147 research outputs found
Mapping stakeholders to maximise the impact of research on health inequalities for people with learning disabilities: the development of a framework for the Making Positive Moves study
© 2024 The Authors. British Journal of Learning Disabilities published by John Wiley & Sons Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background: People with learning disabilities experience health and social inequalities, and research that could improve health services may not be implemented in realâlife settings. Building stakeholder networks that can share and implement research findings may address this. This paper presents a framework for building a stakeholder network that maximises the likelihood of research recommendations being implemented in practice. This was developed as part of the âMaking Positive Movesâ (MPM) study, which explores the experiences of people with learning disabilities following discharge from a residential stay within a hospital inpatient setting. Methods: We reviewed the literature on existing theoretical frameworks to support the development of a model for dissemination of the MPM findings. Stakeholder categories were identified through consultation with the MPM researchers, experts by experience and the steering group and a hub and spoke model to represent all stakeholder categories was created. These categories include person moving; family of the person moving; specialist schools; social care; care providers; regulators; third sector organisations; policy organisations; academic community; and NHS professionals. After establishing the categories, we consulted with people with learning disabilities and other stakeholders and conducted online searches to create a stakeholder database. Through information gathering and direct contact with stakeholders, we assessed levels of interest, power and engagement to determine which stakeholders to prioritise in our dissemination activities. The Stakeholder Wheel was created to present the data captured within the database and engagement profiles in an illustrative way. Findings: We use two stakeholder subâcategories, userâled organisations and care providers, to demonstrate the methodological approach. The examples illustrate how a scoring system helped us to identify highâpriority stakeholders who we then contacted to collaborate within developing our dissemination strategy to maximise the impact of the MPM research findings. Conclusions: We developed a framework to map stakeholders for the MPM study and enable targeted dissemination to increase the impact of the research. This approach has the potential to reduce health inequalities among people with learning disabilities by increasing the awareness of and ability to implement evidenceâbased recommendations in realâlife settings. The stakeholder mapping framework could be applied to research projects associated with learning disabilities to bridge the gap between research and practice and reduce health inequalities.Peer reviewe
The Dark Matter Halos of Moderate Luminosity X-ray AGN as Determined fromWeak Gravitational Lensing and Host Stellar Masses
Understanding the relationship between galaxies hosting active galactic nuclei (AGN) and the dark matter haloes in which they reside is key to constraining how black hole fuelling is triggered and regulated. Previous efforts have relied on simple halo mass estimates inferred from clustering, weak gravitational lensing, or halo occupation distribution modelling. In practice, these approaches remain uncertain because AGN, no matter how they are identified, potentially live a wide range of halo masses with an occupation function whose general shape and normalization are poorly known. In this work, we show that better constraints can be achieved through a rigorous comparison of the clustering, lensing, and cross-correlation signals of AGN hosts to the fiducial stellar-to-halo mass relation (SHMR) derived for all galaxies, irrespective of nuclear activity. Our technique exploits the fact that the global SHMR can be measured with much higher accuracy than any statistic derived from AGN samples alone. Using 382 moderate luminosity X-ray AGN at z < 1 from the COSMOS field, we report the first measurements of weak gravitational lensing from an X-ray-selected sample. Comparing this signal to predictions from the global SHMR, we find that, contrary to previous results, most X-ray AGN do not live in medium size groups â nearly half reside in relatively low mass haloes with M_(200b) ⌠10^(12.5) M_â. The AGN occupation function is well described by the same form derived for all galaxies but with a lower normalization â the fraction of haloes with AGN in our sample is a few per cent. The number of AGN satellite galaxies scales as a power law with host halo mass with a power-law index α = 1. By highlighting the relatively ânormalâ way in which moderate luminosity X-ray AGN hosts occupy haloes, our results suggest that the environmental signature of distinct fuelling modes for luminous quasars compared to moderate luminosity X-ray AGN is less obvious than previously claimed
The role of tau in the pathological process and clinical expression of Huntington's disease.
