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Objectives: Within marriages, loneliness has been linked with individuals' own and their partners' cognitive health. Yet little research has situated Black older adults within a relational, dyadic context., Method: This study analyzed longitudinal dyadic data from the Health and Retirement Study (2010-2016; n  = 1270 participants from 635 couples) from both partners in opposite-sex midlife and older couples where at least one partner reported being Black or African American., Results : Results indicated (1) husbands' loneliness was associated with worse cognitive functioning 4 years later for wives who had high baseline cognitive functioning themselves; (2) wives' loneliness was associated with worse cognitive functioning 4 years later only for oldest-old husbands; and (3) wives' cognitive functioning was associated with slower increases to husbands' loneliness 4 years later., Conclusion: Findings indicate that loneliness has dyadic consequences for cognitive functioning among older Black couples, but that context is crucial for determining who is at greatest risk of harmful repercussions from a partner's loneliness.

The burgeoning domain of telehealth has witnessed substantial transformation through the advent of advanced technologies such as Large Language Models (LLMs). This study examines the integration of LLMs in heart failure management, with a focus on HerzMobil as a pioneering telehealth program. The technical underpinnings of LLMs, their current applications in the medical field, and their potential to enhance telehealth services, have been explored. The paper highlights the benefits of LLMs in patient interaction, clinical documentation, and decision-making processes. Through the HerzMobil case study, improvements in patient self-management and reductions in hospital readmission rates have been observed, showcasing the successful application of telehealth in chronic disease management. The paper also delves into the challenges and ethical considerations of LLM integration, such as data privacy, potential biases, and regulatory compliance, underscoring the need for a balanced approach that prioritizes patient safety and ethical standards.

The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables., (© 2023. The Author(s).)

Despite being bio-epidemiological phenomena, the causes and effects of pandemics are culturally influenced in ways that go beyond national boundaries. However, they are often studied in isolated pockets, and this fact makes it difficult to parse the unique influence of specific cultural psychologies. To help fill in this gap, the present study applies existing cultural theories via linear mixed modeling to test the influence of unique cultural factors in a multi-national sample (that moves beyond Western nations) on the effects of age, biological sex, and political beliefs on pandemic outcomes that include adverse financial impacts, adverse resource impacts, adverse psychological impacts, and the health impacts of COVID. Our study spanned 19 nations (participant N = 14,133) and involved translations into 9 languages. Linear mixed models revealed similarities across cultures, with both young persons and women reporting worse outcomes from COVID across the multi-national sample. However, these effects were generally qualified by culture-specific variance, and overall more evidence emerged for effects unique to each culture than effects similar across cultures. Follow-up analyses suggested this cultural variability was consistent with models of pre-existing inequalities and socioecological stressors exacerbating the effects of the pandemic. Collectively, this evidence highlights the importance of developing culturally flexible models for understanding the cross-cultural nature of pandemic psychology beyond typical WEIRD approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Conway, Woodard, Zubrod, Tiburcio, Martínez-Vélez, Sorgente, Lanz, Serido, Vosylis, Fonseca, Lep, Li, Zupančič, Crespo, Relvas, Papageorgiou, Gianniou, Truhan, Mojtahedi, Hull, Lilley, Canning, Ulukök, Akın, Massaccesi, Chiappini, Paracampo, Korb, Szaflarski, Touré, Camara, Magassouba, Doumbouya, Mutlu, Bozkurt, Grotkowski, Przepiórka, Corral-Frías, Watson, Corona Espinosa, Lucas, Paleari, Tchalova, Gregory, Azrieli, Bartz, Farmer, Goldberg, Rosenkranz, Pickett, Mackelprang, Graves, Orr and Balmores-Paulino.)

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multinational data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 ( N  = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution-individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar results were found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, and collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-neglible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

The tendency to simulate the pain of others within our own sensorimotor systems is a vital component of empathy. However, this sensorimotor resonance is modulated by a multitude of social factors including similarity in bodily appearance, e.g. skin colour. The current study investigated whether increasing self-other similarity via virtual transfer to another colour body reduced ingroup bias in sensorimotor resonance. A sample of 58 white participants was momentarily transferred to either a black or a white body using virtual reality technology. We then employed electroencephalography to examine event-related desynchronization (ERD) in the sensorimotor beta (13-23 Hz) oscillations while they viewed black, white and violet photorealistic virtual agents being touched with a noxious or soft object. While the noxious treatment of a violet agent did not increase beta ERD, amplified beta ERD in response to black agent's noxious vs soft treatment was found in perceivers transferred to a black body. Transfer to the white body dismissed the effect. Further exploratory analysis implied that the pain-related beta ERD occurred only when the agent and the participant were of the same colour. The results suggest that even short-lasting changes in bodily resemblance can modulate sensorimotor resonance to others' perceived pain., (© The Author(s) 2021. Published by Oxford University Press.)

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics., (© 2022. The Author(s).)

