Trait modality distribution of aquatic macrofauna communities as explained by pesticides and water chemistry

Analyzing functional species’ characteristics (species traits) that represent physiological, life history and morphological characteristics of species help understanding the impacts of various stressors on aquatic communities at field conditions. This research aimed to study the combined effects of pesticides and other environmental factors (temperature, dissolved oxygen, dissolved organic carbon, floating macrophytes cover, phosphate, nitrite, and nitrate) on the trait modality distribution of aquatic macrofauna communities. To this purpose, a field inventory was performed in a flower bulb growing area of the Netherlands with significant variation in pesticides pressures. Macrofauna community composition, water chemistry parameters and pesticide concentrations in ditches next to flower bulb fields were determined. Trait modalities of nine traits (feeding mode, respiration mode, locomotion type, resistance form, reproduction mode, life stage, voltinism, saprobity, maximum body size) likely to indicate pesticides impacts were analyzed. According to a redundancy analysis, phosphate -and not pesticides- constituted the main factor structuring the trait modality distribution of aquatic macrofauna. The functional composition could be ascribed for 2–4 % to pesticides, and for 3–11 % to phosphate. The lack of trait responses to pesticides may indicate that species may have used alternative strategies to adapt to ambient pesticides stress. Biomass of animals exhibiting trait modalities related to feeding by predation and grazing, presence of diapause form or dormancy, reproduction by free clutches and ovoviviparity, life stage of larvae and pupa, was negatively correlated to the concentration of phosphate. Hence, despite the high pesticide pollution in the area, variation in nutrient-related stressors seems to be the dominant driver of the functional composition of aquatic macrofauna assembly in agricultural ditches.     

Population pharmacokinetics of tanezumab in phase 3 clinical trials for osteoarthritis pain

AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V ₁), peripheral volume (V ₂), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day^–1, 2.71 l, 1.98 l, 0.371 l day^–1, 8.03 μg day^–1 and 27.7 ng ml^–1, respectively. Inter‐individual variability (IIV) was included on CL, V ₁, V ₂ and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V ₁ and V ₂ significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit.