Bibliothek

Notizen: The search for flavonoids with novel therapeutic effects has been intense. Wogonin, as a naturally existing monoflavonoid, has been shown to have therapeutic potential in vitro and in vivo. Methods for its extraction from herbs and its chemical synthesis have been developed. Pharmacokinetic studies have shown a rapid tissue distribution and prolonged plasma elimination phase of wogonin. It has been shown experimentally that wogonin exerts anti-oxidant activity, which may, in part, underlie its antiinflammatory, anti-cancer, antiviral and neuroprotective actions. The recent discovery of its anxiolytic activity suggests a new mechanism of action, involving interaction with the benzodiazepine (BZD) binding site of the GABAA receptor and modulation of this receptor activity. Although the safety record of wogonin is remarkable and voluminous literature about its pharmacological effects is available, it has not been used in Western medicine in the form of a pure chemical. In this article we review its therapeutic effects, its sources and pharmacokinetic profile to highlight its therapeutic potential.

Notizen: CRF1 antagonists DMP696 and DMP904 were designed as drug development candidates for the treatment of anxiety and depression. Both compounds display nanomolar affinity for human CRF1 receptors, and exhibit 〉1000-fold selectivity for CRF1 over CRF2 receptors and over a broad panel of other proteins. DMP696 and DMP904 block CRF-stimulated adenylyl cyclase activity in cortical homogenates and cell-lines expressing CRF1 receptors. Both compounds inhibit CRF-stimulated ACTH release from rat pituitary corticotropes. Binding and functional studies indicate that DMP696 and DMP904 behave as noncompetitive full antagonists. DMP696 and DMP904 exhibit anxiolytic-like efficacy in several rat anxiety models. In the defensive withdrawal test, both compounds reduce exit latency with lowest effective doses of 3 and 1 mg/kg, respectively. The anxiolytic-like effect is maintained over 14 days of repeated dosing. In the context of a novel environment used in this test, DMP696 and DMP904 reverse mild stress-induced increases in plasma CORT secretion but at doses 3-4-fold greater than those required for anxiolytic-like efficacy. DMP696 and DMP904 are ineffective in three depression models including the learned helplessness paradigm at doses up to 30 mg/kg. At lowest anxiolytic-like doses, DMP696 and DMP904 occupy 〉50% CRF1 receptors in the brain. The in vivo IC50 values (plasma concentrations required for occupying 50% CRF1 receptors) estimated based upon free, but not total, plasma concentrations are an excellent correlation with the in vitro IC50 values. Neither compound produces sedation, ataxia, chlordiazepoxide-like subjective effects or adverse effects on cognition at doses 10-fold higher than anxiolytic-like doses. Neither compound produces physiologically significant changes in cardiovascular, respiratory, gastrointestinal or renal functions at anxiolytic-like doses. DMP696 and DMP904 have favorable pharmacokinetic profiles with good oral bioavailabilities. The overall pharmacological properties suggest that both compounds may be effective anxiolytics with low behavioral side effect liabilities.

Notizen: Glutamate is the major excitatory transmitter in the brain. Recent developments in the molecular biology and pharmacology of the α-amino-3-hydroxy-5-methylisoxa-zole-4-propionic acid (AMPA)-subtype of glutamate receptors have led to the discovery of selective, potent and systemically active AMPA receptor potentiators. These molecules enhance synaptic transmission and play important roles in plasticity and cognitive processes. In the present studies we characterized a novel AMPA receptor potentiator, LY503430, on recombinant human GLUA1-4 and native preparations in vitro, and then evaluated the potential neuroprotective effects of the molecule in rodent models of Parkinson's disease. Results indicated that at submicromolar concentrations LY503430 selectively enhanced glutamate-induced calcium influx into HEK293 cells transfected with human GLUA1, GLUA2, GLUA3, or GLUA4 AMPA receptors. The molecule also potentiated AMPA-mediated responses in native cortical, hippocampal and substantia nigra neurones. LY503430 had good oral bioavailability in both rats and dogs. We also report here that LY503430 provided dose-dependent functional and histological protection in animal models of Parkinson's disease. The neurotoxicity following unilateral infusion of 6-hyrdoxydopamine (6-OHDA) into either the substantia nigra or the striatum of rats and that following systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice were reduced. Interestingly, LY503430 also had neurotrophic actions on functional and histological outcomes when treatment was delayed until well after (6 or 14 days) the lesion was established. LY503430 also produced some increase in brain derived neurotrophic factor (BDNF) in the substantia nigra and a dose-dependent increase in growth associated protein-43 (GAP-43) expression in the striatum. Therefore, we propose that AMPA receptor potentiators such as LY503430 offer the potential of a new disease modifying therapy for Parkinson's disease.

Notizen: Several landmark clinical trials suggest that 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have additional cardiovascular protective activity that may function independently of their ability to lower serum cholesterol. The cardiovascular protective effects of statins are partly caused by the activation of postnatal neovascularization. At therapeutic doses, statins promote proliferation, migration and survival of endothelial cells, induce mobilization and differentiation of bone marrow-derived endothelial progenitor cells by stimulating the serine/threonine protein kinase Akt (also known as protein kinase B) and nitric oxide (NO) signal pathway. However, at excessive doses, statins may decrease protein isoprenylation as well as inhibit endothelial cell growth and migration. NO is an important signaling molecule that regulates a wide range of physiological and pathological processes in different tissues. There is substantial evidence that effective neovascularization requires endothelium-derived NO. Statins have pleiotropic effects on the expression and activity of endothelial nitric oxide synthase (eNOS) and lead to improved NO bioavailability. NO plays an important role in the effects of statins on neovascularization. In this review, we focus on the effects of statins on neovascularization and highlight specific novel targets, such as endothelial progenitor cells and NO.

Notizen: Bivalirudin (Hirulog®, Angiomax®) is a specific, reversible and direct thrombin inhibitor with a predictable anticoagulant effect. It is cleared by both proteolytic cleavage and renal mechanisms, predominantly glomerular filtration. Bivalirudin inhibits both circulating thrombin and fibrin bound thrombin directly by binding to thrombin catalytic site and anion-binding exosite I in a concentration-dependent manner. Bivalirudin prolongs activated partial thromboplastin time, prothrombin time, thrombin time and activated clotting time (ACT). ACT levels with bivalirudin do not correlate with its clinical efficacy. Bivalirudin with a provisional GpIIb/IIIa inhibitor is indicated in elective contemporary percutaneous coronary intervention (PCI). In respect to combined ischemic and hemor-rhagic endpoints of death, myocardial infarction, unplanned urgent revascularization and major bleeding during PCI (including subgroups of patients with renal impairment and diabetes) bivalirudin is not inferior to unfractioned heparin and planned GpIIb/IIIa inhibitors. In addition, bivalirudin has been consistently shown to have significantly less in-hospital major bleeding than heparin alone or heparin in combination with-a GpIIb/IIIa inhibitor. Bivalirudin appears to be also safe and effective during PCI in patients with heparin-induced thrombocytopenia. Finally, data from PCI studies support the safety and efficacy of bivalirudin, although its direct randomized comparison with unfractionated heparin is lacking.

Notizen: Bimatoprost is a safe and well-tolerated intraocular pressure (IOP) lowering drug that was approved in the United States in 2001 for the treatment of glaucoma and ocular hypertension. It is highly efficacious and produces greater mean reductions in IOP than other currently available antiglaucoma drugs. Conjunctival hyperemia is a common side effect of bimatoprost, but the hyperemia is typically mild and transient. No association has been found between signs of inflammation and the presence of hyperemia in bimatoprost-treated patients. Preclinical studies have elucidated the pharmacological mechanism of bimatoprost-related hyperemia and have examined the possible involvement of inflammation. Bimatoprost, as well as the free acid of latanoprost, elicited endothelium-de-pendent vasorelaxation in the rabbit jugular vein preparation, a quantitative in vitro model for ocular surface hyperemia (OSH). The vasorelaxant responses to either bimatoprost or latanoprost free acid were significantly inhibited by L-NAME, a nitric oxide synthase inhibitor. Similarly, the in vivo OSH responses to topically applied bimatoprost or latanoprost in dog eyes were significantly inhibited by L-NAME. As predicted, prostaglandin E2 (PGE2)-induced conjunctival hyperemia was not inhibited by L-NAME, since PGE2 has a direct relaxant effect on the vascular smooth muscle. In-life observations and histopatho-logical assessment of ocular surface tissues following bimatoprost treatment were performed for multiple-dose one month, 6 month, or 12 month safety studies in rabbits, dogs, and non-human primates. Results of these studies showed no evidence of bimatoprost-re-lated inflammation in the ocular surface tissues. In summary, OSH related to bimatoprost treatment in laboratory animals occurs by endothelial-derived nitric oxide-mediated vasodilatation and is not associated with inflammation. These studies suggest that conjunctival hyperemia, a side effect of bimatoprost treatment, results from non-inflammatory, pharmacologically based vasodilatation.

