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PubMed2005

Modelling the effect of a booster vaccination on disease epidemiology.

Despite the effectiveness of vaccines in dramatically decreasing the number of new infectious cases and severity of illnesses, imperfect vaccines may not completely prevent infection. This is because the immunity afforded by these vaccines is not complete and may wane with time, leading to resurgence and epidemic outbreaks notwithstanding high levels of primary vaccination. To prevent an endemic spread of disease, and achieve eradication, several countries have introduced booster vaccination programs. The question of whether this strategy could eventually provide the conditions for global eradication is addressed here by developing a seasonally-forced mathematical model. The analysis of the model provides the threshold condition for disease control in terms of four major parameters: coverage of the primary vaccine; efficacy of the vaccine; waning rate; and the rate of booster administration. The results show that if the vaccine provides only temporary immunity, then the infection typically cannot be eradicated by a single vaccination episode. Furthermore, having a booster program does not necessarily guarantee the control of a disease, though the level of epidemicity may be reduced. In addition, these findings strongly suggest that the high coverage of primary vaccination remains crucial to the success of a booster strategy. Simulations using estimated parameters for measles illustrate model predictions.

Algorithms↗
PubMed1997

A model describing the relationship between lag time and mild temperature increase duration.

When a bacterial population undergoes an unfavourable increase in temperature for a given duration, called stress duration, a death phase followed by a lag and a growth phase are observed. The lag phase is actually of great interest in regard to foodstuff safety in choosing a suitable protocol for the detection of microorganisms which have undergone a mild heat treatment. The extension of lag time with the severity of the increase in temperature has been highlighted by previous papers. Our experimental results concerning Listeria monocytogenes and Escherichia coli revealed that a two phase relationship between lag time and stress duration is observed for a specific increase in temperature. The first phase consists of an increase in lag time up to a peak; the second one consists of a decrease from this peak to a steady threshold. The mathematical model presented, describing the relationship between lag time and stress duration was empirically built from our experimental data concerning L. monocytogenes and E. coli. The fit evaluation carried out led us to consider this model as a good description of the relationship studied. The potential contribution of our model in heat treatment optimization is discussed.

Escherichia coli↗
PubMed2001

A model of salmon louse production in Norway: effects of increasing salmon production and public management measures.

Salmon lice Lepeophtheirus salmonis Krøyer have caused disease problems in farmed Atlantic salmon Salmo salar L. since the mid-1970s in Norway. High infection intensities and premature return of wild sea trout Salmo trutta L. were first reported in 1992. Later emaciated wild Atlantic salmon smolts carrying large amounts of lice have been observed both in fjords and offshore. The Norwegian Animal Health Authority regulations to control the problem, which came into operation in 1998, included compulsory louse level monitoring in farms and maximum legal numbers of lice per fish. Here, we present a model of salmon louse egg production in Norway and show that the effect of the current public management strategy is critically dependent on the yearly increase in salmon production. This is because the infection pressure is the product of the number of fish in the system, and the number of lice per fish. Due to the much larger number of farmed than wild salmonids, it is highly likely that lice originating from farmed salmon infect wild stock. Estimated tolerance limits for wild salmonids vary widely, and the level of louse egg production in farms which would be needed to decimate wild populations is not known. Two possible thresholds for total lice egg production are investigated: (1) 1986 to 1987 level (i.e. before adverse effects on sea trout were recorded), and (2) a level corresponding to a doubling of the estimated natural infection pressure. The farm lice per fish limits that would have to be observed to keep louse production within the 2 thresholds are calculated for the period 1986 to 2005. A steady decrease in the permitted number of lice per fish may keep the total louse production stable, but the number of salmon required for verification of lice numbers will increase as the prevalence to be verified is decreased. At threshold (2), the model estimated that lice limits should have been 0.05 louse per fish in 1999. This would require 60 fish from each pen to be collected, anaesthetised and examined for a good estimate at a confidence level of 95%. Such sample numbers are likely to be opposed by farmers. The use of national delousing programs to solve the problem is discussed.

Animals↗
PubMed2002

Interaural level differences and the level-meter model.

