Polyglutamine (polyQ) diseases are genetically inherited neurodegenerative disorders. They are caused by mutations that result in polyQ expansions of particular proteins. Mutant proteins form intranuclear aggregates, induce cytotoxicity and cause neuronal cell death. Protein interaction data suggest that polyQ regions modulate interactions between coiled‐coil (CC) domains. In the case of the polyQ disease spinocerebellar ataxia type‐1 (SCA1), interacting proteins with CC domains further enhance aggregation and toxicity of mutant ataxin‐1 (ATXN1). Here, we suggest that CC partners interacting with the polyQ (...) region of a mutant protein, increase its aggregation while partners that interact with a different region reduce the formation of aggregates. Computational analysis of genetic screens revealed that CC‐rich proteins are highly enriched among genes that enhance pathogenicity of polyQ proteins, supporting our hypothesis. We therefore suggest that blocking interactions between mutant polyQ proteins and their CC partners might constitute a promising preventive strategy against neurodegeneration. (shrink)

At the end of his attack on my use of the psychoanalytic model for the interpretation of literature, Heller raises the question concerning what the task of the literary critic is or ought to be. His own "sketch of the Kleistean theme's historical ancestry and its later development," he says, seeks to deepen and enrich the reader's appreciation of Kleist's literary art, the artistry of his phrasing, the persuasiveness of his incidents, the conclusiveness of his examples." By implication he suggests (...) that my method does not have this end—that is, appreciation—for its goal. In this he is partially right. "Appreciation" in Heller's sense is not as directly a goal for me. But does Heller's method of intellectual history and literary relation meet his own criteria of deepening and enriching the reader's appreciation of Kleist? In his capsule treatment of Great Thinkers of the Western World from Plato to Marx, we learn that many writers besides Kleist treated Kleist's theme of man's fall from unconscious grace. What exactly does this tell us about Kleist's treatment of it? How does it deepen the reader's appreciation of Kleist's literary art, the artistry of his phrasing, the persuasiveness of his incidents? It doesn't. It isn't even about Kleist. Although Heller tells us that it is the "thought" and "imagery" which "make for the great distinction of the essay" , his evidence for this consists, in the case of the former, in his tracing the history of the essay's thought and, in the case of the latter, in his statements that Kleist's use of the puppet as the exemplar of the unselfconscious graceful being is "unusual" and "novel" and that his bear story, though it may lack "in immediate plausibility," "gains in making Kleist's point" and is "a memorable exemplar" of the "art of grotesque inventions that are capable of floating for quite a while above and between the comic and the serious before landing with scintillating effect in one domain or the other" . Margret Schaefer is a lecturer in the department of psychiatry at Northwestern University Medical School. She responds here to Erich Heller's "The Dismantling of a Marionette Theater; or, Psychology and the Misinterpretation of Literature" , in which he discussed her article, "Kleist's 'About the Puppet Theater,". (shrink)

The force of [Heinrich von] Kleist's story "On the Marionette Theatre" . . . derives from roots deeply sunk into the soil of the past. It is a novel variation on a theme the first author of which may well be Plato. For according to Plato the human mind has been in the dark ever since it lost its place in the community of Truth, in the realm, that is, of the Ideas, the eternal and eternally perfect forms, those now (...) unattainable models which man in his exile is able to see and recognize only as shadows or imperfect copies. And this Platonic parable of the damage suffered by man's soul and consciousness is not unlike the Fall as it is narrated in Genesis. The Fall was the consequence and punishment of man's free will that for the first time had asserted itself against the universal God and rejoiced in a consciousness and pleasure entirely its own—tragically its own; for man had to forsake the indwelling in the supreme Intelligence and thus the harmony between himself and Being as such. The reward for this betrayal was the embarrassment and shame of self-consciousness, the hard labor of maintaining himself in his state of separation, and, soon to follow, the murderous misdeeds of the self-will named Cain. Better to have no mind than a mind thus deprived and impoverished and cruel. Erich Heller, Avalon Foundation Professor in the Humanities at Northwestern University, is the author of The Disinherited Mind: Essays in Modern German Literature and Thought; The Ironic Gentleman: Thomas Mann; The Artist's Journey into the Interior; and Franz Kafka. These books have also appeared in Germany in the author's own translations, and his Dir Wiederkehr der Unschuld [The return of innocence] was recently published there. See also: "Fiction, History, and Empirical Reality" by Murray Krieger in Vol. 1, No. 2; "Psychoanalysis and the Marionette Theater: Interpretation is Not Depreciation" by Margret Schaefer in Vol. 5, No. 1. (shrink)

