‘All the corridors are the same’: a qualitative study of the orientation experiences and design preferences of UK older adults living in a communal retirement development

Environments need to be designed such that they support successful orientation for older adults and those with dementia who often experience marked difficulties in their orientation abilities. To better understand how environments can compensate for decreasing orientation skills, voice should be given directly to those experiencing dementia to describe how they find their way and to understand their design preferences. This study explored the navigational experiences and design preferences of older adults with memory difficulties living in a retirement development. In-depth semi-structured interviews with 13 older adults experiencing memory difficulties were conducted. All participants were residents of one retirement development in the United Kingdom. Questions began broadly, for example, to describe their experiences of navigating in their living environment, before discussing any specific navigation difficulties in detail. Thematic analysis identified three main themes: highlighting environmental design that causes disorientation, strategies to overcome disorientation, and residents’ suggestions to improve the design. The design suggestions were particularly informative, heavily focusing on the importance of having memorable and meaningful spaces which were favoured more than signage as an orientation aid. The findings demonstrate the need to consider environmental design to support orientation for those with memory difficulties. Of particular importance is the use of meaningful and relevant landmarks as orientation aids which can additionally stimulate conversation and increase wellbeing. Given the range of suggestions in dementia-friendly design guidelines aimed to support orientation, it is crucial to speak directly to those living in different environments to learn how they find their way around and what design works in their environment

Decreasing spatial disorientation in care-home settings: How psychology can guide the development of dementia friendly design guidelines

Alzheimer’s disease results in marked declines in navigation skills that are particularly pronounced in unfamiliar environments. However, many people with Alzheimer’s disease eventually face the challenge of having to learn their way around unfamiliar environments when moving into assisted living or care-homes. People with Alzheimer’s disease would have an easier transition moving to new residences if these larger, and often more institutional, environments were designed to compensate for decreasing orientation skills. However, few existing dementia friendly design guidelines specifically address orientation and wayfinding. Those that do are often based on custom, practice or intuition and not well integrated with psychological and neuroscientific knowledge or navigation research, therefore often remaining unspecific. This paper discusses current dementia friendly design guidelines, reports findings from psychological and neuropsychological experiments on navigation and evaluates their potential for informing design guidelines that decrease spatial disorientation for people with dementia

Ionospheric data assimilation and forecasting during storms

Ionospheric storms can have important effects on radio communications and navigation systems. Storm time ionospheric predictions have the potential to form part of effective mitigation strategies to these problems. Ionospheric storms are caused by strong forcing from the solar wind. Electron density enhancements are driven by penetration electric fields, as well as by thermosphere-ionosphere behavior including Traveling Atmospheric Disturbances and Traveling Ionospheric Disturbances and changes to the neutral composition. This study assesses the effect on 1 h predictions of specifying initial ionospheric and thermospheric conditions using total electron content (TEC) observations under a fixed set of solar and high-latitude drivers. Prediction performance is assessed against TEC observations, incoherent scatter radar, and in situ electron density observations. Corotated TEC data provide a benchmark of forecast accuracy. The primary case study is the storm of 10 September 2005, while the anomalous storm of 21 January 2005 provides a secondary comparison. The study uses an ensemble Kalman filter constructed with the Data Assimilation Research Testbed and the Thermosphere Ionosphere Electrodynamics General Circulation Model. Maps of preprocessed, verticalized GPS TEC are assimilated, while high-latitude specifications from the Assimilative Mapping of Ionospheric Electrodynamics and solar flux observations from the Solar Extreme Ultraviolet Experiment are used to drive the model. The filter adjusts ionospheric and thermospheric parameters, making use of time-evolving covariance estimates. The approach is effective in correcting model biases but does not capture all the behavior of the storms. In particular, a ridge-like enhancement over the continental USA is not predicted, indicating the importance of predicting storm time electric field behavior to the problem of ionospheric forecasting.</p

Molecular mimicry in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection1,2, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone