While it has often been assumed that, in humans, synonymous mutations would have no effect on fitness, let alone cause disease, this position has been questioned over the last decade. There is now considerable evidence that such mutations can, for example, disrupt splicing and interfere with miRNA binding. Two recent publications suggest involvement of additional mechanisms: modification of protein abundance most probably mediated by alteration in mRNA stability1 and modification of protein structure and activity,2 probably mediated by induction of translational (...) pausing. These case histories put a further nail into the coffin of the assumption that synonymous mutations must be neutral. BioEssays 29:515–519, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The aim of this article is to analyse the internal mechanisms of corporate governance (board of directors and ownership structure), which influence voluntary disclosure of intangibles. The results appear to corroborate the view that an increase in institutional investor shareholding has a negative effect on voluntary disclosure, supporting the hypothesis of entrenchment, whereas an excessive ownership by institutional investors may have adverse effects on strategic disclosure decisions. The results also indicate that an increase in the number of members of the (...) board to up to 15 has a beneficial effect on the disclosure of intangibles. However, as this number increases, the effect inverts and becomes adverse to improving the capacity for supervision and control in the decision-making process regarding the voluntary disclosure of intangibles. The findings endorse the recommendation of the most of the Corporate Governance Codes regarding an advisable maximum of 15 members on a board to ensure its effectiveness and internal cohesion. (shrink)

In this paper, the structure of a southeastern Spanish population was studied for the first time with respect to its inbreeding patterns and its relationship with demographic and geographic factors. Data on consanguineous marriages from 1900 to 1969 were taken from ecclesiastic dispensations. Our results confirm that the patterns and trends of inbreeding in the study area are consistent with those previously observed in most non-Cantabrian Spanish populations. The rate of consanguineous marriages was apparently stable between 1900 and 1935 and (...) then sharply decreased since 1940, which coincides with industrialization in Spain. A marked departure from Hardy-Weinberg expectations in the ratio of first cousin to second cousin marriages in the study population was observed. The high levels of endogamy and its significant steadiness throughout the twentieth century is noteworthy. Accordingly, our results show that exogamous marriages were not only poorly represented but also that this reduced mobility suggests that the choice of a mate was preferentially local. We found higher mobility in M22 with respect to M33 cousin mating. The relationships between population size and consanguinity rates and inbreeding fit power-law distributions. A significant positive correlation was observed between inbreeding and elevation. Many Spanish populations have experienced a prolonged and considerable isolation across generations, which has led to high proportions of historical and local endogamy that is associated, in general, with high \ values. Thus, assessing genomic inbreeding using runs of homozygosity in current Spanish populations could be an additional pertinent strategy for obtaining a more refined perspective regarding the population history inferred from the extent and frequency of ROH regions. (shrink)

The authors examine the scientific possibility and the legal and ethical implications of using DNA forensic technology, through partial matches to DNA from crime scenes, to turn into suspects the relatives of people whose DNA profiles are in forensic databases.

On 5 August 1968, publication of the Harvard Committee’s report on the subject of “irreversible coma” established a standard for diagnosing death on neurological grounds. On the same day, the 22nd World Medical Assembly met in Sydney, Australia, and announced the Declaration of Sydney, a pronouncement on death, which is less often quoted because it was overshadowed by the impact of the Harvard Report. To put those events into present-day perspective, the authors reviewed all papers published on this subject and (...) the World Medical Association web page and documents, and corresponded with Dr A G Romualdez, the son of Dr A Z Romualdez. There was vast neurological expertise among some of the Harvard Committee members, leading to a comprehensible and practical clinical description of the brain death syndrome and the way to diagnose it. This landmark account had a global medical and social impact on the issue of human death, which simultaneously lessened reception of the Declaration of Sydney. Nonetheless, the Declaration of Sydney faced the main conceptual and philosophical issues on human death in a bold and forthright manner. This statement differentiated the meaning of death at the cellular and tissue levels from the death of the person. This was a pioneering view on the discussion of human death, published as early as in 1968, that should be recognised by current and future generations. (shrink)

This article explores innovative legal tools in built environment settings. Using tangible examples, the discussion will leverage the authors' expertise in the law, public health, and architecture to explore strategies in domestic and international settings to explain how healthy spaces make a direct public health impact on people's lives.

