Analysis of a dose-response assay in Scaptotrigona bipunctata bees, Lepeletier, 1836 (Hymenoptera: Apidae) using the logistic regression model under the Bayesian approach

This paper shows the results of a dose-response study in Scaptotrigona bipunctata bees, Lepeletier, 1836 (Hymenoptera: Apidae) exposed to the insecticide Fastac Duo. The aim was to evaluate the lethal concentration that causes the death of 50% of bees (LC50) and investigate the odd of mortality after exposure to different concentrations, using the logistic regression model under the Bayesian approach. In this approach, it is possible to incorporate a prior information and gives more accurate inferential results. Three independent dose-response experiments were analyzed, dissimilar in their lead time according to guidelines from the Organisation for Economic Co-operation and Development (OECD), in which each assay contained four replicates at the concentration levels investigated, including control. Observing exposure to the agrochemical, it was identified that the higher the concentration, the greater the odd of mortality. Regarding the estimated lethal concentrations for each experiment, the following values were found, 0.03 g a.i. L-1, for 24 hours, 0.04 g a.i. L-1, for 48 hours and 0.06 g a.i. L-1 for 72 hours, showing that in experiments with longer exposure times there was an increase in LC50. Concluding, the study showed an alternative approach to classical methods for dose-response studies in Scaptotrigona bipunctata bees exposed to the insecticide Fastac Duo.

Dose-Response Study to Evaluate Dicamba Tolerance in Selected Wild Tomato Germplasm

A greenhouse dose-response study was conducted to determine the tolerance of three wild tomato accessions (TOM199, TOM198, TOM300) in comparison to a commercial cultivar (Better Boy) against the dicamba application at five rates (0, 70, 140, 210, and 280 g ae ha-1) at 14 and 28 days after treatment (DAT). Several physiological traits were evaluated at 0, 1, 3, 5, and 7 DAT. Wild accessions and cultivar were killed at all rates above 70 g ae ha-1 at 14 and 28 DAT, which is why differences between accessions and cultivar were only evident at 70 g ae ha-1. The GR50 (the herbicide rate that causes 50% reduction in dry weight) of Better Boy was 4.4 g ae ha-1 at 28 DAT, and this cultivar was approximately 11-fold more sensitive than wild accessions. At 7 DAT, the levels of H2O2 for wild accessions were lower than Better Boy up to 5 at 70 g ae ha-1 of dicamba. Furthermore, wild accessions showed lower herbicide absorption than Better Boy at all dicamba doses at 1, 3, and 7 DAT. All the three wild accessions expressed tolerance to the dicamba application at the dose of 70 g ae ha-1. At the same time, Better Boy and wild accessions were susceptible to dicamba application at rates of 140, 210, and 280 g ae ha-1.

Biomarkers of Deoxynivalenol, Citrinin, Ochratoxin A and Zearalenone in Pigs after Exposure to Naturally Contaminated Feed Close to Guidance Values

This study applied multi-mycotoxin liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) methods to determine the biomarkers of exposure in urine and serum samples from a dose-response study with pigs. The 24 studied pigs were divided into three groups: a control and two experimental ones (with different levels of feed contamination). They were exposed to feed prepared from cereals contaminated with deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA) and citrinin (CIT) for 14 days. After that, both experimental groups received the same feed as the control group for the next 14 days to determine the kinetics of the disappearance of mycotoxin biomarkers. Urine samples were collected daily in the morning and blood samples—eight-times during the experiment. The study reported herein was the first prolonged exposure experiment for multiple mycotoxins like OTA and CIT in pigs. The urinary and serum levels of all biomarkers correlated well with the respective toxin intake; thereby demonstrating that they are suitable biomarkers of exposure in pigs. Urine is a good candidate to monitor DON, ZEN, OTA, CIT exposure while serum may be used to monitor DON, OTA and CIT. Additionally, OTA has even been quantified in both matrices in the experimental groups two weeks after changing the contaminated feed back to the control, this result differed from those produced by the other mycotoxins which were only quantified during the first two weeks. Therefore both matrices are suitable candidates to monitor prolonged OTA exposure in pigs.

