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PubMed2004

Current issues and uncertainties in the measurement and modelling of air-vegetation exchange and within-plant processing of POPs.

Air-vegetation exchange of POPs is an important process controlling the entry of POPs into terrestrial food chains, and may also have a significant effect on the global movement of these compounds. Many factors affect the air-vegetation transfer including: the physicochemical properties of the compounds of interest; environmental factors such as temperature, wind speed, humidity and light conditions; and plant characteristics such as functional type, leaf surface area, cuticular structure, and leaf longevity. The purpose of this review is to quantify the effects these differences might have on air/plant exchange of POPs, and to point out the major gaps in the knowledge of this subject that require further research. Uptake mechanisms are complicated, with the role of each factor in controlling partitioning, fate and behaviour process still not fully understood. Consequently, current models of air-vegetation exchange do not incorporate variability in these factors, with the exception of temperature. These models instead rely on using average values for a number of environmental factors (e.g. plant lipid content, surface area), ignoring the large variations in these values. The available models suggest that boundary layer conductance is of key importance in the uptake of POPs, although large uncertainties in the cuticular pathway prevents confirmation of this with any degree of certainty, and experimental data seems to show plant-side resistance to be important. Models are usually based on the assumption that POP uptake occurs through the lipophilic cuticle which covers aerial surfaces of plants. However, some authors have recently attached greater importance to the stomatal route of entry into the leaf for gas phase compounds. There is a need for greater mechanistic understanding of air-plant exchange and the 'scaling' of factors affecting it. The review also suggests a number of key variables that researchers should measure in their experiments to allow comparisons to be made between studies in order to improve our understanding of what causes any differences in measured data between sites.

Air Movements↗
PubMed2004

Species-specific uncertainty factors for compounds eliminated principally by renal excretion in humans.

An uncertainty factor of 100 is used to derive health-based guidance values for human intakes of chemicals based on data from studies in animals. The 100-fold factor comprises 10-fold factors for species differences and for interindividual differences in response. Each 10-fold factor can be subdivided into toxicokinetic and toxicodynamic aspects with a 4.0-fold factor to allow for kinetic differences between test species and humans. The current work determined the extent of interspecies differences in the internal dose (toxicokinetics) of compounds which are eliminated primarily by renal excretion in humans. An analysis of the published data showed that renal excretion was also the main route of elimination in the test species for most of the identified probe substrates. Interspecies differences were apparent for both the mechanism of renal excretion (glomerular filtration, tubular secretion and/or reabsorption) and the extent of plasma protein binding, both of which may affect renal clearance and therefore the magnitude of species differences in the internal dose. For compounds which are eliminated unchanged by both humans and the test species, the average differences in the internal doses between humans and animals were 1.6 for dogs, 3.3 for rabbits, 5.2 for rats and 13 for mice. This suggests that for renal excretion, the differences between humans and the rat and especially the mouse may exceed the 4.0-fold default factor for toxicokinetics.

Animals↗
PubMed2004

[How to avoid the uncertainties of intraoperative examination of the sentinel lymph node in breast cancer?].

The sentinel lymph node procedure is now admitted by many teams for axillary evaluation in the early stage of breast cancer. The classical technique consists in an intraoperative examination of the sentinel lymph node under general anaesthesia during tumorectomy, deciding whether or not complete axillary lymphadenectomy must be done. Intraoperative examination seems to us to have a poor predictive value. In the case of a false positive, the surgeon would perform lymphadenectomy unnecessarily, while a false negative would mean that the patient would have to be re-operated for lymphadenectomy once the definitive results have become available. For all these reasons, we propose the detection of the sentinel lymph node under local anaesthesia and to await its definitive analysis before carrying out tumorectomy on the patient and axillary lymphadenectomy if necessary under general anesthesia. Hence, we consider that the best way to avoid the uncertainties of an intraoperative examination of the sentinel lymph node is not to carry out intraoperative examinations.

Axilla↗
PubMed2006

Multiple regions-of-interest analysis of setup uncertainties for head-and-neck cancer radiotherapy.

