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Galcanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, was recently approved for migraine prophylaxis. The pharmacokinetic/pharmacodynamic (PK/PD) relationship between galcanezumab concentration and inhibition of capsaicin-induced dermal blood flow (CIDBF) was evaluated using first-in-human data following 6 single subcutaneous doses (1 to 600 mg) or multiple (4) 150-mg doses every 2 weeks in 7 cohorts (7 actively treated subjects and 2 placebo-treated healthy subjects). Galcanezumab pharmacokinetics were best described by a 1-compartment model with delayed first-order absorption/linear elimination. Apparent estimates (between-subject variability) of clearance, volume of distribution, absorption rate constant, and lag time were 0.0106 L/h (27%CV), 11.2 L (21%CV), 0.0192 h-1 (89%CV), and 0.202 hours, respectively. Estimated elimination half-life was about 30 days. An effect compartment link model described the concentration-effect relationship; estimated maximum inhibitory effect was 70.5%, and 50% maximum inhibitory effect concentration (IC50 ) was 1060 ng/mL. Galcanezumab showed dose- and concentration-dependent potent and durable inhibition of CIDBF. Simulated effect compartment concentrations were maintained above IC50 after 12 weeks of dosing. Near-maximal CIDBF inhibition occurred with 150 mg biweekly for 12 weeks lasting ≥24 weeks or with ≥30 mg every 2 weeks or 195 mg every 13 weeks. Quantitative modeling of galcanezumab PK/PD supported dose selection for the phase 2 proof-of-concept study.

COVID-19 has radically changed society as we know it. To reduce the spread of the virus, millions across the globe have been forced to work remotely, often in make-shift home offices, and using a plethora of new, unfamiliar digital technologies. In this article, we critically analyse cyber security and privacy concerns arising due to remote working during the coronavirus pandemic. Through our work, we discover a series of security risks emerging because of the realities of this period. For instance, lack of remote-working security training, heightened stress and anxiety, rushed technology deployment, and the presence of untrusted individuals in a remote-working environment (e.g., in flatshares), can result in new cyber-risk. Simultaneously, we find that as organisations look to manage these and other risks posed by their remote workforces, employee's privacy (including personal information and activities) is often compromised. This is apparent in the significant adoption of remote workplace monitoring, management and surveillance technologies. Such technologies raise several privacy and ethical questions, and further highlight the tension between security and privacy going forward., HCI International 2021 (HCII 2021)

Alzheimer’s Disease (AD) tau pathology originates in the brainstem and subsequently spreads to the entorhinal cortex, hippocampus and finally to temporal, parietal and prefrontal association cortices in a relatively stereotyped progression. Current evidence attributes this orderly progression to trans-neuronal spread of misfolded tau protein along the projection pathways of affected neurons. The aggregation of tau is being increasingly recognized as a trustworthy biomarker preceding the appearance of Alzheimer’s disease (AD) symptoms. One major goals of disease modifying therapies has been to stop or slow down the tau aggregation process. In order to evaluate drug efficacy, it would be desirable to have an accurate model predictive of a patient’s future tau burden, against which the tau measurements from drug-receiving cohorts could be compared. Here we report the development of such a model, evaluated in a cohort of 88 subjects clinically diagnosed as Mild Cognitively Impaired (MCI = 60) or Alzheimer’s disease (AD = 28) and tracked over a period of 18 months. Our approach combined data-driven and model-based methodologies, with the goal of predicting changes in tau within suitably specified target regions. We show that traditional statistical methods, allied to a network diffusion model for tau propagation in the brain, provide a remarkable prediction of the magnitude of incremental tau deposited in particular cortical areas of the brain over this period (MCI: R2 = 0.65±0.16; AD: R2 = 0.71±0.11) from baseline data. Our work has the potential to greatly strengthen the repertoire of analysis tools used in AD clinical trials, opening the door to future interventional trials with far fewer sample sizes than currently required.

