bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol Uses cAMP‐Independent Signal Transduction Mechanisms to Activate Proenkephalin Promoter Activity in Rat C6 Glioma Cells
Authors: Yang Xiaoju , Wand Gary
Published: May 2006

Background: Previous in vivo studies show that acute ethanol exposure sequentially increases protein kinase A (PKA) activity, the phosphorylation of the adenosine 3′:5′‐cyclic monophosphate (cAMP) dependent transcription factor, CREB, and finally proenkephalin gene expression. The present study was conducted to determine if ethanol could activate directly the adenylyl cyclase pathway and thus enhance proenkephalin promoter activity.

Methods: Cultured rat C6 glioma cells stably transfected with a segment of the five prime flanking region of rat proenkephalin promoter (nucleotide ‐2700 + 53) ligated to the chloramphenicol acetyltransferase (CAT) reporter gene were employed to study the effects of ethanol on proenkephalin promoter activity. This region of proenkephalin promoter contains two cAMP response elements (CRE‐1 and CRE‐2) and one AP2 site located in the region upstream of the TATA box. Cultures were exposed to ethanol, isoproterenol, and phorbol‐12, myristate 13‐acetate (PMA) alone and in combination, in the presence and absence of PKA and protein kinase C (PKC) inhibitors.

Results: Ethanol and isoproterenol increased proenkephalin promoter activity in a dose‐dependent manner. Ethanol had an additive effect on maximal isoproterenol‐stimulated proenkephalin promoter activity, which suggested that ethanol used a cAMP‐independent signai transduction pathway to increase proenkephalin promoter activation. In contrast with isoproterenol, ethanol exposure did not increase cAMP accumulation, PKA activity, or the phosphorylated form of CREB. However, ethanol exposure modestly increased PKC activity. The PKA‐specific inhibitor, Rp‐cAMP, dampened isoproterenol‐induced activation of CAT activity but did not alter ethanol's ability to increase CAT activity. However, the PKC inhibitors, chelerthyrine and G07874, abrogated ethanol's effect of CAT activity but did not alter isoproterenol's effects.

Conclusions: Ethanol enhanced proenkephalin promoter activity and potentiated isoproterenol stimulated promoter activity through a cAMP‐independent pathway.
Cigarette Smoking Decreases the Prolactin Response to Serotonergic Stimulation in Subgroups of Alcoholics and Controls
Authors: Anthenelli Robert M. , Maxwell Rose A.
Published: May 2006

Background: The prolactin response to serotonergic stimulation has been used as an index of central nervous system serotonin function. We evaluated the prolactin response to d,l‐fenfluramine to determine whether subtypes of alcoholics differed in prolactin responsivity compared with nonalcoholics and whether cigarette smoking affected prolactin response.

Methods: One hundred ten healthy, abstinent men across four groups (controls [23% smokers]; alcoholics [72% smokers]; alcoholics with antisocial personality disorder [94% smokers]; nonalcoholic antisocials [88% smokers]) received d,l‐fenfluramine (100 mg orally) in a randomized, double‐blind, placebo‐controlled study. Plasma prolactin levels were obtained at baseline and at half‐hour intervals for 5 hr after fenfluramine/placebo administration. Plasma fenfluramine and norfenfluramine levels were obtained hourly.

Results: Smokers had a blunted prolactin response to fenfluramine compared with nonsmokers without any alcoholism or antisocial personality effects. Using a cutoff point of Δ peak prolactin < 10 ng/ml, more smokers (41/76, 54%) had a dampened response to fenfluramine than did nonsmokers (7/34, 21%) [X2(1)=10.6, p < 0.003]. The percentage of low responders was greatest among smokers regardless of whether they were healthy controls, alcoholics, or antisocial. Multiple regression revealed that three variables—(1) number of pack‐years of smoking, (2) actual dosage of fenfluramine received, and (3) plasma norfenfluramine level obtained—explained 43% of the variance (R2= 0.43) in Δ prolactin area under the curve. Variables that included alcoholism diagnostic status, antisocial personality diagnostic status, and impulsive aggressive personality, depressive, and suicidal traits failed to explain any additional unique variance.

Conclusions: Cigarette smoking blunted the prolactin response to a pharmacological challenge with d,l‐fenfluramine. Pharmacodynamic and pharmacokinetic factors related to smoking both appear to influence fenfluramine‐induced prolactin secretion. Phenotypes of alcoholics did not differ in their prolactin response to this serotonergic probe.
Intellectual, Cognitive, and Academic Performance Among Sons of Alcoholics During the Early School Years: Differences Related to Subtypes of Familial Alcoholism
Authors: Poon Edwin , Ellis Deborah A. , Fitzgerald Hiram E. , Zucker Robert A.
Published: May 2006

Background: Research on intellectual and cognitive functioning of children of alcoholics has been marked by inconsistency, with some studies unable to document deficits. This discrepancy may reflect the substantial heterogeneity found in the alcoholic population and among families of alcoholics. The current study sought to examine the effects of familial alcoholism subtypes on intellectual, cognitive, and academic performance in early school‐aged sons of alcoholics.

