bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Chronic Ethanol Exposure on Inositol Trisphosphate Receptors in WB Rat Liver Epithelial Cells
Authors: Bokkala Shaila , Rubin Emanuel , Joseph Suresh K.
Published: May 2006

Background: Enhanced agonist‐induced Ca2+ release has been reported in hepatocytes isolated from ethanol‐fed rats. Because myo‐inositol 1,4,5‐trisphosphate receptors (IP3Rs) are involved in the mobilization of Ca2+, we examined the effects of chronic ethanol treatment on IP3R function and levels of IP3R protein by using WB rat liver epithelial cells.

Methods: WB cells were treated with ethanol (50–150 mM) for 24 to 48 hr and were loaded with Fura‐2 to measure agonist‐induced Ca2+ mobilization or saponin permeabilized to measure myo‐inositol 1,4,5‐trisphosphate (IP3)‐mediated Ca2+ release. IP3 levels were measured in [3H]‐inositol labeled cells. Levels of IP3R protein were quantitated by immunoblotting with antibodies to IP3R isoforms. Lysosomal and proteasomal peptidase activities were assayed in cytosol and membrane fractions using specific fluorogenic peptide substrates.

Results: Ethanol treatment enhanced Ca2+ mobilization in response to angiotensin II, vasopressin, and bradykinin. This effect was not due to an increased production of IP3. Chronic ethanol treatment stimulated the mobilization of Ca2+ from saponin‐permeabilized cells in response to subsaturating doses of IP3 and increased the basal levels of both type I and type III IP3Rs by 1.8‐fold and 1.6‐fold, respectively. Ethanol treatment did not prevent angiotensin II‐induced IP3R down‐regulation or alter lysosomal cathepsin B activity or the trypsin‐like and peptidylglutamyl peptidase activities of the proteasome. However, chronic ethanol exposure resulted in a 60% and 41% inhibition of the chymotrypsin‐like activity of the proteasome in cytosol and microsomal membranes, respectively.

Conclusion

: We propose that the enhanced agonist‐mediated Ca2+ mobilization observed in chronic ethanol‐treated WB liver epithelial cells results from increased IP3R expression caused by an inhibition of IP3R degradation pathways by ethanol.
Effects of L‐Type Voltage‐Sensitive Calcium Channel Modulators on the Discriminative Stimulus Effects of Ethanol in Rats
Authors: Green Kristen L. , Grant Kathleen A.
Published: May 2006

The purpose of thc present investigation was to determine whether administration of dihydropyridine‐sensitive calcium channels plays a role in modulating the discriminative stimulus effects of ethanol. A food‐rcinforccd operant methodology was used to train adult male Long‐Evans rats to discriminate either 1.0 g/kg of ethanol from water or 2.0 g/kg of ethanol from water. After training, two sets of experiments were conductcd. First, a tinic course procedure was implemented whereby a single intraperitoneal dose of either nimodipine (3, 10, 30 mg/kg). nifedipinc (3, 10, 30 mgikg), or isradipine (1, 3, 10,17 mg/kg) was administered, and test sessions were conducted 10,20,30,60, and 90 min postinjection. Complete substitution (80% or greater ethanol‐appropriate responding) for ethanol by these dihydropyridine compounds varied among subjects with dose and pretreatment time. Overall, isradipine substituted for the discriminative stimulus effects of ethanol in the greatest percentage of animals in both training groups. However, substitution varicd with dose. Nifedipinc dose dcpendcntly substituted for ethanol in half of the animals trained with 1.0 g/kg of ethanol but was less effective in animals trained with 2.0 g/kg of ethanol. For the second set of experiments, a single dose of nimodipine, nifedipine, isradipine, or (‐)‐BAY k 8644 was administered before determination of the cumulative ethanol dose rcsponse. Nifedipine produced a significant leftward shift and (‐)‐BAY k 8644 produced a significant rightward shift in the ethanol dose‐response curve in animals trained to discriminate 2.0 g/kg of ethanol from water. These results indicate that the administration of VGCC modulators plays an indirect role in the discriminative stimulus effects of ethanol.
Acute and Long Term Effects of Buspirone Treatments on Voluntary Ethanol Intake in a Rat Model of Alcoholism
Authors: Hedlund Lars , Wahlström Göran
Published: May 2006