“The sins of the fathers are to be laid upon the children.”Just after midnight on March 21, 2003, a drunk stood on a footbridge over a motorway in a village in Surrey in southern England. After eight pints of beer, he was drunk enough to decide to drop a brick from the overpass into traffic to see if he could hit something; unfortunately, he was not so drunk that he missed. The brick crashed through the windshield on the driver's side (...) of a truck. It hit the driver, Michael Little, in the chest, triggering a fatal heart attack. He stayed conscious long enough to pull the truck safely to the side of the road, thereby perhaps saving other motorists; then he died. The crime was widely publicized, as was the driver's role in preventing any further accidents. (shrink)

The questions and methods of molecular biology and evolutionary biology are clearly distinct, yet a unified approach can lead to deep insights. Unfortunately, attempts to unify these approaches are fraught with pitfalls. In this informal series of questions and answers, we offer the mechanistically oriented biologist a set of steps to come up with evolutionarily reasonable and meaningful hypotheses. We emphasize the critical power and importance of carefully constructed null hypotheses, and we illustrate our ideas with examples representing a range (...) of topics, from the biology of aging, to protein structure, to speciation, and more. We also stress the importance of mathematics as the lingua franca for biologists of all stripes, and encourage mechanistic biologists to seek out quantitative collaborators to build explicit mathematical models, making their assumptions explicit, and their logic clear and testable. Biologists in all realms of inquiry stand to gain from strong bridges between our disciplines. (shrink)

Why do we find agents less blameworthy when they face mitigating circumstances, and what does this show about philosophical theories of moral responsibility? We present novel evidence that the tendency to mitigate the blameworthiness of agents is driven both by the perception that they are less normatively competent—in particular, less able to know that what they are doing is wrong—and by the perception that their behavior is less attributable to their deep selves. Consequently, we argue that philosophers cannot rely on (...) the case strategy to support the Normative Competence theory of moral responsibility over the Deep Self theory. However, we also outline ways in which further empirical and philosophical work would shift the debate, by showing that there is a significant departure between ordinary concepts and corresponding philosophical concepts, or by focusing on a different type of coherence with ordinary judgments. (shrink)

This article responds to logical and social theses proposed by Professor José Medina in discussing the relativity of identity. In exploring the metaphor of family resemblance, the author argues that its causal mechanism is biological, not social; particular features of being a woman, or of belonging to a racial or ethnic group, cannot be reduced to social constructions. The article skeptically discusses the supposed importance of sex, race, and ethnicity to a person’s individual identity, and suggests that moral significance finds (...) its origin and grounding elsewhere. It concludes that no liberation can be ‘complete, or even adequate’ until it liberates the mind from ‘“scripts” rooted in the delusion of “collective identities”’. (shrink)

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or ‘preapproval’, access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet platforms (...) enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients’ best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee. Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice. (shrink)

Efforts to promote responsible conduct of research (RCR) should take into consideration how scientists already conceptualize the relationship between ethics and science. In this study, we investigated how scientists relate ethics and science by analyzing the values expressed in interviews with fifteen science faculty members at a large midwestern university. We identified the values the scientists appealed to when discussing research ethics, how explicitly they related their values to ethics, and the relationships between the values they appealed to. We found (...) that the scientists in our study appealed to epistemic and ethical values with about the same frequency, and much more often than any other type of value. We also found that they explicitly associated epistemic values with ethical values. Participants were more likely to describe epistemic and ethical values as supporting each other, rather than trading off with each other. This suggests that many scientists already have a sophisticated understanding of the relationship between ethics and science, which may be an important resource for RCR training interventions. (shrink)

