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PubMed1997

Models of ratio schedule performance.

Predictions of P. R. Killeen's (1994) mathematical principles of reinforcement were tested for responding on ratio reinforcement schedules. The type of response key, the number of sessions per condition, and first vs. second half of a session had negligible effects on responding. Longer reinforcer durations and larger grain types engendered more responding, affecting primarily the parameter alpha (specific activation). Key pecking was faster than treadle pressing, affecting primarily the parameter delta (response time). Longer intertrial intervals led to higher overall response rates and shorter postreinforcement pauses and higher running rates, and ruled out some competing explanations. The treadle data required a distinction between the energetic requirements and rate-limiting properties of extended responses. The theory was extended to predict pause durations and run rates on ratio schedules.

Animals↗

PubMed1977

Storing covariance with nonlinearly interacting neurons.

A time-dependent, nonlinear model of neuronal interaction which was probabilistically analyzed in a previous article is shown here to be a natural generalization of the Hartline-Ratliff model of the Limulus retina. Although the primary physical variables in the model are the membrane potentials of neurons, the equations which govern the means and covariances of the membrane potentials are coupled through the average firing rates; as a consequence, the average firing rates control the selective storage and retrieval of covariance information. Motor learning in the cerebellar cortex is treated as a problem of covariance storage, and a predicition is made for the underlying synaptic plasticity: the change in synaptic strength between a parallel fiber and a Purkinje cell should be proportional to the covariance between discharges in the parallel fiber and the climbing fiber. Unlike previous proposals for synaptic plasticity, this prediction requires both facilitation and depression to occur (under different conditions) at the same synapse.

Cerebellum↗

PubMed2005

The ERA-EDTA cohort study--comparison of methods to predict survival on renal replacement therapy.

BACKGROUND: Accurate prediction of patient survival from the time of starting renal replacement therapy (RRT) is desirable, but previously published predictive models have low accuracy. We have attempted to overcome limitations of previous studies by conducting an ambidirectional inception cohort study in patients on RRT from centres throughout Europe. A conventional multivariate regression (MVR) model, a self-learning rule-based model (RBM) and a simple co-morbidity score [the Charlson score modified for renal disease (MCS)] were compared. METHODS: In 1996, all 3640 dialysis centres registered with the ERA-EDTA were invited to identify all patients on RRT for end-stage renal failure (ESRF) who died during the 28 days of February 1997 (training cohort) and all patients who started RRT in the same period (validation cohort). Fifty-four clinical and laboratory variables from the time of starting RRT were collected in both cohorts using a two-page questionnaire. The data from the training cohort were given to statisticians at the Amsterdam Academic Medical Centre to create the MVR model and to engineers in Strathclyde University to create the RBM. They were then given the baseline data from patients in the validation cohort to predict how long each patient would survive. Follow-up questionnaires were sent to the centre of each patient in the validation cohort to determine actual survival. RESULTS: A total of 2310 patients from 793 centres in 37 countries in the ERA-EDTA area were used to construct and validate the models. For predicting 1-year survival, the RBM had the highest positive predictive value (PPV) (84.2%), the MVR model had the highest negative predictive value (NPV) (47%) and the RBM had the highest likelihood ratio (1.59). For predicting 5-year survival, the MCS had the highest PPV (79.4%), the RBM had the highest NPV (74.3%) and the MCS had the highest likelihood ratio (7.0). The proportion of explained variance in survival for MCS, MVR and RBM was 14.6, 12.9 and 3.95%, respectively. CONCLUSION: Using the ambidirectional inception cohort design of this ERA-EDTA Registry survey, we have been able to create and validate two novel instruments to predict survival in patients starting RRT and compare them with a simple scoring model. The models tended to predict 5-year survival with more accuracy than 1-year survival. Examples of potential applications include informing clinical decision making about the likely benefit of starting RRT and listing for transplantation, adjusting for baseline risk in comparative studies and identifying specific risk groups to participate in clinical trials.

Comorbidity↗

PubMed2001

Analysis of mammalian cytochrome P450 structure and function by site-directed mutagenesis.

