From the article: Abstract Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the carcinogenicity study (True Negatives). Cellular hypertrophy appeared to be an unreliable predictor of carcinogenicity. The negative predictivity, the measure of the compounds evaluated that did not show any putative preneoplastic lesion in de sub-chronic studies and were negative in the carcinogenicity studies, was 75%, whereas the sensitivity, a measure of the sub-chronic study to predict a positive carcinogenicity outcome was only 5%. The specificity, the accuracy of the sub-chronic study to correctly identify non-carcinogens was 90%. When the chemicals which induced tumours generally considered not relevant for humans (33 out of 37 False Negatives) are classified as True Negatives, the negative predictivity amounts to 97%. Overall, the results of this retrospective study support the concept that chemicals showing no histopathological risk factors for neoplasia in a sub-chronic study in rats may be considered non-carcinogenic and do not require further testing in a carcinogenicity study.
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This article gives information on an international ring trial of the epidermal-equivalent (EE) sensitizer potency assay.
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Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.
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The built environment requires energy-flexible buildings to reduce energy peak loads and to maximize the use of (decentralized) renewable energy sources. The challenge is to arrive at smart control strategies that respond to the increasing variations in both the energy demand as well as the variable energy supply. This enables grid integration in existing energy networks with limited capacity and maximises use of decentralized sustainable generation. Buildings can play a key role in the optimization of the grid capacity by applying demand-side management control. To adjust the grid energy demand profile of a building without compromising the user requirements, the building should acquire some energy flexibility capacity. The main ambition of the Brains for Buildings Work Package 2 is to develop smart control strategies that use the operational flexibility of non-residential buildings to minimize energy costs, reduce emissions and avoid spikes in power network load, without compromising comfort levels. To realise this ambition the following key components will be developed within the B4B WP2: (A) Development of open-source HVAC and electric services models, (B) development of energy demand prediction models and (C) development of flexibility management control models. This report describes the developed first two key components, (A) and (B). This report presents different prediction models covering various building components. The models are from three different types: white box models, grey-box models, and black-box models. Each model developed is presented in a different chapter. The chapters start with the goal of the prediction model, followed by the description of the model and the results obtained when applied to a case study. The models developed are two approaches based on white box models (1) White box models based on Modelica libraries for energy prediction of a building and its components and (2) Hybrid predictive digital twin based on white box building models to predict the dynamic energy response of the building and its components. (3) Using CO₂ monitoring data to derive either ventilation flow rate or occupancy. (4) Prediction of the heating demand of a building. (5) Feedforward neural network model to predict the building energy usage and its uncertainty. (6) Prediction of PV solar production. The first model aims to predict the energy use and energy production pattern of different building configurations with open-source software, OpenModelica, and open-source libraries, IBPSA libraries. The white-box model simulation results are used to produce design and control advice for increasing the building energy flexibility. The use of the libraries for making a model has first been tested in a simple residential unit, and now is being tested in a non-residential unit, the Haagse Hogeschool building. The lessons learned show that it is possible to model a building by making use of a combination of libraries, however the development of the model is very time consuming. The test also highlighted the need for defining standard scenarios to test the energy flexibility and the need for a practical visualization if the simulation results are to be used to give advice about potential increase of the energy flexibility. The goal of the hybrid model, which is based on a white based model for the building and systems and a data driven model for user behaviour, is to predict the energy demand and energy supply of a building. The model's application focuses on the use case of the TNO building at Stieltjesweg in Delft during a summer period, with a specific emphasis on cooling demand. Preliminary analysis shows that the monitoring results of the building behaviour is in line with the simulation results. Currently, development is in progress to improve the model predictions by including the solar shading from surrounding buildings, models of automatic shading devices, and model calibration including the energy use of the chiller. The goal of the third model is to derive recent and current ventilation flow rate over time based on monitoring data on CO₂ concentration and occupancy, as well as deriving recent and current occupancy over time, based on monitoring data on CO₂ concentration and ventilation flow rate. The grey-box model used is based on the GEKKO python tool. The model was tested with the data of 6 Windesheim University of