After the publication of the 10-year survival data from Milan on the adjuvant use of the block sequential regimen consisting of four cycles of adriamycin followed by eight cycles of intravenous CMF, ...many centres adopted this as standard of care for high risk, multiple node-positive breast cancer. For this reason it was identified as the standard arm for the Anglo-Celtic adjuvant high-dose chemotherapy trial. This study reports on the experience of this regimen in 329 women with early breast cancer involving at least four axillary nodes, who were treated outside any adjuvant chemotherapy trial. At a median follow-up of 3 years, the overall 5-year disease-free survival is 61%, and the overall survival is 70%. These data confirm the efficacy of this regimen in non-trial patients, and, for the same high risk subgroup, indicate that this approach offers an outcome at least as good as that seen in the CALGB 9344 AC-Taxol arm, and the NCIC days 1 and 8 CEF.
While most copepods are holoplanktonic, decapod larvae are meroplanktonic with a pelagic larval development ranging from days (Penaeidae) to weeks (most Palaemonidae, Palinuridae). Reproductive ...strategies result in either the early release of larvae in large numbers of small planktonic forms (Penaeidae) or smaller numbers of advanced larvae after parental incubation (Brachyura, Palaemonidae, Nephropidae, Palinuridae). Commercially-cultured decapod larvae exhibit a wide range of feeding strategies exploiting most of the trophic levels found within the planktonic ecosystem. Studies on these crustacean larvae demonstrate how their digestive physiology is adapted to different feeding strategies during larval development, and provide an insight into the design of appropriate artificial feeds for commercial culture. Comparative measurements of digestive enzyme levels reveal that trypsin-like protease appears to dominate in all larvae investigated. Highest levels occur in herbivorous penaeid and brachyuran larval stages. In contrast, carnivorous lobster and caridean larvae show low protease activity at first feeding and appear to rely upon high-energy digestible live prey for their nutrition. Ontogenetic changes in enzyme type, activity and content are displayed during the penaeid mysis and caridean, brachyuran late zoeal stages as larvae transfer to higher trophic levels. The range and extent of these changes are reviewed for the commercial larval groups of commercially important species.
Central venous catheters are used increasingly in oncology patients. Spontaneous fracture and embolization of a catheter is a rare complication. This report illustrates such a case, in which the ...fragment was retrieved percutaneously. Impending line fracture may be detected by the ‘pinch-off sign’ on a chest radiograph. Prevention may be possible by inserting the catheter more laterally.
Catalytic nucleic acids, such as ribozymes, are central to a variety of origin-of-life scenarios. Typically, they require elevated magnesium concentrations for folding and activity, but their ...function can be inhibited by high concentrations of monovalent salts. Here we show that geologically plausible high-sodium, low-magnesium solutions derived from leaching basalt (rock and remelted glass) inhibit ribozyme catalysis, but that this activity can be rescued by selective magnesium up-concentration by heat flow across rock fissures. In contrast to up-concentration by dehydration or freezing, this system is so far from equilibrium that it can actively alter the Mg:Na salt ratio to an extent that enables key ribozyme activities, such as self-replication and RNA extension, in otherwise challenging solution conditions. The principle demonstrated here is applicable to a broad range of salt concentrations and compositions, and, as such, highly relevant to various origin-of-life scenarios.The correct function of ribozymes in a prebiotic world would be dependent on the presence of optimal salt compositions and concentrations. Now, local heat fluxes have been shown to create an ideal salt habitat for ribozyme activity based on geologically plausible salt-leaching processes.
Over the last decade, hatchery production of mud crabs has become technically and economically more feasible, enabling evaluation of the potential effectiveness of hatchery release in fisheries ...enhancement. The high growth rates and limited movement of released crabs mean that fisheries' yields in isolated mangrove systems with restricted recruitment can be enhanced within a few months. Thus, a release program may be an effective strategy for short-term enhancement in carefully selected specific areas. To date, results are very promising, with recovery rates up to 50% and increases in fisheries' yield up to 46% over baseline catches. In contrast, mark-recapture studies in more open mangrove system populations show that recruitment success and subsequent stock abundance may be largely determined by habitat availability. For these populations, restoration of lost or degraded mangrove areas has been shown to be effective in promoting stock recovery through natural recruitment, with replanted mangroves supporting fisheries of equivalent economic value to that of natural mangroves, though it may take some years to reach these levels. Thus, a balanced approach to stock management could integrate both hatchery-release and habitat restoration programs, depending on local conditions and over different time scales, with parallel co-management to support effectiveness.
Although catalytic mechanisms in natural enzymes are well understood, achieving the diverse palette of reaction chemistries in re-engineered native proteins has proved challenging. Wholesale ...modification of natural enzymes is potentially compromised by their intrinsic complexity, which often obscures the underlying principles governing biocatalytic efficiency. The maquette approach can circumvent this complexity by combining a robust de novo designed chassis with a design process that avoids atomistic mimicry of natural proteins. Here, we apply this method to the construction of a highly efficient, promiscuous, and thermostable artificial enzyme that catalyzes a diverse array of substrate oxidations coupled to the reduction of H
O
. The maquette exhibits kinetics that match and even surpass those of certain natural peroxidases, retains its activity at elevated temperature and in the presence of organic solvents, and provides a simple platform for interrogating catalytic intermediates common to natural heme-containing enzymes.Catalytic mechanisms of enzymes are well understood, but achieving diverse reaction chemistries in re-engineered proteins can be difficult. Here the authors show a highly efficient and thermostable artificial enzyme that catalyzes a diverse array of substrate oxidations coupled to the reduction of H
O
.
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