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Characterization of potential chemical-induced developmental neurotoxicity (DNT) hazard is considered for risk assessment purposes by many regulatory sectors. However, due to test complexity, difficulty in interpreting results and need of substantial resources, the use of the in vivo DNT test guidelines has been limited and animal data on DNT are scarce. To address challenging endpoints such as DNT, the Organisation for Economic Co-Operation and Development (OECD) chemical safety program has been working lately toward the development of integrated approaches for testing and assessment (IATA) that rely on a combination of multiple layers of data (e.g., in vitro, in silico and non-mammalian in vivo models) that are supported by mechanistic knowledge organized according to the adverse outcome pathway (AOP) framework. In 2017, the OECD convened a dedicated OECD expert group to develop a guidance document on the application and interpretation of data derived from a DNT testing battery that relies on key neurodevelopmental processes and is complemented by zebrafish assays. This review will provide a brief overview of the OECD DNT project and summarize various achievements of relevance to the project. The review also presents an opportunity to describe considerations for uptake of the DNT in an in vitro battery in a regulatory context.

With recent rapid advancement of methodological tools, mechanistic understanding of biological processes leading to carcinogenesis is expanding. New approach methodologies such as transcriptomics can inform on non-genotoxic mechanisms of chemical carcinogens and can be developed for regulatory applications. The Organisation for the Economic Cooperation and Development (OECD) expert group developing an Integrated Approach to the Testing and Assessment (IATA) of Non-Genotoxic Carcinogens (NGTxC) is reviewing the possible assays to be integrated therein. In this context, we review the application of transcriptomics approaches suitable for pre-screening gene expression changes associated with phenotypic alterations that underlie the carcinogenic processes for subsequent prioritisation of downstream test methods appropriate to specific key events of non-genotoxic carcinogenesis. Using case studies, we evaluate the potential of gene expression analyses especially in relation to breast cancer, to identify the most relevant approaches that could be utilised as (pre-) screening tools, for example Gene Set Enrichment Analysis (GSEA). We also consider how to address the challenges to integrate gene panels and transcriptomic assays into the IATA, highlighting the pivotal omics markers identified for assay measurement in the IATA key events of inflammation, immune response, mitogenic signalling and cell injury.

The field of intellectual and developmental disabilities (IDD) is currently experiencing a significant transformation that encompasses an integrated approach, especially regarding shared aspects such as a focus on the human and legal rights, the eligibility for services and supports, and an emphasis on individualized supports provided within inclusive community-based environments. Accompanying this transformation is the increased need of precision in both the operational definitions of IDD-related constructs, and the terminology used to describe the respective construct. the specialized literature was revised, and previous works on the subject by the authors were updated. This article provides psychologists with the current definition of intellectual disability, operational definitions of intellectual disability and developmental disabilities constructs and associated terminology, and the parameters of an integrated approach to disability. Implications for psychologists who are involved in diagnosis, classification, and planning supports for persons with intellectual or developmental disability are discussed.

The Brown Marmorated Stink Bug (BMSB), Halyomorpha halys (Stål, 1855) (Hemiptera: Pentatomidae), is one of the most dangerous, invasive agricultural pests globally, causing significant economic losses. This review synthesizes current scientific research on its taxonomy, morphology, biology, ecology, and management, with a focus on the invasion in Europe and the status in Bulgaria. The analysis confirms that H. halis, an invasive pest native to East Asia and established in our country since 2016, is already causing damage to agricultural crops. Key factors for its spread are extreme polyphagy (over 300 host species), its overwintering behavior (entering buildings and vehicles, facilitating anthropochory), and high reproductive potential. Temperature requirements (lower developmental threshold ≈14.2°C and ≈538 DD for a full cycle) and data from the region strongly indicate that species is univoltine or has one and a partial second generation in the main agricultural regions of Bulgaria. Climate change is expected to expand the areas supporting bivoltinism and increase population pressure. Effective management is impossible without implementing an integrated approach (IPM), focusing on behavioral tactics (monitoring at crop borders with pheromone attractants) and urgently researching the potential for biological control with the egg parasitoid Trissolcus japonicus, which is already established adventively in other parts of Europe.

Integrated water planning and management face multiple challenges, among which are the competing interests of several water-using sectors and changing climatic trends. This paper presents integrated and non-integrated climate-environment-water approaches for reservoir operation, illustrated with Karkhe reservoir, Iran. Reservoir operation objectives are meeting municipal, environmental, and agricultural water demands. Results show the integrated approach, which relies on multi-objective optimization of municipal, environmental, and agricultural water supply, improves the municipal, environmental, and agricultural objectives by 70, 32, and 65% compared with the objectives’ values achieved with the non-integrated approach, which implements a standard operating policy.

Parametric thinking has found wide acceptance in both the building industry and environmental sciences. In the context of environmental urban morphology however, parametric thinking has been neglected. This paper critically assesses environmental optimization with a focus on parametric urbanism. The analysis addresses two research questions: “Can parametric thinking and its associated approaches facilitate an environmental urban morphology?” and “If yes, can parametric urbanism support environment optimization in complex urban areas?” Methodologies include a case study in Beijing, qualitative and quantitative analysis, parametric modeling, and environmental simulation. Results indicate that parametric techniques can effectively simulate environmental urban morphology by generating parametric models. These models provide a rational foundation for schematic decision-making about optimizing environments in urban development. Findings include a critique of parametric thinking as applied to city environments and insights about the potential uses of parametric techniques to support quality environmental urban morphology.

