Risk Analysis, Decision Analysis, Causal Analysis, and Economics: A Personal Perspective from More Than 40 years Experience.

I entered the field of risk analysis forty years ago from a background in physics followed by doctoral training and experience in decision analysis. I came into the Society for Risk Analysis (SRA) after participating as a committee member in the 1983 National Academies report, Risk Assessment in the Federal Government: Managing the Process. The insights and recommendations from this report, and successor reports from 1996 and 2008, merit revisiting on this 40th anniversary. Risk analysis includes risk assessment, a process of summarizing applicable science to inform decisions; and risk management, a process of making informed choices, usually involving multiple stakeholders. Inherent in both is the need to deal with complexity, uncertainty, and differing perspectives and goals. The lessons I have learned include the need for a conceptual separation of risk management from risk assessment, the benefit of an iterative dialogue between these activities, and the wisdom of articulating and assessing what we know, what we want, and what we can do as we seek to understand and manage risks affecting ourselves and those we advise.

Whither Risk Assessment: New Challenges and Opportunities a Third of a Century After the Red Book.

Six multi-decade-long members of SRA reflect on the 1983 Red Book in order to examine the evolving relationship between risk assessment and risk management; the diffusion of risk assessment practice to risk areas such as homeland security and transportation; the quality of chemical risk databases; challenges from other groups to elements at the core of risk assessment practice; and our collective efforts to communicate risk assessment to a diverse set of critical groups that do not understand risk, risk assessment, or many other risk-related issues. The authors reflect on the 10 recommendations in the Red Book and present several pressing challenges for risk assessment practitioners.

The application of subset correspondence analysis to address the problem of missing data in a study on asthma severity in childhood.

Non-response in cross-sectional data is not uncommon and requires careful handling during the analysis stage so as not to bias results. In this paper, we illustrate how subset correspondence analysis can be applied in order to manage the non-response while at the same time retaining all observed data. This variant of correspondence analysis was applied to a set of epidemiological data in which relationships between numerous environmental, genetic, behavioural and socio-economic factors and their association with asthma severity in children were explored. The application of subset correspondence analysis revealed interesting associations between the measured variables that otherwise may not have been exposed. Many of the associations found confirm established theories found in literature regarding factors that exacerbate childhood asthma. Moderate to severe asthma was found to be associated with needing neonatal care, male children, 8- to 9-year olds, exposure to tobacco smoke in vehicles and living in areas that suffer from extreme air pollution. Associations were found between mild persistent asthma and low birthweight, and being exposed to smoke in the home and living in a home with up to four people. The classification of probable asthma was associated with a group of variables that indicate low socio-economic status.

Public and stakeholder participation for managing and reducing the risks of shale gas development.

Emerging technologies pose particularly strong challenges for risk governance when they have multidimensional and inequitable impacts, when there is scientific uncertainty about the technology and its risks, when there are strong value conflicts over the perceived benefits and risks, when decisions must be made urgently, and when the decision making environment is rife with mistrust. Shale gas development is one such emerging technology. Drawing on previous U.S. National Research Council committee reports that examined risk decision making for complex issues like these, we point to the benefits and challenges of applying the analytic-deliberative process recommended in those reports for stakeholder and public engagement in risk decision making about shale gas development in the United States. We discuss the different phases of such a process and conclude by noting the dangers of allowing controversy to ossify and the benefits of sound dialogue and learning among publics, stakeholders, industry, and regulatory decision makers.

Risks and risk governance in unconventional shale gas development.

A broad assessment is provided of the current state of knowledge regarding the risks associated with shale gas development and their governance. For the principal domains of risk, we identify observed and potential hazards and promising mitigation options to address them, characterizing current knowledge and research needs. Important unresolved research questions are identified for each area of risk; however, certain domains exhibit especially acute deficits of knowledge and attention, including integrated studies of public health, ecosystems, air quality, socioeconomic impacts on communities, and climate change. For these, current research and analysis are insufficient to either confirm or preclude important impacts. The rapidly evolving landscape of shale gas governance in the U.S. is also assessed, noting challenges and opportunities associated with the current decentralized (state-focused) system of regulation. We briefly review emerging approaches to shale gas governance in other nations, and consider new governance initiatives and options in the U.S. involving voluntary industry certification, comprehensive development plans, financial instruments, and possible future federal roles. In order to encompass the multiple relevant disciplines, address the complexities of the evolving shale gas system and reduce the many key uncertainties needed for improved management, a coordinated multiagency federal research effort will need to be implemented.