Background Previous studies found that [18F]LSN3316612 was a promising positron emission tomography (PET) radioligand for imaging O-GlcNAcase in nonhuman primates and human volunteers. This study sought to further evaluate the suitability of [18F]LSN3316612 for human clinical research. Methods Kinetic evaluation of [18F]LSN3316612 was conducted in a combined set of baseline brain scans from 17 healthy human volunteers and test-retest imaging was conducted in 10 of these volunteers; another 6 volunteers had whole-body scans to measure radiation exposure to body organs. Total distribution volume (VT) estimates were compared for the one- and two-tissue compartment models with the arterial input function. Test-retest variability and reliability were evaluated via mean difference and intraclass correlation coefficient (ICC). The time stability of VT was assessed down to a 30-min scan time. An alternative quantification method for [18F]LSN3316612 binding without blood was also investigated to assess the possibility of eliminating arterial sampling. Results Brain uptake was generally high and could be quantified as VT with excellent identifiability using the two-tissue compartment model. [18F]LSN3316612 exhibited good absolute test-retest variability (12.5%), but the arithmetic test-retest variability was far from 0 (11.3%), reflecting a near-uniform increase of VT on the retest scan in nine of 10 volunteers. VT values were stable after 110 min in all brain regions, suggesting that no radiometabolites accumulated in the brain. Measurements obtained using only brain activity (i.e., area under the curve (AUC) from 150–180 min) correlated strongly with regional VT values during test-retest conditions (R2 = 0.84), exhibiting similar reliability to VT (ICC = 0.68 vs. 0.64). Estimated radiation exposure for [18F]LSN3316612 PET was 20.5 ± 2.1 μSv/MBq, comparable to other 18F-labeled radioligands for brain imaging. Conclusions [18F]LSN3316612 is an excellent PET radioligand for imaging O-GlcNAcase in the human brain. Alternative quantification without blood is possible, at least for within-subject repeat studies. However, the unexplained increase of VT under retest conditions requires further investigation.

The Principles of Robotics were outlined by the EPSRC in 2010. They are aimed at regulating robots in the real world. This paper represents a response to principle number four which reads: “Robots are manufactured artefacts. They should not be designed in a deceptive way to exploit vulnerable users; instead their machine nature should be transparent”. The following critique questions the principle's validity by asking whether it is correct as a statement about the nature of robots, and the relationship between robots and people. To achieve this, the principle is broken down into the following two main component statements: 1 “Robots should not be designed in a deceptive way to exploit vulnerable users”, and, 2 “Machine nature should be transparent”. It is argued that both of the component statements that make up this principle are fundamentally flawed because of the undefined nature of the critical terms: “deceptive”, “vulnerable”, and “machine nature”, and that as such the principle as a whole is misleading.

Cyber crime is rising at an unprecedented rate. Organisations are spending more than ever combating the human element through training and other interventions, such as simulated phishing. Organisations employ “carrots” (rewards) and “sticks” (sanctions) to reduce risky behaviour. Sanctions (such as locking computers and informing one’s line manager) are problematic as they lead to unintended consequences towards employee trust and productivity. This study explored how organisations use rewards and sanctions both in their campaigns and specifically following simulated phishing. We also assessed what factors (such as control over rewards, tendency to blame users) influenced security awareness professionals’ use of rewards and sanctions. The findings revealed that organisations use a variety of rewards and sanctions within their campaigns, with sanctions being used across 90% of the organisations. We did not find any factors that influence security awareness professionals’ usage of rewards and sanctions. Our findings suggest the need for a greater consideration of the human element of cyber security. In particular, campaigns should take a more informed approach to use of behaviour change strategies that consider the organisational structure in which they are implemented and the role (and influence) of security awareness professionals within that structure.

The advent of sophisticated robotics and AI technology makes sending humans into hazardous and distant environments to carry out inspections increasingly avoidable. Being able to send a robot, rather than a human, into a nuclear facility or deep space is very appealing. However, building these robotic systems is just the start and we still need to carry out a range of verification and validation tasks to ensure that the systems to be deployed are as safe and reliable as possible. Based on our experience across three research and innovation hubs within the UK’s “Robots for a Safer World” programme, we present an overview of the relevant techniques and challenges in this area. As the hubs are active across nuclear, offshore, and space environments, this gives a breadth of issues common to many inspection robots.

