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PubMedDate not supplied

[Some problems in the use of the new U.N. model life tables].

"After a brief introduction to new United Nations model life tables for developing countries, we have proceeded to point out some blanks contained in them....[A theoretical] approach has allowed us to demonstrate the inadequacy of some fundamental assumptions on which the methods used are based. [An empirical approach] has enabled us to point out some of the problems that may be encountered when using the tables." (SUMMARY IN ENG AND ITA)

Demography↗
PubMed2005

The birth of the empirical turn in bioethics.

Since its origin, bioethics has attracted the collaboration of few social scientists, and social scientific methods of gathering empirical data have remained unfamiliar to ethicists. Recently, however, the clouded relations between the empirical and normative perspectives on bioethics appear to be changing. Three reasons explain why there was no easy and consistent input of empirical evidence in bioethics. Firstly, interdisciplinary dialogue runs the risk of communication problems and divergent objectives. Secondly, the social sciences were absent partners since the beginning of bioethics. Thirdly, the meta-ethical distinction between 'is' and 'ought' created a 'natural' border between the disciplines. Now, bioethics tends to accommodate more empirical research. Three hypotheses explain this emergence. Firstly, dissatisfaction with a foundationalist interpretation of applied ethics created a stimulus to incorporate empirical research in bioethics. Secondly, clinical ethicists became engaged in empirical research due to their strong integration in the medical setting. Thirdly, the rise of the evidence-based paradigm had an influence on the practice of bioethics. However, a problematic relationship cannot simply and easily evolve into a perfect interaction. A new and positive climate for empirical approaches has arisen, but the original difficulties have not disappeared.

Bioethics↗
PubMed2003

A strategy to improve priority setting in health care institutions.

Priority setting (also known as resource allocation or rationing) occurs at every level of every health system and is one of the most significant health care policy questions of the 21st century. Because it is so prevalent and context specific, improving priority setting in a health system entails improving it in the institutions that constitute the system. But, how should this be done? Normative approaches are necessary because they help identify key values that clarify policy choices, but insufficient because different approaches lead to different conclusions and there is no consensus about which ones are correct, and they are too abstract to be directly used in actual decision making. Empirical approaches are necessary because they help to identify what is being done and what can be done, but are insufficient because they cannot identify what should be done. Moreover, to be really helpful, an improvement strategy must utilize rigorous research methods that are able to analyze and capture experience so that past problems are corrected and lessons can be shared with others. Therefore, a constructive, practical and accessible improvement strategy must be research-based and combine both normative and empirical methods. In this paper we propose a research-based improvement strategy that involves combining three linked methods: case study research to describe priority setting; interdisciplinary research to evaluate the description using an ethical framework; and action research to improve priority setting. This describe-evaluate-improve strategy is a generalizable method that can be used in different health care institutions to improve priority setting in that context.

Empirical Research↗
PubMed1990

Estimating benefits of screening from observational cohort studies.

Analysis and interpretation of observational studies of screening effectiveness is difficult because several biases threaten validity, including the structural healthy screenee bias, length bias, and effects of lead time. Although methods for the analysis of observational studies of screening effectiveness have been proposed, most have limitations such as incomplete control of length bias, or a heavy reliance on distributional assumptions. In this report we present a method for the analysis of observational cohort studies of screening effectiveness. Although developed independently and formulated specifically for estimating benefits of screening, our approach is implied by a more general approach developed previously by Robins. Our approach, in contrast to other available methods, avoids the healthy screenee bias, and length and lead time bias, and allows an empirical approach to analysis that need not depend highly on distributional assumptions. We illustrate application of the approach with analysis of published data from a study of breast cancer screening.

Bias↗
PubMedDate not supplied

Empirical determination of thresholds for case identification: validation of the Personality Diagnostic Questionnaire-Revised.

