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PubMed2006

A probabilistic arsenic exposure assessment for children who contact chromated copper arsenate (CCA)-treated playsets and decks, Part 2: Sensitivity and uncertainty analyses.

A probabilistic model (SHEDS-Wood) was developed to examine children's exposure and dose to chromated copper arsenate (CCA)-treated wood, as described in Part 1 of this two-part article. This Part 2 article discusses sensitivity and uncertainty analyses conducted to assess the key model inputs and areas of needed research for children's exposure to CCA-treated playsets and decks. The following types of analyses were conducted: (1) sensitivity analyses using a percentile scaling approach and multiple stepwise regression; and (2) uncertainty analyses using the bootstrap and two-stage Monte Carlo techniques. The five most important variables, based on both sensitivity and uncertainty analyses, were: wood surface residue-to-skin transfer efficiency; wood surface residue levels; fraction of hand surface area mouthed per mouthing event; average fraction of nonresidential outdoor time a child plays on/around CCA-treated public playsets; and frequency of hand washing. In general, there was a factor of 8 for the 5th and 95th percentiles and a factor of 4 for the 50th percentile in the uncertainty of predicted population dose estimates due to parameter uncertainty. Data were available for most of the key model inputs identified with sensitivity and uncertainty analyses; however, there were few or no data for some key inputs. To evaluate and improve the accuracy of model results, future measurement studies should obtain longitudinal time-activity diary information on children, spatial and temporal measurements of residue and soil concentrations on or near CCA-treated playsets and decks, and key exposure factors. Future studies should also address other sources of uncertainty in addition to parameter uncertainty, such as scenario and model uncertainty.

Arsenates↗

PubMed2006

Consumer-phase Salmonella enterica serovar enteritidis risk assessment for egg-containing food products.

We describe a one-dimensional probabilistic model of the role of domestic food handling behaviors on salmonellosis risk associated with the consumption of eggs and egg-containing foods. Six categories of egg-containing foods were defined based on the amount of egg contained in the food, whether eggs are pooled, and the degree of cooking practiced by consumers. We used bootstrap simulation to quantify uncertainty in risk estimates due to sampling error, and sensitivity analysis to identify key sources of variability and uncertainty in the model. Because of typical model characteristics such as nonlinearity, interaction between inputs, thresholds, and saturation points, Sobol's method, a novel sensitivity analysis approach, was used to identify key sources of variability. Based on the mean probability of illness, examples of foods from the food categories ranked from most to least risk of illness were: (1) home-made salad dressings/ice cream; (2) fried eggs/boiled eggs; (3) omelettes; and (4) baked foods/breads. For food categories that may include uncooked eggs (e.g., home-made salad dressings/ice cream), consumer handling conditions such as storage time and temperature after food preparation were the key sources of variability. In contrast, for food categories associated with undercooked eggs (e.g., fried/soft-boiled eggs), the initial level of Salmonella contamination and the log10 reduction due to cooking were the key sources of variability. Important sources of uncertainty varied with both the risk percentile and the food category under consideration. This work adds to previous risk assessments focused on egg production and storage practices, and provides a science-based approach to inform consumer risk communications regarding safe egg handling practices.

Bacteriophage Typing↗

PubMed1986

Simulation of mechanical to neural transduction in the auditory receptor.

A probabilistic model is described for transmitter release from hair cells, auditory neuron EPSP's, and discharge patterns. The model assumes that the release fraction of the transmitter is a function of stimulus intensity. It further assumes that some of this transmitter substance is taken back into the cell while some is irretrievably lost from the cleft. These assumptions differ from other recent models which propose multiple release sites, fixed release fractions, and no transmitter reuptake. The model produces realistic mammalian rate intensity functions, interval and period histograms, incremental responses, and adaptation effects. It mimics successfully the adaptation of successive EPSP amplitudes of the afferent neuron of the goldfish sacculus and offers a reinterpretation of the implications of these studies for hair cell synaptic mechanism.

