Ethics, ambiguity aversion, and the review of complex translational clinical trials

Clinical trials of novel agents often present several layers of ethical challenge. Because time and resources for ethical and safety review are limited, how investigators, IRBs, and regulators allocate attention to a trial's various safety dimensions itself represents a critical ethical question. In what follows, I use the example of a Parkinson's disease gene transfer trial to show how risks involving unknown probabilities or outcomes (ambiguity), might sometimes draw attention away from risks that involve known probabilities or outcomes. This potentially undermines the goal of 'systematic and nonarbitrary analysis of risk' during ethical review. To counteract the possible effects of such attention biases, I propose that reviewers develop 'cognitive aids' like lists and, where appropriate, set aside time to discuss non-ambiguous risks. I also propose further research for addressing and understanding how attention allocation, emotion, and ambiguity influence ethical decision-making.     

Predator size and phenology shape prey survival in temporary ponds

Theoretical efforts suggest that the relative sizes of predators and their prey can shape community dynamics, the structure of food webs, and the evolution of life histories. However, much of this work has assumed static predator and prey body sizes. The timing of recruitment and the growth patterns of both predator and prey have the potential to modify the strength of predator–prey interactions. In this study, I examined how predator size dynamics in 40 temporary ponds over a 3-year period affected the survival of spotted salamander (Ambystoma maculatum) larvae. Across communities, gape-limited predator richness, but not size, was correlated with habitat duration (pond permanence). Within communities, mean gape-limited predator size diminished as the growing season progressed. This size reduction occurred because prey individuals grew into a body size refuge and because the largest of the predators left ponds by mid-season. Elevated gape-limited predation risk across time and space was predicted by the occurrence of two large predatory salamanders: marbled salamander larvae (Ambystoma opacum) and red-spotted newt adults (Notophthalmus viridescens). The presence of the largest gape-limited predator, A. opacum, predicted A. maculatum larval survival in the field. The distribution of large predatory salamanders among ponds and across time is expected to lead to differing community dynamics and to generate divergent natural selection on early growth and body size in A. maculatum. In general, a dynamic perspective on predator size often will be necessary to understand the ecology and evolution of species interactions. This will be especially true in frequently disturbed or seasonal habitats where phenology and ontogeny interact to determine body size asymmetries. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Mechanism of a plastic phenotypic response: predator-induced shell thickening in the intertidal gastropod Littorina obtusata

Phenotypic plasticity has been the object of considerable interest over the past several decades, but in few cases are mechanisms underlying plastic responses well understood. For example, it is unclear whether predator-induced changes in gastropod shell morphology represent an active physiological response or a by-product of reduced feeding. We address this question by manipulating feeding and growth of intertidal snails, Littorina obtusata, using two approaches: (i) exposure to predation cues from green crabs Carcinus maenas and (ii) reduced food availability, and quantifying growth in shell length, shell mass, and body mass, as well as production of faecal material and shell micro-structural characteristics (mineralogy and organic fraction) after 96 days. We demonstrate that L. obtusata actively increases calcification rate in response to predation threat, and that this response entails energetic and developmental costs. That this induced response is not strictly tied to the animal's behaviour should enhance its evolutionary potential.     

Simulation of potential range expansion of oak disease caused by Phytophthora cinnamomi under climate change

This study examines the effects of climate warming on one of the most widely distributed and destructive forest pathogens, Phytophthora cinnamomi. In Europe, the winter survival of the pathogen is the dominant cue for the development of the disease it causes to oaks, especially Quercus robur and Q. rubra. The potential pathogen and disease geographic ranges were compared in France between two reference periods, 1968–1998 and 2070–2099. Simulations were obtained by combining a physiologically based approach predicting the pathogen winter survival in relation to microhabitat temperature (in the phloem of infected trees) with a regionalized climatic scenario derived from a global circulation model. Positive anomalies in winter temperatures calculated with this scenario were in the range 0.5–5°C between the periods 2070–2099 and the 1968–1998, according to sites and months. As a consequence, higher annual rates of P. cinnamomi survival were predicted, resulting in a potential range expansion of the disease of one to a few hundred kilometers eastward from the Atlantic coast within one century. Based on this example, the study emphasizes the need of a better understanding of the impacts of global change on the biotic constraint constituted by plant pathogens.     

