Ageing, Adaption and Accessibility: Time for the Inclusive Revolution!

Information and Communication Technology (ICT) is becoming increasingly central to many people’s lives, making it possible to be connected in any place at any time, be unceasingly and instantly informed, and benefit from greater economic and educational opportunities. With all the benefits afforded by these new-found capabilities, however, come potential drawbacks. A plethora of new PCs, laptops, tablets, smartphones, Bluetooth, the internet, Wi-Fi (the list goes on) expect us to know or be able to guess, what, where and when to connect, click, double-click, tap, flick, scroll, in order to realise these benefits, and to have the physical and cognitive capability to do all these things. One of the groups most affected by this increase in high-demand technology is older people. They do not understand and use technology in the same way that younger generations do, because they grew up in the simpler electro-mechanical era and embedded that particular model of the world in their minds. Any consequential difficulty in familiarising themselves with modern ICT and effectively applying it to their needs can also be exacerbated by age-related changes in vision, motor control and cognitive functioning. Such challenges lead to digital exclusion. Much has been written about this topic over the years, usually by academics from the area of inclusive product design. The issue is complex and it is fair to say that no one researcher has the whole picture. It is difficult to understand and adequately address the issue of digital exclusion among the older generation without looking across disciplines and at industry’s and government’s understanding, motivation and efforts toward resolving this important problem. To do otherwise is to risk misunderstanding the true impact that ICT has and could have on people’s lives across all generations. In this European year of Active Ageing and Solidarity between Generations and as the British government is moving forward with its Digital by Default initiative as part of a wider objective to make ICT accessible to as many people as possible by 2015, the Engineering Design Centre (EDC) at the University of Cambridge collaborated with BT to produce a book of thought pieces to address, and where appropriate redress, these important and long-standing issues. “Ageing, Adaption and Accessibility: Time for the Inclusive Revolution!” brings together opinions and insights from twenty one prominent thought leaders from government, industry and academia regarding the problems, opportunities and strategies for combating digital exclusion among senior citizens. The contributing experts were selected as individuals, rather than representatives of organisations, to provide the broadest possible range of perspectives. They are renowned in their respective fields and their opinions are formed not only from their own work, but also from the contributions of others in their area. Their views were elicited through conversations conducted by the editors of this book who then drafted the thought pieces to be edited and approved by the experts. We hope that this unique collection of thought pieces will give you a broader perspective on ageing, people’s adaption to the ever changing world of technology and insights into better ways of designing digital devices and services for the older population.

Evaluation of Setup Procedures on Mobile Devices Based on Users’ Initial Experience

Users’ initial perceptions of their competence are key motivational factors for further use. However, initial tasks on a mobile operating system (OS) require setup procedures, which are currently largely inconsistent, do not provide users with clear, visible and immediate feedback on their actions, and require significant adjustment time for first-time users. This paper reports on a study with ten users, carried out to better understand how both prior experience and initial interaction with two touchscreen mobile interfaces (Apple iOS and Google Android) affected setup task performance and motivation. The results show that the reactions to setup on mobile interfaces appear to be partially dependent on which device was experienced first. Initial experience with lower-complexity devices improves performance on higher-complexity devices, but not vice versa. Based on these results, the paper proposes six guidelines for designers to design more intuitive and motivating user interfaces (UI) for setup procedures. The preliminary results indicate that these guidelines can contribute to the design of more inclusive mobile platforms and further work to validate these findings is proposed.

Electrostatic effects in filamentous protein aggregation.

Electrostatic forces play a key role in mediating interactions between proteins. However, gaining quantitative insights into the complex effects of electrostatics on protein behavior has proved challenging, due to the wide palette of scenarios through which both cations and anions can interact with polypeptide molecules in a specific manner or can result in screening in solution. In this article, we have used a variety of biophysical methods to probe the steady-state kinetics of fibrillar protein self-assembly in a highly quantitative manner to detect how it is modulated by changes in solution ionic strength. Due to the exponential modulation of the reaction rate by electrostatic forces, this reaction represents an exquisitely sensitive probe of these effects in protein-protein interactions. Our approach, which involves a combination of experimental kinetic measurements and theoretical analysis, reveals a hierarchy of electrostatic effects that control protein aggregation. Furthermore, our results provide a highly sensitive method for the estimation of the magnitude of binding of a variety of ions to protein molecules.

Influence of specific HSP70 domains on fibril formation of the yeast prion protein Ure2.

Ure2p is the protein determinant of the Saccharomyces cerevisiae prion state [URE3]. Constitutive overexpression of the HSP70 family member SSA1 cures cells of [URE3]. Here, we show that Ssa1p increases the lag time of Ure2p fibril formation in vitro in the presence or absence of nucleotide. The presence of the HSP40 co-chaperone Ydj1p has an additive effect on the inhibition of Ure2p fibril formation, whereas the Ydj1p H34Q mutant shows reduced inhibition alone and in combination with Ssa1p. In order to investigate the structural basis of these effects, we constructed and tested an Ssa1p mutant lacking the ATPase domain, as well as a series of C-terminal truncation mutants. The results indicate that Ssa1p can bind to Ure2p and delay fibril formation even in the absence of the ATPase domain, but interaction of Ure2p with the substrate-binding domain is strongly influenced by the C-terminal lid region. Dynamic light scattering, quartz crystal microbalance assays, pull-down assays and kinetic analysis indicate that Ssa1p interacts with both native Ure2p and fibril seeds, and reduces the rate of Ure2p fibril elongation in a concentration-dependent manner. These results provide new insights into the structural and mechanistic basis for inhibition of Ure2p fibril formation by Ssa1p and Ydj1p.

Nanobodies raised against monomeric α-synuclein distinguish between fibrils at different maturation stages.

Nanobodies are single-domain fragments of camelid antibodies that are emerging as versatile tools in biotechnology. We describe here the interactions of a specific nanobody, NbSyn87, with the monomeric and fibrillar forms of α-synuclein (αSyn), a 140-residue protein whose aggregation is associated with Parkinson's disease. We have characterized these interactions using a range of biophysical techniques, including nuclear magnetic resonance and circular dichroism spectroscopy, isothermal titration calorimetry and quartz crystal microbalance measurements. In addition, we have compared the results with those that we have reported previously for a different nanobody, NbSyn2, also raised against monomeric αSyn. This comparison indicates that NbSyn87 and NbSyn2 bind with nanomolar affinity to distinctive epitopes within the C-terminal domain of soluble αSyn, comprising approximately amino acids 118-131 and 137-140, respectively. The calorimetric and quartz crystal microbalance data indicate that the epitopes of both nanobodies are still accessible when αSyn converts into its fibrillar structure. The apparent affinities and other thermodynamic parameters defining the binding between the nanobody and the fibrils, however, vary significantly with the length of time that the process of fibril formation has been allowed to progress and with the conditions under which formation occurs, indicating that the environment of the C-terminal domain of αSyn changes as fibril assembly takes place. These results demonstrate that nanobodies are able to target forms of potentially pathogenic aggregates that differ from each other in relatively minor details of their structure, such as those associated with fibril maturation.

1.5 GHz picosecond pulse generation from a monolithic waveguide laser with a graphene-film saturable output coupler

We fabricate a saturable absorber mirror by coating a graphenefilm on an output coupler mirror. This is then used to obtain Q-switched mode-locking from a diode-pumped linear cavity channel waveguide laser inscribed in Ytterbium-doped Bismuthate Glass. The laser produces 1.06 ps pulses at ∼1039 nm, with a 1.5 GHz repetition rate, 48% slope efficiency and 202 mW average output power. This performance is due to the combination of the graphene saturable absorber and the high quality optical waveguides in the laser glass. © 2013 Optical Society of America.