Methods: Subjects for the present study were 198 elementary‐age boys who were participants in the larger MSU‐UM Longitudinal Study. Familial alcoholism subtypes were determined based on fathers' alcoholism and antisocial personality disorder diagnoses. Intellectual functioning was measured with the Wechsler Intelligence Scale for Children‐Revised (WISC‐R); academic achievement was measured with the Wide Range Achievement Test–Revised. In addition, Mazes and Freedom from Distractability factor scores of the WISC‐R were used to assess abstract planning and attention abilities.

Results: Children of antisocial alcoholics (AALs) displayed the worst IQ and academic achievement compared with children of nonantisocial alcoholics (NAALs) and controls. In addition, children of AALs displayed relatively poorer abstract planning and attention abilities compared with children from control families. Regression analyses revealed that familial alcoholism subtype continued to account for variance in child intellectual ability even when other factors were excluded.

Conclusions: Findings indicate that children from AAL families are most susceptible to relative intellectual, cognitive, and academic deficits. The study further supports the proposition that familial risk characteristics (i.e., paternal alcoholism and antisociality) may serve as effective indicators of family risk for poor intellectual outcome among offspring as early as the elementary school years.
The Influence of Traits of Disinhibition on the Association Between Alcohol Use and Risky Sexual Behavior
Authors: Justus Alicia N. , Finn Peter R. , Steinmetz Joseph E.
Published: May 2006

Background: Past research has demonstrated a link between alcohol use and risky sexual behavior; the processes that may underlie this association remain largely unexplored, however. Recent studies suggest that personality traits such as excitement seeking, impulsivity, and social deviance proneness may play an important role in both behaviors.

Methods: A structural model of the association between disinhibited personality traits, alcohol use, and risky sexual behavior (sex with stranges/one‐night stands) was tested. We recruited a sample of 410 college students that reported a wide range of scores on self‐reported measures of disinhibition. We hypothesized that disinhibited personality characteristics would be primarily responsible for the association between risky sexual behavior and alcohol problems. A third‐variable model was proposed to demonstrate this association.

Results: The results suggested that the relationship between alcohol use and risky sexual behavior is best explained by their common association with excitement seeking. There was a significant correlation between alcohol use and risky sexual behavior when considered alone. However, when controlling for the effects of personality, the correlation was nonsignificant. In a final model, both excitement seeking and social deviance proneness were found to be significantly associated with alcohol use, and excitement seeking was significantly related to risky sexual behavior.

Conclusions: Results suggest the relationship between alcohol use and risky sexual behavior is best characterized by a common association with excitement seeking.
Role of Alcohol in Unnatural Deaths: A Study of All Deaths in Sweden
Authors: Sjögren Harmeet , Eriksson Anders , Ahlm Kristin
Published: May 2006

Background: Most previous research has concentrated on the role of alcohol in one type of unnatural death in a selected population, but the present objective was to investigate the role of alcohol in all unnatural deaths (autopsied and not autopsied).

Methods: All cases of unnatural death from 1992 through 1996 in Sweden were analyzed (n= 23,132). Death was attributed at least in part to alcohol if the deceased was a “known alcoholic”; if the underlying or contributing cause of death was alcohol‐related; if the deceased had an alcohol‐related inpatient diagnosis during the 3‐year period prior to death; or if the deceased tested positive for blood alcohol.

Results: Just over 28% of the unnatural deaths could be associated with alcohol; the association with alcohol was more than twice as common in deaths of males (35%) as in females (16%). When only autopsied cases or only blood‐tested cases were taken as the denominators, 38% and 44%, respectively, of the deaths were associated with alcohol. Alcohol involvement also was twice as common in intentional deaths (36%) as in unintentional deaths (18%). The intoxication group (78%) had the highest fraction of deaths that could be associated with alcohol, followed by the undetermined group (62%), homicide (49%), fire (41%), suicide (35%), asphyxia (29%), traffic (18%) and fall (9%) groups. In the 20‐ to 59‐year age group, alcohol involvement was found in 51% of the males and 35% of the females (47% for males and females combined).

Conclusions: The present estimates are conservative; alcohol involvement in unnatural deaths probably is even higher, up to 44% of the total. The present estimation is an important step in policy‐making to lower the number of alcohol‐related deaths in Sweden.
Influence of the Number of Alcohol and Water Bottles on Murine Alcohol Intake
Authors: Tordoff M. G. , Bachmanov A. A.
Published: May 2006

Background: Most work to understand the controls of alcohol intake by animals involves the two‐bottle choice method. Recent experiments involving other nutrients suggest that intakes are profoundly influenced by the number of nutrient choices available. Here, we extended these observations by measuring the alcohol consumption of mice and rats given multiple choices of water and alcohol.