Applied Sciences office rooms. The model had low precision deriving the ventilation flow rate, especially at low CO2 concentration rates. The model had a good precision deriving occupancy from CO₂ concentration and ventilation flow rate. Further research is needed to determine if these findings apply in different situations, such as meeting spaces and classrooms. The goal of the fourth chapter is to compare the working of a simplified white box model and black-box model to predict the heating energy use of a building. The aim is to integrate these prediction models in the energy management system of SME buildings. The two models have been tested with data from a residential unit since at the time of the analysis the data of a SME building was not available. The prediction models developed have a low accuracy and in their current form cannot be integrated in an energy management system. In general, black-box model prediction obtained a higher accuracy than the white box model. The goal of the fifth model is to predict the energy use in a building using a black-box model and measure the uncertainty in the prediction. The black-box model is based on a feed-forward neural network. The model has been tested with the data of two buildings: educational and commercial buildings. The strength of the model is in the ensemble prediction and the realization that uncertainty is intrinsically present in the data as an absolute deviation. Using a rolling window technique, the model can predict energy use and uncertainty, incorporating possible building-use changes. The testing in two different cases demonstrates the applicability of the model for different types of buildings. The goal of the sixth and last model developed is to predict the energy production of PV panels in a building with the use of a black-box model. The choice for developing the model of the PV panels is based on the analysis of the main contributors of the peak energy demand and peak energy delivery in the case of the DWA office building. On a fault free test set, the model meets the requirements for a calibrated model according to the FEMP and ASHRAE criteria for the error metrics. According to the IPMVP criteria the model should be improved further. The results of the performance metrics agree in range with values as found in literature. For accurate peak prediction a year of training data is recommended in the given approach without lagged variables. This report presents the results and lessons learned from implementing white-box, grey-box and black-box models to predict energy use and energy production of buildings or of variables directly related to them. Each of the models has its advantages and disadvantages. Further research in this line is needed to develop the potential of this approach.
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The full potential of predictive maintenance has not yet been utilised. Current solutions focus on individual steps of the predictive maintenance cycle and only work for very specific settings. The overarching challenge of predictive maintenance is to leverage these individual building blocks to obtain a framework that supports optimal maintenance and asset management. The PrimaVera project has identified four obstacles to tackle in order to utilise predictive maintenance at its full potential: lack of orchestration and automation of the predictive maintenance workflow, inaccurate or incomplete data and the role of human and organisational factors in data-driven decision support tools. Furthermore, an intuitive generic applicable predictive maintenance process model is presented in this paper to provide a structured way of deploying predictive maintenance solutions https://doi.org/10.3390/app10238348 LinkedIn: https://www.linkedin.com/in/john-bolte-0856134/
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The timely detection of post-stroke depression is complicated by a decreasing length of hospital stay. Therefore, the Post-stroke Depression Prediction Scale was developed and validated. The Post-stroke Depression Prediction Scale is a clinical prediction model for the early identification of stroke patients at increased risk for post-stroke depression. he study included 410 consecutive stroke patients who were able to communicate adequately. Predictors were collected within the first week after stroke. Between 6 to 8 weeks after stroke, major depressive disorder was diagnosed using the Composite International Diagnostic Interview. Multivariable logistic regression models were fitted. A bootstrap-backward selection process resulted in a reduced model. Performance of the model was expressed by discrimination, calibration, and accuracy.
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Objective: To predict mortality with the Tilburg Frailty Indicator (TFI) in a sample of community-dwelling older people, using a follow-up of 7 years. Setting and Participants: 479 Dutch community-dwelling people aged 75 years or older. Measurements: The TFI, a self-report questionnaire, was used to collect data about total, physical, psychological, and social frailty. The municipality of Roosendaal (a town in the Netherlands) provided the mortality dates. Conclusions and Implications: This study has shown the predictive validity of the TFI for mortality in community-dwelling older people. Our study demonstrated that physical and psychological frailty predicted mortality. Of the individual TFI components, difficulty in walking consistently predicted mortality. For identifying frailty, using the integral instrument is recommended because total, physical, psychological, and social frailty and its components have proven their value in predicting adverse outcomes of frailty, for example, increase in health care use and a lower quality of life.
