The hidden side of the Allee effect: correlated demographic traits and extinction risk in experimental populations

Because Allee effects have major impacts on the dynamics of small populations, they are routinely included in demographic models for the evaluation of extinction risks. However, the structure of most common models implies that other demographic parameters (like the maximum growth rate) are modified by the inclusion of an Allee effect, which also affects in return the extinction risk of the population. Whether such correlations between demographic traits occur in natural populations or merely reflect a practical constraint related to model formalism is of primary importance to understand better the dynamics of small populations. We investigated this question using 20 populations of Trichogramma wasps raised under similar conditions, of which 3 were subject to an Allee effect. We showed that these 3 populations were also characterized by lower maximum growth rate and lower carrying capacity, and that their extinction probability was higher than for non-Allee populations. These results provide the first empirical demonstration of a correlation between the presence of positive density-dependence and impaired demographic performance, which increases the extinction risk of population, especially during the establishment phase

Tranexamic acid quantification in human whole blood using liquid samples or volumetric absorptive microsampling devices.

Background: Recent clinical trials demonstrate the benefits of the antifibrinolytic drug tranexamic acid but its pharmacokinetics remain to be investigated more in depth. Although pharmacokinetics studies are usually performed with plasma, volumetric absorptive microsampling devices allow us to analyze dried whole blood samples with several advantages. Materials & methods: High-sensitivity LC-MS/MS methods for the quantification of tranexamic acid in human whole blood using liquid samples or dry samples on volumetric absorptive microsampling devices were developed and validated based on International Association from Therapeutic Drug Monitoring and Clinical Toxicology, European Medicines Agency and US FDA guidance. Conclusion: The method performances were excellent across the range of clinically relevant concentrations. The stability of tranexamic acid in blood samples stored up to 1 month at +50°C was demonstrated. The methods' suitability was confirmed with clinical samples

Life-history traits, pace of life and dispersal among and within five species of Trichogramma wasps: a comparative analysis

Major traits defining the life history of organisms are often not independent from each other, with most of their variation aligning along key axes such as the pace-of-life axis. We can define a pace-of-life axis structuring reproduction and development time as a continuum from less-fecund, longer-developing ″slow″ types to more-fecund, shorter-developing ″fast″ types. Such axes, along with their potential associations or syndromes with other traits such as dispersal, are however not universal; in particular, support for their presence may be taxon and taxonomic scale-dependent. Knowing about such life-history strategies may be especially important for understanding eco-evolutionary dynamics, as these trait syndromes may constrain trait variation or be correlated with other traits. To understand how life-history traits and effective dispersal covary, we measured these traits in controlled conditions for 28 lines from five species of Trichogramma, which are small endoparasitoid wasps frequently used as a biological model in experimental evolution but also in biocontrol against Lepidoptera pests. We found partial evidence of a pace-of-life axis at the interspecific level: species with higher fecundity also had faster development time. However, faster-developing species also were more likely to delay egg-laying, a trait that is usually interpreted as ″slow″. There was no support for similar covariation patterns at the within-species line level. There was limited variation in effective dispersal between species and lines, and accordingly, we did not detect any correlation between effective dispersal probability and life-history traits. We discuss how expanding our experimental design by accounting for the density-dependence of both the pace of life and dispersal might improve our understanding of those traits and how they interact with each other. Overall, our results highlight the importance of exploring covariation at the ″right″ taxonomic scale, or multiple taxonomic scales, to understand the (co)evolution of life-history traits. They also suggest that optimizing both reproductive and development traits to maximize the efficiency of biocontrol may be difficult in programs using only one species

Alternative routes for tranexamic acid treatment in obstetric bleeding (WOMAN-PharmacoTXA trial): a randomised trial and pharmacological study in caesarean section births.

OBJECTIVE: To examine the safety, efficacy and pharmacology of intravenous (IV), intramuscular (IM) and oral tranexamic acid (TXA) use in pregnant women. DESIGN: Randomised, open-label trial. SETTING: Hospitals in Pakistan and Zambia. POPULATION: Women giving birth by caesarean section. METHODS: Women were randomised to receive 1 g IV, 1 g IM, 4 g oral TXA or no TXA. Adverse events in women and neonates were recorded. TXA concentration in whole blood was measured and the concentrations over time were examined with population pharmacokinetics. The relationship between drug exposure and D-dimer was explored. The trial registration is NCT04274335. MAIN OUTCOME MEASURES: Concentration of TXA in maternal blood. RESULTS: Of the 120 women included in the randomised safety study, there were no serious maternal or neonatal adverse events. TXA concentrations in 755 maternal blood and 87 cord blood samples were described by a two-compartment model with one effect compartment linked by rate transfer constants. Maximum maternal concentrations were 46.9, 21.6 and 18.1 mg/L for IV, IM and oral administration, respectively, and 9.5, 7.9 and 9.1 mg/L in the neonates. The TXA response was modelled as an inhibitory effect on the D-dimer production rate. The half-maximal inhibitory concentration (IC50 ) was 7.5 mg/L and was achieved after 2.6, 6.4 and 47 minutes with IV, IM and oral administration of TXA, respectively. CONCLUSIONS: Both IM and oral TXA are well tolerated. Oral TXA took about 1 hour to reach minimum therapeutic concentrations and would not be suitable for emergency treatment. Intramuscular TXA inhibits fibrinolysis within 10 minutes and may be a suitable alternative to IV

High-sensitivity quantification of acetylcholine and choline in human cerebrospinal fluid with a validated LC-MS/MS method

