WHY DOES A METHOD THAT FAILS CONTINUE TO BE USED?

As a critical framework for addressing a diversity of evolutionary and ecological questions, any method that provides accurate and detailed phylogeographic inference would be embraced. What is difficult to understand is the continued use of a method that not only fails, but also has never been shown to work--nested clade analysis is applied widely even though the conditions under which the method will provide reliable results have not yet been demonstrated. This contradiction between performance and popularity is even more perplexing given the recent methodological and computational advances for making historical inferences, which include estimating population genetic parameters and testing different biogeographic scenarios. Here I briefly review the history of criticisms and rebuttals that focus specifically on the high rate of incorrect phylogeographic inference of nested-clade analysis, with the goal of understanding what drives its unfettered popularity. In this case, the appeal of what nested-clade analysis claims to do--not what the method actually achieves--appears to explain its paradoxical status as a favorite method that fails. What a method promises, as opposed to how it performs, must be considered separately when evaluating whether the method represents a valuable tool for historical inference.     

WHAT DOES RESPECT FOR THE PATIENT'S AUTONOMY REQUIRE?

Personal autonomy presupposes the notion of rationality. What is not so clear is whether, and how, a compromise of rationality to various degrees will diminish a person's autonomy. In bioethical literature, three major types of threat to the rationality of a patient's medical decision are identified: insufficient information, irrational beliefs/desires, and influence of different framing effects. To overcome the first problem, it is suggested that patients be provided with information about their diseases and treatment choices according to the objective standard. I shall explain how this should be finessed. Regarding the negative impact of irrational beliefs/desires, some philosophers have argued that holding irrational beliefs can still be an expression of autonomy. I reject this argument because the degree of autonomy of a decision depends on the degree of rationality of the beliefs or desires on which the decision is based. Hence, to promote patient autonomy, we need to eliminate irrational beliefs by the provision of evidence and good arguments. Finally, I argue that the way to smooth out the framing effects is to present the same information in different perspectives: it is too often assumed that medical information can always be given in a complete and unadorned manner. This article concludes with a cautionary note that the protection of patient autonomy requires much more time and effort than the current practice usually allows.     

Cytosolic Bax: DOES IT REQUIRE BINDING PROTEINS TO KEEP ITS PRO-APOPTOTIC ACTIVITY IN CHECK?*

Bax is kept inactive in the cytosol by refolding its C-terminal transmembrane domain into the hydrophobic binding pocket. Although energetic calculations predicted this conformation to be stable, numerous Bax binding proteins were reported and suggested to further stabilize inactive Bax. Unfortunately, most of them have not been validated in a physiological context on the endogenous level. Here we use gel filtration analysis of the cytosol of primary and established cells to show that endogenous, inactive Bax runs 20-30 kDa higher than recombinant Bax, suggesting Bax dimerization or the binding of a small protein. Dimerization was excluded by a lack of interaction of differentially tagged Bax proteins and by comparing the sizes of dimerized recombinant Bax with cytosolic Bax on blue native gels. Surprisingly, when analyzing cytosolic Bax complexes by high sensitivity mass spectrometry after anti-Bax immunoprecipitation or consecutive purification by gel filtration and blue native gel electrophoresis, we detected only one protein, called p23 hsp90 co-chaperone, which consistently and specifically co-purified with Bax. However, this protein could not be validated as a crucial inhibitory Bax binding partner as its over- or underexpression did not show any apoptosis defects. By contrast, cytosolic Bax exhibits a slight molecular mass shift on SDS-PAGE as compared with recombinant Bax, which suggests a posttranslational modification and/or a structural difference between the two proteins. We propose that in most healthy cells, cytosolic endogenous Bax is a monomeric protein that does not necessarily need a binding partner to keep its pro-apoptotic activity in check.     

CAN FAMILISM BE JUSTIFIED?

This paper argues against the continued practice of Confucian familism, even in its moderate form, in East Asian hospitals. According to moderate familism, a physician acting in concert with the patient's family may withhold diagnostic information from the patient, and may give it to the patient's family members without her prior approval. There are two main approaches to defend moderate familism: one argues that it can uphold patient's autonomy and protect her best interests; the other appeals to cultural relativism by construing the principle of 'family autonomy' to be incommensurable with that of individual autonomy. We respond to the first approach by explaining how the familist arguments either depend on some unreasonable assumptions or simply fail to articulate. The critique of the second approach is based on our recent survey showing that there is no dichotomy of relevant values between the East and the West: we believe that the result can effectively block the familist's reliance on certain traditional or cultural values to explain their resistance to the incorporation of pluralist values. Despite our disagreement with familism, we consider the Eastern emphasis on the family to be conducive to the communication between patient, family members and medical personnel, which is indispensible to the patient's well being and autonomy. We conclude that respect for patient autonomy is perfectly consistent with the involvement of the family in making medical decision as long as the family plays a merely consultant role.     

WHY SHOULD LEK-BREEDERS BE MONOMORPHIC?