I will return to the second point in a different context later; at this moment I will discuss only the issue raised by my pointing up the fact that the essay in question was written by someone in Professor Heller's field. What motivated me to make the statement was not my belief that the use of psychoanalysis in the interpretation of art should be restricted to certified psychoanalysts—indeed, I have always been a staunch advocate of the opposite view. My motive (...) for this, I assumed harmless, and not, of course, irrelevant, indiscretion was that I wanted to show that Professor Heller's critique of psychoanalysis was not broadly based, that his representative example was a piece that happened to have crossed his way, that he was not using the work of an established writer in the field that he was condemning. My statement that your essay is an unacceptable text in a sermon preaching against applied analysis is unrelated to the value of your article. Even if in the future it should turn out that your essay—as far as I know your first contribution to applied psychoanalysis—was the forerunner of a significant oeuvre that would put you into the class of the great contributors of psychoanalytic interpretations of literature, it is at this point not an acceptable text for a sermon against our field. Heinz Kohut, M.D., is Professorial Lecturer in Psychiatry at the University of Chicago, teacher and training analyst at the Chicago Institute for Psychoanalysis, and author of many influential works on the psychology of the self. His works include The Restoration of the Self, The Analysis of the Self: A Systematic Approach to the Psychoanalytic Treatment of Narcissistic Personality Disorders - which has appeared in German, French, and Italian translations - and a collection of his essays, Scientific Empathy and Empathic Science. His "Psychoanalysis and the Interpretation of Literature: A Correspondence with Erich Heller" was published in the Spring 1978 issue of Critical Inquiry. (shrink)

Dear Professor Heller . . . Your paper had started out superbly. It was a great aesthetic and cognitive pleasure to follow you as you guided us through the intellectual history of the main idea of Kleist's essay, from Plato through the biblical Fall of Man, to Schiller, and Kierkegaard, and Kafka. Indeed the perceptive listener's experience was so satisfying that his disappointment was doubled when he came to realize that all this erudition and beauty had been displayed only in (...) order to serve as a contrast-providing background for the sharp delineation of a reductionistic explanation which you consider to be characteristic of psychoanalysis: the interpretation of the disturbance of man's naive, unselfconscious pre-Fall state as nothing more than a portrayal of sexual impotence—the reduction of a deep existential preoccupation to a case of phimosis. I am certain that the relief I felt when you then took up Freud's demonological-neurosis paper was not an idiosyncratic response on my part but an experience shared by many open-minded listeners in your psychoanalytic audience. Let us, therefore, disregard the "text" of your sermon and consider the substantial questions that you raised after you turned to Freud; these are to my mind the most central ones that you undertook to examine in your—despite its disappointing aspects—splendid address to us. Put into my own words, your most important question was this: What is the purpose of the psychoanalyst's efforts outside the clinical setting, in particular when his contributions take the form of a pathography? That is, To what end do analysts study the psychopathology of the creators of great works? I, too, have asked myself this question, and since you read my old essay "Beyond the Bounds of the Basic Rule" , you know some of my answers. But important basic questions are hardly ever answered once and for all; and I will, therefore, under the impact of your lecture, respond as if I had heard the question for the first time. Heinz Kohut, M.D., is Professorial Lecturer in Psychiatry at the University of Chicago and a teacher and training analyst at the Chicago Institute for Psychoanalysis. His works include The Restoration of the Self, The Analysis of the Self: A Systematic Approach to the Psychoanalytic Treatment of Narcissistic Personality Disorders—which has appeared in German, French, and Italian translations—, The Restoration of the Self and collection of his essays, Scientific Empathy and Empathic Science. His "A Reply to Margret Schaefer"" was published in the Spring 1978 issue of Critical Inquiry. See also: "Psychoanalysis and the Marionette Theater: Interpretation is Not Depreciation" by Margret Schaefer in Vol. 5, No. 1. (shrink)

The predominant view is that a study using health data is observational research and should require individual consent unless it can be shown that gaining consent is impractical. But recent arguments have been made that citizens have an ethical obligation to share their health information for research purposes. In our view, this obligation is sufficient ground to expand the circumstances where secondary use research with identifiable health information is permitted without explicit subject consent. As such, for some studies the Institutional (...) Review Board/Research Ethics Committee review process should not assess the practicality of gaining consent for data use. Instead the review process should focus on assessing the public good of the research, public engagement and transparency. (shrink)