PURPOSE: To analyze three-dimensional setup uncertainties for multiple regions of interest (ROIs) in head-and-neck region. METHODS AND MATERIALS: In-room computed tomography (CT) scans were acquired using a CT-on-rails system for 14 patients. Three separate bony ROIs were defined: C2 and C6 vertebral bodies and the palatine process of the maxilla. Translational shifts of 3 ROIs were calculated relative to the marked isocenter on the immobilization mask. RESULTS: The shifts for all 3 ROIs were highly correlated. However, noticeable differences on the order of 2-6 mm existed between any 2 ROIs, indicating the flexibility and/or rotational effect in the head-and-neck region. The palatine process of the maxilla had the smallest right-left shifts because of the tight lateral fit in the face mask, but the largest superior-inferior movement because of in-plane rotation and variations in jaw positions. The neck region (C6) had the largest right-left shifts. The positioning mouthpiece was found effective in reducing variations in the superior-inferior direction. There was no statistically significant improvement for using the S-board (8 out of 14 patients) vs. the short face mask. CONCLUSIONS: We found variability in setup corrections for different regions of head-and-neck anatomy. These relative positional variations should be considered when making setup corrections or designing treatment margins.

Algorithms↗
PubMed2006

Performances of a multidimensional on-line SPE-LC-ECD method for the determination of three major catecholamines in native human urine: validation, risk and uncertainty assessments.

A novel, multidimensional on-line SPE-LC method with electrochemical detection is described for the fully automated and direct analysis of the catecholamines norepinephrine, epinephrine and dopamine in urine. The integrated extractive clean-up of the raw biofluid is based on a SPE-column packed with restricted access material (RAM) which is modified with the affinity ligand nitrophenylboronic acid. The method was fully validated according to a recent approach based on an accuracy profile. The acceptance limits were set at +/-15% of the nominal concentration values. The method was found accurate over a concentration range from 15 to 500 microg/l for norepinephrine, from 5 to 500 microg/l for epinephrine and from 50 to 500 microg/l for dopamine. The relative risk for the use of the validated method in routine analysis was also assessed based on this validation strategy. It was found that at most 3.5% of future sample measurements will fall outside the acceptance limits. This demonstrates the high reliability of the analytical method described. Moreover, the measurements uncertainties were deduced from the validation experiments without any additional effort.

Catecholamines↗
PubMed2007

The special theory of Brownian relativity: equivalence principle for dynamic and static random paths and uncertainty relation for diffusion.

The theoretical basis of a recent theory of Brownian relativity for polymer solutions is deepened and reexamined. After the problem of relative diffusion in polymer solutions is addressed, its two postulates are formulated in all generality. The former builds a statistical equivalence between (uncorrelated) timelike and shapelike reference frames, that is, among dynamical trajectories of liquid molecules and static configurations of polymer chains. The latter defines the "diffusive horizon" as the invariant quantity to work with in the special version of the theory. Particularly, the concept of universality in polymer physics corresponds in Brownian relativity to that of covariance in the Einstein formulation. Here, a "universal" law consists of a privileged observation, performed from the laboratory rest frame and agreeing with any diffusive reference system. From the joint lack of covariance and simultaneity implied by the Brownian Lorentz-Poincaré transforms, a relative uncertainty arises, in a certain analogy with quantum mechanics. It is driven by the difference between local diffusion coefficients in the liquid solution. The same transformation class can be used to infer Fick's second law of diffusion, playing here the role of a gauge invariance preserving covariance of the spacetime increments. An overall, noteworthy conclusion emerging from this view concerns the statistics of (i) static macromolecular configurations and (ii) the motion of liquid molecules, which would be much more related than expected.

Journal Article↗
PubMed2005

A Bayesian approach to evaluating net clinical benefit allowed for parameter uncertainty.

