Background: Concern has been expressed about the process of consent to clinical trials, particularly in phase I “first-in-man” trials. Trial participant information sheets are often lengthy and technical. Content-based readability testing of sheets, which is often required to obtain research ethics approval for trials in the USA, is limited and cannot indicate how information will perform. Methods: An independent-groups design was used to study the user-testing performance of the participant information sheet from the phase I TGN1412 trial. Members of the (...) public were asked to read it, then find and demonstrate understanding of 21 key aspects of the trial. The participant information sheet was then rewritten, redesigned and tested on 20 members of the public, using the same 21-item questionnaire. Results: On the original TGN1412 participant information sheet, participants could not find answers and some of the found information was not understood. Six of 21 questions, including those relating to placebo, follow-up visits and the emergency phone number, were found by eight or fewer of 10 participants. The revised information sheet performed better, with the answers to 17 of 21 questions found and understood by all 20 participants. Conclusions: Tests showed that the TGN1412 participant information sheet may not inform participants adequately for consent. Revising its content and design led to significant improvements. Writers of materials for trial participants should take account of good practice in information design. Performance-based user testing may be a useful method to indicate strengths and weaknesses in trial materials. (shrink)

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe symptoms of (...) autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (shrink)

Sextus Empiricus does not reveal anything of himself as distinct from ‘the Sceptic’ except in a passing and incidental way. He does not refer to his contemporaries, nor to his country, nor to any personal experiences, in such a way as to provide a definite picture of his life and times. The few references he makes to his involvement in the medical profession are as perplexing as they are enlightening. The only attachments which Sextus strongly identifies with in his extant (...) writings are the demands of the Pyrrhonean philosophy. (shrink)

I question whether the flourishing that McMullin presents as negotiating the demands of three distinct normative domains is itself normative. If it is, I argue it must be incremental in some way to...

Weil’s essay on Homer’s Iliad contains a philosophical analysis of la force that divides it into two phenomena with one metaphysical ground. Her analysis is a corrective to misunderstandings of force as something that can be possessed. The first half of my elaboration of Weil’s analysis is devoted to the phenomena she identifies in relation to la force, which I call might. In the second half, I elaborate the varieties of misunderstanding of la force. First, might is an illusion sustained (...) by the shared belief of those in submission to might. Second, forces, i.e. the material forces on which weaponry depends, cannot be possessed. Third, what lies behind material forces is necessity, a third meaning of la force, which functions as a superordinate or ultimate force to which everyone and everything is subject. Understanding the last of these is the corrective that Weil means to present. (shrink)

Provision of additional food supplements for the purpose of biological conservation has been widely researched both theoretically and experimentally. The study of these biosystems is usually done using predator–prey models. In this paper, we consider an additional food provided predator–prey system in the presence of the inhibitory effect of the prey. This model is analyzed in the control parameter space using the control parameters, quality and quantity of additional food. The findings suggest that with appropriate choice of additional food to (...) predators, the biosystem can be controlled and steered to a desirable state. It is also possible to eliminate either of the interacting species. The vital role of the quality and quantity of the additional food in the system dynamics cautions the eco manager on the choice of the additional food for realizing the goal in the biological conservation programme. (shrink)

The public revelation in 2003 that medical students perform intimate examinations without patient consent has engendered much debate in the press and scientific journals. Using this case as a springboard for discussion, I will argue that medical schools should encourage students to raise their ethical concerns and call for a change of policy making it easier for students to do so. I will also address the question of medical students’ moral obligations towards their patients, and conclude that medical students ought (...) to express their discontent when faced with unethical practices or attitudes.In early January 2003, a study appeared in the British Medical Journal revealing that nearly a quarter of rectal and vaginal examinations on anaesthetised patients were performed by medical students without patient consent.1 Although the study did not generate the firestorm of controversy many expected, it engendered much discussion on ethical issues surrounding informed consent and patient autonomy, as well as stressing the need for greater ethics training for medical students. As an ethical problem, however, the case of intimate examinations is, to my mind, relatively uninteresting. If we agree that it is wrong for doctors to perform a vaginal examination on a conscious person without their consent, then it follows that it will still be …. (shrink)

This study examined the relationship between unethical employee behavior and the dimensions of the Ethical Climate Questionnaire (ECQ). In order to explore the relationship between the dimensions of the ECQ and unethical behavior, the factor structure of five previously identified empirical models and the hypothesized nine-dimension model for the ECQ was tested with a confirmatory factor analysis. The analysis revealed that the hypothesized nine-dimension model provided as good or even better fit to the data than the five empirically derived models. (...) Therefore, the nine-dimensional model was used to examine the criterion-related validity of the ECQ. The results demonstrated that the nine ethical climate dimensions were correlated with some of the unethical behaviors examined in this study, but not others. However, the results clearly demonstrated that most of the ethical climate dimensions were significantly related to an aggregate measure of unethical behavior. It was suggested that these results might account for the differences in previous studies on the criterion-related validity of the ECQ. The results also replicated a previous report that the association between unethical behavior and ethical climate is stronger in organizations that do not have a code of ethics. Finally, a difference was observed in the ethical climates for organizations with a code of ethics and organizations without a code of ethics. (shrink)