Can Sisyphus succeed? Getting U.S. high-level nuclear waste into a geological repository.

The U.S. government has the obligation of managing the high-level radioactive waste from its defense activities and also, under existing law, from civilian nuclear power generation. This obligation is not being met. The January 2012 Final Report from the Blue Ribbon Commission on America's Nuclear Future provides commendable guidance but little that is new. The author, who served on the federal Nuclear Waste Technical Review Board from 1989 to 1994 and subsequently on the Board on Radioactive Waste Management of the National Research Council from 1994 to 1999, provides a perspective both on the Commission's recommendations and a potential path toward progress in meeting the federal obligation. By analogy to Sisyphus of Greek mythology, our nation needs to find a way to roll the rock to the top of the hill and have it stay there, rather than continuing to roll back down again.

Critical considerations in evaluating scientific evidence of health effects of ambient ozone: a conference report.

The U.S. Environmental Protection Agency (EPA), under the authority of the Clean Air Act (CAA), is required to promulgate National Ambient Air Quality Standards (NAAQSs) for criteria air pollutants, including ozone. Each NAAQS includes a primary health-based standard and a secondary or welfare-based standard. This paper considers only the science used for revision of the primary standard for ozone in 2008. This paper summarizes deliberations of a small group of scientists who met in June 2007 to review the scientific information informing the EPA Administrator's proposed revision of the 1997 standard. The Panel recognized that there is no scientific methodology that, in the absence of judgment, can define the precise numerical level, related averaging time, and statistical form of the NAAQS. The selection of these elements of the NAAQS involves policy judgments that should be informed by scientific information and analyses. Thus, the Panel members did not feel it appropriate to offer either their individual or collective judgment on the specific numerical level of the NAAQS for ozone. The Panel deliberations focused on the scientific data available on the health effects of exposure to ambient concentrations of ozone, controlled ozone exposure studies with human volunteers, long-term epidemiological studies, time- series epidemiological studies, human panel studies, and toxicological investigations. The deliberations also dealt with the issue of background levels of ozone of nonanthropogenic origin and issues involved with conducting formal risk assessments of the health impacts of current and prospective levels of ambient ozone. The scientific issues that were central to the EPA Administrator's 2008 revision of the NAAQS for ozone will undoubtedly also be critical to the next review of the ozone standard. That review should begin very soon if it is to be completed within the 5-year cycle specified in the CAA. It is hoped that this Report will stimulate discussion of these scientific issues, conduct of additional research, and conduct of new analyses that will provide an improved scientific basis for the policy judgment that will have to be made by a future EPA Administrator in considering potential revision of the ozone standard.

Intelligence and EEG phase reset: a two compartmental model of phase shift and lock.

OBJECTIVES: The purpose of this study was to explore the relationship between EEG phase reset and performance on the Wechsler Intelligence test. METHODS: The electroencephalogram (EEG) was recorded from 19 scalp locations from 378 subjects ranging in age from 5 years to 17.6 years. The Wechsler Intelligence test (WISC-R) was administered to the same subjects on the same day but not while the EEG was recorded. Complex demodulation was used to compute instantaneous EEG phase differences between pairs of electrodes and the 1st and 2nd derivatives were used to measure phase reset by phase shift duration and phase lock duration. The dependent variable was full scale I.Q. and the independent variables were phase shift duration (SD) and phase lock duration (LD) with age as a covariate. RESULTS: Phase shift duration (40-90 ms) was positively related to intelligence (P<.00001) and the phase lock duration (100-800 ms) was negatively related to intelligence (P<.00001). Phase reset in short interelectrode distances (6 cm) was more highly correlated to I.Q. (P<.0001) than in long distances (>12 cm). CONCLUSIONS: The duration of unstable phase dynamics and phase locking represent a bounded optimization process, for example, too long a duration of phase locking then less flexibility and too short of a phase shift then reduced neural resources. A two compartmental model of local field coupling and neuron synchrony to a preferred phase was developed to explain the findings.

The Mhc class II DRB genotype of Macaca fascicularis does not influence infection by simian retrovirus type 2.

