sirIn a scholarly and thought-provoking paper, Clarke sets out to debunk the concept of “rational suicide” as nonsensical.1 His motivation in this is to undermine any support that the notion of rational suicide might give to a “categorical right to suicide”. If his enterprise were successful, however, it would go far beyond the “rights issue” and would have a profound impact on all arguments raised in support of euthanasia or physician-assisted suicide.Clarke's major thrust might be termed the argument from posthumous (...) ignorance. He begins with a claim that the process of making a rational decision involves the process of “gaining all possible facts and `imagining' all possible consequences”. He goes on to say that making a rational decision “in the consideration of life or death . . . would seem to be impossible”. It is “impossible” …. (shrink)

Using a longitudinal case study design, we have tracked the recovery of motor function following severe traumatic brain injury (TBI) through a multimodal neuroimaging approach. In 2006, Canadian Soldier Captain (retired) Trevor Greene (TG) was attacked with an axe to the head while on tour in Afghanistan. TG continues intensive daily rehabilitation, which recently included the integration of physical therapy (PT) with neuromodulation using translingual neurostimulation (TLNS) to facilitate neuroplasticity. Recent findings with PT+TLNS demonstrated that recovery of motor function occurred (...) beyond conventional time limits, currently extending past 14-years post-injury. To investigate whether PT+TLNS similarly resulted in associated cognitive function improvements, we examined event-related potentials (ERPs) with the brain vital signs framework. In parallel with motor function improvements, brain vital signs detected significant increases in basic attention (as measured by P300 response amplitude) and cognitive processing (as measured by contextual N400 response amplitude). These objective cognitive improvements corresponded with TG’s self-reported improvements, including a noteworthy and consistent reduction in ongoing symptoms of post-traumatic stress disorder (PTSD). The findings provide valuable insight into the potential importance of non-invasive neuromodulation in cognitive rehabilitation, in addition to initial indications for physical rehabilitation. (shrink)

A crisis continues to brew within the pharmaceutical research and development (R&D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&S) methods. We suggest strategies and scenarios intended to enable new M&S use cases that directly engage R&D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&S requirements (...) must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&S should be actualized within a larger information technology framework—a dynamic knowledge repository—wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

"Neuroscience and Philosophy" begins with an excerpt from "Philosophical Foundations of Neuroscience," in which Maxwell Bennett and Peter Hacker question the ...

In the last decade the use of advance directives or living wills has become increasingly common. This paper is concerned with those advance directives in which the user opts for withdrawal of active treatment in a future situation where he or she is incompetent to consent to conservative management but where that incompetence is potentially reversible. This type of directive assumes that the individual is able accurately to determine the type of treatment he or she would have adopted had he (...) or she been competent in this future scenario. The paper argues that this assumption is flawed and provides theoretical and empirical evidence for this. If the assumption is false, and those taking out advance directives do not realise this, then the ethical bases for the use of these advance directives-the maximisation of the individual's autonomy and minimisation of harm-are undermined. The paper concludes that this form of advance directive should be abolished. (shrink)

Through discourse with international groups of physicians, we conducted a cross-cultural analysis of the types of ethical dilemmas physicians face. Qualitative analysis was used to categorise the dilemmas into seven themes, which we compared among the physicians by country of practice. These themes were a-theoretically-driven and grounded heavily within the text. We then subjected the dilemmas to an analysis of moral intensity, which represents an important theoretical perspective of ethical decision making. These constructs represent salient determinants of ethical behaviour and (...) our cross-cultural sample afforded us the opportunity to consider both the pragmatic aspects of culture, as they are perceived by physicians, as well as the theory-driven concept of moral intensity. By examining both culture and moral intensity, we hope to better elucidate the complexities of ethical decision-making determinants among physicians in their daily practice. Doing so may potentially have practical implications for ethics training of medical students and foreign physicians. (shrink)

Body integrity identity disorder is a very rare condition in which people experience long-standing anguish because there is a mismatch between their bodies and their internal image of how their bodies should be. Most typically, these people are deeply distressed by the presence of what they openly acknowledge as a perfectly normal leg. Some with the condition request that their limb be amputated. 1 We and others have argued that such requests should be acceded to in carefully selected patients.1–4 Consistent (...) with this view, a group at the University of Sydney is developing a programme to better understand and treat BIID and to offer amputation if appropriate. In a recent paper, Patrone argues that such amputations should be prohibited.5 He suggests that authors supporting amputation in BIID depend on analogies with more familiar conditions and then claim that the ‘the desires, choices and requests of BIID patients should be held to exactly the same standards and treated with exactly the same respect as the desires, choices and requests of any more conventional patient’.5 He believes that these analogies are invalid and that therefore the arguments for amputation are invalid.Patrone concentrates a great deal upon whether a decision to have a particular medical intervention is to be regarded as ‘rational’. Unfortunately, he makes no attempt to define what he …. (shrink)

