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PubMed2003

Scaling exponent of the maximum growth probability in diffusion-limited aggregation.

An early (and influential) scaling relation in the multifractal theory of diffusion limited aggregation (DLA) is the Turkevich-Scher conjecture that relates the exponent alpha(min) that characterizes the "hottest" region of the harmonic measure and the fractal dimension D of the cluster, i.e., D=1+alpha(min). Due to lack of accurate direct measurements of both D and alpha(min), this conjecture could never be put to a serious test. Using the method of iterated conformal maps, D was recently determined as D=1.713+/-0.003. In this paper, we determine alpha(min) accurately with the result alpha(min)=0.665+/-0.004. We thus conclude that the Turkevich-Scher conjecture is incorrect for DLA.

Journal Article↗
PubMed2002

[Breast cancer and pregnancy: decision making and the point of view of the mother].

For the treatment of breast cancer, modifications of decision making related to pregnancy could be assessed through three questions. Why a decision had been chosen? In that case, the hypothesis is that decisions are based on the expected utility. The theory assumes weighting and computation of complete possibilities with their associated probabilities and values. However values exhibits a wide inter-individual variation range. Therefore the predictability of choice based on this model is indeed very low. Furthermore it is likely that the willingness of pregnancy after breast cancer contains besides classic constituents of appeals of motherhood, a specific meaning of recovery both of health and femininity. The second question: who is in charge of the decision? And under the paradigm of autonomy, women' decision is, merely by itself, the right decision. The last question is how? For some situations for which foreseeing is quiet complex, the value of the process in itself is increased and could help the end-oriented or self-determined decision. Casuistic analysis could therefore improve women' decisions. The issue is not only about decision but also related to patient-physician relationship, about an issue that is not only a biomedical problem.

Breast Neoplasms↗
PubMed2000

Computer modeling of population exposure to a carcinogen: the example of asbestos and mesothelioma mortality in France.

The multistage theory of carcinogenesis allows models to be constructed that provide the individual probability of a diagnosed tumor at a given age as a function of the person's past exposure to carcinogenic agents (exposure level versus age), the time since exposure, and age. When exposure to a carcinogenic agent and its impact in terms of morbidity and mortality are modeled on the scale of the general population, individual exposures must often be estimated. If appropriate data do not already exist, this difficult task necessitates expensive and difficult investigations. We propose here a method that allows this global exposure to be modeled without needing to know the individual exposures. The method is used and illustrated in the context of modeling the asbestos exposure of the French male population and calculating its mortality rate from mesothelioma (a type of cancer for which asbestos is the only carcinogen and for which a risk function based on the multistage theory of carcinogenesis exists). This method assumes that the exposure functions (how exposure levels vary with age) for all individuals are the same, with the exception of one parameter. That is, it utilizes a hypothesis that we called the hypothesis of the Standard Exposure Window (SEW). We used two methods to calculate the probability of death from mesothelioma in a representative sample of the French male population for whom individual histories of asbestos exposure are known: we applied the risk function to all the individuals, and we applied the SEW hypothesis. The number of deaths obtained by the two methods are very close and fit the observed mortality data satisfactorily.

Aged↗
PubMed1987

On the theory of partially inbreeding finite populations. I. Partial selfing.

Some stochastic theory is developed for monoecious populations of size N in which there are probabilities beta and 1 - beta of reproduction by selfing and by random mating. It is assumed that beta much greater than N-1. Expressions are derived for the inbreeding coefficient of one random individual and the coefficient of kinship of two random separate individuals at time t. The mean and between-lines variance of the fraction of copies of a locus that are identical in two random separate individuals in an equilibrium population are obtained under the assumption that there is an infinite number of possible alleles. It is found that the theory for random mating populations holds if the effective population number is Ne = N'/(1 + FIS), where FIS is the inbreeding coefficient at equilibrium when N is infinite and N' is the reciprocal of the probability that two gametes contributing to random separate adults come from the same parent. When there is a binomial distribution of successful gametes emanating from each adult, N' = N. An approximation to the probability that an allele A survives if it is originally present in one AA heterozygote is found to be 2(N'/N)(FISS1 + (1 - FIS)S2), where S1 and S2 are the selective advantages of AA and AA in comparison with AA. In the last section it is shown that if there is partial full sib mating and binomial offspring distributions Ne = N/(1 + 3FIS).

Alleles↗
PubMed2005

The future of 'pure' medical science: the need for a new specialist professional research system.

Over recent decades, medical research has become mostly an 'applied' science which implicitly aims at steady progress by an accumulation of small improvements, each increment having a high probability of validity. Applied medical science is, therefore, a social system of communications for generating pre-publication peer-reviewed knowledge that is ready for implementation. However, the need for predictability makes modern medical science risk-averse and this is leading to a decline in major therapeutic breakthroughs where new treatments for new diseases are required. There is need for the evolution of a specialized professional research system of pure medial science, whose role would be to generate and critically evaluate radically novel and potentially important theories, techniques, therapies and technologies. Pure science ideas typically have a lower probability of being valid, but the possibility of much greater benefit if they turn out to be true. The domination of medical research by applied criteria means that even good ideas from pure medical science are typically ignored or summarily rejected as being too speculative. Of course, radical and potentially important ideas may currently be published, but at present there is no formal mechanism by which pure science publications may be received, critiqued, evaluated and extended to become suitable for 'application'. Pure medical science needs to evolve to constitute a typical specialized scientific system of formal communications among a professional community. The members of this putative profession would interact via close research groupings, journals, meetings, electronic and web communications--like any other science. Pure medical science units might arise as elite grouping linked to existing world-class applied medical research institutions. However, the pure medical science system would have its own separate aims, procedures for scientific evaluation, institutional organization, funding and support arrangements; and a separate higher-professional career path with distinctive selection criteria. For instance, future leaders of pure medical science institutions would need to be selected on the basis of their specialized cognitive aptitudes and their record of having generated science-transforming ideas, as well as their research management skills. Pure medical science would work most effectively and efficiently if practiced in many independent and competing institutions in several different countries. The main 'market' for pure medical science would be the applied medical scientists, who need radical strategies to solve problems which are not yielding to established methods. The stimulus to create such elite pure medical science institutions might come from the leadership of academic 'entrepreneurs' (for instance, imaginative patrons in the major funding foundations), or be triggered by a widespread public recognition of the probable exhaustion of existing applied medical science approaches to solving major therapeutic challenges.

Biomedical Research↗
PubMedDate not supplied

[The prospective image the psychotherapist holds of his patient and its effect on the therapeutic process].

Psychonalytic theory of the therapeutic process is predominantly determined by the concepts of transference, resistance and countertransference. Decisive through the insight into the relationship between analyst and patient thus derived may be, the range of, potential meanings of these concepts does not in the first place encompass a complete theory of the therapist-patient-relationship. It mainly indicates how to use the therapeutical techniques which in turn define the theoretical scope of these terms. What is called the real aspects in the therapeutic relation, ie, those relatively free from transference, and their influence on the therapeutical process are so far unterrepresented in the theory of psychoanalysis. Yet the prospective view the therapist holds of his patient most probably has a decisive impact on the course of a treatment. Although the notion of countertransference offers some technical possibilities for correcting this image and for adjusting it to reality it is not sufficient to account for the complexity of the process in the psychoanalytic theory. The real features of the therapeutical relationship are the secret condition, the very background which alone allows the phenomena of transference and counter-transference to be detected as such.

Countertransference↗
PubMedDate not supplied

Genetic basis of limited cell proliferation.

Knowledge about the changes that occur as cells traverse their replicative lifespans grows apace, as evidenced by the articles in this issue. Controversy over the interpretation of this knowledge continues, however, and is indeed fuelled by new discoveries (e.g., see Cristofalo, 1990; Holliday, 1990; Smith, 1990). This paper makes a brief commentary on the problems of cellular ageing, with particular emphasis on the unfolding picture of the genetic control of ageing and longevity which derives from evolutionary theory (Kirkwood and Rose, 1991). The case is argued for a synthetic view which recognizes that the immediate causes of limited cell proliferation probably involve some form of active genetic control, but that the ultimate reason for cell ageing is found in evolutionary theories which suggest that the ageing process is not actively programmed and that senescence may be due to the accumulation of damage.

Aging↗
PubMed1997

The influence of systemic lupus erythematosus on fetal development: cognitive, behavioral, and health trends.

In 1985, Gualtieri and Hicks proposed the immunoreactive theory to explain the higher prevalence of childhood neurodevelopmental disorders in males. The theory claimed that male fetuses are more antigenic to mothers, resulting in increased immunologic attack on the developing central nervous system, and increased probability of atypical brain development. Individuals with systemic lupus erythematosus (SLE) provide a unique situation in which to investigate this theory. We evaluated the parent-reported prevalence of five developmental problems (stuttering, other speech problems, hyperactivity, attention deficit, and reading problems) in two groups: 154 individuals ages 8-20 years born to women with SLE, drawn from six cities, and 154 controls of comparable age and sex whose mothers did not have SLE. Controls were drawn from a comparison group ascertained from randomly selected schools in one of the cities. Questions about handedness, immune disorders, and pregnancy and birth complications were also evaluated. Children of SLE mothers were shown to have more evidence of developmental difficulties, immune related disorders, and nonrighthandedness. For developmental problems, these findings were most marked in male children of SLE mothers. These results suggest that maternal immunoreactivity, as represented by women with SLE, may present a special risk factor for subsequent learning difficulties in their children, particularly males.

Adolescent↗
PubMed2003

Punctuated equilibria and 1/f noise in a biological coevolution model with individual-based dynamics.

We present a study by linear stability analysis and large-scale Monte Carlo simulations of a simple model of biological coevolution. Selection is provided through a reproduction probability that contains quenched, random interspecies interactions, while genetic variation is provided through a low mutation rate. Both selection and mutation act on individual organisms. Consistent with some current theories of macroevolutionary dynamics, the model displays intermittent, statistically self-similar behavior with punctuated equilibria. The probability density for the lifetimes of ecological communities is well approximated by a power law with exponent near -2, and the corresponding power spectral densities show 1/f noise (flicker noise) over several decades. The long-lived communities (quasisteady states) consist of a relatively small number of mutualistically interacting species, and they are surrounded by a "protection zone" of closely related genotypes that have a very low probability of invading the resident community. The extent of the protection zone affects the stability of the community in a way analogous to the height of the free-energy barrier surrounding a metastable state in a physical system. Measures of biological diversity are on average stationary with no discernible trends, even over our very long simulation runs of approximately 3.4 x 10(7) generations.

