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PubMed1981

How to make the best decision. Philosophical aspects of clinical decision theory.

An attempt is made to discuss some of the philosophical implications of the use of decision-analytic techniques. The probabilities of a decision analysis are subjective measures of belief, and it is concluded that clinicians base their subjective beliefs on both recorded observations and theoretical knowledge. The clinical decision maker also evaluates the consequences of his actions, and therefore clinical decision theory transcends medical science. A number of different schools of normative ethics are mentioned to illustrate the complexity of everyday decision making. The philosophical terminology is useful for the analysis of clinical problems, and it is argued that clinical decision making has both a teleological and a deontological component. The results of decision-analytic studies depend on such factors as the wealth of the country, the organization of the health service, and cultural norms.

Clinical Competence↗
PubMed2002

Toward a unified theory of decision criterion learning in perceptual categorization.

Optimal decision criterion placement maximizes expected reward and requires sensitivity to the category base rates (prior probabilities) and payoffs (costs and benefits of incorrect and correct responding). When base rates are unequal, human decision criterion is nearly optimal, but when payoffs are unequal, suboptimal decision criterion placement is observed, even when the optimal decision criterion is identical in both cases. A series of studies are reviewed that examine the generality of this finding, and a unified theory of decision criterion learning is described (Maddox & Dodd, 2001). The theory assumes that two critical mechanisms operate in decision criterion learning. One mechanism involves competition between reward and accuracy maximization: The observer attempts to maximize reward, as instructed, but also places some importance on accuracy maximization. The second mechanism involves a flat-maxima hypothesis that assumes that the observer's estimate of the reward-maximizing decision criterion is determined from the steepness of the objective reward function that relates expected reward to decision criterion placement. Experiments used to develop and test the theory require each observer to complete a large number of trials and to participate in all conditions of the experiment. This provides maximal control over the reinforcement history of the observer and allows a focus on individual behavioral profiles. The theory is applied to decision criterion learning problems that examine category discriminability, payoff matrix multiplication and addition effects, the optimal classifier's independence assumption, and different types of trial-by-trial feedback. In every case the theory provides a good account of the data, and, most important, provides useful insights into the psychological processes involved in decision criterion learning.

Animals↗
PubMed2004

Women, men and public health-how the choice of normative theory affects resource allocation.

Women live longer than men in almost all countries, but men are more privileged in terms of power, influence, resources and probably morbidity. This investigation aims at illustrating how the choice of normative framework affects judgements about the fairness in these sex differences, and about desired societal change. The selected theories are welfare economics, health sector extra-welfarism, justice as fairness and feminist justice. By means of five Swedish proposals aiming at improving the population's health or "sex equity", facts and values are applied to resource allocation. Although we do not claim a specific ethical foundation, it seems to us that the feminist criterion has great potential in public health policy. The overall conclusion is that the normative framework must be explicitly discussed and stated in issues of women's and men's health.

Ethical Theory↗
PubMed1999

Quantifying the information value of clinical assessments with signal detection theory.

The aim of clinical assessment is to gather data that allow us to reduce uncertainty regarding the probabilities of events. This is a Bayesian view of assessment that is consistent with the well-known concept of incremental validity. Conventional approaches to evaluating the accuracy of assessment methods are confounded by the choice of cutting points, by the base rates of the events, and by the assessment goal (e.g. nomothetic vs idiographic predictions). Clinical assessors need a common metric for quantifying the information value of assessment data, independent of the cutting points, base rates, or particular application. Signal detection theory (SDT) provides such a metric. We review SDT's history, concepts, and methods and provide examples of its application to a variety of assessment problems.

Journal Article↗
PubMed2006

A Bayesian, combinatorial approach to capture-recapture.

It is shown that, in the capture-recapture method, the widely used formulae of Bailey or Chapman-Seber give the most likely value for the size of the population, but systematically underestimate the probability that the population is larger than any given size. We take here a first step in a combinatorial approach which does not suffer from this flaw: formulae are given which can be used in the closed case (no birth, death or migrations between captures) when at least two animals have been recaptured and when there is homogeneity with regard to capture probability. Numerical and heuristic evidence is presented pointing to the fact that the error incurred when using the formulae of Bailey or Chapman-Seber depends asymptotically only on the number of recaptured animals, and will not diminish if the number of captured animals becomes large while the number of recaptured animals remains constant. A result that was stated and left unproven by Darroch is proven here.

Analysis of Variance↗
PubMed2005

Dynamics of unbinding of cell adhesion molecules: transition from catch to slip bonds.

The unbinding dynamics of complexes involving cell-adhesion molecules depends on the specific ligands. Atomic force microscopy measurements have shown that for the specific P-selectin-P-selectin glycoprotein ligand (sPSGL-1) the average bond lifetime t initially increases (catch bonds) at low (< or =10 pN) constant force, f, and decreases when f > 10 pN (slip bonds). In contrast, for the complex with G1 anti-P-selectin monoclonal antibody t monotonically decreases with f. To quantitatively map the energy landscape of such complexes we use a model that considers the possibility of redistribution of population from one force-free state to another force-stabilized bound state. The excellent agreement between theory and experiments allows us to extract energy landscape parameters by fitting the calculated curves to the lifetime measurements for both sPSGL-1 and G1. Surprisingly, the unbinding transition state for P-selectin-G1 complex is close (0.32 nm) to the bound state, implying that the interaction is brittle, i.e., once deformed, the complex fractures. In contrast, the unbinding transition state of the P-selectin-sPSGL-1 complex is far (approximately 1.5 nm) from the bound state, indicative of a compliant structure. Constant f energy landscape parameters are used to compute the distributions of unbinding times and unbinding forces as a function of the loading rate, rf. For a given rf, unbinding of sPSGL-1 occurs over a broader range of f with the most probable f being an order of magnitude less than for G1. The theory for cell adhesion complexes can be used to predict the outcomes of unbinding of other protein-protein complexes.

Ligands↗
PubMedDate not supplied

[Occurrence of non-Hodgkin's lymphoma in chronic myeloid leukemia].

The authors report the case of a 42-year old woman who developed chronic myelocytic leukemia with Philadelphia chromosome followed, 21 months later, by malignant follicular lymphoma with small cleaved cells and giant cells. This case is comparable to the other associations of acute or chronic myelocytic and lymphocytic blood diseases previously published. Several pathogenic theories are reviewed. They involve chemotherapy with alkylating drugs (but the diagnosis is sometimes simultaneous), cellular oncogens or, more probably, a clonal abnormality of the stem cell sequentially or concomitantly expressed in the cells of both lineages; unfortunately, in the absence of Philadelphia chromosome this theory has not yet been demonstrated on lymphoma cells.

Adult↗
PubMed1996

High phenotypic correlations among siblings with autism and pervasive developmental disorders.

The objective of this study was to examine familial factors influencing clinical variation in sibships that contained at least 2 children affected with autism or another form of pervasive developmental disorder (PDD). The sample included a total of 60 families, 23 with multiple cases of PDD and 37 with a single affected child. Measurements of IQ, adaptive behaviors in socialization and communication, and autistic symptoms were taken on all affected children. A high intraclass correlation, especially on IQ and an index of social behaviors, was observed between affected children from the same family. In contrast, low correlations were observed on measurements of IQ and adaptive behavior between affected and unaffected children from the same family. These data indicate that variation in severity of PDD is influenced by familial, and probably genetic, mechanisms. The results are discussed in relation to current theories on the genetics of autism and the heritable mechanisms underlying variations in clinical severity.

Autistic Disorder↗
PubMed1992

Myokymic discharges and enhanced facial nerve reflex responses after recovery from idiopathic facial palsy.

A functional disorder of facial muscle activity commonly occurs in patients after recovery from Bell's palsy with axonal degeneration. The postparalytic facial dysfunction is probably related to the aberrant growing of regenerating axons, although other theories such as ephaptic transmission, spontaneous generation of impulses, and enhancement of motoneuron excitability should also be considered. In this work, we have carried out a comparative electrophysiological study of both sides of the face in 23 patients who had recovered from a unilateral Bell's palsy with axonal degeneration. At rest, spontaneous firing of motor units was observed in muscles of the previously paralyzed side. Direct motor responses to facial nerve stimulation were smaller in the muscles of the previously paralyzed side, but reflex responses obtained in the same muscles by stimulation of either the facial or trigeminal nerve were larger when compared with those of the contralateral side. These data indicate that patients with "postparalytic facial dysfunction" may have an increased background muscle activity, as well as an enhanced recruitment of facial motoneurons to reflex activation in the side of the previous paralysis. These findings are compatible with an enhanced level of motoneuron excitability in the facial nucleus.

Action Potentials↗
PubMed1992

Finite-state models in the alignment of macromolecules.

Minimum message length encoding is a technique of inductive inference with theoretical and practical advantages. It allows the posterior odds-ratio of two theories or hypotheses to be calculated. Here it is applied to problems of aligning or relating two strings, in particular two biological macromolecules. We compare the r-theory, that the strings are related, with the null-theory, that they are not related. If they are related, the probabilities of the various alignments can be calculated. This is done for one-, three-, and five-state models of relation or mutation. These correspond to linear and piecewise linear cost functions on runs of insertions and deletions. We describe how to estimate parameters of a model. The validity of a model is itself an hypothesis and can be objectively tested. This is done on real DNA strings and on artificial data. The tests on artificial data indicate limits on what can be inferred in various situations. The tests on real DNA support either the three- or five-state models over the one-state model. Finally, a fast, approximate minimum message length string comparison algorithm is described.

Algorithms↗
PubMed2000

Fact finding beyond all reasonable doubt--legal aspects.

A description is provided of the European (esp. German and Austrian) legal concept of "fact finding beyond all reasonable doubt". The uncontested principle of the free evaluation of evidence is closely connected with the dispute about the "probative standard" (= this means the degree of the judge's conviction which is necessary for the fact finding). There can neither be a purely subjective nor a purely objective theory of the probative standard. Because of the human limits of possible perception and of the subjective cognitive faculties the total conviction of truth as demanded by the "conviction-of-truth-theory" could never mean absolute certainty. It is sufficient if "no other reasonable man with a clear view of the conditions of life would be convinced". On the other hand, the objective theory, which sees the judge's task only in consideration of probabilities, becomes more and more important. As a third principle, there is the preponderance principle influenced by the Anglo-American system.

Journal Article↗
PubMed2001

Guiding contact by coupling the taus of gaps.

Animals control contact with surfaces when locomoting, catching prey, etc. This requires sensorily guiding the rate of closure of gaps between effectors such as the hands, feet or jaws and destinations such as a ball, the ground and a prey. Control is generally rapid, reliable and robust, even with small nervous systems: the sensorimotor processes are therefore probably rather simple. We tested a hypothesis, based on general tau theory, that closing two gaps simultaneously, as required in many actions, might be achieved simply by keeping the taus of the gaps coupled in constant ratio. tau of a changing gap is defined as the time-to-closure of the gap at the current closure-rate. General tau theory shows that tau of a gap could, in principle, be directly sensed without needing to sense either the gap size or its rate of closure. In our experiment, subjects moved an effector (computer cursor) to a destination zone indicated on the computer monitor, to stop in the zone just as a moving target cursor reached it. The results indicated the subjects achieved the task by keeping tau of the gap between effector and target coupled to tau of the gap between the effector and the destination zone. Evidence of tau-coupling has also been found, for example, in bats guiding landing using echolocation. Thus, it appears that a sensorimotor process used by different species for coordinating the closure of two or more gaps between effectors and destinations entails constantly sensing the taus of the gaps and moving so as to keep the taus coupled in constant ratio.

Adult↗
PubMed2005

Improving the TMDL process using watershed risk assessment principles.

Ecological risk assessment (ERA) evaluates potential causal relationships between multiple sources and stressors and impacts on valued ecosystem components. ERAs applied at the watershed scale have many similarities to the place-based analyses that are undertaken to develop Total Maximum Daily Loads (TMDLs), in which linkages are established between stressors, sources, and water quality standards, including support of designated uses. TMDLs focus on achieving water quality standards associated with attainment of designated uses. In attempting to attain the water quality standard, many TMDLs focus on the stressor of concern rather than the ecological endpoint or indicators of the designated use that the standard is meant to protect. A watershed ecological risk assessment (WERA), at least in theory, examines effects of most likely stressors, as well as their probable sources in the watershed, to prioritize management options that will most likely result in meeting environmental goals or uses. Useful WERA principles that can be applied to TMDL development include: development and use of comprehensive conceptual models in the Problem Identification step of TMDLs; use of a transparent process for selecting Numeric Targets for TMDLs based on assessment endpoints derived from the management goal or designated use under consideration; analysis of co-occurring stressors likely to cause beneficial use impairment based on the conceptual model; use of explicit uncertainty analyses in the Linkage Analysis step of TMDL development; and frequent stakeholder interactions throughout the process. WERA principles are currently most applicable to those TMDLs in which there is no numeric standard and, therefore, indicators and targets need to be developed, such as many nutrient or sediment TMDLs. WERA methods can also be useful in determining TMDL targets in situations where simply targeting the water quality standard may re-attain the numeric criterion but not the broader designated use. Better incorporation of problem formulation principles from WERA into the TMDL development process would be helpful in improving the scientific rigor of TMDLs.

Ecology↗
PubMed1992

Futility and rationing.

