scholarly journals Mixture toxicity of six pharmaceuticals towards Aliivibrio fischeri, Daphnia magna, and Lemna minor

2021 ◽  
Author(s):  
Anna Białk-Bielińska ◽  
Łukasz Grabarczyk ◽  
Ewa Mulkiewicz ◽  
Alan Puckowski ◽  
Stefan Stolte ◽  
...  
Keyword(s):  
Daphnia Magna ◽  
Lemna Minor ◽  
Opioid Analgesic ◽  
Mixture Toxicity ◽  
Concentration Addition ◽  
Case Scenario ◽  
Worst Case ◽  
Ca Model ◽  
Inflammatory Drugs ◽  
Aliivibrio Fischeri

AbstractAs the knowledge on the joint effects of pharmaceuticals towards different non-target organisms is still limited, the aim of our study was to evaluate the toxicity of mixtures of pharmaceuticals, as well as their baseline toxicity towards three selected organisms, namely the bioluminescent bacteria Aliivibrio fischeri, the crustacean Daphnia magna, and the duckweed Lemna minor. Different mixtures composed of three up to five pharmaceuticals having the same or different mechanisms of action in terms of their therapeutic activity (non-steroidal anti-inflammatory drugs, opioid analgesic, antibacterial and anti-epileptic drugs) were investigated. The observed EC50s were compared with those predicted using the concentration addition (CA) and independent action (IA) models. In general, the EC50 values for mixtures predicted with the CA model were lower than those obtained with the IA model, although, in some cases, test predictions of these two models were almost identical. Most of the experimentally determined EC50 values for the specific mixtures were slightly higher than those predicted with the CA model; hence, a less than additive effect was noted. Based on the obtained results, it might be concluded that the CA model assumes the worst-case scenario and gives overall closer predictions; therefore, it should be recommended also for modeling the mixture toxicity of pharmaceuticals with different modes of action.

scholarly journals Novel Segmented Concentration Addition Method to Predict Mixture Hormesis of Chlortetracycline Hydrochloride and Oxytetracycline Hydrochloride to Aliivibrio fischeri

2020 ◽  
Vol 21 (2) ◽  
pp. 481 ◽  
Author(s):  
Huilin Ge ◽  
Min Zhou ◽  
Daizhu Lv ◽  
Mingyue Wang ◽  
Defang Xie ◽  
...  
Keyword(s):  
Mixture Toxicity ◽  
Practical Significance ◽  
Concentration Addition ◽  
High Concentration ◽  
Cross Point ◽  
Antagonistic Action ◽  
Interval Method ◽  
Molar Ratios ◽  
Ca Model ◽  
Aliivibrio Fischeri

Hormesis is a concentration-response phenomenon characterized by low-concentration stimulation and high-concentration inhibition, which typically has a nonmonotonic J-shaped concentration-response curve (J-CRC). The concentration addition (CA) model is the gold standard for studying mixture toxicity. However, the CA model had the predictive blind zone (PBZ) for mixture J-CRC. To solve the PBZ problem, we proposed a segmented concentration addition (SCA) method to predict mixture J-CRC, which was achieved through fitting the left and right segments of component J-CRC and performing CA prediction subsequently. We selected two model compounds including chlortetracycline hydrochloride (CTCC) and oxytetracycline hydrochloride (OTCC), both of which presented J-CRC to Aliivibrio fischeri (AVF). The seven binary mixtures (M1–M7) of CTCC and OTCC were designed according to their molar ratios of 12:1, 10:3, 8:5, 1:1, 5:8, 3:10, and 1:12 referring to the direct equipartition ray design. These seven mixtures all presented J-CRC to AVF. Based on the SCA method, we obtained mixture maximum stimulatory effect concentration (ECm) and maximum stimulatory effect (Em) predicted by SCA, both of which were not available for the CA model. The toxicity interactions of these mixtures were systematically evaluated by using a comprehensive approach, including the co-toxicity coefficient integrated with confidence interval method (CTCICI), CRC, and isobole analysis. The results showed that the interaction types were additive and antagonistic action, without synergistic action. In addition, we proposed the cross point (CP) hypothesis for toxic interactive mixtures presenting J-CRC, that there was generally a CP between mixture observed J-CRC and CA predicted J-CRC; the relative positions of observed and predicted CRCs on either side of the CP would exchange, but the toxic interaction type of mixtures remained unchanged. The CP hypothesis needs to be verified by more mixtures, especially those with synergism. In conclusion, the SCA method is expected to have important theoretical and practical significance for mixture hormesis.

