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 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)

Islamic ethics in the light of Koranic teachings.

David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USA: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to (...) pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets, neuronal cells, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

In 1982, Jonsen, Siegler and Winslade published Clinical Ethics, in which they described the “four quadrants” approach, a new method of analysing clinical ethics cases. Although the book is now in its 6th edition, a literature search has revealed only one academic paper demonstrating the method at work. This paper is an attempt to start filling this gap. As a way of describing and testing the approach, I apply the four quadrants method to a detailed clinical ethics case. The analysis (...) is interspersed with reflections on the method itself. It is hoped that this experiment will encourage ethicists and clinicians to devote more attention to this neglected approach. (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.

The medical profession’s role should be limited to advice and informationThe medical establishment’s desire to interfere with the autonomous wishes of boxers seems at odds with the principle of respect for autonomy prevalent in contemporary biomedical practice. I argue that the role of the medical profession in boxing should be solely an advisory and informational one. In addition, the distinctions made between boxing and other high risk sports often rely on an insufficient knowledge of the sport. This leads to misdirected (...) criticisms and excessive emphasis on the colourful discourse of boxing, as opposed to the practice of boxing itself. Dr Herrera’s claim in his article that boxing differs from other sports in the acceptability of its acts outside the realm of sport is refuted.1 The importance of consent as a legitimising factor is highlighted, and a number of possible solutions to improve safety within the sport are tentatively suggested.In the United Kingdom, a competent adult may legally refuse medical treatment, irrespective of the severity of his condition or the validity of his reasons. With the pre-eminence of an autonomy based model of bioethics, respecting a patient’s wishes forms an integral part of acting in his best interests. It is puzzling, then, to find that the Australian Medical Association have called for a ban on boxing on the grounds that the activity is excessively hazardous to the health of boxers. The often mentioned principle of respect for autonomy is abandoned once the person drops the privileged title of “patient”. This suggests that being a patient …. (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.

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...