Introduction: Methadone and buprenorphine/naloxone medications are among the most effective treatment options for opioid use disorders, yet many people remain misinformed about their benefits and hold negative perceptions about the use of medications to treat opioid use disorders. Such perceptions, especially negative perceptions based on misinformation, may be especially harmful or stigmatizing within the context of disclosure (i.e., telling another about one's opioid use disorder history or treatment), inhibiting important recovery outcomes and sources of social support., Methods: Therefore, using the Disclosure Process Model as a framework, the current study seeks to characterize and compare participants' perceptions of stigmatizing reactions to their disclosures of MOUD use that stem from misinformation about methadone or buprenorphine/naloxone. Participants included people who are actively receiving MOUD as treatment., Results: Results suggest that participants (N = 52) receiving both types of medications experienced similar stigmatizing reactions to disclosures. Participants also reported treatment consequences of misinformed reactions to their disclosure, such as dropping out of support groups (e.g., Narcotics Anonymous) or prematurely ending their medication use. Further, the paper provides participants' recommendations for avoiding or managing misinformed disclosure reactions., Conclusions: Short-term intervention efforts may promote strategies to manage misinformation, equipping individuals to respond to misinformation surrounding their medication use. Long-term interventions may target misinformation about methadone and buprenorphine/naloxone medications to increase health literacy, reduce stigma, and combat cultural ambivalence within communities, as well as promote recovery among people receiving medications for opioid use disorder., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Advances in head mounted displays (HMDs) have increased the interest in cinematic virtual reality as an art form. However, the freedom of a viewer in 360 video presents challenges in ensuring that audiences do not inadvertently miss important events and locations. We examined whether the high level of immersion provided by HMDs encourages participants to synchronize their attention during viewing. Sixty-four participants watched the 360° documentary Clouds Over Sidra (VRSE.works, 2015) using either an HMD or via a flat screen tablet display. We used intersubject correlation (ISC) analysis to measure attentional synchrony over the course of the video and to examine whether spatial and temporal factors led to different amounts of correlation both within and between groups. We found significantly greater ISC for the HMD compared to the tablet group. This effect was greatest for scenes with a unidirectional focus and at the start of scenes. We discuss our results in terms of the visual properties and the motor affordances of HMDs versus tablets. Our results show the value of HMDs in increasing attentional synchrony and may provide producers of 360° content insight in how to encourage or discourage synchronization of viewing direction. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective: To assess key presenting signs in dogs following Vitis vinifera fruit (VVF) ingestion (grapes, raisins, currants, and sultanas), outcome, and the incidence of acute kidney injury (AKI)., Design: Retrospective study (2012-2016)., Setting: Out-of-hours clinics in the United Kingdom., Animals: The study population included 606 dogs attending 53 emergency clinics across the United Kingdom following ingestion of VVF., Interventions: None., Measurements and Main Results: Vitis vinifera fruits were found in vomit after more than 12 hours after ingestion. There was an increased incidence in December. Serum creatinine or urea was measured in 338 dogs; all were within reference intervals. In this cohort of dogs with VVF ingestion, there is no evidence for significant AKI in 32 of 33 cases within 24 hours of admission where supportive measures were introduced and repeated assessments of creatinine concentration were performed., Conclusions: All dogs survived to discharge. One out of 33 cases with repeated creatinine concentration developed IRIS AKI grade I within 24 hours following VVF ingestion, when current emergency treatment guidelines were followed in whole or part., (© Veterinary Emergency and Critical Care Society 2020.)

The tendency to imitate the actions of others appears to be a fundamental aspect of human social interaction. Emotional expressions are a particularly salient form of social stimuli (Vuilleumier & Schwartz, 2001) but their relationship to imitative behaviour is currently unclear. In this paper we report the results of five studies which investigated the effect of a target's dynamic emotional stimuli on participants' tendency to respond compatibly to the target's actions. Experiment one examined the effect of dynamic emotional expressions on the automatic imitation of opening and closing hand movements. Experiment two used the same basic paradigm but added gaze direction as an additional factor. Experiment three investigated the effect of dynamic emotional expressions on compatibility responses to handshakes. Experiment four investigated whether dynamic emotional expressions modulated response to valenced social gestures. Finally, experiment five compared the effects of dynamic and static emotional expressions on participants' automatic imitation of finger lifting. Across all five studies we reliably elicited a compatibility effect however, none of the studies found a significant modulating effect of emotional expression. This null effect was also supported by a random effects meta-analysis and a series of Bayesian t-tests. Nevertheless, these results must be caveated by the fact that our studies had limited power to detect effect sizes below d = 0.4. We conclude by situating our findings within the literature, suggesting that the effect of emotional expressions on automatic imitation is, at best, minimal., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

There is a growing consensus that our most fundamental sense of self is structured by the ongoing integration of sensory and motor information related to our own body. Depersonalisation (DP) is an intriguing form of altered subjective experience in which people report feelings of unreality and detachment from their sense of self. The current study used the visual remapping of touch (VRT) paradigm to explore self-bias in visual-tactile integration in non-clinical participants reporting high and low levels of depersonalisation experiences. We found that the high-DP group showed an increased overall VRT effect but a no-self-face bias, instead showing a greater VRT effect when observing the face of another person. In addition, across all participants, self-bias was negatively predicted by the occurrence of anomalous body experiences. These results indicate disrupted integration of tactile and visual representations of the bodily self in those experiencing high levels of DP and provide greater understanding of how disruptions in multisensory perception of the self may underlie the phenomenology of depersonalisation.

Background: The COVID-19 pandemic caused >1 million infections during January-March 2020. There is an urgent need for reliable antibody detection approaches to support diagnosis, vaccine development, safe release of individuals from quarantine, and population lock-down exit strategies. We set out to evaluate the performance of ELISA and lateral flow immunoassay (LFIA) devices. Methods: We tested plasma for COVID (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) IgM and IgG antibodies by ELISA and using nine different LFIA devices. We used a panel of plasma samples from individuals who have had confirmed COVID infection based on a PCR result (n=40), and pre-pandemic negative control samples banked in the UK prior to December-2019 (n=142). Results: ELISA detected IgM or IgG in 34/40 individuals with a confirmed history of COVID infection (sensitivity 85%, 95%CI 70-94%), vs. 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 COVID-positive individuals tested ≥10 days after symptom onset (sensitivity 100%, 95%CI 89-100%). IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions: Currently available commercial LFIA devices do not perform sufficiently well for individual patient applications. However, ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following first symptoms., Competing Interests: Competing interests: RC reports personal fees and other from MIROBIO Ltd, outside the submitted work. DWE reports personal fees from Gilead, outside the submitted work. SH reports grants from NIHR, during the conduct of the study. AJP reports grants from NIHR Oxford Biomedical Research Centre, outside the submitted work; and AJP is Chair of UK Dept. Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) and is a member of the WHO’s SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, NIHR or WHO. GRS reports personal fees from GSK Vaccines SAB. MGS reports grants from National Institute of Health Research, grants from Medical Research Council UK, grants from Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool, during the conduct of the study; other from Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work. ASW reports grants from NIHR, during the conduct of the study. No other author has a conflict of interest to declare., (Copyright: © 2020 Adams ER et al.)

In this study, we investigated the effect of intergroup contact on processing of own- and other-race faces using functional Magnetic Resonance Imaging (fMRI). Previous studies have shown a neural own-race effect with greater BOLD response to own race compared to other race faces. In our study, white participants completed a social-categorization task and an individuation task while viewing the faces of both black and white strangers after having answered questions about their previous experiences with black people. We found that positive contact modulated BOLD activity in the right fusiform gyrus (rFG) and left inferior occipital gyrus (lIOC), regions associated with face processing. Within these regions, higher positive contact was associated with higher activity when processing black, compared to white faces during the social categorisation task. We also found that in both regions a greater amount of individuating experience with black people was associated with greater activation for black vs. white faces in the individuation task. Quantity of contact, implicit racial bias and negatively valenced contact showed no effects. Our findings suggest that positive contact and individuating experience directly modulate processing of out-group faces in the visual cortex, and illustrate that contact quality rather than mere familiarity is an important factor in reducing the own race face effect.

During our daily lives, we often learn about the similarity of the traits and preferences of others to our own and use that information during our social interactions. However, it is unclear how the brain represents similarity between the self and others. One possible mechanism is to track similarity to oneself regardless of the identity of the other (Similarity account); an alternative is to track each other person in terms of consistency of their choice similarity with respect to the choices they have made before (consistency account). Our study combined functional Magnetic Resonance Imaging (fMRI) and computational modelling of reinforcement learning (RL) to investigate the neural processes that underlie learning about preference similarity. Participants chose which of two pieces of artwork they preferred and saw the choices of one agent who usually shared their preference and another agent who usually did not. We modelled neural activation with RL models based on the similarity and consistency accounts. Our results showed that activity in brain areas linked to reward and social cognition followed the consistency account. Our findings suggest that impressions of other people can be calculated in a person-specific manner, which assumes that each individual behaves consistently with their past choices., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved.)

Whether pointing at a menu item or rifling through a clothes rack, when we choose we often move. We investigated whether people's tendency to copy the movements of others could influence their choices. Participants saw pairs of pictures in private and indicated which one they preferred. They then entered a virtual art gallery and saw the same picture pairs in the presence of a virtual character. Having observed the virtual character point to indicate her preference with either a high or low movement trajectory, participants indicated their preference. There was either an anatomical (same movement, same choice) or spatial correspondence (same movement, different choice) between the participant's pictures and those of the virtual character. We found that participants copied the movement made by the virtual character rather than her action goal (i.e., her choice of picture). This resulted in a shift towards the virtual character's preferences in the anatomical condition but away from her preferences in the spatial condition. This effect was driven by the observation of the virtual character's high pointing movements. In a further experiment, we did not find any significant differences in imitation behaviour in autism, although autistic participants were less consistent in their choices. Our findings demonstrate that we are not only influenced by other's choices but also the types of movements others make to indicate those choices.

This article focuses on the question of the function of imitation and whether current accounts of imitative function are consistent with our knowledge about imitation's origins. We first review theories of imitative origin concluding that empirical evidence suggests that imitation arises from domain-general learning mechanisms. Next, we lay out a selective account of function that allows normative functions to be ascribed to learned behaviours. We then describe and review four accounts of the function of imitation before evaluating the relationship between the claim that imitation arises out of domain-general learning mechanisms and theories of the function of imitation.

