Risk Assessment Modeling: Beyond Exposure and Effects

Problem formulation, risk analysis, and risk characterization are, respectively, the design, estimation, and interpretation stages of risk assessment. Models traditionally have been used to estimate exposure and effects; now opportunities are growing to use them to design and interpret risk assessments as well. This could raise the level of rigor, reproducibility, and transparency in the risk assessment process, and improve the way information and expertise gets integrated to advise risk managers. The importance of good design and interpretation to the success of risk assessment and risk management, and the role of modeling in that success, is becoming increasingly apparent, but to date models are used only to a fraction of their potential. We provide two examples of the use of models to design and interpret risk assessments. The first looks at the use of models to better characterize risks by modeling uncertainties and exposure from offsite sources, and the second to forecast future risks of a new technology. Following the examples, we discuss some important obstacles to translating new modeling opportunities into practice. These include practical limits on the abilities of organizations to assimilate new tools and methods, and conceptual limits in the way people think about models.     

Risk Assessment Applications Beyond Baseline Risks and Clean-Up Goals

Historically, the phrase “Risk Assessment” brought to mind a thick Superfund-type baseline risk assessment or clean-up goal derivation document filled with pages of tables with endless seemingly unrelated algorithms and numbers. Over the last decade, the principles of risk and exposure assessment have gained wide-reaching acceptance and are increasingly utilized to help solve other environmental impact, occupational health, or risk mitigation design problems. The typical objective of the classic risk assessment is the evaluation of current or future risks from exposure to contaminated media within the framework of a regulatory waste management or remediation program. Risk-based techniques are increasingly being used on a voluntary basis (i.e., outside of the standard regulatory arena) to demonstrate the presence, absence, or extent of environmental or health-related concerns in specific exposure circumstances. Likewise, a risk or exposure evaluation may be useful in determining the need for, or the legitimacy of, a public health advisory, alone or in conjunction with remedial or mitigative actions. Finally, risk-based techniques often find their way into the courtroom. Three case studies are presented in which riskbased solutions were employed to assist in resolving environmental or health-related issues: (1) a reversal of a fish consumption advisory; (2) an evaluation of arsenic in soil on and adjacent to a school facility; and (3) a challenge to a case of alleged methyl bromide exposure in a litigation context. In each case, the use of risk assessment principles was employed beyond the classic baseline risk assessment to address an applied problem of toxicological significance.     

Novel Fluorescein Angiography-Based Computer-Aided Algorithm for Assessment of Retinal Vessel Permeability

Purpose

To present a novel method for quantitative assessment of retinal vessel permeability using a fluorescein angiography-based computer algorithm.

Methods

Twenty-one subjects (13 with diabetic retinopathy, 8 healthy volunteers) underwent fluorescein angiography (FA). Image pre-processing included removal of non-retinal and noisy images and registration to achieve spatial and temporal pixel-based analysis. Permeability was assessed for each pixel by computing intensity kinetics normalized to arterial values. A linear curve was fitted and the slope value was assigned, color-coded and displayed. The initial FA studies and the computed permeability maps were interpreted in a masked and randomized manner by three experienced ophthalmologists for statistical validation of diagnosis accuracy and efficacy.

Results

Permeability maps were successfully generated for all subjects. For healthy volunteers permeability values showed a normal distribution with a comparable range between subjects. Based on the mean cumulative histogram for the healthy population a threshold (99.5%) for pathological permeability was determined. Clear differences were found between patients and healthy subjects in the number and spatial distribution of pixels with pathological vascular leakage. The computed maps improved the discrimination between patients and healthy subjects, achieved sensitivity and specificity of 0.974 and 0.833 respectively, and significantly improved the consensus among raters for the localization of pathological regions.

Conclusion

The new algorithm allows quantification of retinal vessel permeability and provides objective, more sensitive and accurate evaluation than the present subjective clinical diagnosis. Future studies with a larger patients’ cohort and different retinal pathologies are awaited to further validate this new approach and its role in diagnosis and treatment follow-up. Successful evaluation of vasculature permeability may be used for the early diagnosis of brain microvascular pathology and potentially predict associated neurological sequelae. Finally, the algorithm could be implemented for intraoperative evaluation of micovascular integrity in other organs or during animal experiments.     

