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Previous research on body appreciation across the lifespan has produced conflicting results that it increases with age, decreases with age, or is generally stable with an increase in women over 50-years-old. Furthermore, most of the research has been conducted in White, Western populations. Cross-cultural research suggests that both Chinese and African women experience similar sociocultural pressures as White Western women, and that appearance ideals are shifting to resemble a more Western ideal. We cross-sectionally and cross-culturally examined body appreciation across the lifespan, recruiting White Western women (UK, USA, Canada, and Australia), Black Nigerian women, and Chinese women. 1186 women aged 18-80 completed measures of body appreciation, internalisation of thin and athletic ideals, and perceived sociocultural pressure. Body appreciation did not vary with age in women from any country. Nigerian women reported the highest body appreciation, and Western women the lowest. Higher thin/athletic ideal internalisation, and higher perceived sociocultural pressure were significantly associated with lower body appreciation in all countries and age-groups. Overall, our findings indicate that although levels of body appreciation differ drastically between ethnicities and cultures, it is generally stable across age, and shows cross-culturally robust relationships between sociocultural internalisation and pressure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hanson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the risk assessment of agrochemicals, there has been a historical paucity of using data to refine the default adjustment factors, even though large datasets are available to support this. The current state of the science for addressing uncertainty regarding animal to human extrapolation (AF A ) is to develop a "data-derived" adjustment factor (DDEF) to quantify such differences, if data are available. Toxicokinetic (TK) and toxicodynamic (TD) differences between species can be utilized for the DDEF, with human datasets being ideal yet rare. We identified a case for a currently registered herbicide, mesotrione, in which human TK and TD are available. This case study outlines an approach for the development of DDEFs using comparative human and animal data and based on an adverse outcome pathway (AOP) for inhibition of 4-hydroxyphenol pyruvate dioxygenase (HHPD). The calculated DDEF for rat to human extrapolation (AF A ) for kinetics (AF AK = 2.5) was multiplied by the AF A for dynamics (AF AD = 0.3) resulting in a composite DDEF of ∼1 (AF A = 0.75). This reflects the AOP and available scientific evidence that humans are less sensitive than rats to the effects of HPPD inhibitors. Further analyses were conducted utilizing in vitro datasets from hepatocytes and liver cytosols and extrapolated to whole animal using in vitro to in vivo extrapolation (IVIVE) to support toxicodynamic extrapolation. The in vitro datasets resulted in the same AF AD as derived for in vivo data (AF AD = 0.3). These analyses demonstrate that a majority of the species differences are related to toxicodynamics. Future work with additional in vitro/in vivo datasets for other HPPD inhibitors and cell types will further support this result. This work demonstrates utilization of all available toxicokinetic and toxicodynamic data to replace default uncertainty factors for agrochemical human health risk assessment.

'Embodied cognition' suggests that our bodily experiences broadly shape our cognitive capabilities. We study how embodied experience affects the abstract physical problem-solving styles people use in a virtual task where embodiment does not affect action capabilities. We compare how groups with different embodied experience - 25 children and 35 adults with congenital limb differences versus 45 children and 40 adults born with two hands - perform this task, and find that while there is no difference in overall competence, the groups use different cognitive styles to find solutions. People born with limb differences think more before acting but take fewer attempts to reach solutions. Conversely, development affects the particular actions children use, as well as their persistence with their current strategy. Our findings suggest that while development alters action choices and persistence, differences in embodied experience drive changes in the acquisition of cognitive styles for balancing acting with thinking., (© 2023. The Author(s).)

The advancement of motor augmentation and the broader domain of human-machine interaction rely on a seamless integration with users' physical and cognitive capabilities. These considerations may markedly fluctuate among individuals on the basis of their age, form, and abilities. There is a need to develop a standard for considering these diversity needs and preferences to guide technological development, and large-scale testing can provide us with evidence for such considerations. Public engagement events provide an important opportunity to build a bidirectional discourse with potential users for the codevelopment of inclusive and accessible technologies. We exhibited the Third Thumb, a hand augmentation device, at a public engagement event and tested participants from the general public, who are often not involved in such early technological development of wearable robotic technology. We focused on wearability (fit and control), ability to successfully operate the device, and ability levels across diversity factors relevant for physical technologies (gender, handedness, and age). Our inclusive design was successful in 99.3% of our diverse sample of 596 individuals tested (age range from 3 to 96 years). Ninety-eight percent of participants were further able to successfully manipulate objects using the extra thumb during the first minute of use, with no significant influences of gender, handedness, or affinity for hobbies involving the hands. Performance was generally poorer among younger children (aged ≤11 years). Although older and younger adults performed the task comparably, we identified age costs with the older adults. Our findings offer tangible demonstration of the initial usability of the Third Thumb for a broad demographic.