BACKGROUND AND OBJECTIVE: Although randomized controlled trials (RCTs) are conducted to establish whether novel interventions work on average in the patient population, there is a growing desire to move to a more individualized approach to evaluation. The potential benefits and harms of a treatment policy may differ between individuals. If these benefits and harms are not evaluated distinctly, and in a quantitative framework, transparency can be lost in the decision-making process. METHODS: Glasziou and Irwig have outlined the concept of net clinical treatment benefit for identifying the patients for whom the potential benefits of treatment outweigh the possible side effects. This study revisits the decision whether to use warfarin to treat atrial fibrillation. In this analysis, RCT and various sorts of observational data are synthesized. RESULTS: This reanalysis brings into question the conclusions of the original analysis on who would benefit from warfarin; however, caution is advised, due to limitations in the quality of life data available. CONCLUSION: A fully realized Bayesian implementation of the model is presented. This provides a framework for including uncertainty related to the estimation of all model parameters, and permits both direct probability statements and credible intervals for specific patient groups to be expressed.

Anticoagulants↗
PubMed2005

Indivisibility and divisibility in land development over time and under uncertainty.

The quasi-option value (QOV) literature originated by Arrow et al. (Arrow, K.J., Fisher, A.C., 1974. Environmental preservation, uncertainty, and irreversibility. Quarterly Journal of Economics 88, 312-319) and by Henry (Henry, C., 1974. Option values in the economics of irreplaceable assets. Review of Economic Studies 41, 89-104) is largely concerned with the analysis of two-period models of land development. Our paper extends this literature by analyzing two scenarios in which the decision to develop land is made in a multi-period and stochastic framework. In the first scenario, the development decision is indivisible. In contrast, in the second scenario, the development decision is divisible. Specifically, we study the properties of the indivisible development decision when there is a time constraint on when land is to be developed. We then analyze the ways in which the divisible land development decision depends on the extent of a landowner's landholding and on the number of development opportunities awaiting this landowner.

Conservation of Natural Resources↗
PubMed2005

Policy planning under uncertainty: efficient starting populations for simulation-optimization methods applied to municipal solid waste management.

Evolutionary simulation-optimization (ESO) techniques can be adapted to model a wide variety of problem types in which system components are stochastic. Grey programming (GP) methods have been previously applied to numerous environmental planning problems containing uncertain information. In this paper, ESO is combined with GP for policy planning to create a hybrid solution approach named GESO. It can be shown that multiple policy alternatives meeting required system criteria, or modelling-to-generate-alternatives (MGA), can be quickly and efficiently created by applying GESO to this case data. The efficacy of GESO is illustrated using a municipal solid waste management case taken from the regional municipality of Hamilton-Wentworth in the Province of Ontario, Canada. The MGA capability of GESO is especially meaningful for large-scale real-world planning problems and the practicality of this procedure can easily be extended from MSW systems to many other planning applications containing significant sources of uncertainty.

Computer Simulation↗
PubMed2004

Quantifying structure-function uncertainty: a graph theoretical exploration into the origins and limitations of protein annotation.

Since the advent of investigations into structural genomics, research has focused on correctly identifying domain boundaries, as well as domain similarities and differences in the context of their evolutionary relationships. As the science of structural genomics ramps up adding more and more information into the databanks, questions about the accuracy and completeness of our classification and annotation systems appear on the forefront of this research. A central question of paramount importance is how structural similarity relates to functional similarity. Here, we begin to rigorously and quantitatively answer these questions by first exploring the consensus between the most common protein domain structure annotation databases CATH, SCOP and FSSP. Each of these databases explores the evolutionary relationships between protein domains using a combination of automatic and manual, structural and functional, continuous and discrete similarity measures. In order to examine the issue of consensus thoroughly, we build a generalized graph out of each of these databases and hierarchically cluster these graphs at interval thresholds. We then employ a distance measure to find regions of greatest overlap. Using this procedure we were able not only to enumerate the level of consensus between the different annotation systems, but also to define the graph-theoretical origins behind the annotation schema of class, family and superfamily by observing that the same thresholds that define the best consensus regions between FSSP, SCOP and CATH correspond to distinct, non-random phase-transitions in the structure comparison graph itself. To investigate the correspondence in divergence between structure and function further, we introduce a measure of functional entropy that calculates divergence in function space. First, we use this measure to calculate the general correlation between structural homology and functional proximity. We extend this analysis further by quantitatively calculating the average amount of functional information gained from our understanding of structural distance and the corollary inherent uncertainty that represents the theoretical limit of our ability to infer function from structural similarity. Finally we show how our measure of functional "entropy" translates into a more intuitive concept of functional annotation into similarity EC classes.