Notizen: Experimental and clinical studies suggest that oxidative stress contributes to the development and progression of cardiovascular disease. However, clinical trials with classic vitamin antioxidants failed to demonstrate any benefit in cardiovascular outcomes. Recent advances in our understanding of mechanisms involved in free radical generation reinstate that a more comprehensive approach targeting the prevention of reactive oxygen species (ROS) formation early in the disease process may prove beneficial. Experimental studies and reviews in oxidative stress were selected to provide a better understanding of the roles of the reactive species in the initiation and progression of cardiovascular disease (CVD). Clinical studies that evaluated the efficacy of several classes of antioxidants in CVD were included in the second part of this review to discuss future therapeutic guidelines based on currently available evidence. In conclusion, before a potential role for antioxidants in the treatment of CVD is eliminated, more carefully designed studies with classic as well as new antioxidants in well-defined patient populations are warranted to provide a definitive answer.

Notizen: Purpose: The aim of the present study was to determine whether an increased water content during thermal cycling of hot water-treated acrylic was associated with a reduction in surface hardness and an increased opacity or whitening of the surface. Materials and Methods: Ten acrylic samples were treated with 30 soak cycles (cycle duration, 24 hours), using warm water (40°C) and an alkaline peroxide tablet (Efferdent® control group); a further ten samples were treated with boiling water (100°C) and one Efferdent® tablet (experimental group). Indentation hardness of the acrylic specimens was measured prior to and immediately following the completion of the warm and hot water treatments, using an automated micro-indentation system. The hydrated acrylic specimens were then allowed to air dry at room temperature (20°C) and were weighed weekly until they had obtained a constant dry weight. The loss in weight of the acrylic specimens represented the maximum water absorption. Results: The hot water-treated specimens were much whiter than the warm water-treated specimens. The mean reduction in hardness (HIT) of the acrylic specimens following the treatment with hot water and alkaline peroxide tablet was 12.9%. Treatment with warm water and alkaline peroxide resulted in a slight increase in mean hardness (2.63%). There was a significant correlation between the water content of the acrylic specimens after treatment and the percentage of change in indentation hardness (r= 0.495, p= 0.026). Conclusions: The hot water treatment of the acrylic was associated with a significant reduction in hardness. We attribute the whitening and reduction in the hardness of the hot water-treated specimens to absorption of water and a disruption of the acrylic surface structure.

Notizen: A critical factor that needs to be evaluated during the diagnosis and treatment planning phase for patients seeking an implant-tissue-supported overdenture or metal-resin implant fixed denture is the presence of adequate interarch distance. The amount of interarch distance is critical to the selection of appropriate implant abutments and attachments for both implant-tissue-supported overdentures and metal-resin implant fixed complete dentures. This clinical report describes a patient with complications related to the failure to diagnose inadequate interarch distance, and the methods used to resolve the patient's chief complaint. A guide for abutment-attachment selection using one commercially available implant system is given.

Notizen: A technique is described for fabrication of a remount cast for a removable partial denture. This procedure consists of filling the occlusal/incisal third with acrylic resin and injecting polyvinylsiloxane impression material into the irreversible hydrocolloid impression. This technique provides a simple method for making a remount cast and enables the clinician to remove and easily place the partial denture on the cast during occlusal refinement procedures without damage to the removable partial denture or the remount cast.

Notizen: Part III of this series of articles, like Part II, reviews the pioneering efforts in the 19th century to improve the quality of artificial teeth. The focus of this article, unlike that of Part II, is specifically modifications in the design of the occlusal anatomy of the 19th century denture teeth, along with the theories of mandibular movement that inspired those modifications. This article concludes the introductory phase of this project, which seeks to unravel the confusing history of the development of (posterior) denture teeth.

Notizen: Purpose: The primary purposes of this study were: (1) to describe the number and types of complications patients had before and after insertion of a removable prosthesis (i.e., denture) following radiation therapy to the head and neck and (2) to investigate whether the time between radiation therapy and denture insertion might contribute to those complications. Materials and Methods: This research evaluated edentulous patients and those who were rendered edentulous as a result of their cancer treatment. After obtaining institutional approval following HIPAA regulations, a total of 349 charts were identified: 152 patients from Houston Veterans Administration Medical Center (HVAMC) and 197 patients from M. D. Anderson Cancer Center (MDACC). A total of 190 patients met the inclusion criteria with data available for review. Results: No significant differences were found in any of the comparisons made, except when comparing complications that occurred after the dentures were inserted and the amount of time it took for prosthetic rehabilitation. The majority of patients had no complications. The patients who received their dentures in 180 days or less had the same number of complications when compared with those patients who received their dentures in 181 to 365 days and those who had to wait longer than a year for prosthetic rehabilitation. Patients with more pre-insertion complications tended to have delayed prosthetic rehabilitation. Those patients who had complications both before and after denture insertion tended to have bilateral dosing of their radiation treatment. Patients who had received radiation therapy were 1.7 times more likely to have post-prosthesis insertion complications. The majority of patients who experienced complications before and after denture insertion had greater than 5000 cGy. Conclusions: The numbers of complications reviewed in this retrospective analysis were considerably fewer than the number expected. There appears to be no difference in the number of pre- and post-insertion complications as a function of the time delay from oral surgical procedure to start of radiation treatment (10 to 21 days vs. 22 days or more).

Notizen: Background: A commercial mechanical mixer is available to make the mixing of alginate more convenient and more consistent for the practitioner; however, there is very little information on the mechanical properties of alginate mixed with this device as compared with hand mixing. Purpose: To compare the mechanical properties of alginate impression materials mixed with a mechanical mixer (Alginator II, Cadco) and hand mixing. Material and Methods: Three alginate impression materials (Identic, Jeltrate, and Kromopan) were tested. Strain in compression, elastic recovery, and compressive strength were measured according to ANSI/ADA specification no. 18-1992; tear energy was measured using a pants tear test. Five specimens were prepared for each group with 12 groups for the mechanical mixer and 12 groups for hand mixing, for a total of 120 specimens. A two-way analysis of variance and Fisher's PLSD test at the 0.05 level of significance were used to analyze the data. Results: There were statistically significant differences in properties among the materials, but mixing technique had no statistically significant effect on strain in compression and tear energy. Conclusion: The mechanical mixer improved elastic recovery and compressive strength of the alginate impression materials tested and had no effect on strain in compression and tear energy. A mechanical mixer facilitates the mixing of alginate impression materials and improves some mechanical properties.

Notizen: Purpose: Marginal integrity is a very important element in evaluating a restoration; however, there is no agreement in definition of a clinically acceptable margin. The purpose of this investigation was to examine margin acceptability using an explorer versus the actual marginal gap widths at four locations on uncemented crowns on three extracted teeth using both predoctoral students and prosthodontists as evaluators. Materials and Methods: The crown margin evaluation used 16 surfaces of four crowns fitting to three extracted caries-free teeth fitted into a dentiform. The teeth (nos. 14, 20, and 29) were prepared for a full cast (gold) crown using a chamfer finish line configuration, with some margins supragingival and others subgingival. After final impressions and working casts were made, die spacer was applied to the marginal area of the die before waxing to vary the marginal opening. The dentiform was placed in a mannequin in a supine position. Predoctoral students (N = 10) and prosthodontists (N = 9) evaluated each axial surface of each crown in the zone along the margin with an explorer and rated each surface as either “clinically acceptable” or “unacceptable.” After casting, the axial marginal openings were measured with Image Pro Software using a digital microscopic image of the surface. Each participant repeated the margin evaluations 6 months later. Results: Upon casting, marginal gaps ranged from 40 μm to 615 μm. The proportions of prosthodontists and of predoctoral students rating a given surface as “clinically unacceptable” were highly correlated (Spearman rank correlation = 0.81, p= 0.0001). The prosthodontists did not provide more or fewer ratings of clinical acceptability than the students, although kappa results indicated that the prosthodontists might be more consistent among themselves than the student raters. Upon re-evaluation, both groups rated between one and six of the surfaces differently than they had previously: the median number of inconsistencies was 1 for prosthodontists and 3 for predoctoral students. The prosthodontists tended to have fewer inconsistencies than the predoctoral students (0.05 〈 p 〈 0.10 Wilcoxon rank sum test), but this was not statistically significant. Conclusion: The data provided evidence that those surfaces associated with greater margin gaps tended to have a greater proportion of ratings of “clinically unacceptable.” The proportion of prosthodontists and predoctoral students rating a margin “clinically unacceptable” were highly correlated. Prosthodontists tended to have fewer inconsistencies than predoctoral students, but that difference was not statistically significant.