The present study explored the effects of visuomotor synchrony in virtual reality during the embodiment of a full human avatar in children (aged 5-6 years) and adults. Participants viewed their virtual bodies from a first-person perspective while they moved the body during self-generated and structured movement. Embodiment was measured via questions and psychophysiological responses (skin conductance) to a virtual body-threat and during both movement conditions. Both children and adults had increased feelings of ownership and agency over a virtual body during synchronous visuomotor feedback (compared to asynchronous visuomotor feedback). Children had greater ownership compared to adults during synchronous movement but did not differ from adults on agency. There were no differences in SCRs (frequency or magnitude) between children and adults, between conditions (i.e., baseline or movement conditions) or visuomotor feedback. Collectively, the study highlights the importance of visuomotor synchrony for children's ratings of embodiment for a virtual avatar from at least 5 years old, and suggests adults and children are comparable in terms of psychophysiological arousal when moving (or receiving a threat to) a virtual body. This has important implications for our understanding of the development of embodied cognition and highlights the considerable promise of exploring visuomotor VR experiences in children., (© 2024 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Introduction: Acetyl-coenzyme A carboxylase (ACCase) inhibition is an attractive herbicide target. However, issues with fetal developmental toxicity identified at the late stages of the development process can halt progression of previously promising candidates., Objectives: To select and verify predictive lipid biomarkers of ACCase inhibition activity in vivo using liver samples obtained from early stage 7 day repeat dose studies in non-pregnant female Han Wistar rats that could be translated to developmental toxicity endpoints discovered during late-stage studies to provide an early screening tool., Methods: Liver samples from eight rat repeat dose studies, exposed to six ACCase inhibitors from three different chemistries and one alternative mode of action (MoA) that also perturbs lipid biochemistry, were analysed using liquid chromatography - high resolution accurate mass - mass spectrometry. Multivariate and univariate data analysis methods were used for biomarker discovery and validation., Results: A biomarker signature consisting of sixteen lipids biomarkers were selected. Verification of the signature as indicative of ACCase inhibition was established by demonstrating consistent perturbations in the biomarkers using two different ACCase inhibitor chemistries and the lack thereof with an alternate MoA. The fold change profile pattern was predictive of which test substance doses would or would not cause developmental toxicity., Conclusion: A strategy for selecting and verifying a robust signature of lipid biomarkers for predicting a toxicological end point has been described and demonstrated. Differences in lipidomic profiles correlated with developmental toxicity suggesting that indicators of a molecular initiation event resulting in pup developmental toxicity can be predicted from short term, toxicity studies conducted in non-pregnant adult female Han Wistar rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There are vast potential applications for children's entertainment and education with modern virtual reality (VR) experiences, yet we know very little about how the movement or form of such a virtual body can influence children's feelings of control (agency) or the sensation that they own the virtual body (ownership). In two experiments, we gave a total of 197 children aged 4-14 years a virtual hand which moved synchronously or asynchronously with their own movements and had them interact with a VR environment. We found that movement synchrony influenced feelings of control and ownership at all ages. In Experiment 1 only, participants additionally felt haptic feedback either congruently, delayed or not at all - this did not influence feelings of control or ownership. In Experiment 2 only, participants used either a virtual hand or non-human virtual block. Participants embodied both forms to some degree, provided visuomotor signals were synchronous (as indicated by ownership, agency, and location ratings). Yet, only the hand in the synchronous movement condition was described as feeling like part of the body, rather than like a tool (e.g., a mouse or controller). Collectively, these findings highlight the overall dominance of visuomotor synchrony for children's own-body representation; that children can embody non-human forms to some degree; and that embodiment is also somewhat constrained by prior expectations of body form.

