Veterinary drug bioequivalence determination

A bioequivalence trial is a statistically based comparison of two formulations to demonstrate with a controlled consumer (patient) risk that two formulated drug products are interchangeable. The basic assumption underlying a bioequivalence trial is that essentially the same plasma time-course leads to essentially the same effect allowing two formulations to be interchanged. Bioequivalence is generally assessed using kinetic end points and in practice, two formulations in which bioavailability parameters (rate and extent) differ by 20% or less, with a 90% degree of confidence, are considered to be bioequivalent. In this review, the design and evaluation of bioequivalence studies are presented with special attention given to scientific issues.     

Communication between forest scientists and forest policy-makers in Europe — A survey on both sides of the science/policy interface

Improving communication in the science/policy interface has received increased attention from scientists and policy-makers in recent years. This paper discusses recent science/policy interface literature and reports on the results of two surveys, sent out to forest scientists and forest policy-makers, asking them to evaluate communication in the forest science/policy interface in Europe. The questionnaires are based on a model of the communication process between scientists and policy-makers which was developed for this study, comprising information sources, channels, types and topics of information. The results indicate that policy-makers and scientists largely share the same ideas on how they should communicate with each other. However, the results also show that policy-makers' expectations from science differ from scientists' estimations on what policy-makers consider relevant topics of scientific information. Another result of the study is that scientists and policy-makers give largely the same suggestions for improving communication in the science/policy interface.     

Nitrogen-fixation dynamics in a cut-and-carry silvopastoral system in the subhumid conditions of Guadeloupe, French Antilles

This paper summarizes several studies on N recycling in a tropical silvopastoral system for assessing the ability of the system to increase soil fertility and insure sustainability. We analyzed the N₂ fixation pattern of the woody legume component (Gliricidia sepium), estimated the recycling rate of the fixed N in the soil, and measured N outputs in tree pruning and cut grass (Dichanthium aristatum). With this information, we estimated the N balance of the silvopastoral system at the plot scale. The studies were conducted in an 11-year-old silvopastoral plot established by planting G. sepium cuttings at 0.3 m × 2 m spacing in natural grassland. The plot was managed as a cut-and-carry system where all the tree pruning residues (every 2-4 months) and cut grass (every 40-50 days) were removed and animals were excluded. No N fertilizer was applied. Dinitrogen fixation, as estimated by the ¹⁵N natural abundance method, ranged from 60-90% of the total N in aboveground tree biomass depending on season. On average, 76% of the N exports from the plot in tree pruning (194 kg [N] ha^–1 yr^–1) originated from N₂ fixation. Grass production averaged 13 Mg ha^–1 yr^–1 and N export in cut grass was 195 kg [N] ha^–1 yr^–1. The total N fixed by G. sepium, as estimated from the tree and grass N exports and the increase in soil N content, was about 555 kg [N] ha^–1 yr^–1. Carbon sequestration averaged 1.9 Mg [C] ha^–1 yr^–1 and soil organic N in the 0-0.2 m layer increased at a rate of 166 kg [N] ha^–1 yr^–1, corresponding to 30% of N₂ fixation by the tree. Nitrogen released in nodule turnover (10 kg [N] ha^–1 yr^–1) and litter decomposition (40 kg [N] ha^–1 yr^–1) contributed slightly to this increase, and most of the recycled N came from the turnover or the activity of other below-ground tree biomass than nodules. This revised version was published online in June 2006 with corrections to the Cover Date.     

Tree cavities in riverine forests: What determines their occurrence and use by hole-nesting passerines?

We assessed: (1) the relative importance of different macro- and microhabitat characteristics for explaining the occurrence of tree cavities and their occupancy by hole-nesting passerines and (2) the role of woodpeckers as keystone species in riverine aspen and birch stands in central Estonia. In 1999–2003, multiple surveys were carried out in 16 stands with a total area of 104 ha. Of the 713 tree-holes found, 483 were considered suitable for secondary cavity-nesters. The mean density was 4.1 ± 3.0 (S.D.) suitable cavities ha⁻¹ (including 2.0 ± 1.3 suitable for hole-nesting passerines). Woodpeckers had excavated 88% of suitable cavities. The density of breeding woodpeckers explained 78% of variance in the density of woodpecker-excavated cavities (mean = 28 holes per pair) and 51% of natural cavities. Woodpecker-excavated and natural cavities occurred in very similar conditions, determined mostly by tree species, decay and size, stand type, as well as the vicinity of other cavities. Ninety-six of 161 occupancy cases of cavities were by passerines, which – probably to reduce the risk of nest predation or physical destruction – preferred small natural cavities in live trees. We conclude that riverine areas are important centres of cavity supply in forested regions and the value of woodpeckers as keystone species comes mostly from the large quantity, but not quality, of the cavities they provide. The results imply that: (1) for cavity-nesters, large (DBH > 30 cm) broadleaved trees, both live and dead, are the most important to retain during forestry operations in hemiboreal riverine forests and (2) woodpecker censuses may indicate cavity abundance, particularly if woodpecker-holes dominate among all cavities.     

Zero-inflated models for identifying disease risk factors when case detection is imperfect: Application to highly pathogenic avian influenza H5N1 in Thailand

Logistic regression models integrating disease presence/absence data are widely used to identify risk factors for a given disease. However, when data arise from imperfect surveillance systems, the interpretation of results is confusing since explanatory variables can be related either to the occurrence of the disease or to the efficiency of the surveillance system. As an alternative, we present spatial and non-spatial zero-inflated Poisson (ZIP) regressions for modelling the number of highly pathogenic avian influenza (HPAI) H5N1 outbreaks that were reported at subdistrict level in Thailand during the second epidemic wave (July 3rd 2004 to May 5th 2005). The spatial ZIP model fitted the data more effectively than its non-spatial version. This model clarified the role of the different variables: for example, results suggested that human population density was not associated with the disease occurrence but was rather associated with the number of reported outbreaks given disease occurrence. In addition, these models allowed estimating that 902 (95% CI 881–922) subdistricts suffered at least one HPAI H5N1 outbreak in Thailand although only 779 were reported to veterinary authorities, leading to a general surveillance sensitivity of 86.4% (95% CI 84.5–88.4). Finally, the outputs of the spatial ZIP model revealed the spatial distribution of the probability that a subdistrict could have been a false negative. The methodology presented here can easily be adapted to other animal health contexts.     

Effect of Manually Preheparinized Syringes on Packed Cell Volume and Total Solids in Blood Samples Collected from American Alligators (Alligator mississippiensis)

The hemodilution effect of manually preheparinized syringes was determined by evaluating the packed cell volume (PCV) and total solids (TS) from blood samples collected from 50 American alligators (Alligator mississippiensis). A volume of 0.2 mL of blood was drawn into 3 syringes of 1 mL: control with no heparin sodium, heparin sodium drawn to 0.1 mL and then expelled, and heparin sodium drawn to 0.2 mL and then expelled. PCV and TS values were determined from each syringe immediately after collection. Mean PCV and TS values were compared between the control and heparin groups using linear mixed modeling. The syringes coated with heparin resulted in a significantly lower mean PCV and TS values when compared with controls, with no significant difference between the heparin groups. This dilution effect was also found to be inconsistent and not accurate from one syringe to another. An adjunct method of obtaining 0.5 mL from already-collected blood samples into 1-mL syringes that were coated with heparin drawn to 0.2 mL and then expelled also showed a significant decrease in PCV and TS values when compared with the control samples, although to a lesser extent. As a result, it cannot be recommended to manually preheparinize syringes when collecting small volume of blood samples from American alligators because significant and unpredictable hemodilution is likely to occur.     

Effects of shade,altitude and management on multiple ecosystem services in coffee agroecosystems

Agroforestry systems provide diverse ecosystem services that contribute to farmer livelihoods and the conservation of natural resources. Despite these known benefits, there is still limited understanding on how shade trees affect the provision of multiple ecosystem services at the same time and the potential trade-offs or synergies among them. To fill this knowledge gap, we quantified four major ecosystem services (regulation of pests and diseases; provisioning of agroforestry products; maintenance of soil fertility; and carbon sequestration) in 69 coffee agroecosystems belonging to smallholder farmers under a range of altitudes (as representative of environmental conditions) and management conditions, in the region of Turrialba, Costa Rica. We first analyzed the individual effects of altitude, types of shade and management intensity and their interactions on the provision of ecosystem services. In order to identify potential trade-offs and synergies, we then analyzed bivariate relationships between different ecosystem services, and between individual ecosystem services and plant biodiversity. We also explored which types of shade provided better levels of ecosystem services. The effectiveness of different types of shade in providing ecosystem services depended on their interactions with altitude and coffee management, with different ecosystem services responding differently to these factors. No trade-offs were found among the different ecosystem services studied or between ecosystem services and biodiversity, suggesting that it is possible to increase the provision of multiple ecosystem services at the same time. Overall, both low and highly diversified coffee agroforestry systems had better ability to provide ecosystem services than coffee monocultures in full sun. Based on our findings, we suggest that coffee agroforestry systems should be designed with diversified, productive shade canopies and managed with a medium intensity of cropping practices, with the aim of ensuring the continued provision of multiple ecosystem services.