Over the past decade, site-directed mutagenesis has become an essential tool in the study of mammalian cytochrome P450 structure-function relationships. Residues affecting substrate specificity, cooperativity, membrane localization, and interactions with redox partners have been identified using a combination of amino-acid sequence alignments, homology modeling, chimeragenesis, and site-directed mutagenesis. As homology modeling and substrate docking technology continue to improve, the ability to predict more precise functions for specific residues will also advance, making it possible to utilize site-directed mutagenesis to test these predictions. Future studies will employ site-directed mutagenesis to learn more about cytochrome P450 substrate access channels, to define the role of residues that do not lie within substrate recognition sites, to engineer additional soluble forms of microsomal cytochromes P450 for x-ray crystallography, and to engineer more efficient enzymes for drug activation and/or bioremediation.

Animals↗

PubMed2001

The learned symmetry concept in revealing quantitative structure-activity relationships with artificial neural networks.

A method to build QSAR models based on substituent constants for congeneric sets of compounds having several topologically equivalent substituent positions was proposed. The approach is based on the application of artificial neural networks (learning to construct nonlinear structure-activity relationships taking into account necessary symmetry properties of training set structures) to a training set expanded by adding the copies of compounds with the same activity values but with permuted assignment of equivalent substituent positions. The better predictive power of these constructed models, as compared with the performances of neural network models for non-expanded sets was demonstrated for the calcium channel blockers of 1,4-dihydropyridine type and for hallucinogenic phenylalkylamines.

Calcium Channel Blockers↗

PubMed2000

Including weight decay in the Rescorla-Wagner model avoids an unlikely prediction.

Weight decay is a common technique for improving generalization in the field of neural networks. If weight decay is added to the Rescorla-Wagner model, a desirable result emerges in that the effects of prior learning are not expected to be permanent. This revised model accommodates an experimental finding called unblocking that was claimed to refute the Rescorla-Wagner model.

Algorithms↗

PubMed2026

Whole-Genome Deep Learning Predicts Chemotherapy Response in Colorectal Cancer.

Chemotherapy response in colorectal cancer (CRC) exhibits significant heterogeneity, with current clinical predictors failing to capture complex genomic determinants of resistance. We developed a hybrid deep learning framework integrating convolutional neural networks (CNNs) and bidirectional long short-term memory (BiLSTM) networks to analyze whole-genome somatic mutations, evolutionary conservation, chromatin accessibility, and 3D genome architecture in 2,546 TCGA patients. An attention mechanism identified predictive genomic regions. The model achieved an AUC of 0.92 (95% CI: 0.89-0.94) in cross-validation and 0.88 (95% CI: 0.85-0.91) in independent validation, outperforming clinical models (ΔAUC = +0.18, p < 0.001). Key predictors included non-coding variants in TP53, KRAS, and PIK3CA regulatory regions. Triple-positive patients (mutations in all 3 regions) had significantly worse progression-free survival (HR = 4.7, p < 0.001). Our framework enables accurate chemotherapy response prediction and reveals novel non-coding resistance mechanisms, advancing precision oncology in CRC.

Humans↗

PubMed2004

Fitness to work of astronauts in conditions of action of the extreme emotional factors.

The theoretical model for the quantitative determination of influence of a level of emotional exertion on the success of human activity is presented. The learning curves of fixed words in the groups with a different level of the emotional exertion are analyzed. The obtained magnitudes of time constant T depending on a type of the emotional exertion are a quantitative measure of the emotional exertion. Time constants could also be of use for a prediction of the characteristic of fitness to work of an astronaut in conditions of extreme factors. The inverse of the sign of influencing on efficiency of activity of the man is detected. The paper offers a mathematical model of the relation between successful activity and motivations or the emotional exertion (Yerkes-Dodson law). Proposed models can serve by the theoretical basis of the quantitative characteristics of an estimation of activity of astronauts in conditions of the emotional factors at a phase of their selection.

Animals↗

PubMed2004

Parallel processing in an identified neural circuit: the Aplysia californica gill-withdrawal response model system.