Free-to-play online games create significant revenues through sales of virtual items. The argument that the sale of items that provide a competitive advantage (functional items) fuels a pay-to-win culture has attracted developers to business models that are solely based on the sale of non-functional items (items that provide no objective competitive advantage). However, the motivations for purchasing non-functional items remain under-examined. The present study therefore provides an exploration of hedonic, social, and utilitarian motivations underpinning purchase of virtual items within the top-grossing free-to-play game League of Legends. From interviews with 32 players, a number of motivations are identified and presented. In addition, a novel finding is that motivation for purchase may not stem from the value in the item but lie in the act of purchasing itself as a means of transferring money to the developer.

Autonomous systems are increasingly being used in safety-and mission-critical domains, including aviation, manufacturing, healthcare and the automotive industry. Systems for such domains are often verified with respect to essential requirements set by a regulator, as part of a process called certification. In principle, autonomous systems can be deployed if they can be certified for use. However, certification is especially challenging as the condition of both the system and its environment will surely change, limiting the effective use of the system. In this paper we discuss the technological and regulatory background for such systems, and introduce an architectural framework that supports verifiably-correct dynamic self-certification by the system, potentially allowing deployed systems to operate more safely and effectively.

Smartphones are now ubiquitous and valuable in many professions and yet have also been blamed for creating an ‘always on' culture, blurring boundaries between work and home. Research has shown that checking e-mails out-of-hours via computer makes workers feel more overloaded with work but also increases their sense of coping. A total of 94 participants completed a survey exploring whether the same pattern would emerge for accessing e-mail on smartphones, showing that those who use smartphones for work e-mail experienced lower levels of overload, but not coping, and push notifications were associated with greater use of smartphones for e-mail. However, there were no significant correlations between coping or overload and e-mail use or quantity, suggesting that lower overload is not due to the ability to processes or read more e-mails outside of work.

LY2951742, a monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being developed for migraine prevention and osteoarthritis pain. To support the clinical development of LY2951742, capsaicin-induced dermal blood flow (DBF) was used as a target engagement biomarker to assess CGRP activity in nonhuman primates and healthy volunteers. Inhibition of capsaicin-induced DBF in nonhuman primates, measured with laser Doppler imaging, was dose dependent and sustained for at least 29 days after a single intravenous injection of the CGRP antibody. This information was used to generate a pharmacokinetic/pharmacodynamic model, which correctly predicted inhibition of capsaicin-induced DBF in humans starting at a single subcutaneous 5-mg dose. As expected, the degree of inhibition in capsaicin-induced DBF increased with higher LY2951742 plasma concentrations. Utilization of this pharmacodynamic biomarker with pharmacokinetic data collected in phase I studies provided the dose-response relationship that assisted in dose selection for the phase II clinical development of LY2951742.

Background: Calcitonin gene-related peptide (CGRP) is pivotal in the pathophysiology of migraine headaches and represents a promising target for migraine treatment. The humanized monoclonal antibody galcanezumab (LY2951742) binds to CGRP and may be effective in migraine prophylaxis. Objectives: The primary objective was to evaluate the safety and tolerability of single and multiple doses of galcanezumab in humans. Secondary objectives included assessing the pharmacokinetics and evaluating target engagement. Methods: A double-blind, randomized, placebo-controlled study (NCT 01337596) with single escalating and multiple subcutaneous (SC) doses of galcanezumab was performed in healthy male volunteers. Single doses of 1, 5, 25, 75, 200, and 600 mg of galcanezumab (n = 7/dose) or placebo (n = 2/dose) were injected SC in six consecutive cohorts of nine subjects each. One cohort of nine subjects received multiple (4) 150 mg doses of galcanezumab or placebo every other week. Target engagement was evaluated by measuring inhibition of capsaicin-induced increase in dermal blood flow (DBF). Findings: Sixty-three subjects were randomized and included in the safety analyses. Galcanezumab was well tolerated in single doses (1-600 mg SC) and consecutive doses (150 mg SC). There was no dose-dependent difference in type or frequency of treatment-emergent adverse events, and no clinically meaningful difference when compared with placebo. Pharmacokinetics were linear. Galcanezumab induced a robust, dose-dependent, and durable inhibition of capsaicin-induced increase in DBF, supporting the continued clinical development of galcanezumab for prophylaxis in migraine patients. ispartof: Frontiers in Pharmacology vol:8 issue:OCT pages:740- ispartof: location:Switzerland status: published

