The RNAi machinery is not only involved with post‐transcriptional degradation of messenger RNAs, but also used for targeting of chromatin changes associated with transcriptional silencing. Two recent papers determine the global patterns of gene expression and chromatin modifications produced by the RNAi machinery in fission yeast.(9, 10) The major sites include the outer centromere repeats, the mating‐type locus and subtelomeric regions. By comparison, studies of Arabidopsis heterochromatin also implicate transposons as a major target for silencing. Analyses of siRNA libraries from (...) Drosophila, nematodes and Arabidopsis indicate that major repeats at centromeres, telomeres and transposable elements are likely targets of RNAi. Also, intergenic regions are implicated as targets in Arabidopsis. BioEssays 27:1209–1212, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The determination of the place of life in nature has been a major philosophic issue. Some, in their attempt to show the continuity of nature, have resorted to the reductive method and have argued that the living differ in no significant sense from the non-living, unless it be in their complexity; others, in their desire to emphasize the qualitatively varied aspects of nature, have drifted to disjunctive method and have claimed that there is an unbridgeable gap between the living and (...) the non-living. Yet life in its natural setting presents both continuity with the physical world and a distinctive difference from it. One need neither sunder the continuity in nature nor deny the empirically observable qualitative differences. It is this principle that will guide the present discussion of life. (shrink)

Meanings have an empirical genesis and status. This simple claim has often been denied or ignored. Some metaphysicians in their exaltation of the eternal have regarded meanings as essences, or eternal objects, or neutral entities, in a subsistential or supernatural realm that is changeless and has no roots in nature. Some logicians in their zest to manipulate meanings isolate them so completely as forms of reason, or as syntactical symbols that at no point is their connection with natural events made (...) intelligible. Yet meanings, all meanings, have relation to mind. It is this empirical, psychological aspect of meaning that I shall analyze. The larger philosophic question as to what the relation of the psychological aspect is to the metaphysical or the logical will not concern us except indirectly. (shrink)

All these activities of living beings, and the functioning of their organs, and the functioning of instruments demand a teleological explanation. Why do human beings toil? Why do living beings try to maintain the activities of the organism? What are the functions of specific organs or instruments? Intelligible answers can be given in teleological terms. Of course, one could ask many questions about these situations that would not require the teleological explanation; for example, questions concerning the mechanical structure of living (...) beings or of instruments. Yet this fact would not eliminate the legitimacy nor the utility of the teleological category. (shrink)

All these activities of living beings, and the functioning of their organs, and the functioning of instruments demand a teleological explanation. Why do human beings toil? Why do living beings try to maintain the activities of the organism? What are the functions of specific organs or instruments? Intelligible answers can be given in teleological terms. Of course, one could ask many questions about these situations that would not require the teleological explanation; for example, questions concerning the mechanical structure of living (...) beings or of instruments. Yet this fact would not eliminate the legitimacy nor the utility of the teleological category. (shrink)

One of the hot research topics today is relationship marketing. However, little research has been carried out in understanding the complex concepts of Guanxi (relationship) in a Chinese society. This research describes a study to operate the constructs of guanxi and explores the importance of guanxi in relationship development in order to present a new Guanxi framework. A study of both Western and Chinese literature provides foundations of the Guanxi perspectives. The constructs of adaptation, trust, opportunism and favour are identified. (...) Adaptation and trust are found to be positively correlated with sales stability and quality. Whilst, adaptation is negatively correlated with relationship termination costs. Both theoretical framework (a new perceptual map) and managerial implications are given. In addition, recommendations for future research are made. (shrink)

The image of nature as causality has been a major theme of science and poetry. It has been a symbol of hope and fear, of progress and futility. Yet its meaning has seldom been clear. Prior to any statement about the relation of causality to physical nature, life, and mind, its meaning should be established. I shall therefore first define causality, and I shall then discuss its applicability to nature.