The interaural level difference (ILD) plays a significant role in sound localization. However, the definition of ILD for noise is open to some interpretation because it is not obvious how to deal with the inevitable level fluctuations. In this article, the ILD is interpreted as an energylike (time-integrated) measure of stimulus level, independent of other stimulus details-particularly interaural correlation. This concept is called the "level-meter model." The model was tested by measuring human ILD thresholds for noise stimuli that were interaurally correlated, or anticorrelated, or uncorrelated. An additional test (not involving lateralization) measured the threshold for level discrimination based on loudness. According to the level-meter model, all four thresholds should be the same. The experimental results showed that the predictions of the level-meter model held good to within about half a dB, although thresholds for level discrimination were systematically higher than ILDs. Among the ILDs themselves, thresholds were slightly higher for uncorrelated noise. The latter result could be explained by replacing the level-meter model with a loudness-meter model, incorporating temporal integration. The same model accounted for the bandwidth dependence of the threshold.

Adult↗
PubMed2004

Red-bond exponents of the critical and the tricritical Ising model in three dimensions.

Using the Wolff and geometric cluster algorithms and finite-size scaling analysis, we investigate the critical Ising and the tricritical Blume-Capel models with nearest-neighbor interactions on the simple-cubic lattice. The sampling procedure involves the decomposition of the Ising configuration into geometric clusters, each of which consists of a set of nearest-neighboring spins of the same sign connected with bond probability p. These clusters include the well-known Kasteleyn-Fortuin clusters as a special case for p=1-exp(-2K) , where K is the Ising spin-spin coupling. Along the critical line K=Kc , the size distribution of geometric clusters is investigated as a function of p . We observe that, unlike in the case of two-dimensional tricriticality, the percolation threshold in both models lies at pc =1-exp(-2Kc) . Further, we determine the corresponding red-bond exponents as yr =0.757(2) and 0.501(5) for the critical Ising and the tricritical Blume-Capel models, respectively. On this basis, we conjecture yr =1/2 for the latter model.

Journal Article↗
PubMed2002

Biomass-diversity responses and spatial dependencies in disturbed tallgrass prairies.

Monotonic, hump-shaped and zero-correlation productivity-diversity relationships have been found to date in many ecosystems. This diversity of responses has puzzled ecologists in their search for general principles on ecosystem functioning. Some state that the scale of observation is crucial in defining this relationship. We have developed a spatial model of tallgrass prairies where biomass and litter dynamics are defined by uncoupled difference equations. In this system, we periodically apply prescribed fire as a disturbance that propagates through neighboring cells. The model shows percolation thresholds at points where small-scale spatial heterogeneity and large-scale, global correlation coexist, resulting in power-law distributions in available areas for non-dominant species. These points maximize the biomass-diversity relationship. Our results suggest that spatial dependencies and the disturbance heterogeneity hypothesis are the cornerstone processes accounting for unimodality in productivity-diversity relationships.

Biomass↗
PubMed2001

Effect of lateral connections on the accuracy of the population code for a network of spiking neurons.

We study how neuronal connections in a population of spiking neurons affect the accuracy of stimulus estimation. Neurons in our model code for a one-dimensional orientation variable phi. Connectivity between two neurons depends on the absolute difference absolute value(phi - phi') between the preferred orientation of the two neurons. We derive an analytical expression of the activity profile for a population of neurons described by the spike response model with noisy threshold. We estimate the stimulus orientation and the trial-to-trial fluctuations using the population vector method. For stationary stimuli, uniform inhibitory connections produce a more reliable estimation of the stimulus than short-range excitatory connections with long-range inhibitions, although the latter interaction type produces a sharper tuning curve. These results are consistent with previous analytical studies of the Fisher information.

Action Potentials↗
PubMed2003

Wavelet statistics of functional MRI data and the general linear model.