The Personality Diagnostic Questionnaire-Revised (PDQ-R) was sent to first-degree relatives of major psychotic patients for identification of DSM-III-R personality disorders (PDs). Responses to the PDQ-R were interpreted both literally and empirically, and compared with the Structured Interview for DSM-III PDs (SIDP) as the standard. For literal interpretation, symptoms reported were counted directly for case identification using fixed DSM-III-R thresholds. The empirical approach adjusted the threshold for case identification to maximize concordance with the SIDP. Comparison of the two methods showed that using empirically determined thresholds in some scales gives better concordance with the SIDP. For the dependent and histrionic PD scales, the improvements were statistically significant. The area under the receiver operating characteristic (ROC) curve was computed for each PDQ-R scale to summarize its discriminatory capability across all thresholds. Areas under the ROC curve indicated that the schizoid, schizotypal, borderline, dependent, passive-aggressive, and histrionic PD scales in the PDQ-R have better discriminatory qualities than other PDQ-R scales.

Adult↗
PubMed1997

Applications of molecular microbiology to vaccinology.

Genetics, cell biology, and whole-genome sequencing of pathogens have changed dramatically the opportunities to investigate the epidemiology, pathogenesis, diagnosis, and control of microbial diseases. For example, recombinant DNA and PCR are powerful tools used to isolate genes whose role in pathogenicity can be investigated in biologically relevant virulence assays. Vaccines that target one or more of these genes can then be developed. Complete genome sequences of microbes provide an inventory of the genes encoding every virulence factor and potential immunogen. Candidate vaccines can be selected and developed using various approaches, including the recent innovation of immunisation with nucleic acids. Although many successful vaccines have been and will continue to be developed through empirical approaches, molecular microbiology provides a rational basis for discovery, development, and implementation of safer, more effective and, potentially cheaper vaccines.

Animals↗
PubMed1985

Biological response modifiers for the therapy of cancer.

I believe that the prospects for therapy of cancer by biological response modification are quite good, particularly since this offers an approach to affecting tumor cells which is substantially different from conventional chemotherapy or radiotherapy. But in view of the quite limited success from empirical approaches with immunotherapy or other forms of biological response modification, and the quite unimpressive results that have been seen in patients with advanced disease, I feel that a shift in emphasis to more systematic and well planned studies is needed. It will probably be necessary to develop a detailed understanding of the mechanisms of action of the various BRMs to better understand the immunoregulatory processes affected by these agents, and to develop protocols which are able to produce optimal and sustained alterations in immunologic reactivity. Since a variety of BRMs have shown considerable antitumor effects in animal tumor model systems, particularly against micrometastatic disease which represents a major clinical problem, further research in this area may be expected to lead to significant advances in the therapy of patients with cancer.

Animals↗
PubMed1995

Randomized trial comparing oral ciprofloxacin plus penicillin V with amikacin plus carbenicillin or ceftazidime for empirical treatment of febrile neutropenic cancer patients.

Aminoglycoside-containing combination therapy has been the standard empirical approach for febrile neutropenic cancer patients. With the advent of the broad-spectrum oral fluoroquinolones, it is now possible to evaluate an initial empirical alternative therapy. A prospective randomized study was conducted comparing oral ciprofloxacin plus penicillin V (group A) with amikacin plus carbenicillin or ceftazidime (group B). Main criteria for eligibility were febrile patients with solid tumor or nonlymphoblastic lymphoma, a Zubrod PS equal to 1 or 2, no diarrhea, mucositis, or long-term central venous catheter. A total of 108 consecutive neutropenic febrile episodes were randomized (5 exclusions); 55 episodes were assigned to group A and 48 to group B. Most febrile episodes were of unknown origin. There were 10 microbiologically documented episodes with two cases of bacteremia. Both regimens were well tolerated. Oral regimen was substantially cheaper than parenteral regimen. Treatment success without regimen modification was 94.5% for group A and 93.8% for group B (p = .86; CI -0.08-0.10). Oral therapy with ciprofloxacin and penicillin V is a safe alternative to standard parenteral therapy in this low-risk group of neutropenic patients, with unquestionable cost containment.

Administration, Oral↗
PubMed2005

A restructured framework for modeling oxygen transfer in two-phase partitioning bioreactors.