Actions of others automatically prime similar responses in an agent's behavioural repertoire. As a consequence, perceived or anticipated imitation facilitates own action control and, at the same time, imitation boosts social affiliation and rapport with others. It has previously been suggested that basic mechanisms of associative learning can account for behavioural effects of imitation, whereas a possible role of associative learning for affiliative processes is poorly understood at present. Therefore, this study examined whether contingency and contiguity, the principles of associative learning, affect also the social effects of imitation. Two experiments yielded evidence in favour of this hypothesis by showing more social affiliation in conditions with high contingency (as compared to low contingency) and in conditions of high contiguity (compared to low contiguity).

Background: Adults with autosomal dominant polycystic kidney disease (ADPKD) exhibit vascular dysfunction, as evidenced by impaired endothelium-dependent dilation (EDD) and stiffening of the large elastic arteries. However, it is unknown whether vascular dysfunction begins earlier in the course of ADPKD. The aim of the study was to assess EDD and arterial stiffness in children and young adults with ADPKD., Methods: Fifteen children and young adults 6–22 years of age with ADPKD and normal renal function were prospectively recruited for participation in a cross-sectional study. Fifteen healthy controls were enrolled to match cases for age and sex. The primary outcomes were EDD, measured as brachial artery flow-mediated dilation (FMDBA), and arterial stiffness, measured as carotid-femoral pulse wave velocity (CFPWV)., Results: ADPKD cases were more likely to be taking an angiotensin-converting enzyme inhibitor, but otherwise did not differ from controls in clinical characteristics, including blood pressure. FMDBA was 25% lower in children and young adults with ADPKD (7.7 ± 0.9%, mean ± SE) when compared with matched controls (10.2 ± 0.8%) (P < 0.05). CFPWV was 14% higher in children and young adults with ADPKD (544 ± 23 cm/s) when compared with matched controls (478 ± 17 cm/s) (P < 0.05). Secondary measures of arterial stiffness, carotid augmentation index and carotid systolic blood pressure were also increased in cases when compared with controls (P < 0.05)., Conclusions: Impaired EDD and increased arterial stiffness, important independent predictors of future cardiovascular events and mortality, are evident very early in the course of ADPKD in the presence of normal kidney function. Novel interventions to reduce vascular dysfunction in children and young adults with ADPKD should be evaluated, as childhood and young adulthood may represent a critical therapeutic window to reduce future cardiovascular risk in patients with ADPKD.

Our interactions with other people - and our processing of their actions - are shaped by their reputation. Research has identified an Action Observation Network (AON) which is engaged when observing other people's actions. Yet, little is known about how the processing of others' actions is influenced by another's reputation. Is the response of the AON modulated by the reputation of the actor? We developed a variant of the ultimatum game in which participants watched either the visible or occluded actions of two 'proposers'. These actions were tied to decisions of how to split a pot of money although the proposers' decisions on each trial were not known to participants when observing the actions. One proposer made fair offers on the majority of trials, establishing a positive reputation, whereas the other made predominantly, unfair offers resulting in a negative reputation. We found significant activations in two regions of the left dorsal premotor cortex (dPMC). The first of these showed a main effect of reputation with greater activation for the negative reputation proposer than the positive reputation proposer. Furthermore individual differences in trust ratings of the two proposers covaried with activation in the right primary motor cortex (M1). The second showed an interaction between visibility and reputation driven by a greater effect of reputation when participants were observing an occluded action. Our findings show that the processing of others' actions in the AON is modulated by an actor's reputation, and suggest a predictive role for the PMC during action observation., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Research suggests that zoo visitors can have positive, negative, and neutral impacts on captive primate welfare; however, research investigating the implications of visitor-animal feeding experiences is extremely limited. In the UK, a large proportion of BIAZA zoos that house lemur species offer visitor interaction experiences (16 out of 33). This study investigated the impact on the behavior of a family group of crowned lemurs (Eulemur coronatus) housed at Newquay Zoo, UK of visitors, accompanied by a keeper, entering the enclosure to feed the lemurs. Behavior was observed under four conditions: (i) during visitor feed; (ii) 30 min post-visitor feed; (iii) during a keeper feed; and (iv) 30 min post-keeper feed. Keeper feeds were conducted by keepers only, on the day after visitor feeds. The lemur group spent significantly less time performing aggressive behavior and was also significantly more interactive with keepers during visitor feeds compared with keeper-only feeds. There was no significant difference in behaviors performed immediately after interacting with visitors. Over the study period, there was a tendency for interactions with visitors to increase, and for interactions with keepers during visitor feeds to decrease. After a 28-day interval without visitor interaction, the lemurs' interaction with visitors had returned to the level recorded at the start of the study. In conclusion, visitor interaction did not compromise the welfare of the study subjects in either the short- or long-term, while an increase in visitor interactions over time has interesting implications for the enrichment properties of, or habituation to, unfamiliar humans. Zoo Biol. 35:222-227, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The tendency to mimic the behaviour of others is affected by a variety of social factors, and it has been argued that such "mirroring" is often unconsciously deployed as a means of increasing affiliation during interpersonal interactions. However, the relationship between automatic motor imitation and status/power is currently unclear. This paper reports five experiments that investigated whether social status (Experiments 1, 2, and 3) or power (Experiments 4 and 5) had a moderating effect on automatic imitation (AI) in finger-movement tasks, using a series of different manipulations. Experiments 1 and 2 manipulated the social status of the observed person using an associative learning task. Experiment 3 manipulated social status via perceived competence at a simple computer game. Experiment 4 manipulated participants' power (relative to the actors) in a card-choosing task. Finally, Experiment 5 primed participants using a writing task, to induce the sense of being powerful or powerless. No significant interactions were found between congruency and social status/power in any of the studies. Additionally, Bayesian hypothesis testing indicated that the null hypothesis should be favoured over the experimental hypothesis in all five studies. These findings are discussed in terms of their implications for AI tasks, social effects on mimicry, and the hypothesis of mimicry as a strategic mechanism to promote affiliation.

