Ethical Considerations for Outcome‐adaptive Trial Designs: A Clinical Researcher's Perspective

In a typical comparative clinical trial the randomization scheme is fixed at the beginning of the study, and maintained throughout the course of the trial. A number of researchers have championed a randomized trial design referred to as ‘outcome‐adaptive randomization.’ In this type of trial, the likelihood of a patient being enrolled to a particular arm of the study increases or decreases as preliminary information becomes available suggesting that treatment may be superior or inferior. While the design merits of outcome‐adaptive trials have been debated, little attention has been paid to significant ethical concerns that arise in the conduct of such studies. These include loss of equipoise, lack of processes for adequate informed consent, and inequalities inherent in the research design which could lead to perceptions of injustice that may have negative implications for patients and the research enterprise. This article examines the ethical difficulties inherent in outcome‐adaptive trials.     

Radioiodinated surface proteins of separated cell types from rabbit endometrium in relation to the time of implantation

To investigate changes in surface proteins of uterine cells in relation to the time of implantation, epithelial and stromal cells were isolated from rabbit endometrium and maintained in primary culture for 3 days. Surface-iodination of intact cells was carried out before and after culture, using immobilized Iodogen catalyst. The labeled proteins were analyzed by polyacrylamide gel electrophoresis, followed by autoradiography; peak areas were quantitated by scanning densitometry. Different gestational ages showed no marked qualitative differences in the surface-iodination patterns either of epithelial or stromal cells before or after culture. Quantitative differences between the surface-iodination pattern of epithelial cells from days 4 to 6.5 of pregnancy were revealed by canonical variate analysis of labeled peak areas. Values for individual rabbits clustered according to gestational age, with significant (p less than 0.05) separation of the clusters, although the discrimination was less pronounced for cultured than for freshly isolated cells. Changes involving increases in labeling of a protein of 38000 Mr in fresh cells, and decreases in a protein of 42000 Mr in cultured cells, were evident between day 4 and day 6.5. Thus changes in the surface-labeling pattern of uterine epithelial cells in relation to the time of receptivity for ovoimplantation can be distinguished. The functional significance of these changes remains to be elucidated.     

Potential Toxicological Problems Associated with Antioxidants in Plastics and Rubber Consumables

Antioxidants and stabilisers are of critical importance in the manufacture and use of polymer artifacts. Most conventional additives are readily leached from plastics or rubbers by foodstuffs or body fluids with consequent danger associated with the potential toxicity in the body. Strategy for the development of biologically “safe” stabilisation systems for polymers are discussed and it is concluded that the attachment of the appropriate reactive functional group to the polymer backbone by “reactive processing” provides the best means of immobilising the functional group to leaching fluids without sacrificing its protective action.     

EVIDENCE FOR A MOSAIC HYBRID ZONE IN THE GRASS SHRIMP PALAEMONETES KADIAKENSIS (PALAEMONIDAE) AS REVEALED BY MULTIPLE GENETIC MARKERS

Molecular techniques provide powerful tools for studying the geographic structure of hybrid zones and the dynamics of gene exchange between incipient species. We examined allozyme variation at five loci (PGM, GPI, MDH-1, MDH-2, and LDH) for 27 populations of Palaemonetes kadiakensis from the central, coastal, and eastern regions of Texas. Central Texas populations of P. kadiakensis exhibited highly significant linkage disequilibrium and departures from Hardy-Weinberg genotype proportions. In populations with linkage disequilibrium, allelic differences at GPI defined two types of P. kadiakensis, designated A and B. Both types existed in central Texas with little or no evidence of interbreeding, whereas the populations from all other localities showed complete introgression of type B alleles into the type A gene pool. We also examined ribosomal DNA (rDNA) and mitochondrial DNA (mtDNA) variation in a subset of populations, chosen to cover a range of geographic locations and levels of linkage disequilibrium. Two groups of mtDNA haplotypes and two restriction fragment patterns for the rDNA corresponded to allozyme type A and B individuals in populations exhibiting linkage disequilibrium. In populations with ongoing hybridization, all hybrid animals (N= 15) exhibited type A mtDNA. Exhibition of type A mtDNA indicated that type A females had mated successfully with type B males, but type B females had not mated successfully with type A males. Genotype distributions suggest reduced reproduction by hybrid offspring in central Texas populations. These patterns are consistent with a mosaic model of hybrid zone dynamics.