Buspirone, a 5‐HT1A agonist, has been shown to decrease the intake of ethanol when given as a single dose to rats with a psychological dependence induced according to our rat model of alcoholism. The present experiment evaluates the effects different treatments with buspirone have on voluntary ethanol intake in these psychologically dependent rats. As a first treatment, buspirone was given once daily for 23 days at the dose of 20 mg/kg/day. Ethanol was withheld except for the first and the last day of the treatment. On the first day, the buspirone injection decreased ethanol intake from the pretreatment value (1.94 ± 0.18 g/kg/day), down to 1.36 ± 0.18 g/kg (p < 0.01, n= 12). The rats were again given a choice between water and 10% ethanol after the last injection of buspirone. During the following 24 hr period, the ethanol intake was increased to 3.56 ± 0.24 g/kg/day (p < 0.001 vs. the pretreatment intake, n= 12). A loss of correlation with the pretreatment intake of ethanol indicated an altered regulation of ethanol intake for approximately 3 more weeks. Fifteen weeks after the start of the first treatment, buspirone (20 mg/kg) was re‐tested as a single dose, with no effect on ethanol intake. Twenty‐two weeks after the start of the first treatment a 1‐week treatment with 20 mg/kg/day of buspirone was started. During this treatment, the rats had a continuous choice between 10% ethanol and water. There was, as in the first re‐test, no effect on ethanol intake on the first day of the treatment. However, on the last 2 days of the treatment, the ethanol intake was increased to 2.86 ± 0.28 g/kg and to 2.89 ± 0.26 g/kg respectively (p < 0.05, n= 10 on both days, compared with the pretreatment intake of 1.78 ± 0.36 g/kg). Thus, an acute dose of buspirone can decrease voluntary ethanol intake in psychologically dependent rats, but long‐lasting changes in the effect of buspirone seem to develop during a 3‐week treatment period.
Effects of Nitric Oxide Synthase Blockade on the Acute Response of the Reproductive Axis to Ethanol in Pubertal Male Rats
Authors: Emanuele M. A. , LaPaglia N. , Steiner J. , Kirsteins L. , Emanuele N. V.
Published: May 2006

The effects of ethanol (EtOH) and nitric oxide (NO) are well known in the adult male rat reproductive axis. In the present study, we investigate the effects of EtOH, NO, and their interaction on key genes and reproductive hormone levels in mid‐(45‐day) and late pubertal(55‐day) male rats. Using three different NO synthase blockers—N‐nitro‐L‐arginine methyl ester (L‐NAME), N;‐nitro‐L‐arginine (L‐NA), and 7‐nitroi‐ndazole—we show that it is possible to block, in part, some of the disruptive effects of EtOH. L‐NAME totally prevented the EtOH‐induced fall in serum testosterone in both 45‐ and 55‐day‐old rats (p < 0.05 and p < 0.001, respectively). On the other hand, the D‐NAME, an inactive isomer of L‐NAME, did not protect testosterone from suppression caused by EtOH. Similarly, L‐NA and 7‐nitroindazole prevented the suppression of testosterone caused by EtOH in 55‐day‐old animals (p < 0.001 L‐NA and p <0.05 for 7‐nitroindazole), but not in the 45‐day‐old rats. Serum luteinizing hormone (LH) was significantly reduced by EtOH in all the studies in both age groups. L.‐NAME (but not D‐NAME) and L‐NA prevented this inhibition in 55‐day‐old animals (p < 0.001 for L‐NAME and p < 0.01 for L‐NA). However, only L‐NA was able to prevent the effects of EtOH on LH in the 45‐day‐old rats. 7‐Nitroindazole was unable to prevent the decrease in LH in either age group. Despite changes in the other reproductive hormones, there were no consistent changes in hypothalamic concentrations of either LH releasing hormone (LHRH) or its precursor. pro‐LHRH. No treatment caused any change in steady‐state levels of β‐LH mRNA. There were no consistent changes in pro‐LHRH mRNA; but, interestingly, in 45‐day‐old rats, L‐NA given with or without EtOH lead to a significant fall in LHRH gene expression. Our findings indicate that the acute suppressive effects of EtOH on the hypothalamic‐pituitary‐gonadal axis of the purbertal male rat can be at least partially prevented by NO synthase blockade.
Cytokine Regulation of Hepatic Stellate Cells in Liver Fibrosis
Authors: Tsukamoto Hidekazu
Published: May 2006

Cytokines constitute a major class of mediators responsible for “activation” of hepatic stellate cells (HSCs) in vitro and in vivo. They are largely divided into mitogenic (transforming growth factor‐α, platelet‐derived growth factor, interleukin‐1, tumor necrosis factor‐α, and insulin‐like growth factor) and fibrogenic (transforming growth factor‐β and interleukin‐6) cytokines. In addition to their mitogenic (stimulation of cell proliferation) and fibrogenic (induction of matrix proteins) properties, they are also shown to confer in vitro unique cellular changes known to be the key features of HSC “activation,” including loss of vitamin A, stimulation of migration, enhanced cellular contractility, and matrix metalloproteinase and tissue inhibitor of metalloproteinase induction. Potential cellular sources of the cytokines consist of hepatic macrophages, endothelial cells, biliary epithelial cells, lymphocytes, platelets, hepatocytes, and activated HSCs. To better understand the mode of actions and the pathogenetic significance of cytokineskhemokines involved in “activation” of HSCs, the following four questions need to be addressed: (1) What other cytokines are expressed by HSCs to establish critical autocrine stimulation? (2) What are endogenous or exogenous priming factors for HSC stimulation? (3) What is the mechanism of activation for transforming growth factor‐β, the pivotal fibrogenic cytokine? (4) How important are HSC‐derived proinflammatory mediators in liver fibrosis? This review will discuss these questions, along with the current understanding of the role of cytokines in HSC activation.
Role of Transcriptional Factors in Stellate Cell Activation
Authors: Rippe Richard A.
Published: May 2006

Fibrogenic stimuli induce a complex activation process in the hepatic stellate cell (HSC) resulting in numerous changes in gene expression. These changes include increases in the synthesis and deposition of several extracellular matrix (ECM) proteins, most notably type I collagen. The synthesis of type I collagen following HSC activation is controlled, in part, at the transcriptional level. Dramatic changes occur in transcription factor binding to ECM genes following HSC activation. Similarities between type I collagen and biglycan gene expression suggest that common transcriptional mechanisms may regulate ECM expression following HSC activation. Several transcription factors display increased activity with HSC activation. The identification of new potential therapeutic targets may become evident providing novel therapeutic avenues aimed at either blocking or slowing the fibrogenic or inflammatory process in which the activated HSC participates.
Targeting of Therapeutics to the Liver: Liposomes and Viral Vectors
Authors: Di Campli C. , Wu J. , Zern M. A.
Published: May 2006

A successful strategy for the treatment of hepatic damage should be based on the use of nontoxic drugs with a high therapeutic index and safety profile, as well as selective targeting delivery. To achieve these goals, several biological and synthetic vehicles have been formulated with a wide range of chemical and physical properties. These vectors allow the delivery of either traditional drugs or genetic material to the cells. Despite remarkable progress, the design of an ideal carrier is still to be accomplished. Safety issues concerning viral vectors and low efficiency of synthetic delivery systems are the main limitations of present vectors. Once these problems are overcome, the liver‐specific targeting systems will provide new opportunities to treat a vast range of hepatic diseases.
Computerized Estimates of Potential Occupational Health Risk Due to Chemical Exposure
Authors: Pedersen David H. , Hornung Richard W.
Published: May 2006

Estimating the potential health risk encountered by workers due to their exposure to various chemicals is enormously complex, since many chemicals may be involved and each may have multiple toxic effects. As an aid to this estimation process, a computer program, or model, which computes index numbers expressing the relative health risk of occupational groups due to their potential chemical exposures was developed at the National Institute for Occupational Safety and Health (NIOSH). This model considers an inventory of the chemicals to which specific occupational groups are potentially exposed, the published information regarding the toxic effects of each chemical, and the conditions of occupational exposure. The system then develops indices of potential occupational group health risk by considering weighted combinations of eight distinct health effects. No direct comparison with external occupational risk indices is currently possible, but internal testing of the model reveals no obvious inconsistencies.
Sensitivity and Uncertainty Studies of the CRAC2 Computer Code
Authors: Kocher D. C. , Ward R. C. , Killough G. G. , Dunning D. E. , Hicks B. B. , Hosker R. P. , Ku J.‐Y. , Rao K. S.
Published: May 2006

We have studied the sensitivity of health impacts from nuclear reactor accidents, as predicted by the CRAC2 computer code, to the following sources of uncertainty: (1) the model for plume rise, (2) the model for wet deposition, (3) the meteorological bin‐sampling procedure for selecting weather sequences with rain, (4) the dose conversion factors for inhalation as affected by uncertainties in the particle size of the carrier aerosol and the clearance rates of radionuclides from the respiratory tract, (5) the weathering half‐time for external ground‐surface exposure, and (6) the transfer coefficients for terrestrial foodchain pathways. Predicted health impacts usually showed little sensitivity to use of an alternative plume‐rise model or a modified rain‐bin structure in bin‐sampling. Health impacts often were quite sensitive to use of an alternative wet‐deposition model in single‐trial runs with rain during plume passage, but were less sensitive to the model in bin‐sampling runs. Uncertainties in the inhalation dose conversion factors had important effects on early injuries in single‐trial runs. Latent cancer fatalities were moderately sensitive to uncertainties in the weathering half‐time for ground‐surface exposure, but showed little sensitivity to the transfer coefficients for terrestrial foodchain pathways. Sensitivities of CRAC2 predictions to uncertainties in the models and parameters also depended on the magnitude of the source term, and some of the effects on early health effects were comparable to those that were due only to selection of different sets of weather sequences in bin‐sampling.
A Suggested Approach to Overcome California's Inability to Permit Urban Resource Recovery Facilities
Authors: Broiles Steven A.
Published: May 2006

The premature political termination of the permit reviews of five urban resource recovery projects in California may indicate a deficiency in the process under which project health risk assessments are performed and policy biases of the public agencies that control the contents of the assessments. This article examines the permitting process that separates project health risk assessments from environmental impact reports and the anti‐resource‐recovery goals and policies of the state and local agencies that guide the preparation of project health risk assessments. Also examined are two independent studies made of the informational adequacy of the LANCER project documents. The article concludes that it is only by merging the risk assessment process with the environmental review process that control of the agencies can be loosened and project proponents be able to prepare project risk assessments for urban California resource recovery projects that will offer the projects any likelihood of being able to complete the permitting process.
Postnatal Effects of Prenatal Insult
Authors: Johnson E. Marshall , Newman Lois M. , Schmidt Richard R.
Published: May 2006

Exogenous agents may perturb development during the embryonic period and adversely affect the formation of organs. However, adverse effects on development are not limited to the embryonic period nor are the manifestations restricted solely to outright gross structural malformation, but may instead be expressed as a decrement or aibberration of postnatal function. Susceptibility to altered development may extend well into the postnatal period. Studies of functional parameters in several organ systems have demonstrated the broad‐based susceptibility, subtlety of expression and potential of long‐lasting effects of altered development assessed by physiologic assays. Adverse effects on functional development, whether in the CNS, reproductive, gastrointestinal, genitourinary, respiratory, or immune systems, etc., merit continuing investigation. From the viewpoint of risk estimation and hazard detection, evaluations of postnatal functional parameters may be relevant for several reasons. First, such parameters may serve as low‐dose triggers. Second, they may be useful as a focal point for epidemiological studies. Finally, a more thorough understanding of the degree and magnitude of such postnatal functional deficits is needed since an adverse maternal effect may be transient, considered acceptable, or unperceived, but the effect on the conceptus may be permanent and severe. The immune and respiratory systems are discussed as two examples of how subtle and protean adverse effects on functional development may be.
Applying Decision Analysis to Determine the Effect of Smoke Detector Laws on Fire Loss in the United States
Authors: Jensen David D. , Tome Alice E. , Darby William P.
Published: May 2006

Decision analysis is used to examine whether residential smoke detectors should be required by law. Statistics pertaining to fire incidence, fire death, smoke detector efficacy, and the consequences of fire are examined for accuracy and availability and combined in a decision model. A sensitivity analysis is performed on the model inputs. Included in the analysis is the idea that homes with detectors may have lower death rates due to the characteristics of those who purchase detectors rather than the detectors themselves. Results from the base case estimate show an expected cost of $65,000 per life saved when a law is enacted. This value lies well below the value implied by spending on other public safety programs.
The Effects of Publication Selection on Test Probabilities and Estimator Distributions
Authors: Denton Frank T.
Published: May 2006

Editorial decisions, based in part on reported hypothesis test results, affect the probabilities associated with those results: the probabilities of Type I and Type II errors thus become different for readers than for authors. The distributions of published parameter estimates are similarly affected. A framework for studying the consequences of test‐based information filtering is developed and illustrative examples are provided. The examples indicate that filtering can markedly distort the power functions of hypothesis tests and can induce large estimator biases and increases in mean square error. It is argued that test‐based filtering is relevant not only to journal publication but to other forms of information dissemination as well.
Mortality Risks Induced by Economic Expenditures
Authors: Keeney Ralph L.
Published: May 2006

Existing evidence shows that lower incomes are associated with higher mortality risks. This paper examines the implications for fatalities when the relationship is interpreted as an induced relationship, meaning that lower incomes will on average lead to higher mortality risks. A model is developed for estimating the number of fatalities possibly induced by economic expenditures. This model accounts for different allocations of the expenditures on family units with varying income levels. Illustrative calculations provide insights about the possible significance of fatalities induced by economic expenditures. These results suggest that some expensive regulations and programs intended to save lives may actually lead to increased fatalities. Important caveats to reduce the likelihood of misinterpreting or misusing the results are included.
Tissue Dosimetry for Reactive Metabolites
Authors: Travis Curtis C.
Published: May 2006

In recent pharmacokinetically based risk assessments for methylene chloride, Andersen et al.(1) argued that total reactive metabolite (TRM) divided by liver weight was the proper measure of dose to target tissue, while the EPA argued that TRM divided by body weight to the two‐thirds power was more appropriate.(2) We demonstrate that the proper tissue metric for a reactive metabolite is dependent upon the mode of deactivation: metabolic or spontaneous. It is argued that the most appropriate measure of tissue dosimetry is: (1) TRM divided by the three‐fourths power of body weight if the reactive metabolite is metabolically deactivated; or (2) TRM divided by body weight if the reactive metabolite is spontaneously deactivated.
Elicitation of Decision‐Makers’Preferences for Management of Major Hazards
Authors: Hubert P. , Barny M.H. , Moatti J. P.
Published: May 2006

A survey has been conducted among decision‐makers from the urban area of Lyon (France). It aimed at elicitating attitudes toward industrial risk, with an emphasis on major hazards. The sample was quite small (23 individuals), but most of the actual decision‐makers of the area belonged to it. A questionnaire allowed to look at the weights that are given to “catastrophic accidents,” when compared to more usual ones. It showed that decision‐makers are strongly “adverse to catastrophes.” The findings support many risk management approaches that are based on assigning an “extra weight” to potential accidents that may cause a high number of casualties.
An Alternative Approach to Dietary Exposure Assessment
Authors: Petersen Barbara J. , Barraj Leila M. , Muenz Larry R. , Harrison Stanley L.
Published: May 2006

The method of dietary exposure assessment currently used by the Environmental Protection Agency (EPA), the Dietary Residue Evaluation System (DRES), combines a consumption distribution derived from the United States Department of Agriculture (USDA) 1977‐1978 Nationwide Food Consumption Survey (NFCS) with a single estimate of residue level. The National Academy of Sciences‘1’ recommended that EPA incorporate both the distribution of residues and the distribution of consumption into their exposure assessment methodology and proposed using a Monte Carlo approach. This paper presents an alternative method, the Joint Distributional Analysis (JDA), that combines the consumption and residue distributions, without relying on random sampling or fitting theoretical distributions like the Monte Carlo method. This method permits simultaneous analysis of the entire diet, including assessing exposure from residues in different foods.
A Note on Compounded Conservatism
Authors: Bogen Kenneth T.
Published: May 2006

Compounded conservatism (or “creeping safety”) describes the impact of using conservative, upper‐bound estimates of the values of multiple input variates to obtain a conservative estimate of risk modeled as an increasing function of those variates. In a simple multiplicative model of risk, for example, if upper p‐fractile (100pth percentile) values are used for each of several statistically independent input variates, the resulting risk estimate will be the upper p'‐fractile of risk predicted according to that multiplicative model, where p' > p. The amount of compounded conservativism reflected by the difference between p' and p may be substantial, depending on the number of inputs, their relative uncertainties, and the value of p selected. Particular numerical examples of compounded conservatism are often cited, but an analytic approach may better serve to conceptualize and communicate its potential quantitative impact. This note briefly outlines such an approach and illustrates its application to the case of risk modeled as a product of lognormally distributed inputs.
Selection of Probability Distributions in Characterizing Risk of Extreme Events
Authors: Lambert James H. , Matalas Nicholas C. , Ling Con Way , Haimes Yacov Y. , Li Duan
Published: May 2006

Use of probability distributions by regulatory agencies often focuses on the extreme events and scenarios that correspond to the tail of probability distributions. This paper makes the case that assessment of the tail of the distribution can and often should be performed separately from assessment of the central values. Factors to consider when developing distributions that account for tail behavior include (a) the availability of data, (b) characteristics of the tail of the distribution, and (c) the value of additional information in assessment. The integration of these elements will improve the modeling of extreme events by the tail of distributions, thereby providing policy makers with critical information on the risk of extreme events. Two examples provide insight into the theme of the paper. The first demonstrates the need for a parallel analysis that separates the extreme events from the central values. The second shows a link between the selection of the tail distribution and a decision criterion. In addition, the phenomenon of breaking records in time‐series data gives insight to the information that characterizes extreme values. One methodology for treating risk of extreme events explicitly adopts the conditional expected value as a measure of risk. Theoretical results concerning this measure are given to clarify some of the concepts of the risk of extreme events.
Policy Against Science: The Case of Environmental Tobacco Smoke
Authors: Gori Gio Batta
Published: May 2006

The grounds for official policy claims that environmental tobacco smoke is a major health risk remain speculative. In scientific terms, the evidence is compatible with either a slight increase or a decrease of risks, but is impotent to certify either conclusion. Official advocacy of unproven hypotheses presented as valid scientific conclusions raises serious ethical questions, and threatens the credibility of risk assessment as a legitimate policy instrument.
U.S. Aviation Regulations Increase Probability of Midair Collisions
Authors: Patlovany Robert W.
Published: May 2006

A purely stochastic Monte Carlo model is used to compare the relative midair collision course probabilities and mean closing velocities of four systems of rules for aircraft cruising altitudes as a function of altitude error: (1) current U.S. federal rules, (2) random altitudes, and (3) two proposed alternatives to the current rules. This model increments error while: (1) counting collisions among cruising pairs of aircraft following the four rules being tested on random headings between randomly placed airports, and (2) calculating mean closing velocities for each rule. The calculations verify that: (1) federal rules increase collision course probabilities by about four times more than for a chaotic system of aircraft cruising at randomly selected altitudes, (2) risk is directly proportional to the level of compliance, and (3) mean closing velocities resulting from the current rule are slightly less than for random altitudes, while being almost twice as high as for the proposed rules. High closing velocities are shown to increase the collision probability.
Anesthesia Patient Risk: A Quantitative Approach to Organizational Factors and Risk Management Options
Authors: Paté‐Cornell M. Elisabeth , Lakats Linda M. , Murphy Dean M. , Gaba David M.
Published: May 2006