People can communicate by using hand actions, e.g., signs. Understanding communicative actions requires that the observer knows that the actor has an intention to communicate and the meanings of the actions. Here, we investigated how this prior knowledge affects processing of observed actions. We used functional MRI to determine changes in action processing when non-signers were told that the observed actions are communicative (i.e., signs) and learned the meanings of half of the actions. Processing of hand actions activated the left and right inferior frontal gyrus (IFG, BA 44 and 45) when the communicative intention of the actor was known, even when the meanings of the actions remained unknown. These regions were not active when the observers did not know about the communicative nature of the hand actions. These findings suggest that the left and right IFG play a role in understanding the intention of the actor, but do not process visuospatial features of the communicative actions. Knowing the meanings of the hand actions further enhanced activity in the anterior part of the IFG (BA 45), the inferior parietal lobule and posterior inferior and middle temporal gyri in the left hemisphere. These left-hemisphere language regions could provide a link between meanings and observed actions. In sum, the findings provide evidence for the segregation of the networks involved in the neural processing of visuospatial features of communicative hand actions and those involved in understanding the actor's intention and the meanings of the actions., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Humphreys and Sui provide a powerful theoretical framework to explain processing biases toward self-related information. However, the framework is primarily applied to information relevant to a conceptual self-representation. Here, we show a similar processing bias for information related to the bodily self, grounded in sensorimotor representations. Furthermore, we can use bodily illusions to explore the ways in which embodied self-associations can affect our perceptual and attentional processing. It is possible to extend the current framework to take into account these effects, and we argue that this will yield considerable benefits for our understanding of self-relevance.

Anacetrapib is a cholesteryl ester transfer protein inhibitor in Phase III development. This double-blind, double-dummy, randomized, placebo- and active-comparator-controlled, 4-period, balanced crossover study evaluated the effects of anacetrapib (100 mg and 800 mg) on QTcF interval in healthy subjects. QTcF measurements were made up to 24 h following administration of single doses of anacetrapib 100 or 800 mg, moxifloxacin 400 mg, or placebo in the fed state. The primary hypothesis was supported if the 90% CI for the least squares (LS) mean differences between anacetrapib 800 mg and placebo in QTcF interval change from baseline were entirely <10 msec at every post-dose time point (1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 h). The upper bounds of the 90% CIs for LS mean differences from placebo in changes from baseline in QTcF intervals for anacetrapib 100 and 800 mg were <5 msec at every time point. In conclusion, single doses of anacetrapib 100 and 800 mg do not prolong the QTcF interval to a clinically meaningful degree relative to placebo and are generally well tolerated in healthy subjects., (© 2014, The American College of Clinical Pharmacology.)

The effect of multisensory-induced changes on body-ownership and self-awareness using bodily illusions has been well established. More recently, experimental manipulation of bodily illusions have been combined with social cognition tasks to investigate whether changes in body-ownership can in turn change the way we perceive others. For example, experiencing ownership over a dark-skin rubber hand reduces implicit bias against dark-skin groups. Several studies have also shown that processing of skin color and facial features play an important role in judgements of racial typicality and racial categorization independently and in an additive manner. The present study aimed at examining whether using multisensory stimulation to induce feelings of body-ownership over a dark-skin rubber hand would lead to an increase in positive attitudes toward black faces. We here show, that the induced ownership of a body-part of a different skin color affected the participants' implicit attitudes when processing facial features, in addition to the processing of skin color shown previously. Furthermore, when the levels of pre-existing attitudes toward black people were taken into account, the effect of the rubber hand illusion on the post-stimulation implicit attitudes was only significant for those participants who had a negative initial attitude toward black people, with no significant effects found for those who had positive initial attitudes toward black people. Taken together, our findings corroborate the hypothesis that the representation of the self and its relation to others, as given to us by body-related multisensory processing, is critical in maintaining but also in changing social attitudes.

Background: 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is a water-soluble mitochondrial toxin that binds to adenine nucleotide translocase in the inner mitochondrial membrane, thereby targeting cell proliferation. This phase 1 study investigated safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and pharmacokinetics (PK) of GSAO as a daily 1-h infusion for 5 days a week for 2 weeks in every three. Pharmacodynamics of GSAO was evaluated by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and circulating markers of angiogenesis., Methods: Patients with advanced solid tumours received GSAO in a dose-escalation trial according to a standard '3 + 3' design that was guided by toxicity and, for the final dose escalation, by arsenic PK data., Results: A total of 34 patients were treated with GSAO across 9 dose levels (1.3-44.0 mg/m(2)). Treatment was well tolerated with few adverse events. An additional three patients were enrolled at the 12.4 mg/m(2) dose level following a DLT of derangement of liver function tests (grade 4). At the 44.0 mg/m(2) dose level, two out of three patients had DLTs (reversible encephalopathy; paroxysmal atrial fibrillation)., Conclusions: The MTD of GSAO was 22.0 mg/m(2)/day. There was no biomarker evidence from DCE-MRI or circulating markers of angiogenesis of an anti-vascular effect of GSAO.