scholarly journals The predictability of mixture toxicity of demethylase inhibiting fungicides to Daphnia magna depends on life-cycle parameters

2014 ◽  
Author(s):  
Enken Hassold ◽  
Thomas Backhaus
Keyword(s):  
Daphnia Magna ◽  
Mixture Toxicity ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Specific Effects ◽  
Predictive Quality ◽  
Dmi Fungicides ◽  
Reproduction Test ◽  
Fecundity Reduction

A variety of different fungicides is found simultaneously in surface waters, among which demethylase inhibitors (DMIs) are a major group. The joint toxicity of four DMIs from different chemical classes (Fenarimol, Prochloraz, Triadimefon and Pyrifenox) was investigated in the reproduction test with Daphnia magna, following an extended protocol according to ISO 10706. We assessed the toxicity of the DMI mixtures across different endpoints and effect levels and evaluated the predictability of their joint action using Concentration Addition (CA) and Independent Action (IA). The mixture reduced fecundity, delayed molting and caused characteristic malformations in offspring in a concentration-dependend manner which is possibly due to an anti-ecdysteroid action, as previously described for individual DMIs. However, also mixture-specific effects were observed: exposed daphnids reached sexual maturity already after the third juvenile molt, and thus significantly earlier than unexposed daphnids, which needed four juvenile molts to reach maturity. This effect is not caused by any of the DMIs alone. Additionally, the percentage of aborted broods was synergistically higher than expected by either CA or IA. IA underestimates the mixture toxicity for all parameters. The predictive quality of CA differed between life history responses, but was always within a factor of two to the observed toxicity. The parameter “fecundity reduction, counting only normally developed offspring” was the most sensitive endpoint, while the parameter “fecundity reduction, counting all living offspring” was slightly less sensitive. The mixture caused a 90% reduction in fecundity at individual concentrations that only provoke 7% effect or less, which calls for a mixture-specific toxicity assessment of DMI fungicides.

scholarly journals The predictability of mixture toxicity of demethylase inhibiting fungicides to Daphnia magna depends on life-cycle parameters

2013 ◽  
Author(s):  
Enken Hassold ◽  
Thomas Backhaus
Keyword(s):  
Daphnia Magna ◽  
Mixture Toxicity ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Specific Effects ◽  
Predictive Quality ◽  
Dmi Fungicides ◽  
Reproduction Test ◽  
Fecundity Reduction

A variety of different fungicides is found simultaneously in surface waters, among which demethylase inhibitors (DMIs) are a major group. The joint toxicity of four DMIs from different chemical classes (Fenarimol, Prochloraz, Triadimefon and Pyrifenox) was investigated in the reproduction test with Daphnia magna, following an extended protocol according to ISO 10706. We assessed the toxicity of the DMI mixtures across different endpoints and effect levels and evaluated the predictability of their joint action using Concentration Addition (CA) and Independent Action (IA). The mixture reduced fecundity, delayed molting and caused characteristic malformations in offspring in a concentration-dependend manner which is possibly due to an anti-ecdysteroid action, as previously described for individual DMIs. However, also mixture-specific effects were observed: exposed daphnids reached sexual maturity already after the third juvenile molt, and thus significantly earlier than unexposed daphnids, which needed four juvenile molts to reach maturity. This effect is not caused by any of the DMIs alone. Additionally, the percentage of aborted broods was synergistically higher than expected by either CA or IA. IA underestimates the mixture toxicity for all parameters. The predictive quality of CA differed between life history responses, but was always within a factor of two to the observed toxicity. The parameter “fecundity reduction, counting only normally developed offspring” was the most sensitive endpoint, while the parameter “fecundity reduction, counting all living offspring” was slightly less sensitive. The mixture caused a 90% reduction in fecundity at individual concentrations that only provoke 7% effect or less, which calls for a mixture-specific toxicity assessment of DMI fungicides.

scholarly journals The predictability of mixture toxicity of demethylase inhibiting fungicides to Daphnia magna depends on life-cycle parameters

2014 ◽  
Author(s):  
Enken Hassold ◽  
Thomas Backhaus
Keyword(s):  
Daphnia Magna ◽  
Mixture Toxicity ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Specific Effects ◽  
Predictive Quality ◽  
Dmi Fungicides ◽  
Reproduction Test ◽  
Fecundity Reduction

A variety of different fungicides is found simultaneously in surface waters, among which demethylase inhibitors (DMIs) are a major group. The joint toxicity of four DMIs from different chemical classes (Fenarimol, Prochloraz, Triadimefon and Pyrifenox) was investigated in the reproduction test with Daphnia magna, following an extended protocol according to ISO 10706. We assessed the toxicity of the DMI mixtures across different endpoints and effect levels and evaluated the predictability of their joint action using Concentration Addition (CA) and Independent Action (IA). The mixture reduced fecundity, delayed molting and caused characteristic malformations in offspring in a concentration-dependend manner which is possibly due to an anti-ecdysteroid action, as previously described for individual DMIs. However, also mixture-specific effects were observed: exposed daphnids reached sexual maturity already after the third juvenile molt, and thus significantly earlier than unexposed daphnids, which needed four juvenile molts to reach maturity. This effect is not caused by any of the DMIs alone. Additionally, the percentage of aborted broods was synergistically higher than expected by either CA or IA. IA underestimates the mixture toxicity for all parameters. The predictive quality of CA differed between life history responses, but was always within a factor of two to the observed toxicity. The parameter “fecundity reduction, counting only normally developed offspring” was the most sensitive endpoint, while the parameter “fecundity reduction, counting all living offspring” was slightly less sensitive. The mixture caused a 90% reduction in fecundity at individual concentrations that only provoke 7% effect or less, which calls for a mixture-specific toxicity assessment of DMI fungicides.

scholarly journals Mixture toxicity analysis in zebrafish embryo: a time and concentration resolved study on mixture effect predictivity

2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Gianina Jakobs ◽  
Janet Krüger ◽  
Andreas Schüttler ◽  
Rolf Altenburger ◽  
Wibke Busch
Keyword(s):  
Exposure Duration ◽  
Prediction Accuracy ◽  
Mixture Toxicity ◽  
Concentration Addition ◽  
Short Term ◽  
Response Curves ◽  
Low Concentrations ◽  
Short Term Exposure ◽  
Deviation Factor ◽  
Ca Model

Abstract Background Humans and wildlife are continuously exposed to chemical mixtures. These mixtures vary in composition but typically contain hundreds of micropollutants at low concentrations. As it is not feasible to measure the toxicity of all possibly occurring mixtures, there is a need to predict mixture toxicity. Two models, Concentration Addition (CA) and Independent Action (IA), have been applied to estimate mixture toxicity. Here, we compared measured with predicted toxicity of nine mixtures designed from 15 environmentally relevant substances in zebrafish embryos to investigate the usability of these models for predicting phenotypic effects in a whole organism short term acute assay. Results In total, we compared 177 toxicity values derived from 31 exposure scenarios with their predicted counterparts. Our results show that mixture toxicity was either correctly estimated (86%) by the prediction window, the concentration-effect space that is spanned between both models, or was underestimated with both models (14%). The CA model correctly predicted the measured mixture toxicity in 100% of cases when a prediction deviation factor of 2.5 was allowed. However, prediction accuracy of mixture toxicity prediction was dependent on exposure duration and mixture potency. The CA model showed highest prediction quality for long-term exposure with highly potent mixtures, respectively, whereas IA proved to be more accurate for short-term exposure with less potent mixtures. Obtained mixture concentration–response curves were steep and indicated the occurrence of remarkable combined effects as mixture constituents were applied at concentrations below their respective individual effect threshold in 90% of all investigated cases. Conclusions Experimental factors, such as exposure duration or mixture potency, influence the prediction accuracy of both inspected models. The CA model showed highest prediction accuracy even for a set of diverse mixtures and various exposure conditions. However, the prediction window served as the most robust predicator to estimate mixture toxicity. Overall, our results demonstrate the importance of considering mixture toxicity in risk assessment schemes and give guidance for future experiment design regarding mixture toxicity investigations.

