Scientific Models of Human Health Risk Analysis in Legal and Policy Decisions

The quality of scientific predictions of risk in the courtroom and policy arena rests in large measure on how the two differences between normal practice and the legal/policy practice of science are reconciled. This article considers a variety of issues that arise in reconciling these differences, and the problems that remain with scientific estimates of risk when these are used in decisions

A Framework for Assessing the Rationality of Judgments in Carcinogenicity Hazard Identification

Arguing that guidelines for identifying carcinogens now lack a philosophically rigorous framework, the authors present an alternative that draws clear attention to the process of reasoning towards judgments of carcinogenicity

Application of Probabilistic Risk Assessment in Establishing Perchlorate and Goitrogen Risk Mitigation Strategies.

This paper applies probabilistic risk assessment in quantifying risks from cumulative and aggregate risk pathways for selected goitrogens in water and food. Results show that the percentages of individuals with a Hazard Index (HI) value above 1 ranges between 30% and 50% both with and without serum half-life correction when a traditional regulatory assessment approach based on establishment of a No Observed Effects Level (NOEL) is used. When an exposure-response curve is instead used and a threshold of 50% inhibition is assumed, 1.1% or less of the population exceeds an HI value of 1 with no serum half-life correction, rising to as high as 11% when serum half-life correction is applied. If 0% to 5% threshold for iodide uptake inhibition is assumed for production of adverse effects, the percentage of the population with an HI above 1 is 46.2% or less with no serum half-life correction, and 47.2% or less when serum half-life correction is applied. The probabilistic analysis shows that while there are exposed groups for whom perchlorate exposures are the primary cause of individuals having HI values above 1, these constitute significantly less than 1% of the population. Instead, the potential risk from exposure to goitrogens is dominated by nitrates without serum half-life correction and thiocyanates with serum half-life correction, suggesting public health protection is better accomplished by a focus on these and other goitrogens expect in highly limited cases where waterborne perchlorate is at unusually high concentrations.The author acknowledges funding contributions from the Cambridge Centre for Climate Change Mitigation Research and the American Water Works Association Research Foundation.This is the final version of the article. It first appeared from MDPI via http://dx.doi.org/10.3390/ijerph12091037

Brainstem Control Of Three-dimensional Eye Movements

This thesis examines the neural mechanisms that generate torsional and vertical eye movements, and how they handle the kinematics of three-dimensional rotations. Three-dimensional eye rotations were recorded in alert monkeys, and the midbrain was studied using single unit recording, electrical microstimulation, and pharmacological inactivation.;The direction of VOR slow phases was usually opposite to that of head rotation, as required for optimal visual stabilization. However, direction errors sometimes occurred because of low gain about a head-fixed torsional axis. This axis was orthogonal to Listing\u27s plane of saccadic eye positions, which suggests that saccades and the VOR share the same coordinate system. As predicted by the laws of rotational kinematics, even slow phase axes with zero torsional components produced torsional violations of Listing\u27s law. This proves that mechanics of the plant are not responsible for Listing\u27s law. Furthermore, the final positions were held. This signifies that the eye velocity signal is multiplied by position feedback before entering the oculomotor integrator. Finally, these violations of Listing\u27s law were corrected by VOR quick phases.;Microstimulation and inactivation of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) demonstrated two right riMLF burst neuron populations that generate clockwise-upward-rightward and clockwise-downward-leftward rotations respectively, and two left riMLF populations for counterclockwise-upward-leftward and counterclockwise-downward-rightward rotations. The torsional axes of eye rotation evoked by riMLF stimulation were orthogonal to Listing\u27s plane, whereas axes that remained after riMLF inactivation aligned with Listing\u27s plane. This suggests that the neural coordinates of motor systems reflect their behavioral constraints.;The neural integrator, which generates the eye position signal, is central to oculomotor control. Post-saccadic drift during inactivation of the midbrain interstitial nucleus of Cajal (INC) showed that this nucleus is the integrator for vertical and torsional eye positions. Stimulation showed that the right INC controls clockwise rotations and the left INC controls counterclockwise rotations. Simulations of the drift suggested that the INC distributes integration over parallel independent neural compartments. This makes the integrator more computationally robust, and suggests a similar role for the modular connectivity observed throughout the brain

Functional genomics does not have to be limited to a few select organisms

A response to Whither genomics by Andrew W Murray, Genome Biology 2000, 1:comment003.1-003.

