The mechanistic significance of a kinetic isotope effect on a cytochrome P‐450catalyzed reaction depends, fundamentally, on the nature of the interaction of the substrate with the active site of the enzyme as well as on the nature of the chemistry of the reaction catalyzed. Consequently, kinetic isotope effects can be used to extract information on the topology of the enzyme and the mechanism of substrate oxidation. Kinetic isotope effect studies are sometimes accompanied by ‘metabolic switching’ or a change in metabolic (...) pathway, catalyzed either by the same enzyme or by a different enzyme. For the specific case where ‘metabolic switching’ gives rise to a change in regional specificity for the cytochrome P‐450 catalyzed metabolism of a compound, this change can be explained in terms of the topological constraints on substrate binding imposed by the active site of the enzyme. (shrink)

Explaining how stereotypes and norms influence role-identities during reflected appraisal processes, we develop a theory about diverse groups of minority men—the “minority masculinity stress theory”—and apply it to Asian American men. We conceptually integrate hegemonic masculinity, stereotypes, and mental health to examine how Asian American men experience masculinity and how their experiences are uniquely stressful. We analyze elicited text from an open-ended questionnaire to explain two experiences of masculinity-related stress: trying to live up to the masculine ideal and enacting work-related (...) role-identities. Regarding the former, we discuss four illustrations—toughness, body image, restrictive emotionality, and heterosexuality—and two involving the latter—achiever and provider. We found that Asian American men receive stereotypical reflected appraisals that contradict potentially positive self-concepts and emphasize achievement beyond typical standards of hegemonic masculinity. Moreover, Asian American men’s role-identities contradict hegemonic masculinity, resulting in reflected appraisals that predispose them toward stress. (shrink)

Theorists, historians, and artists address the precarious futurity of the notion of the future. Not long ago, a melancholic left and a manic neoliberalism seemed to arrive at an awkward consensus: the foreclosure of futurity. Whereas the former mourned the failure of its utopian project, the latter celebrated the triumph of a global marketplace. The radical hope of realizing a singularly different, more equitable future displaced by a belief that the future had already come to pass, limiting post-historical society to (...) an uneventful life of endless accumulation. Today, amidst an abundance of neofuturisms, posthumanisms, futurologies, speculative philosophies and accelerationist scenarios, there is as well an expanding awareness of a looming planetary catastrophe driven by the extractionist logic of capitalism. Despite this return to the future, the temporal horizon of our present moment is perhaps more aptly characterized by the “shrinking future” of just-in-time production, risk management, high-frequency trading, and the futures market. In Futurity Report, theorists, historians, and artists address the precarious futurity of the notion of the future itself. Contributors McKenzie Wark, China Miéville, Kerstin Stakemeier, Diedrich Diederichsen, Natascha Sadr Haghighian, Marina Vishmidt, Johannes Paul Raether, Felicity D. Scott, Silvia Maglioni, Graeme Thomson, Doreen Mende, Pedro Neves Marques, Achille Mbembe, Kodwo Eshun, Haytham El-Wardany, T. J. Demos, Ana Teixeira Pinto. (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...

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)

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...