Previous work shows that in adults, illusory embodiment of a virtual avatar can be induced using congruent visuomotor cues. Furthermore, embodying different-sized avatars influences adults' perception of their environment's size. This study (N = 92) investigated whether children are also susceptible to such embodiment and size illusions. Adults and 5-year-old children viewed a first-person perspective of different-sized avatars moving either congruently or incongruently with their own body. Participants rated their feelings of embodiment over the avatar and also estimated the sizes of their body and objects in the environment. Unlike adults, children embodied the avatar regardless of visuomotor congruency. Both adults and children freely embodied different-sized avatars, and this affected their size perception in the surrounding virtual environment; they felt that objects were larger in a small body and vice versa in a large body. In addition, children felt that their body had grown in the large body condition. These findings have important implications for both our theoretical understanding of own-body representation, and our knowledge of perception in virtual environments., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Knowledge of one's own body size is a crucial facet of body representation, both for acting on the environment and perhaps also for constraining body ownership. However, representations of body size may be somewhat plastic, particularly to allow for physical growth in childhood. Here we report a developmental investigation into the role of hand size in body representation (the sense of body ownership, perception of hand position, and perception of own-hand size). Using the rubber hand illusion paradigm, this study used different fake hand sizes (60%, 80%, 100%, 120% or 140% of typical size) in three age groups (6- to 7-year-olds, 12- to 13-year-olds, and adults; N = 229). We found no evidence that hand size constrains ownership or position: participants embodied hands which were both larger and smaller than their own, and indeed judged their own hands to have changed size following the illusion. Children and adolescents embodied the fake hands more than adults, with a greater tendency to feel their own hand had changed size. Adolescents were particularly sensitive to multisensory information. In sum, we found substantial plasticity in the representation of own-body size, with partial support for the hypothesis that children have looser representations than adults., (© 2022. The Author(s).)

Adults' body representation is constrained by multisensory information and knowledge of the body such as its possible postures. This study (N = 180) tested for similar constraints in children. Using the rubber hand illusion with adults and 6- to 7-year olds, we measured proprioceptive drift (an index of hand localization) and ratings of felt hand ownership. The fake hand was either congruent or incongruent with the participant's own. Across ages, congruency of posture and visual-tactile congruency yielded greater drift toward the fake hand. Ownership ratings were higher with congruent visual-tactile information, but unaffected by posture. Posture constrains body representation similarly in children and adults, suggesting that children have sensitive, robust mechanisms for maintaining a sense of bodily self., (© 2020 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Background: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far., Objectives: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research., Materials and Methods: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson's disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20-30 Hz and optimized in an iterative manner., Results: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSP patients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit., Conclusions: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSP patients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation., (© 2020 S. Karger AG, Basel.)

Species differences in hepatic metabolism of thyroxine (T4) by uridine diphosphate glucuronosyl transferase (UGT) and susceptibility to thyroid hormone imbalance could underlie differences in thyroid carcinogenesis caused by hepatic enzyme inducers in rats and humans. To investigate this hypothesis we examined profiles of hepatic UGT induction by the prototypical CAR activator phenobarbital (PB) in rat and human liver 3D microtissues. The rationale for this approach was that 3D microtissues would generate data more relevant to humans. Rat and human liver 3D microtissues were exposed to PB over a range of concentrations (500 u M - 2000 u M) and times (24-96 hr). Microarray and proteomics analyses were performed on parallel samples to generate integrated differentially expressed gene (DEG) datasets. Bioinformatics analysis of DEG data, including CAR response element (CRE) sequence analysis of UGT promoters, was used to assess species differences in UGT induction relative to CAR-mediated transactivation potential. A higher proportion of human UGT promoters were found to contain consensus CREs compared to the rat homologs. UGTs 1a6, 2b17 and 2b37 were upregulated by PB in rat liver 3D microtissues, but unaltered in human liver 3D microtissues. By contrast, human UGTs 1A8, 1A10 and 2B10 showed higher levels of induction (RNA and /or protein) compared to the rat homologs. There was general concordance between the presence of CREs and the induction of UGT RNA. As UGT1A and 2B isoforms metabolise T4, these results suggest that differences in UGT induction could contribute to differential susceptibility to CAR-mediated thyroid carcinogenesis in rats and humans., Competing Interests: The authors report no declarations of interest., (© 2020 The Author(s).)

In everyday contexts, children must respond to both self-related constraints (their own skills and abilities) and environmental constraints (external obstacles and goals). How do young children simultaneously accommodate these to support skilled and flexible behaviour? We used walking in a complex environment as a testbed for two hypotheses. Hypothesis 1: children will accommodate the self-related constraint of high foot placement variability via dynamic scaling. Hypothesis 2: children will plan ahead, even in complex environments. In our task, 3- to 5-year-olds and adults walked over obstacle sequences of varying complexity. We measured foot placement around the first obstacle in the sequence. Hypothesis 1 was partially supported. In simple, single obstacle environments, children engaged in dynamic scaling like adults. Those with more variable foot placement left greater margins of error between the feet and the obstacle. However, in complex, multiple obstacle settings, children employed large, un-tailored margins of error. This parallels other multisensory tasks in which children do not rely on the relative variability of sensory inputs. Hypothesis 2 was supported. Like adults, children planned ahead for environmental constraints. Children adjusted foot placement around the first obstacle depending on the upcoming obstacle sequence. In doing so, they demonstrate surprisingly sophisticated planning. We, therefore, show that in the motor domain, even very young children simultaneously control both self-related and environmental constraints. This allows flexible, safe and efficient behaviour.

Tactile perception is referenced to, and modulated by, body parts and their boundaries. For example, tactile distances presented over the wrist are perceptually elongated relative to those presented within the hand or arm. This phenomenon is argued to result from a segmentation of tactile space according to body parts and their boundaries, i.e., touches presented within a body part are perceived as being more similar, and therefore closer together, whereas those that straddle a body part boundary (e.g. presented across two body parts) are perceived as more distinct and thus further apart. We tested the hypothesis that language shapes this effect by providing consolidatory labels for categories and boundaries, as it does in other perceptual domains. We examined the perceptual elongation of distance over the wrist in a group of Croatian adults (n = 37) whose first language does not differentiate between hand and arm at the wrist in common noun terms (instead, the Croatian word "ruka" encompasses the entire limb). Croatian adults, like UK adults reported in a previous study (Le Cornu Knight, Longo, & Bremner, 2014), perceived distances presented proximodistally over the wrist boundary as longer than those presented mediolaterally, whereas the reverse was found for both the hand and the arm. This pattern of results was remained when Croatian participants were split into two groups of inexperienced or proficient English-language speakers. This is striking evidence that body part boundaries consistently modulate tactile perception, despite differences in the linguistic distinctions of such body parts made by one's first language., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The effects of hypercapnia on regional cerebral oxygen saturation (rSO 2 ) during surgery are unclear. We conducted a randomised controlled trial to investigate the relationship between mild hypercapnia and rSO 2 . We hypothesised that, compared with targeted normocapnia (TN), targeted mild hypercapnia (TMH) during major surgery would increase rSO 2 ., Design: A prospective, randomised, controlled trial in adult participants undergoing elective major surgery., Setting: A single tertiary centre in Heidelberg, Victoria, Australia., Participants: 40 participants were randomised to either a TMH or TN group (20 to each)., Interventions: TMH (partial pressure of carbon dioxide in arterial blood, PaCO 2 , 45-55 mm Hg) or TN (PaCO 2 35-40 mm Hg) was delivered via controlled ventilation throughout surgery., Primary and Secondary Outcome Measures: The primary endpoint was the absolute difference between the two groups in percentage change in rSO 2 from baseline to completion of surgery. Secondary endpoints included intraoperative pH, bicarbonate concentration, base excess, serum potassium concentration, incidence of postoperative delirium and length of stay (LOS) in hospital., Results: The absolute difference between the two groups in percentage change in rSO 2 from the baseline to the completion of surgery was 19.0% higher in both hemispheres with TMH (p<0.001). On both sides, the percentage change in rSO 2 was greater in the TMH group than the TN group throughout the duration of surgery. The difference between the groups became more noticeable over time. Furthermore, postoperative delirium was higher in the TN group (risk difference 0.3, 95% CI 0.1 to 0.5, p=0.02). LOS was similar between groups (5 days vs 5 days; p=0.99)., Conclusion: TMH was associated with a stable increase in rSO 2 from the baseline, while TN was associated with a decrease in rSO 2 in both hemispheres in patients undergoing major surgery. This resulted in a clear separation of percentage change in rSO 2 from the baseline between TMH and TN over time. Our findings provide the rationale for larger studies on TMH during surgery., Trial Registration Number: The Australian New Zealand Clinical Trials Registry (ACTRN12616000320459)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Evidence from the Full Body Illusion (FBI) has shown that adults can embody full bodies which are not their own when they move synchronously with their own body or are viewed from a first-person perspective. However, there is currently no consensus regarding the time course of the illusion. Here, for the first time, we examined the effect of visuomotor synchrony (synchronous/asynchronous/no movement) on the FBI over time. Surprisingly, we found evidence of embodiment over a virtual body after five seconds in all conditions. Embodiment decreased with increased exposure to asynchronous movement, but remained high in synchronous and no movement conditions. We suggest that embodiment of a body seen from a first-person perspective is felt by default, and that embodiment can then be lost in the face of contradictory cues. These results have significant implications for our understanding of how multisensory cues contribute to embodiment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