PURPOSE: To improve the signal-to-noise ratio (SNR) of functional magnetic resonance imaging (fMRI) data, an approach is developed that combines wavelet-based methods with the general linear model. MATERIALS AND METHODS: Ruttimann et al. (1) developed a wavelet-based statistical procedure to test wavelet-space partitions for significant wavelet coefficients. Their method is applicable for the detection of differences between images acquired under two experimental conditions using long blocks of stimulation. However, many neuropsychological questions require more complicated event-related paradigms and more experimental conditions. Therefore, in order to apply wavelet-based methods to a wide range of experiments, we present a new approach that is based on the general linear model and wavelet thresholding. RESULTS: In contrast to a monoresolution filter, the application of the wavelet method increased the SNR and showed a set of clearly dissociable activations. Furthermore, no relevant decrease of the local maxima was observed. CONCLUSION: Wavelet-based methods can increase the SNR without diminishing the signal amplitude, while preserving the spatial resolution of the image. The anatomical localization is strongly improved.

Adult↗
PubMed2002

Medical management versus investigate-and-operate strategy in asymptomatic carotid stenosis: a decision analysis.

OBJECTIVE: The objective of this study was to determine whether asymptomatic patients at high risk for carotid stenosis should undergo screening Duplex ultrasound (DUS), with a view to offering carotid endarterectomy (CE) to those patients with significant stenosis. METHOD: We constructed a decision analysis model to evaluate the impact of an investigate-and-operate strategy, compared with medical management alone, on the risk of stroke in patients at high risk for carotid stenosis. We studied five investigate-and-operate models addressing different thresholds for intervention (in terms of degree of stenosis) and the effects of using or not using preoperative angiography. RESULTS: For each of the strategies, under the base case conditions (30% prevalence of >50% carotid stenosis), the number needed to screen (NNS) and the number needed to treat (NNT) are high (213 to 769 and 13 to 144, respectively). The strategy of angiography for >50% stenosis and CE for >70% stenosis was harmful. Other strategies were unattractive because of unacceptably high NNT (no angiography, CE >50% stenosis), or because of unacceptably high NNS (angiography >70%, CE >70% stenosis), or both (angiography >50% stenosis, CE >50% stenosis; no angiography, CE > 70% stenosis). At 50% prevalence of >50% stenosis, two models produced more reasonable combinations of NNT and NNS: 11 and 370, respectively, for angiography >70%, CE >70% stenosis; and 27 and 286, respectively, for no angiography, CE >70% stenosis. Within the range of clinically plausible values for sensitivity and specificity of DUS, results were not greatly influenced by the measurement properties of DUS. However, angiographic or surgical rates of stroke or death were critical to the outcomes with any strategy. Only 3% to 12% of strokes in the studied population were prevented. CONCLUSIONS: Screening is acceptable only in populations at >40% to 50% risk for >50% carotid stenosis, who are surgical candidates, and who would undergo surgery if recommended. Acceptable investigate-and-operate strategies include angiography for DUS stenosis >70%, with CE if this level of stenosis is confirmed, and CE for DUS-measured stenosis >70% without angiographic confirmation. Surgery for asymptomatic carotid stenosis is unlikely to have a large impact upon the burden of stroke in society.

Carotid Stenosis↗
PubMed2004

Modeling of methyl isothiocyanate air concentrations associated with community illnesses following a metam-sodium sprinkler application.

BACKGROUND: A series of illnesses occurred in Earlimart, CA on November 13, 1999 following a metam-sodium sprinkler application to a potato field on the southern edge of the town. METHODS: Case information was obtained from direct interviews, from illness complaints filed with state or county agencies, or from illness reports filed by community physicians for 173 subjects. Air concentrations of the by-product methyl isothiocyanate (MITC) during the episode were estimated based upon the Industrial Source Complex Short-Term (ISC3) air dispersion model, estimates from prior metam-sodium monitoring studies, and data from weather stations in two adjoining communities. RESULTS: Weather station data indicated that the November 13th incident corresponded with a temperature inversion at approximately 5:00 p.m. and a shift in the direction of prevailing wind from northwest to southeast. On the edge of Earlimart, 1-hr time weighted average (TWA) MITC concentration estimates ranged from 0.5 to 1 ppm. Of the 173 subjects, 170 had MITC-compatible symptoms, including eye or upper respiratory irritation (77.6%), non-specific systemic symptoms (64.7%), and lower respiratory symptoms (20.0%). 78.2% were exposed within 0.5 miles of the northern edge of the treated field where average 1 hr MITC concentrations exceeded the 800 ppb ocular irritation threshold. CONCLUSIONS: ISC3 modeling is a useful means of evaluating MITC concentrations for illness episodes when industrial hygiene assessment is not possible.