Some have objected to human enhancement on the grounds that it violates the autonomy of the enhanced. These objections, however, overlook the interesting possibility that autonomy itself could be enhanced. How, exactly, to enhance autonomy is a difficult problem due to the numerous and diverse accounts of autonomy in the literature. Existing accounts of autonomy enhancement rely on narrow and controversial conceptions of autonomy. However, we identify one feature of autonomy common to many mainstream accounts: reasoning ability. Autonomy can then (...) be enhanced by improving people’s reasoning ability, in particular through cognitive enhancement; given how valuable autonomy is usually taken to be, this gives us extra reason to pursue such cognitive enhancements. Moreover, autonomy-based objections will be especially weak against such enhancements. As we will argue, those who are worried that enhancements will inhibit people’s autonomy should actually embrace those enhancements that will improve autonomy. (shrink)

Moral enhancement is an ostensibly laudable project. Who wouldn’t want people to become more moral? Still, the project’s approach is crucial. We can distinguish between two approaches for moral enhancement: direct and indirect. Direct moral enhancements aim at bringing about particular ideas, motives or behaviors. Indirect moral enhancements, by contrast, aim at making people more reliably produce the morally correct ideas, motives or behaviors without committing to the content of those ideas, motives and/or actions. I will argue, on Millian grounds, (...) that the value of disagreement puts serious pressure on proposals for relatively widespread direct moral enhancement. A more acceptable path would be to focus instead on indirect moral enhancements while staying neutral, for the most part, on a wide range of substantive moral claims. I will outline what such indirect moral enhancement might look like, and why we should expect it to lead to general moral improvement. (shrink)

While philosophers are often concerned with the conditions for moral knowledge or justification, in practice something arguably less demanding is just as, if not more, important – reliably making correct moral judgments. Judges and juries should hand down fair sentences, government officials should decide on just laws, members of ethics committees should make sound recommendations, and so on. We want such agents, more often than not and as often as possible, to make the right decisions. The purpose of this paper (...) is to propose a method of enhancing the moral reliability of such agents. In particular, we advocate for a procedural approach; certain internal processes generally contribute to people’s moral reliability. Building on the early work of Rawls, we identify several particular factors related to moral reasoning that are specific enough to be the target of practical intervention: logical competence, conceptual understanding, empirical competence, openness, empathy and bias. Improving on these processes can in turn make people more morally reliable in a variety of contexts and has implications for recent debates over moral enhancement. (shrink)

The future of health research will be characterised by three continuing trends: rising demand for health data; increasing impracticability of obtaining specific consent for secondary research; and decreasing capacity to effectively anonymise data. In this context, governments, clinicians and the research community must demonstrate that they can be responsible stewards of health data. IRBs and RECs sit at heart of this process because in many jurisdictions they have the capacity to grant consent waivers when research is judged to be of (...) particular value. However, several different terms are used to refer to this value, indicating a lack of conceptual clarity regarding the appropriate test for access to health data for research without consent. In this paper we do three things. First we describe the current confusion and instability in terminology relating to public interest in the context of consent waivers. Second we argue for harmonisation of terminology on the grounds of clarity, transparency and consistency. Third we argue that the term ‘public interest’ best reflects the normative work required to justify consent waivers because it is the broadest of the competing terms. ‘Public interest’ contains within its scope positive and negative implications of a study, as well as welfare, justice and rights considerations. In making this argument, we explain the normative basis for consent waivers, and provide a starting place for further discussion about the precise conditions in which a given study can be said to advance the public interest. Ipsos MORI study found that: … the public would be broadly happy with administrative data linking for research projects provided Those projects have social value, broadly defined. Data are de-identified. Data are kept secure. Businesses are not able to access the data for profit. (shrink)

It has recently been argued that reproductive genetic manipulation technologies like mitochondrial replacement and germline CRISPR modifications cannot be said to save anyone’s life because, counterfactually, no one would suffer more or die sooner absent the intervention. The present article argues that, on the contrary, reproductive genetic manipulations may be life-saving (and, from this, have therapeutic value) under an appropriate population health perspective. As such, popular reports of reproductive genetic manipulations potentially saving lives or preventing disease are not necessarily mistaken, (...) though such terminology still requires further empirical validation. (shrink)

