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PubMed1999

A generalized signal detection model to predict rational variation in base rate use.

The predominant models of rational behavior currently used to analyze a large class of experiments imply that subjects neglect or place insufficient weight on base rates when making probabilistic judgments. We argue that the evidence is inadequate for this conclusion because the models make needlessly restrictive assumptions about how base rates should be used. The restrictive assumptions stem from a misuse of Bayes' rule that ignores specific aspects of how the proportions arose. We develop a model of rational behavior that generalizes signal detection theory to reflect the environment subjects routinely face and we reexamine the relevant experimental literature. Variation observed in subjects' responses to base rate information is explained by the present rational model more fully than by extant models.

Adult↗
PubMed1990

An exercise in rational taxonomy.

The quest for a rational taxonomy of living forms began in the 17th century. Since the general acceptance of Darwin's theory of descent with modification, however, students of morphology became preoccupied with a systematics based on the genealogy of groups; and the rise of molecular phylogenies in recent years results in a further decline in the science of morphology. Reconstructing phylogenies by itself brings us no closer to the goal of rational taxonomy, which is to uncover the natural order inherent in the forms of living things. It is proposed that the rational taxonomy of forms should be derived from a study of development, much as von Baer had envisaged. To illustrate the method, a set of segmentation abnormalities in Drosophila larvae (previously exposed to either vapour) is considered, which can be individually classified as distinct disturbances in the process responsible for establishing normal segmental pattern. The process consists of a hierarchy of four successive bifurcations dividing the embryo's body first into two parts, then four, eight, and finally 16 subdivisions or segments. This gives rise to a taxonomic map of all possible transformations which contains the "phylogeny" of the actual forms and provides a natural system for classifying them. Attempts to recover the "true" phylogeny by various numerical methods are summarized and their implications for the validity of the basic assumptions of contemporary systematics discussed.

Animals↗
PubMed1989

Impact of an essential drugs programme on availability and rational use of drugs.

Availability and rational use of drugs was assessed in a random sample of 19 peripheral health units in two governorates in Democratic Yemen in which an essential drugs programme has been operational for the past few years. Findings were compared with those from seven health units in one governorate in which no such programme had been started. On average, 27 essential drugs were available in the programme area, compared with 17 in the control area. Programme areas carried on average 1 non-essential drug, compared with 17 in control areas. Average stock was adequate for 4 weeks in programme areas and for 1 week in control areas. Health workers in the programme area scored slightly, but not significantly, better in a test on theoretical knowledge on rational drug use. However, programme areas differed considerably from control areas in patterns of drug use, with fewer injections (24.8% vs 57.8% of prescriptions) and fewer antibiotics (46.3% vs 66.8%) being prescribed in programme areas, which also had fewer drugs per prescription (1.5 vs 2.4). The programme has significantly improved the availability and rational use of essential drugs in peripheral health units.

Community Health Centers↗
PubMed1995

Randomised controlled trial of routine individual feedback to improve rationality and reduce numbers of test requests.

Feedback can be described as a way to provide information on doctors' performance to enable changes in future behaviour. Feedback is used with the aim of changing test-ordering behaviour. It can lead to reductions in test usage and cost savings. It is not sufficiently clear, however, whether feedback leads to more appropriate test use. Since 1985, the Diagnostic Coordinating Center Maastricht has been giving feedback on diagnostic tests as a routine health care activity to all family doctors in its region. Both quantity and quality of requests are discussed. In a randomised, controlled trial over 2.5 years, discussion of tests not included previously was added to the existing routine feedback. One group of family doctors (n = 39) received feedback on test-group A (electrocardiography, endoscopy, cervical smears, and allergy tests), the other (n = 40) on test-group B (radiographic and ultrasonographic tests). Thus, each group of doctors acted as a control group for the other. Changes in volume and rationality of requests were analysed. The number of requests decreased during the trial (p = 0.036). Request numbers decreased particularly for test-group A (p = 0.04). The proportion of requests that were non-rational decreased more in the intervention than in the control groups (p = 0.009). Rationality improved predominantly for test-group B (p = 0.043). Thus, routine feedback can change the quantity and quality of requests.

Diagnostic Services↗
PubMed2001

Rational evolution of a medium chain-specific cytochrome P-450 BM-3 variant.