This communication proposes a mechanistic modification to a recently published method for analyzing oxygen mass transfer in two-phase partitioning bioreactors (Nielsen et al., 2003), and corrects an oversight in that paper. The newly proposed modification replaces the earlier empirical approach, which treated the two liquid phases as a single, homogeneous liquid phase, with a two-phase mass transfer model of greater fundamental rigor. Additionally, newly developed empirical models are presented that predict the mass transfer coefficient of oxygen absorption in both aqueous medium and an organic phase (n-hexadecane) as a function of bioreactor operating conditions. Experimental values and theoretical predictions of mass transfer coefficients in two-phase dispersions, k(L)a(TP), are compared. The revised approach more clearly demonstrates the potential for oxygen mass transfer enhancement by organic phase addition, one of the motivations for employing a distinct second phase in a partitioning bioreactor.

Absorption↗
PubMed2005

Error estimation and global fitting in transverse-relaxation dispersion experiments to determine chemical-exchange parameters.

Off-resonance effects can introduce significant systematic errors in R2 measurements in constant-time Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation dispersion experiments. For an off-resonance chemical shift of 500 Hz, 15N relaxation dispersion profiles obtained from experiment and computer simulation indicated a systematic error of ca. 3%. This error is three- to five-fold larger than the random error in R2 caused by noise. Good estimates of total R2 uncertainty are critical in order to obtain accurate estimates in optimized chemical exchange parameters and their uncertainties derived from chi2 minimization of a target function. Here, we present a simple empirical approach that provides a good estimate of the total error (systematic + random) in 15N R2 values measured for the HIV protease. The advantage of this empirical error estimate is that it is applicable even when some of the factors that contribute to the off-resonance error are not known. These errors are incorporated into a chi2 minimization protocol, in which the Carver-Richards equation is used fit the observed R2 dispersion profiles, that yields optimized chemical exchange parameters and their confidence limits. Optimized parameters are also derived, using the same protein sample and data-fitting protocol, from 1H R2 measurements in which systematic errors are negligible. Although 1H and 15N relaxation profiles of individual residues were well fit, the optimized exchange parameters had large uncertainties (confidence limits). In contrast, when a single pair of exchange parameters (the exchange lifetime, tau(ex), and the fractional population, p(a)), were constrained to globally fit all R2 profiles for residues in the dimer interface of the protein, confidence limits were less than 8% for all optimized exchange parameters. In addition, F-tests showed that quality of the fits obtained using tau(ex), p(a) as global parameters were not improved when these parameters were free to fit the R2 profiles of individual residues. Finally, nearly the same optimized global tau(ex), p(a) values were obtained, when the 1H and 15N data sets for residues in the dimer interface, were fit independently; the difference in optimized global parameters, ca. 10%, was of marginal significance according to the F-test.

Data Interpretation, Statistical↗
PubMed2001

Empirical and hermeneutic approaches to phenomenological research in psychology: a comparison.

Empirical phenomenology and hermeneutic phenomenology, the 2 most common approaches to phenomenological research in psychology, are described, and their similarities and differences examined. A specific method associated with each form of phenomenological inquiry was used to analyze an interview transcript of a woman's experience of work-family role conflict. A considerable degree of similarity was found in the resulting descriptions. It is argued that such convergence in analyses is due to the human capacities of reflection and intuition and the presence of intersubjective meanings. The similarity in the analyses is also encouraging about researchers' ability to reveal meaning despite the use of different methods and the difficulties associated with interpreting meaning.

Adult↗
PubMed2000

Evaluating patients with arthritis of recent onset: studies in pathogenesis and prognosis.