Notizen: Purpose: To compare the debonding/crack initiation strength (D/CIS) of a low-fusing pressable leucite-based glass ceramic (PC) fused to metal to a feldspathic porcelain (FP) fused to metal. Materials & Methods: As per ISO 9693:1999, 40 rectangular metal specimens (25.0 mm × 0.5 mm × 3.0 mm) were prepared. Twenty of the specimens were cast in a base metal nickel-chromium alloy (BA), and 20 were cast in a noble metal palladium-silver alloy (NA). Ten randomly selected NA and BA alloy specimens had FP applied. The remaining 10 NA and BA alloy specimens had ash-free wax patterns applied, the metal-wax complexes invested, and were pressed with a PC. The dimensions of the ceramic specimens were 8.0 mm × 1.0 mm × 3.0 mm, creating a combined metal-ceramic complex thickness of 1.5 mm. All specimens were subject to a three-point bending test at a crosshead speed of 1.5 mm/min. Fracture loads were recorded in Newtons and D/CISs calculated by the formula τb=k×Ffail. Results: Mean D/CISs, measured in MPa (standard deviations): NA-FP 32.56 (4.62), NA-PC 30.23 (5.06), BA-FP 30.98 (4.41), and BA-PC 31.81 (3.48). A two-way ANOVA (p 〉 0.05) did not demonstrate significant difference between groups. Conclusion: The debonding/crack initiation strength of a low-fusing pressable leucite-based glass ceramic fused to metal was equivalent to that of a feldspathic porcelain fused to metal.

Notizen: Trust in risk managers appears to be an important antecedent of public acceptance for many hazards. However, such trust may be fragile since research suggests that negative performance information has a greater impact than positive performance information (Slovic, 1993). Closer examination of these findings suggests two potential moderators of this valence-related asymmetry—information specificity and hazard risk potential. First, we predicted that the asymmetry would be less evident for low versus high specificity information (risk management policies vs. concrete events). Second, we predicted that it would also be less evident for a low- versus high-risk hazard (pharmaceutical vs. nuclear industry). Study 1 reanalyzed Slovic's original trust asymmetry data for the nuclear industry. In line with Prediction 1, trust asymmetry was less evident for policy than event-related information. Using a new set of items with more clearly defined levels of specificity, Study 2 replicated and extended these findings for the high-risk hazard (nuclear power). In line with Prediction 2, trust asymmetry was even less evident for the low-risk hazard (pharmaceuticals). Positive policies in this industry actually had a greater impact on trust than negative ones, in contrast to previous findings. Results support an information diagnosticity account of earlier findings and suggest that trust in risk managers may be more robust than previously believed.

Notizen: Much attention has been addressed to the question of whether Europe or the United States adopts a more precautionary stance to the regulation of potential environmental, health, and safety risks. Some commentators suggest that Europe is more risk-averse and precautionary, whereas the United States is seen as more risk-taking and optimistic about the prospects for new technology. Others suggest that the United States is more precautionary because its regulatory process is more legalistic and adversarial, while Europe is more lax and corporatist in its regulations. The flip-flop hypothesis claims that the United States was more precautionary than Europe in the 1970s and early 1980s, and that Europe has become more precautionary since then. We examine the levels and trends in regulation of environmental, health, and safety risks since 1970. Unlike previous research, which has studied only a small set of prominent cases selected nonrandomly, we develop a comprehensive list of almost 3,000 risks and code the relative stringency of regulation in Europe and the United States for each of 100 risks randomly selected from that list for each year from 1970 through 2004. Our results suggest that: (a) averaging over risks, there is no significant difference in relative precaution over the period, (b) weakly consistent with the flip-flop hypothesis, there is some evidence of a modest shift toward greater relative precaution of European regulation since about 1990, although (c) there is a diversity of trends across risks, of which the most common is no change in relative precaution (including cases where Europe and the United States are equally precautionary and where Europe or the United States has been consistently more precautionary). The overall finding is of a mixed and diverse pattern of relative transatlantic precaution over the period.

Notizen: This article tests the hypothesis that the exposure to the threat to societies posed by the introduction of new technologies is associated with a normalization of risk perception. Data collected in 2000 by the International Social Survey Programme (ISSP) on environmental issues were used to explore this hypothesis. Representative samples from 25 countries were employed to assess the national levels of perceived threat to the environment associated with a series of technologies and activities. These values were correlated with economic indicators (mainly from the World Bank) of the diffusion of each of the technologies or activities in each country. Results indicate a negative association of risk perception with the level of technological prevalence (societal normalization effect) and a positive association with the rate of growth of the technology (societal sensitivity effect). These results indicate that the most acute levels of perceived environmental risk are found in those countries where the level of technological prevalence is low but where there has recently been substantial technological development. Environmental awareness is a mediator of the relationship between risk perception and the indices of technological diffusion. This result means that: (1) societal normalization of risk is not a direct consequence of prevalence of the technology, but is driven by awareness of technological development and that (2) societal sensitivity to risk is associated with lower levels of environmental awareness.

Notizen: This article investigates whether the choice experiment approach can be used to assess people's preferences and the determinants of these preferences in order to estimate the costs and benefits of different configurations of the transport of hazardous materials by rail. Changes in the exposure to hazardous materials that people are subjected to are used rather than changes in accident risk. To the best knowledge of the author, this has not been done before in a study of people's preferences toward hazardous materials. A mail survey, carried out in two cities in Sweden, is used to obtain tentative estimates of the willingness to pay for a reduction in exposure as well as the willingness to accept an increase in exposure. Special attention is given to viability, since the complexity of the activity studied, transport of hazardous materials, and the method used pose particular challenges. The response rate and tests of validity and consistency indicate that this method can be applied. Moreover, the results suggest that studies of this kind may provide guidance on changes in the transport of hazardous materials, especially because policymakers may influence the attributes presented here. Referring to the exposure of hazardous materials highlights the importance of providing the respondents with adequate information regarding hazardous transports. An important finding is that the amount of background information may have some effect on the stated preferences.

Notizen: This article presents a Listeria monocytogenes growth model in milk at the farm bulk tank stage. The main objective was to judge the feasibility and value to risk assessors of introducing a complex model, including a complete thermal model, within a microbial quantitative risk assessment scheme. Predictive microbiology models are used under varying temperature conditions to predict bacterial growth. Input distributions are estimated based on data in the literature, when it is available. If not, reasonable assumptions are made for the considered context. Previously published results based on a Bayesian analysis of growth parameters are used. A Monte Carlo simulation that forecasts bacterial growth is the focus of this study. Three scenarios that take account of the variability and uncertainty of growth parameters are compared. The effect of a sophisticated thermal model taking account of continuous variations in milk temperature was tested by comparison with a simplified model where milk temperature was considered as constant. Limited multiplication of bacteria within the farm bulk tank was modeled. The two principal factors influencing bacterial growth were found to be tank thermostat regulation and bacterial population growth parameters. The dilution phenomenon due to the introduction of new milk was the main factor affecting the final bacterial concentration. The results show that a model that assumes constant environmental conditions at an average temperature should be acceptable for this process. This work may constitute a first step toward exposure assessment for L. monocytogenes in milk. In addition, this partly conceptual work provides guidelines for other risk assessments where continuous variation of a parameter needs to be taken into account.

Notizen: Limited time and resources usually characterize environmental decision making at policy organizations such as the U.S. Environmental Protection Agency. In these climates, addressing uncertainty, usually considered a flaw in scientific analyses, is often avoided. However, ignoring uncertainties can result in unpleasant policy surprises. Furthermore, it is important for decisionmakers to know how defensible a chosen policy option is over other options when the uncertainties of the data are considered. The purpose of this article is to suggest an approach that is unique from other approaches in that it considers uncertainty in two specific ways—the uncertainty of stakeholder values within a particular decision context and data uncertainty in the light of the decision-contextual data–values relationship. It is the premise of this article that the interaction between data and stakeholder values is critical to how the decision options are viewed and determines the effect of data uncertainty on the relative acceptability of the decision options, making the understanding of this interaction important to decisionmakers and other stakeholders. This approach utilizes the recently developed decision analysis framework and process, multi-criteria integrated resource assessment (MIRA). This article will specifically address how MIRA can be used to help decisionmakers better understand the importance of uncertainty on the specific (i.e., decision contextual) environmental policy options that they are deliberating.

Notizen: Perceptions of risks associated with mobile phones, base stations, and other sources of electromagnetic fields (EMF) were examined. Data from a telephone survey conducted in the German- and French-speaking parts of Switzerland are presented (N= 1,015). Participants assessed both risks and benefits associated with nine different sources of EMF. Trust in the authorities regulating these hazards was assessed as well. In addition, participants answered a set of questions related to attitudes toward EMF and toward mobile phone base stations. According to respondents' assessments, high-voltage transmission lines are the most risky source of EMF. Mobile phones and mobile phone base stations received lower risk ratings. Results showed that trust in authorities was positively associated with perceived benefits and negatively associated with perceived risks. People who use their mobile phones frequently perceived lower risks and higher benefits than people who use their mobile phones infrequently. People who believed they lived close to a base station did not significantly differ in their level of risks associated with mobile phone base stations from people who did not believe they lived close to a base station. Regarding risk regulation, a majority of participants were in favor of fixing limiting values based on the worst-case scenario. Correlations suggest that belief in paranormal phenomena is related to level of perceived risks associated with EMF. Furthermore, people who believed that most chemical substances cause cancer also worried more about EMF than people who did not believe that chemical substances are that harmful. Practical implications of the results are discussed.