International audienceAcetylcholine is the neurotransmitter of the parasympathetic nervous system, synthesized from choline and involved in several neurodegenerative diseases. Exploration of cholinergic neurotransmission in the human central nervous system is limited by the lack of a sensitive and specific method for the determination of acetylcholine and choline expression. We developed an hydrophilic interaction liquid chromatography – mass spectrometry method for the quantification of both molecules in human cerebrospinal fluid samples. An extensive selectivity study towards endogenous interfering compounds, in particular γ-butyrobetain, was performed and the method was validated according to the European Medicine Agency and Food and Drug Administration guidelines for the validation of bioanalytical methods. The performance of the method was excellent with a lower limit of quantification at 5 ng/L (34.2 pmol/L) for acetylcholine and 5 μg/L for choline, a precision in the range 1.3–11.9% and an accuracy between 85.2 and 113.1%. This suitability of the method for the quantification of acetylcholine and choline in clinical samples was demonstrated with the analysis of patient cerebrospinal fluid samples. Altogether, this validated method allows the simultaneous quantitative analysis of acetylcholine and choline in human cerebrospinal fluid with high sensitivity and selectivity. It will allow to better characterize the cholinergic neurotransmission in human pathologies and to study the effects of drugs acting on this system

The hidden side of the Allee effect: correlated demographic traits and extinction risk in experimental populations

Because Allee effects have major impacts on the dynamics of small populations, they are routinely included in demographic models for the evaluation of extinction risks. However, the structure of most common models implies that other demographic parameters (like the maximum growth rate) are modified by the inclusion of an Allee effect, which also affects in return the extinction risk of the population. Whether such correlations between demographic traits occur in natural populations or merely reflect a practical constraint related to model formalism is of primary importance to understand better the dynamics of small populations. We investigated this question using 20 populations of Trichogramma wasps raised under similar conditions, of which 3 were subject to an Allee effect. We showed that these 3 populations were also characterized by lower maximum growth rate and lower carrying capacity, and that their extinction probability was higher than for non-Allee populations. These results provide the first empirical demonstration of a correlation between the presence of positive density-dependence and impaired demographic performance, which increases the extinction risk of population, especially during the establishment phase

Inbreeding depression of mating behavior and its reproductive consequences in a freshwater snail

Inbreeding is expected to impair male and female reproductive performance, but little is known on how inbreeding depression varies between sexes and different levels of competition. We studied inbreeding depression in mating behavior and its reproductive consequences in a hermaphroditic freshwater snail and demonstrate that inbreeding depresses mating success in both sex functions. However, the magnitude of inbreeding depression does not differ between sex functions and is not affected by the opportunity for mate choice and male-male competition.Theoretical work predicts that the magnitude of inbreeding depression is particularly high in traits that are closely related to fitness. Despite the extensive work on inbreeding depression of male and female reproductive performance, relatively little is known on how inbreeding impairs male and female mating behavior. We studied inbreeding depression of male and female mating behavior in the simultaneously hermaphroditic freshwater snail Physa acuta to test 1) whether there is inbreeding depression of mating behavior, 2) whether the potential of mate competition and mate choice has an effect on the strength of inbreeding depression, 3) whether the magnitude of inbreeding depression differs between both sex functions, and 4) how inbreeding depression of mating behavior translates into inbreeding depression of reproductive success. For this, we compared the mating behavior between selfed (inbred) and outcrossed (outbred) focal snails in a series of mating trials, in which we manipulated experimentally the potential of mate competition and mate choice. Our results provide evidence for moderate inbreeding depression of the number of copulatory encounters, the number of copulations, and the total time spent mating in both sex functions. The magnitude of inbreeding depression did not differ between the levels of competition and between both sex functions. Finally, our results suggest that inbreeding depression of mating behavior only explains a small fraction of the observed inbreeding depression of reproductive success. We discuss the implications of these findings with respect to precopulatory sexual selection and sex-specific inbreeding depression

Molecular adsorbent recirculating system (MARS) and continuous veno-venous hemodiafiltration (CVVHDF) for diltiazem removal: An in vitro study

International audienceThe objective of the present study was to evaluate the efficacy of the molecular adsorbent recirculating system (MARS) vs continuous veno-venous hemodiafiltration (CVVHDF). Diltiazem poisoning was simulated in a central compartment consisting in a 5L dialysis solute spiked with diltiazem at two different toxic concentrations: 750 and 5000 µg/L. For CVVHDF, mean extraction coefficients (EC = (in concentration − out concentration)/in concentration) were concentration-dependent with a decrease all along the dialysis. At the end of the sessions the mean amounts remaining in the central compartment were 8% and 7% of the initial dose at 750 and 5000 µg/L, respectively. The mean cumulative amounts found in the effluent were 60% and 75% of the initial dose, respectively. The missing amounts accounted for 32% and 18% of the initial dose, respectively, corresponding to an adsorption to the dialysis membrane. In contrast, the different compartments of the MARS resulted in undetectable output concentration earlier that the end of the session. The mean concentrations of diltiazem remaining in the central compartment were <1 µg/L at the end of the sessions. Global ECs were around 50% all along the experiment at both concentrations, and the average charcoal cartridge ECs was 80% throughout the experiments. CVVHDF system in the developed model was efficient for diltiazem removal, mainly by diffusion, convection and to a lesser extent by adsorption to the dialysis membrane. In MARS system, resin cartridge and hemodialysis components are ineffective, charcoal cartridge is responsible for almost all drug removal