Assessment of Elk Highway Permeability by Using Global Positioning System Telemetry

Abstract: Highways have significant direct and indirect impact on natural ecosystems, including wildlife barrier and fragmentation effects, resulting in diminished habitat connectivity and highway permeability. We used Global Positioning System (GPS) telemetry to assess Rocky Mountain elk (Cervus elaphus nelsoni) permeability across a 30-km stretch of highway in central Arizona, USA, currently being reconstructed with 11 wildlife underpasses, 6 bridges, and associated ungulate-proof fencing. The highway was reconstructed in phases, allowing for comparison of highway crossing and passage rates during various stages of reconstruction. We instrumented 33 elk (25 F, 8 M) with GPS receiver collars May 2002 to April 2004. Our collars accrued 101,506 GPS fixes with 45% occurring within 1 km of the highway. Nearly 2 times the proportion of fixes occurred within 1 km of the highway compared with random. We think elk were attracted to the highway corridor by riparian—meadow foraging habitats that were 7 times more concentrated within the 1-km zone around the highway compared with the mean proportion within elk use areas encompassing all GPS fixes. Elk crossed the highway 3,057 times; crossing frequency and distribution along the highway were aggregated compared with random. Crossing frequency within 0.16-km highway segments was negatively associated with the distance to riparian—meadow habitats (r_s = -0.714, n = 190, P < 0.001). Mean observed crossing frequency (92.6 ± 23.5 [SE] crossings/elk) was lower than random (149.6 ± 27.6 crossings/elk). Females crossed 4.5 times as frequently as males. Highway permeability among reconstruction classes was assessed using passage rates (ratio of highway crossings to approaches); our overall mean passage rate was 0.67 ± 0.08 crossings per approach. The mean passage rate for elk crossing the highway section where reconstruction was completed (0.43 ± 0.15 crossings/approach) was half that of sections under reconstruction and control sections combined (0.86 ± 0.09 crossings/approach). Permeability was jointly influenced by the size of the widened highway and associated vehicular traffic on all lanes. Crossing frequency was used to delineate where ungulate-proof fencing yielded maximum benefit in intercepting and funneling crossing elk toward underpasses, promoting highway safety. Use of passage rates provides a quantitative measure to assess permeability, conduct future pre- and postconstruction comparisons, and to develop mitigation strategies to minimize highway impacts to wildlife.     

Micropipette Aspiration‐Based Assessment of Single Channel Water Permeability

Measurements of the unitary hydraulic conductivity of membrane channels, p_f, may be hampered by difficulties in producing sufficient quantities of purified and reconstituted proteins. Low yield expression, the purely empiric choice of detergents, as well as protein aggregation and misfolding during reconstitution may result in an average of less than one reconstituted channel per large unilamellar vesicle. This limits their applicability for p_f measurements, independent of whether light scattering or fluorescence quenching of encapsulated dyes is monitored. Here the micropipette aspiration technique is adopted because its superb sensitivity allows resolving p_f values for one order of magnitude smaller protein densities in sphingomyelin and cholesterol rich giant unilamellar vesicles (GUVs). Protein density is derived from intensity fluctuations that fluorescently labeled channels in the aspirated GUV induce by diffusing through the diffraction limited spot. A perfusion system minimizes unstirred layers in the immediate membrane vicinity as demonstrated by the distribution of both encapsulated and extravesicular aqueous dyes. p_f amounted to 2.4 ± 0.1 × 10^?13 cm³ s^?1 for aquaporin‐1 that served as a test case. The new assay paves the way for directly monitoring the effect that interaction of aquaporins with other proteins or inhibitors may have on p_f on a single sample.     

Quantitative Ultrasound Assessment of Cortical Bone Properties Beyond Bone Mineral Density

The development of quantitative ultrasound (QUS) technologies to measure bone is motivated by the need to overcome the limitations of X-ray based methods, measuring bone mineral density (BMD) which is the gold standard to date for the diagnosis of osteoporosis. Because it uses mechanical waves, the ultrasound modality is a particularly relevant means to probe bone mechanical resistance. The vast majority of QUS technologies commercialized to date merely aim to provide surrogate markers for BMD. During the past decade, innovative QUS approaches have emerged to assess bone beyond BMD. This may be achieved by (1) specifically assessing the cortical bone compartment, independently of trabecular bone, and (2) providing intrinsic bone properties such as cortical bone thickness and material properties. One specific motivation is to estimate intracortical porosity, a quantity reflected in material properties. This article aims at an overview of recent QUS developments to measure cortical bone properties. We also draw a picture of the current knowledge on bone material properties of interest for bone QUS. We discuss the potential of ultrasound to provide novel biomarkers of bone health through the assessment of material properties.     

