Local Area Coordination: Summative Evaluation

Project funded by ESRC Impact Accelerator Account (Co-Production). Project partners University of York and City of York Counci

P175 Work Ready Champions for Young People::the role of occupational therapy in addressing the pre-vocational and early-employment needs of young people with long term health conditions

Item is not available in this repository.https://doi.org/10.1093/rheumatology/keac133.17461pubpubSupplement_

P50 addressing the vocational development of young people with long-term health conditions in health care settings:a systematic review and mixed methods synthesis

INTRODUCTION/BACKGROUND: Long term health conditions (LTHC) such as rheumatic conditions have significant impact on the biopsychosocial development of young people (YP) including vocational development. Educational transitions are prominent during adolescence and young adulthood yet not all transitional care programmes in rheumatology address this area [1]. The aim of this study was to identify and synthesise the benefits and experiences of addressing the vocational development of YP with LTHC in health care settings. DESCRIPTION/METHOD: A mixed methods synthesis approach [2] was employed. We systematically searched 10 bibliographic databases. Restrictions were applied on publication date (1996-2020) and publication language (English). Articles reporting quantitative and/or qualitative primary research on addressing vocational needs/issues of YP with LTHC in health care settings were included. YP was defined as 10-24 years [3]. Two reviewers independently screened records using predetermined inclusion/exclusion criteria [4]. Quality appraisal was undertaken following study selection. Qualitative data were synthesised thematically. Quantitative data were synthesised narratively, given that a pooled synthesis was not considered appropriate. A cross-study synthesis integrated findings from both the qualitative and quantitative syntheses. DISCUSSION/RESULTS: 43 articles were included. The quality of qualitative evidence was good; however, the quality of quantitative evidence was poor. The thematic synthesis of stakeholders’ perspectives (n = 23 qualitative studies) resulted in seven recommendations for interventions: provide skills training; provide psychological support; offer to liaise with key stakeholders in educational/workplace settings; provide specialist career advice; provide information, signposting and facilitate access to supporting services; provide/facilitate access to social support; provide flexible care and optimal disease management to support education/employment transitions. The narrative synthesis summarised the results of 17 interventions. The cross-study synthesis mapped interventions against the set of recommendations arising from stakeholders’ perspectives: four interventions met five recommendations; two interventions met four recommendations; five interventions met three recommendations; six interventions met two recommendations. Transitional care interventions were the type of intervention that most comprehensively met the recommendations. The way in which interventions addressed vocational issues was not always clear, with some interventions addressing them directly and others indirectly. No interventions had vocational issues as the core, defining component of the intervention. KEY LEARNING POINTS/CONCLUSION: Existing stakeholder evidence highlights that vocational development is an important area to address in the care of YP with LTHC such as rheumatic diseases. The resulting set of recommendations provides guidance for future research in this area and transitional care developments in rheumatology. Further work in this area should address these aspects to enable better quality evidence and ensure consistency. References [1] Clemente D et al. Pediatr Rheumatol Online J. 2017 Jun 9;15(1):49. [2] Kavanagh, J et al Synthesizing Qualitative Research: Choosing the Right Approach. Wiley-Blackwell, Chichester, UK, pp. 113–136 [3] World Health Organization, 2001. The second decade: improving adolescent health and development. Geneva. [4] Farre A et al. PROSPERO 2016 CRD42016051359

Local Area Coordination: Process Evaluation

Project funded under the ESRC Impact Accelerator Account (Co-Production). Project partners University of York and City of York Council

Comparative genomics of apomictic root-knot nematodes:Hybridization, ploidy, and dynamic genome change

The Root-Knot Nematodes (RKN; genus Meloidogyne) are important plant parasites causing substantial agricultural losses. The Meloidogyne incognita group (MIG) of species, most of which are obligatory apomicts (mitotic parthenogens), are extremely polyphagous and important problems for global agriculture. While understanding the genomic basis for their variable success on different crops could benefit future agriculture, analyses of their genomes are challenging due to complex evolutionary histories that may incorporate hybridization, ploidy changes, and chromosomal fragmentation. Here we sequence 19 genomes, representing five species of key RKN collected from different geographic origins. We show that a hybrid origin that predated speciation within the MIG has resulted in each species possessing two divergent genomic copies. Additionally, the apomictic MIG species are hypotriploids, with a proportion of one genome present in a second copy. The hypotriploid proportion varies among species. The evolutionary history of the MIG genomes is revealed to be very dynamic, with non-crossover recombination both homogenising the genomic copies, and acting as a mechanism for generating divergence between species. Interestingly, the automictic MIG species M. floridensis differs from the apomict species in that it has become homozygous throughout much of its genome