Approximately one-quarter of all lek-breeding bird species are sexually monomorphic. Understanding the significance, if any, of this exception to the usual correlation between sexual selection and dimorphism requires detailed data on the mating systems of both monomorphic and dimorphic species. The capuchinbird (Perissocephalus tricolor) is a sexually monomorphic, lek-breeding member of the cotinga family. I studied the social and sexual behavior of this species, and compared it with the Guianan cock-of-the-rock (Rupicola rupicola), a dimorphic, lekking member of the same family. Male–male competition in capuchinbirds involved direct contests for dominance, rather than territorial displays as in classic lek species. In each year, one dominant individual was able to control the most desired display site on the 8-male lek, and was the only male that copulated. In contrast to dimorphic lek birds, female as well as male capuchinbirds engaged in frequent and intense aggression at the lek, and both males and females engaged in sexual mimicry. I suggest that plumage monomorphism in lek birds has evolved as a result of social competition affecting both sexes. This hypothesis accounts for the exaggerated plumage characters shared by males and females in capuchinbirds and a number of other monomorphic lek birds. The evolution of plumage can best be analyzed as an arms race, in which the balance of selective forces acting on each sex can produce a variety of equilibrium states, ranging from sexual indistinguishability to extreme dimorphism.     

DOES GENETIC DIVERSITY REDUCE SIBLING COMPETITION?

An enduring hypothesis for the proximal benefits of sex is that recombination increases the genetic variation among offspring and that this genetic variation increases offspring performance. A corollary of this hypothesis is that mothers that mate multiply increase genetic variation within a clutch and gain benefits due to genetic diversity alone. Many studies have demonstrated that multiple mating can increase offspring performance, but most attribute this increase to sexual selection and the role of genetic diversity has received less attention. Here, we used a breeding design to generate populations of full-siblings, half-siblings, and unrelated individuals of the solitary ascidian Ciona intestinalis. Importantly, we preclude the potentially confounding influences of maternal effects and sexual selection. We found that individuals in populations with greater genetic diversity had greater performance (metamorphic success, postmetamorphic survival, and postmetamorphic size) than individuals in populations with lower genetic diversity. Furthermore, we show that by mating with multiple males and thereby increasing genetic variation within a single clutch of offspring, females gain indirect fitness benefits in the absence of mate-choice. Our results show that when siblings are likely to interact, genetic variation among individuals can decrease competition for resources and generate substantial fitness benefits within a single generation.     

DOES YOUR HOSPITAL NEED A RECOVERY ROOM?

In a survey made to estimate the need for a special room in which patients could recover from anesthesia after operation, it was found that of 475 cases in which this service might have been used, it would have been desirable in 296; that recovery room care would probably have relieved ward nurses of the duty of special care during their busiest hours; that recovery room care was indicated in a high percentage of cases in which certain anesthetics were employed, and that the need for recovery room care appeared to increase in proportion to the amount of pre-sedation given.     

DOES PROFESSIONAL AUTONOMY PROTECT MEDICAL FUTILITY JUDGMENTS?

Despite substantial controversy, the use of futility judgments in medicine is quite common, and has been backed by the implementation of hospital policies and professional guidelines on medical futility. The controversy arises when health care professionals (HCPs) consider a treatment futile which patients or families believe to be worthwhile: should HCPs be free to refuse treatments in such a case, or be required to provide them? Most physicians seem convinced that professional autonomy protects them from being forced to provide treatments they judge medically futile, given the lack of patient benefit as well as the waste of medical resources involved. The argument from professional autonomy has been presented in a number of articles, but it has not been subjected to much critical scrutiny. In this paper I distinguish three versions of the argument: 1) that each physician should be free to exercise his or her own medical judgment; 2) that the medical profession as a whole may provide futility standards to govern the practice of its members; and 3) that the moral integrity of each physician serves as a limit to treatment demands. I maintain that none of these versions succeeds in overcoming the standard objection that futility determinations involve value judgments best left to the patients, their designated surrogates, or their families. Nor do resource considerations change this fact, since they should not influence the properly patient‐centered judgment about futility.     

DOES IMBALANCE IN PHYLOGENIES REFLECT ONLY BIAS?

Phylogenetic tree imbalance was originally believed to indicate differences in evolutionary rates within trees, but other sources of imbalance have been identified, such as tree incompleteness and low quality of the data. To examine the effect of data quality, I calculated Colless's index for 69 recent complete phylogenies. On average, these phylogenies were more unbalanced than phylogenies generated by the equal rates Markov (ERM) model. I tried Mooers's (1995) method to correct for tree size, but his measure appeared to become dependent on tree size when there are large trees (i.e., > 14 tips) in a collection. Instead I corrected for tree size by taking the difference between Colless's index of observed trees and the ERM model expectation for a tree of the same size. The balance measure thus obtained did not correlate significantly to consistency and retention indices as indicators of data quality. It was also independent of the factors kingdom (plants and animals) and taxon level at the tips and type of data (molecular, morphological, and combined).