Background — This phase 1/2 study investigated the safety of percutaneous catheter-based gene transfer of naked plasmid DNA encoding for vascular endothelial growth factor 2 (phVEGF2) to left ventricular (LV) myocardium in a prospective, randomized, double-blind, placebo-controlled, dose-escalating study of inoperable patients with class III or IV angina. Methods and Results — A steerable deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced percutaneously to the endocardial surface of the LV in 19 patients (age, 61±2 years) with chronic myocardial ischemia who were not candidates for conventional revascularization. Patients were randomized in a double-blind fashion to receive 6 injections (total volume, 6.0 mL) of placebo or phVEGF2 in doses of 200 μg (n=9), 800 μg (n=9), or 2000 μg (n=1) guided by LV electromechanical (NOGA) mapping with a gene-to-placebo ratio of 2:1. A total of 114 LV injections were delivered and caused no hemodynamic alterations, sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforation. End-point analysis at 12 weeks disclosed a statistically significant improvement in Canadian Cardiovascular Society (CCS) angina class in phVEGF2-treated versus placebo-treated patients (−1.3 versus −0.1, P =0.04). Remaining efficacy end points—including change in exercise duration (91.8 versus 3.9 seconds), functional improvement by ≥2 CCS classes (9 of 12 versus 1 of 6), and Seattle Angina Questionnaire data—all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment. Conclusions — This phase 1/2, double-blind, randomized trial provides preliminary data that support safety of phVEGF2 catheter-mediated myocardial gene transfer. The statistically significant reduction in anginal class and strong positive trends for remaining end points suggest that a larger phase 2/3 trial is warranted.

Pelagic larval duration (PLD) has been hypothesized to be the primary predictor of connectivity in marine fishes; however, few studies have examined the effects that adult reproductive behaviour may have on realized dispersal. We assessed gene flow (connectivity) by documenting variation in microsatellites and mitochondrial DNA sequences in two protogynous species of groupers, the aggregate spawning red hind, Epinephelus guttatus, and the single-male, harem-spawning coney, Cephalopholis fulva, to ask whether reproductive strategy affects connectivity. Samples of both species were obtained from waters off three islands (Puerto Rico, St. Thomas and St. Croix) in the Caribbean Sea. Despite the notion that aggregate spawning of red hind may facilitate larval retention, stronger signals of population structure were detected in the harem-spawning coney. Heterogeneity and/or inferred barriers, based on microsatellites, involved St. Croix (red hind and coney) and the west coast of Puerto Rico (coney). Heterogeneity and/or inferred barriers, based on mitochondrial DNA, involved St. Croix (coney only). Genetic divergence in both species was stronger for microsatellites than for mitochondrial DNA, suggesting sex-biased dispersal in both species. Long-term migration rates, based on microsatellites, indicated asymmetric gene flow for both species in the same direction as mean surface currents in the region. Red hind had higher levels of variation in microsatellites and lower levels of variation in mitochondrial DNA. Long-term effective size and effective number of breeders were greater for red hind; estimates of θ(f) , a proxy for long-term effective female size, were the same in both species. Patterns of gene flow in both species appear to stem in part from shared aspects of larval and adult biology, local bathymetry and surface current patterns. Differences in connectivity and levels of genetic variation between the species, however, likely stem from differences in behaviour related to reproductive strategy.

Population‐genetic structure and average long‐term effective size of yellowtail snapper, Ocyurus chrysurus (Bloch), sampled offshore from the Florida Keys and four localities in the US Caribbean, were investigated using nuclear‐encoded microsatellites and a fragment of the mitochondrially encoded ND‐4 gene. Analysis of spatial genetic variation revealed occurrence of up to four groupings (stocks) of yellowtail snapper: one in the Florida Keys, one along the west coast of Puerto Rico, one that includes the east coast of Puerto Rico and St. Thomas and one offshore of St. Croix. The observed genetic differences among localities are not strong, and additional sampling to examine whether the observed patterns of population structure are temporally stable is warranted. Levels of genetic variability and estimates of average, long‐term effective size (Ne) indicate that yellowtail snapper at all five localities have, at present, sufficient genetic variation to maintain long‐term integrity and sustainability.