Considerations for the development of guidance on dose level selection for developmental and reproductive toxicity studies.

In 2022, the European Chemicals Agency issued advice on the selection of high dose levels for developmental and reproductive toxicity (DART) studies indicating that the highest dose tested should aim to induce clear evidence of reproductive toxicity without excessive toxicity and severe suffering in parental animals. In addition, a recent publication advocated that a 10% decrease in body weight gain should be replaced with a 10% decrease in bodyweight as a criterion for dose adequacy. Experts from the European Centre for Ecotoxicology and Toxicology of Chemicals evaluated these recent developments and their potential impact on study outcomes and interpretation and identified that the advice was not aligned with OECD test guidelines or with humane endpoints guidance. Furthermore, data analysis from DART studies indicated that a 10% decrease in maternal body weight during gestation equates to a 25% decrease in body weight gain, which differs from the consensus of experts at a 2010 ILSI/HESI workshop. Dose selection should be based on a biological approach that considers a range of other factors. Excessive dose levels that cause frank toxicity and overwhelm homeostasis should be avoided as they can give rise to effects that are not relevant to human health assessments.

Predicting the safety of medicines in pregnancy: A workshop report.

The framework for developmental toxicity testing has remained largely unchanged for over 50 years and although it remains invaluable in assessing potential risks in pregnancy, knowledge gaps exist, and some outcomes do not necessarily correlate with clinical experience. Advances in omics, in silico approaches and alternative assays are providing opportunities to enhance our understanding of embryo-fetal development and the prediction of potential risks associated with the use of medicines in pregnancy. A workshop organised by the Medicines and Healthcare products Regulatory Agency (MHRA), "Predicting the Safety of Medicines in Pregnancy - a New Era?", was attended by delegates representing regulatory authorities, academia, industry, patients, funding bodies and software developers to consider how to improve the quality of and access to nonclinical developmental toxicity data and how to use this data to better predict the safety of medicines in human pregnancy. The workshop delegates concluded that based on comparative data to date alternative methodologies are currently no more predictive than conventional methods and not qualified for use in regulatory submissions. To advance the development and qualification of alternative methodologies, there is a requirement for better coordinated multidisciplinary cross-sector interactions coupled with data sharing. Furthermore, a better understanding of human developmental biology and the incorporation of this knowledge into the development of alternative methodologies is essential to enhance the prediction of adverse outcomes for human development. The output of the workshop was a series of recommendations aimed at supporting multidisciplinary efforts to develop and validate these alternative methodologies.

A comparison of children's performance on two recognition memory tasks: delayed nonmatch-to-sample versus visual paired-comparison.

Although 4- to 6-month-old children have a significant tendency to look at new stimuli in a visual paired-comparison task (VPC), they have difficulty in consistently choosing novel objects in a delayed nonmatch-to-sample task (DNMS). To evaluate which factors could account for this difficulty, we tested human infants (10-107 months) and adults (17-25 years) in a DNMS task while monitoring eye fixations. The results indicated that children at all ages reliably looked at (VPC scores) or chose (DNMS scores) the new stimuli about 60% of the time, indicating that both tasks measure visual recognition memory. A videotape analysis of visual attention revealed that children younger than 22 months, but not older children, spent significantly more time visually exploring the objects rather than looking at the food reward under it. Although this visual attraction to objects in children younger than 22 months of age may have impaired the formation of stimulus-reinforcer association needed to solve the DNMS task, this was not the case for older children, since beyond 22 months of age children consistently looked at the reward while displacing the objects. These results suggest that other cognitive abilities required by the DNMS task may not be fully functional even in children 22 months and older.

Utilisation of private hospital beds in Auckland for long term geriatric care.

A cross-sectional survey at 25 February 1985 was conducted to determine the utilisation of beds in Auckland's private hospitals. Fifty-three licensed private hospitals accepted patients under the geriatric hospital special assistance scheme (GHSAS). Eighty point eight percent of all patients were receiving public subsidies additional to the universal Department of Health benefit. Ninety-five percent of patients were aged 65 years or more and receiving long term care; of these nearly all had been assessed by a geriatrician and 81.5% were subsidised by the GHSAS. The actual proportion of elderly receiving long term hospital care in Auckland, at 23.3/1000 aged 65 years and over, corresponded closely to newly proposed national guidelines; a previously unrecognised use of private beds for psychogeriatric patients was demonstrated.

Anxiety, cognitive style, and mathematics achievement.

This study examined the relationship among state and trait anxiety, cognitive style, and mathematics achievement. The Ss were 50 junior college students enrolled in a mathematics course. The results confirmed the hypothesis that high state anxiety would be associated with poor mathematics achievement; trait anxiety showed no significant relationship to achievement. The need to develop learning aids and strategies to counteract the possible debilitating effects of state anxiety in learning and mathematics assessment was discussed.