The transition to technology-enriched supported accommodation (TESA) for people living with dementia: the experience of formal carers

Brendan McCormack - ORCID: 0000-0001-8525-8905 https://orcid.org/0000-0001-8525-8905This paper presents the experiences of formal carers working in technology-enriched supported accommodation for people living with dementia, examining their care-giving role from a person-centred care perspective. Within a qualitative study, 21 semi-structured interviews were conducted with formal carers and data were analysed following a thematic approach. Four main themes were identified that mapped to the attributes of the person-centred practice framework (PCPF): promoting choice and autonomy, staffing model, using assistive technology and feeling that ‘you're doing a good job’. Central to person-centred practice in these settings was the promotion of choice, autonomy and independence. The dichotomy between safety and independence was evident, curtailing the opportunities within the environmental enablers and associated embedded assistive technologies. Formal carers reported considerable job satisfaction working in these settings. The small-scale, home-like facilities seemed to have a positive effect on job satisfaction. These findings are relevant to policy makers, commissioners and service providers, highlighting the facilitators of person-centred care in community dwellings for people living with dementia and the role of formal carers in promoting this approach.This project was funded by the Health and Social Care (HSC) Research & Development Division of the Public Health Agency in Northern Ireland (Reference COM/4955/14) in conjunction with the Atlantic Philanthropies, an international grant-awarding body. The project is part of the HSC research strand into the ‘Care of People with Dementia in Northern Ireland’. None of the awarding bodies have participated in any of the activities related to the research.https://doi.org/10.1017/S0144686X1900058840pubpub1

Social and clinical determinants of preferences and their achievement at the end of life: Prospective cohort study of older adults receiving palliative care in three countries

© 2017 The Author(s). Background: Achieving choice is proposed as a quality marker. But little is known about what influences preferences especially among older adults. We aimed to determine and compare, across three countries, factors associated with preferences for place of death and treatment, and actual site of death. Methods: We recruited adults aged ≥65-years from hospital-based multiprofessional palliative care services in London, Dublin, New York, and followed them for >17 months. All services offered consultation on hospital wards, support for existing clinical teams, outpatient services and received funding from their National Health Service and/or relevant Insurance reimbursements. The New York service additionally had 10 inpatient beds. All worked with and referred patients to local hospices. Face-to-face interviews recorded most and least preferred place of death, treatment goal priorities, demographic and clinical information using validated questionnaires. Multivariable and multilevel analyses assessed associated factors. Results: One hundred and thirty eight older adults (64 London, 59 Dublin, 15 New York) were recruited, 110 died during follow-up. Home was the most preferred place of death (77/138, 56%) followed by inpatient palliative care/hospice units (22%). Hospital was least preferred (35/138, 25%), followed by nursing home (20%) and home (16%); hospice/palliative care unit was rarely least preferred (4%). Most respondents prioritised improving quality of life, either alone (54%), or equal with life extension (39%); few (3%) chose only life extension. There were no significant differences between countries. Main associates with home preference were: cancer diagnosis (OR 3.72, 95% CI 1.40-9.90) and living with someone (OR 2.19, 1.33-3.62). Adults with non-cancer diagnoses were more likely to prefer palliative care units (OR 2.39, 1.14-5.03). Conversely, functional independence (OR 1.05, 1.04-1.06) and valuing quality of life (OR 3.11, 2.89-3.36) were associated with dying at home. There was a mismatch between preferences and achievements - of 85 people who preferred home or a palliative care unit, 19 (25%) achieved their first preference. Conclusion: Although home is the most common first preference, it is polarising and for 16% it is the least preferred. Inpatient palliative care unit emerges as the second most preferred place, is rarely least preferred, and yet was often not achieved for those who wanted to die there. Factors affecting stated preferences and met preferences differ. Available services, notably community support and palliative care units, require expansion. Contrasting actual place of death with capacity for meeting patient and family needs may be a better quality indicator than simply 'achieved preferences'

Predictive Genes in Adjacent Normal Tissue Are Preferentially Altered by sCNV during Tumorigenesis in Liver Cancer and May Rate Limiting

Background: In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings: Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ~250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance: This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. © 2011 Lamb et al.published_or_final_versio

Genome-wide epistatic expression quantitative trait loci discovery in four human tissues reveals the importance of local chromosomal interactions governing gene expression