Biochemical Phenomena↗
PubMed2005

Assigning uncertainties in the inversion of NMR relaxation data.

Recovering the relaxation-time density function (or distribution) from NMR decay records requires inverting a Laplace transform based on noisy data, an ill-posed inverse problem. An important objective in the face of the consequent ambiguity in the solutions is to establish what reliable information is contained in the measurements. To this end we describe how upper and lower bounds on linear functionals of the density function, and ratios of linear functionals, can be calculated using optimization theory. Those bounded quantities cover most of those commonly used in the geophysical NMR, such as porosity, T(2) log-mean, and bound fluid volume fraction, and include averages over any finite interval of the density function itself. In the theory presented statistical considerations enter to account for the presence of significant noise in the signal, but not in a prior characterization of density models. Our characterization of the uncertainties is conservative and informative; it will have wide application in geophysical NMR and elsewhere.

Journal Article↗
PubMed2006

Stabilization of inhomogeneous patterns in a diffusion-reaction system under structural and parametric uncertainties.

Many phenomena such as neuron firing in the brain, the travelling waves which produce the heartbeat, arrythmia and fibrillation in the heart, catalytic reactions or cellular organization activities, among others, can be described by a unifying paradigm based on a class of nonlinear reaction-diffusion mechanisms. The FitzHugh-Nagumo (FHN) model is a simplified version of such class which is known to capture most of the qualitative dynamic features found in the spatiotemporal signals. In this paper, we take advantage of the dissipative nature of diffusion-reaction systems and results in finite dimensional nonlinear control theory to develop a class of nonlinear feedback controllers which is able to ensure stabilization of moving fronts for the FHN system, despite structural or parametric uncertainty. In the context of heart or neuron activity, this class of control laws is expected to prevent cardiac or neurological disorders connected with spatiotemporal wave disruptions. In the same way, biochemical or cellular organization related with certain functional aspects of life could also be influenced or controlled by the same feedback logic. The stability and robustness properties of the controller will be proved theoretically and illustrated on simulation experiments.

Diffusion↗
PubMed2004

Feature uncertainty: a novel test to probe prefrontal dysfunction in unaffected siblings of schizophrenia patients.

Previous studies indicated that neuropsychological impairments are potential endophenotypes of schizophrenia. However, the sensitivity of these procedures is not sufficient and their brain substrates are poorly defined. The aim of this study was to measure the behavioral performance of siblings of schizophrenia patients and controls on a novel feature uncertainty (FU) task that selectively activates dorsal anterior cingulate cortex relative to orientation (OR) and spatial frequency (SF) discrimination. During the FU task, two subsequent sinusoidal gratings are presented and participants are asked to remember both the OR and SF of the gratings. After the disappearance of the gratings, a color cue signifies the perceptual dimension (OR or SF) to discriminate. Results revealed that the siblings of schizophrenia patients (n = 25) showed a selective deficit on the FU task as compared with controls (n = 20). The FU deficit was more severe than that found on neuropsychological tests of executive functions, psychomotor speed, and verbal memory. These results suggest that anterior cingulate dysfunction is a potential endophenotype of schizophrenia.

Adult↗
PubMed2005

Uncertainty, anxiety, and brain oscillations.

Influence of anxious expectation on spectral power and delta-gamma coupling was studied in 39 subjects (27 females) aged 19-30 years who also filled out the State Trait Anxiety Inventory. The situation of uncertainty was associated with general increase in spectral power of all EEG bands, which was particularly pronounced in high-trait anxiety subjects. In low-trait anxiety subjects, association between delta and gamma power significantly increased when they had to expect bad news but did not change when they expected good news. In high-trait anxiety subjects, this association tended to increase in both cases. Higher baseline delta power predicted higher gamma power in the situation where a bad news was expected. These findings are discussed in terms of Gray and McNaughton's theory of anxiety and evolutionary interpretation linking delta oscillations with reward motivation. Increase of delta-gamma coupling in anxiogenic situation is interpreted to reflect higher cortical arousal, which appears in a frustrating situation in subjects with higher activity of "motivational" delta system.

