Characterisation of data resources for in silico modelling: benchmark datasets for ADME properties.

Introduction: The cost of in vivo and in vitro screening of ADME properties of compounds has motivated efforts to develop a range of in silico models. At the heart of the development of any computational model are the data; high quality data are essential for developing robust and accurate models. The characteristics of a dataset, such as its availability, size, format and type of chemical identifiers used, influence the modelability of the data. Areas covered: This review explores the usefulness of publicly available ADME datasets for researchers to use in the development of predictive models. More than 140 ADME datasets were collated from publicly available resources and the modelability of 31selected datasets were assessed using specific criteria derived in this study. Expert opinion: Publicly available datasets differ significantly in information content and presentation. From a modelling perspective, datasets should be of adequate size, available in a user-friendly format with all chemical structures associated with one or more chemical identifiers suitable for automated processing (e.g. CAS number, SMILES string or InChIKey). Recommendations for assessing dataset suitability for modelling and publishing data in an appropriate format are discussed

Are We Speaking the Same Language? Recommendations for a Definition and Categorization Framework for Plastic Debris

Embargo until 04 Jan 2020The accumulation of plastic litter in natural environments is a global issue. Concerns over potential negative impacts on the economy, wildlife, and human health provide strong incentives for improving the sustainable use of plastics. Despite the many voices raised on the issue, we lack a consensus on how to define and categorize plastic debris. This is evident for microplastics, where inconsistent size classes are used and where the materials to be included are under debate. While this is inherent in an emerging research field, an ambiguous terminology results in confusion and miscommunication that may compromise progress in research and mitigation measures. Therefore, we need to be explicit on what exactly we consider plastic debris. Thus, we critically discuss the advantages and disadvantages of a unified terminology, propose a definition and categorization framework, and highlight areas of uncertainty. Going beyond size classes, our framework includes physicochemical properties (polymer composition, solid state, solubility) as defining criteria and size, shape, color, and origin as classifiers for categorization. Acknowledging the rapid evolution of our knowledge on plastic pollution, our framework will promote consensus building within the scientific and regulatory community based on a solid scientific foundation.acceptedVersio

Pathways and Management of Phosphorus in urban areas

Due to the finite nature of mineral phosphorus reserves, effective management of anthropogenic phosphorus flows is currently under investigation by the international research community. This article emphasizes the importance of urban phosphorus flows, which are often marginalized due to the greater magnitude of agricultural phosphorus flows. A study on phosphorus flows in Gothenburg, Sweden, points out the potential role of solid waste in nutrient management, as the amounts of phosphorus in solid waste and in wastewater were found to be equal. Importation of food commodities accounts for 50% of the total inflow of phosphorus, and food waste is a major contributor of phosphorus to solid waste. The results suggest that solid waste incineration residues represent a large underestimated sink of phosphorus. Focusing on wastewater as the sole source of recovered phosphorus is not sufficient. The Swedish national goal on phosphorus recycling, which is limited to sewage sludge, targets only a part of the total phosphorus flow that can potentially be recovered. In contrast to previous studies, agricultural flows in Gothenburg were marginal compared to flows related to the urban waste management infrastructure. We emphasize the need for debate on preferable routes for disposal of waste with a high phosphorus content. Both recovery potential and usefulness of the recovered product for agricultural purposes have to be considered. Impacts of five waste management strategies on phosphorus flows were evaluated: incineration of all the waste, comprehensive food waste separation, installation of kitchen grinders, urine diversion, and separation of blackwater and food waste

Making the construction industry resilient to extreme weather:lessons from construction in hot weather conditions

The construction industry is susceptible to extreme weather events (EWEs) due to most of its activities being conducted by manual workers outdoors. Although research has been conducted on the effects of EWEs, such as flooding and snowfall, limited research has been conducted on the effects of heatwaves and hot weather conditions. Heatwaves present a somewhat different risk profile to construction, unlike EWEs such as flooding and heavy snowfall that present physical obstacles to work onsite. However, heatwaves have affected the construction industry in the UK, and construction claims have been made due to adverse weather conditions. With heatwaves being expected to occur more frequently in the coming years, the construction industry may suffer unlike any other industry during the summer months. This creates the need to investigate methods that would allow construction activities to progress during hot summer months with minimal effect on construction projects. Hence, the purpose of this paper. Regions such as the Middle East and the UAE in particular flourish with mega projects, although temperatures soar to above 40̊C in the summer months. Lessons could be learnt from such countries and adapted in the UK. Interviews have been conducted with a lead representative of a client, a consultant and a contractor, all of which currently operate on UAE projects. The key findings include one of the preliminary steps taken by international construction companies operating in the UAE. This involves restructuring their entire regional team by employing management staff from countries such as Lebanon, Palestine, Iraq, and their labour force from the sub-continent such as India and Pakistan. This is not only due to the cheap wage rate but also to the ability to cope and work in such extreme hot weather conditions. The experience of individuals working in the region allows for future planning, where the difference in labour productivity during the extreme hot weather conditions is known, allowing precautionary measures to be put in place

The effect of perfluorocarbon vapour on the measurement of respiratory tidal volume during partial liquid ventilation

During partial liquid ventilation perfluorocarbon vapour is present in the exhaled gases. The volumes of these gases are measured by pneumotachometers. Error in measuring tidal volumes will give erroneous measurement of lung compliance during partial liquid ventilation. We aim to compare measured tidal volumes with and without perfluorocarbon vapour using tidal volumes suitable for use in neonates. Tidal volumes were produced with a 100 ml calibration syringe from 20 to 100 ml and with a calibrated Harvard rodent ventilator from 2.5 to 20 ml. Control tidal volumes were drawn from a humidifier chamber containing water vapour and the PFC tidal volumes were drawn from a humidifier chamber containing water and perfluorocarbon (FC-77) vapour. Tidal volumes were measured by a fixed orifice, target, differential pressure flowmeter (VenTrak) or a hot-wire anenometer (Bear Cub) placed between the calibration syringe or ventilator and the humidifier chamber. All tidal volumes measured with perfluorocarbon vapour were increased compared with control (ANOVA p < 0.001 and post t-test p < 0.0001). Measured tidal volume increased from 7 to 16% with the fixed orifice type flow-meter, and from 35 to 41% with the hot-wire type. In conclusion, perfluorocarbon vapour flowing through pneumotachometers gives falsely high tidal volume measurements. Calculation of lung compliance must take into account the effect of perfluorocarbon vapour on the measurement of tidal volume

Thresholds of Toxicological Concern for Cosmetics-Related Substances: New Database, Thresholds, and Enrichment of Chemical Space

A new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-Adverse-Effect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 μg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 μg/kg-bw/day are broadly similar to those of the original Munro dataset