Notizen: Experts contend that weather and climate forecasts could have an important role in risk management strategies for community water systems. Yet, most water managers make minimal use of these forecasts. This research explores the determinants of the use of weather and climate forecasts by surveying managers of community water systems in two eastern American states (South Carolina and the Susquehanna River Basin of Pennsylvania). Assessments of the reliability of weather and climate forecasts are not driving their use as water managers who find forecasts reliable are no more likely to use them than are managers who find them unreliable. Although larger systems and those depending on surface water are more likely to use forecasts for some (but not all) purposes, the strongest determinant of forecast use is risk perceptions. Water managers who expect to face problems from weather events in the next decade are much more likely to use forecasts than are water managers who expect few problems. Their expectations of future problems are closely linked with past experience: water managers who have had problems with specific types of weather events (e.g., flood emergencies) in the last 5 years are likely to expect to experience problems in the next decade. Feeling at risk, regardless of the specific source of that weather-related risk, stimulates a decision to use weather and climate forecasts.

Notizen: The growing international trade in live wildlife has the potential to result in continuing establishment of nonnative animal populations in the United States. Snakes may pose particularly high risks as potentially invasive species, as exemplified by the decimation of Guam's vertebrate fauna by the accidentally introduced brown tree snake. Herein, ecological and commercial predictors of the likelihood of establishment of invasive populations were used to model risk associated with legal commercial imports of 23 species of boas, pythons, and relatives into the United States during the period 1989–2000. Data on ecological variables were collected from multiple sources, while data on commercial variables were collated from import records maintained by the U.S. Fish and Wildlife Service. Results of the risk-assessment models indicate that species including boa constrictors (Boa constrictor), ball pythons (Python regius), and reticulated pythons (P. reticulatus) may pose particularly high risks as potentially invasive species. Recommendations for reducing risk of establishment of invasive populations of snakes and/or pathogens include temporary quarantine of imports to increase detection rates of nonnative pathogens, increasing research attention to reptile pathogens, reducing the risk that nonnative snakes will reach certain areas with high numbers of federally listed species (such as the Florida Keys), and attempting to better educate individuals purchasing reptiles.

Notizen: This study examines the perceived risks to forest biodiversity and perceived effectiveness of biodiversity conservation strategies among the general public. It tests the hypotheses that perceived risk to forest biodiversity is influenced by cognitive factors (value orientation and knowledge) and social-cultural factors (such as gender and environmental membership) and that risk perceptions influence other cognitive constructs such as support for natural resource policy and management. Data were collected from a sample of the general public (n= 596) in British Columbia, Canada by mail survey in 2001. Results show that insects and disease were perceived as the greatest risk. Educating the public and industry about biodiversity issues was perceived as a more effective conservation strategy than restricting human uses of the forest. Value orientation was a better predictor of perceptions of risk and perceived effectiveness of conservation strategies than knowledge indicators or social-cultural variables. Examining the indirect effects of social-cultural variables, however, revealed that value orientation may amplify the effect of these variables and suggests that alternative paths of influence should be included. Perceived risk showed an inconsistent association with perceived effectiveness of conservation strategies.

Notizen: A unique multidisciplinary perspective on the risk literature is used to establish a fresh and provocative argument regarding the epistemological understanding and definition of risk. Building on economic conceptualizations that distinguish risk from uncertainty and argue that risk is an ordered application of knowledge to the unknown, the survey identifies each of the disciplines as having a particular knowledge approach with which they confront the unknown so as to order its randomness and convert it into a risk proposition. This epistemological approach suggests the concept of risk can act as a mirror, reflecting the preoccupations, strengths, and weaknesses of each discipline as they grapple with uncertainty. The conclusion suggests that the different disciplines can, and desirably should, act in concert toward a cumulative appreciation of risk that progresses our understanding of the concept. One way in which the article challenges risk experts to join disciplinary forces in a collaborative effort is to holistically appreciate and articulate the concept of political risk calculation.

Notizen: By displaying a risk reduction of 50% graphically rather than numerically, Stone, Yates, and Parker significantly increased professed risk-avoidant behavior. The current experiments replicated this effect at various risk ratios. Specifically, participants were willing to spend more money to reduce a risk when the risk information was displayed by asterisks rather than by numbers for risk-reduction ratios ranging from 3% to 97%. Transforming the amount participants were willing to spend to logarithms significantly improved a linear fit to the data, suggesting that participants convert this variable within the decision-making process. Moreover, a log-linear model affords an exceptional fit to both the graphical and numerical data, suggesting that a graphical presentation elicits the same decision-making mechanism as does the numerical display. In addition, the data also suggest that each person removed from harm is weighted more by some additional factor in the graphical compared to the numerical presentations.

Notizen: While quantitative estimates of risk have been a standard practice in cancer risk assessment for many years, no similar practice is evident in noncancer risk assessment. We use two recent examples involving methylmercury and arsenic to illustrate the negative impact of this discrepancy on risk communication and cost-benefit analysis. We argue for a more balanced treatment of cancer and noncancer risks and suggest an approach for reaching this goal.

Notizen: Experimental animal studies often serve as the basis for predicting risk of adverse responses in humans exposed to occupational hazards. A statistical model is applied to exposure-response data and this fitted model may be used to obtain estimates of the exposure associated with a specified level of adverse response. Unfortunately, a number of different statistical models are candidates for fitting the data and may result in wide ranging estimates of risk. Bayesian model averaging (BMA) offers a strategy for addressing uncertainty in the selection of statistical models when generating risk estimates. This strategy is illustrated with two examples: applying the multistage model to cancer responses and a second example where different quantal models are fit to kidney lesion data. BMA provides excess risk estimates or benchmark dose estimates that reflects model uncertainty.

Notizen: Following a comprehensive evaluation of the health risks of radon, the U.S. National Research Council (US-NRC) concluded that the radon inside the homes of U.S. residents is an important cause of lung cancer. To assess lung cancer risks associated with radon exposure in Canadian homes, we apply the new (US-NRC) techniques, tailoring assumptions to the Canadian context. A two-dimensional uncertainty analysis is used to provide both population-based (population attributable risk, PAR; excess lifetime risk ratio, ELRR; and life-years lost, LYL) and individual-based (ELRR and LYL) estimates. Our primary results obtained for the Canadian population reveal mean estimates for ELRR, PAR, and LYL are 0.08, 8%, and 0.10 years, respectively. Results are also available and stratified by smoking status (ever versus never). Conveniently, the three indices (ELRR, PAR, and LYL) reveal similar output uncertainty (geometric standard deviation, GSD ≈ 1.3), and in the case of ELRR and LYL, comparable variability and uncertainty combined (GSD ≈ 4.2). Simplifying relationships are identified between ELRR, LYL, PAR, and the age-specific excess rate ratio (ERR), which suggest a way to scale results from one population to another. This insight is applied in scaling our baseline results to obtain gender-specific estimates, as well as in simplifying and illuminating sensitivity analysis.

Notizen: Air pollution is a current and growing concern for Canadians, and there is evidence that ambient levels that meet current exposure standards may be associated with mortality and morbidity in Toronto, Canada. Evaluating exposure is an important step in understanding the relationship between particulate matter (PM) exposure and health outcomes. This report describes the PEARLS model (Particulate Exposure from Ambient to Regional Lung by Subgroup), which predicts exposure distributions for 11 age-gender population subgroups in Toronto to PM2.5 (PM with a median aerodynamic diameter of 2.5 μm or less) using Monte Carlo simulation techniques. The model uses physiological and activity pattern characteristics of each subgroup to determine region-specific lung exposure to PM2.5, which is defined as the mass of PM2.5 deposited per unit time to each of five lung regions (two extrathoracic, bronchial, bronchiolar, and alveolar). The modeling results predict that children, toddlers, and infants have the broadest distributions of exposure, and the greatest chance of experiencing extreme exposures in the alveolar region of the lung. Importance analysis indicates that the most influential model variables are air exchange rate into indoor environments, time spent outdoors, and time spent at high activity levels. Additionally, a “critical point” was defined and introduced to the PEARLS to investigate the effects of possible threshold-pathogenic phenomena on subgroup exposure patterns. The analysis indicates that the subgroups initially predicted to be most highly exposed were likely to have the highest proportion of their population exposed above the critical point. Substantial exposures above the critical point were predicted in all subgroups for ambient concentrations of PM2.5 commonly observed in Toronto after continuous exposure of 24 hours or more.

