SummaryThere is a paucity of information concerning the developmental neurotoxicity (DNT) hazard posed by industrial and environmental chemicals. New testing approaches will most likely be based on batteries of alternative and complementary (non-animal) tests. As DNT is assumed to result from the modulation of fundamental neurodevelopmental processes (such as neuronal differentiation, precursor cell migration or neuronal network formation) by chemicals, the first generation of alternative DNT tests target these processes. The advantage of such types of assays is that they capture toxicants with multiple targets and modes-of-action. Moreover, the processes modelled by the assays can be linked to toxicity endophenotypes, i.e. alterations in neural connectivity that form the basis for neurofunctional deficits in man. The authors of this review convened in a workshop to define criteria for the selection of positive/negative controls, to prepare recommendations on their use, and to initiate the setup of a directory of reference chemicals. For initial technical optimization of tests, a set of >50 endpoint-specific control compounds was identified. For further test development, an additional “test” set of 33 chemicals considered to act directly as bona fide DNT toxicants is proposed, and each chemical is annotated to the extent it fulfills these criteria. A tabular compilation of the original literature used to select the test set chemicals provides information on statistical procedures, and toxic/non-toxic doses (both for pups and dams). Suggestions are provided on how to use the >100 compounds (including negative controls) compiled here to address specificity, adversity and use of alternative test systems.

This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19–21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work.

Introduction:Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy WorkGroup convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results:The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies.Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.

Low‐rate dynamic contact angles of 13 liquids on a polystyrene polymer are measured by an automated axisymmetric drop shape analysis – profile (ADSA‐P). It is found that 7 liquids yielded non‐constant contact angles, and/or dissolved the polymer on contact. From the experimental contact angles of the other 6 liquids, it is found that the liquid‐vapor surface tension times cosine of the contact angle changes smoothly with the liquid‐vapor surface tension, i.e. γlvcosθ depends only on γlv for a given solid surface (or solid surface tension). This contact angle pattern is in harmony with those from other inert and non‐inert (polar and non‐polar) surfaces (7–13, 24–26). The solid‐vapor surface tension calculated from the equation‐of‐state approach for solid‐liquid interfacial tensions (33) is found to be 29.8 mJ/m2, with a 95% confidence limit of ±0.5 mJ/m2 from the experimental contact angles of 6 liquids.

The overall RSV-hospitalization rate in our study was within the range found in previous reports (1.3%-5.3%), although it did not mimic the declining rates of the US Palivizumab Outcomes Registry. This could be due to increased testing for RSV when hospitalized and increasing rates of prophylaxis of infants with underlying medical disorders.