WHICH BENEFITS OF RESEARCH PARTICIPATION COUNT AS ‘DIRECT’?

It is widely held that individuals who are unable to provide informed consent should be enrolled in clinical research only when the risks are low, or the research offers them the prospect of direct benefit. There is now a rich literature on when the risks of clinical research are low enough to enroll individuals who cannot consent. Much less attention has focused on which benefits of research participation count as ‘direct’, and the few existing accounts disagree over how this crucial concept should be defined. This disagreement raises concern over whether those who cannot consent, including children and adults with severe dementia, are being adequately protected. The present paper attempts to address this concern by considering first what additional protections are needed for these vulnerable individuals. This analysis suggests that the extant definitions of direct benefits either provide insufficient protection for research subjects or pose excessive obstacles to appropriate research. This analysis also points to a modified definition of direct benefits with the potential to avoid these two extremes, protecting individuals who cannot consent without blocking appropriate research.     

Coeliac disease in children and adolescents with type 1 diabetes mellitus: to screen or not, to treat or not?

Coeliac disease is more prevalent in individuals with type 1 diabetes mellitus than in the normal population. It often presents in an atypical or silent form. Specific autoantibodies are found in almost all cases. Untreated coeliac disease may be associated with long-term health risks, so screening and early treatment with a gluten-free diet seem to be justified. However, extended follow-up is needed to document the clinical benefits of screening and treatment in diabetic patients.     

Silicone breast implants and magnetic resonance imaging screening for rupture: do U.S. Food and Drug Administration recommendations reflect an evidence-based practice approach to patient care?

Regular magnetic resonance imaging has been recommended for the purpose of screening for silicone implant rupture. However, when its use as a screening test is critically examined, it appears that evidence to support its use is lacking. For example, there is no conclusive evidence at this time to show that using magnetic resonance imaging screening of asymptomatic women leads to a reduction in patient morbidity. Furthermore, based on existing data, it is unclear whether the potential benefits of screening magnetic resonance imaging tests outweigh the risks and potential costs for the patient. In the face of this uncertainty, shared medical decision making can be recommended. For different women, underlying beliefs and values will sway decision making in different directions. By engaging a woman in the process of shared medical decision making, however, the plastic surgeon and her or his patients can make a mutually agreeable choice that reflects the patient's individual values and health preferences.     

Applications of Personalized Estimates of Absolute Breast Cancer Risk

Absolute risk is the probability that a given health outcome will be observed in a defined time period in the presence of competing causes of death. In this commentary I discuss some applications of models of absolute breast cancer risk that account for a woman’s particular risk factors. Such models can be useful in counseling by giving perspective on the level of risk, and as an aid to weighing risks and benefits, as in deciding whether or not to take tamoxifen to prevent breast cancer. Absolute risk models also have applications in public health, such as in designing intervention trials to prevent breast cancer and in assessing the potential reductions in absolute risk of disease that might result from reducing exposures. Other potential public health applications that require models with high discriminatory accuracy are to identify “high risk” subsets of the population that might benefit from a preventive intervention or screening, or to rank members of the population on risk to allocate preventive resources under cost constraints.     

Risks of nutrigenomics and nutrigenetics? What the scientists say

Nutrigenomics and nutrigenetics (hereafter NGx) have stimulated expectations for beneficial applications in public health and individuals. Yet, the potential achievability of such promise is not without socioethical considerations that challenge NGx implementation. This paper focuses on the opinions of NGx researchers about potential risks raised by NGx. The results of an online survey show that these researchers (n = 126) are fairly confident about the potential benefits of NGx, and that most downplay its potential risks. Researchers in this field do not believe that NGx will reconfigure foods as medication or transform the conception of eating into a health hazard. The majority think that NGx will produce no added burden on individuals to get tested or to remain compliant with NGx recommendations, nor that NGx will threaten individual autonomy in daily food choice. The majority of researchers do not think that NGx will lead to discrimination against and/or stigmatization of people who do not comply with NGx dietary recommendations. Despite this optimism among NGx researchers, we suggest that key risk factors raised by the socioethical context in which NGx applications will be implemented need to be considered.     