Methods: Four experiments were conducted. In experiments 1 and 2, male C57BL6/J (B6) mice, 129X1/SvJ mice, or Sprague‐Dawley rats received a series of six 72‐ or 48‐hr tests in which the number of bottles of 10% alcohol and water was manipulated. One test involved the typical two‐bottle choice. In the other five, the rodents always had six bottles with one, two, three, four, or five containing 10% alcohol and the rest containing water. In experiment 3, separate groups of B6 mice received for 16 days (a) the typical two‐bottle test, (b) five alcohol bottles and one water bottle, (c) three alcohol bottles and three water bottles, or (d) one alcohol bottle and five water bottles. In experiment 4, groups of B6 mice received either a two‐bottle test or five alcohol bottles and one water bottle for 24 days.

Results: In all experiments, the volume of alcohol consumed was strongly and positively related to the number of alcohol bottles available and inversely related to the number of water bottles available. The effect of alcohol availability on alcohol intake persisted for at least 24 days.

Conclusions: Alcohol intake is strongly influenced by availability. The results point to a simple method of manipulating murine alcohol intake over a wide range. They provide an animal model that might be useful for understanding the influence of alcohol availability on human alcohol consumption.
Theta Power in the EEG of Alcoholics
Authors: Rangaswamy Madhavi , Porjesz Bernice , Chorlian David B. , Choi Keewhan , Jones Kevin A. , Wang Kongming , Rohrbaugh John , O'Connor Sean , Kuperman Sam , Reich Theodore , Begleiter Henri
Published: May 2006

Background: In this study, the magnitude and spatial distribution of theta power in the resting EEG were examined to explore the changes in the neurophysiological status of the alcoholic brain. Some state‐ and trait‐related issues of theta power increases in the EEG of alcoholics were also examined.

Methods: Absolute theta (3–7 Hz) power in eyes‐closed EEGs of 307 alcohol‐dependent subjects and 307 age‐ and gender‐matched unaffected controls were compared by using a repeated‐measures ANOVA for the entire region and three subregions (frontal, central, and parietal) separately. Supplementary to the main analysis, the effect of three clinical variables on absolute theta power was examined separately for each gender by using correlation and regression analyses. Gender differences in the theta log power difference between alcoholics and controls were explored by using regional repeated‐measures ANOVA.

Results: Increased absolute theta power was seen in alcohol‐dependent subjects at all scalp locations. The theta log power increase in male alcoholics was prominent at the central and parietal regions and in female alcoholics at the parietal region when compared with the respective matched controls. Correlation of drinking variables with log theta power exhibited no group‐specific differences.

Conclusions: Increased tonic theta power in the EEG may reflect a deficiency in the information‐processing capacity of the central nervous system in alcoholics. The theta power increase may also be an electrophysiological index of the imbalance in the excitation‐inhibition homeostasis in the cortex. It is likely that the theta power increase is a trait‐related phenomenon and is expressed to differing degrees in the two genders.
Testosterone Increases in Men After a Low Dose of Alcohol
Authors: Sarkola Taisto , Eriksson C. J. Peter
Published: May 2006

Background: Heavy acute alcohol drinking decreases blood testosterone in men due to an effect on the testicular level. An acute increase in blood testosterone levels after a low alcohol dose has, however, recently been reported in women. The objective of this investigation was to study the effect of a low alcohol dose on testosterone in men and further elucidate the mechanism behind the effect by using 4‐methylpyrazole, an inhibitor of alcohol metabolism.

Methods: A double‐blind placebo‐controlled interventional crossover trial in random order (n= 13).

Results: After intake of alcohol (0.5 g/kg, 10% w/v), an acute increase in plasma testosterone (from 13.5 ± 1.2 nmol/liter to 16.0 ± 1.6 nmol/liter, mean ± SEM;p < 0.05), a decrease in androstenedione (from 5.1 ± 0.4 nmol/liter to 4.0 ± 0.3 nmol/liter;p < 0.05), and an increase in the testosterone:androstenedione ratio (from 2.8 ± 0.3 to 4.2 ± 0.4;p < 0.01) were observed. The effects were not observed during pretreatment with 4‐methylpyrazole (10–15 mg/kg orally), which inhibited the ethanol elimination rate by 37 ± 3%.

Conclusions: Alcohol intake affects the androgen balance in men through an effect mediated by the alcohol‐induced change in the redox state in the liver.
The Effects of Chronic Ethanol Consumption During Early Pregnancy on Conceptus Health and Uterine Function in Pigs
Authors: Kubotsu Stephanie L. , Hu Jianbo , Carnahan Kevin G. , DeAvila Jeanene , Ott Troy L. , Mirando Mark A.
Published: May 2006

Background: Maternal ethanol consumption impairs fetal health, but it is unclear if this occurs through direct actions on the conceptus or indirectly through effects on the uterus. The objective of this study was to determine if chronic ethanol consumption in swine would impair early embryonic and fetal health either through direct effects on the conceptus or indirect effects on the endometrium.

Methods: Four experiments evaluated the effects of chronic ethanol consumption during early pregnancy. Female pigs were fed either 350 ml of 95% ethanol or an isocaloric amount of dextrose at 10 to 14‐hr intervals beginning on day 10 after pubertal estrus and continuing until ovariohysterectomy 11 to 35 days after mating. At the second estrus, pigs were mated to a fertile boar that did not consume alcohol.

