NIHRDataInsights/HRCSData huggingface dataset:
Title: Children of parents with chronic inflammatory musculoskeletal diseases: Experiences, needs and resources.
Funder: Arthritis Research UK

Abstract: Background: There are currently no educational resources for the children of parents with chronic inflammatory musculoskeletal diseases._x000D_ _x000D_ Objectives:_x000D_ _x000D_ 1) To establish how the parent’s inflammatory musculoskeletal condition is perceived to impact upon individual and family life from the perspectives of the child(ren), parent and partner_x000D_ _x000D_ 2) To ascertain what kind of information the child(ren) would like to have about their parent’s condition, the format of this, how and when this should be delivered and possibly by whom. _x000D_ _x000D_ Design: Mixed qualitative methodologies will include interviews, supplemented by drawings, posters/story-boards._x000D_ _x000D_ Analysis: Interview and visual data analysis will be carried out using Interpretative Phenomenological Analysis (IPA)._x000D_ _x000D_ Outcomes: These data will help us to understand the impact of a parent’s chronic inflammatory musculoskeletal disorder upon the family unit and what educational resources the children within these families would like to have to help them understand their parents’ condition.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Arthritis Research UK Centre for Research into Adolescent Arthritis
Funder: Arthritis Research UK

Abstract: This proposal is to support a Centre of Excellence for Adolescent Rheumatology, focusing on scientific and translational research, as well as addressing the health needs of Adolescents with arthritis, to be supported through a partnership between Arthritis Research UK, and a consortium of ‘Bloomsbury’ stakeholders: University College London, University College London Hospital and Great Ormond Street Hospital NHS Trusts, and Great Ormond Street Children’s Charity._x000D_ _x000D_ The overall mission of the Centre is to improve the health and well being of adolescents with arthritis and other rheumatological conditions, through high quality research which informs and improves clinical care and pathways. We will achieve our key goals of establishing a critical mass in basic and translational research, through the appointment of senior academic Centre staff posts, underpinned by existing strengths in Paediatric and Adult Rheumatology at UCL. We will work to increase participation of adolescents in clinical trials, and to create seamless transition of research and clinical care from paediatric to adolescent and adult environments. The Centre will provide training, education and new opportunities in Adolescent Rheumatology and enable the creation of a National Network in Adolescent Rheumatology, which will greatly enhance this emerging field at both National and International levels.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;6.1 PHARMACEUTICALS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: A study of the effectiveness of nurse education of patients taking Methotrexate.
Funder: Arthritis Research UK

Abstract: Education of patients prior to commencing Methotrexate is essential for safe and effective use. We have identified gaps in the knowledge of patients and lack of confidence of nurses who give this education. Our proposed study will explore the learning needs of these nurses._x000D_ _x000D_ Phase 1 will be a national questionnaire study of nurses involved in this education to explore their confidence, training, training needs and knowledge. This will give broad high number data that will complement the more detailed information that we will get from phase 2. _x000D_ _x000D_ Phase 2 will be a qualitative study of semi structured interviews of nurses of varying experience exploring the themes above in more detail. _x000D_ _x000D_ Phase 3 will be a pilot study of videoing the educational encounter and developing a framework for analysis._x000D_ _x000D_ The study will inform the content of a nurse education package that could be developed for nurses commencing DMARD education.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: The effectiveness of spreading a health message using a shareable online video targeted at the social networks of recently diagnosed individuals
Funder: Arthritis Research UK

Abstract: Delays in referral to specialist care adversely effect outcomes for children and young people with Juvenile Idiopathic Arthritis (JIA). Reasons for delay include lack of awareness about JIA amongst families and doctors to whom children present. There is a real need to develop educational interventions to reduce delays and increase awareness of the early presentation of JIA and the need for specialist care to optimise outcomes. _x000D_ Although the potential of a widely shared or “viral” online video to spread a health message is recognised, the most effective methods of doing so are unknown. One practical method would be to ask recently diagnosed patients and/or their family members to view and share online videos amongst their real life and electronic social networks. The aim of this novel project is to assess the effectiveness of this technique in "seeding" a shareable video and thereby spreading health messages about JIA.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Developing a service user-informed and evidence-based bio-psychosocial intervention in rheumatic diseases using primary Sjogren's syndrome (pSS) as a disease model
Funder: Arthritis Research UK

