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[Psychopathology and genetics of schizophrenia].

The history of psychopathology of schizophrenia from Kahlbaum to Kraepelin is reviewed: Bleulers concept of symptoms and his construct of primary disorder. Today symptomatology and syndrom - construction by modern techniques of evaluation are prominent aims of research. The ego-psychopathology is an example of a new empirical approach. The hereditary predisposition for the manifestation of schizophrenialike psychoses is empirically well founded.

Affective Disorders, Psychotic↗

Oral empirical treatment of pneumonia. The challenge of choosing the best agent.

Knowledge of the respiratory pathogens that cause pneumonia, combined with data obtained from the initial history, physical examination, and laboratory studies, provides the framework for an empirical approach to the treatment of community-acquired pneumonia. Selection of empirical therapy is based in large part on which of three broad groups the patient belongs to: previously well young adults, adults who are older or have a history of smoking or alcoholism, or HIV-infected adults. Several newer oral agents offer subtle advantages and disadvantages when compared with traditional agents, and these must be carefully weighed when prescribing treatment.

Administration, Oral↗

[Aging and life-history: aims and approaches to a life-span oriented gerontology].

The paper discusses the contributions of American theoretical and empirical approaches in life span developmental psychology to the understand of aging in a life-span frame of reference. The main part of the paper consists of a report on longitudinal as well as biographical studies on psychological and social development in adolescence, middle, and late adulthood which started at the Psychology Department of the University of Bonn in 1952 and are continued into the 80's. These studies point to close relationships between the social and psychological conditions in earlier and later periods of life and stress the relevance of promoting not only mental, but also social and effective-emotional competence for the coping with crisis situation in old age.

Adolescent↗

Revealing the relation between temperament and behavior problem symptoms by eliminating measurement confounding: expert ratings and factor analyses.

This study examined the hypothesis that item overlap, or measurement confounding, accounts for the correlation between temperament and behavior problem symptoms in children. First, a conceptual approach was taken in which 41 experts rated temperament (Children's Behavior Questionnaire, CBQ) and behavior problem symptom items (Preschool Behavior Questionnaire, PBQ) for their fit to both constructs. With this approach, 10% of temperament and 38% of symptom items were confounded. Second, an empirical approach was taken and CBQ and PBQ items were factor analyzed with data from a multi-informant longitudinal study of 451 children. Using this method, 9% of temperament and 23% of symptom items were confounded. Most importantly, removing the confounded items from the CBQ and PBQ scales did not affect the relation between temperament and symptoms, suggesting that the associations were not due to measurement confounding. In addition, the predictive power of earlier temperament for DSM-IV symptoms (Health and Behavior Questionnaire) remained high with the purified CBQ scale. The findings of this study contribute to the understanding of the relation between normal-range temperament and extreme behavior.

Child↗

Cough in children: definitions and clinical evaluation.

The aetiology and management approach for cough in children differs greatly to that in adults, so the empirical approach commonly used in adults is unsuitable for children. Clinical evaluation of cough in children should include an assessment of environmental factors, particularly tobacco smoke, parental concerns and expectations. Most children with acute cough are likely to have an uncomplicated viral acute respiratory tract infection, but the possibility of a more serious problem, especially aspiration of foreign material, should always be considered. Isolated chronic cough in children is rarely asthma, and the term "cough variant asthma" should not be used. Over-the-counter and prescription medications are ineffective for the symptomatic relief of acute cough. Treatment for chronic cough should be based on aetiology. Because of the favourable natural history of cough, a "positive" response in medication trials should not be assumed to be due to the medication. Children should be reassessed within the expected timeframe of response to therapy.

Acute Disease↗

Linear regression estimation of minimal detectable concentration. Thyrotropin as an example.