Indirect risk effects reduce feeding efficiency of ducks during spring

Indirect risk effects of predators on prey behavior can have more of an impact on prey populations than direct consumptive effects. Predation risk can elicit more vigilance behavior in prey, reducing the amount of time available for other activities, such as foraging, which could potentially reduce foraging efficiency. Understanding the conditions associated with predation risk and the specific effects predation risk have on prey behavior is important because it has direct influences on the profitability of food items found under various conditions and states of the forager. The goals of this study were to assess how ducks perceived predation risk in various habitat types and how strongly perceived risk versus energetic demand affected foraging behavior. We manipulated food abundance in different wetland types in Illinois, USA to reduce confounding between food abundance and vegetation structure. We conducted focal‐animal behavioral samples on five duck species in treatment and control plots and used generalized linear mixed‐effects models to compare the effects of vegetation structure versus other factors on the intensity with which ducks fed and the duration of feeding stints. Mallards fed more intensively and, along with blue‐winged teal, used longer feeding stints in open habitats, consistent with the hypothesis that limited visibility was perceived to have a greater predation risk than unlimited visibility. The species temporally nearest to nesting, wood ducks, were willing to take more risks for a greater food reward, consistent with an increase in a marginal value of energy as they approached nesting. Our results indicate that some duck species value energy differently based on the surrounding vegetation structure and density. Furthermore, increases in the marginal value of energy can be more influential than perceived risk in shaping foraging behavior patterns. Based on these findings, we conclude that the value of various food items is not solely determined by energy contained in the item but by conditions in which it is found and the state of the forager.     

The relationship between established coronary risk factors and serum copper and zinc concentrations in a large Persian Cohort

IntroductionThe relationship between demographic and biochemical characteristics, including several established coronary risk factors, and serum copper and zinc was assessed in a large Iranian population sample.Materials and methodsA group of 2233 individuals, 15–65 years of age [1106 (49.5%) males and 1127 (50.5%) females] was recruited from residents of the Greater Khorasan province in northeast of Iran. Demographic data were collected using questionnaires. Coronary risk factors were determined using standard protocols, and trace elements were measured in serum using atomic absorption spectroscopy.ResultsDegree of glucose tolerance and smoking habit were not associated with serum zinc and copper levels. Serum copper levels were significantly higher in obese and hypertensive than in normal subjects (p<0.001). In the whole group and for the female subgroup, serum zinc (p<0.01) and copper (p<0.001) were both significantly lower in individuals with normal versus high levels of low-density lipoprotein cholesterol.A strong positive correlation was found between serum copper and body mass index (BMI) (r=0.85, p<0.001). Weaker positive associations were found between serum copper and calculated 10 years’ coronary risk (r=0.11, p<0.001). Serum zinc/copper ratio was strongly inversely associated with calculated 10 years’ coronary risk (r=?0.10, p<0.001). The partial Eta squared (PES) values for factors determining serum zinc were hypertension (0.007, p=0.01) and BMI (0.004, p=0.01); and for serum copper, they were gender (0.02, p=0.001), hypertension (0.004, p=0.009), and 10 years’ coronary risk for men (0.003, p=0.03) and women (0.002, p=0.07).ConclusionSignificant associations between serum trace element concentrations and several coronary risk factors, including calculated 10 years’ coronary risk scores, were found.     