The risk of death or brain damage to anesthesia patients is relatively low, particularly for healthy patients in modern hospitals. When an accident does occur, its cause is usually an error made by the anesthesiologist, either in triggering the accident sequence, or failing to take timely corrective measures. This paper presents a pilot study which explores the feasibility of extending probabilistic risk analysis (PRA) of anesthesia accidents to assess the effects of human and management components on the patient risk. We develop first a classic PRA model for the patient risk per operation. We then link the probabilities of the different accident types to their root causes using a probabilistic analysis of the performance shaping factors. These factors are described here as the “state of the anesthesiologist” characterized both in terms of alertness and competence. We then analyze the effects of different management factors that affect the state of the anesthesiologist and we compute the risk reduction benefits of several risk management policies. Our data sources include the published version of the Australian Incident Monitoring Study as well as expert opinions. We conclude that patient risk could be reduced substantially by closer supervision of residents, the use of anesthesia simulators both in training and for periodic recertification, and regular medical examinations for all anesthesiologists.
Conservatism of the Accident Sequence Evaluation Program HRA Procedure
Authors: Gore Bryan F. , Dukelow James S. , Mitts Timothy M. , Nicholson Wesley L.
Published: May 2006

This paper presents a limited assessment of the conservatism of the Accident Sequence Evaluation Program (ASEP) human reliability analysis (HRA) procedure described in NUREG/CR‐4772. The data for this study are derived from simulator examination reports from the NRC requalification examination cycle for nuclear power plant operators. The ASEP procedure was used to estimate human error probability (HEP) values for critical tasks, and the HEP results were compared with the failure rates observed in the examinations. The ASEP procedure was applied by PNNL operator license examiners who supplemented the limited information in the examination reports with expert judgment based upon their extensive simulator examination experience. Comparison of the average of the ASEP HEP values with the fraction of the population actually failed and demonstrated that the ASEP HEP values are larger (conservative) by a statistically significant average factor of two. Partitioning of tasks into subgroups based on the ASEP HEP values and comparison of the subgroup average ASEP HEP values with observed subgroup failure rates showed little or no conservatism for small ASEP HEP values, but considerable conservatism for larger ASEP HEP values.
A Score Comparison Method as an Aid to Integrating Separate Comparative Risk Rankings into a Single, Comparative Risk Ranking
Authors: Deisler Paul F.
Published: May 2006

A Score Comparison Method (SCM), for use in comparative risk projects, is described. It provides a degree of analytical guidance for those undertaking to integrate environmental issues which have been placed into separate, qualitative rankings according to different types of risk into a single, qualitative, integrated risk ranking. Its use in an actual case is shown.
Does Diesel Exhaust Cause Human Lung Cancer?
Authors: Cox Louis Anthony
Published: May 2006

Recent reviews of epidemiological evidence on the relation between exposure to diesel exhaust (DE) and lung cancer risk have reached conflicting conclusions, ranging from belief that there is sufficient evidence to conclude that DE is a human lung carcinogen (California EPA, 1994) to conclusions that there is inadequate evidence to support a causal association between DE and human lung cancer (Muscat and Wynder, 1995). Individual studies also conflict, with both increases and decreases in relative risks of lung cancer mortality being cited with 95% statistical confidence. On balance, reports of elevated risk outnumber reports of reduced risk. This paper reexamines the evidence linking DE exposures to lung cancer risk. After briefly reviewing animal data and biological mechanisms, it surveys the relevant epidemiological literature and examines possible explanations for the discrepancies. These explanations emphasize the distinction between statistical associations, which have been found in many studies, and causal associations, which appear not to have been established. Methodological threats to valid causal inference are identified and new approaches for controlling them are proposed using recent techniques from artificial intelligence (AI) and computational statistics. These threats have not been adequately controlled for in previous epidemiological studies. They provide plausible noncausal explanations for the reported increases in relative risks, making it impossible to infer causality between DE exposure and lung cancer risk from these studies. A key contribution is to show how recent techniques developed in the AI‐and‐statistics literature can help clarify the causal interpretation of complex multivariate data sets used in epidemiological risk assessments. Applied to the key study of Garshick et al. (1988), these methods show that DE concentration has no positive causal association with occupational lung cancer mortality risk.
Use of Technical Expert Panels: Applications to Probabilistic Seismic Hazard Analysis*
Authors: Budnitz Robert J. , Apostolakis George , Boore David M. , Cluff Lloyd S. , Coppersmith Kevin J. , Cornell C. Allin , Morris Peter A.
Published: May 2006

Probabilistic Seismic Hazard Analysis (PSHA) is a methodology that estimates the likelihood that various levels of earthquake‐caused ground motions will be exceeded at a given location in a given future time period. Due to large uncertainties in all of the geosciences data and in their modeling, multiple model interpretations are often possible. This leads to disagreements among the experts, which in the past has led to disagreement on the selection of a ground motion for design at a given site. This paper reports on a project, co‐sponsored by the U.S. Nuclear Regulatory Commission, the U.S. Department of Energy, and the Electric Power Research Institute, that was undertaken to review the state‐of‐the‐art and improve on the overall stability of the PSHA process, by providing methodological guidance on how to perform a PSHA. The project reviewed past studies and examined ways to improve on the present state‐of‐the‐art. In analyzing past PSHA studies, the most important conclusion is that differences in PSHA results are commonly due to process rather than technical differences. Thus, the project concentrated heavily on developing process recommendations, especially on the use of multiple experts, and this paper reports on those process recommendations. The problem of facilitating and integrating the judgments of a diverse group of experts is analyzed in detail. The authors believe that the concepts and process principles apply just as well to non‐earthquake fields such as volcanic hazard, flood risk, nuclear‐plant safety, and climate change.
The Role of the Community in the Implementation of the EPA's Rule on Risk Management Programs for Chemical Accidental Release Prevention
Authors: Rosenthal Isadore , McNulty Patrick J. , Helsing Lyse D.
Published: May 2006