Adolescent↗
PubMed2004

Clinical ototoxicity of teicoplanin.

No strong evidence of ototoxicity of teicoplanin can be found in the literature, possibly because of conservative definitions of ototoxicity. We performed audiometry over time to compare the ototoxicity of teicoplanin with that of cloxacillin as a non-ototoxic standard. The data were analyzed with a linear mixed-effects model. The hearing thresholds of 12 patients who were treated with teicoplanin for severe staphylococcal infections showed a slight but significant increase over time, whereas the thresholds of 5 patients treated with cloxacillin decreased significantly during treatment. This improvement in hearing with cloxacillin may be attributed to improvement of the clinical condition. This outcome implies that previous reports that suggest a lack of ototoxicity of teicoplanin potentially underestimate the risk and should be interpreted accordingly.

Anti-Bacterial Agents↗
PubMed1995

Oesophageal sensation assessed by electrical stimuli and brain evoked potentials--a new model for visceral nociception.

Sensory thresholds and brain evoked potentials were determined in 12 healthy volunteers using electrical stimulation of the oesophagus 28 and 38 cm from the nares. The peaks of the evoked potentials were designated N for negative deflections and P for positive. Continuous electrical stimulation (40 Hz) at the 38 cm position resembled heartburn (five of 12 subjects) while non-specific ('electrical') sensations were provoked at 28 cm (10 of 12). Thresholds of sensation and of pain were lower at the initial than the second determination, but did not differ with respect to stimulation site. The pain summation threshold to repeated stimuli (2 Hz, 5 stimuli) was determined for the first time in a viscus. This threshold was lower than the pain threshold to single stimuli at 38 cm (p < 0.02). Evoked potential latencies did not change significantly over a six month period while the N1/P2 amplitude was higher at the first measurement (p < 0.05). P1 and N1 latencies were significantly shorter 38 cm (medians 100 and 141 ms) than 28 cm from the nares (102 and 148 ms) (p = 0.04 and p = 0.008). Electrical stimulation of the oesophagus may serve as a human experimental model for visceral pain. Longer evoked potential latencies from the proximal compared with distal stimulations provide new information about the sensory pathways of the oesophagus.

Adult↗
PubMed2000

Mechanical signalling and angiogenesis. The integration of cell-extracellular matrix couplings.

In vitro angiogenesis assays have shown that the couplings between fibrin gel and cell traction forces trigger biogel pre-patterning, consisting, in the formation of lacunae which evolve toward capillary-like structures (CLS) networks. Depending on the experimental conditions (number of seeded cells, gel elasticity,...), this pre-patterning can be enhanced or inhibited. A theoretical model based on a description of the cell-biogel biochemical and mechanical interactions is proposed as a basis for understanding how integrating these interactions can lead to the pre-patterning of the biogel. We showed that the critical parameter values corresponding to the bifurcation of the model solutions correspond to threshold values of the experimental variables. Furthermore, simulations of the mechanocellular model give rise to dynamic remodelling patterns of the biogel which are in good agreement both with the lacunae morphologies and with the time and space scales derived from the in vitro angiogenesis assays. Special attention has been paid in the simulations to cell proteolytic activity and to the amplitude of cell traction forces. We finally discussed how modelling guided experiments can be inferred from these results.

Biomechanical Phenomena↗
PubMed2003

Context effects: the proportional difference model and the reflection of preference.