The response of the gill of Aplysia calfornica Cooper to weak to moderate tactile stimulation of the siphon, the gill-withdrawal response or GWR, has been an important model system for work aimed at understanding the relationship between neural plasticity and simple forms of non-associative and associative learning. Interest in the GWR has been based largely on the hypothesis that the response could be explained adequately by parallel monosynaptic reflex arcs between six parietovisceral ganglion (PVG) gill motor neurons (GMNs) and a cluster of sensory neurons termed the LE cluster. This hypothesis, the Kupfermann-Kandel model, made clear, falsifiable predictions that have stimulated experimental work for many years. Here, we review tests of three predictions of the Kupfermann-Kandel model: (1) that the GWR is a simple, reflexive behaviour graded with stimulus intensity; (2) that central nervous system (CNS) pathways are necessary and sufficient for the GWR; and (3) that activity in six identified GMNs is sufficient to account for the GWR. The available data suggest that (1) a variety of action patterns occur in the context of the GWR; (2) the PVG is not necessary and the diffuse peripheral nervous system (PNS) is sufficient to mediate these action patterns; and (3) the role of any individual GMN in the behaviour varies. Both the control of gill-withdrawal responses, and plasticity in these responses, are broadly distributed across both PNS and CNS pathways. The Kupfermann-Kandel model is inconsistent with the available data and therefore stands rejected. There is, no known causal connection or correlation between the observed plasticity at the identified synapses in this system and behavioural changes during non-associative and associative learning paradigms. Critical examination of these well-studied central pathways suggests that they represent a 'wetware' neural network, architecturally similar to the neural network models of the widely used 'Perceptron' and/or 'Back-propagation' type. Such models may offer a more biologically realistic representation of nervous system organisation than has been thought. In this model, the six parallel GMNs of the CNS correspond to a hidden layer within one module of the gill-control system. That is, the gill-control system appears to be organised as a distributed system with several parallel modules, some of which are neural networks in their own right. A new model is presented here which predicts that the six GMNs serve as components of a 'push-pull' gain control system, along with known but largely unidentified inhibitory motor neurons from the PVG. This 'push-pull' gain control system sets the responsiveness of the peripheral gill motor system. Neither causal nor correlational links between specific forms of neural plasticity and behavioural plasticity have been demonstrated in the GWR model system. However, the GWR model system does provide an opportunity to observe and describe directly the physiological and biochemical mechanisms of distributed representation and parallel processing in a largely identifiable 'wetware' neural network.

Animals↗

PubMed1978

Performance satisfaction of depressives under high and low success conditions.

Evaluated two competing predictions about the effects of high and low success experiences on depressives' satisfaction with performance. No support was found for the prediction derived from Beck's cognitive theory, which posits distorted, negative cognitions about the self as the central dynamic of depression. However, results did tend to support the learned helplessness model's contention that depression is characterized by the perception that reinforcements occur independent of the individual's responses.

Achievement↗

PubMed2006

Communication in genetic counselling for breast/ovarian cancer.

Cancer genetic counselling represents a very special situation of interaction between the geneticist and the counselee, marked by a number of specificities that account for its complexity. Cancer genetic counselling has multiple repercussions, such as identification of a deleterious genetic mutation associated with a high probability of developing breast and/or ovarian cancer, the implementation of preventive measures ranging from close surveillance to the decision to perform mutilating prophylactic surgical procedures, or the impact of the information on the other members of the counselee's family also concerned by the genetic risk. This chapter is based on a review of the literature that has been rapidly growing over recent years and on our clinical expertise as psycho-oncologists and geneticists. We will first present the reasons that make the information so critical. These reasons are both objective (complexity of the genetic information per se, difficulties of understanding the concept of risk) and subjective (information given to people with an emotionally charged family history and a perception of risks closely linked to their representation of cancer). At the same time, the counsellees are charged with the transmission of this information to members of their own family. We will then discuss the various modalities of communication in this setting. While unidirectional transfer of information from the geneticist to the counselee has been the preferred method in cancer genetics for a long time, a model based on patient-centered communication is more adequate in predictive medicine and allows shared decision making. In all cases, the different professionals involved in the process have to learn how to work in a performing cohesion. We also present the main guidelines on the subject and the various underlying objectives with regard to information delivery and the subject's personal experience. Although the psychological impact of genetic counselling consultations raises a number of questions, the results of preliminary studies are reassuring, demonstrating psychological benefits. However, a number of aspects concerning communication in predictive medicine remain to be investigated and improved.