Doctor of Philosophy

dissertationThe method of moments in conjunction with the maximum entropy method of reconstructing density distributions is applied to the energy dependent neutron diffusion equation to solve for neutron flux within a critical assembly. The energy dependent neutron diffusion equation (EDNDE) is converted into a moment equation which is solved analytically for a bare spherical critical assembly of pure 235U in the radial direction. The normalized energy dependent neutron diffusion moments (NEDNDM) generated analytically is verified to NEDNDM, as calculated by Monte Carlo N Particle 5 version 1.40 (MCNP5) and Attila-7.1.0-beta version (Attila). The normalized NEDNDM are validated with the bare spherical critical assembly experiment, named GODIVA. The NEDNDM are then put into the maximum entropy method to solve for neutron flux within the two critical assemblies (100% 235U and GODIVA) and the neutron flux is verified with MCNP5 and Attila and validated with GODIVA. The analytic NEDNDM values fall between the NEDNDM from MCNP5 (lower bound) and Attila (upper bound). The error is taken to be relative to the Monte Carlo simulation. The error range is from 0% to 14%. The error range of the NEDNDM compared to NEDNDM from GODIVA is 0% to 24%. The verification and validation error of the maximum entropy method is 12% to 25% where MCNP5 is taken to be the comparison standard. The error range of the reconstructed flux validated with GODIVA is 0% to 10%. The error range of the neutron flux spectrum from MCNP5 compared to GODIVA is 0%-20% and the Attila error range compared to the GODIVA is 0%-35%. The method of moments coupled with the maximum entropy method for reconstructing flux is shown to be a fast reliable method, compared to either Monte Carlo methods (MCNP5) or 30 multienergy group methods (Attila) and to GODIVA the bare sphere critical assembly experiment

A Computational Model to Account for Dynamics of Spatial Updating of Remembered Visual Targets across Slow and Rapid Eye Movements

Despite the ever-changing visual scene on the retina between eye movements, our perception of the visual world is constant and unified. It is generally believed that this space constancy is due to the brain’s ability of spatial updating. Although many efforts have been made to discover the mechanism underlying spatial updating across eye movements, still there are many unanswered questions about the neuronal mechanism of this phenomenon. We developed a state space model for updating gaze-centered spatial information. To explore spatial updating, we considered two kinds of eye movements, saccade and smooth pursuit. The inputs to our proposed model are: a corollary discharge signal, an eye position signal and 2D visual topographic maps of visual stimuli. The state space is represented by a radial basis function neural network and we can obtain a topographic map of the remembered visual target in its hidden layer. Finally, the decoded location of the remembered target is the output of the model. We trained the model on the double step saccade-saccade and pursuit-saccade tasks. Training this model revealed that the receptive fields of state-space units are remapped predictively during saccades and updated continuously during smooth pursuit. Moreover, during saccades, receptive fields also expanded (to our knowledge, this predicted expansion has not yet been reported in the published literature). We believe that incorporating this model can shed light on the underlying neural mechanism for Trans-saccadic perception

Variation in tissue-specific gene expression among natural populations

BACKGROUND: Variation in gene expression is extensive among tissues, individuals, strains, populations and species. The interactions among these sources of variation are relevant for physiological studies such as disease or toxic stress; for example, it is common for pathologies such as cancer, heart failure and metabolic disease to be associated with changes in tissue-specific gene expression or changes in metabolic gene expression. But how conserved these differences are among outbred individuals and among populations has not been well documented. To address this we examined the expression of a selected suite of 192 metabolic genes in brain, heart and liver in three populations of the teleost fish Fundulus heteroclitus using a highly replicated experimental design. RESULTS: Half of the genes (48%) were differentially expressed among individuals within a population-tissue group and 76% were differentially expressed among tissues. Differences among tissues reflected well established tissue-specific metabolic requirements, suggesting that these measures of gene expression accurately reflect changes in proteins and their phenotypic effects. Remarkably, only a small subset (31%) of tissue-specific differences was consistent in all three populations. CONCLUSIONS: These data indicate that many tissue-specific differences in gene expression are unique to one population and thus are unlikely to contribute to fundamental differences between tissue types. We suggest that those subsets of treatment-specific gene expression patterns that are conserved between taxa are most likely to be functionally related to the physiological state in question

Verification of analytic energy moments for the one-dimensional energy dependent neutron diffusion equation with MCNP5 and Attila-7.1.0

pre-printThe energy dependent neutron diffusion equation (EDNDE) is converted into a moment equation which is solved analytically for the 1-D problem of a bare sphere of pure 235U. The normalized moments 0-5 generated analytically are compared to normalized energy moments, from Monte Carlo N Particle 5 version 1.40 (MCNP5) and Attila-7.1.0-beta version (Attila). The analytic normalized neutron energy moments, fall between the results from MCNP5 (lower bound) and Attila (upper bound) and are accurate compared to MCNP5 neutron energy moments when error in this Monte Carlo simulation are considered. The error range is from 0% to 14%. The Attila moments are less accurate when compared to MCNP5 than the analytical moments derived in this work. The method of moments is shown to be a fast reliable method, compared to either Monte Carlo methods (MCNP5) or 30 multi-energy group methods (Attila)