Notizen: It has been shown that bathroom-type water uses dominate personal exposure to water-borne contaminants in the home. Therefore, in assessing exposure of specific population groups to the contaminants in the water, understanding population water-use behavior for bathroom activities as a function of demographic characteristics is vital to realistic exposure estimates. In this article, shower and bath frequencies and durations are analyzed, presented, and compared for various demographic groups derived from analyses of the National Human Activities Pattern Survey (NHAPS) database and the Residential End Uses of Water Study (REUWS) database as well as from a review of current literature. Analysis showed that age and level of education significantly influenced shower and bath frequency and duration. The frequency of showering and bathing reported in NHAPS agreed reasonably well with previous studies; however, durations of these events were found to be significantly longer. Showering frequency reported in REUWS was slightly less than that reported for NHAPS; however, durations of showers reported in REUWS are consistent with other studies. After considering the strengths and weaknesses of each data set and comparing their results to previous studies, it is concluded that NHAPS provides more reliable frequency data, while REUWS provides more reliable duration data. The shower- and bath-use behavior parameters recommended in this article can aid modelers in appropriately specifying water-use behavior as a function of demographic group in order to conduct reasonable assessments of exposure to contaminants that enter the home via the water supply.

Notizen: Information about two uncertainties is superadditive in value if the value of information for resolving both uncertainties together exceeds the sum of the value of information for resolving each uncertainty alone. For the two-act linear loss decision problem with normal priors, conditions are derived for which the expected value of perfect information about two independent risks is superadditive. An approximate condition is also presented. The level of additivity of information value has implications for how risk-management resources should be allocated to acquisition of information. Several applications show how a variety of decision problems can reduce to the basic problem, and how the general results obtained here can be translated simply to prescriptions for specific situations.

Notizen: Reference values, including an oral reference dose (RfD) and an inhalation reference concentration (RfC), were derived for propylene glycol methyl ether (PGME), and an oral RfD was derived for its acetate (PGMEA). These values were based on transient sedation observed in F344 rats and B6C3F1 mice during a two-year inhalation study. The dose-response relationship for sedation was characterized using internal dose measures as predicted by a physiologically-based pharmacokinetic (PBPK) model for PGME and its acetate. PBPK modeling was used to account for changes in rodent physiology and metabolism due to aging and adaptation, based on data collected during Weeks 1, 2, 26, 52, and 78 of a chronic inhalation study. The peak concentration of PGME in richly perfused tissues (i.e., brain) was selected as the most appropriate internal dose measure based on a consideration of the mode of action for sedation and similarities in tissue partitioning between brain and other richly perfused tissues. Internal doses (peak tissue concentrations of PGME) were designated as either no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) based on the presence or the absence of sedation at each time point, species, and sex in the two-year study. Distributions of the NOAEL and LOAEL values expressed in terms of internal dose were characterized using an arithmetic mean and standard deviation, with the mean internal NOAEL serving as the basis for the reference values, which was then divided by appropriate uncertainty factors. Where data were permitting, chemical-specific adjustment factors were derived to replace default uncertainty factor values of 10. Nonlinear kinetics, which was predicted by the model in all species at PGME concentrations exceeding 100 ppm, complicate interspecies, and low-dose extrapolations. To address this complication, reference values were derived using two approaches that differ with respect to the order in which these extrapolations were performed: (1) default approach of interspecies extrapolation to determine the human equivalent concentration (PBPK modeling) followed by uncertainty factor application, and (2) uncertainty factor application followed by interspecies extrapolation (PBPK modeling). The resulting reference values for these two approaches are substantially different, with values from the latter approach being seven-fold higher than those from the former approach. Such a striking difference between the two approaches reveals an underlying issue that has received little attention in the literature regarding the application of uncertainty factors and interspecies extrapolations to compounds where saturable kinetics occur in the range of the NOAEL. Until such discussions have taken place, reference values based on the former approach are recommended for risk assessments involving human exposures to PGME and PGMEA.

Notizen: In the process of screening a soil against a certain contaminant, we define the health-risk-based preliminary remediation goal (PRG) as the contaminant concentration above which some remedial action may be required. Thus, PRG is the first standard (or guidance) for judging a site. An overestimated PRG (a too-large value) may cause us to miss some contaminated sites that can threaten human health and the environment. An underestimated PRG (a too-small value), on the other hand, may lead to unnecessary cleanup and waste tremendous resources. The PRGs for soils are often calculated on the assumption that the contaminant concentration in soil does not change with time. However, that concentration usually decreases with time as a result of different chemical and transport mechanisms. The static assumption thus exaggerates the long-term exposure dose and results in a too-small PRG. We present a box model that considers all important transport processes and obeys the law of mass conservation. We can use the model as a tool to estimate the transient contaminant concentrations in air, soil, and ground water. Using these concentrations in conjunction with appropriate health-risk parameters, we may estimate the PRGs for different contaminants. As an example, we calculated the tritium PRG for residential soils. The result is quite different from, but within the range of, the two versions of the corresponding PRG previously recommended by the U.S. EPA.

Notizen: The extreme importance of critical infrastructures to modern society is widely recognized. These infrastructures are complex and interdependent. Protecting the critical infrastructures from terrorism presents an enormous challenge. Recognizing that society cannot afford the costs associated with absolute protection, it is necessary to identify and prioritize the vulnerabilities in these infrastructures. This article presents a methodology for the identification and prioritization of vulnerabilities in infrastructures. We model the infrastructures as interconnected digraphs and employ graph theory to identify the candidate vulnerable scenarios. These scenarios are screened for the susceptibility of their elements to a terrorist attack, and a prioritized list of vulnerabilities is produced. The prioritization methodology is based on multiattribute utility theory. The impact of losing infrastructure services is evaluated using a value tree that reflects the perceptions and values of the decisionmaker and the relevant stakeholders. These results, which are conditional on a specified threat, are provided to the decisionmaker for use in risk management. The methodology is illustrated through the presentation of a portion of the analysis conducted on the campus of the Massachusetts Institute of Technology.

Notizen: This study assesses the fire safety risks associated with compressed natural gas (CNG) vehicle systems, comprising primarily a typical school bus and supporting fuel infrastructure. The study determines the sensitivity of the results to variations in component failure rates and consequences of fire events. The components and subsystems that contribute most to fire safety risk are determined. Finally, the results are compared to fire risks of the present generation of diesel-fueled school buses. Direct computation of the safety risks associated with diesel-powered vehicles is possible because these are mature technologies for which historical performance data are available. Because of limited experience, fatal accident data for CNG bus fleets are minimal. Therefore, this study uses the probabilistic risk assessment (PRA) approach to model and predict fire safety risk of CNG buses. Generic failure data, engineering judgments, and assumptions are used in this study. This study predicts the mean fire fatality risk for typical CNG buses as approximately 0.23 fatalities per 100-million miles for all people involved, including bus passengers. The study estimates mean values of 0.16 fatalities per 100-million miles for bus passengers only. Based on historical data, diesel school bus mean fire fatality risk is 0.091 and 0.0007 per 100-million miles for all people and bus passengers, respectively. One can therefore conclude that CNG buses are more prone to fire fatality risk by 2.5 times that of diesel buses, with the bus passengers being more at risk by over two orders of magnitude. The study estimates a mean fire risk frequency of 2.2 × 10−5 fatalities/bus per year. The 5% and 95% uncertainty bounds are 9.1 × 10−6 and 4.0 × 10−5, respectively. The risk result was found to be affected most by failure rates of pressure relief valves, CNG cylinders, and fuel piping.

Notizen: Laypeople's perceptions of health and safety risks have been widely studied, but only a few studies have addressed perceptions of ecological hazards. We assembled a list of 39 attributes of ecological hazards from the literatures on comparative risk assessment, ecological health, environmental conservation and management, environmental psychology, and risk perception. In Study 1, 125 laypeople evaluated 83 hazards on subsets of this attribute set. Factor analysis of attribute ratings (averaged over participants) revealed six oblique factors: ecological impacts, human impacts, human benefits, aesthetic impacts, scientific understanding, and controllability. These factors predicted mean judgments of overall riskiness, ecological riskiness, acceptability, and regulatory strictness. In Study 2, 30 laypeople each evaluated 34 hazards on 17 attributes and 3 dependent variables. Aggregate-level factor analysis of these data replicated the appropriate portion of the factor solution and yielded similar regression results. Parallel analyses at the individual-participant level yielded factors that explained less variance in judgments of overall riskiness, ecological riskiness, and acceptability. However, the decrease in explanatory power was much less than is often reported for disaggregate-level analyses of psychometric data. This discrepancy illustrates the importance of distinguishing between the level of analysis (aggregate versus disaggregate) and the focus of analysis (distinctions among hazards versus distinctions among participants). In a hybrid analysis, aggregate-level factor scores predicted individual participants' riskiness judgments reasonably well. Psychometric studies such as these provide a sound empirical basis for selecting attributes of ecological hazards for use in comparative risk assessment.