BACKGROUND: Minimal detectable concentration is an important analytic feature of certain clinical immunoassays. We believe that accuracy is an important component of the minimal detectable concentration; for a given observed concentration to be meaningful, it should reflect a consistent linear relationship with the amount of analyte actually present. METHODS: To evaluate the minimal detectable concentration, we developed a linearity regression protocol based on accuracy and also accounting for between-run variability. Using serial twofold dilutions of serum samples, we regressed the log of concentration (x) and of dilution (y) with linear, second-, and third-order polynomials. Initially, we evaluated two elements to find the linear region of the dataset, establishing the statistical significance of the beta coefficients with a t test and the reduction of the sum of square of the residuals between the linear regression and the higher-order regressions by means of an F test. As needed, we successively eliminated the lowest point until the linear regression was the best fit. Once we found the best fit, we added the most recently removed point back and calculated the difference between the value predicted by the first-order regression and the observed value. If the difference was not analytically significant, then we considered the point to be part of the linear set; otherwise, it was not included. In either case, the lowest included point was considered to be the minimal detectable concentration. RESULTS: We applied the technique in evaluating two automated systems for serum thyrotropin. One system appeared linear and accurate down to 0.02 mU/L, or better, approximately 77% of the time, and to 0.01 mU/L 68% of the time. The second system was linear infrequently and appeared to be useful down to 0.02 mU/L, or better, only about 20% of the time. CONCLUSIONS: This accuracy-based approach to determining the minimal detectable concentration is an attractive alternative to current empiric approaches, which are based only on interassay variability.

Humans↗

Strategies for biological testing of biomaterials.

Current perspectives on empirical, modeling, and mechanistic methods of medical device safety testing are reviewed. Empirical approaches, such as the U.S. Pharmacopeial biological tests for plastics, evaluate the total system to discover aberrations and abnormalities. Models consist of a single aspect of an integrated approach, whereas mechanistic methods are based on a thorough knowledge of the materials and the organism's biological response. Empirical studies develop data on general hazard potential, such as overt toxicity. Model approaches target the specific application and specific hazard potential. Mechanistic studies identify the cause of toxicity and can produce advances in the biocompatibility of medical devices.

Biocompatible Materials↗

The role of antimicrobial therapy in acute exacerbations of chronic bronchitis.

Acute exacerbations of chronic bronchitis (AECB) result in increased morbidity and mortality. The role of bacteria in AECB, the importance of antimicrobial therapy, and the choice of antimicrobial agents have been debated for decades. Fortunately, within the past few years, a number of studies and one consensus statement have been reported that have increased the understanding of the role of bacteria in AECB and suggest approaches in selecting antimicrobial therapy. This article will review these studies and present an empiric approach in treating AECB based upon the patient's presenting findings, related risk factors, and potential antimicrobial resistance patterns that may be encountered.

Acute Disease↗

Modelling atypical CYP3A4 kinetics: principles and pragmatism.

The Michaelis-Menten model, and the existence of a single active site for the interaction of substrate with drug metabolizing enzyme, adequately describes a substantial number of in vitro metabolite kinetic data sets for both clearance and inhibition determination. However, in an increasing number of cases (involving most notably, but not exclusively, CYP3A4), atypical kinetic features are observed, e.g., auto- and heteroactivation; partial, cooperative, and substrate inhibition; concentration-dependent effector responses (activation/inhibition); limited substrate substitution and inhibitory reciprocity necessitating sub-group classification. The phenomena listed above cannot be readily interpreted using single active site models and the literature indicates that three types of approaches have been adopted. First the 'nai ve' approach of using the Michaelis-Menten model regardless of the kinetic behaviour, second the 'empirical' approach (e.g., employing the Hill or uncompetitive inhibition equations to model homotropic phenomena of sigmoidicity and substrate inhibition, respectively) and finally, the 'mechanistic' approach. The later includes multisite kinetic models derived using the same rapid equilibrium/steady-state assumptions as the single-site model. These models indicate that 2 or 3 binding sites exist for a given CYP3A4 substrate and/or effector. Multisite kinetic models share common features, depending on the substrate kinetics and the nature of the effector response observed in vitro, which allow a generic model to be proposed. Thus although more complex than the other two approaches, they show more utility and can be comprehensively applied in relatively simple versions that can be readily generated from generic model. Multisite kinetic features, observed in isolated hepatocytes as well as in microsomes from hepatic tissue and heterologous expression systems, may be evident in substrate depletion-time profiles as well as in metabolite formation rates. Failure to adequately account for multisite kinetic phenomena will compromise any attempts to predict human drug clearance and drug-drug interaction potential from in vitro data.

Animals↗

Blends of reverse enteric polymer with Enteric and pH-independent polymers: mechanistic investigations for tailoring drug release.

