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At least 1,747 records · Page 97Linked to original sources
PubMed2006

Partially observed branching processes for stochastic epidemics.

At the offset of a (stochastic) epidemic, it is of importance to have a mathematical model that will assist in the making of an informed judgement on whether the epidemic will explode, or will be minor and die out. In this paper, we consider probabilistic inferences related to the event of extinction of a discrete time branching process when this cannot be directly observed. Instead, we are able to observe only a random "trace" of the process, which not only trails the latter, but also directly affects it (in terms of interventions). A simple model is proposed that provides tractability, preserves a marginal branching property, and gives reasonable closed form expressions.

Disease Outbreaks↗
PubMed2003

A probabilistic approach to interpreting verbal autopsies: methodology and preliminary validation in Vietnam.

AIMS: Verbal autopsy (VA) has become an important tool in the past 20 years for determining cause of death in communities where there is no routine registration. In many cases, expert physicians have been used to interpret the VA findings and so assign individual causes of death. However, this is time consuming and not always repeatable. Other approaches such as algorithms and neural networks have been developed in some settings. This paper aims to develop a method that is simple, reliable and consistent, which could represent an advance in VA interpretation. METHODS: This paper describes the development of a Bayesian probability model for VA interpretation as an attempt to find a better approach. This methodology and a preliminary implementation are described, with an evaluation based on VA material from rural Vietnam. RESULTS: The new model was tested against a series of 189 VA interviews from a rural community in Vietnam. Using this very basic model, over 70% of individual causes of death corresponded with those determined by two physicians increasing to over 80% if those cases ascribed to old age or as being indeterminate by the physicians were excluded. DISCUSSION: Although there is a clear need to improve the preliminary model and to test more extensively with larger and more varied datasets, these preliminary results suggest that there may be good potential in this probabilistic approach.

Autopsy↗
PubMed2002

Generalisation: mechanistic and functional explanations.

An overview of mechanistic and functional accounts of stimulus generalisation is given. Mechanistic accounts rely on the process of spreading activation across units representing stimuli. Different models implement the spread in different ways, ranging from diffusion to connectionist networks. A functional account proposed by Shepard analyses the probabilistic structure of the world for invariants. A universal law based on one such invariant claims that under a suitable scaling of the stimulus dimension, generalisation gradients should be approximately exponential in shape. Data from both vertebrates and invertebrates so far uphold Shepard's law. Some data on spatial generalisation in honeybees are presented to illustrate how Shepard's law can be used to determine the metric for combining discrepancies in different stimulus dimensions. The phenomenon of peak shift is discussed. Comments on mechanistic and functional approaches to generalisation are given.

Adaptation, Physiological↗
PubMed1995

A measurement-theoretic analysis of the fuzzy logic model of perception.

The fuzzy logic model of perception (FLMP) is analyzed from a measurement-theoretic perspective. FLMP has an impressive history of fitting factorial data, suggesting that its probabilistic form is valid. The authors raise questions about the underlying processing assumptions of FLMP. Although FLMP parameters are interpreted as fuzzy logic truth values, the authors demonstrate that for several factorial designs widely used in choice experiments, most desirable fuzzy truth value properties fail to hold under permissible rescalings, suggesting that the fuzzy logic interpretation may be unwarranted. The authors show that FLMP's choice rule is equivalent to a version of G. Rasch's (1960) item response theory model, and the nature of FLMP measurement scales is transparent when stated in this form. Statistical inference theory exists for the Rasch model and its equivalent forms. In fact, FLMP can be reparameterized as a simple 2-category logit model, thereby facilitating interpretation of its measurement scales and allowing access to commercially available software for performing statistical inference.

Attention↗
PubMed2000

Cost effectiveness of human immunodeficiency virus postexposure prophylaxis for healthcare workers.

