Effects of the visual environment on object localization in posterior cortical atrophy and typical Alzheimer's disease.

Introduction: Visual processing deficits in Alzheimer's disease are associated with diminished functional independence. While environmental adaptations have been proposed to promote independence, recent guidance gives limited consideration to such deficits and offers conflicting recommendations for people with dementia. We evaluated the effects of clutter and color contrasts on performances of everyday actions in posterior cortical atrophy and memory-led typical Alzheimer's disease. Methods: 15 patients with posterior cortical atrophy, 11 with typical Alzheimer's disease and 16 healthy controls were asked to pick up a visible target object as part of two pilot repeated-measures investigations from a standing or seated position. Participants picked up the target within a controlled real-world setting under varying environmental conditions: with/without clutter, with/without color contrast cue and far/near target position. Task completion time was recorded using a target-mounted inertial measurement unit. Results: Across both experiments, difficulties locating a target object were apparent through patient groups taking an estimated 50-90% longer to pick up targets relative to controls. There was no evidence of effects of color contrast when locating objects from standing/seated positions and of any other environmental conditions from a standing position on completion time in any participant group. Locating objects, surrounded by five distractors rather than none, from a seated position was associated with a disproportionately greater effect on completion times in the posterior cortical atrophy group relative to the control or typical Alzheimer's disease groups. Smaller, not statistically significant but directionally consistent, ratios of relative effects were seen for two distractors compared with none. Discussion: Findings are consistent with inefficient object localization in posterior cortical atrophy relative to typical Alzheimer's disease and control groups, particularly with targets presented within reaching distance among visual clutter. Findings may carry implications for considering the adverse effects of visual clutter in developing and implementing environmental modifications to promote functional independence in Alzheimer's disease.

The Association between Physical Environment and Externalising Problems in Typically Developing and Neurodiverse Children and Young People: A Narrative Review.

The physical environment is of critical importance to child development. Understanding how exposure to physical environmental domains such as greenspace, urbanicity, air pollution or noise affects aggressive behaviours in typical and neurodiverse children is of particular importance given the significant long-term impact of those problems. In this narrative review, we investigated the evidence for domains of the physical environment that may ameliorate or contribute to the display of aggressive behaviours. We have considered a broad range of study designs that include typically developing and neurodiverse children and young people aged 0-18 years. We used the GRADE system to appraise the evidence. Searches were performed in eight databases in July 2020 and updated in June 2022. Additional articles were further identified by hand-searching reference lists of included papers. The protocol for the review was preregistered with PROSPERO. Results: We retrieved 7174 studies of which 67 are included in this review. The studies reported on green space, environmental noise and music, air pollution, meteorological effects, spatial density, urban or rural setting, and interior home elements (e.g., damp/sensory aspects/colour). They all used well validated parent and child reported measures of aggressive behaviour. Most of the studies were rated as having low or unclear risk of bias. As expected, noise, air pollution, urbanicity, spatial density, colour and humidity appeared to increase the display of aggressive behaviours. There was a dearth of studies on the role of the physical environment in neurodiverse children. The studies were heterogeneous and measured a range of aggressive behaviours from symptoms to full syndromes. Greenspace exposure was the most common domain studied but certainty of evidence for the association between environmental exposures and aggression problems in the child or young person was low across all domains. We found a large knowledge gap in the literature concerning neurodiverse children, which suggests that future studies should focus on these children, who are also more likely to experience adverse early life experiences including living in more deprived environments as well as being highly vulnerable to the onset of mental ill health. Such research should also aim to dis-aggregate the underlying aetiological mechanisms for environmental influences on aggression, the results of which may point to pathways for public health interventions and policy development to address inequities that can be relevant to ill health in neurodiverse young people.

The impact of a passenger-safety-driven acceleration limit on the operation of a bus service.

