C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and (...) be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD can form both methylating and non‐methylating ribonucleoprotein complexes, providing an indication of the likely physical basis for such diverse new functions. Thus, SNORDs are more structurally and functionally diverse than previously thought, and their role in gene expression is under‐appreciated. The action of SNORDs in non‐methylating complexes can be substituted with oligonucleotides, allowing devising therapies for diseases like Prader‐Willi syndrome. (shrink)

A study in philosophical logic of the meaning of 'true'. Dr Williams demonstrates the shortcomings of various analyses which interpret 'true' as a predicate or truth as a relational property, and clears up a number of important points about propositions, quantification, definite descriptions and correspondence. This 'deflationary metaphysics' is interwoven with a positive theory of his own, which seeks to develop ideas about the late Arthur Prior. The work is marked throughout by great clarity, precision and thoroughness.

Our trust in the word of others is often dismissed as unworthy, because the illusory ideal of "autonomous knowledge" has prevailed in the debate about the nature of knowledge. Yet we are profoundly dependent on others for a vast amount of what any of us claim to know. Coady explores the nature of testimony in order to show how it might be justified as a source of knowledge, and uses the insights that he has developed to challenge certain widespread assumptions (...) in the areas of history, law, mathematics, and psychology. (shrink)

Tuberculosis (TB) is a potentially fatal infectious disease that, in Aotearoa New Zealand (NZ), inequitably affects Asian, Pacific, Middle Eastern, Latin American, and African (MELAA), and Māori people. Medical research involving genome sequencing of TB samples enables more nuanced understanding of disease strains and their transmission. This could inform highly specific health interventions. However, the collection and management of TB isolate samples for research are currently informed by monocultural biomedical models often lacking key ethical considerations. Drawing on a qualitative kaupapa (...) Māori–consistent study, this paper reports on preliminary discussions with groups of Māori, Pacific, and Afghan people in NZ, whose communities have been harmed by TB and TB stigma. Participants’ discussions highlight key concerns and meanings that ought to inform the development of guidelines and a more robust consultative process for the governance of how TB isolate samples are collected and used both retrospectively and in future research. We argue for ethical processes to be culturally nuanced and community-generated, flexible and meaningful, and situated in relation to the physical and symbolic effects of TB. We discuss the significance of Indigenous data sovereignty, rights, and kāwanatanga (governorship) in shaping a multicultural data sovereignty model. (shrink)

Sandia National Laboratories, located in Albuquerque, New Mexico, was originally a part of Los Alamos Laboratory. In 1949, AT&T agreed to manage Sandia, which they did for the next 44 years. During those Cold War years, Sandia was the prime weapons engineering laboratory for Los Alamos and Lawrence Livermore. As such, it bore prime responsibility for designing and adapting nuclear weapons for the military services' delivery systems, and ensuring the safety and reliability of the stockpile. The Labs' history has been (...) unevenly documented, hindered by the secret nature of its work and the desire of management to maintain a low public profile. There have been three history programs at Sandia: a restricted history published internally in 1963; another history program in the early 1980s that resulted in a history of the Labs' first decade; and the current history program dating from the mid-1990s, which has published a general history and several monographs. This article discusses the challenges and problems inherent in documenting the history of a national weapons laboratory during the last 50 years. (shrink)

The Mental Capacity Act received Royal Assent on 7 April 2005, and it will be implemented in 2007. The Act defines when someone lacks capacity and it supports people with limited decision-making ability to make as many decisions as possible for themselves. The Act lays down rules for substitute decision making. Someone taking decisions on behalf of the person lacking capacity must act in the best interests of the person concerned and choose the options least restrictive of his or her (...) rights and freedoms. Decision making will be allowed without any formal procedure unless specific provisions apply, such as a written advance decision, lasting powers of attorney or a decision by the court of protection. (shrink)

This paper begins with a discussion of different definitions of “terrorism” and endorses one version of a tactical definition, so-called because it treats terrorism as involving the use of a quite specific tactic in the pursuit of political ends, namely, violent attacks upon the innocent. This contrasts with a political status definition in which “terrorism” is defined as any form of sub-state political violence against the state. Some consequences of the tactical definition are explored, notably the fact that it allows (...) for the possibility of state terrorism against individuals, sub-state groups and other states. But a major problem for the tactical definition is the account to be given of “the innocent.” In line with justwar thinking, the idea of “the innocent” is unpacked in terms of the concept of non-combatants and this in turn is treated as the category of those who are not prosecuting the harm that allows for a legitimate violent response. Problems with this approach are explored, with particular reference to criticisms made by Gregory Kavka. The recent drive to expand the class of those who may be legitimately attacked is subjected to scrutiny. Particular attention is paid to the role of “collective responsibility” and “deserving your government” in these arguments. (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

The seminal 1993 article by LaFollette and Shanks “Animal Models in Biomedical Research: Some Epistemological Worries” introduced an influential taxonomy into the debate about the value of animal experimentation. The distinction they made between hypothetical and causal analog models served to highlight a concern regarding extrapolating results obtained in animal models to human subjects, which endures today. Although their taxonomy has made a significant contribution to the field, we maintain that it is flawed, and instead, we offer a new practice-oriented (...) taxonomy of animal models as a means to allow philosophers, modelers, and other interested parties to discuss the epistemic merits and shortcomings, purpose, and predictive capacities of specific modeling practices. (shrink)

Why is it that philosophers find it so hard to come to agreement? Many disputes that have gone on for centuries or even millennia are still unresolved, even though there has been increased conceptual sophistication on the part of the contending parties. Consider, for example, the question of free will, where libertarians still contest the field with determinists and compatibilists.

Background: Funding organisations and research ethics committees should play a part in strengthening attention to gender equality in clinical research. In the research policy of European Union , funding measures have been taken to realise this, but such measures are lacking in the EU policy regarding RECs.Objective: To explore how RECs in Austria, Germany, Ireland, The Netherlands and Sweden deal with gender equality issues by asking two questions: Do existing procedures promote representation of women and gender expertise in the committee? (...) How are sex and gender issues dealt with in protocol evaluation?Methods: Two RECs were selected from each country. Data were obtained through interviews with key informants and content analysis of relevant documents .Results: All countries have rules to ensure the presence of women on RECs; gender expertise is not required. Drug study protocols are carefully evaluated, sometimes on a formal basis, as regards the inclusion of women of childbearing age. The reason for excluding either one of the sexes or including specific groups of women or making a gender-specific risk–benefit analysis are investigated by some RECs. Such measures are, however, neither defined in the regulations nor integrated in review tools.Conclusions: The RECs investigated in five European member states are found to pay limited attention to gender equality in their working methods and, in particular in protocol evaluation. Policy and regulations of EU are needed to strengthen attention to gender equality in the work of RECs. (shrink)

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)

abstract This paper aims to gain a deeper understanding of the different forms of moralism in order to throw light upon debates about the role of morality in international affairs. In particular, the influential doctrine of political realism is reinterpreted as objecting not to a role for morality in international politics, but to the baneful effects of moralism. This is a more sympathetic reading than that usually given by philosophers to the realist doctrines. I begin by showing the ambiguity and (...) elusiveness of realist claims about morality in politics and then distinguish six forms of moralism, understood as a distortion of genuine morality: moralism of scope, of imposition, of abstraction, of absolutism, of inappropriate explicitness, and of deluded power. I argue that most of these are relevant to typical realist claims and can make their objections more plausible. But, though realists can be interpreted as rightly drawing attention to the dangers of moralism in international and national affairs, their conflation of moralism with morality wrongly leads them to an exaltation of the pursuit of national interest and to the rejection of policies and judgements that are not in fact moralistic. (shrink)

El debate que se gestó alrededor del concepto de existencia en manos de Willard Van Orman Quine y Rudolf Carnap, dio al siglo XX un cúmulo de aportes significativos a la ontología. La postura realista, con algunas variantes, de Quine y el criterio anti-realista de Carnap, otorga insumos para pensar de mejor forma cómo se intenta dar descripciones acerca del inmobiliario del mundo. Conocer este debate es importante, ya que, se expone los alcances y limitaciones que implican las explicaciones ontológicas (...) acerca de la realidad que deben ser tenidas en cuenta en la actualidad. Este trabajo cumple esa función, la de explicar sintéticamente uno de los debates más importantes para la ontología. (shrink)

Any attempt to justify war in the fashion of just war theories risks underestimating its morally problematic nature. This becomes clear if we ask how the individual soldier or citizen is supposed to use just war theory in his own thinking. Michael Walzer's recent book, Just and Unjust Wars, illustrates the problem nicely. Walzer's view is that whether a state is justified in going to war is not a matter for the citizen to judge, and with regard to the way (...) the war is conducted the individual soldier can have only minimal moral responsibility for what is done. Walzer's position is criticized in detail and the conclusion drawn that such an understanding of just war theory undermines the theory's significance as a moral outlook on war. It is also argued that a more pertinent version of just war theory must have strong implications for social change. (shrink)

Objective: To analyse the time variation of topics in bioethical publications as a proxy of the relative importance.Methods: We searched the Medline database for bioethics publications using the words “ethics or bioethics”, and for 360 specific topics publications, associating Medical Subject Heading topic descriptors to those words. We calculated the ratio of bioethics publications to the total publications of Medline, and the ratio of each topic publications to the total bioethics publications, for five-year intervals, from 1970 to 2004. We calculated (...) the time variation of ratios, dividing the difference between the highest and lowest ratio of each topic by its highest ratio. Four topics were described, selected to illustrate different patterns of variation: “Induced Abortion”, “Conflict of Interest”, “Acquired Immunodeficiency Syndrome”, “Medical Education.”Results: The ratio of bioethics publications to total Medline publications increased from 0.003 to 0.012. The variation of the topic’s ratios was higher than 0.7 for 68% of the topics. The Induced Abortion ratios decreased from 0.12 to 0.02. Conflict of Interest ratios increased from zero to 0.07. The Acquired Immunodeficiency Syndrome ratios were nearly zero in the first three intervals, had a peak of 0.06 during 1985–9, followed by a decrease to 0.01. Medical Education ratios varied few, from 0.04 to 0.03.Conclusions: There was an increase of bioethical publications in the Medline database. The topics in bioethics literature have an important time variation. Some factors were suggested to explain this variation: current legal cases, resolution of the issue, saturation of a discussion and epidemiologic importance. (shrink)