The rapid rise of international collaborative science has enabled access to genomic data. In this article, it is argued that to move beyond mapping genomic variation to understanding its role in complex disease aetiology and treatment will require extending data sharing for the purposes of clinical research translation and implementation.

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

I met Ernie in 1965 on the wrestling mats of our high school in North Bergen, New Jersey, a township on top of the plateau overlooking Hoboken and across the Hudson River from Manhattan. Hoboken then was still the Hoboken of Elia Kazan’s “On the Waterfront” (1954).1 Even though the Hudson was less than a mile across at that point, it was a wide spiritual divide. We were Jersey boys, not New Yorkers. Ernie was as ambitious as I (...) was about wrestling, and, so, after the season was over, we used to take a bus to Journal Square in Jersey City, and then walk about eight city blocks to a gym to lift weights. In those days, high schools didn’t have weight rooms; and gyms were scarce, men only, quite filthy, and entirely devoid of cardio equipment and Nautilus machines. They were all sweat, grunts, groans, and clanking iron. By 1968, on Tuesdays and Thursdays, after a grueling wrestling practice at the high school, we would take a bus to New York City (it took about a half hour to get into “the City” by bus, less if the Lincoln Tunnel was not crowded), and then a short subway ride up to the New York Athletic Club on 59th street, across from Central Park, to spend a couple of hours working out with former university wrestling stars—guys in their mid-twenties from places like Oklahoma, Nebraska, and Iowa—who were training to make the Olympic team. Even with all of this wrestling time, we were frustrated by the fact that there was nowhere to work out on Sundays. We investigated and found out that the Jersey City YMCA had a wrestling mat and was open on Sundays. We then spent our Sunday afternoons working out there, so as not to miss a day of wrestling. Wrestling was our savior: a healthy way to get out anger.2 But it wasn’t all wrestling. We did something else too: We talked. We spent many hours together introspecting out loud, and just trying to make sense of things. Ernie has mentioned in print one early topic of discussion: “We spent years trying to solve various logical conundra like how on earth the Virgin Mary could have been a virgin.... (shrink)

Sometimes ordinary disagreements become deep as a result of epistemic injustice. The paper explores a hitherto unnoticed connection between two phenomena that have received ample attention in recent social epistemology: deep disagreement and epistemic injustice. When epistemic injustice comes into play in a regular disagreement, this can lead to higher-order disagreement about what counts as evidence concerning the original disagreement, which deepens the disagreement. After considering a common definition of deep disagreement, it is proposed that the depth of disagreements is (...) best understood as a matter of degree. Then, a case study of real-life disagreement is introduced: the disagreement about whether racism is a significant issue in the Netherlands, illustrated by the tradition of ‘Black Pete’. It is argued that there is disagreement about what counts as evidence in the case study because of two forms of epistemic injustice: testimonial and hermeneutical injustice. Specifically, there is disagreement about epistemic principles concerning whether private first-personal experience of racism is a weighty source of evidence in this domain, whether victims of racism count as important testifiers in this domain, and how to assess testimony that is not intelligible to you because it employs concepts and terminology you are unfamiliar with. By dismissing the relevant testimony and epistemic resources, the disagreement boils down to disagreement on the level of epistemic principles concerning,, and. Introducinginjustice-based deep disagreementhighlights moral and political aspects of disagreements that might seem factual. (shrink)

How do we think about animals? How do we decide what they deserve and how we ought to treat them? Subhuman takes an interdisciplinary approach to these questions, drawing from research in philosophy, neuroscience, psychology, law, history, sociology, economics, and anthropology. Subhuman argues that our attitudes to nonhuman animals, both positive and negative, largely arise from our need to compare ourselves to them.