Buses are a form of active transportation and can improve people's well-being. However, their high level of acceleration can make them less attractive to users. Even worse, they can be responsible for severe injuries that require hospitalisation or for the development of fear of falling, particularly experienced by older people. Evidence has shown that, bus acceleration up to 1.0 m/s2 enables passengers to move in a natural way inside the moving vehicle, hence reducing instability and increasing safety. Although operators might be willing to implement such an intervention, they might also be skeptical about its impact on the operation of a service, such as timetabling, travel times, waiting times, etc. The effect of a safety-driven acceleration limit on the operational characteristics of a round trip of a bus service in London is investigated by this study. Data regarding speed, acceleration and journey time were extracted from the engine of a bus and recorded at 2 Hz. Further computations estimated the passenger waiting times and headways between the examined bus and its preceding and following buses. A vehicle movement model was used to test how these operational characteristics would be affected if the acceleration limit of 1.0 m/s2 were to be implemented. The results suggest that the journey time of the proposed accessible service would be 6 min longer than the current service and passenger waiting time would increase by 2 min. One additional bus would be required to serve the same number of passengers. A discussion of the results is provided.

Effects of lighting variability on locomotion in posterior cortical atrophy.

INTRODUCTION: Clinical reports describe patients with Alzheimer's disease (AD) exhibiting atypical adaptive walking responses to the visual environment; however, there is limited empirical investigation of such behaviors or factors modulating their expression. We aim to evaluate effects of lighting-based interventions and clinical presentation (visual- vs memory-led) on walking function in participants with posterior cortical atrophy (PCA) and typical AD (tAD). METHODS: Participants with PCA (n = 10), tAD (n = 9), and healthy controls (n = 12) walked to visible target destinations under different lighting conditions within two pilot repeated-measures design investigations (Experiment 1: 32 trials per participant; Experiment 2: 36 trials per participant). Participants walked to destinations with the floorpath interrupted by shadows varying in spatial extent (Experiment 1: no, medium, high shadow) or with different localized parts of the environment illuminated (Experiment 2: target, middle, or distractor illuminated). The primary study outcome for both experimental tasks was completion time; secondary kinematic outcomes were proportions of steps identified as outliers (Experiment 1) and walking path directness (Experiment 2). RESULTS: In Experiment 1, PCA participants overall demonstrated modest reductions in time taken to reach destinations when walking to destinations uninterrupted by shadows compared to high shadow conditions (7.1% reduction [95% confidence interval 2.5, 11.5; P = .003]). Experiment 2 found no evidence of differences in task performance for different localized lighting conditions in PCA participants overall. Neither experiment found evidence of differences in task performance between conditions in tAD or control participants overall. Completion time in both patient groups was longer relative to controls, and longer in PCA relative to tAD groups. DISCUSSION: Findings represent a quantitative characterization of a clinical phenomenon involving patients misperceiving shadows, implicating dementia-related cortico-visual impairments. Results contribute to evidence-based design guidelines for dementia-friendly environments.

Validation of a Vision-Guided Mobility Assessment for RPE65-Associated Retinal Dystrophy.

Purpose: To validate a vision-guided mobility assessment for individuals affected by RPE65-associated retinal dystrophy (RPE65-RD). Methods: In this comparative cross-sectional study, 29 subjects, comprising 19 subjects with RPE65-RD and 10 normally-sighted subjects undertook three assessments of mobility: following a straight line, navigating a simple maze, and stepping over a sidewalk "kerb." Performance was quantified as the time taken to complete each assessment, number of errors made, walking speed, and percent preferred walking speed, for each assessment. Subjects also undertook assessments of visual acuity, contrast sensitivity, full-field static perimetry, and age-appropriate quality of life questionnaires. To identify the most relevant metric to quantify vision-guided mobility, we investigated repeatability, as well as convergent, discriminant, and criterion validity. We also measured the effect of illumination on mobility. Results: Walking speed through the maze assessment best discriminated between RPE65-RD and normally-sighted subjects, with both convergent and discriminant validity. Walking speed also approached statistical significance when assessed for criterion validity (P = 0.052). Subjects with RPE65-RD had quantifiably poorer mobility at lower illumination levels. A relatively small mean difference (-0.09 m/s) was identified in comparison to a relatively large repeatability coefficient (1.10 m/s). Conclusions: We describe a novel, quantifiable, repeatable, and valid assessment of mobility designed specifically for subjects with RPE65-RD. The assessment is sensitive to the visual impairment of individuals with RPE65-RD in low illumination, identifies the known phenotypic heterogeneity and will furthermore provide an important outcome measure for RPE65-RD. Translational Relevance: This assessment of vision-guided mobility, validated in a dedicated cohort of subjects with RPE65-RD, is a relevant and quantifiable outcome measure for RPE65-RD.