Notizen: Government and private sector organizations are increasingly turning to the use of maps and other visual models to provide a depiction of environmental hazards and the potential risks they represent to humans and ecosystems. Frequently, the graphic presentation is tailored to address a specific contaminant, its location and possible exposure pathways, and potential receptors. Its format is usually driven by the data available, choice of graphics technology, and the audience being served. A format that is effective for displaying one contaminant at one scale at one site, however, may be ineffective in accurately portraying the circumstances surrounding a different contaminant at the same site, or the same contaminant at a different site, because of limitations in available data or the graphics technology being used. This is the daunting challenge facing the U.S. Department of Energy (DOE), which is responsible for the nation's legacy wastes from nuclear weapons research, testing, and production at over 100 sites in the United States. In this article, we discuss the development and use of integrated geospatial mapping and conceptual site models to identify hazards and evaluate alternative long-term environmental clean-up strategies at DOE sites located across the United States. While the DOE probably has the greatest need for such information, the Department of Defense and other public and private responsible parties for many large and controversial National Priority List or Superfund sites would benefit from a similar approach.

Notizen: The research team interviewed over 90 Finnish battalion members in Kosovo, visited 22 units or posts, registered its observations, and made any necessary measurements. Key persons were asked to list the most important risks for occupational safety and health in their area of responsibility. Altogether, 106 accidents and 40 cases of disease resulted in compensation claims in 2000. The risks to the peacekeeping force were about twice those of the permanent staff of military trainees in Finland. Altogether, 21 accidents or cases of disease resulted in sick leave for at least 3 months after service. One permanent injury resulted from an explosion. Biological, chemical, and physical factors caused 8 to 9 occupational illnesses each. Traffic accidents, operational factors, and munitions and mines were evaluated to be the three most important risk factors, followed by occupational hygiene, living conditions (mold, fungi, dust), and general hygiene. Possible fatal risks, such as traffic accidents and munitions and explosives, received a high ranking in both the subjective and the objective evaluations. One permanent injury resulted from an explosion, and two traffic accidents involved a fatality, although not of a peacekeeper. The reduction of sports and military training accidents, risk-control programs, and, for some tasks, better personal protection is considered a development challenge for the near future.

Notizen: The aim of this study was to determine the impact on risk perceptions of disclosing genetic test results used to estimate the risk of Alzheimer's disease (AD). Adult children (n= 149) of people with AD were randomized to one of two groups—Intervention group: lifetime risk estimates of AD based on age, gender, family history, and Apolipoprotein E (APOE) genotype; Control group: lifetime risk estimates of AD based on the same risk factors excluding APOE genotype. Perceptions of personal risk (PPR) for AD were assessed six weeks after risk assessments. PPR were correlated with actual lifetime risk estimates (r= 0.501; p 〈 0.0001). After controlling for lifetime risks communicated to participants, age, and number of affected relatives, PPR scores among those with an ɛ4-positive test result (the test result associated with increased AD susceptibility) (adjusted mean: 3.4 (SD: 0.7)) were not different from the PPR scores in the Control group (adjusted mean: 3.4 (SD: 0.7) (F(1,91)= 1.98; p= 0.162). Again, controlling for lifetime risk estimates, age, and number of affected relatives, the PPR score of those receiving an ɛ4-negative test result was significantly lower (adjusted mean: 3.1 (SD: 0.8)) than those in the Control group (adjusted mean: 3.4 (SD: 0.7) (F(1,95)= 6.23; p= 0.014). Perceptions of risk of developing AD are influenced by genetic test disclosure in those receiving ɛ4-negative, but not those receiving ɛ4-positive test results. Despite the reduced perceptions of risk in the former group, there was no evidence of false reassurance (i.e., perceiving risks as equal to or lower than population risks of AD), although this possibility should be assessed in other testing contexts.

Notizen: Society often sets social standards that define thresholds of damage to society or the environment above which compensation must be paid to the state or other parties. In this article, we analyze the interdependence between the use of social standards and investment evaluation under dynamic uncertainty where a negative externality above a threshold established by society requires an assessment and payment of damages. Under uncertainty, the party considering implementing a project or new technology must not only assess when the project is economically efficient to implement but when to abandon a project that could potentially exceed the social standard. Using real-option theory and simple models, we demonstrate how such a social standard can be integrated into cost-benefit analysis through the use of a development option and a liability option coupled with a damage function. Uncertainty, in fact, implies that both parties interpret the social standard as a target for safety rather than an inflexible barrier that cannot be overcome. The larger is the uncertainty, in fact, the greater will be the tolerance for damages in excess of the social standard from both parties.

Notizen: There is increasing interest in being able to express the consequences of exposure to potentially toxic compounds in monetary terms in order to evaluate potential cost-benefit relationships of controlling exposure. Behavioral effects of acute toluene exposure could be subjected to cost-benefit analysis if the effects of toluene were quantitatively compared to those of ethanol ingestion, which has been monetized for applied contexts. Behavioral effects of toluene and ethanol were quantified by meta-analysis of studies from the peer-reviewed literature describing their effects on choice reaction time (reaction time in a test requiring a subject to choose among two or more alternatives before responding). The internal doses of these compounds were estimated by a general physiological and toxicokinetic (GPAT) simulation from exposure parameters provided in the reports. The reported effects were converted to a common metric (proportion of baseline) and related to the estimated internal doses of toluene and ethanol, from which dose-effect equations were fitted. The estimated effect of toluene was compared to the estimated effect of ethanol on the same dependent variable by deriving a dose-equivalence equation (DEE) to express the dose of toluene as an equivalent dose of ethanol on the basis of equal effect magnitude. A nomogram was constructed by GPAT simulation to relate the environmental exposure concentration of toluene to the equivalent effect magnitude of a range of ethanol internal doses. Behavioral effects and their evaluation are determined by internal doses, which in turn are determined by a variety of variables. In addition to concentration and duration of exposure, which determine internal dose by pharmacokinetic processes, the activity level of exposed persons is a major factor. This analysis provides a continuous function of the consequences of toluene exposure expressed as ethanol-equivalent doses within confidence limits. The resulting function has the potential to estimate the monetary values of behavioral deficits caused by a range of exposures to toluene from existing monetized information on ethanol.

Notizen: Clostridium perfringens is a pathogen that mainly causes food poisoning outbreaks when large quantities of food are prepared. Therefore, a model was developed to predict the effect of different cooling procedures on the growth of this pathogen during cooling of food: Dutch pea soup. First, a growth rate model based on interpretable parameters was used to predict growth during linear cooling of pea soup. Second, a temperature model for cooling pea soup was constructed by fitting the model to experimental data published earlier. This cooling model was used to estimate the effect of various cooling environments on average cooling times, taking into account the effect of stirring and product volume. The growth model systematically overestimated growth of C. perfringens during cooling in air, but this effect was limited to less than 0.5 log N/ml and this was considered to be acceptable for practical purposes. It was demonstrated that the growth model for C. perfringens combined with the cooling model for pea soup could be used to sufficiently predict growth of C. perfringens in different volume sizes of pea soup during cooling in air as well as the effect of stirring, different cooling temperatures, and various cooling environments on the growth of C. perfringens in pea soup. Although fine-tuning may be needed to eliminate inaccuracies, it was concluded that the combined model could be a useful tool for designing good manufacturing practices (GMP) procedures.

Notizen: The management of microbial risk in food products requires the ability to predict growth kinetics of pathogenic microorganisms in the event of contamination and growth initiation. Useful data for assessing these issues may be found in the literature or from experimental results. However, the large number and variety of data make further development difficult. Statistical techniques, such as meta-analysis, are then useful to realize synthesis of a set of distinct but similar experiences. Moreover, predictive modeling tools can be employed to complete the analysis and help the food safety manager to interpret the data. In this article, a protocol to perform a meta-analysis of the outcome of a relational database, associated with quantitative microbiology models, is presented. The methodology is illustrated with the effect of temperature on pathogenic Escherichia coli and Listeria monocytogenes, growing in culture medium, beef meat, and milk products. Using a database and predictive models, simulations of growth in a given product subjected to various temperature scenarios can be produced. It is then possible to compare food products for a given microorganism, according to its growth ability in these products, and to compare the behavior of bacteria in a given foodstuff. These results can assist decisions for a variety of questions on food safety.