The reflection effect (D. Kahneman & A. Tversky, 1979) was investigated using the stochastic model of choice developed by C. Gonzalez-Vallejo (2002). The model assumes that individuals make trade-offs among attribute values by relying on a difference variable. The model also specifies a threshold representing individual proclivities to reach to attribute differences. Two experiments demonstrated that changes in risk attitudes, from a gain to a loss situation, depended on the stimuli as well as on individuals' thresholds. Thresholds were generally lower in losses than in gains, indicating a risk-taking tendency. Thresholds were also lower when participants were endowed with greater savings. Model testing revealed better fits for the stochastic model than cumulative prospect theory (A. Tversky &. D. Kahneman, 1992).

Choice Behavior↗
PubMed2000

Animal models of craving for ethanol.

Craving has various meanings but can be defined generally in terms of a desire for the previously experienced effects of ethanol. Animal models provide a means by which to study the underlying mechanisms associated with craving and are most useful when they fulfill the requirements for predictive validity and reliability. Craving is a key part of the process of addiction that can lead to relapse and is conceptualized as having at least three components: preoccupation/anticipation, binge/intoxication and withdrawal/negative affect. Animal models of craving are hypothesized at this time to involve three domains of motivation to take drugs: excessive drinking, negative affective states and conditioned reinforcement. Excessive drinking includes the alcohol deprivation effect, drinking during withdrawal and drinking after a history of dependence. Models of the negative affective state include increases in brain reward thresholds, and conditioned reinforcement models include cue-induced resistance to extinction or cue-induced reinstatement. Experimental psychology is a rich resource of sensitive behavioral techniques by which to measure hypothetical constructs associated with the motivation to drink ethanol. Rigorous tests of predictive validity and reliability will be necessary to make them useful for understanding the neurobiology of craving and for the development of new medications for treating craving.

Acamprosate↗
PubMed2003

Meta-analysis of EEG test performance shows wide variation among studies.

BACKGROUND: EEG results are used for counseling patients with seizures about prognosis and deciding on medications. Published sensitivities of interictal EEG vary widely. OBJECTIVE: To account for variation in test characteristics between studies. METHODS: Meta-analysis. Medline search, 1970 to 2000, of English language studies. Standard methods for meta-analysis of diagnostic test performance were used to determine the ability of EEG results to distinguish between patients who will and will not have seizures. Using linear regression, the authors assessed the influence of readers' thresholds for classifying the EEG as positive, sample probability of seizure, percent of subjects with prior neurologic impairment, percent treated, and years followed. RESULTS: Twenty-five studies involving 4,912 EEG met inclusion criteria. Specificity (range 0.13 to 0.99) and sensitivity (range 0.20 to 0.91) of epileptiform EEG interpretations varied widely and were heterogeneous by chi(2) analysis (p < 0.001 for each). Diagnostic accuracy of EEG and the thresholds for classifying EEG as positive varied widely. In the multivariate model, differences in readers' thresholds accounted for 37% of the variance in EEG diagnostic accuracy, and no other reported factors were significant. CONCLUSION: This analysis suggests that there is wide interreader variation in sensitivity and specificity of EEG interpretations, and that this variation influences the ability of EEG to discriminate between those who will and will not have seizure recurrences. In clinical practice, interpreting the degree to which a positive EEG result predicts increased seizure risk in an individual patient is difficult. Interpreting EEG with higher specificity yields more accurate predictions.

Adult↗
PubMed2005

On the lack of comonotonicity between likert scores and Rasch-based measures.

The Rating Scale Model (RSM) and the Partial Credit Model (PCM) are fairly well-known examples of Rasch models for polytomously scored items. In addition to a number of threshold parameters, both the models contain two scalar parameters characterizing item and person location on a common interval-level scale. The rank order of items and persons defined by the Likert summative scores (i.e. the raw total scores) is compared with that obtained from the Rasch-based measures (i.e. the maximum likelihood estimates of person and item parameters). It is proved that: 1) the property of comonotonicity between Likert summative scores and Rasch-based measures holds for both the person and item parameters of the RSM; 2) the property of comonotonicity between Likert summative scores and Rasch-based measures holds for the PCM only with reference to the person parameters; 3) violations of comonotonicity are possible, for particular datasets, for the item parameters of the PCM.

Data Collection↗