Background Several jurisdictions, including Singapore, Australia, New Zealand and most recently Ireland, have a public interest or public good criterion for granting waivers of consent in biomedical research using secondary health data or tissue. However, the concept of the public interest is not well defined in this context, which creates difficulties for institutions, institutional review boards and regulators trying to implement the criterion. Main text This paper clarifies how the public interest criterion can be defensibly deployed. We first explain the (...) ethical basis for requiring waivers to only be granted to studies meeting the public interest criterion, then explore how further criteria may be set to determine the extent to which a given study can legitimately claim to be in the public interest. We propose an approach that does not attempt to measure magnitude of benefit directly, but rather takes into account metrics that are more straightforward to apply. To ensure consistent and justifiable interpretation, research institutions and IRBs should also incorporate procedural features such as transparency and public engagement in determining which studies satisfy the public interest requirement. Conclusion The requirement of public interest for consent waivers in secondary biomedical research should be guided by well-defined criteria for systematic evaluation. Such a criteria and its application need to be periodically subject to intra-committee and intra-institution review, reflection, deliberation and amendment. (shrink)

It is generally unquestioned that human subjects research review boards should assess the ethical acceptability of protocols. It says so right on the tin, after all: they are explicitly called research ethics committees in the UK. But it is precisely those sorts of unchallenged assumptions that should, from time to time, be assessed and critiqued, in case they are in fact unfounded. John Stuart Mill's objection to suppressers of dissent is instructive here: “If the opinion is right, they are deprived (...) of the opportunity of exchanging error for truth: if wrong, they lose, what is almost as great a benefit, the clearer perception and livelier impression of truth, produced by its collision with error”.1 Andrew Moore and Andrew Donnelly's compelling article, “The job of ‘ethics committees’”, is just this sort of challenge to conventional wisdom, a rejection of the notion that review boards should be considering ethical matters at all.2 If true, we should be substantially reforming our research ethics policies. And if false, rebuttals would help strengthen and ground the otherwise unquestioned assumption of the role of ethics committees. As it happens, I will argue that their critiques fall into the second category. While mistaken, they present a valuable opportunity to clarify the role of ethics committees and their relationship to relevant codes. In particular, I will defend a hybrid account where codes have strict primacy, but leave significant room for review boards …. (shrink)

The need for better incorporation of the construct emotional intelligence (EI) into counterproductive work behavior (CWB) research may be achieved via a unified conceptual framework. Accordingly, the purpose of this paper is to use the Profile Analysis via Multidimensional Scaling (PAMS) approach, a conceptual framework that unifies motivational process with antecedents and outcomes, to assess differences in EI concerning a variety of constructs: organizational justice, CWB, emotional exhaustion, job satisfaction, and intrinsic motivation. Employing established scales within a framework unifying CWB, (...) intrinsic motivation, EI, organizational justice, and outcome constructs, two EI-based profiles displayed associations with CWB based on responses from 3,293 employees. Both the first core profile, high overall justice and low emotional intelligence, and the second core profile, high emotional intelligence and low work motivation, displayed associations with interpersonal deviance and organizational deviance, as well as emotional exhaustion and job satisfaction. The results are discussed with respect to possible underlying theory and an overarching unified motivation framework that incorporates goal choice, intrinsic motivation, antecedents, and outcomes. We also provide directions for future research and implications for managers in the workplace based on heuristic conceptual frameworks that combine multiple motivational perspectives into a unified model. (shrink)

With the recent report of a live birth after use of Mitochondrial replacement therapy, sometimes called ‘Three-parent IVF’, the clinical application of the technique is fast becoming a reality. While the United Kingdom allows the procedure under regulatory scrutiny, it remains effectively outlawed in many other countries. We argue that such prohibitions may violate individuals’ procreative rights, grounded in individuals’ interest in genetic affinity. The interest in genetic affinity was recently endorsed by Singapore’s highest court, reflecting an emphasis on the (...) importance of biological ties found across the globe. We apply that reasoning to make the case for a right to ‘Three-parent IVF’. (shrink)

Keine ausführliche Beschreibung für "Weltgebäude, Weltgesetze, Weltentwicklung" verfügbar.

This commentary examines the role of sustainability in the latest draft of the WHO pandemic accord, highlighting its notable absence from the official list of guiding principles despite being mentioned frequently throughout the text. It argues that sustainability should be explicitly acknowledged as a core principle and given a clear definition tailored to pandemic preparedness, and proposes defining sustainability as ensuring that immediate emergency responses don't compromise future pandemic preparedness and response capabilities. Including sustainability as a guiding principle would serve (...) two key purposes: validating the relevance of ethical principles in the accord's provisions and emphasizing the importance of long-term planning in pandemic preparedness. The commentary notes that while humans naturally discount future consequences, sustainable pandemic planning requires considering impacts beyond the next pandemic. It recommends coupling any reforms, such as intellectual property changes, with alternative innovation incentives to maintain a balanced approach to pandemic preparedness and response. (shrink)

Volume 20, Issue 2, February 2020, Page 20-22.