Results: In experiment 1, ethanol consumption increased (p < 0.01) blood alcohol concentrations that peaked 2–3 hr after feeding. In experiment 2, ethanol was detectable in uterine flushings 2 hr after feeding on day 11 of pregnancy and was highly correlated (r= 0.989, p < 0.001) with blood alcohol concentration. In experiment 3, ethanol consumption did not affect endometrial phospholipase C activity on days 11 and 16 of pregnancy but decreased (p < 0.05) basal endometrial prostaglandin F2α production on day 16. However, ethanol consumption did not decrease the number of conceptuses on day 11 or conceptus DNA content on days 11 or 16. In experiment 4, ethanol consumption decreased (p < 0.05) fetal survival rate to 58% versus 85% in dextrose‐fed controls on day 35 of pregnancy. For viable conceptuses, ethanol consumption reduced (p < 0.01) fetal weight, fetal crown‐rump length, placental weight and volume of placental (chorio‐allantoic + amniotic) fluid.

Conclusion: These results indicate that chronic ethanol consumption may impair conceptus health directly or indirectly through actions upon the endometrium. Thus, the pig may be a valuable experimental model for studies on the effects of maternal alcohol consumption on conceptus development.
Neither Antisocial Personality Disorder Nor Antisocial Alcoholism Is Associated With the MAO‐A Gene in Han Chinese Males
Authors: Lu Ru‐Band , Lin Wei‐Wen , Lee Jia‐Fu , Ko Huei‐Chen , Shih Jean Chen
Published: May 2006

Background: Recent studies on the genetics of alcoholism have suggested an association between antisocial alcoholism and the MAO‐A gene. However, previous studies have failed to include subjects with antisocial personality disorder without alcoholism even though there is a high comorbidity between antisocial personality disorder and alcoholism. Consequently, the finding of an association between the MAO‐A gene and alcoholism or antisocial personality disorder seems tenuous. In Taiwan, about 70% of the Han Chinese population have the ADH2*2 allele and 50% show ALDH2*1/*2 or ALDH2*2/*2 genotypes, which offer protection against drinking behavior and the risk of developing alcoholism. Thus, it is possible to recruit individuals with antisocial personality disorder but without alcoholism in Taiwan. Therefore, association studies of alcoholism or antisocial personality disorder in Chinese may be more reliable if pure antisocial alcoholics, pure antisocial personality disorders, and normal controls as MAO‐A gene are examined.

Methods: In this study, the associations among antisocial alcoholism, antisocial personality disorder, and the uVNTR and Eco RV polymorphisms of the MAO‐A gene, both individually and as a haplotype, were investigated among male adults recruited from jails in Taipei. A total of 129 Chinese Han males were studied, including 41 with antisocial personality disorder with alcoholism, 50 with antisocial personality disorder but without alcoholism, and 38 without either disorder as a jail control group. The diagnoses of alcohol dependence and antisocial personality disorder were made according to DSM‐IV criteria. In addition, 77 normal controls were collected from the community.

Results: Strong linkage disequilibrium was found for the uVNTR and Eco RV variants of MAO‐A gene in each study group.

Conclusions: No significant association was observed between these two polymorphisms and antisocial personality disorder with alcoholism, either individually or for the haplotype, or for antisocial personality disorder without alcoholism. Thus, neither antisocial alcoholism nor antisocial personality disorder was associated with the genetic variants of MAO‐A gene.
Schedule‐Induced Ethanol Self‐Administration in DBA/2J and C57BL/6J Mice
Authors: Mittleman Guy , Van Brunt Carrie L. , Matthews Douglas B.
Published: May 2006

Background: The purpose of these experiments was to provide an initial investigation into ethanol self‐administration elicited in the schedule‐induced polydipsia (SIP) paradigm.

Methods: Mature male mice were food deprived to between 80 and 85% of their baseline weight and received 20 daily 1 hr SIP test sessions in which a food pellet (20 mg) was delivered on a fixed‐time 60 sec schedule. In different groups, the acquisition of drinking 5% (v/v) ethanol solution (experiment 1) or water (experiment 2) was recorded along with other behaviors that occurred in the test chambers.

Results: Results indicated that C57BL/6J mice drank significantly more ethanol than DBA/2J mice and that C57 mice achieved blood alcohol concentrations as high as 300 mg/dl. Blood alcohol concentrations were consistently correlated with g/kg ethanol intake. The groups did not differ in consumption of water. SIP test sessions using higher concentrations of ethanol (10–20% v/v, experiment 1) or sucrose solutions (0.1–2% w/v, experiment 2) then were performed. Group differences in ethanol consumption were maintained at all ethanol concentrations. Although DBAs drank more of a low concentration of sucrose (0.1%), when expressed as g/kg, sucrose intake was equivalent in the two strains at all concentrations. Analysis of the time course of drinking clearly showed that this behavior was adjunctive in nature.