Animals↗

PubMed2004

Species coextinctions and the biodiversity crisis.

To assess the coextinction of species (the loss of a species upon the loss of another), we present a probabilistic model, scaled with empirical data. The model examines the relationship between coextinction levels (proportion of species extinct) of affiliates and their hosts across a wide range of coevolved interspecific systems: pollinating Ficus wasps and Ficus, parasites and their hosts, butterflies and their larval host plants, and ant butterflies and their host ants. Applying a nomographic method based on mean host specificity (number of host species per affiliate species), we estimate that 6300 affiliate species are "coendangered" with host species currently listed as endangered. Current extinction estimates need to be recalibrated by taking species coextinctions into account.

Animals↗

PubMed1999

A computational screen for methylation guide snoRNAs in yeast.

Small nucleolar RNAs (snoRNAs) are required for ribose 2'-O-methylation of eukaryotic ribosomal RNA. Many of the genes for this snoRNA family have remained unidentified in Saccharomyces cerevisiae, despite the availability of a complete genome sequence. Probabilistic modeling methods akin to those used in speech recognition and computational linguistics were used to computationally screen the yeast genome and identify 22 methylation guide snoRNAs, snR50 to snR71. Gene disruptions and other experimental characterization confirmed their methylation guide function. In total, 51 of the 55 ribose methylated sites in yeast ribosomal RNA were assigned to 41 different guide snoRNAs.

Algorithms↗

PubMed2000

Homologs of small nucleolar RNAs in Archaea.

In eukaryotes, dozens of posttranscriptional modifications are directed to specific nucleotides in ribosomal RNAs (rRNAs) by small nucleolar RNAs (snoRNAs). We identified homologs of snoRNA genes in both branches of the Archaea. Eighteen small sno-like RNAs (sRNAs) were cloned from the archaeon Sulfolobus acidocaldarius by coimmunoprecipitation with archaeal fibrillarin and NOP56, the homologs of eukaryotic snoRNA-associated proteins. We trained a probabilistic model on these sRNAs to search for more sRNAs in archaeal genomic sequences. Over 200 additional sRNAs were identified in seven archaeal genomes representing both the Crenarchaeota and the Euryarchaeota. snoRNA-based rRNA processing was therefore probably present in the last common ancestor of Archaea and Eukarya, predating the evolution of a morphologically distinct nucleolus.

Archaea↗

PubMed1978

Computer-assisted identification of anaerobic bacteria.

A computer program was developed to identify anaerobic bacteria by using simultaneous pattern recognition via a Bayesian probabilistic model. The system is intended for use as a rapid, precise, and reproducible aid in the identification of unknown isolates. The program operates on a data base of 28 genera comprising 238 species of anaerobic bacteria that can be separated by the program. Input to the program consists of biochemical and gas chromatographic test results in binary format. The system is flexible and yields outputs of: (i) most probable species, (ii) significant test results conflicting with established data, and (iii) differential tests of significance for missing test results.

Anaerobiosis↗

PubMed1988

The classification of ethnic status using name information.

Methodology is developed to classify ethnic status by name using a simple probabilistic model. This method involves the consideration of four rules which may be used to classify individuals using three name components (first, middle and last names). In order to do this, conditional probabilities of ethnic status are estimated from a sample in which the ethnic status is known. Using a split sample technique the sensitivity and specificity of this methodology were examined in a data set of death registrations. Each of the classification rules performed well on the data from which they were constructed but were not as efficient when applied to another population. Nevertheless a model (linear), in which the sum of the conditional probabilities of each home component is used, achieved a sensitivity and specificity of 97% and 100% respectively in males and 89% and 100% in females.

Canada↗

PubMed2003

Decomposing gene expression into cellular processes.

We propose a probabilistic model for cellular processes, and an algorithm for discovering them from gene expression data. A process is associated with a set of genes that participate in it; unlike clustering techniques, our model allows genes to participate in multiple processes. Each process may be active to a different degree in each experiment. The expression measurement for gene g in array a is a sum, over all processes in which g participates, of the activity levels of these processes in array a. We describe an iterative procedure, based on the EM algorithm, for decomposing the expression matrix into a given number of processes. We present results on Yeast gene expression data, which indicate that our approach identifies real biological processes.

