Was Phanerozoic reef history controlled by the distribution of non-enzymatically secreted reef carbonates (microbial carbonate and biologically induced cement)?

Throughout most of the Phanerozoic, reef rigidity resulted as much, or more, from early lithification by microbial carbonates and biologically induced cements (non-enzymatic carbonates) than from biological encrustation of, or by, large, enzymatically secreted metazoan skeletons. Reef framework is divided into four categories: (1) skeletal metazoan; (2) non-skeletal microbialite (stromatolite and thrombolite); (3) calcimicrobe; and (4) biocementstone, in which small or delicate organisms serve as scaffolds for rigid cement crusts. The last three categories are dominated by non-enzymatic carbonates. Skeletal framework and non-skeletal microbialite framework were the most abundant framework types through the Phanerozoic. The composition and abundance of skeletal framework was controlled largely by mass extinction events, but most reefs consisted of both microbialite and skeletal organisms in a mutually beneficial relationship. Microbialite framework was abundant throughout the Palaeozoic and early Mesozoic, but declined after the Jurassic. Calcimicrobe framework was important during the Cambrian-Early Ordovician and Devonian and biocementstone framework was important from the late Mississippian to the Late Triassic. The Phanerozoic history of reefs does not correlate well with the stratigraphic distribution of large, skeletal 'reef builders', or with a variety of physicochemical parameters, including sea-level history, Wilson Cycle or global climate cycles. Because non-enzymatic carbonates result from induction by non-obligate calcifiers, and not enzymatic precipitation by obligate calcifiers, the distribution of these carbonates was controlled to a larger extent by temporal changes in physicochemical parameters affecting the saturation state of sea water with respect to carbonate minerals. Changes in pCO, Ca/Mg ratios, cation concentrations and temperature may have affected the abundance of non-enzymatic carbonates and, hence, reefs, independently from the effects of these same parameters and mass extinction events on skeletal reef biota. The decline in abundance of reefal microbialite and absence of calcimicrobe and biocementstone reef framework after the Jurassic may be a result of relatively low saturation states of sea water owing to increased removal and sequestration of finite marine carbonate resources by calcareous plankton since the Jurassic. Reef history is difficult to correlate with temporal changes in specific global parameters because these parameters affect skeletal biota and biologically induced carbonate precipitation independently. Hence, reef history was regulated not just by skeletal reef biota, but by parameters governing non-enzymatic carbonates

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