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Individuals with autism increasingly enroll in universities, but little is known about predictors for their success. This study developed predictive models for the academic success of autistic bachelor students (N=101) in comparison to students with other health conditions (N=2465) and students with no health conditions (N=25,077). We applied propensity score weighting to balance outcomes. The research showed that autistic students’ academic success was predictable, and these predictions were more accurate than predictions of their peers’ success. For first-year success, study choice issues were the most important predictors (parallel program and application timing). Issues with participation in pre-education (missingness of grades in pre-educational records) and delays at the beginning of autistic students’ studies (reflected in age) were the most influential predictors for the second-year success and delays in the second and final year of their bachelor’s program. In addition, academic performance (average grades) was the strongest predictor for degree completion in 3 years. These insights can enable universities to develop tailored support for autistic students. Using early warning signals from administrative data, institutions can lower dropout risk and increase degree completion for autistic students.
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Abstract Purpose To determine the predictive value of quality of life for mortality at the domain and item levels. Methods This longitudinal study was carried out in a sample of 479 Dutch people aged 75 years or older living independently, using a follow-up of 7 years. Participants completed a self-report questionnaire. Quality of life was assessed with the WHOQOL-BREF, including four domains: physical health, psychological, social relationships, and environment. The municipality of Roosendaal (a town in the Netherlands) indicated the dates of death of the individuals. Results Based on mean, all quality of life domains predicted mortality adjusted for gender, age, marital status, education, and income. The hazard ratios ranged from 0.811 (psychological) to 0.933 (social relationships). The areas under the curve (AUCs) of the four domains were 0.730 (physical health), 0.723 (psychological), 0.693 (social relationships), and 0.700 (environment). In all quality of life domains, at least one item predicted mortality (adjusted). Conclusion Our study showed that all four quality of life domains belonging to the WHOQOL-BREF predict mortality in a sample of Dutch community-dwelling older people using a follow-up period of 7 years. Two AUCs were above threshold (psychological, physical health). The findings offer health care and welfare professionals evidence for conducting interventions to reduce the risk of premature death.
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Background: Modern modeling techniques may potentially provide more accurate predictions of dichotomous outcomes than classical techniques. Objective: In this study, we aimed to examine the predictive performance of eight modeling techniques to predict mortality by frailty. Methods: We performed a longitudinal study with a 7-year follow-up. The sample consisted of 479 Dutch community-dwelling people, aged 75 years and older. Frailty was assessed with the Tilburg Frailty Indicator (TFI), a self-report questionnaire. This questionnaire consists of eight physical, four psychological, and three social frailty components. The municipality of Roosendaal, a city in the Netherlands, provided the mortality dates. We compared modeling techniques, such as support vector machine (SVM), neural network (NN), random forest, and least absolute shrinkage and selection operator, as well as classical techniques, such as logistic regression, two Bayesian networks, and recursive partitioning (RP). The area under the receiver operating characteristic curve (AUROC) indicated the performance of the models. The models were validated using bootstrapping. Results: We found that the NN model had the best validated performance (AUROC=0.812), followed by the SVM model (AUROC=0.705). The other models had validated AUROC values below 0.700. The RP model had the lowest validated AUROC (0.605). The NN model had the highest optimism (0.156). The predictor variable “difficulty in walking” was important for all models. Conclusions: Because of the high optimism of the NN model, we prefer the SVM model for predicting mortality among community-dwelling older people using the TFI, with the addition of “gender” and “age” variables. External validation is a necessary step before applying the prediction models in a new setting.
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