Physicians accept fallibility in technical matters as a condition of medical practice. When it comes to moral considerations, physicians are often loathe to act without a good deal more certitude and seem less willing to accept error. This article argues that ethics is intrinsic to medical decision making, that error is the inevitable risk of any action and that inaction carries even greater risk of error. Whether in the moral or the technical sphere, error must be accepted by physicians as (...) part of the learning process which informs and enriches future decisions. Moral virtue, it is concluded, resides more in the making of a decision and in the agony of making it than it does in the potentially fallible decision itself. (shrink)

This paper critically assesses the “procedural” accounts of political justice set forth by John Rawls in A Theory of Justice (1971) and Robert Nozick in Anarchy, State, and Utopia (1974). I argue that the areas of agreement between Rawls and Nozick are more significant than their disagreements. Even though Nozick offers trenchant criticisms of Rawls's argument for economic redistribution (the “difference principle”), Nozick's own economic libertarianism is undermined by his “principle of rectification,” which he offers as a possible ground in (...) practice for the application of something like the difference principle. Both Rawls's and Nozick's accounts of justice fail because of their abstraction from human nature as a ground of right. At the same time the libertarianism on which they agree in the non-economic sphere would deprive a free society of its necessary moral underpinning. Rawls and Nozick err, finally, by demanding that the policies pursued by a just society conform to theoretical formulas concocted by philosophy professors, rather than leaving room (as Lockean liberalism does) for the adjustment of policies to particular circumstances based on statesmen's prudential judgment and the consent of the governed. Particularly troubling from the perspective of a citizen seriously concerned with the advancement of justice and freedom is both thinkers' shrill denunciations of existing liberal societies for failing to conform to their particular strictures. (shrink)

Individual health assessments (IHAs) for asymptomatic individuals provide a challenge to traditional distinctions between patient care and non-medical practice. They may involve undue radiation exposure, lead to false positives, and involve high out-of-pocket costs for recipients. A recent paper (Journal of the American College of Radiology 13(12): 1447–1457.e1, 2016) has criticised the use of IHAs and argued that recipients should be classified as ‘presenters’, not ‘patients’, to distinguish it from regular medical care. I critique this classificatory move, on two grounds: (...) one, it is conceptually suspect. Two, it obviates the medical ethics framework for IHAs, potentially exposing recipients of IHAs to lower standards of oversight and protection. Responsible regulation of IHAs will be easier to ethically justify if those seeking IHAs are considered patients and not merely presenters. (shrink)

Our brains are characterized by sensory pathways that are highly reflexive, allowing higher cortical centres to control neural activity patterns at peripheral sensory areas. This feature is characterized as an internal sketchpad and involves recursive interactions between central symbols and peripheral images. The process is assumed to be the fundamental mechanism underlying most cognitive functions. The paper attempts to portray the beginnings of art and language as natural extensions of these pre-existing internal processes, made possible by the greatly enlarged human (...) prefrontal cortex. It views these highly social activities as originating in subjective, private discourse between the emerging self and its externalized expressions. (shrink)

Religia jest dla człowieka życiowy i życiodajny sprawy, dlatego namysł nad jej powstaniem, funkcji i istoty jest zawsze na czasie, tym bardziej w okresie postmodernistycznego zagubienia. Jeśli religia jest dla człowieka tak ważną sprawą to jego namysł nad nią nie jest niczym innym, jak myśleniem samego siebie. Jest ona bowiem tą rzeczywistością, która trafia w serce człowieka, w nerw jego życia. Religia, tak jak życie człowieka, jest uwarunkowana historycznie, to znaczy: czasowo, lokalnie, kulturowe, ma okresy wzlotów i upadków. Wydaje się, (...) że dla człowieka nowożytnego, a zwłaszcza człowieka ostatnich dwóch wieków, religia straciła na życiowej i życiodajnej wartości, przestała być jego fundamentalną, wewnętrzną postawy wobec Boga, stała się raczej wyrazem jego kulturowo-społecznego, zewnętrznego funkcjonowania. Początki przemiany tej postawy można dzisiaj dokładnie zanalizować, jej konsekwencje dla współczesnego człowieka można opisać. (shrink)