Is there ever any reason for a doctor to lie to a patient? In this paper, we critically review the literature on lying to patients and challenge the common notion that while lying is unacceptable, a related entity--'benevolent deception' is defensible. Further, we outline a rare circumstance when treating psychotic patients where lying to the patient is justified. This circumstance is illustrated by a clinical vignette.

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)

The slippery slope argument has been the mainstay of many of those opposed to the legalisation of physician-assisted suicide and euthanasia. In this paper I re-examine the slippery slope in the light of two recent studies that examined the prevalence of medical decisions concerning the end of life in the Netherlands and in Australia. I argue that these two studies have robbed the slippery slope of the source of its power--its intuitive obviousness. Finally I propose that, contrary to the warnings (...) of the slippery slope, the available evidence suggests that the legalisation of physician-assisted suicide might actually decrease the prevalence of non-voluntary and involuntary euthanasia. (shrink)

Objectives: The mental health legislation of most developed countries includes either a dangerousness criterion or an obligatory dangerousness criterion (ODC). A dangerousness criterion holds that mentally ill people may be given treatment without consent if they are deemed to be a risk to themselves or others. An ODC holds that mentally ill people may be given treatment without consent only if they are deemed to be a risk to themselves or others. This paper argues that the dangerousness criterion is unnecessary, (...) unethical and, in the case of the ODC, potentially harmful to mentally ill people and to the rest of the community. Methods: We examine the history of the dangerousness criterion, and provide reasoned argument and empirical evidence in support of our position. Results: Dangerousness criteria are not required to balance the perceived loss of autonomy arising from mental health legislation. Dangerousness criteria unfairly discriminate against the mentally ill, as they represent an unreasonable barrier to treatment without consent, and they spread the burden of risk that any mentally ill person might become violent across large numbers of mentally ill people who will never become violent. Mental health legislation that includes an ODC is associated with a longer duration of untreated psychosis, and probably contributes to a poorer prognosis and an increase risk of suicide and violence in patients in their first episode of psychosis. Conclusions: Dangerousness criteria should be removed from mental health legislation and be replaced by criteria that focus on a patient’s capacity to refuse treatment. (shrink)

Cells fine‐tune their DNA repair, selecting some regions of the genome in preference to others. In the paradigm case, excision of UV‐induced pyrimidine dimers in mammalian cells, repair is concentrated in transcribed genes, especially in the transcribed strand. This is due both to chromatin structure being looser in transcribing domains, allowing more rapid repair, and to repair enzymes being coupled to RNA polymerases stalled at damage sites; possibly other factors are also involved. Some repair‐defective diseases may involve repair‐transcription coupling: three (...) candidate genes have been suggested.However, preferential excision of pyrimidine dimers is not uniformly linked to transcription. In mammals it varies with species, and with cell differentiation. In Drosophila embryo cells it is absent, and in yeast, the determining factor is nucleosome stability rather than transcription.Repair of other damage departs further from the paradigm, even in some UV‐mimetic lesions. No selectivity is known for repair of the very frequent minor forms of base damage. And the most interesting consequence of selective repair, selective mutagenesis, normally occurs for UV‐induced, but not for spontaneous mutations. The temptation to extrapolate from mammalian UV repair should be resisted. (shrink)

In this paper we try to answer the question whether diffusion is a possible mechanism to explain mesoderm induction in Amphibians. First the embryological data are discussed and a hypothesis for mesoderm formation is set forth. The blastula being essentially a hollow sphere, we assume that the induction mechanism in an embryo at the blastula stage can be simulated by diffusion-reaction processes on spherical surfaces. A model is constructed for the simple case when the source is held constant with respect (...) to time, the decay proportional to the concentration and the diffusion coefficient a constant, From simulation we find a (best) value for the decay constant to be 6 × 10–5/sec and for the diffusion constant to be 0.24 × 10– 6 cm2/sec. The relation between the parameters is derived from an analytic solution for the diffusion process on a spherical surface with a continuously producing point source and the concentration proportional to the decay. The form and regulative properties of the steady concentration gradient are discussed. (shrink)