Evaluation of the Lung Cancer Risks at Which to Screen Ever- and Never-Smokers: Screening Rules Applied to the PLCO and NLST Cohorts

BackgroundLung cancer risks at which individuals should be screened with computed tomography (CT) for lung cancer are undecided. This study''s objectives are to identify a risk threshold for selecting individuals for screening, to compare its efficiency with the U.S. Preventive Services Task Force (USPSTF) criteria for identifying screenees, and to determine whether never-smokers should be screened. Lung cancer risks are compared between smokers aged 55–64 and ≥65–80 y.ConclusionsThe USPSTF criteria for CT screening include some low-risk individuals and exclude some high-risk individuals. Use of the PLCO_m2012 risk ≥0.0151 criterion can improve screening efficiency. Currently, never-smokers should not be screened. Smokers aged ≥65–80 y are a high-risk group who may benefit from screening. Please see later in the article for the Editors'' Summary     

Focus: A Multifaceted Battle Against Cancer: The Benefit and Burden of Cancer Screening in Li-Fraumeni Syndrome: A Case Report

Li-Fraumeni syndrome is a rare cancer predisposition syndrome classically associated with remarkably early onset of cancer in families with a typical spectrum of malignancies, including sarcoma, breast cancer, brain tumors, and adrenocortical carcinoma. Because the risks of cancer development are strikingly high for Li-Fraumeni syndrome, aggressive cancer surveillance is often pursued in these individuals. However, optimal screening methods and intervals for Li-Fraumeni syndrome have yet to be determined. In addition, there may be a significant psychosocial burden to intensive cancer surveillance and some prevention modalities. Here, we describe a case of a young woman with a de novo mutation in TP53 and multiple malignancies, with her most recent cancers found at early, curable stages due to aggressive cancer screening. The potential benefits and risks of intensive cancer surveillance in hereditary cancer syndromes is discussed.     

The diffusion of new genetic tests for predicting disease.

This paper examines the pathways by which new genetic tests will become available to the public. In view of the scarcity of genetic specialists, the pathway is likely to involve primary care physicians. Other pathways entail state-mandated testing, community-based programs, or testing by laboratories without much involvement of primary care physicians. When testing does become available the "destination" will be either family-centered testing or population-oriented screening. The deterrent to screening will not be the inability to detect disease-causing mutations but the costs and attitudes of providers and the public. When tests are provided primarily to provide information about risks to future children, some people will oppose screening on religious or moral grounds. When there are no inexpensive treatments, some will fear that insurance companies and employers will use tests to deny them health care coverage. Some may not want to know their risks for disorders about which little can be done. For common, multifactorial disorders, genetic tests will have low predictive value. Because of these problems, the decision to be tested, regardless of the destination, requires that "testees" be fully informed and consent to testing. When acceptance rates are low, screening is less likely to be cost-effective; family-centered testing becomes the default destination.     

The screening and selection of inoculant arbuscular-mycorrhizal and ectomycorrhizal fungi

The initiation of a programme of screening and selection of arbuscular-mycorrhizal fungi (AM fungi) and ectomycorrhizal fungi (ECM fungi) for use as inoculant fungi in agriculture, horticulture of forestry will depend on whether inoculation is more appropriate as a management option than manipulation of the indigenous mycorrhizal populations. The greatest immediate potential for the successful use of mycorrhizal inoculants will be in soils and growth media where phosphorus (P) limits plant growth and where the indigenous mycorrhizal fungi are either ineffective at increasing P uptake by the plant or their numbers have been drastically reduced by human influence or natural disturbance. In recent investigations, however, additional benefits to the plant following colonization of roots by effective AM or ECM fungi have been demonstrated. These additional benefits of an effective mycorrhizal association have necessitated a re-evaluation of the optimum screening procedures for isolates of AM and ECM fungi. Both current methodologies and suggestions for alternative approaches to the screening of AM and ECM fungi are discussed in this paper. The problems inherent in choosing suitable experimental conditions to compare different isolates at the screening stage are also addressed. The review also stresses the importance of continued monitoring of introduced mycorrhizal fungi to learn more about their longer-term ecological role, particularly within reforestation or revegetation studies.     

Time is money. Waiting costs explain why selection favors steeper time discounting in deprived environments

Individuals exposed to deprivation tend to show a characteristic behavioral syndrome suggestive of a short time horizon. This pattern has traditionally been attributed to the intrinsically higher unpredictability of deprived environments, which renders waiting for long term rewards more risky (i.e. collection risks are high). In the current paper, based on a simple dynamic life history model, we show that a significant portion of individuals' propensity to discount future rewards might have a completely distinct origin. Upon collecting a resource, individuals have the opportunity to accumulate “capital” (e.g. grow muscular tissue, build a protective shelter, buy a car, etc.), which eventually increases their productivity and/or their chances of survival. As a result, delaying the collection of a resource creates an opportunity cost in the sense that during the waiting time, the benefits otherwise generated by the increment in capital are lost. These forgone benefits are independent of collection risks and constitute waiting costs per se. Using optimal control theory we show that these costs can lead to the evolution of short time horizons even in the complete absence of collection risks. Moreover, assuming diminishing returns to capital, we show that the evolutionarily stable time horizon increases with the amount of capital already owned by individuals. When individuals possess little capital, they have a lot of room to improve their productivity and/or survival, hence they should be impatient to collect resources; that is, their time horizon should be short. On the contrary, when individuals already possess a lot of capital, the benefits of further accumulation are plateauing, hence patience becomes a more profitable strategy and individuals should lengthen their time horizon. This means that individuals get more patient as they age and that people in deprivation, who still have important productive and survival needs that can be satisfied, should have a shorter time horizon. This result leads us to interpret the behavioral constellation of deprivation in a new way.     

Risk-seeking or impatient? Disentangling variance and time in hazardous behaviors

Individual observations of risky behaviors present a paradox: individuals who take the most risks in terms of hazards (smoking, speeding, risky sexual behaviors) are also less likely to take risks when it comes to innovation, financial risks or entrepreneurship. Existing theories of risk-preferences do not explain these patterns. From a simple model, we argue that many decisions involving risk have a temporal dimension, and that this dimension is often the main determinant of individual choices. In many real life instances, risk taking amounts to damaging the individual's capital (whether embodied capital, financial capital, social reputation, etc.), which would affect her over a long period of time after the risky decision. In evolutionary terms, the marginal cost of this type of risky behavior depends on the relative importance of the future in the individual's fitness (e.g. her time horizon). Individuals with short time horizons will give less importance to a degradation of their capital because this degradation will be paid effectively for a shorter period of time. This approach explains patterns of behaviors observed across socio-economic groups and puts forward new approaches to prevent hazardous behaviors such as smoking.     

Genetic information and insurance: some ethical issues.

Life is risky, and insurance provides one of the best developed ways of controlling risks. By pooling, and so transferring risks, those who turn out to suffer antecedently uncertain harms can be assured in advance that they will be helped if those harms arise; they can then plan their lives and activities with confidence that they are less at the mercy of ill fortune. Both publicly organized and commercial insurance can organize the pooling of risk in ways that are beneficial for all concerned. They provide standard ways of securing fundamental ethical values such as solidarity and mutuality. Although policy holders do not know or contract with one another, each benefits from the contribution of others to a shared scheme for pooling and so controlling risk. Although there is a limit to the degree to which commercially-based insurance, where premiums depend on risk level, can go beyond mutuality towards solidarity, in practice it too often achieves a measure of solidarity by taking a broad brush approach to pooling risk. However, the ordinary practices of insurance, and in particular of commercial insurance, also raise ethical questions. These may be put in simple terms by contrasting the way in which an insurance market discriminates between different people, on the basis of characteristics that (supposedly) determine their risk level, and our frequent abhorrence of discrimination, in particular on the basis on religious, racial and gender characteristics. Are the discriminations on which insurance practice relies upon as standard acceptable or not? The increasing availability of genetic information, which testing (of individuals) and screening (of populations) may provide, could lend urgency to these questions. Genetic information may provide a way of obtaining more accurate assessment of individual risks to health and life. This information could be used to discriminate more finely between the risk levels of different individuals, and then to alter the availability and the costs of health, life and unemployment insurance to them. Since all of these forms of insurance bear very directly on the way most people live, it will matter to them how (if at all) insurers take account of genetic information. Will use of this information improve or damage the capacity of insurance to provide confidence in the face of uncertain harms, and help if they happen? Will it discriminate in acceptable or in unacceptable ways? Will it support or damage the sorts of mutuality and solidarity various sorts of insurance schemes have successfully institutionalized?     