Conclusion: These results demonstrate the effectiveness of this procedure in inducing ethanol self‐administration and its utility for investigating the genetic bases of vulnerability toward excessive ethanol consumption.
Differential Responding for Brain Stimulation Reward and Sucrose in High–Alcohol‐Drinking (HAD) and Low–Alcohol‐Drinking (LAD) Rats
Authors: Woods James E. , McKay Peter F. , Masters Jacob , Seyoum Regat , Chen Annabel , La Duff Lorie , Lewis Michael J. , June Harry L.
Published: May 2006

Background: This study examined the associations among selective breeding for alcohol preference, intake of sweet solutions, and responding for brain stimulation reward (BSR), a nonoral reinforcer, in alcohol‐preferring high–alcohol‐drinking (HAD)‐1 and nonpreferring low–alcohol‐drinking (LAD)‐1 rats.

Methods: Adult male HAD‐1 and LAD‐1 rats were trained to lever press for medial forebrain bundle stimulation. Current intensity was varied in separate sessions to generate a rate/intensity function. To further examine BSR responding, the animals responded for stimulation at 100 Hz and at a fixed current intensity on an FR1 schedule. In subsequent sessions, the schedule was increased to FR6 and then to FR12. To examine responding for the sucrose solution, we trained a separate group of HAD‐1/LAD‐1 rats to bar press for sucrose on an FR1 schedule. Similar to the BSR experiment, in following sessions, the schedule was increased to an FR6 and then to an FR12 schedule.

Results: No significant differences were observed between the two rat lines across a range of current intensities. As the reinforcement schedule increased, HAD‐1 rats exhibited a dramatic decrease in BSR responding, whereas the LAD‐1 rats displayed a more protracted reduction. In contrast to BSR, marked elevations in responding were observed for sucrose as the schedule increased. However, in HAD‐1 rats, response rates were similar on the FR6 and FR12 schedules, whereas LAD‐1 rats showed a reduction in response rates from the FR6 to FR12 schedule. Furthermore, HAD‐1 rats exhibited significantly more responses compared with LAD‐1 rats across the three reinforcement schedules. An analysis of the response profile for the three reinforcement schedules suggested that few if any postreinforcement pauses were exhibited when the reinforcer was BSR compared with sucrose in both lines.

Conclusion: Medial forebrain bundle BSR is a powerful reinforcer in both HAD‐1 and LAD‐1 lines. However, BSR responding was not associated with selective breeding for alcohol preference. In contrast, selective breeding for alcohol preference was associated with sucrose consumption, especially as the amount of work increased. The lack of correspondence between BSR and sweet taste rewards in HAD‐1 and LAD‐1 lines may suggest important differences yet an overlapping brain reward mechanism in the control of motivated behaviors in these selected lines.
Immunohistochemical Characterization of Hepatic Malondialdehyde and 4‐Hydroxynonenal Modified Proteins During Early Stages of Ethanol‐Induced Liver Injury
Authors: Sampey Brante P. , Korourian Soheila , Ronis Martin J. , Badger Thomas M. , Petersen Dennis R.
Published: May 2006

Background: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde‐adducted proteins postulated to be involved in alcohol‐induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde‐protein adducts during early stages of alcohol‐induced liver injury.

Methods: Female Sprague Dawley® rats were subjected to the intragastric administration of a low‐carbohydrate/high‐fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P‐4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4‐hydroxynonenal (4‐HNE) for subsequent quantitative image analysis.

Results: After 36 days of treatment, rats receiving the alcohol‐containing diet displayed hepatic histopathologies characterized by marked micro‐ and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3‐fold elevation of plasma alanine aminotransferase activity and 3‐fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5‐fold increases in MDA‐ and 4‐HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA‐ or 4‐HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde‐modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation.

Conclusions: These results suggest that alcohol‐induced lipid peroxidation is an early event during alcohol‐mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events.
Risk in Benefit‐Cost Analysis
Authors: Schulze William D. , Kneese Allen V.
Published: May 2006

In recent years, benefit‐cost analysis has been increasingly applied to large societal decision problems (such as developing a fast breeder energy economy) which involve both risks to society and analysis of very long‐term consequences possibly extending over many human generations. This paper examines the philosophical underpinnings of the technique which is a special case of utilitarianism, and compares implications of the technique to those arising from alternative ethical systems in analyzing questions of public safety. Ethical systems which emphasize the good of the whole, such as utilitarianism, are shown to differ sharply in decision outcomes from those which emphasize the rights of the individual, such as libertarianism. It is suggested that benefit‐cost analysis should be broadened to include alternative weightings of benefits and costs consistent with a variety of ethical views.
On The Method of Discrete Probability Distributions in Risk and Reliability Calculations–Application to Seismic Risk Assessment
Authors: Kaplan Stanley
Published: May 2006