Journal Article↗
PubMed1996

Game theory and reciprocity in some extensive form experimental games.

We examine decision making in two-person extensive form game trees using nine treatments that vary matching protocol, payoffs, and payoff information. Our objective is to establish replicable principles of cooperative versus noncooperative behavior that involve the use of signaling, reciprocity, and backward induction strategies, depending on the availability of dominated direct punishing strategies and the probability of repeated interaction with the same partner. Contrary to the predictions of game theory, we find substantial support for cooperation under complete information even in various single-play treatments.

Bayes Theorem↗
PubMed2000

A sampling approach to biases in conditional probability judgments: beyond base rate neglect and statistical format.

Conditional probability judgments of rare events are often inflated. Early accounts assumed a general deficit in using statistical base rates. More recent approaches predict improvement when problems are presented in frequency format or refer to natural categories. The present theory focuses on sampling processes. Experiment 1 showed that a seeming advantage of frequency over probability formats is due to a confounded factor, the need to mentally transform stimulus samples. An information search paradigm was used in Experiment 2. When sampling by the predictor, the probability to be estimated, p(criterion/predictor), was conserved in the samples and judgments were quite accurate. However, when sampling by the criterion, the low base-rate event was strongly overrepresented, accounting for the entire bias. Judgments were quite sensitive to the sampled data, but failed to take sampling constraints into account, as shown in Experiments 3 and 4.

Adult↗
PubMed1994

Recognition of mental state terms. Clinical findings in children with autism and a functional neuroimaging study of normal adults.

BACKGROUND: The mind's ability to think about the mind has attracted substantial research interest in cognitive science in recent decades, as 'theory of mind'. No research has attempted to identify the brain basis of this ability, probably because it involves several separate processes. As a first step, we investigated one component process-the ability to recognise mental state terms. METHOD: In Experiment 1, we tested a group of children with autism (known to have theory of mind deficits) and a control group of children with mental handicap, for their ability to recognise mental state terms in a word list. This was to test if the mental state recognition task was related to traditional theory of mind tests. In Experiment 2, we investigated if in the normal brain, recognition of mental state terms might be localised. The procedure employed single photon emission computerised tomography (SPECT) in normal adult volunteers. We tested the prediction (based on available neurological and animal lesion studies) that there would be increased activation in the orbito-frontal cortex during this task, relative to a control condition, and relative to an adjacent frontal area (frontal-polar cortex). RESULTS: In Experiment 1, the group with autism performed significantly worse than the group without autism. In Experiment 2, there was increased cerebral blood flow during the mental state recognition task in the right orbito-frontal cortex relative to the left frontal-polar region. CONCLUSIONS: This simple mental state recognition task appears to relate to theory of mind, in that both are impaired in autism. The SPECT results implicate the orbito-frontal cortex as the basis of this ability.

Adolescent↗
PubMed1996

Medical causation analysis heuristics.

Medical causation analysis determines whether or not a specific patient's illness is the result of a work site or an environmental exposure. In the past, this has been conducted implicitly with little analysis of the process per se. Our review suggests that there are several distinct heuristics that may be utilized; these include probability-based models, application of group-based data (epidemiology) to individuals, Bayesian analysis, a priori assumptions about which conclusions are better, and others. Some methods consider only work causes, whereas others explicitly consider alternative explanations. There are considerable differences among the methods in process, outcome, and fundamental assumptions. Formal assessment of the medical causation analysis process can provide insight and may ultimately lead to its standardization and improvement.

Causality↗
PubMed2004

Ideal observers and optimal ROC hypersurfaces in N-class classification.

The likelihood ratio, or ideal observer, decision rule is known to be optimal for two-class classification tasks in the sense that it maximizes expected utility (or, equivalently, minimizes the Bayes risk). Furthermore, using this decision rule yields a receiver operating characteristic (ROC) curve which is never above the ROC curve produced using any other decision rule, provided the observer's misclassification rate with respect to one of the two classes is chosen as the dependent variable for the curve (i.e., an "inversion" of the more common formulation in which the observer's true-positive fraction is plotted against its false-positive fraction). It is also known that for a decision task requiring classification of observations into N classes, optimal performance in the expected utility sense is obtained using a set of N-1 likelihood ratios as decision variables. In the N-class extension of ROC analysis, the ideal observer performance is describable in terms of an (N2-N-1)-parameter hypersurface in an (N2-N)-dimensional probability space. We show that the result for two classes holds in this case as well, namely that the ROC hypersurface obtained using the ideal observer decision rule is never above the ROC hypersurface obtained using any other decision rule (where in our formulation performance is given exclusively with respect to between-class error rates rather than within-class sensitivities).

Bayes Theorem↗