The single mutant F87A of cytochrome P-450 BM-3 from Bacillus megaterium was engineered by rational evolution to achieve improved hydroxylation activity for medium chain length substrates (C8-C10). Rational evolution combines rational design and directed evolution to overcome the drawbacks of these methods when applied individually. Based on the X-ray structure of the enzyme, eight mutation sites (P25, V26, R47, Y51, S72, A74, L188, and M354) were identified by modeling. Sublibraries created by site-specific randomization mutagenesis of each single site were screened using a spectroscopic assay based on omega-p-nitrophenoxycarboxylic acids (pNCA). The mutants showing activity for shorter chain length substrates were combined, and these combi-libraries were screened again for mutants with even better catalytic properties. Using this approach, a P-450 BM-3 variant with five mutations (V26T, R47F, A74G, L188K, and F87A) that efficiently hydrolyzes 8-pNCA was obtained. The catalytic efficiency of this mutant towards omega-p-nitrophenoxydecanoic acid (10-pNCA) and omega-p-nitrophenoxydodecanoic acid (12-pNCA) is comparable to that of the wild-type P-450 BM-3.

Bacillus megaterium↗
PubMed2002

Rational eating: can it lead to overweightness or underweightness?

Although a deviation from the physiologically optimal weight increases the probability of dying, the steady state for an expected lifetime-utility maximiser is a state of overweightness. However, even a small initial deviation from this rationally stationary weight is followed by explosive oscillations. These oscillations might lead to severe and chronic underweightness in a late stage of life. In the presence of socio-cultural norms of appearance, the rationally stationary weight of fat people is lower than otherwise and the rationally stationary weight of lean people is greater than otherwise.

Activity Cycles↗
PubMed1998

The impact of the UK NHS purchaser-provider split on the 'rational' introduction of new medical technologies.

This article uses evidence from case studies of the introduction of three new medical technologies to explore the impact of the UK NHS purchaser--provider split on the diffusion of new medical technologies. A desirable policy objective is assumed to be the 'rational' diffusion of medical technologies according to evidence that they are clinically and cost effective. Theoretical mechanisms are identified through which diffusion could be controlled, and the case studies are used to explore the extent to which rational technology diffusion occurs in practice in the NHS. They illustrate the influence of purchasers and providers on the introduction and early use of new technologies and explore the extent to which research about clinical and cost effectiveness is used to inform decisions about technology adoption. The results demonstrate the limited influence of purchasers and the short term clinical and organisational objectives pursued by providers in relation to technology adoption. It is suggested that initiatives to promote rational technology diffusion might be most effective if they are focused on decision making in providers, and if they aim to balance the influence on decisions of administrative and financial information about the technologies with more systematic use of research about clinical and cost effectiveness.

Cost-Benefit Analysis↗
PubMed2002

[Rational use of medications in the treatment of urinary infections].

OBJECTIVES: MAIN: to encourage the rational use of medication in the treatment of uncomplicated acute cystitis (UAC). SECONDARY: to find the most common germs in our area and their sensitivity to medication, the most common anti-microbials used and patients age, and to evaluate the savings made through a policy of rational use of medication.Design. Retrospective, descriptive, observational study. SETTING: La Solana Health Centre jointly with the biochemistry laboratory of the Talavera Area. PARTICIPANTS: Probabilistic randomised sampling of clinical histories of women between 20 and 80 with episodes of UAC (349 in all) between 01/10/95 and 01/10/00. MEASUREMENTS AND RESULTS: First, the laboratory evaluated 591 urine cultures of complicated/uncomplicated UTI from 01/01/00 to 01/10/00, with study of the germs involved and their sensitivities. 373 positives were isolated: E. coli (78.3%), which had the greatest sensitivity to amoxycillin/clavulanic acid, fosfomycin, nitrofurantoin and cefixime; Proteus (7.2%) and Streptococcus D (5.8%). Second, clinical records were analysed for the following: antibiotics (norfloxacine and cyprofloxacine, the most common); length of treatment (average of 6.52.34 days); age of patient (greater number in under-65s). CONCLUSIONS: E. coli is the most common germ in UTI and is highly sensitive to amoxy/clavulanic acid, nitrofurantoin, fosfomycin and cefixime. Resistance to cyprofloxacine and norfloxacine are starting to be significant. In UAC the three-day model should be encouraged for young women; and 7 days is recommended for the over-65s. More rational use of medication would increase efficacy and suppose a considerable economic saving in our area.

Acute Disease↗
PubMed2001

[Rational choice, prediction, and medical decision. Contribution of severity scores].

The aim of this study was to determine what type of representation the medical doctor adopted concerning the uncertainty about the future in critically ill patients in the context of preoperative evaluation and intensive care medicine and to explore through the representation of the patient health status the different possibilities of choice he was able to make. The role played by the severity classification systems in the process of medical decision-making under probabilistic uncertainty was assessed according to the theories of rational behaviour. In this context, a medical rationality needed to be discovered, going beyond the instrumental status of the objective and/or subjective constructions of rational choice theories and reaching a dimension where means and expected ends could be included.

