Outcomes of home design to support healthy cognitive ageing: modified e-Delphi exercise with older people and housing-related professionals

Background There is emerging agreement that living in a home designed to support healthy cognitive ageing can enable people to live better with dementia and cognitive change. However, existing literature has used a variety of outcome measures that have infrequently been informed by the perspectives of older people or of professional in design and supply of housing. The DesHCA (Designing Homes for Healthy Cognitive Ageing) study aimed to identify outcomes that were meaningful for these groups and to understand their content and meanings. Methods A presurvey of older people and housing professionals (n = 62) identified potential outcomes. These were then used in three rounds of a modified e-Delphi exercise with a panel of older people and housing professionals (n = 74) to test meanings and identify areas of agreement and disagreement. Descriptive statistics were used to present findings from previous rounds. Results The survey confirmed a wide range of possible outcomes considered important. Through the e-Delphi rounds, panellists prioritised outcomes relating to living at home that could be influenced by design, and clarified their understanding of the meanings of outcomes. In subsequent rounds, they commented on earlier results. The exercise enabled five key outcome areas to be identified-staying independent, feeling safe, living in an adaptable home, enabling physical activity and enabling enjoyed activities-which were then tested for their content and applicability in panellists' views. Conclusion The five key outcome areas appeared meaningful to panellists, whilst also demonstrating nuanced meanings. They indicate useful outcomes for future research, though will require careful definition in each case to become measures. Importantly, they are informed by the views of those most immediately affected by better or poorer home design

Housing Design Evaluation Research for People Living with Cognitive Change: A Systematic Literature Review

Research suggests that improvements to home design may enable us to live better with cognitive change as we age. However, few innovations have been fully evaluated. The paper systematically reviews 47 items of evaluative literature. Research design and quality are varied. Qualitative analysis of literature demonstrates the need for a holistic approach that includes older people’s diverse perspectives, examples of promising practice that responds to individual needs, and gaps in research on scalability and economic viability of innovations. The context of design improvements is found to be critical

Comparison of screening strategies to improve the diagnosis of latent tuberculosis infection in the HIV-positive population: a cohort study

Background HIV is the most important risk factor for progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB). Detection and treatment of LTBI is necessary to reduce the increasing burden of TB in the UK, but a unified LTBI screening approach has not been adopted. Objective To compare the effectiveness of a TB risk-focused approach to LTBI screening in the HIV-positive population against current UK National Institute for Health and Clinical Excellence (NICE) guidance. Design Prospective cohort study. Setting Two urban HIV treatment centres in London, UK. Participants 114 HIV-infected individuals with defined TB risk factors were enrolled prospectively as part of ongoing studies into HIV and TB co-infection. Outcome measures The yield and case detection rate of LTBI cases within the research study were compared with those generated by the NICE criteria. Results 17/114 (14.9%, 95% CI 8.3 to 21.5) had evidence of LTBI. Limiting screening to those meeting NICE criteria for the general population (n=43) would have detected just over half of these, 9/43 (20.9%, 95% CI 8.3 to 33.5) and those meeting criteria for HIV co-infection (n=74) would only have captured 8/74(10.8%, 95% CI 3.6 to 18.1) cases. The case detection rates from the study and NICE approaches were not significantly different. LTBI was associated with the presence of multiple TB risk factors (p=0.002). Conclusion Adoption of a TB risk-focused screening algorithm that does not use CD4 count stratification could prevent more cases of TB reactivation, without changing the case detection rate. These findings should be used to inform a large-scale study to create unified guidelines

Phosphorus and nitrogen limitation and impairment of headwater streams relative to rivers in Great Britain: a national perspective on eutrophication

This study provides a first national-scale assessment of the nutrient status of British headwater streams within the wider river network, by joint analysis of the national Countryside Survey Headwater Stream and Harmonised River Monitoring Scheme datasets. We apply a novel Nutrient Limitation Assessment methodology to explore the extent to which nutrients may potentially limit primary production in headwater streams and rivers, by coupling ternary assessment of nitrogen (N), phosphorus (P), and carbon (C) depletion, with N:P stoichiometry, and threshold P and N concentrations. P limitation was more commonly seen in the rivers, with greater prevalence of N limitation in the headwater streams. High levels of potential P and N co-limitation were found in the headwater streams, especially the Upland-Low-Alkalinity streams. This suggests that managing both P and N inputs may be needed to minimise risks of degradation of these sensitive headwater stream environments. Although localised nutrient impairment of headwater streams can occur, there were markedly lower rates of P and N impairment of headwater streams relative to downstream rivers at the national scale. Nutrient source contributions, relative to hydrological dilution, increased with catchment scale, corresponding with increases in the extent of agricultural and urban land-use. The estimated nutrient reductions needed to achieve compliance with Water Framework Directive standards, and to reach limiting concentrations, were greatest for the Lowland-High-Alkalinity rivers and streams. Preliminary assessments suggest that reducing P concentrations in the Lowland-High-Alkalinity headwater streams, and N concentrations in the Upland-Low-Alkalinity rivers, might offer greater overall benefits for water-quality remediation at the national scale, relative to the magnitude of nutrient reductions required. This approach could help inform the prioritisation of nutrient remediation, as part of a directional approach to water quality management based on closing the gaps between current and target nutrient concentrations

Othering Older People’s Housing: Gaming Ageing to Support Future-Planning

The ‘othering’ of ageing is linked to an integrated process of ageism and hinders future planning for both individuals and practitioners delivering housing and health services. This paper aims to explore how creative interventions can help personalise, exchange knowledge and lead to systems change that tackles the ‘othering’ of ageing. The Designing Homes for Healthy Cognitive Ageing (DesHCA) project offers new and creative insights through an innovative methodology utilising ‘serious games’ with a co-produced tool called ‘Our House’ that supports insight on how to deliver housing for older people for ageing well in place. In a series of playtests with over 128 people throughout the UK, the findings show that serious games allow interaction, integration and understanding of how ageing affects people professionality and personally. The empirical evidence highlights that the game mechanisms allowed for a more in-depth and nuanced consideration of ageing in a safe and creative environment. These interactions and discussions enable individuals to personalise and project insights to combat the ‘othering’ of ageing. However, the solutions are restrained as overcoming the consequences of ageism is a societal challenge with multi-layered solutions. The paper concludes that serious gaming encourages people to think differently about the concept of healthy ageing – both physically and cognitively – with consideration of scalable and creative solutions to prepare for ageing-in-place

Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups

Objectives: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. Methods: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. Results: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9x10(-5). Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28x10(-53) and HLA-DRB1*03:01, p=3.25x10(-9)), anti-PM/Scl (HLA-DQB1*02:01, p=1.47x10(-26)) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40x10(-11)). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92x10(-13)) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09x10(-6)). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47x10(-64)) and position 9 of HLA-B (p=7.03x10(-11)). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies. Conclusions: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research

Detailed Molecular and Immune Marker Profiling of Archival Prostate Cancer Samples Reveals an Inverse Association between TMPRSS2:ERG Fusion Status and Immune Cell Infiltration

Prostate cancer is a significant global health issue and limitations to current patient management pathways often result in over- or under-treatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow utilizing an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA-Seq, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA-seq in 27/27 cases and a significantly higher TIL count was noted in tumors without a TMPRSS2:ERG fusion compared to those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n=436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-High and TIL-Low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1/27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion positive tumors. Detailed profiling, as shown here, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort

Omics and multi-omics analysis for the early identification and improved outcome of patients with psoriatic arthritis

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent. As with other IMIDs, the detection of multimodal molecular biomarkers offers some hope for the early diagnosis of PsA and the initiation of effective management and treatment strategies. However, specific biomarkers are not yet available for PsA. The assessment of new markers by genomic and epigenomic profiling, or the analysis of blood and synovial fluid/tissue samples using proteomics, metabolomics and lipidomics, provides hope that complex molecular biomarker profiles could be developed to diagnose PsA. Importantly, the integration of these markers with high-throughput histology, imaging and standardized clinical assessment data provides an important opportunity to develop molecular profiles that could improve the diagnosis of PsA, predict its occurrence in cohorts of individuals with psoriasis, differentiate PsA from other IMIDs, and improve therapeutic responses. In this review, we consider the technologies that are currently deployed in the EU IMI2 project HIPPOCRATES to define biomarker profiles specific for PsA and discuss the advantages of combining multi-omics data to improve the outcome of PsA patients

Qualitative impact assessment of land management interventions on ecosystem services ("QEIA"). Report-1: executive summary QEIA evidence review & integrated assessment

The focus of this project was to provide a rapid qualitative assessment of land management interventions on Ecosystem Services (ES) proposed for inclusion in Environmental Land Management (ELM) schemes. This involved a review of the current evidence base by ten expert teams drawn from the independent research community in a consistent series of ten Evidence Reviews. These reviews were undertaken rapidly at Defra’s request and together captured more than 2000 individual sources of evidence. These reviews were then used to inform an Integrated Assessment (IA) to provide a more accessible summary of these evidence reviews with a focus on capturing the actions with the greatest potential magnitude of change for the intended ES and their potential co-benefits and trade-offs across the Ecosystem Services and Ecosystem Services Indicators. The final IA table captured scores for 741 actions across 8 Themes, 33 ES and 53 ES-indicators. This produced a total possible matrix of 39,273 scores. It should be noted that this piece of work is just one element of the wider underpinning work Defra has commissioned to support the development of the ELM schemes. The project was carried out in two phases with the environmental and provisioning services commissioned in Phase 1 and cultural and regulatory services in a follow-on Phase 2. Due to the urgency of the need for these evidence reviews, there was insufficient time for systematic reviews and therefore the reviews relied on the knowledge of the team of the peer reviewed and grey literature with some rapid additional checking of recent reports and papers. This limitation of the review process was clearly explained and understood

Qualitative impact assessment of land management interventions on ecosystem services (‘QEIA’). Report-2: integrated assessment

This project assessed the impacts of 741 potential land management actions, suitable for agricultural land in England, on the Farming & Countryside Programme’s Environmental Objectives (and therefore Environment Act targets and climate commitments) through 53 relevant environmental and cultural service indicators. The project used a combination of expert opinion and rapid evidence reviews, which included 1000+ pages of evidence in 10 separate reports with reference to over 2400 published studies, and an Integrated Assessment comprising expert-derived qualitative impact scores. The project has ensured that ELM schemes are evidence-based, offer good value for money, and contribute to SoS priorities for farming