Algorithms↗

PubMed1985

Microsphere passage through intestinal circulation: via shunts or capillaries?

Significant quantities of 9-micron microspheres (20-30%) are not trapped in the intestine following intracardiac or intra-arterial injection, but reach venous blood. Some investigators propose that the passage of 9-micron spheres measures blood flow through noncapillary connections. Because frequency distributions of intestinal capillary diameters and 9-micron spheres overlap, microspheres could simply pass through capillaries. Therefore, we developed simple probabilistic models to predict both the size distribution and the percentage of injected spheres [9 +/- 1 (SD) micron] that should appear in venous blood. Chief assumptions in models are that microsphere delivery and sphere diameter are independent and that microspheres pass through capillaries of equal or larger size. The passage predicted by the models was consistent with values in canine intestinal circulation, demonstrating that passage through capillaries [7.38 +/- 1.4 (SD) micron] adequately accounts for spheres in venous blood. Because the diameters of nominal 9-micron spheres were distributed too narrowly to show a marked sieving effect on passage through the intestinal circulation, we also injected microspheres varying from 5 to 20 micron in diameter. This mixture demonstrated a marked sieving effect. The predicted frequency distribution for microsphere diameters in venous blood agreed with the observed distribution. Our models demonstrate that the passage of 9-micron spheres through capillaries, rather than through "shunts," adequately accounts for the appearance of spheres in venous blood and suggests that the frequency distribution of venous microspheres can provide an in vivo method for estimating the frequency distribution of intestinal capillary diameters.

Animals↗

PubMed1992

Predicting the time of occurrence of decompression sickness.

Probabilistic models and maximum likelihood estimation have been used to predict the occurrence of decompression sickness (DCS). We indicate a means of extending the maximum likelihood parameter estimation procedure to make use of knowledge of the time at which DCS occurs. Two models were compared in fitting a data set of nearly 1,000 exposures, in which greater than 50 cases of DCS have known times of symptom onset. The additional information provided by the time at which DCS occurred gave us better estimates of model parameters. It was also possible to discriminate between good models, which predict both the occurrence of DCS and the time at which symptoms occur, and poorer models, which may predict only the overall occurrence. The refined models may be useful in new applications for customizing decompression strategies during complex dives involving various times at several different depths. Conditional probabilities of DCS for such dives may be reckoned as the dive is taking place and the decompression strategy adjusted to circumstance. Some of the mechanistic implications and the assumptions needed for safe application of decompression strategies on the basis of conditional probabilities are discussed.

Decompression Sickness↗

PubMed2001

On the likelihood of decompression sickness during H(2) biochemical decompression in pigs.

A probabilistic model was used to predict decompression sickness (DCS) outcome in pigs during exposures to hyperbaric H(2) to quantify the effects of H(2) biochemical decompression, a process in which metabolism of H(2) by intestinal microbes facilitates decompression. The data set included 109 exposures to 22-26 atm, ca. 88% H(2), 9% He, 2% O(2), 1% N(2), for 0.5-24 h. Single exponential kinetics described the tissue partial pressures (Ptis) of H(2) and He at time t: Ptis = integral (Pamb - Ptis). tau(-1) dt, where Pamb is ambient pressure and tau is a time constant. The probability of DCS [P(DCS)] was predicted from the risk function: P(DCS) = 1 - e(-r), where r = integral (Ptis(H(2)) + Ptis(He) - Thr - Pamb). Pamb(-1) dt, and Thr is a threshold parameter. Inclusion of a parameter (A) to estimate the effect of H(2) metabolism on P(DCS): Ptis(H(2)) = integral (Pamb - A - Ptis(H(2))). tau(-1) dt, significantly improved the prediction of P(DCS). Thus lower P(DCS) was predicted by microbial H(2) metabolism during H(2) biochemical decompression.

Animals↗

PubMed1988

Nonuniform release probabilities underlie quantal synaptic transmission at a mammalian excitatory central synapse.

1. Excitatory postsynaptic potentials (EPSPs) evoked by impulses in single group I muscle afferents were recorded in dorsal spinocerebellar tract (DSCT) neurons in the spinal cords of anesthetized cats. Fluctuations in the amplitude of these single-fiber EPSPs were determined from measurements of EPSP peak amplitude and contaminating noise (800-4600 trials). 2. In a previous study at this connection, we found that these single-fiber EPSPs fluctuated in amplitude between approximately equal, or quantal, increments. However, these quantal fluctuations could not be described by simple binomial statistics (39). In the present study we have applied further analysis procedures to the same single-fiber EPSPs to formulate a more appropriate probabilistic model of transmission at this connection. 3. In the first stage we have demonstrated that each single-fiber EPSP is composed of the sum of a number (3-30) of uniform quantal events, and that there is extremely little variability in the amplitude of the single quantal event. 4. In a further procedure, we have demonstrated that these quantal fluctuations can be described by a compound binomial model in which each underlying quantal event is associated with a particular, but independent, release probability. The results of this analysis indicate that the probability of transmitter release varies considerably between release sites at this connection. (The use of such a compound binomial model reemphasized previous warnings concerning the interpretation of the results of all statistical models of quantal release. Problems regarding the non-unique nature of N, the total population of quantal events, and other such difficulties are discussed.) 5. A model of transmission at this connection is proposed, in which there are a number of "active" release sites, exhibiting generally high release probabilities, and a number of "reserve" release sites, with zero, or close to zero, release probability. The physiological consequences of such a scheme are discussed.

Afferent Pathways↗

PubMed1997

Synaptic connectivity in cultured hypothalamic neuronal networks.

We have developed a novel approach to analyze the synaptic connectivity of spontaneously active networks of hypothalamic neurons in culture. Synaptic connections were identified by recording simultaneously from pairs of neurons using the whole cell configuration of the patch-clamp technique and testing for evoked postsynaptic current responses to electrical stimulation of one of the neurons. Excitatory and inhibitory responses were distinguished on the basis of their voltage and time dependence. The distribution of latencies between presynaptic stimulation and postsynaptic response showed multiple peaks at regular intervals, suggesting that responses via both monosynaptic and polysynaptic paths were recorded. The probability that an excitatory event is transmitted to another excitatory neuron and results in an above-threshold stimulation was found to be only one in three to four. This low value indicates that in addition to evoked synaptic responses other sources of excitatory drive must contribute to the spontaneous activity observed in these networks. The various types of synaptic connections (excitatory and inhibitory, monosynaptic, and polysynaptic) were counted, and the observations analyzed using a probabilistic model of the network structure. This analysis provides estimates for the ratio of inhibitory to excitatory neurons in the network (1:1.5) and for the ratio of postsynaptic cells receiving input from a single GABAergic or glutamatergic neuron (3:1). The total number of inhibitory synaptic connections was twice that of excitatory connections. Cell pairs mutually connected by an excitatory and an inhibitory synapse occurred significantly more often than predicted by a random process. These results suggests that the formation of neuronal networks in vitro is controlled by cellular mechanisms that favor inhibitory connections in general and specifically enhance the formation of reciprocal connections between pairs of excitatory and inhibitory neurons. These mechanisms may contribute to network formation and function in vivo.

Animals↗

PubMed1998

The statistical distribution of wrist movements during sleep.

The purpose of this work was to describe the basic statistical properties of the process of production of movements measured with a wrist actimeter, along a complete sleep period in normal human subjects. Two distinct types of random magnitudes were considered to analyze the data, the times between successive groups of movements and the number of movements at each fixed time (1 min) measurement epoch. Suitable probabilistic models for the two variates were chosen, fitting theoretical distribution functions to the observed data. It is concluded that interval data fit a one-parameter exponential distribution, while the number of movements fit a two-parameter negative binomial distribution. The estimated values of these parameters, besides being necessary to perform further statistical analysis, are a measure of the intensity and frequency of the movements. Finally the relationship between polysomnography measures and the elicited parameters was studied.

