Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion/exclusion criteria and ethics

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are (1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; (2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and (3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent

Morphological and molecular variation within an ocean basin in wedge-tailed shearwaters (Puffinus pacificus)

Micro-evolutionary processes that underpin genetic and morphological variation in highly mobile pelagic vertebrates are virtually unknown. Previous findings preferentially invoke vicariant isolation due to large-scale physical barriers such as continental landmasses, followed by genetic drift. However increasingly, evidence for divergence by non-random processes (e.g. selection, plasticity) is being presented. Wedge-tailed shearwaters are wide-ranging seabirds with breeding colonies located such that they experience a variety of environmental pressures and conditions. Previous work on this species has provided evidence of inter-colony divergence of adult morphology and foraging modes, as well as chick developmental patterns, suggesting that reinforcement among colonies is possible. In order to evaluate the micro-evolutionary processes driving this observed variation, our study compared patterns of gene flow with morphological and environmental variation among four colonies of wedge-tailed shearwater breeding within the Indo-Pacific Ocean basin. Estimates of gene flow differed according to the genetic marker used; most likely, this is a function of different mutation rates. Nuclear introns suggest that gene flow among wedge-tailed shearwater breeding colonies within the Indo-Pacific Ocean basin is substantial, however microsatellite markers imply that gene flow is reduced. In general, levels of genetic divergence were relatively low and did not correlate with geographic distance, morphological distance or environmental differences (sea-surface temperature and chlorophyll a concentration) among colonies. We suggest that genetic drift alone is unlikely to be the major source of morphological variation seen in this species. Instead, we propose that non-random processes (selection, plasticity) underpin morphological diversity seen in this and possibly other seabird species