Genetic evidence for panmixia in a colony-breeding crater lake cichlid fish

Fine-scaled genetic structuring, as seen for example in many lacustrine fish, typically relates to the patterns of migration, habitat use, mating system or other ecological factors. Because the same processes can also affect the propensity of population differentiation and divergence, assessments of species from rapidly speciating clades, or with particularly interesting ecological traits, can be especially insightful. For this study, we assessed the spatial genetic relationships, including the genetic evidence for sex-biased dispersal, in a colony-breeding cichlid fish, Amphilophus astorquii, endemic to Crater Lake Apoyo in Nicaragua, using 11 polymorphic microsatellite loci (n = 123 individuals from three colonies). We found no population structure in A. astorquii either within colonies (no spatial genetic autocorrelation, r ~0), or at the lake-wide level (pairwise population differentiation FST = 0-0.013 and no clustering), and there was no sex-bias (male and female AIc values bounded 0) to this lack of genetic structure. These patterns may be driven by the colony-breeding reproductive behaviour of A. astorquii. The results suggest that strong philopatry or spatial assortative mating are unlikely to explain the rapid speciation processes associated with the history of this species in Lake Apoyo

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin