more frequently believed that "powerful others" were responsible for their health. There was a marginally significant difference in knowledge, with children in poorer metabolic control showing better knowledge about diabetes and its management than children in optimal control. The study illustrates an empirical approach to the selection of psychosocial treatment targets for children with diabetes, and underscores the importance of parental involvement with the diabetes regimen to ensure optimal control of diabetes in both children and adolescents.

Adaptation, Psychological↗
PubMed1993

An empirical Bayes approach to the estimation of the incidence curve of HIV infection.

A new approach is proposed for estimating the incidence curve of HIV infection and obtaining short term prediction of AIDS incidence. It is based on the method of back calculation which utilizes the fact that AIDS incidence is generated from HIV infection incidence by convolution with the incubation period distribution, but avoids the difficulties associated with approximating the infection incidence curve by a class of step functions. Instead, the infection incidence is modelled as a simple stochastic epidemic process which ensures smoothness of the estimate. We first derive the distribution of AIDS incidence knowing infection incidence. The best linear estimators of infection incidence as well as future AIDS incidence are given; a smoothed past AIDS incidence is also obtained. The parameters of the stochastic infection process can be estimated by maximum likelihood using a normal approximation to the marginal distribution of the AIDS incidence. This approach is applied to AIDS incidence data in the United States up to mid 1987. We find that the epidemic started in mid 1976, peaked at the end of 1983 and dropped afterwards.

Acquired Immunodeficiency Syndrome↗
PubMed2004

The predictive power of Horney's psychoanalytic approach: an empirical study.

This study investigated the construct validity of a measure of Karen Horney's (1945) psychoanalytic theory that postulated three neurotic trends: compliant, aggressive, and detached. Her theory was operationalized by the Horney-Coolidge Type Indicator (HCTI). One hundred seventy-two adults completed the HCTI and the short form of the Coolidge Axis II Inventory, a measure of the three DSM-IV personality disorder clusters. Multiple regression and canonical correlation analyses revealed significant and differential patterns of the three HCTI dimensions with the three clusters. Because Paris (1994) has noted that Horney's neurotic trends may today be conceived of as personality disorders, one implication of the present findings is that Horney's dynamic theory can be valid and useful in the general understanding of personality disorders from a cluster perspective.

Adolescent↗
PubMed2001

Treating childhood shyness and related behavior: empirically evaluated approaches to promote positive social interactions.

Behavioral and cognitive-behavioral strategies, including exposure, social skills training, and peer-mediated approaches, used to treat childhood shyness and related impairments are described. In addition, relevant outcome studies published within the past 20 years are evaluated, and limitations regarding the generalization, maintenance, and social validity of the reported treatment gains are addressed. Although the interventions reviewed have demonstrated short-term merit in ameliorating social and emotional impairments, such as problematic peer relations and internalizing difficulties, there currently is a lack of evidence to support the social validity and long-term generalization and maintenance of such behavioral gains. Thus, recommendations for future research are made, including the need to (a) assess the social validity of treatment outcomes, (b) utilize important socialization agents (e.g., parents, teachers, peers), and (c) conduct prevention research and longitudinal outcome studies.

Adolescent↗
PubMed2006

An empirical, quantitative approach to predict the reactivity of some substituted aromatic compounds towards reactive radical species (Cl2-*, Br2-*, *NO2, SO3-*, SO4-*) in aqueous solution.

The Hammett approach, applied to the reaction of various classes of aromatic compounds with the radicals Cl2-*, Br2-*, *NO2, SO3-*, and SO4-* yielded good predictive models, supported by high values of the correlation coefficient r2 in the case of phenols with Cl2-* and of phenolates with *NO2 and SO3-*. Lower but statistically significant correlation coefficients could be obtained for benzoates with Cl2-*, phenolates with Br2-*, and benzoates and anisoles with SO4-*.

Bromine↗