Simian retrovirus type 2 (SRV-2) is a natural pathogen of Macaca fascicularis. Although SRV-2 may be endemic in macaque colonies, it is not necessarily detected in all individuals suggesting differential susceptibility to SRV-2; factors contributing to this susceptibility are not fully understood. We have investigated the role of host genetic origin on virus susceptibility. We have shown that high levels of anti-SRV-2 antibodies correlate with failure to establish persistent virus infection, thus we targeted our genetic analysis of virus susceptibility with an investigation of the role of the polymorphic macaque major histocompatibility complex (MHC) class II locus. DRB genotypes, both novel and previously characterised, were identified in individuals and family groups. A discordance with SRV-2 infection status suggests that an Mhc II DRB genotype is not overtly associated with the outcome of viral infection.

A review of whole animal bioassays of the carcinogenic potential of naphthalene.

This report provides a summary of deliberations conducted under the charge for members of Module A participating in the Naphthalene State-of-the-Science Symposium (NS3), Monterey, CA, October 9-12, 2006. Whole animal bioassays have been performed by the National Toxicology Program in mice and rats to ascertain the carcinogenic potential of naphthalene by inhalation exposure. A statistically significant increased incidence of pulmonary alveolar/bronchiolar adenoma (a benign lesion), was observed among female mice; an observed increase among the males did not reach statistical significance. No nasal tumors were observed in either sex. A tumorigenic response was observed in both sexes of rats, in males an increased incidence of nasal respiratory epithelium adenoma (a benign rather than malignant lesion) and in females, olfactory epithelial neuroblastoma. Interpretations of these studies vary. On the one hand, evidence of extensive non-neoplastic response in both sexes of both species indicates cytotoxicity occurred at all doses, and strongly suggests that cytotoxicity played a significant role in the tumor responses observed in the target tissues. On the other hand, olfactory epithelial neuroblastoma has rarely been observed in NTP bioassays. This review seeks to develop a consensus understanding of the scientific evidence provided by these studies, taking into account that they have been used as the basis for quantitative human cancer risk assessment, and suggests scientific studies that, if performed, could resolve scientific uncertainties.

The naphthalene state of the science symposium: objectives, organization, structure, and charge.

This report provides a summary of the objectives, organization, structure and charge for the naphthalene state of the science symposium (NS(3)), Monterey, CA, October 9-12, 2006. A 1-day preliminary conference was held followed by a 3-day state of the science symposium covering four topics judged by the Planning Committee to be crucial for developing valid and reliable scientific estimates of low-dose human cancer risk from naphthalene. The Planning Committee reviewed the relevant scientific literature to identify singularly knowledgeable researchers and a pool of scientists qualified to serve as expert panelists. In two cases, independent scientists were commissioned to develop comprehensive reviews of the relevant science in a specific area for which no leading researcher could be identified. Researchers and expert panelists alike were screened for conflicts of interest. All policy issues related to risk assessment practices and risk management were scrupulously excluded. NS(3) was novel in several ways and provides an innovative model for the effective use of peer review to identify scientific uncertainties and propose research strategies for reducing or eliminating them prior to the conduct of risk assessment.

Burns Centre and fire services: What information can be exchanged to manage the burn patient?

AIM: To describe the experience of using a "Burns Extrication Form" at a regional Burns Centre. Communication between the fire services and burns team previously has been regarded as poor. Significant information is collected by the fire services at the scene and this can aid the management of the patient. METHODS: The Burns Extrication Form was devised to provide a clear framework of communication between the two services. Information regarding time frames, exposure to heat & smoke, fire loading (potential severity of a fire in a given space by measuring amount of combustible material in confined space), building construction, chemicals involved is passed to the medical team through this form through a National Health Service mailbox. Also, treatment provided by the fire service was documented. All data collected by this form was collated for the purpose of this study. Data ranging from 2014 to 2017 was included in this descriptive study. RESULTS: The patient journey following contact by fire services shows that out of the 598 persons who were involved in a fire only 92 (15%) attended the Accident and Emergency (A&E) department at the Queen Elizabeth Hospital. Signs of smoke inhalation, singed nose hair and coughing were found in 190 (32%) patients; the fire service administered oxygen to 106 (18%) of these patients although this may have been initiated by Ambulance crews who were on scene prior to the Fire Crew. The remaining 506 (85%) may have not attended A&E at UHB or may have attended another A&E in the West Midlands base on the location of the incident and clinical needs. Of the 92 patients who attended the A&E at UHB 48 (52%) were admitted to the Burns Centre in the hospital. Nine (19%) of these patients had smoke inhalation and three of these patients were managed by intubation. Birmingham North and Black Country North had the highest incidence of burns incidents, 120 and 103 respectively. Whilst, the lowest numbers were found in Birmingham South and Coventry and Solihull with 65 and 61 respectively. Additional results are described in the study. CONCLUSION: Data provided by the Fire Extrication forms helps us to assess the magnitude of fire-related injury across the West Midlands. The fire services have been shown to provide important first aid as one of the first responders at the scene. Their value in assessing the environment in and patient status helps clinicians further down the patient's journey.