Critical Care↗
PubMed1993

Rational suicide among older adults: a cause for concern?

Society is collectively having to examine questions it has never had to face before and nurses are frequently confronted with the difficult issue of whether suicide can or should be a rational choice for older adults. They may be faced with the question of whether an older person should ever be restrained from suicide. Arguments for and against rational suicide are highlighted and the author makes the case for a rational approach to the affirmation of life, rather than its rejection, even to the very end.

Aged↗
PubMed2003

Rational design and engineering of therapeutic proteins.

An increasing number of engineered protein therapeutics are currently being developed, tested in clinical trials and marketed for use. Many of these proteins arose out of hit-and-miss efforts to discover specific mutations, fusion partners or chemical modifications that confer desired properties. Through these efforts, several useful strategies have emerged for rational optimization of therapeutic candidates. The controlled manipulation of the physical, chemical and biological properties of proteins enabled by structure-based simulation is now being used to refine established rational engineering approaches and to advance new strategies. These methods provide clear, hypothesis-driven routes to solve problems that plague many proteins and to create novel mechanisms of action. We anticipate that rational protein engineering will shape the field of protein therapeutics dramatically by improving existing products and enabling the development of novel therapeutic agents.

Animals↗
PubMed2003

Rational models as theories - not standards - of behavior.

When people's behavior in laboratory tasks systematically deviates from a rational model, the implication is that real-world performance could be improved by changing the behavior. However, recent studies suggest that behavioral violations of rational models are at least sometimes the result of strategies that are well adapted to the real world (and not necessarily to the laboratory task). Thus, even if one accepts that certain behavior in the laboratory is irrational, compelling evidence that real-world behavior ought to change accordingly is often lacking. It is suggested here that rational models be seen as theories, and not standards, of behavior.

Journal Article↗
PubMed2005

Rational attachment of synthetic triptycene orthoquinone onto carbon nanotubes for electrocatalysis and sensitive detection of thiols.

This study demonstrates a novel electrochemical method for sensitive determination of biological thiols including homocysteine, cysteine, and glutathione based on rational functionalization of single-walled carbon nanotubes (SWNTs) with synthetic triptycene orthoquinone (TOQ). Unlike previous strategies used for the functionalization of the carbon nanotubes to fabricate new kind of electrochemically functional nanostructures, the method demonstrated here is essentially based on understanding of the redox properties inherent in the SWNTs themselves. It is demonstrated that the electrochemical oxidation of the thiols at the SWNT-modified electrode is redox-mediated by the quinone-like functional groups at the tube ends and that the low density of such functional groups leads to a follow-up oxidation of the thiols at a more positive potential at the electrode. To mimic the redox properties of the SWNTs and thus to increase the catalytic sites onto the SWNTs, we rationally choose the synthetic TOQ and attach such a compound onto the SWNTs. As a result, it is found that the rational attachment of TOQ onto the SWNTs substantially results in a sufficient electrocatalysis toward the thiols at a low potential of 0.0 V with enhanced sensitivities (i.e., almost by a factor of 10-fold) for the determination of such kind of species in relative to those at the SWNT-modified electrode. The high sensitivity and the good stability as well as the high reproducibility of the TOQ/SWNT-modified electrodes substantially make them very useful for reliable and durable determination of the biological thiols.

Adsorption↗
PubMed2004

Considering rational self-interest as a disposition: organizational implications of other orientation.

In contrast with major theories of attitudes and behavior, the authors propose that individuals are not equally motivated to pursue their self-interests. The authors show that differences in other orientation affect the extent to which actions and attitudes reflect self-interested calculation (instrumental rationality) and the extent to which beliefs represent their external environment (epistemic rationality). These differences have consequences for processes underlying a wide range of attitudes and behavior typically assumed to be rationally self-interested. Thus, the authors' model exposes a common explanation for diverse organizational phenomena. It also clarifies inconsistencies surrounding the validity of certain attitudinal and motivational models, the relationship between job attitudes and actions, cross-cultural differences in attitudes and behavior, escalation of commitment, and the relationship between chief executive officer characteristics and organizational performance.

Culture↗
PubMed2026

Early life sugar rationing and ageing related diseases, biological ageing and mortality.