It seems more than coincidental that at a time of great concern over rising health care costs and fears of rampant technology, debates are suddenly taking place about medical futility and health care rationing. This article examines the economic, historical, and demographic factors that have motivated increased attention to both these concepts, explores differences and similarities in the meaning of these terms, and discusses their ethical implications. Specifically, we identify four common sources of current debates on futility and rationing: the rise in health care costs; the development of high-technology medicine; the aging of society; and the effort to limit the scope of patient autonomy. We propose that when rationing criteria refer to medical benefit, the meanings of futility and rationing share certain common features. Futility and rationing differ, however, in important ways. Futility refers to treatment and outcome relationships not in a general population but in a specific patient. Rationing criteria usually are supported by reference to theories of justice, whereas the definition of futility, if achieved, will probably be arrived at by empirical community agreement. Rationing always occurs against a backdrop of resource scarcity, but futility need not. Toward the end of the paper, we clarify how the various connotations and contexts we associate with each term enhance or frustrate ethical debate.

Aged↗
PubMed1993

Functional size of the thylakoid phosphatases determined by radiation inactivation.

Radiation inactivation technique was employed to determine the functional size of phosphatases from thylakoid membrane. The enzymatic activities of phosphatases decayed in a simple function with the increase of radiation dosage. D37 values of 18.8 +/- 2.4-14.1 +/- 1.5 Mrad were obtained, using phosphoserine, phosphothreonine, p-nitrophenol phosphate, and phospho-histone V-S, respectively, as substrates. The molecular masses of 48.2 +/- 6.3-61 +/- 5.7 kDa were yielded by target theory analysis. We thus speculate that the thylakoid alkaline phosphatase is probably a monomer while acid phosphatase is functionally a dimer in situ.

Acid Phosphatase↗
PubMed1993

Is 'senescence' of diploid cells an ad hoc mechanism suppressing 'replicon' or not?

So-called 'limited life span' of diploid cells does not depend on their unresponsiveness to growth factors from the data obtained by complete protein-free culture of tumor cells. Limited proliferation (called limited life span) of diploid cells is one of the 'ad-hoc' negative regulatory mechanisms in animals, and can not be differentiated from other inhibitory mechanisms called 'tumor suppression' and 'terminal differentiation'. Metabolic imbalance induced by proliferation-dependent time-bomb mechanisms including infidelity of DNA repair is suggested to explain limited proliferation of cells. After maturation, autonomic progression of negative regulators in cells is induced by no prohibition of terminal differentiation, since organisms prepare no programs to stop development and differentiation. It is an attractive hypothesis that a proliferation-dependent time-bomb has been developed to control organogenesis for maturation and to determine body size. It is true that limited proliferation of cells can not explain longevity of individuals, although the so-called longevity genes play roles in ageing. Teleologically, longevity of individuals has been developed to produce genetic heterogeneity according to the selfish gene theory. This inter- and intra-species genetic heterogeneity increases the probability of selfish gene replication in germ cell line. After maturation and reproduction of DNA in germ cell line, individuals as vehicles for the DNA can be discarded by the 'selfish' genes.

Animals↗
PubMed1994

Psychological influences in disease: a decision theory model.

The integrity of living organisms depends on analyzing information from an uncertain and hostile world and responding appropriately to it. Statistical decision theory indicates that an optimum decision strategy takes into account information, probability and subjective values ascribed to correct and incorrect responses. It follows that decisions at all levels, including the molecular level, can be strongly influenced by psychological and emotional states which influence subjective evaluation. This concept provides a framework within which psychological influences in disease can be analyzed.

Decision Making↗
PubMed2005

Loop entropy and cytochrome c stability.

The loop entropy model proposes that loop closure in a protein becomes entropically more costly as the length of the loop increases. A model protein, cytochrome c, is composed of four loops connecting five helices surrounding a heme-containing core. To test the loop entropy model a series of mutant proteins are constructed with (Gly)n or (Thr)n segments (n = 4-20) inserted between Gly23 and Gly24 of omega loop A of a pseudo wild-type reference protein. Scanning calorimetry shows that protein stability decreases as n increases in the (Gly)n or (Thr)n segment. The dependence of stability on loop length is analyzed with the loop entropy model. Fitting to the model gives a quantitative description of stability differences for the mutant proteins, but with a smaller power-dependence of the probability of loop closure (c-value) than expected from polymer theory. A possible explanation for the discrepancy is that thermodynamically unfavorable loop entropy is partially offset by interactions between the inserted homopolymer and flanking heteropolymer portions of the unfolded protein. The interactions may involve molecular crowding that favors coalescence of the heteropolymer at the insert site and thus closure of the homopolymer loops, possibly as an aspect of the folding code. This may allow use of loop insert mutants to assess the strength of the heteropolymer-encoded folding signals that facilitate loop closure at the insert site.

Amino Acid Sequence↗