Inflammatory synovitis of recent onset poses a diagnostic and prognostic challenge to primary care physicians and rheumatologists. A lack of understanding of the underlying etiologic and pathogenic processes limits the ability to distinguish forms of arthritis that follow a benign, self-limiting course from forms that proceed to an aggressive, erosive disease requiring intensive immunosuppressive therapy. It is estimated that between 30% and 40% of patients presenting with early synovitis have disease that remains unclassified. Using data from a cohort of patients with early synovitis and reviewing current literature, we discuss investigational approaches toward a new classification of patients with early synovitis. Although a lack of understanding of this heterogeneous clinical syndrome has led clinicians to take a largely empirical approach to treatment thus far, the evolving awareness of disease predisposition at a genetic level and the expanding ability to specifically manipulate biological pathways may ultimately change the approach to this clinical problem. JAMA. 2000;284:2368-2373.

Adult↗
PubMed2001

Experimental validation of the use of Kramers-Kronig relations to eliminate the phase sheet ambiguity in broadband phase spectroscopy.

The technique of broadband phase spectroscopy proposed in 1978 by Sachse and Pao [J. Appl. Phys. 49, 4320-4327 (1978)] determines the phase velocity as a function of frequency from the Fourier transforms of a received reference and through-sample signal. Although quite successful, this approach can be influenced by an ambiguity in the phase velocity calculation which stems from the boundedness of the inverse tangent operation used to calculate phase. Several empirical approaches to resolve the phase ambiguity have been reported. An alternative approach that has not previously been considered appeals to the causal nature of the measurements. This article experimentally validates a method which uses the causally consistent Kramers-Kronig relations to eliminate the ambiguity in phase spectroscopy-derived phase velocity calculations. Broadband pulse and narrow-band tone burst measurements were performed on three gelatin-based phantoms containing different concentrations of graphite particles (0%, 10%, and 20% by volume). The phantoms were constructed to have attenuation coefficients which vary approximately linear-with-frequency, a dependence exhibited by many soft tissues. The narrow-band phase velocity measurements do not suffer from a phase ambiguity, and thus they serve as a "gold standard" against which the broadband phase velocity measurements are compared. The experimental results illustrate that using the Kramers-Kronig dispersion relations in conjunction with phase spectroscopy-derived phase velocity measurements is an effective means by which to resolve the phase sheet ambiguity in broadband phase spectroscopy.

Fourier Analysis↗
PubMed1994

Treatment of ventricular arrhythmias after recovery from myocardial infarction.

Demonstrated associations between postmyocardial infarction ventricular arrhythmias and a higher subsequent risk of both sudden and all-cause mortality have prompted a search for effective and safe treatment modalities. Recently completed clinical trials have provided a rationale for treatment recommendations in some specific settings. Beta-blocking therapy is recommended for postinfarction patients with frequent or complex ventricular premature beats. In contrast, calcium antagonist therapy is not helpful in these cases, and Class I antiarrhythmic therapy is actually harmful. Early indications of benefit from Class III antiarrhythmic therapies, particularly amiodarone, are under evaluation in large trials. Patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) occurring late after myocardial infarction require therapy. Viable therapeutic methods include individualized antiarrhythmic therapy selected by the noninvasive approach, individualized antiarrhythmic therapy selected by the invasive approach, empiric amiodarone therapy, transcatheter or surgical ablative therapy (for VT), and use of an implantable cardioverter defibrillator. Clinical trial data have yet to determine which of these approaches is most effective under which circumstances. Postinfarction patients with nonsustained VT are the focus of several ongoing treatment trials. Early data suggest that risks requiring specific therapy are reached only by those patients who also have significant left ventricular dysfunction. The presence of inducible sustained ventricular tachycardia at an electrophysiologic study may further risk stratify such patients. High-risk patients with nonsustained ventricular tachycardia, left ventricular dysfunction, and inducible sustained ventricular tachycardia should participate in ongoing clinical trials. In the absence of this opportunity, intensive treatment should be considered.

Anti-Arrhythmia Agents↗
PubMed2001

Assessing the child psychopathology beast: a reply to Achenbach and Dumenci's (2001) commentary.