Many theists of a traditional bent have been bothered by the apparent tension between God's essential omnipotence and his essential moral goodness. Nelson Pike draws attention to the conflict between these two attributes in his article ‘Omnipotence and God's Ability to Sin’, and there have been many attempts to respond to it since that time. Most of these responses argue that the essential omnipotence and essential goodness of God are not logically incompatible, so that the traditional conception of God is (...) not incoherent; I think the arguments have been largely successful. However, some theists have found the typical responses to Pike less than convincing, and are tempted to surrender the claim that God has moral perfection essentially in favour of the more modest claim that God is morally perfect in the actual world though in some possible worlds God is morally defective. I argue in this paper that this fall-back position is incoherent. More accurately, I argue that a necessary being who is essentially omniscient and essentially omnipotent cannot be contingently morally perfect or contingently morally defective. Any such being is either essentially good or essentially evil. Since the latter alternative seems unattractive, I argue that theists should embrace the essential moral perfection of God. (shrink)

Do cultural models facilitate particular ways of perceiving interactions in nature? We explore variability in folkecological principles of reasoning about interspecies interactions. In two studies, Indigenous Panamanian Ngöbe and U.S. participants interpreted an illustrated, wordless nonfiction book about the hunting relationship between a coyote and badger. Across both studies, the majority of Ngöbe interpreted the hunting relationship as cooperative and the majority of U.S. participants as competitive. Study 2 showed that this pattern may reflect different beliefs about, and perhaps different (...) awareness of, plausible interspecies interactions. Further probes suggest that these models of ecological interaction correlate with recognition of social agency in nonhuman animals. We interpret our results in terms of cultural models of nature and nonhuman agency. (shrink)

I first sketch an account of humility as a character trait in which we are unimpressed with our good, envied, or admired features, achievements, etc., where these lack significant salience for our image of ourselves, because of the greater prominence of our limitations and flaws. I situate this view among several other recent conceptions of humility (also called modesty), dividing them between the inward-directed and outward-directed, distinguish mine from them, pose problems for each alternative account, and show how my understanding (...) of humility captures truths present but exaggerated in several of them. Responding to some problems for my view, including what I call “Driver’s Paradox”(i.e., the strangeness of someone’s proclaiming ‘I’m humble!’), I suggest that some over-ambitious claims about our moral responsibilities may indicate a lack of proper humility. I discuss the relationship of the character trait of humility both to what humiliates and to what humbles, concluding with consideration of the background assumptions against which, and the circumstances in which, humility may reasonably be classified as a moral virtue. (shrink)

In the seventh and most recent edition of their classic book, Principles of Biomedical Ethics, Tom Beauchamp and James Childress define a virtue as a character trait that is “socially valuable and reliably present” and a moral virtue as such a trait that is also both “dispositional” and “morally valuable”. The virtues that they single out as “focal” within biomedical ethics are compassion, discernment, trustworthiness, integrity, and conscientiousness. Not all is well in their treatment of virtue. Beauchamp and Childress seem (...) to worry that an ethical theory in which virtues are fundamental will neglect duties, rights, and societal needs. Further, they insist that there is no reason to think that, within ethical theory, one family of ethical concepts is the most important, nor that one theoretical approach is correct, or even superior to others. I will try to show, that there are strong reasons to see language, concepts, and matters of virtue as fundamental within normative ethical theory, both generally and in such specialized subareas as medical ethics. These reasons reveal themselves when we analyze concepts at the core of the alternative approaches to theorizing ethics that Beauchamp and Childress identify. (shrink)

Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or of the AS pattern of those sequences itself. Less is known about the evolution of the regulation of AS, but several studies, working from different perspectives, have recently made significant progress. Here, we categorize the different levels of AS evolution, (...) and summarize the studies on evolution of AS regulation, which point to a high level of evolutionary conservation of the regulation of AS events conserved between related species. This suggests that the quantitative regulation of AS is an intrinsic part of AS function. We discuss the potential role of changes in developmental regulation of AS as an additional layer in complex gene regulatory networks and in the emergence of genetic novelties. (shrink)

The paper defends the thesis that for S to V intentionally is for S to V as (in the way) S intended to. For the normal agent the relevant sort of intention is an intention that one's intention to V generate an instance of one's V-ing along some (usually dimly-conceived) productive path. Such an account allows us to say some actions are intentional to a greater or lesser extent (a desirable option for certain cases of wayward causal chains), preserves the (...) intuitive link between intention and intentionally, and supports the common sense view that the concept of intending is more basic than those of acting with an intention and of acting intentionally. The remainder of the paper responds to certain apparent counter-examples offered by Audi, Harman, and Bratman. In the course of this, I discuss connections between intending to V and hoping to V, and I argue that one can intend to do what one doesn't expect to do, and that one always intends what one attempts. (shrink)

Drawing chiefly on recent sources, in Part One I sketch an untraditional way of articulating what I claim to be central elements of traditional Catholic morality, treating it as based in virtues, focused on the recipients (“patients”) of our attention and concern, and centered in certain person-to-person role-relationships. I show the limited and derivative places of “natural law,” and therefore of sin, within that framework. I also sketch out some possible implications for medical ethics of this approach to moral theory, (...) and briefly contrast these with the influential alternative offered by the “principlism” of Beauchamp and Childress. In Part Two, I turn to a Catholic understanding of the nature and meaning of human suffering, drawing especially on writings and addresses of the late Pope John Paul II. He reminds us that physical and mental suffering can provide an opportunity to share in Christ's salvific sacrifice, better to see the nature of our earthly vocation, and to reflect on the dependence that inheres in human existence. At various places, and especially in my conclusion, I suggest a few ways in which this can inform bioethical reflection on morally appropriate responses to those afflicted by physical or mental pain, disability, mental impairment, disease, illness, and poor health prospects. My general point is that mercy must be informed by appreciation of the person's dignity and status. Throughout, my approach is philosophical rather than theological. (shrink)

Morality and religion: intimately wed, violently opposed, or something else? Discussion of this issue appears in pop culture, the academy, and the media—often generating radically opposed views. At one end of the spectrum are those who think that unless God exists, ethics is unfounded and the moral life is unmotivated. At the other end are those who think that religious belief is unnecessary for—and even a threat to—ethical knowledge and the moral life. -/- This volume provides an accessible, charitable discussion (...) that represents a range of views along this spectrum. The book begins with a lively debate between Paul Kurtz and William Lane Craig on the question, Is goodness without God good enough? Kurtz defends the affirmative position and Craig the negative. Following the debate are new essays by prominent scholars. These essays comment on the debate and advance the broader discussion of religion and morality. The book closes with final responses from Kurtz and Craig. (shrink)

This work presents a novel approach to forecast streaming big time series based on nearest similar patterns. This approach combines a clustering algorithm with a classifier and the nearest neighbours algorithm. It presents two separate stages: offline and online. The offline phase is for training and finding the best models for clustering, classification and the nearest neighbours algorithm. The online phase is to predict big time series in real time. In the offline phase, data are divided into clusters and a (...) forecasting model based on the nearest neighbours is trained for each cluster. In addition, a classifier is trained using the cluster assignments previously generated by the clustering algorithm. In the online phase, the classifier predicts the cluster label of an instance, and the proper nearest neighbours model according to the predicted cluster label is applied to obtain the final prediction using the similar patterns. The algorithm is able to be updated incrementally for online learning from data streams. Results are reported using electricity consumption with a granularity of |$10$| minutes for 4-hour-ahead forecasting and compared with well-known online benchmark learners, showing a remarkable improvement in prediction accuracy. (shrink)