Walker Greene (nylonbacon17)
The "Peira LLBO 180" is a Laser Light-Based Opacitometer that can be used as an alternative for the standard OP-KIT device in the Bovine Corneal Opacity and Permeability (BCOP) test Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 437 to identify chemicals inducing serious eye damage as defined by United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS), i.e. chemicals to be classified as UN GHS Category 1 and chemicals not requiring classification for eye irritation or serious eye damage under the UN GHS classification system (No Category). • The Peira LLBO 180 offers the advantage of analysing the complete corneal surface and is therefore able to detect more efficiently opaque spots located around the periphery of the excised corneas. • This new device will allow not only a more accurate definition of the eye irritating potential of compounds, but also a more precise ranking of moderate to mild and non-irritating compounds. • The value of Peira LLBO 180 is confirmed during in-house and multi-laboratory evaluation studies and is now included in the updated OECD TG 437, dated 26th of June 2020. The results demonstrate that the presented methodology is an improved new approach methodology (NAM) for ocular irritation testing of liquids and solids.Drug-induced cholestasis (DIC) is a major cause of clinical failure of drug candidates. Numerous patients worldwide are affected when exposed to marketed drugs exhibiting a DIC signature. Prospective identification of DIC during early compound development remains challenging. Here we describe the optimized in vitro procedure for early assessment and prediction of an increased DIC risk. Our method is based on three principles•Exposure of primary human hepatocyte cultures to test compounds in the absence and presence of a physiologically relevant mixture of endogenous bile salts.•Rapid and quantitative assessment of the influence of concomitant bile salt exposure on hepatocyte functionality and integrity after 24 h or 48 h of incubation.•Translation of the in vitro result, expressed as a DIC index (DICI) value, into an in vivo safety margin.Using our historical control data, a new (data driven) DICI cut-off value of 0.78 was established for discerning cholestatic and non-cholestatic compounds. Our DIC assay protocol was further improved by now relying on the principle of the no observable adverse effect level (NOAEL) for determining the highest test compound concentration corresponding to a DICI ≥ 0.78. Predicted safety margin values were subsequently calculated for compounds displaying hepatotoxic and/or cholestatic effects in patients, thus enabling evaluation of the performance of our DIC assay. Of note, this assay can be extended to explore the role of drug metabolites in precipitating DIC.There is a necessity to increase the performance of food production in agriculture, this means, that precise management support in farming systems is required to reduce water use and drainage while avoiding crop stress. Management support based on model predictions is used to increase the performance of food production. However, sources of uncertainty affect the model predictions. Uncertainty in soil properties and uncertain evapotranspiration translate into uncertain predictions, and consequently in risk of performance loss. This paper presents the code and method to analyze performance uncertainty (and risk of performance loss) due to uncertain circumstances. The method is based on using the De Graaf evapotranspiration model and the EMMAN3G model, a Richards equation-based soil water model, as modules to conduct a performance uncertainty study.In this study, the volume of dirty money in Iran was estimated. The data belonged to the period of 1997-2019, and was taken from the Central Bank of Iran (website https//). Fuzzy logic was used to estimate the underground economy. Fuzzy theory can mathematically formulate man