Beyond biodiversity: fish metagenomes

Biodiversity and intra-specific genetic diversity are interrelated and determine the potential of a community to survive and evolve. Both are considered together in Prokaryote communities treated as metagenomes or ensembles of functional variants beyond species limits.Many factors alter biodiversity in higher Eukaryote communities, and human exploitation can be one of the most important for some groups of plants and animals. For example, fisheries can modify both biodiversity and genetic diversity (intra specific). Intra-specific diversity can be drastically altered by overfishing. Intense fishing pressure on one stock may imply extinction of some genetic variants and subsequent loss of intra-specific diversity. The objective of this study was to apply a metagenome approach to fish communities and explore its value for rapid evaluation of biodiversity and genetic diversity at community level. Here we have applied the metagenome approach employing the barcoding target gene coi as a model sequence in catch from four very different fish assemblages exploited by fisheries: freshwater communities from the Amazon River and northern Spanish rivers, and marine communities from the Cantabric and Mediterranean seas.Treating all sequences obtained from each regional catch as a biological unit (exploited community) we found that metagenomic diversity indices of the Amazonian catch sample here examined were lower than expected. Reduced diversity could be explained, at least partially, by overexploitation of the fish community that had been independently estimated by other methods.We propose using a metagenome approach for estimating diversity in Eukaryote communities and early evaluating genetic variation losses at multi-species level.     

Virtual Reality: Beyond Visualization

Virtual reality (VR) has recently become an affordable technology. A wide range of options are available to access this unique visualization medium, from simple cardboard inserts for smartphones to truly advanced headsets tracked by external sensors. While it is now possible for any research team to gain access to VR, we can still question what it brings to scientific research. Visualization and the ability to navigate complex three-dimensional data are undoubtedly a gateway to many scientific applications; however, we are convinced that data treatment and numerical simulations, especially those mixing interactions with data, human cognition, and automated algorithms will be the future of VR in scientific research. Moreover, VR might soon merit the same level of attention to imaging data as machine learning currently has. In this short perspective, we discuss approaches that employ VR in scientific research based on some concrete examples.     

Beyond Body Mass Index - Body Composition Assessment by Bioimpedance in Routine Endocrine Practice

ObjectiveTo explore the body composition of pediatric patients referred for endocrine evaluation.MethodsThis real-life observational study conducted between January 2018 and January 2020 included 10 001 clinic visits of 3500 children and adolescents; first visits of 5 to 18-year-old patients were included. Anthropometric data, blood pressure levels, pubertal status, and bioelectrical impedance analysis (BIA, Tanita MC-780 MA) were extracted from medical files. Excluded from the analysis were patients participating in other studies.ResultsA total of 1001 patients (48% boys, mean age 11.3 ± 3.4 years, 33.5% prepubertal) were included. Mean anthropometric z-scores were normal and similar for boys and girls. Sex differences in body composition were as follows: boys had lower fat percentage, lower truncal fat percentage, higher appendicular skeletal muscle mass, and a higher muscle-to-fat ratio (MFR) than girls (P < .001 for all). MFR correlated with body mass index-standard deviation scores (BMI-SDS) in overweight/obese patients (r = −0.558, P < .001), although not in underweight patients. Systolic blood pressure (SBP) correlated with BMI-SDS in overweight/obese patients (r = 0.262, P < .001), although not in underweight patients. Diastolic blood pressure (DBP) did not correlate with BMI-SDS in either group of extreme weight status. MFR correlated with SBP and DBP in overweight/obese patients (r = −0.230, P < .001 and r = −0.141, P = .018, respectively) as well as in underweight patients (r = 0.331, P < .001 and r = 0.264, P = .005, respectively).ConclusionsOur findings support BIA for a more refined characterization of patients referred for endocrine evaluation than BMI-SDS. MFR may be a better surrogate marker of blood pressure levels than BMI-SDS in both underweight and overweight/obese pediatric patients.     

Two-Dimensional Monte Carlo Simulation and Beyond: A Comparison of Several Probabilistic Risk Assessment Methods Applied to a Superfund Site

Four different probabilistic risk assessment methods were compared using the data from the Sangamo Weston/Lake Hartwell Superfund site. These were one-dimensional Monte Carlo, two-dimensional Monte Carlo considering uncertainty in the concentration term, two-dimensional Monte Carlo considering uncertainty in ingestion rate, and microexposure event analysis. Estimated high-end risks ranged from 2.0×10^?4 to 3.3×10^?3. Microexposure event analysis produced a lower risk estimate than any of the other methods due to incorporation of time-dependent changes in the concentration term.     

Beyond abortion: refusal of caesarean section

Social pressures and legal restrictions are proliferating against pregnant women. A dramatic infringement on women's rights is the court ordered cesarean section, as illustrated by the case of Angela C., a terminally ill cancer patient, 26 weeks pregnant, whose refusal of a cesarean section was overridden by a District of Columbia court. The premature infant and the mother died within two days. This case epitomizes a developing judicial pattern whose ethical reasoning the author criticizes. Within the context of the right to privacy and the concept of viability, which could legally override that right, Mahowald analyzes different situations where cesarean delivery is refused. After arguing that court ordered cesarean sections are inconsistent with court refusals to force persons to undergo less invasive procedures (e.g., bone marrow donation for the benefit of family members), she proposes alternatives to the present inconsistent practice.