Breast Neoplasms↗

PubMedDate not supplied

Alcohol consumption and presenting problems in an out-patient mental health clinic.

Alcohol use has been shown to co-occur with a range of psychiatric disorders and psycho-social problems in both clinical and general population studies. The current survey of 683 out-patient mental health clients examined the relationship of self-reported alcohol use (as measured by the Quantity-Frequency index and the Retrospective Diary) with self-ratings of common mental health concerns. The South Shore Problem Inventory was developed as a brief self-report instrument to be used for routine assessment and research. The inventory yielded three factors after principal components analysis and Varimax rotation: affective/physiological signs and symptoms (Factor 1), interpersonal/family problems (Factor 2), and vocational/legal difficulties (including a self-rating of substance abuse) (Factor 3). MANOVA revealed that heavy drinking predicted significantly higher problem scores for all three factors. The SSPI showed good initial reliability and utility, and the three sub-scales were theoretically congruent with a social learning model of assessment. The use of similar problem scales and substance abuse indices can be used with a wider variety of both mental health and substance abuse treatment populations to provide routine self-report data for clinical and research applications.

Adult↗

PubMed2005

Decision support of inspired oxygen selection based on Bayesian learning of pulmonary gas exchange parameters.

OBJECTIVE: To investigate if the real-time Bayesian learning of physiological model parameters can be used to support and improve the selection of inspired oxygen fraction. METHODS AND MATERIAL: Supporting the selection of inspired oxygen fraction relies on predictions of arterial oxygen saturation. The efficacy of using these predictions to select inspired oxygen was tested retrospectively in a system for estimating gas exchange parameters of the lung (Automatic Lung Parameter Estimator, ALPE). For the predictions to offer effective decision support they need to be accurate and above all safe. These qualities were tested with data from 16 post-operative cardiac patients, using two different tests. The aim of the first test was to assess retrospectively if the predictions could have supported clinical decisions. The second test sought to establish if the predictions could support improving the efficiency of inspired oxygen selection during an ALPE oxygen titration. RESULTS: The predictions were found to be reasonably accurate, and most importantly safe in both of the tests. CONCLUSION: The method described can be used to support the selection of inspired oxygen fraction, and it has the potential to improve the efficiency of inspired oxygen selection during an oxygen titration.

Bayes Theorem↗

PubMed2002

The acquisition of bimanual coordination is mediated by anisotropic coupling between the hands.

The present study was designed to test two predictions from the coupled oscillator model of multifrequency coordination. First, it was predicted that multifrequency tasks that match the inherent manual asymmetry (i.e., the preferred hand assigned to the faster tempo) would be easier to learn than tasks that do not match the inherent dynamics (i.e., the non-preferred hand assigned to the faster tempo). Second, in the latter case acquisition of the multifrequency coordination would involve a reorganisation of the coupling dynamics such that the faster hand would exert a greater influence on the slower hand than vice versa. Sixteen right-handed volunteers received extensive training on a 2:1 coordination pattern involving a bimanual forearm pronation-supination task. Participants were randomly assigned to one of two groups: 1L:2R in which the preferred right hand performed the higher frequency, or 2L:1R in which the non-preferred left hand performed the higher frequency. The dynamic stability of the patterns was assessed by the ability of participants to maintain the coordination pattern as movement frequency was increased. Changes in the directional coupling between the hands was assessed by transition pathways and lead-lag relationship evident in a 1:1 anti-phase frequency-scaled coordination task performed prior to and following three practice sessions of the 2:1 task. The predicted differential stability between the multifrequency patterns was evident in the initial acquisition sessions but by the end of training the two patterns evidenced equivalent stability. Unexpectedly, for both groups the fast hand displayed greater variability in amplitude and movement frequency than the slow hand perhaps reflecting anchoring afforded to the slow hand by synchronising movement endpoints with the auditory pacing metronome. Analysis of pre- to post-training changes to the coupling dynamics in the 1:1 anti-phase task support the hypothesis that acquisition of the 2L:1R pattern involved reorganisation of the inherent dynamics.