Reducing Probabilistic Weather Forecasts to the Worst Case Scenario: Anchoring Effects

2008 ◽  
Author(s):  
Sonia Savelli ◽  
Susan Joslyn ◽  
Limor Nadav-Greenberg ◽  
Queena Chen
Keyword(s):  
Case Scenario ◽  
Worst Case ◽  
Weather Forecasts ◽  
Worst Case Scenario ◽  
Anchoring Effects

EXPEDITION TO MALI, 2020

2020 ◽  
pp. 12-28
Author(s):  
D. V. Vaniukova ◽  
◽  
P. A. Kutsenkov ◽  
Keyword(s):  
Mass Murder ◽  
The State ◽  
Case Scenario ◽  
Worst Case ◽  
Traditional Art ◽  
Peter The Great ◽  
State Museum ◽  
Bobo Dioulasso ◽  
Oriental Studies ◽  
The Village

The research expedition of the Institute of Oriental studies of the Russian Academy of Sciences has been working in Mali since 2015. Since 2017, it has been attended by employees of the State Museum of the East. The task of the expedition is to study the transformation of traditional Dogon culture in the context of globalization, as well as to collect ethnographic information (life, customs, features of the traditional social and political structure); to collect oral historical legends; to study the history, existence, and transformation of artistic tradition in the villages of the Dogon Country in modern conditions; collecting items of Ethnography and art to add to the collection of the African collection of the. Peter the Great Museum (Kunstkamera, Saint Petersburg) and the State Museum of Oriental Arts (Moscow). The plan of the expedition in January 2020 included additional items, namely, the study of the functioning of the antique market in Mali (the “path” of things from villages to cities, which is important for attributing works of traditional art). The geography of our research was significantly expanded to the regions of Sikasso and Koulikoro in Mali, as well as to the city of Bobo-Dioulasso and its surroundings in Burkina Faso, which is related to the study of migrations to the Bandiagara Highlands. In addition, the plan of the expedition included organization of a photo exhibition in the Museum of the village of Endé and some educational projects. Unfortunately, after the mass murder in March 2019 in the village of Ogossogou-Pel, where more than one hundred and seventy people were killed, events in the Dogon Country began to develop in the worst-case scenario: The incessant provocations after that revived the old feud between the Pel (Fulbe) pastoralists and the Dogon farmers. So far, this hostility and mutual distrust has not yet developed into a full-scale ethnic conflict, but, unfortunately, such a development now seems quite likely.

Risk-Based Robust Bidding Strategies for EVs’ Aggregators in Day-ahead Markets with Uncertainty

2020 ◽  
Author(s):  
Ahmed Abdelmoaty ◽  
Wessam Mesbah ◽  
Mohammad A. M. Abdel-Aal ◽  
Ali T. Alawami
Keyword(s):  
Robust Optimization ◽  
Electricity Market ◽  
Real Life ◽  
Optimization Approach ◽  
Case Scenario ◽  
Worst Case ◽  
Bidding Strategies ◽  
Wind Generators ◽  
Proposed Model ◽  
Optimal Bidding

In the recent electricity market framework, the profit of the generation companies depends on the decision of the operator on the schedule of its units, the energy price, and the optimal bidding strategies. Due to the expanded integration of uncertain renewable generators which is highly intermittent such as wind plants, the coordination with other facilities to mitigate the risks of imbalances is mandatory. Accordingly, coordination of wind generators with the evolutionary Electric Vehicles (EVs) is expected to boost the performance of the grid. In this paper, we propose a robust optimization approach for the coordination between the wind-thermal generators and the EVs in a virtual<br>power plant (VPP) environment. The objective of maximizing the profit of the VPP Operator (VPPO) is studied. The optimal bidding strategy of the VPPO in the day-ahead market under uncertainties of wind power, energy<br>prices, imbalance prices, and demand is obtained for the worst case scenario. A case study is conducted to assess the e?effectiveness of the proposed model in terms of the VPPO's profit. A comparison between the proposed model and the scenario-based optimization was introduced. Our results confirmed that, although the conservative behavior of the worst-case robust optimization model, it helps the decision maker from the fluctuations of the uncertain parameters involved in the production and bidding processes. In addition, robust optimization is a more tractable problem and does not suffer from<br>the high computation burden associated with scenario-based stochastic programming. This makes it more practical for real-life scenarios.<br>

scholarly journals A Thermally Conductive Pt/AAO Catalyst for Hydrogen Passive Autocatalytic Recombination