Blends of conventional reverse enteric polymer with enteric polymers result in insoluble polyelectrolyte complexes and hence cannot be used in film coatings. We report a new set of miscible blends of a new reverse enteric polymer (NREP) synthesized by us with enteric and pH-independent polymers. The nature of interactions between polymers in the blends has been established by analyzing Fourier transform infrared (FTIR) spectra. The extent of interaction has been investigated by thermal analysis and quantified in terms of parameters K1 and K2 in the Schneider equation. Based on these values, the interactions between NREP and these polymers have been ranked in the order EC (ethylcellulose) < ES (Eudragit S) < HPMCP (hydroxypropyl methylcellulose phthalate). The quantification of interactions in blends helps explain the release pattern of cefuroxime axetil (CA) at gastric pH and tailor the release of other drugs according to their pharmacokinetic characteristics. The understanding also provides a more rational approach for selection of polymers and their content in the coating compositions, rather than an empirical approach.

Cellulose↗

Thermal stability of vaccines.

Worldwide vaccination programs against infectious diseases and toxins are estimated to save approximately 3 million lives yearly. Tragically, however, another 3 million individuals (primarily children) die of vaccine-preventable diseases. A significant portion of this problem results from the thermal instability of many of the currently used vaccines. This review argues that modern methods of physical and chemical analysis permit for the first time characterization of the degradative pathways of thermally labile vaccines. A rigorous description of these pathways permit a more rational and systematic approach to the stabilization of vaccines. A direct result of the replacement of currently employed, primarily empirical, approaches to vaccine stabilization with a more molecular-based methodology should be the development of more universally available vaccinations against life-threatening diseases. This has the potential to have a dramatic impact on world health.

Animals↗

Carrying capacity as "Informed Judgment": the values of science and the science of values.

Contemporary park and wilderness carrying capacity frameworks rely on formulation of standards of quality, which are defined as minimum acceptable resource and social conditions. Formulation of standards of quality involves elements of both science and values, and both of these elements must be integrated into informed judgments on the part of park and wilderness managers. That is, managers must ultimately make value-based judgments about the maximum acceptable level of visitor-caused impacts to the resource base and the quality of the visitor experience. However, such judgments should be as informed as possible by scientific data on the relationships between visitor use and resulting impacts and the degree to which park and wilderness visitors and other interest groups judge such impacts to be acceptable. Such information represents the "values of science" to managing carrying capacity in parks and wilderness. A growing body of literature has begun to address the corresponding "science of values," and how this type of information might be integrated in park and wilderness management. Visitor-based research has employed normative theory and techniques to explore the acceptability of a range of resource and social impacts related to visitor use, and findings from these studies are being integrated into a body of knowledge and applied in management decision-making. Conceptual and methodological extensions of the normative approach are currently being explored in a variety of park and wilderness contexts, and new theoretical and empirical approaches are being adapted to address trade-offs inherent in carrying capacity. In these ways, the science of values is progressing to meet the opportunities and challenges of the values of science to park and wilderness management. The concept of carrying capacity, along with the theoretical and methodological approaches described in this paper, can be extended to a large number of natural resource and environmental issues.

Conservation of Natural Resources↗

On the existence and stability of liquid water on the surface of mars today.

The recent discovery of high concentrations of hydrogen just below the surface of Mars' polar regions by Mars Odyssey has enlivened the debate about past or present life on Mars. The prevailing assumption prior to the discovery was that the liquid water essential for its existence is absent. That assumption was based largely on the calculation of heat and mass transfer coefficients or theoretical climate models. This research uses an experimental approach to determine the feasibility of liquid water under martian conditions, setting the stage for a more empirical approach to the question of life on Mars. Experiments were conducted in three parts: Liquid water's existence was confirmed by droplets observed under martian conditions in part 1; the evolution of frost melting on the surface of various rocks under martian conditions was observed in part 2; and the evaporation rate of water in Petri dishes under Mars-like conditions was determined and compared with the theoretical predictions of various investigators in part 3. The results led to the conclusion that liquid water can be stable for extended periods of time on the martian surface under present-day conditions.

Climate↗

Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by ketoconazole.