Regulations under the 1990 Clean Air Act Amendments (CAAA) include requirements for preventing accidental chemical releases. Section 112(r) of the CAAA, the Accidental Release Provisions, requires the U.S. Environmental Protection Agency (EPA) to develop and implement regulations for preventing accidental releases to the air of regulated substances and to minimize the consequences of releases that do occur. The regulations require regulated facilities to have in place the structural elements of a sound process safety program, and to practice, document, and communicate the elements of their program. The rule requires also that registered facilities calculate and make available worst case accidental chemical release information. The rule does not set a level of risk that a facility must achieve after it takes the required compliance steps, the level of risk a community must accept, the limit of consequences the community might suffer from a worst case chemical release, nor the specific actions a community must take in its response plan. These are issues that local communities and local officials must decide. Because the regulation involves the community in many unsettled risk issues the Wharton School initiated a project within the City Philadelphia to evaluate the proposition that productive dialogue on the implementation of the Rule and resolution of unsettled risk issues can take place in advance of a crisis occasioned by a major accidental release. This paper describes the steps taken by Wharton to bring together various stakeholders in the community to explore the implementation of the rule and the reaction of those stakeholders to be involved in such a process. It outlines some principal choices communities will have to make in order to implement 112(r) and explains some of the dilemmas associated with these choices. It describes the stakeholder‐based implementation effort being undertaken in Philadelphia in the hope that others may benefit from what has been learned there.
Use of an ISO 14000 Option in Implementing EPA's Rule on Risk Management Programs for Chemical Accidental Release Prevention
Authors: Rosenthal Isadore , Theiler Donald F.
Published: May 2006

EPA's rule of Risk Management Programs for Chemical Accidental Release Prevention applies to facilities that manufacture, process, use, store, or otherwise handle regulated substances at or above specified threshold quantities. EPA estimates that approximately 66,000 facilities nationwide will be regulated under the rule. This paper examines the use of a structured ISO 14000 mechanism as option‐regulated facilities could elect for implementation of the rule. Under the ISO 14000 option, facilities would commit to additional obligations regarding information disclosure, discussions with potentially affected publics, and timely correction of deficiencies noted in annual ISO 14000 audits of their compliance with the Risk Management Program they submit to the EPA under the rule. In return, facilities would be granted significant relief in regard to both EPA audit frequency and the penalties that might be applied for any items of noncompliance with the rule noted during the course of implementing agency reviews of the facility. The paper concludes with a discussion of the advantages and disadvantages of this option to potentially affected stakeholders.
Empirical Scaling of Single Oral Lethal Doses Across Mammalian Species Based on a Large Database
Authors: Rhomberg Lorenz R. , Wolff Scott K.
Published: May 2006

The scaling of administered doses to achieve equal degrees of toxic effect in different species has been relatively poorly examined for noncancer toxicity, either empirically or theoretically. We investigate empirical patterns in the correspondence of single oral dose LD, values across several mammalian species for a large number of chemicals based on data reported in the RTECSQ database maintained by the National Institute for Occupational Safety and Health. We find a good correspondence of LD, values across species when the dose levels are expressed in terms of mgadministered per kg of body mass. Our findings contrast with earlier analyses that support scaling doses by the 3/4‐power of body mass to achieve equal subacute toxicity of antineoplastic agents. We suggest that, especially for severe toxicity, single‐ and repeated‐dosing regimes may have different cross‐species scaling properties, as they may depend on standing levels of defenses and rate of regeneration of defenses, respectively.
Adverse Health Experiences, Environmental Attitudes, and Pesticide Usage Behavior of Farm Operators
Authors: Lichtenberg Erik , Zimmerman Rae
Published: May 2006

Water pollution from agricultural pesticides continues to be a public concern. Given that the use of such pesticides on the farm is largely governed by voluntary behavior, it is important to understand what drives farmer behavior. Health belief models in public health and social psychology argue that persons who have adverse health experiences are likely to undertake preventive behavior. An analogous hypothesis set was tested here: farmers who believe they have had adverse health experiences from pesticides are likely to have heightened concerns about pesticides and are more likely to take greater precautions in dealing with pesticides. This work is based on an original survey of a population of 2700 corn and soybean growers in Maryland, New York, and Pennsylvania using the U.S. Department of Agriculture data base. It was designed as a mail survey with telephone follow‐up, and resulted in a 60 percent response rate. Farm operators report experiencing adverse health problems they believe are associated with pesticides that is equivalent to an incidence rate that is higher than the reported incidence of occupational pesticide poisonings, but similar to the reported incidence of all pesticide poisonings. Farmers who report experiencing such problems have more heightened concerns about water pollution from fertilizers and pesticides, and illness and injury from mixing, loading, and applying pesticides than farmers who have not experienced such problems. Farmers who report experiencing such problems also are more likely to report using alternative pest management practices than farmers who do not report having such problems. This implies that farmers who have had such experiences do care about the effects of application and do engage in alternative means of pest management, which at least involve the reduction in pesticide use.
Dental caries and dental registration status in nursery school children in Newry, Northern Ireland
Authors: McCabe M. , Kinirons M. J.
Published: May 2006

Abstract 294 children aged 2–4 yr attending nursery schools in Northern Ireland were examined for dental caries and dental registration status under the capitation system in general dental practice. Their mean age was 3 yr 10 months. Sixty eight per cent were caries free, mean dmft was 1.10 and dt, mt and ft scores were 0.74, 0.28 and 0.09, respectively. With increasing age the prevalence of caries increased, though the very low care index (d/dmft) did improve in the older children. Seventy per cent reported being registered for dental care and their levels of dental caries were significantly higher than those who were not yet enrolled (P < 0.001). For those not enrolled for dental care the main perceived barriers to seeking care related to lack of symptoms (33.6%) and apathy (31.6%) while few reported fear as a barrier (4.5%).
What is the effective concentration of fluoride'
Authors: Ismail Amid I.
Published: May 2006

Abstract This paper discusses the historical and current epidemiological evidence of the effectiveness of fluoride in caries prevention and proposes that in vivo concentrations of fluoride in the oral environment should be determined for different caries challenges.
Restoration of approximal carious lesions – application of decision analysis
Authors: Kay Elizabeth Jane , Brickley Mark , Knill‐Jones Robin
Published: May 2006

Abstract This study uses decision analysis in order to explore the maximum expected utility of positive and negative restorative decisions, made on the basis of bitewing radiography. The a posteriori probabilities of disease, given a positive/negative treatment decision were derived from a study in which 20 dentists made 7200 decisions about 15 pairs of simulated bitewing radiographs. Lesion depths in the teeth examined were ascertained by light microscopy. A review of the available data on lesion progression/regression was undertaken to provide probability values for the decision model, and population utilities for the outcomes of the decision were derived from a survey of 110 members of the public. The decision analysis showed that negative treatment decisions always attracted the highest maximum expected utility, except in highly disease‐prone individuals. This analysis demonstrates that lesion depth, likelihood of pain, and the rate of lesion progression have minimal effect on the utility of a positive treatment decision. It is concluded that an over‐concentration on the biomedical model of dental health may cause dentists to make decisions which are inappropriate to their patients' values and preferences.
Unmet orthodontic treatment need in rural Nigerian adolescents
Authors: Otuyemi Olayinka D. , Ugboko Vincent I. , Adekoya‐Sofowora Comfort A. , Ndukwe Kizito C.
Published: May 2006

Abstract A survey of orthodontic treatment need was carried out among randomly selected rural Nigerian adolescents using the index of orthodontic treatment need. Altogether, 704 subjects (381 boys and 323 girls) aged 12–18 years (mean 14.8, SD 1.79) were recruited in the study. The results indicated that 12.6% of the population were in objective need of orthodontic treatment. Whilst there was a discrepancy in the proportions of Nigerian adolescents needing orthodontic treatment on aesthetic and dental health grounds, girls were found to have a more attractive dental appearance and less orthodontic treatment need than boys. However, the differences were not statistically significant (P > 0.05). The correlation between the orthodontist's and the subject's rating of dental appearance was found to be low (r=0.35). The study also provided reliable baseline data for planning orthodontic services in Nigeria especially in areas where there are no dental services.
A survey of time management and particular tasks undertaken by consultant microbiologists in the UK
Authors: Riordan Terry , Cartwright Keith , Cunningham Richard , Logan Margaret , Wright Paul
Published: May 2006

Background:Medical microbiology practice encompasses a diverse range of activities. Consultant medical microbiologists (CMMs) attribute widely differing priorities to, and spend differing proportions of time on various components of the job.

Aim:To obtain a professional consensus on what are high-priority and low-priority activities, and to identify the time spent on low-priority activities.

Method:National survey.

Results:Many respondents felt that time spent on report authorisation and telephoning of results was excessive, whereas time spent on ward-based work was inadequate. Timesaving could also be achieved through better prioritisation of infection-control activities.

Conclusion:CMMs should apportion their time at work focusing on high-priority activities identified through professional consensus.
FIXED ENERGY R-SEPARATION FOR SCHRÖDINGER EQUATION
Authors: CHANU CLAUDIA , RASTELLI GIOVANNI
Published: May 2006

We extend the classical approach of the R-separation of the Laplace equation Δψ = 0 (as a null eigenvalue problem) to the general steady state Schrödinger equation including cases where a scalar potential V is present and the energy is a fixed constant.