The problem of the human individual and the multiple manifestations of the essence of that individual made its appearance along with that of human beings themselves. Having arisen at the dawn of history, as a product of the as-yet-primitive consciousness of the primeval human, this problem, constantly developing and changing in form in accordance with the socio-economic conditions of the life of society, is assuming increasingly pervasive significance. The mandate of the ancients to "Know thyself" today has the ring not (...) only of a troubling need for individual self-awareness, and therefore of a heuristic problem in natural science and philosophy, but also of a categorical social imperative. (shrink)

It is conventional to try to arrive at the Boltzmann principle and the Second Law starting with the laws of dynamics at the microscopic level. In this article the opposite view is presented: Starting with the Second Law, microscopic properties are derived. A classical result of Wien is developed into a general theorem, and the possibility of deriving the Boltzmann principle as a consequence of Carnot's theorem is discussed.

Scientific developments of the last 20 years have made the transplantation of cadaveric solid organs a viable and expected treatment alternative for patients suffering from various forms of End Stage Organ Disease. Of the number of organs that could be utilized for this, only a small percentage of them are actually made available. North American legislation explicitly categorizes the transfer of cadaveric organs as an anatomical or tissue “gift”. The concept of the gift is mediated by transculturally consistent unwritten, but (...) powerfully felt, rules of conduct. Among the most profound elements of the concept is the obligatory gift-exchange which is central to the gift-relationship. Obviously, neither of these are permitted by the organ transplant scenario. As a result, dissonance is created within the thought process of the individual which cannot be easily resolved, paralyzing many into inaction. We maintain that the present legal framework, designed to facilitate the transfer of organs, clashes with the human phenomenon of giving, and may actually prevent organs from being made available. In a search for a solution to this gift-relationship dilemma, giving organs is contrasted with taking organs as a basis upon which to ground ethically sound public policy. Liberty-limiting principles and the concept of harm are considered within this context. (shrink)

This work is a volume in the series Ancient Commentators on Aristotle, edited by Richard Sorabji. The aim of the series is to make the Greek commentaries available in English. Konstan does an admirable job of this. The translation is extremely careful, clear, and readable. Konstan succeeds in staying close to the text without sacrificing intelligibility. Whenever necessary, he inserts words or phrases in brackets to complete the sense of an accurately translated passage. Konstan also makes use of brackets to (...) give precise citations to fill out Simplicius' references. The footnotes, too, are excellent. There the reader finds information about deviations from Diels's text, about alternative readings, and explanations of renderings into English that might be controversial. In the introduction, Sorabji gives a thumbnail sketch of the philosophical issues raised by Physics 6. Several useful documents are appended to the commentary, namely, a list of all departures from Diels's text, an appendix written by the editor providing a brief survey of the ancient Greek commentators, and a list of the philosophers cited by Simplicius with a onesentence description of each. (shrink)

Context: Few professional philosophers have addressed in any detail radical constructivism, but have focused instead on the related assumptions and limitations of postmodern epistemology, various anti-realisms, and subjective relativism. Problem: In an attempt to supply a philosophical answer to the guest editors’ question, “Why isn’t everyone a radical constructivist?” I address the realist (hence non-radical) implications of the theory’s invocation of “others” as an invariable, observer-independent, “external” constraint. Results: I argue that constructivists cannot consistently defend a radically subjectivist theory of (...) knowing while remaining entirely agnostic about the nature and existence of the larger world (including independent others). That is, any non-solipsistic account of human experience must explicitly acknowledge its extra-subjective, ontological dimension. Implications: It follows that no pedagogical, social, philosophical, or commonsensical insight associated with so-called “trivial” or “social” constructivism survives or receives any support from the move to radical constructivism. (shrink)

Theoretical and experimental studies on prey–predator systems where predator is supplied with alternate sources of food have received significant attention over the years due to their relevance in achieving biological conservation and biological control. Some of the outcomes of these studies suggest that with appropriate quality and quantity of additional food, the system can be steered towards any desired state eventually with time. One of the limitations of previous studies is that the desired state is reached asymptotically, which makes the (...) outcomes not easily applicable in practical scenarios. To overcome this limitation, in this work, we formulate and study optimal control problems to achieve the desired outcomes in minimum (finite) time. We consider two different models of additional food provided prey–predator systems involving Holling type IV functional response (with inhibitory effect of prey). In the first scenario, additional food is incorporated implicitly into the predator’s functional response with a possibility of achieving biological conservation through co-existence of species and biological control by maintaining prey at a level that is least harmful to the system. In the second, the effect of additional food is incorporated explicitly into the predator’s compartment with the goal of pest management by maintaining prey density at a very minimal damaging level. For both cases, appropriate optimal control strategies are derived and the theoretical findings are illustrated by numerical simulations. We also discuss the ecological significance of the theoretical findings for both models. (shrink)

The interest in supererogation and supererogatory actions derives from the perception that there is something problematic about them. I shall argue that there is nothing problematic about them. The perception to the contrary arises from preconceptions common in ethical theory. When these are relaxed or dismissed, supererogatory actions are easily assimilated as well-motivated, responses to moral situations. Assimilating, rather than denying, them is important for a sound moral philosophy.