Public's perspective on COVID-19 adenovirus vector vaccines after thrombosis with thrombocytopenia syndrome (TTS) reports and associated regulatory actions - A cross-sectional study in six EU member states.

OBJECTIVE: In 2021, thrombosis with thrombocytopenia syndrome (TTS) was confirmed by the European Medicines Agency (EMA) as a rare side effect of the COVID-19 adenovirus vector vaccines Vaxzevria® and Jcovden®. This study aimed to describe the public's knowledge of TTS and how it affected the willingness to be vaccinated with COVID-19 vaccines and other vaccines in six European countries. METHODS: From June to October of 2022, a multi-country cross-sectional online survey was conducted in Denmark, Greece, Latvia, Netherlands, Portugal, and Slovenia. The minimum target of participants to be recruited was based on the size of the country's population. The results were analysed descriptively. RESULTS: In total, 3794 respondents were included in the analysis; across the six countries, 33.3 %-68.3 % reported being familiar with signs and symptoms of TTS, although 3.1-61.4 % of those were able to identify the symptoms correctly. The reported changes in willingness to be vaccinated against COVID-19 and with other vaccines varied per country. The largest reported change in the willingness to be vaccinated with Vaxzevria® and Jcovden® was observed in Denmark (61.2 %), while the willingness to be vaccinated with other COVID-19 vaccines changed most in Slovenia (30.4 %). The smallest decrease in willingness towards future vaccination against COVID-19 was reported in the Netherlands (20.9 %) contrasting with the largest decrease observed in Latvia (69.1 %). CONCLUSION: Knowledge about TTS seemed to have influenced the public's opinion in Europe resulting in less willingness to be vaccinated with Vaxzevria® and Jcovden®. Willingness for vaccination against COVID-19 with other vaccines and widespread use of vaccines to prevent other diseases also differed and seemed to be determined by the approaches taken by national health authorities when reacting to and communicating about COVID-19 vaccination risks. Further investigation of optimal risk communication strategies is warranted.

Incorporating inter-individual variability in experimental design improves the quality of results of animal experiments.

Inter-individual variability in quantitative traits is believed to potentially inflate the quality of results in animal experimentation. Yet, to our knowledge this effect has not been empirically tested. Here we test whether inter-individual variability in emotional response within mouse inbred strains affects the outcome of a pharmacological experiment. Three mouse inbred strains (BALB/c, C57BL/6 and 129S2) were behaviorally characterized through repeated exposure to a mild aversive stimulus (modified Hole Board, five consecutive trials). A multivariate clustering procedure yielded two multidimensional response types which were displayed by individuals of all three strains. We show that systematic incorporation of these individual response types in the design of a pharmacological experiment produces different results from an experimental pool in which this variation was not accounted for. To our knowledge, this is the first study that empirically confirms that inter-individual variability affects the interpretation of behavioral phenotypes and may obscure experimental results in a pharmacological experiment.

Inter-individual variability in habituation of anxiety-related responses within three mouse inbred strains.

Inter-individual variability in behavioral and physiological response has become a well-established phenomenon in animal models of anxiety and other disorders. Such variability is even demonstrated within mouse inbred strains. A recent study showed that adaptive and non-adaptive anxiety phenotypes (measured as habituation and/or sensitization of anxiety responses) may differ within cohorts of 129 mice. This variability was expressed across both anxiety- and activity-related behavioral dimensions. These findings were based however on re-analysis of previously published data. The present study therefore aimed to empirically validate these findings in 129 mice. In addition, we assessed such inter-individuality in two other strains: BALB/c and C57BL/6. Males of three mouse inbred strains (BALB/c, C57BL/6 and 129S2) were behaviorally characterized through repeated exposure to a mild aversive stimulus (modified Hole Board, 4 consecutive trials). Behavioral observations were supplemented with assessment of circulating corticosterone levels. Clustering the individual response trajectories of behavioral and endocrine responses yielded two multidimensional response types of different adaptive value. Interestingly, these response types were displayed by individuals of all three strains. The response types differed significantly on anxiety and activity related behavioral dimensions but not on corticosterone concentrations. This study empirically confirms that adaptive capacities may differ within 129 cohorts. In addition, it extends this inter-individual variability in behavioral profiles to BALB/c and C57BL/6. Whether these two sub-types constitute differential anxiety phenotypes may differ per strain and requires further study.

An individual based, multidimensional approach to identify emotional reactivity profiles in inbred mice.

BACKGROUND: Despite extensive environmental standardization and the use of genetically and microbiologically defined mice of similar age and sex, individuals of the same mouse inbred strain commonly differ in quantitative traits. This is a major issue as it affects the quality of experimental results. Standard analysis practices summarize numerical data by means and associated measures of dispersion, while individual values are ignored. Perhaps taking individual values into account in statistical analysis may improve the quality of results. NEW METHOD: The present study re-inspected existing data on emotional reactivity profiles in 125 BALB/cJ and 129 mice, which displayed contrasting patterns of habituation and sensitization when repeatedly exposed to a novel environment (modified Hole Board). Behaviors were re-analyzed on an individual level, using a multivariate approach, in order to explore whether this yielded new information regarding subtypes of response, and their expression between and within strains. RESULTS: Clustering individual mice across multiple behavioral dimensions identified two response profiles: a habituation and a sensitization cluster. COMPARISON WITH EXISTING METHOD(S): These retrospect analyses identified habituation and sensitization profiles that were similar to those observed in the original data but also yielded new information such as a more pronounced sensitization response. Also, it allowed for the identification of individuals that deviated from the predominant response profile within a strain. CONCLUSIONS: The present approach allows for the behavioral characterization of experimental animals on an individual level and as such provides a valuable contribution to existing approaches that take individual variation into account in statistical analysis.

Differences in the nonverbal requests of great apes and human infants.

This study investigated how great apes and human infants use imperative pointing to request objects. In a series of three experiments (infants, N = 44; apes, N = 12), subjects were given the opportunity to either point to a desired object from a distance or else to approach closer and request it proximally. The apes always approached close to the object, signaling their request through instrumental actions. In contrast, the infants quite often stayed at a distance, directing the experimenters' attention to the desired object through index-finger pointing, even when the object was in the open and they could obtain it by themselves. Findings distinguish 12-month-olds' imperative pointing from ontogenetic and phylogenetic earlier forms of ritualized reaching.