Some philosophers have thought that life could only be meaningful if there is no God. For Sartre and Nagel, for example, a God of the traditional classical theistic sort would constrain our powers of self-creative autonomy in ways that would severely detract from the meaning of our lives, possibly even evacuate our lives of all meaning. Some philosophers, by contrast, have thought that life could only be meaningful if there is a God. God and the Meanings of Life is interested (...) in exploring the truth in both these schools of thought, seeking to discover what God could and couldn't do to make life meaningful (as well as what he would and wouldn't do). Mawson espouses a version of the 'amalgam' or 'pluralism' thesis about the issue of life's meaning – in essence, that there are a number of different legitimate meanings of 'meaning' (and indeed 'life') in the question of life's meaning. According to Mawson, God, were he to exist, would help make life meaningful in some of these senses and hinder in some others. He argues that whilst there could be meaning in a Godless universe, there could be other sorts of meaning in a Godly one and that these would be deeper. (shrink)

The standard approach to protecting privacy in healthcare aims to control access to personal information. We cannot regain control of information after it has been shared, so we must restrict access from the start. This ‘control’ conception of privacy conflicts with data-intensive initiatives like precision medicine and learning health systems, as they require patients to give up significant control of their information. Without adequate alternatives to the control-based approach, such data-intensive programmes appear to require a loss of privacy. This paper (...) argues that the control view of privacy is shortsighted and overlooks important ways to protect health information even when widely shared. To prepare for a world where we no longer control our data, we must pursue three alternative strategies: obfuscate health data, penalise the misuse of health data and improve transparency around who shares our data and for what purposes. Prioritising these strategies is necessary when health data are widely shared both within and outside of the health system. (shrink)

Recent highly publicized privacy breaches in health care and genomics research have led many to question whether current standards of data protection are adequate. Improvements in de-identification techniques, combined with pervasive data sharing, have increased the likelihood that external parties can track individuals across multiple databases. This paper focuses on the communication of identifiability risks in the process of obtaining consent for donation and research. Most ethical discussions of identifiability risks have focused on the severity of the risk and how (...) it might be mitigated, and what precisely is at stake in pervasive data sharing. However, there has been little discussion of whether and how to communicate the risk to potential donors. We review the ethical arguments behind favoring different types of risk communication in the consent process, and outline how identifiability concerns can be incorporated into either a detailed or simplified method of communicating risks during the consent process. (shrink)

Monotheism and the Meaning of Life explores the role of God, and the relationship to the question 'What is the meaning of life?' for adherents of the main monotheistic religions - Judaism, Christianity and Islam. Exploring the various senses of 'meaning' and 'life', Mawson argues that there are various questions implicit in the notion of the meaning of life and that the God of monotheistic religion is central to the correct answers to all of them.

Beskow and Weinfurt (2019) present an excellent and timely discussion of how to respond to evidence that individuals do not fully understand a biobank consent form. We faced similar challenges afte...

Ethicists have tended to treat the psychology of attributing mental states to animals as an entirely separate issue from the moral importance of animals’ mental states. In this paper I bring these two issues together. I argue for two theses, one descriptive and one normative. The descriptive thesis holds that ordinary human agents use what are generally called phenomenal mental states to assign moral considerability to animals. I examine recent empirical research on the attribution of phenomenal states and agential states (...) to argue that phenomenal mental states are the primary factor, psychologically, for judging an animal to be morally considerable. I further argue that, given the role of phenomenal states in assigning moral considerability, certain theories in animal ethics will meet significant psychological resistance. The normative thesis holds that ethicists must take the psychology of attributing mental states into account when constructing moral ideals concerning animals. I draw from the literature in political philosophy on ideal and non-ideal theory to argue that non-ideal theories for animals must account for human psychology because—like current social and political conditions—human psychology limits the achievement of moral ideals. (shrink)

T.J. Reed's study has long established itself as the standard work in English on Thomas mann, and offers as comprehensive a view of Mann's fiction and thought as is available in any language. It is based on a coherent close reading of Mann's oeuvre, literary and political, and also on manuscripts and sources, and was part of the first phase of literary scholarship that opened up the resources of the Zurich Thomas Mann Archive. Further documents that have appeared since then (...) - Mann's diaries, notebooks, and other correspondences - have not fundamentally altered the individual interpretations or the overall picture the study offers, and in some respects have emphatically confirmed them. A further chapter added to this edition covers the new documentation, gives a vigorous account of the main curents in Mann scholarship and criticism over the last two decades suggesting how we should now see the writer, the man, and the political figure, and above all the complex relationship between the three. (shrink)

In a series of articles, I set out my belief that investigators and subjects of research should work together in a partnership based in shared aims. Such a relationship – quite different from what is usual today – would impose duties on both partners. In earlier papers I explored the origin and nature of the duties that would fall on patients; here I examine their limits.