Detection and localisation of hesitant steps in people with Alzheimer's disease navigating routes of varying complexity.

People with Alzheimer's disease (AD) have characteristic problems navigating everyday environments. While patients may exhibit abnormal gait parameters, adaptive gait irregularities when navigating environments are little explored or understood. The aim of this study was to assess adaptive locomotor responses of AD subjects in a complex environment requiring spatial navigation. A controlled environment of three corridors was set up: straight (I), U-shaped (U) and dog-leg (S). Participants were asked to walk along corridors as part of a counterbalanced repeated-measures design. Three groups were studied: 11 people with posterior cortical atrophy (PCA), 10 with typical Alzheimer's disease (tAD) and 13 controls. Spatio-temporal gait parameters and position within the corridors were monitored with shoe-mounted inertial measurement units (IMUs). Hesitant steps were identified from statistical analysis of the distribution of step time data. Walking paths were generated from position data calculated by double integration of IMU acceleration. People with PCA and tAD had similar gait characteristics, having shorter steps and longer step times than controls. Hesitant steps tended to be clustered within certain regions of the walking paths. IMUs enabled identification of key gait characteristics in this clinical population (step time, length and step hesitancy) and environmental conditions (route complexity) modifying their expression.

Navigational cue effects in Alzheimer's disease and posterior cortical atrophy.

OBJECTIVE: Deficits in spatial navigation are characteristic and disabling features of typical Alzheimer's disease (tAD) and posterior cortical atrophy (PCA). Visual cues have been proposed to mitigate such deficits; however, there is currently little empirical evidence for their use. METHODS: The effect of visual cues on visually guided navigation was assessed within a simplified real-world setting in individuals with tAD (n = 10), PCA (n = 8), and healthy controls (n = 12). In a repeated-measures design comprising 36 trials, participants walked to a visible target destination (an open door within a built environment), with or without the presence of an obstacle. Contrast and motion-based cues were evaluated; both aimed to facilitate performance by applying perceptual changes to target destinations without carrying explicit information. The primary outcome was completion time; secondary outcomes were measures of fixation position and walking path directness during consecutive task phases, determined using mobile eyetracking and motion capture methods. RESULTS: Results illustrate marked deficits in patients' navigational ability, with patient groups taking an estimated two to three times longer to reach target destinations than controls and exhibiting tortuous walking paths. There were no significant differences between tAD and PCA task performance. Overall, patients took less time to reach target destinations under cue conditions (contrast-cue: 11.8%; 95% CI: [2.5, 20.3]) and were more likely initially to fixate on targets. INTERPRETATION: The study evaluated navigation to destinations within a real-world environment. There is evidence that introducing perceptual changes to the environment may improve patients' navigational ability.

Dataset of the livability performance of the city of Birmingham, UK, as measured by its citizen wellbeing, resource security, resource efficiency and carbon emissions.

This data article presents the UK City LIFE1 data set for the city of Birmingham, UK. UK City LIFE1 is a new, comprehensive and holistic method for measuring the livable sustainability performance of UK cities. The Birmingham data set comprises 346 indicators structured simultaneously (1) within a four-tier, outcome-based framework in order to aid in their interpretation (e.g., promote healthy living and healthy long lives, minimize energy use, uncouple economic vitality from CO2 emissions) and (2) thematically in order to complement government and disciplinary siloes (e.g., health, energy, economy, climate change). Birmingham data for the indicators are presented within an Excel spreadsheet with their type, units, geographic area, year, source, link to secondary data files, data collection method, data availability and any relevant calculations and notes. This paper provides a detailed description of UK city LIFE1 in order to enable comparable data sets to be produced for other UK cities. The Birmingham data set is made publically available at http://epapers.bham.ac.uk/3040/ to facilitate this and to enable further analyses. The UK City LIFE1 Birmingham data set has been used to understand what is known and what is not known about the livable sustainability performance of the city and to inform how Birmingham City Council can take action now to improve its understanding and its performance into the future (see "Improving city-scale measures of livable sustainability: A study of urban measurement and assessment through application to the city of Birmingham, UK" Leach et al. [2]).