Adult↗

PubMed2006

Complexation between a macromolecule and an amphiphile by Monte Carlo technique.

Using a simple modified version of Larson's model, we studied the complexation between a macromolecule and an amphiphile in a dilute range of concentrations. The main characteristic of amphiphile molecules, that is, the hydrophobicity of the tails and hydrophilicity of the heads, is used to model the self-assembling process. Contrary to the molecular thermodynamics approaches, no prior shape was considered for the aggregates and the system was allowed to choose the most stable structure. For true ensemble averaging, without any synthetic results, configurational bias Monte Carlo and reptation moves are used to produce a Markov chain of configurations. From the results, it is found that the macromolecule causes the clusters of surfactants to be formed at a concentration much lower than the critical micelle concentration. Furthermore, the shape of the clusters tends to be more spherical, which is in line with theory and experiments. From the results, it is learned how a polymer can change the behavior of an amphiphilic molecule. All of the results are in good qualitative agreement with experimental and molecular thermodynamics results. Furthermore, the model predicts network formation between bound clusters at high concentrations of the surfactant.

Journal Article↗

PubMed2006

Quantitative structure-toxicity relationships (QSTRs): a comparative study of various non linear methods. General regression neural network, radial basis function neural network and support vector machine in predicting toxicity of nitro- and cyano- aromatics to Tetrahymena pyriformis.

Prediction of toxicity of 203 nitro- and cyano-aromatic chemicals to Tetrahymena pyriformis was carried out by radial basis function neural network, general regression neural network and support vector machine, in non-linear response surface methodology. Toxicity was predicted from hydrophobicity parameter (log Kow) and maximum superdelocalizability (Amax). Special attention was drawn to prediction ability and robustness of the models, investigated both in a leave-one-out and 10-fold cross validation (CV) processes. The influence that the corresponding changes in the learning sets during these CV processes could have on a common external test set including 41 compounds was also examined. This allowed us to establish the stability of the models. The non linear results slightly outperform (as expected) multilinear relationships (MLR) and also favourably compete with various other non linear approaches recently proposed by Ren (J. Chem. Inf. Comput. Sci., 43 1679 (2003)).

Animals↗

PubMedDate not supplied

Different parameters support generalization and discrimination learning in Drosophila at the flight simulator.

We have used a genetically tractable model system, the fruit fly Drosophila melanogaster to study the interdependence between sensory processing and associative processing on learning performance. We investigated the influence of variations in the physical and predictive properties of color stimuli in several different operant-conditioning procedures on the subsequent learning performance. These procedures included context and stimulus generalization as well as color, compound, and conditional discrimination (colors and patterns). A surprisingly complex dependence of the learning performance on the colors' physical and predictive properties emerged, which was clarified by taking into account the fly-subjective perception of the color stimuli. Based on estimates of the stimuli's color and brightness values, we propose that the different tasks are supported by different parameters of the color stimuli; generalization occurs only if the chromaticity is sufficiently similar, whereas discrimination learning relies on brightness differences.

Animals↗

PubMed2004

Performance of the Alex AVX-2 MIMD architecture in learning the NetTalk database.

The process of training neural networks on parallel architectures has been used to assess the performance of so many parallel machines. In this paper, we are investigating the implementation of backpropagation (BP) on the Alex AVX-2 coarse-grained MIMD machine. A host-worker parallel implementation is carried out in order to train different networks to learn the NetTalk dictionary. First, a computational model is constructed using a single processor to complete the learning process. Also, a communication model for the host-worker topology is developed in order to compute the communication overhead in the broadcasting/gathering process. Both models are then used to predict the machine performance when p processors are used and a comparison with the actual measured performance of the parallel architecture implementation is carried out. Simulation results show that both models can be used effectively to predict the machine performance for the NetTalk problem. Finally, a comparison between the AVX-2 NetTalk implementation and the performance of other parallel platforms is presented.

Artificial Intelligence↗