Ultrafast non-thermal electron dynamics in single layer graphene

We study the ultrafast dynamics of non-thermal electron relaxation in graphene upon impulsive excitation. The 10-fs resolution two color pump-probe allows us to unveil the non-equilibrium electron gas decay at early times. © Owned by the authors, published by EDP Sciences, 2013.

Confidence in beliefs about pain predicts expectancy effects on pain perception and anticipatory processing in right anterior insula.

Psychological factors play a major role in exacerbating chronic pain. Effective self-management of pain is often hindered by inaccurate beliefs about the nature of pain which lead to a high degree of emotional reactivity. Probabilistic models of perception state that greater confidence (certainty) in beliefs increases their influence on perception and behavior. In this study, we treat confidence as a metacognitive process dissociable from the content of belief. We hypothesized that confidence is associated with anticipatory activation of areas of the pain matrix involved with top-down modulation of pain. Healthy volunteers rated their beliefs about the emotional distress that experimental pain would cause, and separately rated their level of confidence in this belief. Confidence predicted the influence of anticipation cues on experienced pain. We measured brain activity during anticipation of pain using high-density EEG and used electromagnetic tomography to determine neural substrates of this effect. Confidence correlated with activity in right anterior insula, posterior midcingulate and inferior parietal cortices during the anticipation of pain. Activity in the right anterior insula predicted a greater influence of anticipation cues on pain perception, whereas activity in right inferior parietal cortex predicted a decreased influence of anticipatory cues. The results support probabilistic models of pain perception and suggest that confidence in beliefs is an important determinant of expectancy effects on pain perception.

Modulation of pain ratings by expectation and uncertainty: Behavioral characteristics and anticipatory neural correlates.

Expectations about the magnitude of impending pain exert a substantial effect on subsequent perception. However, the neural mechanisms that underlie the predictive processes that modulate pain are poorly understood. In a combined behavioral and high-density electrophysiological study we measured anticipatory neural responses to heat stimuli to determine how predictions of pain intensity, and certainty about those predictions, modulate brain activity and subjective pain ratings. Prior to receiving randomized laser heat stimuli at different intensities (low, medium or high) subjects (n=15) viewed cues that either accurately informed them of forthcoming intensity (certain expectation) or not (uncertain expectation). Pain ratings were biased towards prior expectations of either high or low intensity. Anticipatory neural responses increased with expectations of painful vs. non-painful heat intensity, suggesting the presence of neural responses that represent predicted heat stimulus intensity. These anticipatory responses also correlated with the amplitude of the Laser-Evoked Potential (LEP) response to painful stimuli when the intensity was predictable. Source analysis (LORETA) revealed that uncertainty about expected heat intensity involves an anticipatory cortical network commonly associated with attention (left dorsolateral prefrontal, posterior cingulate and bilateral inferior parietal cortices). Relative certainty, however, involves cortical areas previously associated with semantic and prospective memory (left inferior frontal and inferior temporal cortex, and right anterior prefrontal cortex). This suggests that biasing of pain reports and LEPs by expectation involves temporally precise activity in specific cortical networks.

Temporal difference models describe higher-order learning in humans.

The ability to use environmental stimuli to predict impending harm is critical for survival. Such predictions should be available as early as they are reliable. In pavlovian conditioning, chains of successively earlier predictors are studied in terms of higher-order relationships, and have inspired computational theories such as temporal difference learning. However, there is at present no adequate neurobiological account of how this learning occurs. Here, in a functional magnetic resonance imaging (fMRI) study of higher-order aversive conditioning, we describe a key computational strategy that humans use to learn predictions about pain. We show that neural activity in the ventral striatum and the anterior insula displays a marked correspondence to the signals for sequential learning predicted by temporal difference models. This result reveals a flexible aversive learning process ideally suited to the changing and uncertain nature of real-world environments. Taken with existing data on reward learning, our results suggest a critical role for the ventral striatum in integrating complex appetitive and aversive predictions to coordinate behaviour.