Psychology distinguishes between a bodily and a narrative self. Within neuroscience, models of the bodily self are based on exteroceptive sensorimotor processes or on the integration of interoceptive sensations. Recent research has revealed interactions between interoceptive and exteroceptive processing of self-related information, for example that mirror self-observation can improve interoceptive awareness. Using heartbeat perception, we measured the effect on interoceptive awareness of two experimental manipulations, designed to heighten attention to bodily and narrative aspects of the self. Participants gazed at a photograph of their own face or at self-relevant words. In both experimental conditions interoceptive awareness was significantly increased, compared to baseline. Results show that attention to narrative aspects of self, previously regarded as relying on higher-order processes, has an effect similar to self-face stimuli in improving interoceptive awareness. Our findings extend the previously observed interaction between the bodily self and interoception to more abstract amodal representations of the self., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In this open-label study, 24 healthy volunteers received a single intravenous (IV) dose of 0.5 mg of midazolam on day 1 and a single oral dose each of 2 mg of midazolam and 0.5 mg of digoxin on day 3. Telaprevir 750 mg every 8 hours was administered from day 8 through day 23, along with a single IV dose of 0.5 mg of midazolam on day 17 and single oral doses of 2 mg of midazolam and 0.5 mg of digoxin on day 19. Midazolam, 1'-hydroxymidazolam, digoxin, and telaprevir concentrations in plasma and digoxin concentrations in urine were measured and pharmacokinetic parameters calculated. On comparing administration with versus without telaprevir, the geometric least squares mean ratios (with 90% confidence limits) for IV midazolam were 1.02 (0.80, 1.31) for maximum observed concentrations (C(max)) and 3.40 (3.04, 3.79) for area under the curve from 0 to 24 hours (AUC(0-24h)); for oral midazolam 2.86 (2.52, 3.25) for C(max) and 8.96 (7.75, 10.35) for AUC(0-24h); and for oral digoxin 1.50 (1.36, 1.65) for C(max) and 1.85 (1.70, 2.00) for area under the curve from 0 to infinity (AUC(0-∞)). Coadministration of telaprevir with oral midazolam resulted in approximately 3-fold decrease in the mean AUC(0-∞) of 1'-hydroxymidazolam. The renal clearance of digoxin was similar with or without telaprevir. Results show that telaprevir is an inhibitor of CYP3A and P-glycoprotein.

Multisensory stimulation has been shown to alter the sense of body-ownership. Given that perceived similarity between one's own body and those of others is crucial for social cognition, we investigated whether multisensory stimulation can lead participants to experience ownership over a hand of different skin colour. Results from two studies using introspective, behavioural and physiological methods show that, following synchronous visuotactile (VT) stimulation, participants can experience body-ownership over hands that seem to belong to a different racial group. Interestingly, a baseline measure of implicit racial bias did not predict whether participants would experience the RHI, but the overall strength of experienced body-ownership seemed to predict the participants' post-illusion implicit racial bias with those who experienced a stronger RHI showing a lower bias. These findings suggest that multisensory experiences can override strict ingroup/outgroup distinctions based on skin colour and point to a key role for sensory processing in social cognition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The novel organoarsenical GSAO, 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid, has potential anti-angiogenic capability with application in cancer where tumour metastasis relies on neo-vascularisation. As GSAO arsenic is trivalent, the arsenoxide moiety reacts with appropriately spaced cysteine residues on adenine nucleotide translocase (ANT) mitochondrial membrane protein. Molecular oxidation of the arsenic to the pentavalent structure, as in the degradant GSAA (4-(N-(S-glutathionylacetyl)amino) phenylarsonic acid), prevents sulphydryl interaction and risks abolition of activity. We report here on formulation studies aiming to produce a parenteral product with the primary objective of restricting GSAA transformation from GSAO to protect maximal potency of the molecule. Successful anti-oxidant strategy primarily came from pH control. The presence of glycine was proposed to form a stabilising five-membered oxazarsolidinone ring with arsenoxide and this was investigated using potentiometric assays. We report on these tritration studies identifying a pK(a) of 8.2 associated with an As-OH, but not confirming ring presence. An original clinical trial pharmaceutical was successfully realised by lyophilisation of 50 mg/mL GSAO in 100 mM glycine solution, pH 7 to obtain a 48-month shelf life for the freeze-dried vials. The Phase I clinical study is ongoing in patients with solid tumours refractory to standard therapy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Viewing another person's hand actions enhances excitability in an observer's left and right primary motor (M1) cortex. We aimed to determine whether viewing communicative hand actions alters this bilateral sensorimotor resonance. Using single-pulse transcranial magnetic stimulation (TMS), we measured excitability in the left and right M1 while right-handed non-signing participants observed bimanual communicative hand actions, i.e., meaningful signs in British Sign Language. TMS-induced motor evoked potentials were recorded from hand muscles during sign observation before and after teaching the participants to associate meanings with half of the signs. Before this teaching, when participants did not know that the presented hand actions were signs, excitability of left and right M1 was modulated equally. After learning the meanings of half the signs, excitability of the left, but not right, M1 was significantly enhanced. This left-lateralized enhancement of M1 excitability occurred during observation of signs with known and unknown meanings. The findings suggest that awareness of the communicative nature of another person's hand actions strengthens sensorimotor resonance in the left M1 cortex and alters hemispheric balance during action observation., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