Huntington's disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic modifiers, distinct from the Huntington's disease locus itself, have been identified as being linked to the clinical expression and progression of Huntington's disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated in Huntington's disease. We explored this association in more detail at the neuropathological, genetic and clinical level. We first investigated tau pathology by looking for the presence of hyperphosphorylated tau aggregates, co-localization of tau with mutant HTT and its oligomeric intermediates in post-mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some instances with mutant HTT. We confirmed this related to the disease process rather than age, by showing it is also present in two patients with young-onset Huntington's disease (26 and 40 years old at death). In addition we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau entity) are present in the Huntington's disease brains. Finally we highlight the clinical significance of this pathology by demonstrating that the MAPT haplotypes affect the rate of cognitive decline in a large cohort of patients with Huntington's disease. Our findings therefore highlight a novel important role of tau in the pathogenic process and clinical expression of Huntington's disease, which in turn opens up new therapeutic avenues for this incurable condition.The authors thank the EHDN REGISTRY Study Group investigators (listed in the Supplementary material) for collecting the data and all participating REGISTRY patients for their time and efforts, the Cambridge Brain Bank for the post-mortem tissue which is supported by a grant to the NIHR Cambridge Biomedical Research Centre and in particular to J. Wilson and Dr D. Oâ Donovan. We are grateful to S. Sawcer and M. Ban in the Neurology Unit at the University of Cambridge, for their help with the genotyping, C.H. Williams-Gray at the John van Geest Centre for Brain Repair, University of Cambridge, for her help with the statistical analyses, J. Hardy, J.L. Holton, and T. Revesz at the UCL Institute of Neurology for their helpful discussions as well as K. Strand, F. Javad and A. Posada BĂłrbon, at the UCL Institute of Neurology, for their support with the experimental work, R. Kayed at the University of Texas Medical Branch, Galveston, for providing the TOMA and T22 antibodies. Finally, P. Tyers, R. Raha-Chowdhury, A. Tolkovsky, B. Ossola and J. Simpson for their support and encouragement throughout this work.This is the final version of the article. It was first available from Oxford University Press viahttp://dx.doi.org/10.1093/brain/awv10
Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions
Genetic effects on gene expression and splicing can be modulated by cellular and environmental factors; yet interactions between genotypes, cell type and treatment have not been comprehensively studied together. We used an induced pluripotent stem cell system to study multiple cell types derived from the same individuals and exposed them to a large panel of treatments. Cellular responses involved different genes and pathways for gene expression and splicing, and were highly variable across contexts. For thousands of genes, we identified variable allelic expression across contexts and characterized different types of gene-environment interactions, many of which are associated with complex traits. Promoter functional and evolutionary features distinguished genes with elevated allelic imbalance mean and variance. On average half of the genes with dynamic regulatory interactions were missed by large eQTL mapping studies, indicating the importance of exploring multiple treatments to reveal previously unrecognized regulatory loci that may be important for disease
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Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions
Genetic effects on gene expression and splicing can be modulated by cellular and environmental factors; yet interactions between genotypes, cell type and treatment have not been comprehensively studied together. We used an induced pluripotent stem cell system to study multiple cell types derived from the same individuals and exposed them to a large panel of treatments. Cellular responses involved different genes and pathways for gene expression and splicing, and were highly variable across contexts. For thousands of genes, we identified variable allelic expression across contexts and characterized different types of gene-environment interactions, many of which are associated with complex traits. Promoter functional and evolutionary features distinguished genes with elevated allelic imbalance mean and variance. On average half of the genes with dynamic regulatory interactions were missed by large eQTL mapping studies, indicating the importance of exploring multiple treatments to reveal previously unrecognized regulatory loci that may be important for disease
Visualisation of Mycobacterium avium subsp. paratuberculosis in cultured cells, infected sheep and human tissue sections using fluorescent in situ hybridization (FISH)
We describe the development, testing and specificity of a modified oligonucleotide probe for the specific detection of Mycobacterium avium subsp. paratuberculosis (MAP) in culture and in infected tissue using fluorescent in situ hybridisation and confocal microscopy. The detection of MAP in both animal and human tissue using our modified probe allows for a more rapid diagnosis of MAP infection compared to the more often applied detection methods of culture and PCR and has the potential for quantification of cellular abundance. This approach would enable earlier treatment intervention and therefore the potential for reduced morbidity