On Your Feet to Earn Your Seat: pilot RCT of a theory-based sedentary behaviour reduction intervention for older adults.

BACKGROUND: Of all age groups, older adults spend most of the time sitting and are least physically active. This sequential, mixed-methods feasibility study used a randomised controlled trial design to assess methods for trialling a habit-based intervention to displace older adults' sedentary behaviour with light activity and explore impact on behavioural outcomes. METHODS: Eligibility criteria were age 60-74 years, retired, and ≥6 h/day leisure sitting. Data were collected across four sites in England. The intervention comprised a booklet outlining 15 'tips' for disrupting sedentary habits and integrating activity habits into normally inactive settings, and eight weekly self-monitoring sheets. The control was a non-habit-based factsheet promoting activity and sedentary reduction. A computer-generated 1:1 block-randomisation schedule was used, with participants blinded to allocation. Participants self-reported sedentary behaviour (two indices), sedentary habit, physical activity (walking, moderate, vigorous activity) and activity habit, at pre-treatment baseline, 8- and 12-week follow-ups and were interviewed at 12 weeks. Primary feasibility outcomes were attrition, adverse events and intervention adherence. The secondary outcome was behavioural change. RESULTS: Of 104 participants consented, 103 were randomised (intervention N = 52, control N = 51). Of 98 receiving allocated treatment, 91 (93%; intervention N = 45; control N = 46) completed the trial. One related adverse event was reported in the intervention group. Mean per-tip adherence across 7 weeks was ≥50% for 9/15 tips. Qualitative data suggested acceptability of procedures, and, particularly among intervention recipients, the allocated treatment. Both groups appeared to reduce sedentary behaviour and increase their physical activity, but there were no apparent differences between groups in the extent of change. CONCLUSIONS: Trial methods were acceptable and feasible, but the intervention conferred no apparent advantage over control, though it was not trialled among the most sedentary and inactive population for whom it was developed. Further development of the intervention may be necessary prior to a large-scale definitive trial. One possible refinement would combine elements of the intervention with an informational approach to enhance effectiveness. TRIAL REGISTRATION: ISRCTN47901994 (registration date: 16th January 2014; trial end date 30th April 2015).

The Automatic Detection of Chronic Pain-Related Expression: Requirements, Challenges and the Multimodal EmoPain Dataset.

Pain-related emotions are a major barrier to effective self rehabilitation in chronic pain. Automated coaching systems capable of detecting these emotions are a potential solution. This paper lays the foundation for the development of such systems by making three contributions. First, through literature reviews, an overview of how pain is expressed in chronic pain and the motivation for detecting it in physical rehabilitation is provided. Second, a fully labelled multimodal dataset (named 'EmoPain') containing high resolution multiple-view face videos, head mounted and room audio signals, full body 3D motion capture and electromyographic signals from back muscles is supplied. Natural unconstrained pain related facial expressions and body movement behaviours were elicited from people with chronic pain carrying out physical exercises. Both instructed and non-instructed exercises were considered to reflect traditional scenarios of physiotherapist directed therapy and home-based self-directed therapy. Two sets of labels were assigned: level of pain from facial expressions annotated by eight raters and the occurrence of six pain-related body behaviours segmented by four experts. Third, through exploratory experiments grounded in the data, the factors and challenges in the automated recognition of such expressions and behaviour are described, the paper concludes by discussing potential avenues in the context of these findings also highlighting differences for the two exercise scenarios addressed.

Long-term effect of gene therapy on Leber's congenital amaurosis.

BACKGROUND: Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. METHODS: We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. RESULTS: Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. CONCLUSIONS: Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).

Locomotion and eye behaviour under controlled environment in individuals with Alzheimer's disease.