If the point of view is adopted that in calculations of real‐world phenomena we almost invariably have significant uncertainty in the numerical values of our parameters, then, in these calculations, numerical quantities should be replaced by probability distributions and mathematical operations between these quantities should be replaced by analogous operations between probability distributions. Also, practical calculations one way or another always require discretization or truncation. Combining these two thoughts leads to a numerical approach to probabilistic calculations having great simplicity, power, and elegance. The philosophy and technique of this approach is described, some pitfalls are pointed out, and an application to seismic risk assessment is outlined.
Reflections on Risk Perception and Policy1,2
Authors: Otway Harry , Thomas Kerry
Published: May 2006

This paper looks critically at the emergence and present status of risk analysis with the aim of assessing its usefulness for policy decisions on risk regulation and the acceptability of risk‐bearing innovations. The authors adopt a personal narrative to illustrate their own involvement in risk research and to comment on empirical trends that have resulted in the current fashion for risk workshops. The second part of the paper confronts specific issues in risk research. These are not new problems‐indeed several of the questions asked have been taken directly from a list used to structure a recent risk seminar; but the stand taken here is rather less conciliatory than is usual when these issues are discussed. The pessimistic message of this paper is that risk research, especially in the area of risk perception, is being used as a panacea with which to attempt to remedy what are essentially societal and political matters. Risk research is being used as a tool in a discourse which is not concerned with risks per se, nor with the cognitive processes by which people misperceive the risks of new technologies, but whose hidden agenda is the legitimacy of decision‐making institutions and the equitable distribution of hazards and benefits. The authors take a subjectivist view, not just of risk but in general, and query the natural science approach to risk perception, with its assumption that universal dimensions of risk perception can be discovered and used in policy‐making and setting regulatory standards. Although it is possible to collect subjective data on the wider meanings that risks and benefits associated with technological innovations have for lay publics, the interpretation and recombination of these data into useful policy guidelines is seen as fraught with technical and, above all, political problems.
Risk‐Perception Studies and Policy Priorities
Authors: O'Riordan Timothy
Published: May 2006

The current fascination with risk acceptability, risk benefit analysis and other devices for relating risk to social gain is a manifestation of the loss of faith amongst certain groups in modern western society with the honesty and competence of those who assess and finally make judgements about public safety. The problem lies as much in a suspicion over the motives of leading personalities and the fidelity of assessment procedures as it does with the collective psychology of individual beliefs and judgements. “Real world” studies involving carefully sampled households monitored over a period of time may well reveal better information on the complexities of risk cognition and evaluation than laboratory investigation of the views of individuals responding in isolation.
The Role of Interdisciplinary Analysis in Bridging the Gap Between the Technical and Human Sides of Risk Assessment1
Authors: Spangler Miller B.
Published: May 2006

It is readily observable that there is a wide gulf between the manner by which the lay public and the manner by which technical experts assess the risks of complex technologies and assimilate these assessments in decisions regarding the acceptance or rejection of technological options. On the public side, this gap in methods and value assessments is a major source of distrust of technical experts and disaffection with the social management of technology. From the viewpoint of the technical experts who introduce or regulate technologies, this gap is both a cauldron of frustration and a perceived justification for paternalistic technocratic decision‐making that further alienates important segments of the public. It is the author's belief that unless our society learns how to progress in bridging these gaps within the framework of a comparative mode of risk‐cost‐benefit analysis of options, the potential net benefits of certain technologies such as commercial nuclear power could well be lost to our society. Research on public risk perception, while potentially an important component in achieving this objective, needs to be restructured from its present static orientation to meet the needs of forward‐looking decision‐making that accommodates dynamic learning processes of both the public and technical experts as well as the “learning curves” of technological improvements historically accompanying successful innovations. Moreover, no less attention needs to be devoted to improved benefit assessment along with ethical and equity considerations in decision‐making involving the reconciliation of conflict between individual and societal interests. This paper examines the vital importance of interdisciplinary analysis in fulfilling these needs.
Matrix Theory Formalism for Event Tree Analysis: Application to Nuclear‐Risk Analysis
Authors: Kaplan Stanley
Published: May 2006

It is pointed out that the familiar analytical device of “event tree”, widely used in risk analysis, can be viewed as a transition matrix expressing the likelihood of going from “entry states” to “exit states”. This point of view is shown to have numerous interesting conceptual and computational features which promise to make it a very useful addition to the arsenal of tools for risk analysis. The basic idea is explained first in terms of a simple, made‐up example. The application of the idea to a very real and complicated problem, nuclear‐plant risk assessment, is then outlined.
Estimation and Extrapolation of Tumor Probabilities from a Mouse Bioassay with Survival/Sacrifice Components
Authors: Farmer John H. , Kodell Ralph L. , Gaylor David W.
Published: May 2006

A nonparametric estimator of the probability distribution of time‐to‐tumor is incorporated into an algorithm for calculating linearly extrapolated dosage limits from an animal carcino‐genesis bioassay. The procedure is illustrated with tumor data from a mouse bioassay with 2‐acetylaminofluorene. Extrapolated dosage limits for an excess risk of 10‐6 differ by only a factor of 2 across the six replicates of the experiment.
Risk Perception in an Interest Group Context: An Examination of the TMI Restart Issue1
Authors: Soderstrom E. Jonathan , Sorensen John H. , Copenhaver Emily D. , Carnes Sam A.
Published: May 2006