Conventional methods to forecast CYP3A-mediated drug-drug interactions have not employed stochastic approaches that integrate pharmacokinetic (PK) variability and relevant covariates to predict inhibition in terms of probability and uncertainty. Empirical approaches to predict the extent of inhibition may not account for nonlinear or non-steady-state conditions, such as first-pass effects or accumulation of inhibitor concentration with multiple dosing. A physiologically based PK model was developed to predict the inhibition of CYP3A by ketoconazole (KTZ), using midazolam (MDZ) as the substrate. The model integrated PK models of MDZ and KTZ, in vitro inhibition kinetics of KTZ, and the variability and uncertainty associated with these parameters. This model predicted the time- and dose-dependent inhibitory effect of KTZ on MDZ oral clearance. The predictive performance of the model was validated using the results of five published KTZ-MDZ studies. The model improves the accuracy of predicting the inhibitory effect of increasing KTZ dosing on MDZ PK by incorporating a saturable KTZ efflux from the site of enzyme inhibition in the liver. The results of simulations using the model supported the KTZ dose of 400 mg once daily as the optimal regimen to achieve maximum inhibition by KTZ. Sensitivity analyses revealed that the most influential variable on the prediction of inhibition was the fractional clearance of MDZ mediated by CYP3A. The model may be used prospectively to improve the quantitative prediction of CYP3A inhibition and aid the optimization of study designs for CYP3A-mediated drug-drug interaction studies in drug development.

Age Factors↗

[A sociological approach to the family].

"This paper discusses the range and limits of some concepts of the family, related to theoretical perspectives and to possibilities of an empirical approach to this social group. It argues that in recent studies of the family one can find the symbolic outlook of anthropology on the one hand, which deepens the analysis of dynamics of family relationships, but is limited to strict segments of society. On the other hand, one can find demography and sociology surveys, capable of framing broad portraits which, although liable to generalization, are static and limited to family relations within the household. As an example of possible methodology, the paper describes the proceedings and results of [a study on] family structure and daily life in the city of Sao Paulo [Brazil], in which the author assembles some of the commented approaches, trying to overcome their limitations." (SUMMARY IN ENG)

Americas↗

Future prospects for the chemotherapy of human trypanosomiasis. 1. Novel approaches to the chemotherapy of trypanosomiasis.

Chemotherapy of trypanosomiasis and leishmaniasis is far from satisfactory and the discovery of new drugs has been slow. Emphasis on the empirical approach to drug development is now shifting towards a more rational, directed approach, which employs the modern tools of science. This is illustrated with respect to the newly discovered drug target, trypanothione, a unique metabolite which is critical for survival of Trypanosoma and Leishmania and absent from the host.

Animals↗

Psychological factors in failure to wear the Milwaukee brace for treatment of idiopathic scoliosis.

Youngsters who fail to successfully adapt to a Milwaukee Brace displayed measurable psychological differences from those who do adapt satisfactorily to this treatment approach. The study did not encompass all conceivable variables which might affect orthotic wearing, however, use of logical and empirical approach to further delineate important variables seems feasible and desirable. In fact, one can hypothesize a predictive test battery which will detect high risk patients and thus afford the physician the option of alternative treatment modes, or intensified psychological intervention if the orthosis is preferred. The nature of such a psychological test battery, as well as the actions which would constitute effective intervention, will depend on future research. Based on our data, adolescent idiopathic scoliosis patients can be considered high risks for compliance with a Milwaukee Brace program if they display the following psychological characteristics: lower overall intelligence uith relative deficits in general information, reading recognition and reading comprehension skills; greater potential for acting-out/rebellious behavior; relatively lower sense of personal power or "potency", less tension associated with doctors; self reports of very active personal and family life styles.

Achievement↗

Causal factors of corporate crime in Taiwan: qualitative and quantitative findings.

Street crimes are a primary concern of most criminologists in Taiwan. In recent years, however, crimes committed by corporations have increased greatly in this country. Employing the empirical approach to collect data about causal factors of corporate crime, the research presented in this article is the first systematic empirical study concerning corporate crime in Taiwan. The research sample was selected from a corporation with a criminal record of pollution caused by the release of toxic chemicals into the environment and a corporation with no criminal record. Questionnaire survey and interviews of corporate employees and managers were conducted, and secondary data were collected from official agencies. This research indicated the causal factors of corporate crime as follows: the failure of government regulation, lack of corporate self-regulation, lack of public concern about corporate crime, corporate mechanistic structure, and the low self-control tendency of corporate managers.

Crime↗