Notizen: The uncertainty associated with estimates should be taken into account in quantitative risk assessment. Each input's uncertainty can be characterized through a probabilistic distribution for use under Monte Carlo simulations. In this study, the sampling uncertainty associated with estimating a low proportion on the basis of a small sample size was considered. A common application in microbial risk assessment is the estimation of a prevalence, proportion of contaminated food products, on the basis of few tested units. Three Bayesian approaches (based on beta(0, 0), beta 〈inlineGraphic alt="inline image" href="urn:x-wiley:02724332:RISA565:RISA_565_mu1" location="equation/RISA_565_mu1.gif"/〉, and beta(l, 1)) and one frequentist approach (based on the frequentist confidence distribution) were compared and evaluated on the basis of simulations. For small samples, we demonstrated some differences between the four tested methods. We concluded that the better method depends on the true proportion of contaminated products, which is by definition unknown in common practice. When no prior information is available, we recommend the beta 〈inlineGraphic alt="inline image" href="urn:x-wiley:02724332:RISA565:RISA_565_mu2" location="equation/RISA_565_mu2.gif"/〉 prior or the confidence distribution. To illustrate the importance of these differences, the four methods were used in an applied example. We performed two-dimensional Monte Carlo simulations to estimate the proportion of cold smoked salmon packs contaminated by Listeria monocytogenes, one dimension representing within-factory uncertainty, modeled by each of the four studied methods, and the other dimension representing variability between companies.

Notizen: A poultry-processing model for a quantitative microbiological risk assessment (QMRA) of campylobacter is presented, which can also be applied to other QMRAs involving poultry processing. The same basic model is applied in each consecutive stage of industrial processing. It describes the effects of inactivation and removal of the bacteria, and the dynamics of cross-contamination in terms of the transfer of campylobacter from the intestines to the carcass surface and the environment, from the carcasses to the environment, and from the environment to the carcasses. From the model it can be derived that, in general, the effect of inactivation and removal is dominant for those carcasses with high initial bacterial loads, and cross-contamination is dominant for those with low initial levels. In other QMRA poultry-processing models, the input-output relationship between the numbers of bacteria on the carcasses is usually assumed to be linear on a logarithmic scale. By including some basic mechanistics, it is shown that this may not be realistic. As nonlinear behavior may affect the predicted effects of risk mitigations; this finding is relevant for risk management. Good knowledge of the variability of bacterial loads on poultry entering the process is important. The common practice in microbiology to only present geometric mean of bacterial counts is insufficient: arithmetic mean are more suitable, in particular, to describe the effect of cross-contamination. The effects of logistic slaughter (scheduled processing) as a risk mitigation strategy are predicted to be small. Some additional complications in applying microbiological data obtained in processing plants are discussed.

Notizen: A linear population risk model used by the U.S. Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM) estimates the risk of human cases of campylobacteriosis caused by fluoroquinolone-resistant Campylobacter. Among the cases of campylobacteriosis attributed to domestically produced chicken, the fluoroquinolone resistance is assumed to result from the use of fluoroquinolones in poultry in the United States. Properties of the linear population risk model are contrasted with those of a farm-to-fork model commonly used for microbial risk assessments. The utility of the linear population model for the purpose for which it was used by CVM is discussed.

Notizen: A mathematical model is presented, which addresses individual hygiene practices during food preparation and consumption patterns in private homes. Further, the model links food preparers and consumers based on their relationship to household types. For different age and gender groups, the model estimates (i) the probability of ingesting a meal where precautions have not been taken to avoid the transfer of microorganisms from raw food to final meal (a risk meal), exemplified by the event that the cutting board was not washed during food preparation, and (ii) the probability of ingesting a risk meal in a private home, where chicken was the prepared food item (a chicken risk meal). Chicken was included in the model, as chickens are believed to be the major source of human exposure to the foodborne pathogen Campylobacter. Monte Carlo simulations showed that the probability of ingesting a risk meal was highest for young males (aged 18–29 years) and lowest for the elderly above 60 years of age. Children aged 0–4 years had a higher probability of ingesting a risk meal than children aged 5–17 years. This difference between age and gender groups was ascribed to the variations in the hygiene levels of food preparers. By including the probability of ingesting a chicken meal at home, simulations revealed that all age groups, except the group above 60 years of age, had approximately the same probability of ingesting a chicken risk meal, the probability of females being slightly higher than that of males. The simulated results show that the probability of ingesting a chicken risk meal at home does not only depend on the hygiene practices of the persons preparing the food, but also on the consumption patterns of consumers, and the relationship between people preparing and ingesting food. This finding supports the need of including information on consumer behavior and preparation hygiene in the consumer phase of exposure assessments.

Notizen: Background.  The babA2 gene, which encodes a blood-group antigen-binding adhesin that mediates attachment of Helicobacter pylori to human Lewisb antigens on gastric epithelial cells, has been associated with a higher risk of peptic ulcer and gastric cancer. The purpose of this study was to ascertain the frequency of babA2 genotype in H. pylori strains of patients with peptic ulcer and to correlate with other virulence factors.Materials and Methods.  vacA, cagA, and babA2 genotypes of H. pylori were determined by using polymerase chain reaction (PCR). DNA was extracted from positive urease test gastric samples of 150 patients with peptic ulcer. Antrum and corpus biopsies were taken for histologic examination according to the updated Sydney system classification.Results.  babA2 genotype was present in 104 (69.3%) and cagA in 113 (75.3%) gastric samples. No significant correlation was observed between babA2 and vacAs1 genotype or between babA2 and cagA status. The correlation of vacAs1 genotype with positive cagA was statistically significant ( p 〈 .001). The babA2-positive strain was more frequently found from the gastric samples of men, than of women (p = .01). Strains harboring cagA, vacAs1, and babA2 genotypes had no association to the grading of gastritis, presence of glandular atrophy, or intestinal metaplasia. The simultaneous presence of cagA, vacAs1, and babA2 was found in 32.6% of the H. pylori strains.Conclusions.  babA2 genotype is frequently found in H. pylori strains from peptic ulcer disease in Brazil, although it has no significant correlation to the worsening of the gastritis and to other virulence markers such as vacAs1 and cagA.

Notizen: The diagnosis of Helicobacter pylori infection continues to challenge practicing physicians around the world. In the last year, several reports from Africa tried to examine the epidemiology of H. pylori infection in nursing babies, while others investigated the association between recurrent abdominal pain symptoms and H. pylori. In the diagnostic arena, attempts were made to improve diagnostic accuracy, mainly by using a new monoclonal version of the stool antigen test, and by applying the urea breath test in smaller children. In the current report, the most important studies on H. pylori infection in children published in the last year are also reviewed.

Notizen: The involvement of Helicobacter pylori in the pathogenesis of extragastric diseases continues to be an interesting topic in the field of Helicobacter-related pathology.Although conflicting findings have been reported for most of the disorders, a role of H. pylori seems to be important especially for the development of cardiovascular and hematologic disorders.Previously isolated human and animal Helicobacter sp. flexispira and “Helicobacter heilmannii” strains have been validated using polyphasic taxonomy. A novel enterohepatic Helicobacter has been isolated from mastomys and mice, adding to the list of helicobacters that colonize the liver. Genetic targets that may aid the classification of novel Helicobacter species have emerged. Animal models of Helicobacter-induced gastric and hepatobiliary diseases have offered insights to the mechanisms associated with premalignant transformation.

Notizen: Abstract:  While sentinel lymph node biopsy (SLNB) has virtually replaced axillary dissection as the initial diagnostic procedure for invasive breast cancer, the role of SLNB in ductal carcinoma in situ (DCIS) remains controversial. The purpose of this study was to review our experience with SLNB in DCIS. All patients with DCIS or DCIS with microinvasion (DCISM) who underwent SLNB from June 1997 to April 2002 at the University of Florida were included for analysis. The indications for SLNB were at the discretion of the treating surgeon. Lymphatic mapping involved a sequential dermal-peritumoral radiocolloid injection and dynamic lymphoscintigraphy followed by an intraoperative assessment of radioactivity with a handheld gamma probe. All sentinel lymph nodes (SLNs) with radioactive counts ≥10% of the ex vivo counts of the most radioactive SLN were removed. Pathologic analysis consisted of slicing the SLN at 2 mm intervals for permanent section. All paraffin blocks of the SLNs were step sectioned in 4 µm sections (92 µm spacing) through the entire lymph node. Slides were then stained with an immunohistochemical stain for cytokeratin (AE1/AE3) and evaluated by microscopy. Nodal metastases were classified using the 6th edition of the American Joint Committee on Cancer (AJCC) staging manual. From April 1998 to April 2002, 43 patients with DCIS underwent SLNB at the University of Florida. Seven patients (16%) with multifocal or extensive DCIS (five patients) or DCISM (two patients) who underwent SLNB had a positive sentinel node. Two of the three patients considered positive by immunohistochemistry alone had either DCISM or invasive disease. Four (80%) of the five patients with extensive DCIS and a positive sentinel node were ultimately determined to have invasive or microinvasive disease. While SLNB remains controversial in DCIS, our data suggest that patients with extensive DCIS should undergo SLNB at the initial procedure to avoid the need for a second operation. Data from clinical trials are needed to determine the impact of SLNB results on overall survival in patients with DCIS.