Human response to environmental hazards and risks has been the subject of considerable research by social scientists. Work has traditionally focused on either individual response to the risks of an ongoing or future threat (hazards research), or group and organizational response to a specific disaster event (disaster research). As part of a larger investigation of the restart of the Unit 1 reactor at Three Mile Island (TMI), we examined the response of interest groups active in the restart issue to the continued threat of TMI and to future risks due to restart. After reviewing the restart issue in general, the paper examines the local dimensions of the restart issue from interest group perspectives. A method for defining appropriate issues at the community level is reviewed. We then discuss differences in the perceived local impacts of alternative decisions, and systems of beliefs associated with differing perceptions. Finally, we discuss the implications of interest group versus individual perceptions of local issues for decision making about TMI, in particular, and about technological hazards management, in general. Associated implications for determining socially acceptable risk levels are identified. Our research led us to three major conclusions: (1) in contrast to other types of hazards, interest groups are a critical unit of analysis for understanding how beliefs and behaviors form in response to the presence of technological hazards; (2) the divergence of positions between groups, even though they may have shared the same physical experience, is understandable if not always predictable, (3) the resolution of policy debates where risks are a major focus of the arguments should recognize the legitimacy of these divergent positions by allowing participation of the various interest groups in the decision process. Such participation helps ensure that the decision strategy is responsive to local concerns, thereby increasing the likelihood of acceptance of the ultimate decision and thus producing a publicly acceptable level of risk.
Recent Case Studies and Advancements in Probabilistic Risk Assessment
Authors: Garrick B. John
Published: May 2006

During the period from 1977 to 1984, Pickard, Lowe and Garrick, Inc., had the lead in preparing several full scope probabilistic risk assessments for electric utilities. Five of those studies are discussed from the point of view of advancements and lessons learned. The objective and trend of these studies is toward utilization of the risk models by the plant owners as risk management tools. Advancements that have been made are in presentation and documentation of the PRAs, generation of more understandable plant level information, and improvements in methodology to facilitate technology transfer. Specific areas of advancement are in the treatment of such issues as dependent failures, human interaction, and the uncertainty in the source term. Lessons learned cover a wide spectrum and include the importance of plant specific models for meaningful risk management, the role of external events in risk, the sensitivity of contributors to choice of risk index, and the very important finding that the public risk is extremely small. The future direction of PRA is to establish less dependence on experts for in‐plant application. Computerizing the PRAs such that they can be accessed on line and interactively is the key.
Nuclear Plant Systems Analysis Research at EPRI
Authors: Worledge David H. , Chu Boyer B. , Wall Ian B.
Published: May 2006

A synopsis is given of research projects on probabilistic systems analysis conducted by the Risk Assessment Program of the Electric Power Research Institute. A brief outline of the value of systems analysis both within PRA and as a stand‐alone discipline is used to show how the objectives of the research program are related to industry needs. Research projects and their deliverables are discussed in relation to three objectives: (1) to improve the credibility of the methods and results, (2) to provide computer tools and technology transfer, and (3) to develop use of the methods to improve safety and availability in operation. Recent achievements and future plans are briefly described and an up to date list of relevant EPRI publications is provided.
Managing Risk: A Joint U.S.‐German Perspective
Authors: Lave Lester B. , Menkes Joshua
Published: May 2006

Ideas from a USA‐FRG conference on risk management are presented. In general, the difficulties confronted by risk management authorities in the two countries are similar, from discovering important risks at an early stage to setting acceptable goals. Government regulation is overburdened and somewhat inefficient in both countries, leading to greater search for alternatives. The many differences in approach between the two countries can inform both. German risk management is done largely through negotiations among the affected parties; when this does not resolve a dispute, a specialized administrative court takes charge. In both countries nonregulatory methods of managing risk should be enhanced and given a larger role. A matrix of risk management method versus criteria proved stimulating in comparing and ranking approaches. The conceptual differences between managing discrete events (auto crashes, boiler explosions, etc.) and chronic exposures have not been appreciated. Although uncertainty and probability are involved in both, there are qualitative differences in both analysis and management. Public perceptions of risk and the role these should play have been characterized by “objectivist” and “subjectivist” positions. In the former view, risks are subject to analysis, are calculable, and the public must be educated to accept the conclusions of experts. In the latter view what people perceive is what is most important, both psychologically and politically, and the risk experts must understand public fears and desires. These are important opportunities for cross cultural studies.
Managing a Low‐Incidence Risk: The Example of Toxic Shock Syndrome
Authors: Weber Elke U.
Published: May 2006

This article demonstrates a methodology that allows individuals to reach a personal decision on the use of products which carry very small risks to health and life but also offer considerable benefits. A combination of the principles of dominance, extended dominance, and various methods of direct risk–benefit tradeoffs are shown to reduce the number of possible decisions regarding product use to the one optimal for the value structure of a particular individual. An historical examination of toxic‐shock syndrome identifies tampons as a product with risks too small to warrant public intervention but too sizeable to be ignored. The methodology described here can be applied for all such products.
A Computer Aid for Risk and Other Policy Analysis
Authors: Henrion Max , Morgan M. Granger
Published: May 2006