OBJECTIVE: The United States Public Health Service (USPHS) published recommendations for human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) of healthcare workers in May 1998. The aim of this study was to analyse the cost effectiveness of the USPHS PEP guidelines. DESIGN AND SETTING: This was a modelling study in the setting of the US healthcare system in 1989. The analysis was performed from the societal perspective; however, only HIV healthcare costs were considered and health-related losses of productivity were not included. METHODS: A decision tree incorporating a Markov model was created for 4 PEP strategies: the current USPHS recommendations, triple drug therapy, zidovudine monotherapy or no prophylaxis. A probabilistic sensitivity analysis using a Monte Carlo simulation was performed. Confidence intervals (CIs) around cost-effectiveness estimates were estimated by a bootstrapping method. RESULTS: The costs (in 1997 US dollars) per quality-adjusted life-year (QALY) save by each strategy were as follows: monotherapy $US688 (95% CI: $US624 to $US750); USPHS recommendations $US5211 (95% CI: $US5126 to $US5293); and triple drug therapy $US8827 (95% CI: $US8715 to $US8940). The marginal cost per year of life saved was: USPHS recommendations $US81 987 (95% CI: $US80 437 to $US83 689); triple drug therapy $US970 451 (95% CI: $US924 786 to $US 1 014 429). Sensitivity testing showed that estimates of the probability of seroconversion for each category of exposure were most influential, but did not change the order of strategies in the baseline analysis. With the prolonged HIV stage durations and increased costs associated with recent innovations in HIV therapy, the marginal cost effectiveness of the USPHS PEP strategy was decreased to $US62 497/QALY saved. All 3 intervention strategies were cost effective compared with no postexposure prophylaxis. CONCLUSIONS: Current USPHS PEP recommendations are marginally cost effective compared with monotherapy, but the additional efficacy of triple drug therapy for all risk categories is rewarded by only a small reduction in HIV infections at great expense. For the foreseeable future, assuming innovations in therapy that employ expensive drug combinations earlier in the HIV disease course to extend life expectancy and the increasing prevalence of HIV drug resistance, our model supports the use of the USPHS PEP guidelines.

Cost-Benefit Analysis↗
PubMed2007

Spatial localization accuracy of radiologists in free-response studies: Inferring perceptual FROC curves from mark-rating data.

RATIONALE AND OBJECTIVES: Free-response data consist of a set of mark-ratings pairs. Before analysis, the data are classified or "scored" into lesion and non-lesion localizations. The scoring is done by choosing an acceptance-radius and classifying marks within the acceptance-radius of lesion centers as lesion localizations, and all other marks are classified as non-lesion localizations. The scored data are plotted as a free-response receiver operating characteristic (FROC) curve, essentially a plot of appropriately normalized numbers of lesion localizations vs. non-lesion localizations. Scored FROC curves are frequently used to compare imaging systems and computer-aided detection (CAD) algorithms. However, the choice of acceptance-radius is arbitrary. This makes it difficult to compare curves from different studies and to estimate true performance. MATERIALS AND METHODS: To resolve this issue the concept of two types of marks is introduced: perceptual hits and perceptual misses. A perceptual hit is a mark made in response to the observer seeing the lesion. A perceptual miss is a mark made in response to the observer seeing a (lesion-like) non-lesion. A method of estimating the most probable numbers of perceptual hits and misses is described. This allows one to plot a perceptual FROC operating point and by extension a perceptual FROC curve. Unlike a scored FROC operating point, a perceptual point is independent of the choice of acceptance-radius. The method does not allow one to identify individual marks as perceptual hits or misses-only the most probable numbers. It is based on a three-parameter statistical model of the spatial distributions of perceptual hits and misses relative to lesion centers. RESULTS: The method has been applied to an observer dataset in which mammographers and residents with different levels of experience were asked to locate lesions in mammograms. The perceptual operating points suggest superior performance for the mammographers and equivalent performance for residents in the first and second mammography rotations. These results and the model validation are preliminary as they are based on a small dataset. CONCLUSION: The significance of this study is showing that it is possible to probabilistically determine if a mark resulted from seeing a lesion or a non-lesion. Using the method developed in this study one could perform acceptance-radius independent estimation of observer performance.

Image Interpretation, Computer-Assisted↗
PubMedDate not supplied

SARA: a cognitive process model to simulate the anchoring effect and hindsight bias.

The cognitive process model "SARA" aims to explain the anchoring effect and hindsight bias by making detailed assumptions about the representation and alteration of item-specific knowledge. The model assumes that all processes, namely generating an estimate, encoding new information (i.e., the "anchor"), and reconstructing a previously generated estimate, are based on a probabilistic sampling process. Sampling probes long-term memory in order to retrieve information into working memory. Retrieval depends on the associative strength between this information and the currently active retrieval cues. Encoding the anchor may alter this associative pattern ("selective activation") or the anchor may serve as a retrieval cue, thus directing memory search ("biased reconstruction"). Both processes lead to systematically changed retrieval probabilities, thus causing the anchoring effect or hindsight bias. The model is completely formalised and implemented as a computer program. A series of simulations demonstrates the power of SARA to reproduce empirical findings and to predict new ones.

Association↗
PubMed2006

A generalization of the PST algorithm: modeling the sparse nature of protein sequences.

MOTIVATION: A central problem in genomics is to determine the function of a protein using the information contained in its amino acid sequence. Variable length Markov chains (VLMC) are a promising class of models that can effectively classify proteins into families and they can be estimated in linear time and space. RESULTS: We introduce a new algorithm, called Sparse Probabilistic Suffix Trees (SPST), that identifies equivalence between the contexts of a VLMC. We show that, in many cases, the identification of these equivalence can improve the classification rate of the classical Probabilistic Suffix Trees (PST) algorithm. We also show that better classification can be achieved by identifying representative fingerprints in the amino acid chains, and this variation in the SPST algorithm is called F-SPST.

Algorithms↗
PubMed2003

Control of LH secretory-burst frequency and interpulse-interval regularity in women.

Hypothalamic neurons generate discrete bursts of gonadotropin-releasing hormone (GnRH) and thereby pulses of luteinizing hormone (LH) at randomly timed intervals centered on a probabilistic mean frequency. We tested the hypothesis that physiological mechanisms govern not only the number but also the stochastic dispersion of the GnRH/LH pulse-renewal process in humans; for example, in young women in the early (EF) and late (LF) follicular and midluteal (ML) phases of the menstrual cycle (n = 18) and in postmenopausal individuals (PM, n = 16). To this end, we quantify stochastic interpulse variability by way of the order-independent, two-parameter Weibull renewal process (Keenan DM and Veldhuis J. Am J Physiol Regul Integr Comp Physiol 281: R1917-R1924, 2001) and the sequence-specific, model-free approximate-entropy statistic (ApEn) (Pincus SM. Proc Natl Acad Sci USA 88: 2297-2301, 1991). Statistical testing unveiled 1) reduced probabilistic mean LH secretory-burst frequency (lower lambda of the Weibull distribution) in ML compared with each of EF, LF, and PM (P < 0.001); 2) quantifiably more regular LH interburst-interval sets (elevated gamma of the Weibull density) in PM than in each of EF, LF, and ML (P < 0.01); 3) uniquely prolonged latency to maximal LH secretion within individual secretory bursts in ML (P < 0.01); and 4) comparably mean random, sequential LH interburst-interval and mass values (normalized ApEn) among the distinct hormonal milieus. From these data, we postulate that sex steroids and age determine daily LH secretory-burst number, quantifiable pulse-renewal variability, and secretory-waveform evolution.

Adolescent↗
PubMed2005

The dynamics of scaling: a memory-based anchor model of category rating and absolute identification.

A memory-based scaling model--ANCHOR--is proposed and tested. The perceived magnitude of the target stimulus is compared with a set of anchors in memory. Anchor selection is probabilistic and sensitive to similarity, base-level strength, and recency. The winning anchor provides a reference point near the target and thereby converts the global scaling problem into a local comparison. An explicit correction strategy determines the final response. Two incremental learning mechanisms update the locations and base-level activations of the anchors. This gives rise to sequential, context, transfer, practice, and other dynamic effects. The scale unfolds as an adaptive map. A hierarchy of models is tested on a battery of quantitative measures from 2 experiments in absolute identification and category rating.

Humans↗
PubMedDate not supplied

Impact of generic drug entry on cost-effectiveness analysis.

The market share of generic drugs has grown substantially since the passage of the Waxman-Hatch Act, increasing from 19% in 1984 to 50% in 2001. At entry, the generic drugs typically are priced lower than brand-name drugs; thus, incorporating the impact of the generic drug entry introduces an additional source of uncertainty in economic models as both the timing of entry and the level of generic drug pricing are subject to variation. In this article, the authors explored the impact of generic drug entry on cost-effectiveness analyses of new or brand-name drugs. Using a mathematical model, they argue that failure to incorporate the impact of generic drug entry will underestimate the incremental cost-effectiveness ratio (ICER) and, thus, overstate the economic benefit of the new product. The authors provide 2 examples to illustrate such impact on short-term and long-term cost-effectiveness analyses. To better assess the uncertainty associated with the impact of generic drug entry, in addition to a deterministic analysis, they also employed a Bayesian probabilistic approach to analyze these examples and presented the results using cost-effectiveness acceptability curves. They conclude that incorporating generic drug entry into pharmacoeconomic models will yield more accurate projections of the ICER and lead to better decision making.

Bayes Theorem↗
PubMed1997

Estimation of the interindividual variability in the one-compartment pharmacokinetic model for methylmercury: implications for the derivation of a reference dose.

A critical step in the U.S. EPA's derivation of an Reference Dose (RfD) for methylmercury is conversion of the maternal hair Hg concentration of 11 ppm to average daily intake using the one-compartment pharmacokinetic model. A default uncertainty factor (UF) adjustment of 3 for interindividual variability was then applied to this conversion. A probabilistic (Monte Carlo) analysis is presented estimating the interindividual variability inherent in this dose conversion for women 18-40 years old based on data in the scientific literature. The dose of 1.1 micrograms/kg/day, calculated by the U.S. EPA to correspond to 11 ppm Hg in hair, is estimated in this analysis to be larger than 94-99% of corresponding doses. The application of a UF of 3 to this U.S. EPA value gives a dose which is estimated to be larger than 28-73% of corresponding doses. This analysis suggests that if the dose conversion in the RfD is intended to be inclusive of 95-99% of women 18-40, the daily intake should be set at 0.1-0.3 microgram/kg/day. The RfD of 0.03-0.1 microgram/kg/day, derived from this dose by the U.S. EPA's application of an additional UF of 3 for additional toxicologic concerns, is somewhat smaller than the current RfD of 0.1 microgram/kg/day.

Absorption↗
PubMed1995

WENDEC: a deconvolution program for processing hormone time-series.

The estimation of the glandular secretory rate from time-series of hormone concentration in plasma can be formulated as a deconvolution problem. In particular, the paper addresses the analysis of frequently sampled data collected in order to study spontaneous pulsatile secretion. Standard deconvolution methods do not allow for the non-negativity constraint and the presence of high-frequency components in the secretory rate. In order to overcome the intrinsic ill-conditioning of the problem, the maximum entropy method is used to obtain a probabilistic representation of the prior knowledge concerning the unknown secretory signal, thus leading to a White Exponential Noise (WEN) model. The deconvolution problem is then posed within a Bayesian framework and solved by means of Maximum-A-Posteriori estimation. The program that implements the algorithm handles non-negativity constraints, provides confidence intervals, and is computationally and memory efficient.

Algorithms↗
PubMed2002

Origins and estimates of uncertainty in predictions of twenty-first century temperature rise.

Predictions of temperature rise over the twenty-first century are necessarily uncertain, both because the sensitivity of the climate system to changing atmospheric greenhouse-gas concentrations, as well as the rate of ocean heat uptake, is poorly quantified and because future influences on climate-of anthropogenic as well as natural origin-are difficult to predict. Past observations have been used to help constrain the range of uncertainties in future warming rates, but under the assumption of a particular scenario of future emissions. Here we investigate the relative importance of the uncertainty in climate response to a particular emissions scenario versus the uncertainty caused by the differences between future emissions scenarios for our estimates of future change. We present probabilistic forecasts of global-mean temperatures for four representative scenarios for future emissions, obtained with a comprehensive climate model. We find that, in the absence of policies to mitigate climate change, global-mean temperature rise is insensitive to the differences in the emissions scenarios over the next four decades. We also show that in the future, as the signal of climate change emerges further, the predictions will become better constrained.

Journal Article↗
PubMed2003

Classification analysis of P-glycoprotein substrate specificity.

Prediction of P-glycoprotein substrate specificity (S(PGP)) can be viewed as a constituent part of a compound's "pharmaceutical profiling" in drug design. This task is difficult to achieve due to several factors that raised many contradictory opinions: (i) the disparity between the S(PGP) values obtained in different assays, (ii) the confusion between Pgp substrates and inhibitors, (iii) the confusion between lipophilicity and amphiphilicity of Pgp substrates, and (iv) the dilemma of describing class-specific relationships when Pgp has no binding sites of high ligand specificity. In this work, we compiled S(PGP) data for 1000 compounds. All data were represented in a binary format, assigning S(PGP) = 1 for substrates and S(PGP) = 0 for non-substrates. Each value was ranked according to the reliability of experimental assay. Two data sets were considered. Set 1 included 220 compounds with S(PGP) from polarized transport across MDR1 transfected cell monolayers. Set 2 included the entire list of 1000 compounds, with S(PGP) values of generally lower reliability. Both sets were analysed using a stepwise classification structure-activity relationship (C-SAR) method, leading to derivation of simple rules for crude estimation of S(PGP) values. The obtained rules are based on the following factors: (i) compound's size expressed through molar weight or volume, (ii) H-accepting given by the Abraham's beta (that can be crudely approximated by the sum of O and N atoms), and (iii) ionization given by the acid and base pKa values. Very roughly, S(PGP) can be estimated by the "rule of fours". Compounds with (N + O) > or = 8, MW > 400 and acid pKa > 4 are likely to be Pgp substrates, whereas compounds with (N + O) < or = 4, MW < 400 and base pKa < 8 are likely to be non-substrates. The obtained results support the view that Pgp functioning can be compared to a complex "mini-pharmacokinetic" system with fuzzy specificity. This system can be described by a probabilistic version of Abraham's solvation equation, suggesting a certain similarity between Pgp transport and chromatographic retention. The chromatographic model does not work in the case of "marginal" compounds with properties close to the "global" physicochemical cut-offs. In the latter case various class-specific rules must be considered. These can be associated with the "amphiphilicity" and "biological similarity" of compounds. The definition of class-specific effects entails construction of the knowledge base that can be very useful in ADME profiling of new drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Probabilistic secretion of quanta in the central nervous system: granule cell synaptic control of pattern separation and activity regulation.

The implications of probabilistic secretion of quanta for the functioning of neural networks in the central nervous system have been explored. A model of stochastic secretion at synapses in simple networks, consisting of large numbers of granule cells and a relatively small number of inhibitory interneurons, has been analysed. Such networks occur in the input to the cerebellum Purkinje cells as well as to hippocampal CA3 pyramidal cells and to pyramidal cells in the visual cortex. In this model the input axons terminate on granule cells as well as on an inhibitory interneuron that projects to the granule cells. Stochastic secretion at these synapses involves both temporal variability in secretion at single synapses in the network as well as spatial variability in the secretion at different synapses. The role of this stochastic variability in controlling the size of the granule cell output to a level independent of the size of the input and in separating overlapping inputs has been determined analytically as well as by simulation. The regulation of granule-cell output activity to a reasonably constant value for different size inputs does not occur in the absence of an inhibitory interneuron when both spatial and temporal stochastic variability occurs at the remaining synapses; it is still very poor in the presence of such an interneuron but in the absence of stochastic variability. However, quite good regulation is achieved when the inhibitory interneuron is present with spatial and temporal stochastic variability of secretion at synapses in the network. Excellent regulation is achieved if, in addition, allowance is made for the nonlinear behaviour of the input-output characteristics of inhibitory interneurons. The capacity of granule-cell networks to separate overlapping patterns of activity on their inputs is adequate, with spatial variability in the secretion at synapses, but is improved if there is also temporal variability in the stochastic secretion at individual synapses, although this is at the expense of reliability in the network. Other factors which improve pattern separation are control of the output to very low activity levels, and a restriction on the cumulative size of the excitatory input terminals of each granule cell. Application of the theory to the input neural networks of the cerebellum and the hippocampus shows the role of stochastic variability in quantal transmission in determining the capacity of these networks for pattern separation and activity regulation.

Animals↗
PubMed2001

Nature of phase transitions in a probabilistic cellular automaton with two absorbing states.

We present a probabilistic cellular automaton with two absorbing states, which can be considered a natural extension of the Domany-Kinzel model. Despite its simplicity, it shows a very rich phase diagram, with two second-order and one first-order transition lines that meet at a bicritical point. We study the phase transitions and the critical behavior of the model using mean field approximations, direct numerical simulations and field theory. The second-order critical curves and the kink critical dynamics are found to be in the directed percolation and parity conservation universality classes, respectively. The first-order phase transition is put in evidence by examining the hysteresis cycle. We also study the "chaotic" phase, in which two replicas evolving with the same noise diverge, using mean field and numerical techniques. Finally, we show how the shape of the potential of the field-theoretic formulation of the problem can be obtained by direct numerical simulations.

Journal Article↗
PubMed1976

Styles of decision-making and probability appraisal in selected obsessional and phobic patients.

A questionnaire was administered to obsessional and phobic patients and normal subjects. The results of this survey confirmed the prediction that a sizeable proportion of phobic patients report irrational expectations associated with their most feared situations. A group of phobics who reported irrational expectations, a group of obsessionals who reported an abnormal degree of checking behaviour and a group of normal subjects, took part in a probabilistic inference task. Several predictions about the differential performance of these groups were fulfilled. (i) Deviations from the optimal model for individual responses were greatest in the obsessional group. (ii) When Neuroticism was partialled out, the three groups differed with respect to amount of evidence required prior to a decision, the obsessional group having the highest score on this variable. (iii) The phobic group were more likely than the other two groups to make irrational event predictions.

Age Factors↗