Physical ecology of hypolithic communities in the central Namib desert : the role of fog, rain, rock habitat, and light
[1] Hypolithic microbial communities are productive niches in deserts worldwide, but many facets of their basic
ecology remain unknown. The Namib Desert is an important site for hypolith study because it has abundant
quartz rocks suitable for colonization and extends west to east across a transition from fog- to rain-dominated
moisture sources. We show that fog sustains and impacts hypolithic ecology in several ways, as follows: (1) fog
effectively replaces rainfall in the western zone of the central Namib to enable high (â„95%) hypolithic abundance
at landscape (1â10 km) and larger scales; and (2) high water availability, through fog (western zone) and/or
rainfall (eastern zone), results in smaller size-class rocks being colonized (mean 6.3 ± 1.2 cm) at higher
proportions (e.g., 98% versus approximately 3%) than in previously studied hyperarid deserts. We measured
0.1% of incident sunlight as the lower limit for hypolithic growth on quartz rocks in the Namib and found that
uncolonized ventral rock surfaces were limited by light rather than moisture. In situ monitoring showed that
although rainfall supplied more liquid water (36 h) per event than fog (mean 4 h), on an equivalent annual basis,
fog provided nearly twice as much liquid water as rainfall to the hypolithic zone. Hypolithic abundance reaches
100% at a mean annual precipitation (MAP) of approximately 40â60 mm, but at a much lower MAP
(approximately 25 mm) when moisture from fog is available.This work was partially supported through NASAâs ASTEP Programhttp://agupubs.onlinelibrary.wiley.com/agu/jgr/journal/10.1002/(ISSN)2169-8961hb201
Hypolithic and soil microbial community assembly along an aridity gradient in the Namib Desert
The Namib Dessert is considered the oldest desert in the world and hyperarid for the last 5 million years. However, the environmental buffering provided by quartz and other translucent rocks supports extensive hypolithic microbial communities. In this study, open soil and hypolithic microbial communities have been investigated along an EastâWest transect characterized by an inverse fog-rainfall gradient. Multivariate analysis showed that structurally different microbial communities occur in soil and in hypolithic zones. Using variation partitioning, we found that hypolithic communities exhibited a fog-related distribution as indicated by the significant Eastâ West clustering. Sodium content was also an important environmental factor affecting the composition of both soil and hypolithic microbial communities. Finally, although null models for patterns in microbial communities were not supported by experimental data, the amount of unexplained variation (68â97 %) suggests that stochastic processes also play a role in the assembly of such communities in the Namib Desert.Web of Scienc
Understanding patients' satisfaction with physician assistant/associate encounters through communication experiences: a qualitative study in acute hospitals in England.
BACKGROUND: Physician assistants/associates (PAs) are a recent innovation in acute hospital teams in England and many other countries worldwide. Although existing evidence indicates generally high levels of patient satisfaction with their PA hospital encounters, little is known about the factors associated with this outcome. There is a lack of evidence on the process of PA-patient communication in hospital encounters and how this might influence satisfaction. This study therefore aimed to understand patients' satisfaction with PA acute hospital encounters through PA-patient communication experiences. METHODS: A qualitative study was conducted among patients and representatives of patients seen by or receiving care from one of the PAs working in acute hospital services in England. Semi-structured interviews were undertaken face-to-face with study participants in the hospital setting and shortly after their PA encounter. Data were coded and analysed using thematic analysis. The study was framed within a theoretical model of core functions of medical encounter communication. RESULTS: Fifteen patients and patient representatives who had experienced a PA encounter participated in interviews, across five hospitals in England. Four interrelated communication experiences were important to participants who were satisfied with the encounter in general: feeling trust and confidence in the relationship, sharing relevant and meaningful information, experiencing emotional care and support, and sharing discussion on illness management and treatment. However, many participants misconceived PAs to be doctors, raising a potential risk of reduced trust in the PA relationship and negative implications for satisfaction with their PA encounter. Participants considered it beneficial that patients be informed about the PA role to prevent confusion. CONCLUSIONS: PA encounters offer a constructive example of successful clinician-patient communication experiences in acute hospital encounters from the patient's perspective. Study participants were generally naĂŻve to the PA role. Hospital services and organisations introducing these mid-level or advanced care practitioner roles should consider giving attention to informing patients about the roles
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