People use sensory, in particular visual, information to guide actions such as walking around obstacles, grasping or reaching. However, it is presently unclear how malleable the sensorimotor system is. The present study investigated this by measuring how click-based echolocation may be used to avoid obstacles while walking. We tested 7 blind echolocation experts, 14 sighted, and 10 blind echolocation beginners. For comparison, we also tested 10 sighted participants, who used vision. To maximize the relevance of our research for people with vision impairments, we also included a condition where the long cane was used and considered obstacles at different elevations. Motion capture and sound data were acquired simultaneously. We found that echolocation experts walked just as fast as sighted participants using vision, and faster than either sighted or blind echolocation beginners. Walking paths of echolocation experts indicated early and smooth adjustments, similar to those shown by sighted people using vision and different from later and more abrupt adjustments of beginners. Further, for all participants, the use of echolocation significantly decreased collision frequency with obstacles at head, but not ground level. Further analyses showed that participants who made clicks with higher spectral frequency content walked faster, and that for experts higher clicking rates were associated with faster walking. The results highlight that people can use novel sensory information (here, echolocation) to guide actions, demonstrating the action system's ability to adapt to changes in sensory input. They also highlight that regular use of echolocation enhances sensory-motor coordination for walking in blind people. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Adults use vision during stepping and walking to fine-tune foot placement. However, the developmental profile of visually guided stepping is unclear. We asked (1) whether children use online vision to fine-tune precise steps and (2) whether precision stepping develops as part of broader visuomotor development, alongside other fundamental motor skills like reaching. With 6-(N = 11), 7-(N = 11), 8-(N = 11)-year-olds and adults (N = 15), we manipulated visual input during steps and reaches. Using motion capture, we measured step and reach error, and postural stability. We expected (1) both steps and reaches would be visually guided (2) with similar developmental profiles (3) foot placement biases that promote stability, and (4) correlations between postural stability and step error. Children used vision to fine-tune both steps and reaches. At all ages, foot placement was biased (albeit not in the predicted directions). Contrary to our predictions, step error was not correlated with postural stability. By 8 years, children's step and reach error were adult-like. Despite similar visual control mechanisms, stepping and reaching had different developmental profiles: step error reduced with age whilst reach error was lower and stable with age. We argue that the development of both visually guided and non-visually guided action is limb-specific.

Characterisation of the mode of action (MOA) of constitutive androstane receptor (CAR)-mediated rodent liver tumours involves measurement 5 key events including activation of the CAR receptor, altered gene expression, hepatocellular proliferation, clonal expansion and increased hepatocellular adenomas/carcinomas. To test whether or not liver 3D microtissues (LiMTs) recapitulate CAR- mediated procarcinogenic key events in response to the prototypical CAR activator phenobarbital (PB) we performed hepatocyte proliferation (LI%) analysis in rat and human LiMTs using a microTMA technology in conjunction with integrated transcriptomics (microarray) and proteomics analysis. The rationale for this approach was that LiMTs containing parenchymal and non-parenchymal cells (NPCs) are more physiologically representative of liver and thus would generate data more relevant to the in vivo situation. Rat and human LiMTs were treated with PB over a range of concentrations (500 uM - 2000 uM) and times (24 h - 96 h) in a dose-response/time-course analysis. There was a dose-dependent induction of LI% in rat LiMTs, however there was little or no effect of PB on LI% in human LiMTs. ATP levels in the rat and human LiMTs were similar to control in all of the PB treatments. There was also a dose- and time-dependent PB-mediated RNA induction of CAR regulated genes CYP2B6/Cyp2b2, CYP3A7/Cyp3a9 and UGT1A6/Ugt1a6 in human and rat LiMTs, respectively. These CAR regulated genes were also upregulated at the protein level. Ingenuity pathways analysis (IPA) indicated that there was a significant (Z score >2.0;-log p value >) activation of CAR by PB in both human and rat LiMTs. These results indicate that human and rat LiMTs showed the expected responses at the level of PB-induced hepatocyte proliferation and enzyme induction with rat LiMTs showing significant dose-dependent effects while human LiMTs showed no proliferation response but did show dose-dependent enzyme induction at the RNA and protein levels. In conclusion LiMTs serve as a model to provide mechanistic data for 3 of the 5 key events considered necessary to establish a CAR-mediated MOA for liver tumourigenesis and thus can potentially reduce the use of animals when compiling mechanistic data packages., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (© 2019 The Authors.)