Aims Chronic pain is an impeding condition that affects day‐to‐day life and poses a substantial economic burden, surpassing many other health conditions. This study employs a cross‐species integrated approach to uncover novel pain mediators/regulators. Methods We used weighted gene coexpression network analysis to identify pain‐enriched gene module. Functional analysis and protein‐protein interaction (PPI) network analysis of the module genes were conducted. RNA sequencing compared pain model and control mice. PheWAS was performed to link genes to pain‐related GWAS traits. Finally, candidates were prioritized based on node degree, differential expression, GWAS associations, and phenotype correlations. Results A gene module significantly over‐enriched with the pain reference set was identified (referred to as “pain module”). Analysis revealed 141 pain module genes interacting with 46 pain reference genes in the PPI network, which included 88 differentially expressed genes. PheWAS analysis linked 53 of these genes to pain‐related GWAS traits. Expression correlation analysis identified Vdac1, Add2, Syt2, and Syt4 as significantly correlated with pain phenotypes across eight brain regions. NCAM1, VAMP2, SYT2, ADD2, and KCND3 were identified as top pain response/regulator genes. Conclusion The identified genes and molecular mechanisms may enhance understanding of pain pathways and contribute to better drug target identification. Cross‐species analysis was used to identify novel pain mediators based on human DRG expression profiles and RNA‐seq data from a mouse model of neuropathic pain injury.

Challenges calling for integrated approaches to health, such as the One Health (OH) approach, typically arise from the intertwined spheres of humans, animals, and ecosystems constituting their environment. Initiatives addressing such wicked problems commonly consist of complex structures and dynamics. As a result of the EU COST Action (TD 1404) \"Network for Evaluation of One Health\" (NEOH), we propose an evaluation framework anchored in systems theory to address the intrinsic complexity of OH initiatives and regard them as subsystems of the context within which they operate. Typically, they intend to influence a system with a view to improve human, animal, and environmental health. The NEOH evaluation framework consists of four overarching elements, namely: (1) the definition of the initiative and its context, (2) the description of the theory of change with an assessment of expected and unexpected outcomes, (3) the process evaluation of operational and supporting infrastructures (the \"OH-ness\"), and (4) an assessment of the association(s) between the process evaluation and the outcomes produced. It relies on a mixed methods approach by combining a descriptive and qualitative assessment with a semi-quantitative scoring for the evaluation of the degree and structural balance of \"OH-ness\" (summarised in an OH-index and OH-ratio, respectively) and conventional metrics for different outcomes in a multi-criteria-decision-analysis. Here, we focus on the methodology for Elements (1) and (3) including ready-to-use Microsoft Excel spreadsheets for the assessment of the \"OH-ness\". We also provide an overview of Element (2), and refer to the NEOH handbook for further details, also regarding Element (4) (http://neoh.onehealthglobal.net). The presented approach helps researchers, practitioners, and evaluators to conceptualise and conduct evaluations of integrated approaches to health and facilitates comparison and learning across different OH activities thereby facilitating decisions on resource allocation. The application of the framework has been described in eight case studies in the same Frontiers research topic and provides first data on OH-index and OH-ratio, which is an important step towards their validation and the creation of a dataset for future benchmarking, and to demonstrate under which circumstances OH initiatives provide added value compared to disciplinary or conventional health initiatives.

Organophosphorus flame retardants (OPFRs) are abundant and persistent in the environment but have limited toxicity information. Their similarity in structure to organophosphate pesticides presents great concern for developmental neurotoxicity (DNT). However, current in vivo testing is not suitable to provide DNT information on the amount of OPFRs that lack data. Over the past decade, an in vitro battery was developed to enhance DNT assessment, consisting of assays that evaluate cellular processes in neurodevelopment and function. In this study, behavioral data of small model organisms were also included. To assess if these assays provide sufficient mechanistic coverage to prioritize chemicals for further testing and/or identify hazards, an integrated approach to testing and assessment (IATA) was developed with additional information from the Integrated Chemical Environment (ICE) and the literature. Human biomonitoring and exposure data were identified and physiologically-based toxicokinetic models were applied to relate in vitro toxicity data to human exposure based on maximum plasma concentration. Eight OPFRs were evaluated, including aromatic OPFRs (triphenyl phosphate (TPHP), isopropylated phenyl phosphate (IPP), 2-ethylhexyl diphenyl phosphate (EHDP), tricresyl phosphate (TMPP), isodecyl diphenyl phosphate (IDDP), tert-butylphenyl diphenyl phosphate (BPDP)) and halogenated FRs ((Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(2-chloroethyl) phosphate (TCEP)). Two representative brominated flame retardants (BFRs) (2,2′4,4′-tetrabromodiphenyl ether (BDE-47) and 3,3′,5,5′-tetrabromobisphenol A (TBBPA)) with known DNT potential were selected for toxicity benchmarking. Data from the DNT battery indicate that the aromatic OPFRs have activity at similar concentrations as the BFRs and should therefore be evaluated further. However, these assays provide limited information on the mechanism of the compounds. By integrating information from ICE and the literature, endocrine disruption was identified as a potential mechanism. This IATA case study indicates that human exposure to some OPFRs could lead to a plasma concentration similar to those exerting in vitro activities, indicating potential concern for human health.