T-box 2 (TBX2) is a transcription factor involved in mammary development and is known to be overexpressed in a subset of aggressive breast cancers. TBX2 has previously been shown to repress growth control genes such as p14(ARF) and p21(WAF1/cip1). In this study we show that TBX2 drives proliferation in breast cancer cells and this is abrogated after TBX2 small interfering RNA (siRNA) knockdown or after the expression of a dominant-negative TBX2 protein. Using microarray analysis we identified a large cohort of novel TBX2-repressed target genes including the breast tumour suppressor NDRG1 (N-myc downregulated gene 1). We show that TBX2 targets NDRG1 through a previously undescribed mechanism involving the recruitment of early growth response 1 (EGR1). We show EGR1 is required for the ability of TBX2 to repress NDRG1 and drive cell proliferation. We show that TBX2 interacts with EGR1 and that TBX2 requires EGR1 to target the NDRG1 proximal promoter. Abrogation of either TBX2 or EGR1 expression is accompanied by the upregulation of cell senescence and apoptotic markers. NDRG1 can recapitulate these effects when transfected into TBX2-expressing cells. Together, these data identify a novel mechanism for TBX2-driven oncogenesis and highlight the importance of NDRG1 as a growth control gene in breast tissue.

Raltegravir, a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has pH-dependent solubility. Raltegravir plasma concentration increases with omeprazole coadministration in healthy subjects; this is likely secondary to an increase in bioavailability attributable to increased gastric pH. Increased gastric pH has been reported in HIV-1-infected individuals, and the effects of omeprazole in this intended population may be diminished. Further investigation is necessary.

CHR-2797 is a novel metalloenzyme inhibitor that is converted into a pharmacologically active acid product (CHR-79888) inside cells. CHR-79888 is a potent inhibitor of a number of intracellular aminopeptidases, including leucine aminopeptidase. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines in vitro and in vivo and shows selectivity for transformed over nontransformed cells. Its antiproliferative effects are at least 300 times more potent than the prototypical aminopeptidase inhibitor, bestatin. However, the mechanism by which inhibition of these enzymes leads to proliferative changes is not understood. Gene expression microarrays were used to profile changes in mRNA expression levels in the human promyelocytic leukemia cell line HL-60 treated with CHR-2797. This analysis showed that CHR-2797 treatment induced a transcriptional response indicative of amino acid depletion, the amino acid deprivation response, which involves up-regulation of amino acid synthetic genes, transporters, and tRNA synthetases. These changes were confirmed in other leukemic cell lines sensitive to the antiproliferative effects of CHR-2797. Furthermore, CHR-2797 treatment inhibited phosphorylation of mTOR substrates and reduced protein synthesis in HL-60 cells, both also indicative of amino acid depletion. Treatment with CHR-2797 led to an increase in the concentration of intracellular small peptides, the substrates of aminopeptidases. It is suggested that aminopeptidase inhibitors, such as CHR-2797 and bestatin, deplete sensitive tumor cells of amino acids by blocking protein recycling, and this generates an antiproliferative effect. CHR-2797 is orally bioavailable and currently undergoing phase II clinical investigation in the treatment of myeloid leukemia.

Pre-synaptic norepinephrine (NE) and dopamine (DA) transporters (NET and DAT) terminate catecholamine synaptic transmission through reuptake of released neurotransmitter. Recent studies reveal that NET and DAT are tightly regulated by receptor and second messenger-linked signaling pathways. Common approaches for studying these transporters involve use of radiolabeled substrates or antagonists, methods possessing limited spatial resolution and that bear limited opportunities for repeated monitoring of living preparations. To circumvent these issues, we have explored two novel assay platforms that permit temporally resolved quantitation of transport activity and transporter protein localization. To monitor the binding and transport function of NET and DAT in real-time, we have investigated the uptake of the fluorescent organic compound 4-(4-diethylaminostyryl)-N-methylpyridinium iodide (ASP+). We have extended our previous single cell level application of this substrate to monitor transport activity via high-throughput assay platforms. Compared to radiotracer uptake methods, acquisition of ASP+ fluorescence is non-isotopic and allows for continuous, repeated transport measurements on both transfected and native preparations. Secondly, we have extended our application of small-molecule-conjugated fluorescent CdSe/ZnS nanocrystals, or quantum dots (Qdots), to utilize antibody and peptide ligands that can identify surface expressed transporters, receptors and other membrane proteins in living cell systems. Unlike typical organic fluorophores, Qdots are highly resistant to bleaching and can be conjugated to multiple ligands. They can also be illuminated by conventional light sources, yet produce narrow, gaussian emission spectra compatible with multiple target visualization (multiplexing). Together, these approaches offer novel opportunities to investigate changes in transporter function and distribution in real-time with superior spatial and temporal resolution.

BRCA1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to breast and other cancers. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key pathway in the repair of DNA single-strand breaks. We show here that BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis. This seems to be because the inhibition of PARP leads to the persistence of DNA lesions normally repaired by homologous recombination. These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer.

Individuals harboring germ-line mutations in the BRCA1 or BRCA2 genes are at highly elevated risk of a variety of cancers. Ten years of research has revealed roles for BRCA1 and BRCA2 in a wide variety of cellular processes. However, it seems likely that the function of these proteins in DNA repair is critically important in maintaining genome stability. Despite this increasing knowledge of the defects present in BRCA-deficient cells, BRCA mutation carriers developing cancer are still treated similarly to sporadic cases. Here we describe our efforts, based on understanding the DNA repair defects in BRCAdeficient cells, to define the optimal existing treatment for cancers arising in BRCA mutation carriers and, additionally, the development of novel therapeutic approaches. Finally, we discuss how therapies developed to treat BRCA mutant tumors might be applied to some sporadic cancers sharing similar specific defects in DNA repair.

In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.

Familial cylindromatosis is an autosomal dominant predisposition to tumours of skin appendages called cylindromas. Familial cylindromatosis is caused by mutations in a gene encoding the CYLD protein of previously unknown function. Here we show that CYLD is a deubiquitinating enzyme that negatively regulates activation of the transcription factor NF-kappaB by specific tumour-necrosis factor receptors (TNFRs). Loss of the deubiquitinating activity of CYLD correlates with tumorigenesis. CYLD inhibits activation of NF-kappaB by the TNFR family members CD40, XEDAR and EDAR in a manner that depends on the deubiquitinating activity of CYLD. Downregulation of CYLD by RNA-mediated interference augments both basal and CD40-mediated activation of NF-kappaB. The inhibition of NF-kappaB activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TNFR-associated factor 2 (TRAF2) and, to a lesser extent, TRAF6. These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is required for appropriate cellular homeostasis of skin appendages.

The Hira gene encodes a nuclear WD40 domain protein homologous to the yeast transcriptional corepressors Hir1p and Hir2p. Using targeted mutagenesis we demonstrate that Hira is essential for murine embryogenesis. Analysis of inbred 129Sv embryos carrying the null mutation revealed an initial requirement during gastrulation, with many mutant embryos having a distorted primitive streak. Mutant embryos recovered at later stages have a range of malformations with axial and paraxial mesendoderm being particularly affected, a finding consistent with the disruption of gastrulation seen earlier in development. This phenotype could be partially rescued by a CD1 genetic background, although the homozygous mutation was always lethal by embryonic day 11, with death probably resulting from abnormal placentation and failure of cardiac morphogenesis.

Different observations suggest that dihydropyridine calcium antagonists alter endothelial NO release. Therefore, in a first step we investigated whether part of the nisoldipine (a dihydropyridine calcium antagonist with a possible selectivity for coronaries)-induced vasorelaxation was due to an NO release from the endothelium in porcine coronary arteries. Secondly, we directly measured whether nisoldipine increased NO release from rabbit aorta or the nisoldipine enantiomers (Bay R 1223, Bay R 1224) from rat aorta. Thirdly, we determined whether nisoldipine exerted antioxidative properties in segments of porcine aorta with intact endothelium. Blocking endothelial NO synthase with N-nitro-L-arginine resulted in a significant shift of the relaxation curve to higher concentrations. Accordingly, nisoldipine induced a concentration-dependent release of NO (direct electrochemical detection) from native endothelium which already started at a therapeutical level (1 nmol/l nisoldipine/6.5 +/- 1.2 nmol/l NO). To evaluate whether this effect was due to an antioxidative protection of NO, we examined the influence of nisoldipine on a hyperglycemia (30 mmol/l, 20 min)-induced reactive oxygen species release of vascular endothelium from porcine coronary arteries. Nisoldipine concentration-dependently reduced the reactive oxygen species release (>50%; 10 micromol/l). Moreover, a carbachol-induced NO release (rabbit aorta) which was significantly diminished by hyperglycemia was completely restored in the presence of nisoldipine (3 micromol/l). We conclude that nisoldipine increases the NO bioavailability which may result in an ameliorated endothelial function.

To find a solution to the problem of friction between the nylon fishing line and the outrigger of a low-profile dynamic splint, a jig was manufactured to bend notches in 2.5-mm copper-coated welding rod. This type of outrigger was compared with an adjustable stainless-steel outrigger to determine which of the two types produces the least amount of friction. As one of each type of outrigger was covered with a layer of Teflon paint, four different outriggers were compared with each other: welding rod only, welding rod with Teflon, stainless steel with Teflon, and stainless steel only. Equal traction units were attached to each of the outriggers and the amount of elongation of a 50-mm tension spring was measured when a 300-g weight was hooked onto it. This was compared with the elongation of the same spring when no friction was present. The results show that the Teflon-covered outriggers displayed significantly (on a 5% level) less friction than did the uncovered outriggers. The stainless-steel outrigger with Teflon performed slightly better than the welding-rod outrigger with Teflon. However, there was no significant difference between these two outriggers, and because the welding-rod outrigger is cheaper and more readily available, it is recommended for clinical use.