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Although culture can be considered as a set of subjective values that oppose scientific objectivity, we challenge this view in this Commission by claiming that all people have systems of value that are unexamined. Such systems are, at times, diffuse, and often taken for granted, but are always dynamic and changing. They produce novel and sometimes perplexing needs, to which established caregiving practices often adjust slowly.

A form of Leber's congenital amaurosis is caused by mutant RPE65 , a critical component of the visual cycle. Two early clinical trials to assess subretinal injection of a viral vector containing RPE65 in young adults with advanced retinal degeneration show that this approach is generally safe in the short term, although one group reported an adverse event: macular hole. The authors observed improvement in some measures of visual function. Two early clinical trials to assess subretinal injection of a viral vector containing RPE65 in young adults with advanced retinal degeneration show that this approach is generally safe in the short term, although one group reported an adverse event: macular hole. The authors observed improvement in some measures of visual function. Leber's congenital amaurosis is a term used to describe a group of recessively inherited, severe, infantile-onset rod–cone dystrophies. 1 Mutation of one of several genes, including RPE65 , causes disease that involves impaired vision from birth 2 , 3 and typically progresses to blindness in the third decade of life. There is no effective treatment. RPE65 is expressed in the retinal pigment epithelium and encodes a 65-kD protein that is a key component of the visual cycle, 1 , 4 – 8 a biochemical pathway that regenerates the visual pigment after exposure to light. 9 – 14 A lack of functional RPE65 results in deficiency of 11- cis . . .

Objective: Visual processing deficits arising in dementia are associated with particular functional disability. This study aimed to investigate the effects of the built environment on mobility and navigation in people with dementia-related visual loss. Methods: Participants with posterior cortical atrophy (PCA; “visual-variant Alzheimer’s”; n = 11), typical Alzheimer’s disease (tAD; N = 10), and controls (n = 13) repeatedly walked down routes within a simplified real-world setting. Participant groups were of comparable age and gender. Routes were of different complexity (straight, U-shaped, and S-shaped), overhead lighting levels (low and high) and with or without a dynamic LED (light-emitting diode) cue (trial n = 24). Ratios of walking times for each experimental condition (each complex route vs the straight route, high lighting vs low, and LED cue vs no cue) were compared between participant groups. Kinematic measures were produced from a total of 10,813 steps using wearable inertial measurement units (IMUs). Results: The walking time ratios relating to route complexity were higher in the PCA group than in controls: 30.3% (95% CI [13.5%, 49.5%] higher for U-shaped vs straight and 31.9% [21.1%, 55.3%] for S-shaped vs straight, averaged over other conditions). The analogous results relating to route complexity for the tAD group were intermediate between those for the PCA and control groups. There was no evidence that walking time ratios differed according to lighting level or the presence of the LED cue. Conclusions: Findings contribute to evidence-based design for dementia-friendly environments, emphasizing consequences of environmental complexity for functional independence and mobility in people with dementia-related visual loss. Findings inform recommendations for environmental design to support the independence of individuals with dementia.

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. 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. 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. 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.

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.

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)

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.

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.

Long-term follow-up of 12 persons with Leber's congenital amaurosis treated with gene therapy showed that about half of them had improvements in retinal sensitivity (although the extent varied markedly among patients), followed by a decline. Leber’s congenital amaurosis is a group of inherited, early-onset, severe retinal dystrophies that cause substantial sight impairment in childhood. 1 One of the causes of this condition is mutations in the gene encoding RPE65 (retinal pigment epithelium–specific protein 65 kDa). The encoded retinoid isomerase converts all- trans retinyl esters to 11- cis retinal for the regeneration of visual pigment after exposure to light. RPE65 deficiency causes photoreceptor-cell dysfunction and impaired vision from birth. Severe dysfunction of rod photoreceptor cells, which are wholly reliant on retinal pigment epithelium–derived RPE65, causes severely impaired night vision. The function of cone photoreceptor cells, which mediate . . .

This chapter argues that for transport to be truly 'public', it must be accessible to everyone. This has implications for the way in which transport systems are designed but also in how they are planned within the context of the geographical and temporal situations in which they happen. To achieve this, it is necessary to delve beneath the superficial issues of measurements and regulations to see how people function in relation to the environment - in the transport system in particular. The chapter will then consider how this sets the requirements for the design of the system - as a whole but also in its constituent parts - so as to achieve a transport system which is truly accessible to all.