Catalysts ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 491
Author(s):  
Alina E. Kozhukhova ◽  
Stephanus P. du Preez ◽  
Aleksander A. Malakhov ◽  
Dmitri G. Bessarabov
Keyword(s):  
Electron Microscopy ◽  
Particle Size ◽  
Combustion Temperature ◽  
Volume Fraction ◽  
Morphological Characteristics ◽  
Al Alloy ◽  
Impregnation Method ◽  
Case Scenario ◽  
Worst Case ◽  
Thermal Distribution

In this study, a Pt/anodized aluminum oxide (AAO) catalyst was prepared by the anodization of an Al alloy (Al6082, 97.5% Al), followed by the incorporation of Pt via an incipient wet impregnation method. Then, the Pt/AAO catalyst was evaluated for autocatalytic hydrogen recombination. The Pt/AAO catalyst’s morphological characteristics were determined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The average Pt particle size was determined to be 3.0 ± 0.6 nm. This Pt/AAO catalyst was tested for the combustion of lean hydrogen (0.5–4 vol% H2 in the air) in a recombiner section testing station. The thermal distribution throughout the catalytic surface was investigated at 3 vol% hydrogen (H2) using an infrared camera. The Al/AAO system had a high thermal conductivity, which prevents the formation of hotspots (areas where localized surface temperature is higher than an average temperature across the entire catalyst surface). In turn, the Pt stability was enhanced during catalytic hydrogen combustion (CHC). A temperature gradient over 70 mm of the Pt/AAO catalyst was 23 °C and 42 °C for catalysts with uniform and nonuniform (worst-case scenario) Pt distributions. The commercial computational fluid dynamics (CFD) code STAR-CCM+ was used to compare the experimentally observed and numerically simulated thermal distribution of the Pt/AAO catalyst. The effect of the initial H2 volume fraction on the combustion temperature and conversion of H2 was investigated. The activation energy for CHC on the Pt/AAO catalyst was 19.2 kJ/mol. Prolonged CHC was performed to assess the durability (reactive metal stability and catalytic activity) of the Pt/AAO catalyst. A stable combustion temperature of 162.8 ± 8.0 °C was maintained over 530 h of CHC. To confirm that Pt aggregation was avoided, the Pt particle size and distribution were determined by TEM before and after prolonged CHC.

scholarly journals A Comparison of Match Demands Using Ball-in-Play versus Whole Match Data in Professional Soccer Players of the English Championship

Sports ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 76
Author(s):  
Dylan Mernagh ◽  
Anthony Weldon ◽  
Josh Wass ◽  
John Phillips ◽  
Nimai Parmar ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Soccer Players ◽  
Training Methods ◽  
Case Scenario ◽  
Worst Case ◽  
Repeated Measures Design ◽  
Worst Case Scenario ◽  
Professional Soccer ◽  
Peak Match ◽  
Playing Time

This is the first study to report the whole match, ball-in-play (BiP), ball-out-of-play (BoP), and Max BiP (worst case scenario phases of play) demands of professional soccer players competing in the English Championship. Effective playing time per soccer game is typically <60 min. When the ball is out of play, players spend time repositioning themselves, which is likely less physically demanding. Consequently, reporting whole match demands may under-report the physical requirements of soccer players. Twenty professional soccer players, categorized by position (defenders, midfielders, and forwards), participated in this study. A repeated measures design was used to collect Global Positioning System (GPS) data over eight professional soccer matches in the English Championship. Data were divided into whole match and BiP data, and BiP data were further sub-divided into different time points (30–60 s, 60–90 s, and >90 s), providing peak match demands. Whole match demands recorded were compared to BiP and Max BiP, with BiP data excluding all match stoppages, providing a more precise analysis of match demands. Whole match metrics were significantly lower than BiP metrics (p < 0.05), and Max BiP for 30–60 s was significantly higher than periods between 60–90 s and >90 s. No significant differences were found between positions. BiP analysis allows for a more accurate representation of the game and physical demands imposed on professional soccer players. Through having a clearer understanding of maximum game demands in professional soccer, practitioners can design more specific training methods to better prepare players for worst case scenario passages of play.

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