PMIP4-CMIP6: the contribution of the Paleoclimate Modelling Intercomparison Project to CMIP6

The goal of the Palaeoclimate Modelling Intercomparison Project (PMIP) is to understand the response of the climate system to changes in different climate forcings and to feedbacks. Through comparison with observations of the environmental impacts of these climate changes, or with climate reconstructions based on physical, chemical or biological records, PMIP also addresses the issue of how well state-of-the-art models simulate climate changes. Palaeoclimate states are radically different from those of the recent past documented by the instrumental record and thus provide an out-of-sample test of the models used for future climate projections and a way to assess whether they have the correct sensitivity to forcings and feedbacks. Five distinctly different periods have been selected as focus for the core palaeoclimate experiments that are designed to contribute to the objectives of the sixth phase of the Coupled Model Intercomparison Project (CMIP6). This manuscript describes the motivation for the choice of these periods and the design of the numerical experiments, with a focus upon their novel features compared to the experiments performed in previous phases of PMIP and CMIP as well as the benefits of common analyses of the models across multiple climate states. It also describes the information needed to document each experiment and the model outputs required for analysis and benchmarking

Investigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci

Objective. Five loci—the shared epitope (SE) of HLA-DRB1, the PTPN22 gene, a locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic region—have now been unequivocally confirmed as conferring susceptibility to RA. The largest single effect is conferred by SE. We hypothesized that combinations of susceptibility alleles may increase risk over and above that of any individual locus alone

The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma

BACKGROUND: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial. METHODS: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy. Immunohistochemistry for HIF-1α, CAIX and GLUT1 was performed on tissue microarrays and assessed by two scorers (one pathologist). Prognostic analysis of disease-free survival (DFS) used Kaplan-Meier and Cox regression. RESULTS: Biobank and outcome data were available for 203 out of 216 randomised patients. High CAIX expression was associated with worse DFS (hazard ratio 2.28, 95% confidence interval: 1.44-3.59, P<0.001). Hypoxia-inducible factor-1α and GLUT1 were not prognostic. Carbonic anhydrase IX remained prognostic in multivariable analysis. CONCLUSIONS: The VorteX-Biobank contains tissue with linked outcome data and is an important resource for research. This study confirms hypoxia is linked to poor prognosis in STS and suggests that CAIX may be the best known marker. However, overlap between single marker positivity was poor and future work will develop an STS hypoxia gene signature to account for tumour heterogeneity

Concurrent Oral 1 - Rheumatoid Arthritis: Treatment [OP4-OP9]: OP4. Inhibition of Radiographic Progression and Improvements in Physical Function at 2 Years, with Increasing Clinical Efficacy Over Time, in Rheumatoid Arthritis (Ra) Patients Treated with Tocilizumab (Tcz): The Lithe Study

Background: Patients with moderate to severe RA who remained on methotrexate (MTX) despite inadequate response were treated with TCZ in a double-blind, randomized, controlled phase 3 trial. Results of a 2-year planned analysis from this study are presented. Methods: Patients were randomized to treatment with TCZ 4 mg/kg + MTX (TCZ4), TCZ 8 mg/kg + MTX (TCZ8) or placebo + MTX (CON) every 4 weeks. If patients failed to respond ( 60% of patients and the DAS28 remission (DAS28 < 2.6) rate was 48% at week 52 and continued to increase to week 104. By week 52, patients treated with TCZ8 had clinically significant improvements in SJC that were maintained through week 104. Rates per 100 PY for adverse events (AEs) were higher in TCZ8 and TCZ4 (263.6, 275.4) vs CON patients (251.4) while rates for serious AEs were comparable (11.4, 12.1, 10.9, respectively). Rates per 100 PY of AEs leading to withdrawal (7.4, 32.5, 4.8) and treatment modification (8.4, 30.7, 20.4) were higher in TCZ8 and TCZ4 vs CON patients, respectively and death rates were comparable (0.6, 0.2, 0.4). Conclusions: Treatment with TCZ + MTX inhibits radiographic progression over 2 years and improves physical function as shown by DAS28 remission, LDAS and low SJC, with a manageable safety profile. Disclosure statement: E.A., F. Hoffmann-La Roche - Employee. P.A., F. Hoffmann-La Roche - Employee. R.B.-V., F. Hoffmann-La Roche - Honoraria. R.F., Genentech - Research Funding, Honoraria. J.K., F. Hoffmann-La Roche - Research funding, Honorari