Early-life nutrition may influence lifelong ageing, yet human evidence is scarce. Using Britain's postwar sugar rationing as a natural experiment, we examine its long-term effects in 64,809 United Kingdom Biobank participants. Exposure to sugar rationing during the first 1,000 days of life is associated with a 9% lower incidence of hallmark-related disease, with a hazard ratio of 0.91 and a 95% confidence interval of 0.88-0.94, and a 19% lower risk of all-cause mortality, with a hazard ratio of 0.81 and a 95% confidence interval of 0.69-0.93. Mediation analysis indicates that the survival association is statistically mediated, by approximately 60%, through differences in incident hallmark-related disease. Rationed individuals show 1.0-1.2-year younger biological ages across multiple clocks and lower organ ages, particularly in the lung, heart, and liver. Proteomic profiling identifies 47 altered proteins, with enrichment of adenosine monophosphate-activated protein kinase and longevity pathways and suppression of mechanistic target of rapamycin signaling. These findings are consistent with international recommendations to limit free or added sugars from the World Health Organization, United States Dietary Guidelines, and American Heart Association, and may inform policy discussions related to sugar taxation and infant food and marketing policies under the United Nations 2030 Agenda.

Humans↗
PubMed2001

Towards a more rational use of psychoactive substances in clinical practice.

Complex knowledge and data intensive nature of the psychoactive drug selection and prescription process often makes for irrational and inconsistent use of psychoactive drugs in clinical practice. After describing the state of the art with respect to psychoactive drug prescription practices and selection processes, our aim is to analyze the advantages of computer support systems in assisting the clinician in his clinical decisions. Finally, we will review the neuropsychiatric expert systems developed for the neuropsychiatric domain. Suboptimal psychoactive drug therapy is common practice, which leads to hospital admissions, extended length of hospital stay, ineffective therapy and increased costs. Furthermore, the psychoactive drug selection process is a complex decision process, using up-to-date integrative knowledge of drugs from basic sciences to the clinical level. Due to the information load, the lack of appropriate up-to-date information at the point of clinical care and the problem of integrating and weighing all information relatively equally, it is questionable whether any clinician can manage such a complex situation with optimal effectiveness. As has been shown in a number of experiments, clinicians can benefit from computer-based systems that provide access to accurate, up-to-date information. We maintain that more rational use of psychoactive drugs in clinical practice is needed, and conclude that rational psychoactive drug prescription is a knowledge and data-intensive task requiring true expertise derived from clinical, pathophysiological and pharmacotherapeutic knowledge. We will be developing a Multidisciplinary Psychoactive Drug Selection advisor system, M-PADS, to support the integration of various types of biomedical information and deliver that integrated information supportive to evidence-based rational drug prescription in the practice of medicine for the drug treatment of individual patients.

Decision Making, Computer-Assisted↗
PubMed2005

Efficient methods for finding transition states in chemical reactions: comparison of improved dimer method and partitioned rational function optimization method.

A combination of interpolation methods and local saddle-point search algorithms is probably the most efficient way of finding transition states in chemical reactions. Interpolation methods such as the growing-string method and the nudged-elastic band are able to find an approximation to the minimum-energy pathway and thereby provide a good initial guess for a transition state and imaginary mode connecting both reactant and product states. Since interpolation methods employ usually just a small number of configurations and converge slowly close to the minimum-energy pathway, local methods such as partitioned rational function optimization methods using either exact or approximate Hessians or minimum-mode-following methods such as the dimer or the Lanczos method have to be used to converge to the transition state. A modification to the original dimer method proposed by [Henkelman and Jonnson J. Chem. Phys. 111, 7010 (1999)] is presented, reducing the number of gradient calculations per cycle from six to four gradients or three gradients and one energy, and significantly improves the overall performance of the algorithm on quantum-chemical potential-energy surfaces, where forces are subject to numerical noise. A comparison is made between the dimer methods and the well-established partitioned rational function optimization methods for finding transition states after the use of interpolation methods. Results for 24 different small- to medium-sized chemical reactions covering a wide range of structural types demonstrate that the improved dimer method is an efficient alternative saddle-point search algorithm on medium-sized to large systems and is often even able to find transition states when partitioned rational function optimization methods fail to converge.

Journal Article↗
PubMed1983

Rational approximations to linear forms of exponentials and binomials.

Mahler proved the following quantitative result supplementing the Lindemann-Weierstrass theorem: Sigma(i=0) (n)C(i)e(ri) > H(-n-epsilon) for any distinct rational numbers r(0),r(1),..., r(n) and rational integers C(0),C(1),...,C(n) with H = max(0</=i</=n) C(i). We improve Mahler's estimate by replacing exponentials e(ri) by linearly independent linear forms L(i) = Sigma L(ij)e(sij) with rational L(ij),s(ij)i = 0,1,...,n. Similar results are obtained for binomials (a/b)(ri) or Sigma L(ij)(a/b)(sij) with integers a,b and logb/loga > 1 - epsilon. The simplest examples of new numbers with the irrationality exponent "2 + epsilon" are sinh 1 or sin 1.

Journal Article↗