Modification by suppressor cells and serum factors of the cell-mediated immune response in experimental pyelonephritis.

A marked suppression of the thymusderived (T)-lymphocyte response to concanavalin A has been demonstrated in vitro during renal infection. Suppression of the T-lymphocyte response in vitro was seen as early as 2 h after the induction of renal infection, but maximum suppression was found 24-72 h later. A population of suppressor cells in the splenic lymphocyte population, generated during the host's response to infection, contributed to the depressed lymphocyte response. Removal of suppressor cells restored the mitogenic responsiveness of the remaining splenic lymphocytes. Conversely, in co-culture experiments, a suppressor cell present in the splenic lymphocyte population of pyelonephritic animals was shown to be capable of suppressing the mitogenic responsiveness of normal splenic lymphocytes. Significantly reduced host vs. graft responses by the pyelonephritic animals confirmed, in vivo, the depression of cell-mediated immune mechanisms. An additional suppressive factor was found in the serum of pyelonephritic animals which depressed in vitro the mitogenic responsiveness of splenic lymphocytes from normal animals. Support for the suppressive role of this serum factor was found when splenic lymphocytes from pyelonephritic animals were tested in vivo in the absence of homolgous serum (graft vs. host). Under these conditions, the lymphocytes showed an enhanced reaction compared with lymphocytes from normal animals. The presence of a suppressor cell population and a serum factor, both capable of depressing cell-mediated mechanisms, may be major factors contributing to the establishment of infection in the kidney.

Implications of experimental technique for analysis and interpretation of data from animal experiments: outliers and increased variability resulting from failure of intraperitoneal injection procedures.

Intraperitoneal (i.p.) injections are widely used in laboratory animal experiments. This technique has a failure rate that is typically reported to be of the order of 10-20%. It is not apparent that failures of i.p. injection and their consequences for the experimental results are as widely recognized as the use of the technique. We illustrate the consequences of i.p. injection failure for the analysis and interpretation of several bioassays. We suggest approaches to data analysis that should be considered, and emphasize the need to recognize and allow for the possibility of i.p. injection failure in the analysis and interpretation of laboratory animal experiments involving this technique.

Nephrogenic Adenoma Complicating Renal Transplantation: A Case Report and Discussion.

Nephrogenic adenoma (NA) is a benign adenomatous lesion of the urinary tract. Long considered to be a rare phenomenon, case series from the renal transplant population suggest that it may be much more common within this group. Although NA is considered to be a lesion with low premalignant potential, hematuria, lower urinary tract symptoms, and recurrent urinary tract infections (UTIs) are frequently observed in the context of NA. Furthermore, after resection of NA, lesion recurrence and persistent symptoms are frequently observed. Here we present the case of a 69-year-old male renal transplant recipient with NA and associated recurrent UTIs despite cystoscopic resection of the primary lesion. This case is illustrative of the clinical impact of NA and the need for ongoing work into the development of strategies to manage this problematic phenomenon.

Intelligence and eeg measures of information flow: efficiency and homeostatic neuroplasticity.

The purpose of this study was to explore the relationship between the magnitude of EEG information flow and intelligence. The electroencephalogram (EEG) was recorded from 19 scalp locations from 371 subjects ranging in age from 5 years to 17.6 years. The Wechler Intelligence Scale for Children (WISC-R) was administered for individuals between 5 years of age and 16 years and the Weschler Adult Intelligence Scale revised (WAIS-R) was administered to subjects older than 16 years to estimate I.Q. The phase slope index estimated the magnitude of information flow between all electrode combinations for difference frequency bands. Discriminant analyses were performed between high I.Q. (>120) and low I.Q. groups (<90). The magnitude of information flow was inversely related to I.Q. especially in the alpha and beta frequency bands. Long distance inter-electrode distances exhibited greater information flow than short inter-electrode distances. Frontal-parietal correlations were the most significant. It is concluded that higher I.Q. is related to increased efficiency of local information processing and reduced long distance compensatory dynamics that supports a small-world model of intelligence.