If a hereditary predisposition to colorectal cancer or breast cancer is diagnosed, most guidelines state that clinical geneticists should request index patients to inform their at-risk relatives about the existence of this condition in their family, thus enabling them to consider presymptomatic genetic testing. Those identified as mutation carriers can undertake strategies to reduce their risk of developing the disease or to facilitate early diagnosis. This procedure of informing relatives through the index patient has been criticised, as it results in (...) relatively few requests for genetic testing, conceivably because a certain number of relatives remain uninformed. This pilot study explored attitudes toward informing family members and relevant practices among clinical geneticists. In general, clinical geneticists consider it to be in the interests of family members to be informed and acknowledge that this goal is not accomplished by current procedures. The reasons given for maintaining present practices despite this include clinical ‘mores’, uncertainty about the legal right of doctors to inform family members themselves, and, importantly, a lack of resources. We discuss these reasons from an ethical point of view and conclude that they are partly uninformed and inconsistent. If informing relatives is considered to be in their best interests, clinical geneticists should consider informing relatives themselves. In the common situation in which index patients do not object to informing relatives, no legal obstacles prevent geneticists from doing so. An evaluation of these findings among professionals may lead to a more active approach in clinical practice. (shrink)

Florijn’s helpful discussion of the Heringa case illustrates the difficulties in drawing a boundary on eligibility conditions for EAS. In Heringa, the Dutch Supreme Court reaffirmed...

Should the assessment of decision‐making capacity (DMC) be risk sensitive, that is, should the threshold for DMC vary with risk? The debate over this question is now nearly five decades old. To many, the idea that DMC assessments should be risk sensitive is intuitive and commonsense. To others, the idea is paternalistic or incoherent, or both; they argue that the riskiness of a given decision should increase the epistemic scrutiny in the evaluation of DMC, not increase the threshold for DMC. (...) We respond to the critics’ main concerns by providing a comprehensive account of how risk‐sensitive DMC is coherent, avoids paternalism, and best fulfills the epistemic goal of DMC evaluations. (shrink)

Book Information On the Emotions. By R. Wollheim. Yale University Press. New Haven/London. 1999. Pp. xiii + 269. Hardback, US$25.00.

Subjects enrolled in studies testing high risk interventions for incurable or progressive brain diseases may be vulnerable to deficiencies in informed consent, such as the therapeutic misconception. However, the definition and measurement of the therapeutic misconception is a subject of continuing debate. Our qualitative pilot study of persons enrolled in a phase I trial of gene transfer for Parkinson disease suggests potential avenues for both measuring and preventing the therapeutic misconception. Building on earlier literature on the topic, we developed and (...) tested an interview guide that focuses on how the subjects decided to participate, emphasizing the integration of subjects’ various statements that are relevant to assessing the therapeutic misconception, rather than evaluating them as isolated statements. The results indicate that a subject’s understanding of the purpose of research is best explored in juxtaposition to the subject’s motivation for participating. (shrink)

By the time this essay is published, it will be a matter of weeks before doctors and nurse practitioners in Canada can legally end the lives (by medical assistance in dying, or MAID) of non-dying p...

Although informed consent is important in clinical research, questions persist regarding when it is necessary, what it requires, and how it should be obtained. The standard view in research ethics is that the function of informed consent is to respect individual autonomy. However, consent processes are multidimensional and serve other ethical functions as well. These functions deserve particular attention when barriers to consent exist. We argue that consent serves seven ethically important and conceptually distinct functions. The first four functions pertain (...) principally to individual participants: (1) providing transparency; (2) allowing control and authorization; (3) promoting concordance with participants' values; and (4) protecting and promoting welfare interests. Three other functions are systemic or policy focused: (5) promoting trust; (6) satisfying regulatory requirements; and (7) promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals. (shrink)

Shavelson et al. (2023) raise the familiar question of parity or fairness in the assisted dying1 debate: if we legally permit the practice for one person, should we not permit everyone similarly si...