Abstract: Objectives: To develop an evidence-based, service user-informed, bio-psychosocial intervention aimed at improving function and quality of life (QOL) for people with primary Sjögren’s syndrome (pSS)._x000D_ _x000D_ Design: This proposal consists of 3 work packages. (1) Systematic review of the literature on the effectiveness of pharmacological and non-pharmacological interventions on everyday function in pSS. (2) To use a technique called "concept mapping" to explore and analyse perspectives from pSS patients, their carers, health professionals and NHS managers regarding what could improve function for people with pSS. Through focus groups and individual participation online, ideas from different stakeholder groups will be collected, condensed, arranged into groups as appropriate and then be ranked. Multivariate analysis will be performed in order to generate graphical representations (concept maps) demonstrating priority areas for intervention and acceptability of different interventions. (3) Using the data from (1) and (2), an evidence-based intervention and associated training materials for staff to deliver the intervention will be developed._x000D_ _x000D_ Outcomes/benefits: (1) An intervention package and associated training materials to improve function and QOL for pSS patients. (2) Raise awareness of pSS within the NHS. (3) Enlarge concept mapping skill-base which is rare in the UK, (4) Develop a strategy for complex intervention development.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Phase 3: Development of a wrist-hand orthosis for use in the management of patients with rheumatoid arthritis
Funder: Arthritis Research UK

Abstract: Wrist hand orthoses (WHOs), for the management of rheumatoid arthritis (RA), were shown to underperform during phase one testing of the previous phases of the project. Phase two resulted in a prototype design WHO. The present application seeks funding to continue development of this prototype in conjunction with industrial and user input.The key goals are to:_x000D_ _x000D_ _x000D_ repeat as necessary the procedures included in phase 2 to optimise the design._x000D_ as a result of each round of testing, redefine the product design specification of the improved WHO_x000D_ conduct structural testing of the design and materials for each iteration of the new device _x000D_ conduct functional testing of each iteration of the product on normals_x000D_ seek industrial collaboration to help ascertain if the suggested materials and design are appropriate for large scale manufacture. Computational analysis(finite element analysis) and structural testing will then be completed to determine that the new materials perform to the desired functionality._x000D_ patient focus group sessions for each iteration of the new device. This will be used to determine if the design requires further modification to meet users’ requirements. To this end, it may be necessary to undertake the analysis, testing and the user focus group session more than once.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Men, masculinity and rheumatoid arthritis: Impact, self-management, education needs and potential solutions
Funder: Arthritis Research UK

Abstract: Evidence shows that men experience particular impacts from long-term conditions, possibly from threats to socially/personally constructed masculinities and they struggle to maintain these. The candidate’s thesis (Arthritis Research UK PhD Studentship) identified men with RA who have negative feelings, struggle to cope and must relinquish traditional physical coping strategies, but are uncomfortable with (perceived) female-oriented coping self-management education groups. Following the MRC Guidelines on Complex Interventions, this Fellowship uses qualitative methods (interpretative phenomenological analysis of individual interviews and thematic analysis of focus group discussions) and quantitative analysis of patient preferences (Q-methodology) to ensure the validity of a large survey to determine how widespread the problems are, the extent to which male-oriented coping support is needed, and the basic content of potential self-management interventions._x000D_ _x000D_ This Fellowship will provide the training necessary to develop a future musculo-skeletal psychology researcher. It will build on the candidate’s PhD skills to an advanced level of both qualitative and Q-methodology, and provide a grounding in epidemiological methods and complex interventions development. Thus, the Fellowship will result in the answers to important questions of relevance to patients, and a well-grounded post-doctoral researcher with a strong project for a mid-term Fellowship.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: PTPN22 and the pathways that regulate T-cell activation and differentiation
Funder: Arthritis Research UK

Abstract: One of the strongest genetic variants associated with RA is a single nucleotide polymorphism C1858T in gene PTPN22. PTPN22 encodes Lyp or Pep in mice, which is a protein tyrosine phosphatase that acts as a negative regulator of TCR signalling, setting the thresholds that control T-cell activation/differentiation. The C1858T SNP is thought to be a gain of function mutation, though how Lyp regulates T-cell responses is not understood. Attenuated TCR signalling and reduced IL-2/IL-10 secretion has been observed in 1858T donors. Our preliminary data indicate that Lyp variants affect T-cell responses by modulating dendritic cell(DC):T-cell interactions and by promoting inflammatory T-cell responses as a direct consequence of altered TCR and integrin signalling thresholds. I now plan to investigate, in detail, how alterations in Lyp expression/function affect T-cell responses._x000D_ _x000D_ Specifically, my aims are to:_x000D_ _x000D_ 1. Define the mechanisms by which Lyp/Pep regulates DC function._x000D_ _x000D_ 2. Determine how Lyp/Pep influences the integrity of T cell:DC interactions at the immune synapse._x000D_ _x000D_ 3. Characterise pathways of T-helper cell differentiation in Lyp/Pep mutant T cells and DC._x000D_ _x000D_ By understanding how heritable genetic variants perturb T-cell and dendritic cell signal transduction pathways my research will uncover fundamental mechanisms through which aberrant immune responses underpin disease susceptibility.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: How is HLA-B27 function modified by ERAP1 to cause Ankylosing Spondylitis?
Funder: Arthritis Research UK