The use of appropriately designed computer aids for policy could improve the standards of risk analysis and other quantitative policy analysis in several important ways. They could make it easier to treat uncertainties more thoroughly and systematically than is now typical. To do this, they should provide a broad variety of techniques for representing uncertain quantities as ranges of alternative values or as probability distributions, for propagating uncertainties through a model, for analyzing and comparing the impacts of different sources of uncertainty, and for displaying results in various numerical and graphic formats. A nonprocedural modeling language allowing interactive editing of input values and model structure could encourage exploration and progressive refinement of models, and comparison of alternative formulations. The integration of model documentation and explanatory text within the computer representation could encourage maintenance of consistency between different versions of the mathematical structure and their descriptions. It could also allow interactive scrutiny of the model assumptions and sensitivities by outside reviewers. We describe a particular system, Demos, designed to provide these facilities and test their usefulness. The use of Demos is illustrated by an analysis of the risks and optimal control level for a hypothetical air pollutant, with uncertainty about the population exposure, health effects, and control costs. This example demonstrates progressive refinement of a model, and various kinds of parametric and probabilistic uncertainty analysis. Demos is now being used by a growing number of risk analysts, students, and policy researchers in a wide variety of tasks.
A Fuzzy Set Theoretic Foundation for Vagueness in Uncertainty Analysis
Authors: Unwin Stephen D.
Published: May 2006

We emphasize the distinction between two forms of uncertainty that arise in risk and reliability analyses: (1) that due to the randomness inherent in the system under investigation and (2) that due to the vagueness inherent in the assessor's perception and judgement of that system. It is proposed that whereas the probabilistic approach to the former variety of uncertainty is an appropriate one, the same may not be true of the latter. Through seeking to quantify the imprecision that characterizes our linguistic description of perception and comprehension, fuzzy set theory provides a formal framework for the representation of vagueness. In connection with the second form of uncertainty, fuzzy sets and the associated theory of “possibility” are considered as a basis upon which to model the imprecision and vagueness attached to the expert judgement of event likelihood (e.g. component failure). It is noted that from the perspective of the technical complexity of propagation, the possibilistic treatment of uncertainty compares favorably with the more familiar Bayesian approach.
Improving Risk Communication
Authors: Keeney Ralph L. , von Winterfeldt Detlof
Published: May 2006

This paper explores reasons for difficulties in communicating risks among analysts, the laypublic, media, and regulators. Formulating risk communication problems as decisions involving objectives and alternatives helps to identify strategies for overcoming these difficulties. Several strategies are suggested to achieve risk communication objectives like improving public knowledge about risks and risk management, encouraging risk reduction behavior, understanding public values and concerns, and increasing trust and credibility.
An Analysis of the de minimis Strategy for Risk Management
Authors: Mumpower Jeryl
Published: May 2006

A de minimis risk management strategy sets a threshold so that risks below the specified level are defined as trivial and exempted from further consideration. The intended purpose is to help avoid inappropriate and wasteful concern with insignificant low‐level risks. In most instances a de minimis strategy is likely to have beneficial or innocuous effects, but under certain circumstances large differences may develop between nominal and actual de minimis levels. The potential for such discrepancies illustrates why de minimis (and all other risk management) strategies should be evaluated on the basis of the portfolio of risks that would accumulate from applying such strategies over time, rather than on the apparent reasonableness of any single instance of application.
Thyroid Cancer Risk from Exposure to Ionizing Radiation: A Case Study in the Comparative Potency Model
Authors: Laird Nan M.
Published: May 2006

Considerable controversy exists about the relative risk of thyroid cancer following exposure to external radiation compared to the risk after exposure to internally deposited 131I. The human epidemiological data are equivocal, and studies are not directly comparable owing to differing ages at exposure, dose ranges, and periods of follow‐up. Limited experimental data at low dose ranges support the hypothesis of equal potency in animals. This report utilizes a relative potency model to reconcile data from different sources, and to provide an estimate of thyroid cancer risk following human exposure to 131I. We utilize data from epidemiological studies of external radiation and 131I exposure in humans and data from an experimental animal study. This analysis shows that the data provide no compelling evidence to suggest that the risks accompanying external radiation or 131I exposure are different.
Probabilistic Reliability Analysis, Quantitative Safety Goals, and Nuclear Licensing in the United Kingdom
Authors: Cannell William
Published: May 2006

Although unpublicized, the use of quantitative safety goals and probabilistic reliability analysis for licensing nuclear reactors has become a reality in the United Kingdom. This conclusion results from an examination of the process leading to the licensing of the Sizewell B PWR in England. The licensing process for this reactor has substantial implications for nuclear safety standards in Britain, and is examined in the context of the growing trend towards quantitative safety goals in the United States.