Environment-Sensitive Epigenetics and the Heritability of Complex Diseases

Genome-wide association studies have thus far failed to explain the observed heritability of complex human diseases. This is referred to as the “missing heritability” problem. However, these analyses have usually neglected to consider a role for epigenetic variation, which has been associated with many human diseases. We extend models of epigenetic inheritance to investigate whether environment-sensitive epigenetic modifications of DNA might explain observed patterns of familial aggregation. We find that variation in epigenetic state and environmental state can result in highly heritable phenotypes through a combination of epigenetic and environmental inheritance. These two inheritance processes together can produce familial covariances significantly higher than those predicted by models of purely epigenetic inheritance and similar to those expected from genetic effects. The results suggest that epigenetic variation, inherited both directly and through shared environmental effects, may make a key contribution to the missing heritability

Computational Opioid Prescribing: A Novel Application of Clinical Pharmacokinetics

We implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist pre-scribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety

Investigating variation in replicability

Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently. One effect – imagined contact reducing prejudice – showed weak support for replicability. And two effects – flag priming influencing conservatism and currency priming influencing system justification – did not replicate. We compared whether the conditions such as lab versus online or US versus international sample predicted effect magnitudes. By and large they did not. The results of this small sample of effects suggest that replicability is more dependent on the effect itself than on the sample and setting used to investigate the effect

Anti‑predatory chemical defences in Antarctic benthic fauna

Antarctic benthic communities are largely structured by predation, which leads to the development of mechanisms of repellence. Among those mechanisms, chemical defences are quite extensive, yet poorly understood. To increase knowledge about the role of chemical defences in the Southern Ocean ecosystems, we assessed the incidence of feeding repellents in sessile and vagile invertebrates from nine phyla: Porifera, Cnidaria, Nemertea, Annelida, Mollusca, Bryozoa, Echinodermata, Hemichordata, and Tunicata (Ascidiacea). Samples were collected at depths of 120–789 m in the eastern Weddell Sea and Bouvet Island, and at depths ranging 0–100 m in the South Shetland Islands. When possible, specimens were dissected to study anatomical allocation of repellents. The common, eurybathic sea star Odontaster validus was chosen to perform feeding repellence bioassays, using diethyl ether (lipophilic) and butanol (hydrophilic) extracts from these samples. Among the 75 species tested, 52 % were studied for the first time for anti-predatory properties. Results provide further evidence of the prevalence of defensive metabolites in Antarctic organisms, with 47 % of the species exhibiting significant repellence within their lipophilic extracts. They also suggest a wider use of nonpolar defensive chemicals. Sessile taxa displayed highest repellence activities, with ascidians, cnidarians, and sponges being the most chemically protected. Overall, the present study indicates that natural products by mediating trophic interactions between prey and their potential predators play an important role in structuring Antarctic benthic ecosystems.Versión del editor2,011

Deliberating Animal Values: a Pragmatic-Pluralistic Approach to Animal Ethics.

Debates in animal ethics are largely characterized by ethical monism, the search for a single, timeless, and essential trait in which the moral standing of animals can be grounded. In this paper, we argue that a monistic approach towards animal ethics hampers and oversimplifies the moral debate. The value pluralism present in our contemporary societies requires a more open and flexible approach to moral inquiry. This paper advocates the turn to a pragmatic, pluralistic approach to animal ethics. It contributes to the development of such an approach in two ways. It offers a pragmatist critique of ethical monism in animal ethics and presents the results of a qualitative study into the value diversity present in the different ways of thinking about animals in the Netherlands. Carefully arranged group discussions resulted in the reconstruction of four distinctive moral value frameworks that may serve as instruments in the future process of moral inquiry and deliberation in the reflection on animal use. © 2010 The Author(s)

Ethical communication and intercultural responsibility: a philosophical perspective

The ethical dimension of dialogue represents a major concern in the context of current research in intercultural responsibility. In this paper, I discuss the modalities in which the notion of competence is used to conceptualise responsibility and the relationship between self and other in intercultural research, in order to critique the Cartesian presuppositions of intercultural communication theory. I argue that models of competence and responsibility that are employed to design intercultural training operate within the paradigm of the autonomous rational agent that informs Kantian ethical thinking. I contrast the model of the competent intercultural speaker that emerges in intercultural research with the distinction proposed by Levinas between the saying and the said (le dire and le dit, meaning the event of speech and the content of speech), to suggest two scenarios of intercultural interaction that show two different approaches to responsibility, one operating in the dimension of the said and the other in the dimension of the saying. Thus, in this paper, I discuss the implications of Levinas's reflection on the nature of language for the development of an ethical framework that addresses the limitations of current conceptualisations in intercultural communication theory of competence and responsibility