Adult↗

PubMedDate not supplied

A probabilistic estimation of fluoride intake by infants up to the age of 4 months from infant formula reconstituted with tap water in the fluoridated regions of Ireland.

Two probabilistic models were developed to estimate the acute and chronic exposure to fluoride of exclusively formula-fed infants aged 0-4 months as a result of the consumption of infant formula reconstituted with fluoridated tap water in Ireland. The estimates were based on calculated infant formula consumption and accepted body weight standards, together with reported concentrations of fluoride in infant formula powder and measured values for the fluoride content of water in Ireland. The mean acute exposure of infants to fluoride on any single day in areas served by 387 fluoridated water supplies was estimated to be between 0.11 and 0.14 mg/kg body weight depending on age group (95th percentiles 0.2 and 0.26 mg/kg b.w., respectively). These predicted intakes were well below the intake of fluoride associated with acute toxic effects, which is considered to be 5 mg fluoride (F(-))/kg body weight. The mean chronic exposure of infants to fluoride was estimated to be between 0.106 and 0.170 mg/kg b.w./day depending on body weight (95th percentiles 0.108 and 0.172 mg/kg b.w./day, respectively). This estimate described the average daily fluoride intake of infants during the first 4 months of life residing in the areas served by 226 water supplies that achieved an average yearly fluoride concentration below 1.03 mg/l. Dental fluorosis may be considered to be the only risk at these low doses and from our work it is estimated that there is a very low risk of moderate dental fluorosis of the permanent dentition in infants exposed to fluoride at these levels.

Age Factors↗

PubMed2005

Cost-effectiveness analysis of thrombolytic treatment for stroke.

PURPOSE: Thrombolysis is used to treat stroke patients based on the National Institute of Neurological Disorders and Stroke study and meta-analysis results. We present a cost-effectiveness analysis based on a probabilistic model of the use of thrombolytic therapy in stroke treatment. METHODS: We surveyed patients who had had a stroke during their hospital stay and examined them again 1 year after release from the hospital to obtain data on costs and natural history. We then calculated utility weights using the European Quality of Life Questionnaire. When the model runs, 4,000 Monte Carlo simulations are undertaken in which each parameter value changes depending on its probability distribution. The results are expressed in terms of the cost-effectiveness plane and the cost-effectiveness acceptability curve. RESULTS: We studied 435 patients, of whom 304 had had an ischemic stroke. One year later, 216 were still alive. The mean utility values were 0.22 for disabled patients and 0.77 for autonomous patients. The incremental cost-effectiveness ratio (ICER) obtained by means of the parameters was -19,000 EUR/quality-adjusted life year, reflecting a saving of 6,000 EUR and a health benefit for patients. The cost-effectiveness plane showed that thrombolysis was a dominant variable in 96.1% of simulations. In the acceptability curves, only 0.4 of simulations obtained an ICER higher than the societal threshold. CONCLUSIONS: Thrombolytic therapy seems to be a useful intervention because it is inexpensive and cost-effective. The key factor is the decreased rate of disability, which results in a better quality of life of the patient and lower costs.

Cost-Benefit Analysis↗

PubMed1987

Segmentation of the EEG by minimization of the total gain in information.

A new procedure for detecting departures from constancy of the parameters of a probabilistic model over a period of time is proposed. It basically consists of specification of a joint probability distribution for data and models and minimization of the total gain in information. In contrast to conventional techniques, this procedure can be used to determine both the number of different models and the positions of the points at which the switches from one model to another occur. It is demonstrated how this new method can be applied to the problem of identification of different stages of EEG background activity. The lengths of these stages might serve as indicators for drug effects in the EEG.

Cerebral Cortex↗