A new method for identifying rapid decline dynamics in wild vertebrate populations

Tracking trends in the abundance of wildlife populations is a sensitive method for assessing biodiversity change due to the short time‐lag between human pressures and corresponding shifts in population trends. This study tests for proposed associations between different types of human pressures and wildlife population abundance decline‐curves and introduces a method to distinguish decline trajectories from natural fluctuations in population time‐series. First, we simulated typical mammalian population time‐series under different human pressure types and intensities and identified significant distinctions in population dynamics. Based on the concavity of the smoothed population trend and the algebraic function which was the closest fit to the data, we determined those differences in decline dynamics that were consistently attributable to each pressure type. We examined the robustness of the attribution of pressure type to population decline dynamics under more realistic conditions by simulating populations under different levels of environmental stochasticity and time‐series data quality. Finally, we applied our newly developed method to 124 wildlife population time‐series and investigated how those threat types diagnosed by our method compare to the specific threatening processes reported for those populations. We show how wildlife population decline curves can be used to discern between broad categories of pressure or threat types, but do not work for detailed threat attributions. More usefully, we find that differences in population decline curves can reliably identify populations where pressure is increasing over time, even when data quality is poor, and propose this method as a cost‐effective technique for prioritizing conservation actions between populations.     

RISK DETECTION IN INDIVIDUAL HEALTH CARE: ANY LIMITS?

Background: Biomedical science is producing an avalanche of data about risk factors, often with a small predictive value, associated with a broad diversity of diseases. Prevention and screening are increasingly moving from public health into the clinic. Therefore, the question of which risk factors to investigate and disclose in the individual patient, becomes ethically increasingly urgent. In line with Wilson and Jungner's public health‐related 10 principles for screening, it seems crucial to distinguish important from unimportant health risks. Aim: to explore the ways in which clinicians distinguish important from unimportant health risks. Methods: We interviewed 36 respondents (gastroenterologists and gynaecologists/obstetrics) in 5 focus group interviews and 15 open in‐depth interviews on their interpretation of what makes a health risk important. Results: Physicians primarily interpreted importance as the severity of the possible harm, less often its probability. Possibilities of prevention or reassurance strongly influenced their judgment on importance. Discussion: It is not likely that interpreting ‘important’ as ‘severe’ will help in differentiating meaningful from meaningless risk knowledge. A more fundamental change in our ways of dealing with risk may be called for. We discuss existing literature on resilience as an alternative way to deal with risk. Balancing prevention and risk reduction with resilience could be a fruitful direction.     

Effects of alternative styles of risk information on EMF risk perception

Risk scenarios characterized by exposures to new technologies with unknown health effects, together with limited appreciation of benefits pose a challenge to risk communication. The present report illustrates this situation through a study of the perceived risk from mobile phones and mobile masts in residential areas. Good information should objectively convey the current state of knowledge. The research question is then how to inform lay people so that they trust and understand the information. We used an Internet‐based survey with 1687 Danish participants randomized to three types of information about radiation from mobile phones and masts. The objective was to study whether different types of information were rated as equally useful, informative, comprehensible, and trustworthy. Moreover, an important issue was whether information would influence risk perception and intended behavior. The conclusion is that lay people rate information about risks associated with a new and largely unknown technology more useful and trustworthy when provided with brief statements about how to handle the risk, rather than more lengthy technical information about why the technology may or may not entail health hazards. Further, the results demonstrate that information may increase concern among a large proportion of the population, and that discrepancies exist between expressed concern and intended behavior. Bioelectromagnetics 31:504–512, 2010. © 2010 Wiley‐Liss, Inc.     

An inducible morphological defence is a passive by-product of behaviour in a marine snail

Many organisms have evolved inducible defences in response to spatial and temporal variability in predation risk. These defences are assumed to incur large costs to prey; however, few studies have investigated the mechanisms and costs underlying these adaptive responses. I examined the proximate cause of predator-induced shell thickening in a marine snail (Nucella lamellosa) and tested whether induced thickening leads to an increase in structural strength. Results indicate that although predators (crabs) induce thicker shells, the response is a passive by-product of reduced feeding and somatic growth rather than an active physiological response to predation risk. Physical tests indicate that although the shells of predator-induced snails are significantly stronger, the increase in performance is no different than that of snails with limited access to food. Increased shell strength is attributable to an increase in the energetically inexpensive microstructural layer rather than to material property changes in the shell. This mechanism suggests that predator-induced shell defences may be neither energetically nor developmentally costly. Positive correlations between antipredator behaviour and morphological defences may explain commonly observed associations between growth reduction and defence production in other systems and could have implications for the evolutionary potential of these plastic traits.