This article is a response to T. M. Achenbach and L. Dumenci's (2001) commentary concerning L. J. Lengua, C. A. Sadowski, W. N. Friedrich, and J. Fisher's (2001) article proposing an alternative scoring approach for the Child Behavior Checklist. The authors note that T. M. Achenbach and L. Dumenci do not comment on the stated goals of the alternative scoring approach and focus on a limited set of the results to make their argument. Although the original and proposed scoring approaches operate similarly, important differences suggest that the proposed scoring approach is promising for use in specific instances, including identifying distinct etiologies, developmental course, and co-occurrence of specific syndromes. The importance of combining rational and empirical approaches in articulating conceptual definitions and developing measures of child psychopathology is discussed.

Adolescent↗
PubMed1989

Neutrophil kinetics in the fetus and neonate.

Delineation of neutrophilic pool sizes and kinetics during the steady state and during various perturbations has improved the clinical approach to adult patients with abnormalities of blood neutrophil concentration. Perhaps a better understanding of neutrophil kinetics in the fetus and neonate might similarly permit a less empiric approach to neutropenia and neutrophilia in newborn infants. The relatively few studies that have been performed suggest that substantial differences in pool sizes and kinetics exist between neonates and adults, with even greater differences between extremely preterm infants and those delivered at term.

Animals↗
PubMed2002

Approaches to the description and prediction of the binding affinity of small-molecule ligands to macromolecular receptors.

The influence of a xenobiotic compound on an organism is usually summarized by the expression biological activity. If a controlled, therapeutically relevant, and regulatory action is observed the compound has potential as a drug, otherwise its toxicity on the biological system is of interest. However, what do we understand by the biological activity? In principle, the overall effect on an organism has to be considered. However, because of the complexity of the interrelated processes involved, as a simplification primarily the "main action" on the organism is taken into consideration. On the molecular level, biological activity corresponds to the binding of a (low-molecular weight) compound to a macromolecular receptor, usually a protein. Enzymatic reactions or signal-transduction cascades are thereby influenced with respect to their function for the organism. We regard this binding as a process under equilibrium conditions; thus, binding can be described as an association or dissociation process. Accordingly, biological activity is expressed as the affinity of both partners for each other, as a thermodynamic equilibrium quantity. How well do we understand these terms and how well are they theoretically predictable today? The holy grail of rational drug design is the prediction of the biological activity of a compound. The processes involving ligand binding are extremely complicated, both ligand and protein are flexible molecules, and the energy inventory between the bound and unbound states must be considered in aqueous solution. How sophisticated and reliable are our experimental approaches to obtaining the necessary insight? The present review summarizes our current understanding of the binding affinity of a small-molecule ligand to a protein. Both theoretical and empirical approaches for predicting binding affinity, starting from the three-dimensional structure of a protein-ligand complex, will be described and compared. Experimental methods, primarily microcalorimetry, will be discussed. As a perspective, our own knowledge-based approach towards affinity prediction and experimental data on factorizing binding contributions to protein-ligand binding will be presented.

Animals↗
PubMed1991

Cigarette smoking and birthweight: type of cigarette smoked and a possible threshold effect.

The effects on birthweight of the number of cigarettes smoked and their tar, nicotine and carbon monoxide yields were investigated prospectively in 1309 pregnant women of whom 414 were smokers. Several approaches to modelling the effect of smoking were tried. These suggested that while both yield and quantity smoked were important, yield had the greatest effect. This led to an empirical approach whereby consistent smokers were divided into four categories according to whether they smoked a low or high quantity of cigarettes per day and whether they smoked low or high yield cigarettes. Using these four groups it emerged that women smoking a low quantity of low yield cigarettes had babies of a similar mean birthweight to those of non-smokers whereas those smoking a low quantity of high yield cigarettes had babies whose birthweight was reduced to the same degree (6% or more) as those of mothers who smoked higher quantities. This apparent threshold was estimated as 13 cigarettes/day and 15 mg/cigarette carbon monoxide. We conclude that brand smoked is at least as important as quantity and that in this population there is evidence for a threshold for tobacco smoke intake below which no discernible effect on birthweight is seen.

Birth Weight↗