Dietary Supplementation with Casein Glycomacropeptide, Leucine and Tryptophan Reduces Plasma Amino Acid Levels in Men

Background The treatment of mania in bipolar disorders needs to be more efficient, as the manic condition creates severe problems for the patient when it comes to work, finances, relationships, and health. This proof-of-concept study examines to what extent casein glycomacropeptide (CGMP) may reduce the precursors of dopamine, phenylalanine, and tyrosine, in plasma, and therefore be a potential new intervention to treat acute manic episodes. Method The study was designed as a double-blind randomised dose-response study of CGMP (with added leucine and tryptophan) in 15 healthy men, receiving 3 different doses of CGMP with an interval of at least 14 days. Results Administration of CGMP produced a dose dependent depletion of plasma aromatic amino acids. The total area under the curve of plasma ratios of phenylalanine-tyrosine compared to the level of leucine-isoleucine-valine-tryptophan was CGMP(20g): 3.648 [SE:0.3281]; CGMP(40g): 2.368 [SE:0.1858]; CGMP(60g)1.887 [SE:0.2591]. A comparison of the groups showed a dose dependent statistical difference, with a One-Way ANOVA summary (Dunnett) F= 11.87, p= 0.0003, CGMP 20g vs CGMP 40g, p= 0.0042, CGMP 20g vs CGMP 60g, p= 0.0002. No significant side effects were observed. Conclusions This study demonstrate CGMP is a well-tolerated and effective mixture, and that 60 g CGMP produced the highest depletion of plasma aromatic amino acids (phenylalanine and tyrosine). The effect seems to be highest after 3-4 hours. We therefore conclude that this dose should be the one considered for future studies involving CGMP in humans.

Adaptive Contrast Test For Dose-Response Studies

Background: A confirmation of dose-response is complicated by the need to adjust for multiplicity. We propose a simple and powerful adaptive contrast test with ordinal constraint contrast coefficients determined by observed responses.Methods: The adaptive contrast test can perform using easily calculated contrast coefficients and existing statistical software. We provide the sample SAS program codes of analysis and calculation of power for the adaptive contrast test. After the adaptive contrast test shows the statistically significant dose-response, we consider to select the best dose-response model from multiple dose-response models. Based on the best model, we identify a recommended dose. We demonstrate the adaptive contrast test for sample data. In addition, we show the calculation of coefficient, test statistic, and recommended dose for the actual study. We perform the simulation study with eleven scenarios to evaluate the performance of the adaptive contrast test.Results: We confirmed the statistically significant dose-response for the sample data and the actual study. In the simulation study, we confirmed that the adaptive contrast test has higher power in most scenarios compared to the conventional method. In addition, we confirmed that the type 1 error rate of the adaptive contrast test was maintained at a significance level when there was no difference between the treatment groups.Conclusions: We conclude that the adaptive contrast test can be applied unproblematically to the dose-response study.

Benchmarking of a Bayesian single cell RNAseq differential gene expression test for dose-response study designs

The application of single-cell RNA sequencing (scRNAseq) for the evaluation of chemicals, drugs, and food contaminants presents the opportunity to consider cellular heterogeneity in pharmacological and toxicological responses. Current differential gene expression analysis (DGEA) methods focus primarily on two group comparisons, not multi-group dose-response study designs used in safety assessments. To benchmark DGEA methods for dose-response scRNAseq experiments, we proposed a multiplicity corrected Bayesian testing approach and compare it against 8 other methods including two frequentist fit-for-purpose tests using simulated and experimental data. Our Bayesian test method outperformed all other tests for a broad range of accuracy metrics including control of false positive error rates. Most notable, the fit-for-purpose and standard multiple group DGEA methods were superior to the two group scRNAseq methods for dose-response study designs. Collectively, our benchmarking of DGEA methods demonstrates the importance in considering study design when determining the most appropriate test methods.