The Patient Preference Predictor (PPP) proposal places a high priority on the accuracy of predicting patients’ preferences and finds the performance of surrogates inadequate. However, the quest to develop a highly accurate, individualized statistical model has significant obstacles. First, it will be impossible to validate the PPP beyond the limit imposed by 60%–80% reliability of people’s preferences for future medical decisions—a figure no better than the known average accuracy of surrogates. Second, evidence supports the view that a sizable minority of (...) persons may not even have preferences to predict. Third, many, perhaps most, people express their autonomy just as much by entrusting their loved ones to exercise their judgment than by desiring to specifically control future decisions. Surrogate decision making faces none of these issues and, in fact, it may be more efficient, accurate, and authoritative than is commonly assumed. (shrink)

Volume 19, Issue 10, October 2019, Page 3-7.

Most jurisdictions require that a mental capacity assessment be conducted using a functional model whose definition includes several abilities. In England and Wales and in increasing number of countries, the law requires a person be able to understand, to retain, to use or weigh relevant information and to communicate one’s decision. But interpreting and applying broad and vague criteria, such as the ability ‘to use or weigh’ to a diverse range of presentations is challenging. By examining actual court judgements of (...) capacity, we previously developed a descriptive typology of justifications used in the application of the Mental Capacity Act criteria. We here critically optimise this typology by showing how clear definitions—and thus boundaries—between the criteria can be achieved if the ‘understanding’ criterion is used narrowly and the multiple rationales that fall under the ability to ‘use or weigh’ are specifically enumerated in practice. Such a typology-aided practice, in theory, could make functional capacity assessments more transparent, accountable, reliable and valid. It may also help to create targeted supports for decision making by the vulnerable. We also discuss how the typology could evolve legally and scientifically, and how it lays the groundwork for clinical research on the abilities enumerated by the MCA. No data are available. This paper does not report any original data. (shrink)

We are grateful to Jongsma et al 1 for their interest in our article analysing the case of ‘Mrs A’, a Dutch woman with Alzheimer’s disease who received euthanasia based on her advance euthanasia directive.2 Their commentary criticises two elements of our analysis. First, the authors believe our reasons for doubting that Mrs A had the capacity to write and revise an AED rely on ‘partial’ empirical data and rest on normative errors. Second, they use two of our statements to (...) suggest we must endorse some implausible claims, for example, that ‘… in all situations and for all people, current well-being should always take precedence over all other values’. Jongsma et al assert: ‘Miller et al argue that people with dementia are impaired to make decisions.’ This casts our probabilistic claim about Mrs A’s capacity as an absolute claim about persons with dementia in general. It also implies we are using an outdated diagnosis-based view of capacity. The accusation then becomes explicit : > … several empirical studies have shown that patients with dementia are able to actively participate in qualitative studies and can respond to open questions in a meaningful way,[2-8] as well that they are able to complete an advance directive in the early phases of dementia.[9, 10] One can therefore not simply conclude on the basis of the diagnosis of dementia …. (shrink)

Bioethicists have long been concerned that seriously ill patients entering early phase (‘phase I’) treatment trials are motivated by therapeutic benefit even though the likelihood of benefit is low. In spite of these concerns, consent forms for phase I studies involving seriously ill patients generally employ indeterminate benefit statements rather than unambiguous statements of unlikely benefit. This seeming mismatch between attitudes and actions suggests a need to better understand research ethics committee members’ attitudes toward communication of potential benefits and risks (...) of early phase studies to potential subjects. We surveyed the members of two U.S. research ethics committees using a phase I gene transfer study scenario, and compared the results to a previous survey of potential subjects’ perceptions and attitudes toward benefit and risk for the same protocol. The results show that there is indeed a gap between the subjects’ perceptions and the committee members’ views on what is appropriate to be communicated to research subjects. This discrepancy is the product of both the commonly assumed optimism of the subjects and to a “protective pessimism” of the research ethics committee members. We discuss this discrepancy using “frameworks of trust” and demonstrate the need to incorporate these frameworks into the existing model of informed consent. (shrink)