Abstract: Ankylosing Spondylitis is a common inflammatory rheumatic disease of unknown pathogenesis. The strongest genetic associations are with the Human Leucocyte Antigen HLA-B27 (present in over 90% of patients) and with polymorphisms of Endoplasmic Reticulum Aminopeptidase 1 (ERAP1). The ERAP1 association is restricted to HLA-B27-positive AS patients, indicating a genetic interaction. We will use immunological, biochemical and proteomic strategies to determine the effects of ERAP1 on HLA-B27 function. We hypothesize that ERAP1 acts by altering either peptide presentation by HLA-B27, misfolding of HLA-B27 in the ER, or the expression of pro-inflammatory B27 forms at the cell surface._x000D_ _x000D_ _x000D_ _x000D_ We will determine if HLA-B27 binds and presents peptide antigens differently in the absence of ERAP1 or in the presence of ERAP1 mutants either associated with or protective against AS. We will quantify differences in the HLA-B27 peptide repertoire in cells (including AS patient-derived cell lines) with disease-associated and protective ERAP1 types, using mass spectrometry, and T and NK cell recognition assays. We will also determine if different ERAP1 types alter either HLA-B27 misfolding or cell-surface expression of aberrant HLA-B27 forms known to stimulate inflammatory responses. These findings will deepen our understanding of the pathogenesis of AS and identify testable therapeutic targets and strategies.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Post GWAS: A Functional Genomic Analysis of the SLE Susceptibility Gene IKZF1
Funder: Arthritis Research UK

Abstract: Genome-wide association studies have identified IKZF1 as a novel risk locus for SLE. We are interested in IKZF1, which encodes a transcription factor (TF) because low levels of Ikzf1 in mice is implicated in impaired B-cell development and in B-cell hyperactivity, both of which are characteristics of SLE. Furthermore, PBMCs from lupus patients express reduced levels of IKZF1._x000D_ _x000D_ The associated interval for IKZF1 is within the proximal 120kb upstream. However, little is known about the TF regulating IKZF1 itself, which may cause reduced IKZF1 levels and underlie the observed association. If we can narrow down the susceptibility interval for IKZF1, using trans-ancestral mapping, we can pinpoint variants responsible for the biological activity of the protein. We will identify the core promoter of IKZF1 responsible for regulating IKZF1 levels and determine the TF(s) controlling the IKZF1 differential regulation._x000D_ _x000D_ Using ChIP-Seq we will determine the downstream regulatory targets bound by IKZF1 and RNA-Seq to establish whether this binding triggers changes in expression of the target genes. We will establish the fundamental pathways within B-cells that are affected by changing levels of IKZF1 and discover how genetic variation in IKZF1 dysregulates B-cells in SLE.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: dried blood spot viability for protein sample storage in Clinical Trials (DeteCT)
Funder: Arthritis Research UK

Abstract: Multicentre, prospective longitudinal research in arthritis especially JIA is hampered by the difficulty in obtaining useful samples in a timely manner._x000D_ _x000D_ Samples such as plasma need to be rapidly processed and stored at -200C. This is time consuming for the physician and expensive for long-term storage. _x000D_ _x000D_ The advent of INBANK has highlighted this dilemma. If we wish all centres to have the opportunity to be involved in long term studies we need to provide a simple means of sample collection and transport in the short term._x000D_ _x000D_ Reducing the cost of long term storage at INBANK would also be of enormous value._x000D_ _x000D_ We have been looking at the feasibility of using dried blood spots, collected on pretreated cards, for protein analysis. Preliminary results reveal that, proteins analysed so far e.g. CRP and TNF, can be recovered at least in the short term from spots stored at room temperature. Furthermore the levels correlate well with those obtained from conventionally stored plasma samples._x000D_ _x000D_ The purpose of this pilot study is to investigate whether relevant proteins can be reliably retrieved from dried blood spots stored at room temperature, with values that correlate to those found in conventionally processed plasma samples.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Functional characterisation of regulatory genetic variants associated with ankylosing spondylitis
Funder: Arthritis Research UK