Animal-Computer Interaction (ACI) is a new and quickly developing discipline, which is closely related to HCI and is making reference to some of its theoretical frameworks and research methodologies. The first edition of the Workshop on Research Methods in ACI (RM4ACI) was co-located with the Third International Conference on Animal-Computer Interaction, which took place in Milton-Keynes, UK in November 2016. This paper presents an overview of the workshop, including insights from discussions on some of the challenges faced by the ACI community as it works to develop ACI as a discipline, and on important opportunities for cross-fertilization between HCI and ACI that the HCI community could consider.

Long-term health risks associated with unhealthy lifestyles present a significant current and future burden for healthcare providers. Adolescence represents a critical time for intervention, as habits formed during this period can persist throughout adult life. Given the prevalence of gaming as an entertainment medium amongst adolescents, and subsequent potential for engagement, the use of serious games to promote changes in lifestyle behaviour offers a potential solution. Creating such games requires a breadth of multidisciplinary expertise, working collaboratively to create research-informed designs which reflect both behavioural theory and entertainment game design best practices. In this chapter, challenges and benefits associated with multidisciplinary design are identified and discussed, with strategies presented to overcome and avoid potential issues. With reference to a current project, the perspectives of the theorist, iterative designer, and game developer are contrasted, providing a reference for future projects implementing multidisciplinary approaches to serious game design.

Networking is a vital but stressful aspect of academic life, one which digital games may be able to make more playful. Existing examples of networking games require players to interact as part of the game-play, and therefore do not bypass the stressful part of networking. In contrast, many other games successfully encourage interaction between players whilst avoiding causing stress to the players. Flashbulb is a networking game that only requires a photograph of another player to be taken in order to progress. Players can choose whether to start a conversation depending on the target and situation. Thematic analysis of interviews with Flashbulb players found that despite not including an icebreaking requirement, it encouraged networking and widened the scope of those spoken to. The act of photographing players promoted conversations without forcing players to engage in uncomfortable discussions. We make recommendations for the design of future iterations of networking games.

This work presents the safety and verification arguments for the development of an autonomous robot platform capable of leading humans around a building. It uses Goal Structuring Notation (GSN) to develop a pattern, a re-usable GSN fragment, that can form part of the safety case surrounding the interaction of a mobile guide robot to: record the decisions taken during the design phase, ensure safe operation around humans, and identify where mitigation must be introduced.

For assistive robots (in roles such as carers, guides, companions, and assistants) to be most effective, they will need to engender trust in their users. The ROBO-GUIDE (ROBOtic GUidance and Interaction DEvelopment) project is an interdisciplinary project bringing together engineers and scientists working in computational neuroscience, control systems, formal verification, natural language, and psychology, to address how such a system can be designed. This paper outlines our approach, which focuses on the key trust influencers: safety, verification, communication, and behaviour.

Human robot interaction (HRI) often considers the human impact of a robot serving to assist a human in achieving their goal or a shared task. There are many circumstances though during HRI in which a robot may make errors that are inconvenient or even detrimental to human partners. Using the ROBOtic GUidance and Interaction DEvelopment (ROBO-GUIDE) model on the Pioneer LX platform as a case study, and insights from social psychology, we examine key factors for a robot that has made such a mistake, ensuring preservation of individuals’ perceived competence of the robot, and individuals’ trust towards the robot. We outline an experimental approach to test these proposals.