The use of biomarkers in surveillance, medical screening, and intervention

Building on mechanistic information, much of molecular epidemiologic research has focused on validating biomarkers, that is, assessing their ability to accurately indicate exposure, effect, disease, or susceptibility. To be of use in surveillance, medical screening, or interventions, biomarkers must already be validated so that they can be used as outcomes or indicators that can serve a particular function. In surveillance, biomarkers can be used as indicators of hazard, exposure, disease, and population risk. However, to obtain rates for these measures, the population at risk will need to be assessed. In medical screening, biomarkers can serve as early indicators of disease in asymptomatic people. This allows for the identification of those who should receive diagnostic confirmation and early treatment. In intervention (which includes risk assessment and communication, risk management, and various prevention efforts), biomarkers can be used to assess the effectiveness of a prevention or control strategy as well as help determine whether the appropriate individuals are assigned to the correct intervention category. Biomarkers can be used to provide group and individual risk assessments that can be the basis for marshalling resources. Critical for using biomarkers in surveillance, medical screening, and intervention is the justification that the biomarkers can provide information not otherwise accessible by a less expensive and easier-to-obtain source of information, such as medical records, surveys, or vital statistics. The ability to use validated biomarkers in surveillance, medical screening, and intervention will depend on the extent to which a strategy for evidence-based procedures for biomarker knowledge transfer can be developed and implemented. This will require the interaction of researchers and decision-makers to collaborate on public health and medical issues.     

Evaluation of assisted colonization strategies under global change for a rare,fire‐dependent plant

As a clear consensus is emerging that habitat for many species will dramatically reduce or shift with climate change, attention is turning to adaptation strategies to address these impacts. Assisted colonization is one such strategy that has been predominantly discussed in terms of the costs of introducing potential competitors into new communities and the benefits of reducing extinction risk. However, the success or failure of assisted colonization will depend on a range of population‐level factors that have not yet been quantitatively evaluated – the quality of the recipient habitat, the number and life stages of translocated individuals, the establishment of translocated individuals in their new habitat and whether the recipient habitat is subject to ongoing threats all will play an important role in population persistence. In this article, we do not take one side or the other in the debate over whether assisted colonization is worthwhile. Rather, we focus on the likelihood that assisted colonization will promote population persistence in the face of climate‐induced distribution changes and altered fire regimes for a rare endemic species. We link a population model with species distribution models to investigate expected changes in populations with climate change, the impact of altered fire regimes on population persistence and how much assisted colonization is necessary to minimize risk of decline in populations of Tecate cypress, a rare endemic tree in the California Floristic Province, a biodiversity hotspot. We show that assisted colonization may be a risk‐minimizing adaptation strategy when there are large source populations that are declining dramatically due to habitat contractions, multiple nearby sites predicted to contain suitable habitat, minimal natural dispersal, high rates of establishment of translocated populations and the absence of nonclimatic threats such as altered disturbance regimes. However, when serious ongoing threats exist, assisted colonization is ineffective.     

Rational choice theory and suicide

The implications of viewing the decision to kill oneself as a rational choice, based on an analysis of the costs and benefits, were explored. Suicide is but one symptom for an individual in distress to choose, and if suicide is prevented, other symptoms may appear in its place. Similarly, a critical question to be asked in suicide prevention is whether restriction of the availability of one method for suicide (such as detoxifying domestic gas or car exhaust) will result in suicidal individuals switching to a different method for suicide or to a different symptom of distress.     

The Role of Convictions and Trust for Public Protest Potential in the Case of Carbon Dioxide Capture and Storage (CCS)

For the public to accept new technologies, trust and convictions play an important role. In the present research, we used structural equation modeling to examine an extensive causal model of the role of convictions and trust for the public's protest potential against carbon dioxide capture and storage (CCS) among a large sample of the general population (N = 769). Trust, convictions, perceived benefits, and risks were included in the model. Our model fitted the data well. Convictions regarding emission reduction, decentralization of energy production, and tampering with natural structures in the deep subsurface influenced the perception of benefits and risks. Trust, in contrast, was barely influential. Perceived benefits were more prominent for public protest potential than perceived risks. However, perceived benefits did not dominate perceived risks as much as earlier studies found for acceptance. We argue that trust can become fully effective as a determinant of perceived risks and benefits only when the public perceives the distinct positioning of the stakeholders involved. Until then, laypeople are likely to draw on their own convictions and intuitive mental concepts for making decisions about accepting a new technology or protesting it.     

Female Bechstein's Bats Share Foraging Sites with Maternal Kin but do not Forage Together with them – Results from a Long‐Term Study

In many social animals, group members exchange information about where to feed. Thereby, they may gain direct benefits, for example, if social hunting enhances individual foraging success. Alternatively, individuals may receive indirect fitness benefits by preferentially sharing information about suitable feeding sites with kin. Indeed, in some species, a positive correlation between the degree of relatedness among individuals and the overlap among their foraging areas was found. However, sharing foraging sites with kin can also have costs if it increases food competition, which is not compensated by direct benefits. The goal of this study was to investigate whether sharing of individual foraging areas in female Bechstein's bats is best explained by kin selection or by direct benefits through social foraging. To assess their individual foraging behaviour, we analysed radio‐tracking data of 22 members of one maternity colony, including nine mother–daughter pairs, seven pairs of less closely related individuals and six pairs of unrelated bats. We examined the bats' fidelity to specific foraging areas during several years and quantified the influence of kinship on the overlap among individual foraging areas. By measuring how close to each other the bats foraged, we assessed whether individuals with overlapping areas are likely to forage together. Our study confirms previous findings that Bechstein's bats show high fidelity to foraging areas across years. Moreover, we found that relatives share foraging areas significantly more often compared with unrelated colony members. Finally, our data reveal for the first time that most colony members that share foraging areas are unlikely to forage together. This suggests that female Bechstein's bats gain no direct benefits from sharing foraging areas with members of the same maternal lineage. Our findings also have implications for conservation as habitat loss within a colony's home range might expose entire matrilines to high risks.     

The value of glucocorticoid co-therapy in different rheumatic diseases - positive and adverse effects

Glucocorticoids play a pivotal role in the management of many inflammatory rheumatic diseases. The therapeutic effects range from pain relief in arthritides, to disease-modifying effects in early rheumatoid arthritis, and to strong immunosuppressive actions in vasculitides and systemic lupus erythematosus. There are multiple indications that adverse effects are more frequent with the longer use of glucocorticoids and use of higher dosages, but high-quality data on the occurrence of adverse effects are scarce especially for dosages above 10 mg prednisone daily. The underlying rheumatic disease, disease activity, risk factors and individual responsiveness of the patient should guide treatment decisions. Monitoring for adverse effects should also be tailored to the patient. Continuously balancing the benefits and risks of glucocorticoid therapy is recommended. There is an ongoing quest for new drugs with glucocorticoid actions without the potential to cause harmful effects, such as selective glucocorticoid receptor agonists, but the application of a new compound in clinical practice will probably not occur within the next few years. In the meantime, basic research on glucocorticoid effects and detailed reports on therapeutic efficacy and occurrence of adverse effects will be valuable in weighing benefits and risks in clinical practice.     

Assortative mating for relatedness in a large naturally occurring population of Drosophila melanogaster

New theoretical work on kin selection and inclusive fitness benefits predicts that individuals will sometimes choose close or intermediate relatives as mates to maximize their fitness. However, empirical examples supporting such predictions are rare. In this study, we look for such evidence in a natural population of Drosophila melanogaster. We compared mating and nonmating individuals to test whether mating was nonrandom with respect to relatedness. Consistent with optimal inbreeding, males were more closely related to their mate than to randomly sampled females. However, all individuals collected mating showed higher relatedness and males were not significantly more related to their mate than to other mating females. We also found a negative relationship between relatedness and fecundity. Our results are consistent with the hypothesis that inclusive fitness benefits may drive inbreeding tolerance despite direct costs to fitness; however, an experimental approach is needed to investigate the link between mate preference and relatedness.     

A Computational Approach to Characterizing the Impact of Social Influence on Individuals’ Vaccination Decision Making

In modeling individuals vaccination decision making, existing studies have typically used the payoff-based (e.g., game-theoretical) approaches that evaluate the risks and benefits of vaccination. In reality, whether an individual takes vaccine or not is also influenced by the decisions of others, i.e., due to the impact of social influence. In this regard, we present a dual-perspective view on individuals decision making that incorporates both the cost analysis of vaccination and the impact of social influence. In doing so, we consider a group of individuals making their vaccination decisions by both minimizing the associated costs and evaluating the decisions of others. We apply social impact theory (SIT) to characterize the impact of social influence with respect to individuals interaction relationships. By doing so, we propose a novel modeling framework that integrates an extended SIT-based characterization of social influence with a game-theoretical analysis of cost minimization. We consider the scenario of voluntary vaccination against an influenza-like disease through a series of simulations. We investigate the steady state of individuals’ decision making, and thus, assess the impact of social influence by evaluating the coverage of vaccination for infectious diseases control. Our simulation results suggest that individuals high conformity to social influence will increase the vaccination coverage if the cost of vaccination is low, and conversely, will decrease it if the cost is high. Interestingly, if individuals are social followers, the resulting vaccination coverage would converge to a certain level, depending on individuals’ initial level of vaccination willingness rather than the associated costs. We conclude that social influence will have an impact on the control of an infectious disease as they can affect the vaccination coverage. In this respect, our work can provide a means for modeling the impact of social influence as well as for estimating the effectiveness of a voluntary vaccination program.