This study aimed to examine simple locomotion and eye behaviour of individuals with Posterior Cortical Atrophy (PCA) and typical Alzheimer's disease (tAD) within a simulated real-world environment. Posterior cortical atrophy (PCA) is a neurodegenerative condition characterised by parietal, occipital and occipito-temporal tissue loss and progressive impairment of higher-order visual function in contrast to relatively spared memory and language. Targeted types of locomotion were walking in a series of corridors, up or down stairs, and across an open room with or without the presence of an obstacle. Eye tracking measures and inertial moment units (IMU) were used in this experiment, and resultant acceleration of left foot and fixation duration were extracted. Findings from three participants are presented as a case series: one control, one PCA and one tAD patient. The averaged resultant acceleration of PCA patient was the slowest in all types of locomotion, especially in stairs. The averaged resultant accelerations of PCA and tAD participants were slower than the control participant. The PCA participant had longer mean fixation durations than the tAD and control participants, however, mean fixation duration was similar between tAD and control participants. Results may help characterise locomotion and eye behaviour in PCA and tAD and may suggest ways to support effective diagnosis and assessment of disease progression.

'On Your Feet to Earn Your Seat', a habit-based intervention to reduce sedentary behaviour in older adults: study protocol for a randomized controlled trial.

BACKGROUND: Many older adults are both highly sedentary (that is, spend considerable amounts of time sitting) and physically inactive (that is, do little physical activity). This protocol describes an exploratory trial of a theory-based behaviour change intervention in the form of a booklet outlining simple activities ('tips') designed both to reduce sedentary behaviour and to increase physical activity in older adults. The intervention is based on the 'habit formation' model, which proposes that consistent repetition leads to behaviour becoming automatic, sustaining activity gains over time. METHODS: The intervention is being developed iteratively, in line with Medical Research Council complex intervention guidelines. Selection of activity tips was informed by semi-structured interviews and focus groups with older adults, and input from a multidisciplinary expert panel. An ongoing preliminary field test of acceptability among 25 older adults will inform further refinement. An exploratory randomized controlled trial will be conducted within a primary care setting, comparing the tips booklet with a control fact sheet. Retired, inactive and sedentary adults (n = 120) aged 60 to 74 years, with no physical impairments precluding light physical activity, will be recruited from general practices in north London, UK. The primary outcomes are recruitment and attrition rates. Secondary outcomes are changes in behaviour, habit, health and wellbeing over 12 weeks. DISCUSSION: Data will be used to inform study procedures for a future, larger-scale definitive randomized controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47901994.

Assisting control for attendant propelled wheelchair based on force velocity relationship.

There is a need to develop an assisting device which can be adapted to the individual capabilities of elderly attendants, which would allow them to maintain a level of fitness when pushing a wheelchair, while minimising the risk of injury to them. Furthermore there is a need to reduce the overall energy consumption of the device in keeping with the current trends of reducing carbon emissions. The control system for attendants pushing wheelchairs that reduces the energy needed by the assisting device is an increasing trend of optimisation of assistive technology devices to individual capabilities to ensure less energy expenditure of the attendant. The control parameters for existing assisting systems for attendant wheelchair propulsion are difficult to optimise for individual capabilities. We focus on the individual propelling performance, and propose an assisting control method based on the force velocity relationship of the individual. Our proposed assisting controller generates an assisting force when the attendant's propelling force exceeds an assisting boundary defined by the force velocity relationship. In this paper, we tested the performance of the assisting controller based on force velocity (FV) relationship using simulation. The simulation used an attendant wheelchair model with parameters determined from experiments. From the simulated results of the assisting force trajectories, the FV assisting system worked as we defined. The FV assisting system used less energy consumption than the existing proportional assisting systems. Also the FV assisting system would have a limit of maximum attendant propelling power, so the distribution between the attendant force and the assisting force can be easily adjusted to the individual's force velocity relationship. Our proposed FV assisting system would be useful as it would allow an optimised system based on individual capabilities to be created for rehabilitation/training systems, which would allow optimum energy consumption when propelling a wheelchair.

Effect of gene therapy on visual function in Leber's congenital amaurosis.

Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium-specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov].).