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)

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)

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)

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)

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)

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)

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)

At Theaetetus 163d-164b Socrates objects to the thesis that knowledge is perception by pointing out that a man who has seen something can still remember it, and so has knowledge of it; but this is impossible, if knowledge is perception, since he is no longer perceiving it.To this Protagoras is made to reply with two sentences at 166b 1–4:.Cornford translates ‘ For instance, do you think you will find anyone to admit that one's present memory of a past impression is (...) an impression of the same character as one had during the original experience, which is now over? It is nothing of the sort’.Cornford understands this as the suggestion that the memory and the original perception are of different things: ‘ All that the objection in fact established was that “ perception” must be stretched to include awareness of memory images’. So too Lee: ‘Protagoras’ “way out”… appears to be to say that what we now know is not properly X but rather our memory trace of X - some present πά θ ο ς quite distinct from X and very different from that ’. McDowel. (shrink)

When disaster disrupts healthcare and other systems, the ethical allocation of resources should follow principles of justice, defined as fairness, established for normal clinical practice. Standards of clinical practice may be altered during disaster, but ethical standards must remain centered on prioritizing the treatment of patients according to need and the effectiveness of treatment. Should resources become extremely limited, it is fair to restrict their use to patients who have the highest needs, provided that the intervention is effective. When resources (...) become more available, patients with lower priority can be increasingly accommodated. (shrink)

The first solid bit of argumentation you get in Plato's Phaedo goes something like this: Whatever comes to be, comes to be from its opposite. If at a certain time t a given thing a begins to be F, before that time t it must have been non-F. Wherever a pair of predicates, F and G, are genuine contradictories; where, that is, they stand to each other in the same relation as F stands in to non-F; it is necessarily true (...) that if a began to be F at t before then a was G. The only trouble comes from the difficulty of finding substitutes for F and G that people will allow to be genuine contradictories. It the butter began to be soft at four o'clock, we may suggest, before four it was hard. A tiresome opponent will retort that there is a state in which butter cannot properly be called either hard or soft. We try again: If Ann began to be asleep at eight, before eight she was awake; if my shirt became dirty on Tuesday, before Tuesday it was clean; if Bonzo died last week, before last week he was alive. And when the advocate of the borderline state reminds us of the various twilight areas of consciousness or cleanliness, we are reduced to legislation: “asleep” shall henceforth apply to every mental state short of complete wakefulness, “alive” to every condition of the body before the onset of putrefaction, “clean” to every shirt incapable of producing a certain measurable discoloration in the water in which it is washed. “Let F and G be contradictories”, we still guardedly maintain: “then if a comes to be F at time t, before time t a was G”. (shrink)

The extraordinary events surrounding the measles, mumps, and rubella vaccine in the United Kingdom have not only placed in jeopardy the use of this triple vaccine but have also spread concern to other parts of the world. Examination of the public’s worry about MMR vaccine reveals they have been exposed to a range of conflicting views resulting in the feeling of having been misled about the safety of the vaccine. There are various groups and individuals who have legitimate roles in (...) informing the public about such subjects. But is each one behaving in an ethically responsible way? And if confidence falters, vaccine coverage dips, and an outbreak of measles, mumps, or rubella ensues, who, if anyone, will stand and say “I misled them, I confused them, this is my responsibility”? We examine the ethical issues of each group with a voice in the debate about vaccine safety. (shrink)

Kaplan claims that (1) ‘I am here now’, though analytic, is not a necessary truth. But this sentence is not a proposition, in a sense of proposition in which some, but not all, sentences are propositions. Since it is not a proposition, it is not true, and consequently not analytic. It is in fact a fragment of a proposition, the same fragment as ‘he was there then’ in (2) ‘CJFW said in Oxford on 23 September 1991 that he was there (...) then’. Sentences containing indexicals in general owe their sense to the corresponding fragments of sentences containing ‘quasi‐indexicals’(‘then’, for example, is the quasi‐indexical to ‘now’ as indexical). Someone uttering (1) assertively will thereby make a proposition like (2) true. (2) entails (3) ‘CJFW said in Oxford on 23 September 1993 that CJFW was in Oxford on 23 September 1991′. So by uttering (1) in the appropriate circumstances I made it true that I had asserted the proposition (4) ‘CJFW was in Oxford on 23 September 1991′. What is analytic and necessarily true is the proposition ‘If (3) then (4)’. (shrink)

ABSTRACT In his paper ‘The Survival Lottery’John Harris suggested that there could be situations where the rational thing to do would be to kill a healthy person and harvest his organs for transplantation, thereby saving several lives at the cost of one. Anne Maclean claims that such a proposal, far from being rational, does not qualify as a moral proposal at all since what it suggests is ‘plain murder’. I argue that she is correct to claim that the proposal is (...) not uniquely rational and that doctors could quite rationally reject it, but that she overreaches herself when she holds it not to be a moral proposal at all. (shrink)