Notizen: Abstract:  Our goal was to identify the treatment, personal, interpersonal, and hormonal (testosterone) factors in breast cancer survivors (BCSs) that determine sexual dysfunction. The treatment variables studied were type of surgery, chemotherapy, radiation, and tamoxifen. The personal, interpersonal, and physiologic factors were depression, body image, age, relationship distress, and testosterone levels. A sample of 55 female breast cancer survivors seen for routine follow-up appointments from July 2002 to September 2002 were recruited to complete the Female Sexual Functioning Index (FSFI), Hamilton Depression Inventory (HDI), Body Image Survey (BIS), Marital Satisfaction Inventory-Revised (MSI-R), a demographic questionnaire, and have a serum testosterone level drawn. The average time since diagnosis was 4.4 years (SD 3.4 years). No associations were found between the type of cancer treatment, hormonal levels, and sexual functioning. BCS sexual functioning was significantly poorer than published normal controls in all areas but desire. The BCSs’ level of relationship distress was the most significant variable affecting arousal, orgasm, lubrication, satisfaction, and sexual pain. Depression and having traditional role preferences were the most important determinants of lower sexual desire. BCSs on antidepressants had higher levels of arousal and orgasm dysfunction. Women who were older had significantly more concerns about vaginal lubrication and pain. Relationship concerns, depression, and age are important influences in the development of BCS sexual dysfunction. The relationship of testosterone and sexual dysfunction needs further study with larger samples and more accurate assay techniques.

Notizen: Abstract:  Erdheim-Chester disease (ECD) is a rare xanthomatous non-Langerhans cell histiocytosis which involves the marrow space of the long bones. Extraosseous sites most commonly affected include the eyes, lungs, pituitary glands, and kidneys. We report the case of a 49-year-old woman who presented with palpable breast nodules, followed by progressive soft tissue and subcutaneous disease, and involvement of the long bones, dysarthria, and dysphagia. The histopathologic features and skeletal radiography findings are consistent with ECD. This case represents an unusual presentation, which led to delayed diagnosis, as ECD of the breast has been rarely reported. ECD should be considered in the differential diagnosis of histiocytoid breast lesions, including fat necrosis and histiocytoid invasive mammary carcinoma.

Notizen: Abstract:  Numerous studies have documented increased breast cancer risks with hormone replacement therapy (HRT), but these do not give a woman her specific absolute risk for the remainder of her life. This article estimates the magnitude of the effect of HRT on breast cancer incidence in California and calculates a woman's cumulative risk of breast cancer with different formulations and durations of HRT use. The effects of HRT on the underlying breast cancer incidence were estimated using the attributable fraction method, applying HRT prevalence data from the 2001 California Health Interview Survey and published rates of higher relative risk (RR) from HRT use from the Women's Health Initiative (WHI) study and Million Women's Survey (MWS). The annual number of breast cancers potentially attributable to HRT in California was estimated, along with individual cumulative risk of breast cancer for various ages to 79 years according to HRT use, duration, and formulation. Using the WHI data, 829 of 19,000 breast cancers (4.3%) in California may be attributable to HRT. This figure increases to 3401 (17.4%) when the MWS RRs are applied. Use of estrogen-only HRT or short-term (approximately 5 years) use of combined HRT has a minimal effect on the cumulative risk calculated to the age of 79 years; application of the MWS data to a Californian woman commencing HRT at the age of 50 years (no HRT, 8.5%; estrogen only, 8.6%; combined, 9.1%). Prolonged (approximately 10 years) use of combined HRT increases the cumulative risk to 10.3%. This article demonstrates that HRT will generate a small additional risk of breast cancer in an individual. The reduction in perimenopausal symptoms may be considered sufficient to warrant this extra risk. However, this view needs to be balanced because the small increases in individual risk will be magnified, producing a noticeable change in population cancer caseload where HRT use is high.

Notizen: Abstract:  The diagnostic power of an integrated positron emission tomography/computed tomography (PET/CT) system for whole-body 2-fluoro-2-deoxy-d-glucose (FDG) imaging is clearly demonstrated in this case report. The precise anatomic localization of FDG uptake with CT in a PET/CT scan of a patient with known breast carcinoma helped identify a contralateral breast tumor with axillary lymph node metastasis despite the presence of extensive physiologic brown fat FDG uptake. Accordingly, the patient received appropriate surgical management and pathologic confirmation of the disease.

Notizen: Abstract:   Advances in the therapeutic agents used for neoadjuvant chemotherapy (NAC) have recently achieved higher response rates and induced a greater number of pathologic complete responses (pCR) than ever before. The aim of this study is the diagnosis of pCR after NAC by diagnostic imaging of clinical complete response (cCR) patients. This study included 35 breast cancer patients who demonstrated cCR after receiving NAC with a combination of anthracycline and taxane from May 1998 to August 2003. Surgical treatment included breast-conserving therapy followed by radiotherapy or mastectomy. The identity of post-NAC lesions as either a complete response (CR) or partial response (PR) were made by mammography, ultrasonography, and contrast-enhanced computed tomography (CT). Among the 35 patients, 11 achieved pCR, including the disappearance of both invasive and intraductal components. Of the patients achieving pCR, eight were defined as CR and three were determined to be PR by CT. There was a significant relationship between the pCR and the determination of CR by CT. The determination of CR by ultrasonography was indicative of the disappearance of pathologic invasive components. While mammography appeared to reflect the observed histologic results, we did not observe any statistical differences. A subset of cases exhibited discrepancies between the imaging and pathologic results, likely due to the replacement of destroyed tumor cells by fibrosis and granulomatous tissue. The evaluation of CR by CT was significantly indicative of pCR. The positive predictive value, however, was not large enough to avoid surgical treatment. Further studies will be needed to establish a diagnosis of pCR. 

Notizen: Abstract:  The purpose of this study was to determine the negative predictive value of mammography and sonography in a population of patients with focal breast pain referred for imaging evaluation. Eighty-six consecutive patients with focal breast pain in the absence of a breast mass were retrospectively identified from an imaging database. The electronic inpatient and outpatient records for the 86 patients were reviewed. For patients who were diagnosed with breast cancer, pathology reports were reviewed to determine whether the painful area corresponded to the patient's cancer. In addition, patient records were linked to the institution's cancer registry. Of the 86 patients, 26 patients were lost to follow-up and did not appear in the institution's cancer registry. Four patients were diagnosed with breast carcinoma, two of whom had incidental cancers that were detected mammographically by microcalcifications and were separate from and unrelated to the area of pain. Seven patients underwent biopsy at the site of breast pain with benign diagnosis. Imaging and clinical follow-up for the 51 patients with benign or negative imaging at the site of pain showed no abnormality with a mean follow-up of 26.5 months. The negative predictive value of mammography and sonography in patients with breast pain was 100%. The negative predictive value of mammography and sonography for focal breast pain is high. Negative mammography and sonography can be reassuring to the treating clinician if follow-up is planned when physical examination is not suspicious. However, if physical examination is suspicious, biopsy should not be delayed. 

Notizen: Abstract:  We present our results regarding the cosmetic outcome achieved and the rate of infection using the MammoSite breast brachytherapy applicator to treat patients with partial breast irradiation. In addition, factors associated with cosmetic outcome and infection are analyzed. The study population consisted of 30 patients with early stage breast cancer treated using the MammoSite device from October 28, 2002, to February 13, 2004. Cosmetic outcome was analyzed for its association with the following parameters: volume of the balloon, balloon-to-skin distance, maximal skin point dose per fraction, V100 (percent of volume that received 100% of the prescription dose), V150 (percent of volume that received 150% of the prescription dose), and V200 (percent of volume that received 200% of the prescription dose). The occurrence of infection at the time of treatment and during follow-up was also recorded. At a median follow-up of 13 months (range 1–16 months), 53.3% of the patients (16/30) were reported to have an excellent cosmetic outcome and 40.0% (12/30) had a good cosmetic outcome. Excellent cosmetic outcome was associated with a greater mean balloon-to-skin distance compared to those who achieved a good cosmetic outcome (1.5 cm versus 1.2 cm) (p = 0.164). The mean V100, V150, and V200 of those in the excellent cosmetic outcome group were 92.1%, 34.5%, and 7.6% versus 93.0%, 34.7%, and 7.6% in the good cosmetic outcome group (p = 0.642, 0.926, and 0.853), The mean balloon volumes were 47.7 cm3 and 56.9 cm3, respectively (p = 0.063) in the excellent and good outcome groups. The mean maximal skin doses per fraction in the excellent and good outcome groups were 354.8 cGy and 422.3 cGy (p = 0.286), respectively. Infection occurred in 13.3% of the patients (4/30). An excellent or good cosmetic outcome was achieved in 93.3% of patients and infection occurred in 13.3% of patients treated with the MammoSite breast brachytherapy applicator. Excellent cosmetic outcome was associated with a greater balloon-to-skin distance, lower maximal skin dose per fraction, and smaller mean balloon volume; however, the results did not reach statistical significance.