Background: Epistasis (synergistic interaction) among SNPs governing gene expression is likely to arise withintranscriptional networks. However, the power to detect it is limited by the large number of combinations to betested and the modest sample sizes of most datasets. By limiting the interaction search space firstly to cis-trans andthen cis-cis SNP pairs where both SNPs had an independent effect on the expression of the most variabletranscripts in the liver and brain, we greatly reduced the size of the search space.Results: Within the cis-trans search space we discovered three transcripts with significant epistasis. Surprisingly, allinteracting SNP pairs were located nearby each other on the chromosome (within 290 kb-2.16 Mb). Despite theirproximity, the interacting SNPs were outside the range of linkage disequilibrium (LD), which was absent betweenthe pairs (r2 < 0.01). Accordingly, we redefined the search space to detect cis-cis interactions, where a cis-SNP waslocated within 10 Mb of the target transcript. The results of this show evidence for the epistatic regulation of 50transcripts across the tissues studied. Three transcripts, namely, HLA-G, PSORS1C1 and HLA-DRB5 share commonregulatory SNPs in the pre-frontal cortex and their expression is significantly correlated. This pattern of epistasis isconsistent with mediation via long-range chromatin structures rather than the binding of transcription factors intrans. Accordingly, some of the interactions map to regions of the genome known to physically interact inlymphoblastoid cell lines while others map to known promoter and enhancer elements. SNPs involved in interactionsappear to be enriched for promoter markers.Conclusions: In the context of gene expression and its regulation, our analysis indicates that the study of cis-cisor local epistatic interactions may have a more important role than interchromosomal interactions.Irish Research CouncilScience Foundation IrelandICON-Newman Fellowshi

CRISPR screening identifies T cell-intrinsic regulators of CD3-bispecific antibody responses.

CD3-engaging bispecific antibodies (BsAbs) enable the formation of an immune synapse between T cells and tumor cells, resulting in robust target cell killing not dependent on a preexisting tumor specific T cell receptor. While recent studies have shed light on tumor cell-specific factors that modulate BsAb sensitivity, the T cell-intrinsic determinants of BsAb efficacy and response durability are poorly understood. To better clarify the genes that shape BsAb-induced T cell responses, we conducted targeted analyses and a large-scale unbiased in vitro CRISPR/Cas9-based screen to identify negative regulators of BsAb-induced T cell proliferation. These analyses revealed that CD8+ T cells are dependent on CD4+ T cell-derived signaling factors in order to achieve sustained killing in vitro. Moreover, the mammalian target of rapamycin (mTOR) pathway and several other candidate genes were identified as intrinsic regulators of BsAb-induced T cell proliferation and/or activation, highlighting promising approaches to enhancing the utility of these potent therapeutics

beta-Hydroxybutyrate deactivates Neutrophil NLRP3 inflammasome to relieve gout flares

Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1 beta (IL-1 beta) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases beta-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1 beta in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout

A risk assessment and prioritisation approach to the selection of indicator species for the assessment of multi-species, multi-gear, multi-sector fishery resources

Assessing the stock status of mixed and/or multi-species fishery resources is challenging. This is especially true in highly diverse systems, where landed catches are small, but comprise many species. In these circumstances, whole-of-ecosystem management requires consideration of the impact of harvesting on a plethora of species. However, this is logistically infeasible and cost prohibitive. To overcome this issue, selected ‘indicator’ species are used to assess the risk to sustainability of all ‘like’ species susceptible to capture within a fishery resource. Indicator species are determined via information on their (1) inherent vulnerability, i.e. biological attributes; (2) risk to sustainability, i.e. stock status; and (3) management importance, i.e. commercial prominence, social and/or cultural amenity value of the resource. These attributes are used to determine an overall score for each species which is used to identify ‘indicator’ species. The risk status (i.e. current risk) of the indicator species then determines the risk-level for the biological sustainability of the entire fishery resource and thus the level of priority for management, monitoring, assessment and compliance. A range of fishery management regimes are amenable to the indicator species approach, including both effort limited fisheries (e.g. individually transferable effort systems) and output controlled fisheries (e.g. species-specific catch quotas). The indicator species approach has been used and refined for fisheries resources in Western Australia over two decades. This process is now widely understood and accepted by stakeholders, as it focuses fishery dependent- and/or independent-monitoring, biological sampling, stock assessment and compliance priorities, thereby optimising the use of available jurisdictional resources

Shifts in Labridae geographical distribution along a unique and dynamic coastline

[Aim] Compare the distribution and composition of temperate Labridae (wrasse) assemblages on shallow water coastal reefs in South-Western Australia between 2006 and 2015, after a decade characterized by both gradual ocean warming and severe heatwave events.[Location] South-Western Australia from Port Gregory to the Recherché Archipelago.[Methods] Surveys of Labridae fishes were conducted in 2006 and repeated in 2015 across 112 reefs spanning 2,000 km of coastline, using diver-operated stereo-video systems (stereo-DOVs). We used a hierarchical design with seven regions, four locations in each region, four reef sites in each location and twelve transects in each site.[Results] In 2015, we found an increase in abundance of tropical and subtropical labrid species that were rarely observed in 2006. Three temperate species declined in abundance, which tended to be large and slow growing fish. Twenty-two labrid species increased in abundance. There was also a discernible poleward shift in 20 of the 25 most abundant and representative labrid species from 2006 to 2015. The labrid community composition was explained predominantly by sea surface temperature (SST), physical reef structure and kelp (Ecklonia radiata) cover.[Main conclusions] Our study reveals that labrid assemblages associated with the shallow water temperate reefs of South-Western Australia have undergone rapid changes across almost 2,000 km of coastline, with warm-temperate waters showing the strongest change. However, cool-temperate waters on the south coast also showed significant changes in the composition of the labrid assemblages. Our findings provide important insights into the effects of warming and habitat loss on warm-temperate assemblages and the potential trajectory of change for cool-temperate assemblages under a warmer future