Here we present MIRO, a companion robot designed to engage users in science and robotics via edutainment. MIRO is a robot that is biomimetic in aesthetics, morphology, behaviour, and control architecture. In this paper, we review how these design choices affect its suitability for a companionship role. In particular, we consider how MIRO's emulation of familiar mammalian body language as one component of a broader biomimetic expressive system provides effective communication of emotional state and intent. We go on to discuss how these features contribute to MIRO's potential in other domains such as healthcare, education, and research.

Observational studies of situated displays have suggested that they are rarely looked at, and when they are it is typically only for a short period of time. Using a mobile eye tracker during a realistic shopping task in a shopping center, we show that people look at displays more than would be predicted from these observational studies, but still only short glances and often from quite far away. We characterize the patterns of eye-movements that precede looking at a display and discuss some of the design implications for the design of situated display technologies that are deployed in public space.

Recently, the concept of a 'companion robot' as a healthcare tool has been popularised, and even commercialised. We present MIRO, a robot that is biomimetic in aesthetics, morphology, behaviour, and control architecture. In this paper, we review how these design choices affect its suitability for a companionship role. In particular, we consider how emulation of the familiar body language and other emotional expressions of mammals may facilitate effective communication with naive users through the reliable evocation of intended perceptions of emotional state and intent. We go on to present a brief pilot study addressing the question of whether shared cultural signals can be relied upon, similarly, as components of communication systems for companion robots. Such studies form part of our ongoing effort to understand and quantify human responses to robot expressive behaviour and, thereby, develop a methodology for optimising the design of social robots by accounting for individual and cultural differences.

The dramatic rise in the use of social network sites (SNS) has resulted in a number of users feeling stressed about the extent of their personal use. Previous work has established that daily retrospective estimations of SNS use and access to RescueTime not only improve accuracy of estimations but also reduce perceived stress. The present study aimed to extend this by also exploring the influence of prospective estimations on stress and perceived time management. However, the study was thwarted by incredibly low engagement with RescueTime and consequently, no improvement in estimation accuracy and no reduction in stress. This indicates substantial individual differences in engagement and a requirement for external sources of motivation for using personal informatics, beyond the tasks of the study.

The Expressive Agents for Symbiotic Education and Learning (EASEL) project will explore human-robot symbiotic interaction (HRSI) with the aim of developing an understanding of symbiosis over long term tutoring interactions. The EASEL system will be built upon an established and neurobiologically grounded architecture - Distributed Adaptive Control (DAC). Here we present the design of an initial experiment in which our facially expressive humanoid robot will interact with children at a public exhibition. We discuss the range of measurements we will employ to explore the effects our robot’s expressive ability has on interaction with children during HRSI, with the aim of contributing optimal robot personality parameters to the final EASEL model.

Recent advances in mobile technology have had many positive effects on the ways in which people can combine work and home life. For example, having remote access enables people to work from home, or work flexible hours that fit around caring responsibilities. They also support communication with colleagues and family members, and enable digital hobbies. However, the resulting 'always-online' culture can undermine work-home boundaries and cause stress to those who feel under pressure to respond immediately to digital notifications. This workshop will explore how a socio-technical perspective, which views boundaries as being constituted by everyday socio-technical practices, can inform the design of technologies that help maintain boundaries between work and home life.

Action video game players have been found to outperform nonplayers on a variety of cognitive tasks. However, several failures to replicate these video game player advantages have indicated that this relationship may not be straightforward. Moreover, despite the discovery that problematic video game players do not appear to demonstrate the same superior performance as nonproblematic video game players in relation to multiple object tracking paradigms, this has not been investigated for other tasks. Consequently, this study compared gamers and nongamers in task switching ability, visual short-term memory, mental rotation, enumeration, and flanker interference, as well as investigated the influence of self-reported problematic video game use. A total of 66 participants completed the experiment, 26 of whom played action video games, including 20 problematic players. The results revealed no significant effect of playing action video games, nor any influence of problematic video game play. This indicates that the previously reported cognitive advantages in video game players may be restricted to specific task features or samples. Furthermore, problematic video game play may not have a detrimental effect on cognitive performance, although this is difficult to ascertain considering the lack of video game player advantage. More research is therefore sorely needed.