Adult↗
PubMed2006

The effect of response uncertainty on illusory biases of perception and action.

When task requirements were known in advance, Glazebrook et al. [C.M. Glazebrook, V.P. Dhillon, K.M. Keetch, J. Lyons, E. Amazeen, D.J. Weeks, D. Elliott, Perception-action and the Müller-Lyer illusion: amplitude or endpoint bias?, Exp. Brain Res. 160 (2005) 71-78.] demonstrated that perceptual biases associated with the Müller-Lyer illusion resulted from a misperception of figure extent, while manual aiming biases resulted from a misperception of vertex position. In this study, we examined the degree to which prior knowledge of task requirements influenced how participants coded visual-spatial information associated with Müller-Lyer configurations. Specifically, we investigated how illusory biases are affected when uncertainty exists as to whether participants will be required to make a perceptual-cognitive decision about the length of a figure or complete a rapid aiming movement to a figure vertex. Although aiming movements were completed in a similar manner regardless of the prior knowledge condition, perceptual biases were associated with a misperception of extent when the task was known and a misperception of both extent and position when the task was unknown. These findings indicate that people are flexible in the manner in which they code visual-spatial information.

Adult↗
PubMed2006

Resolution of uncertainty in prefrontal cortex.

Making optimal decisions in the face of uncertain or incomplete information arises as a common problem in everyday behavior, but the neural processes underlying this ability remain poorly understood. A typical case is navigation, in which a subject has to search for a known goal from an unknown location. Navigating under uncertain conditions requires making decisions on the basis of the current belief about location and updating that belief based on incoming information. Here, we use functional magnetic resonance imaging during a maze navigation task to study neural activity relating to the resolution of uncertainty as subjects make sequential decisions to reach a goal. We show that distinct regions of prefrontal cortex are engaged in specific computational functions that are well described by a Bayesian model of decision making. This permits efficient goal-oriented navigation and provides new insights into decision making by humans.

Adult↗
PubMed2005

Some certainty for the "zone of uncertainty"? Exploring the function of the zona incerta.

The zona incerta (ZI), first described over a century ago by Auguste Forel as a "region of which nothing certain can be said," forms a collection of cells that derives from the diencephalon. To this day, we are still not certain of the precise function of this "zone of uncertainty" although many have been proposed, from controlling visceral activity to shifting attention and from influencing arousal to maintaining posture and locomotion. In this review, I shall outline the recent advances in the understanding of the structure, connectivity and functions of the ZI. I will then focus on a possible and often neglected global role for the ZI, one that links its diverse functions together. In particular, I aim to highlight the idea that the ZI forms a primal center of the diencephalon for generating direct responses (visceral, arousal, attention and/or posture-locomotion) to a given sensory (somatic and/or visceral) stimulus. With this global role in mind, I will then address recent results indicating that abnormal ZI activity manifests in clinical symptoms of Parkinson disease.

Animals↗
PubMed2005

Explicit estimation of visual uncertainty in human motion processing.

We examine whether human observers have explicit access to an estimate of their own uncertainty in extrapolating the motion trajectories of moving objects. Objects moved across a display area at constant speed changing direction at short time intervals. Each new direction was obtained by adding a random perturbation to the previous direction. The perturbation distribution was always symmetric with mean zero (no change in direction) but could differ in variability: objects with low directional variability tended to travel in straight lines while objects with high directional variability moved more erratically. Objects eventually disappeared behind the near edge of an occluder. Observers marked a 'capture region' along the far edge of the occluder that they estimated would contain the object when it re-emerged. We varied both occluder width and directional variability across trials and found that observers correctly compensated for these changes. We present a two-stage model of observer performance in which the visual system first estimates the directional variability of the object and then uses this estimate to set a capture region.

Cues↗