Managers of many ungulate populations seek to maximize the number and quality of mature males that can be harvested each year rather than the total harvest. Since competition between the sexes in dimorphic ungulates is commonly asymmetric and increasing population density depresses the growth and survival of males more than females, different culling policies may need to be applied to the two sexes to realize this objective. In this paper, we use observed density-dependent changes in reproduction and survival in an unculled red deer (Cervus elaphus) population in the North Block of the Isle of Rum to model the responses of males and females to different levels of culling or predation
No abstract is provided for this article.
Indirect clinical measures assessing anti-malarial drug transmission-blocking activity in falciparum malaria include measurement of the duration of gametocytaemia, the rate of gametocyte clearance or the area under the gametocytaemia-time curve (AUC). These may provide useful comparative information, but they underestimate dose-response relationships for transmission-blocking activity. Following 8-aminoquinoline administration P. falciparum gametocytes are sterilized within hours, whereas clearance from blood takes days. Gametocytaemia AUC and clearance times are determined predominantly by the more numerous female gametocytes, which are generally less drug sensitive than the minority male gametocytes, whereas transmission-blocking activity and thus infectivity is determined by the more sensitive male forms. In choosing doses of transmission-blocking drugs there is no substitute yet for mosquito-feeding studies.
No abstract is provided for this article.
Our aim is to raise awareness of the issues faced by researchers in developing countries and to introduce an initiative we are developing. We propose that the gaps and issues we have outlined could be largely addressed by building a community of researchers from all the various roles who will be able to access the information, guidance and resources they need, whilst also be able to share methods and pragmatic operational practices that have been locally derived and known to work. Some examples include template consent forms, data management systems, and example protocols and laboratory sample collection and handling methods. We emphasize that this initiative is entirely based on an ethos of collaboration, open access, and sharing practice; indeed it will only be successful if research groups both use the resource and contribute to its development. The development of a prototype of web site for this initiative is underway and can be found at http://pilot.globalhealthtrials.org/. We are making this public at this early juncture as we are seeking involvement from our colleagues right from the outset in line with the open and collaborative ethos that is envisaged. Therefore, we encourage colleagues to become part of this initiative by providing content, commenting on the Web site, and sharing their operational tools. We also welcome all those engaged in trials to register and build their own personal professional development record to track their career and training record, and to provide a review structure.
Following anti-malarial drug treatment asexual malaria parasite killing and clearance appear to be first order processes. Damaged malaria parasites in circulating erythrocytes are removed from the circulation mainly by the spleen. Splenic clearance functions increase markedly in acute malaria. Either the entire infected erythrocytes are removed because of their reduced deformability or increased antibody binding or, for the artemisinins which act on young ring stage parasites, splenic pitting of drug-damaged parasites is an important mechanism of clearance. The once-infected erythrocytes returned to the circulation have shortened survival. This contributes to post-artesunate haemolysis that may follow recovery in non-immune hyperparasitaemic patients. As the parasites mature Plasmodium vivax-infected erythrocytes become more deformable, whereas Plasmodium falciparum-infected erythrocytes become less deformable, but they escape splenic filtration by sequestering in venules and capillaries. Sequestered parasites are killed in situ by anti-malarial drugs and then disintegrate to be cleared by phagocytic leukocytes. After treatment with artemisinin derivatives some asexual parasites become temporarily dormant within their infected erythrocytes, and these may regrow after anti-malarial drug concentrations decline. Artemisinin resistance in P. falciparum reflects reduced ring stage susceptibility and manifests as slow parasite clearance. This is best assessed from the slope of the log-linear phase of parasitaemia reduction and is commonly measured as a parasite clearance half-life. Pharmacokinetic-pharmacodynamic modelling of anti-malarial drug effects on parasite clearance has proved useful in predicting therapeutic responses and in dose-optimization.
Gluconeogenesis and liver blood flow (LBF) in severe falciparum malaria were assessed from the clearance and metabolic response to intravenously administered glycerol (0.3 g/kg) and Indocyanine Green ([ICG] 0.4 mg/kg), respectively. Fasting baseline blood glycerol concentrations (mean ± SD) were significantly higher in acute malaria (133 ± 65 μmol/L, n = 14), than in convalescence (65 ± 31 μmol/L, n = 9, P = .01), but basal triacylglycerol concentrations were similar. Estimated glycerol turnover was also more than twice as high in acute malaria compared with convalescence (1.36 ± 0.87 v 0.54 ± 0.15 μmol · min−1 · kg−1, P = .015). The increment in plasma glucose (AUC0–55 min) following glycerol infusion was greater during acute malaria compared with convalescence (median [range], +31.6 [−0.9 to + 107.6] v + 14.5 [−103 to +27.1] mmol · min · L−1, P < .05), but the insulin increments were similar (P = .9), indicating reduced tissue insulin sensitivity. The increment in venous lactate (AUC0–55 min) was higher in severely ill patients (17.2 [−7.8 to +53.4] mmol · min · L−1, n = 10) compared with patients with moderately severe malaria (−3.1 [−8.7 to 3.2] mmol · min · L−1, n = 4, P = .01). LBF estimated from ICG clearance was lower during acute illness than in convalescence (mean ± SD, 15.5 ± 2.3 v 18.6 ± 2.9 mL · min−1 · kg−1, P = .007) and correlated inversely with the basal venous lactate concentration (r s = .53, P < .05). LBFs less than 15 mL · min−1 · kg−1 were associated with hyperlactatemia, and all four fatal cases had LBFs of less than 12 mL · min−1 · kg−1. Thus, despite the propensity to hypoglycemia in severe falciparum malaria, the clearance and metabolic responses to glycerol were relatively unaffected. These data also provide evidence of increased glycolysis and an association between reduced LBF and lactic acidosis in severe malaria.