Genetic information is widely thought to pose unique risks of reidentifying individuals. Genetic data reveals a great deal about who we are and, the standard view holds, should consequently be treated differently from other types of data. Contrary to this view, we argue that the dangers of reidentification for genetic and nongenetic data—including health, financial, and consumer information—are more similar than has been recognized. Before different requirements are imposed around sharing genetic information, proponents of the standard view must show that (...) they are in fact necessary. We further argue that the similarities between genetic and nongenetic information have important implications for communicating risks during consent for health care and research. While patients and research participants need to be more aware of pervasive data‐sharing practices, consent forms are the wrong place to provide this education. Instead, health systems should engage with patients throughout patient care to educate them about data‐sharing practices. (shrink)

Together with the majority of modern commentators, Professor Skutsch believes that the ‘devotio’ prayer in lines 191–4 of Ennius' Annals was spoken by the consul P. Decius Mus before the battle of Ausculum in 279 B.c. This seems to me unlikely for several reasons, and I am still not persuaded after reading his note.

If patients are to be partners rather than subjects, contributing effectively to clinical research in which they have an interest, both they and investigators must change their ways. The case is argued here that the conduct of clinical research fulfils an essential need of society and that, therefore, in the interests of society, there is a moral imperative that it be done. Further essays will develop this theme, questioning along the way whether consent is a redundant concept.

Amongst other countries, the Netherlands currently allows euthanasia, provided the physician performing the procedure adheres to a strict set of requirements. In 2016, Second Chamber member Pia Dijkstra submitted a law proposal which would also allow euthanasia without the reason necessarily having any medical foundation; euthanasia on the basis of a completed life. The debate on this topic has been ongoing for over two decades, but this law proposal has made the discussion much more immediate and concrete. This paper considers (...) the moral permissibility of Pia Dijkstra’s law proposal, focusing on the ethics of the implementation Dijkstra describes in her proposal. I argue that, at present, Dijkstra’s law proposal is unsuitable for implementation, due to a number of as of yet unaddressed problems, including the possible development of an ageist stigma and undue pressure on the profession of end-of-life coordinator. Perhaps adequate responses can be conceived to address these issues. However, the existence of a radically different, yet currently equally unacceptable position regarding the implementation of euthanasia for a completed life as proposed by fellow party member Paul Schnabel suggests it may be difficult to formulate an ethically acceptable implementation for this, in principle, ethically acceptable concept. (shrink)

Male superiority in mathematical ability (along with female superiority in verbal fluency) may reflect the operation of an X-Y homologous gene (the right-shift-factor) influencing the relative rates of development of the cerebral hemispheres. Alleles at the locus on the Y chromosome will be selected at a later mean age than alleles on the X, and only by females.

The present study explored psychological predictors of response to a series of three 25 second inhalations of 20% carbon dioxide-enriched air in 60 nonclinical participants. Multiple regression analyses indicated that only anxiety sensitivity physical concerns predicted self-reported fear, whereas both physical anxiety sensitivity concerns and behavioural inhibition sensitivity independently predicted affective ratings of emotional arousal. In contrast, the psychological concerns anxiety sensitivity dimension predicted ratings of emotional displeasure (valence), and both psychological anxiety sensitivity concerns and behavioural inhibition sensitivity independently predicted (...) emotional dyscontrol. No variables significantly predicted heart rate. These data are in accord with current models of emotional reactivity that highlight the role of cognitive variables in the production of anxious and fearful responding to somatic perturbation, and help further clarify the particular predictors of anxiety-related responding to biological challenge. (shrink)