Abstract: Ankylosing spondylitis (AS) is a common severe inflammatory arthritis whose pathogenesis remains incompletely understood. The disease is highly heritable and shows a strong genetic association with the Major Histocompatibility Complex (MHC), in particular HLA-B27. However only a minority of individuals carrying HLA-B27 develop AS and recent genome-wide association studies (GWAS) have led to dramatic advances, in particular the identification of at least 14 AS associated genomic loci outside the MHC. This PhD studentship will aim to perform detailed functional characterisation of specific GWAS loci that are also associated with differential gene expression based on recent work in the host lab arising from expression quantitative trait mapping in primary immune cells. This research will seek to resolve causal functional alleles involving non-coding genetic variants, the target gene whose expression has been modulated and mechanism of action. Bioinformatic and functional genomic approaches will be used to validate and fine-map regulatory variants, determine mechanism and disease relevance. This work will generate new insights into disease pathogenesis, provide novel targets for drug development or drug repositioning and generate new biomarkers. It will constitute part of an expanding translational research programme in the functional genomics of inflammatory arthritis and immune-related disease by the host lab.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: SLE pathogenesis: the molecular basis for multiple association signals in IKZF2
Funder: Arthritis Research UK

Abstract: Genome-wide association studies have identified IKZF2 as a novel risk locus for SLE. We are interested in IKZF2, which encodes a transcription-factor because our GWAS revealed two independent association signals at the locus. IKZF2 is a member of the ikaros family of transcription-factors, of which two other members (IKZF1 and IKZF2) are associated with SLE at the level of genome-wide signficiance (P<5x10-8)._x000D_ _x000D_ _x000D_ _x000D_ Member of the ikaros family act as dimers, being able to form homo-dimers but also to heter-dimerise with other members of the family. We have focused on IKZF2 in this application because very little is known about biology of this molecule in order to interpret the genetic associations._x000D_ _x000D_ _x000D_ _x000D_ The student will investigate the molecular mechanism of for the two associations in IKZF2: upstream putative enhancer region correlated with increases in IKZF2 gene expression and a 3’ haplotype which includes a proposed coding activation region, the C-terminal dimerization domain and the 3’UTR. S/he will use DNA-sequencing and/or genotyping to fine-map each haplotype, yeast-one hybrid analysis and allelic imbalance studies to investigate allele-dependent gene expression, transient expression analysis, gel-filtration and immunoblot to study dimerization potential, inducible expression to understand mRNA decay and 3C techniques to explore enhancer activity.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Control of T cell retention at inflammatory sites
Funder: Arthritis Research UK

Abstract: Inflammatory sites contain a number of different cell types that contribute to the swelling and destruction of surrounding tissue. In rheumatoid arthritis this inflammation occurs at joints and the cells implicated in coordinating and amplifying this damage are CD4 T cells. Much is known about the cells and soluble molecules responsible for attracting CD4 T cells to migrate into inflammatory sites. However, the signals responsible for retaining these cells at inflammatory sites are only poorly characterised. Understanding which key signals control the retention of CD4 T cells and what cell types provide these signals could lead to novel treatment strategies that force CD4 T cells to leave inflammatory sites. This project will use novel, cutting edge in vivo mouse models to examine CD4 T cells and the immune cells which they interact with at inflammatory sites. By manipulating the cells and signals present in inflammatory sites and determining the effect this has on CD4 T cells, the project will determine the signals that contribute to the retention of the CD4 T cells. A greater understanding of the molecular mechanisms that control this cellular retention will provide an innovative framework for alternative therapeutic targets that alleviate chronic inflammation in rheumatoid arthritis.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Does galectin-9 recruit neutrophils with a suppressive phenotype?
Funder: Arthritis Research UK

Abstract: The factors that cause recruitment and persistence of leukocyte infiltrates in the arthritic joint are not fully understood and therapies aimed at inhibiting leukocyte recruitment have had limited success clinically due to increased infection risk. Galectins are beta-galactoside binding proteins that are endowed with immunoregulatory properties, including both positive and negative regulatory effects on leukocyte recruitment. My preliminary studies have demonstrated that Gal-9 recruits neutrophils in vitro and in vivo, however its effects on neutrophil recruitment and phenotype have not been systematically studied. Evidence in the literature suggests that Gal-9 is both anti-inflammatory and anti-arthritic and that it may recruit neutrophils with an anti-inflammatory, suppressive phenotype. The aims of this project are therefore to investigate the role of Gal-9 in leukocyte recruitment during inflammation. A murine model of arthritis, dependent on neutrophils for disease pathogenesis, will be used to determine not only the role of Gal-9 in inflammatory arthritis but also whether it recruits neutrophils to the arthritic joint that have a suppressive phenotype. These investigations may point to a new potential avenue for therapy in which the inflammatory response is not compromised but rather the chronicity of disease is altered through suppression of the adaptive immune response.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM