Mapping Metaphor with the Historical Thesaurus: a new resource for investigating metaphor in names

The AHRC-funded ‘Mapping Metaphor with the Historical Thesaurus’ project has traced the development of metaphor in English from Anglo-Saxon times to the present day using the unique evidence base of the Historical Thesaurus of the Oxford English Dictionary. The Historical Thesaurus organises the contents of the OED semantically, making it possible to see how vocabulary for any given concept has developed over time. One of the major outputs of the Mapping Metaphor project is the online Metaphor Map, which can be used to investigate metaphor in names and is freely available at: http://mappingmetaphor.arts.gla.ac.uk/

Sleep Quality, Fatigue, and Quality of Life Among Teenage and Young Adult Cancer Survivors

Purpose: Teenage and young adult (TYA) cancer survivors experience a range of health-related problems during and beyond the active treatment period. This study examined associations between fatigue, sleep quality, and health-related quality of life (HRQOL) among TYA survivors.Methods: Self-reported data on sleep quality (Pittsburgh Sleep Quality Index), fatigue (Functional Assessment of Chronic Illness Therapy Fatigue), and HRQOL (EuroQoL-5) were gathered from United Kingdom TYA survivors between 13 and 24 years of age. TYA survivors were stratified into those on (n = 67) and off (n = 135) treatment. Linear regression analyses were used with HRQOL as the dependent variable to investigate potential associations. Fatigue and sleep were entered separately and together in the same model. Age at survey and diagnosis, gender, and ethnicity were included as covariates.Results: 85.07% of TYAs on and 62.69% of TYAs off treatment had sleep quality scores suggestive of clinically significant sleep disorders. 56.72% of TYAs on and 26.67% of TYAs off treatment reported clinically significant levels of fatigue. Strong independent associations between sleep (B = 0.05, 95% confidence intervals [CI] = 0.03–0.07, p < 0.001), fatigue (B = 0.02, 95% CI = 0.01–0.03, p < 0.001), and HRQOL were observed among TYA survivors on treatment. TYAs off treatment showed moderate to strong associations between sleep (B = 0.04, 95% CI = 0.02–0.05, p < 0.001) and fatigue (B = 0.02, 95% CI = 0.01–0.02, p < 0.001), and HRQOL, when examined separately. Sleep was not independently associated with HRQOL among TYAs off treatment (B = 0.01, 95% CI = −0.01 to 0.02, p = 0.296).Conclusion: The significant associations reported suggest that sleep quality and fatigue are potential modifiable factors associated with HRQOL. Further research is warranted to understand the direction of associations

Sleep Quality, Fatigue, and Quality of Life Among Teenage and Young Adult Cancer Survivors

Purpose: Teenage and young adult (TYA) cancer survivors experience a range of health-related problems during and beyond the active treatment period. This study examined associations between fatigue, sleep quality, and health-related quality of life (HRQOL) among TYA survivors.Methods: Self-reported data on sleep quality (Pittsburgh Sleep Quality Index), fatigue (Functional Assessment of Chronic Illness Therapy Fatigue), and HRQOL (EuroQoL-5) were gathered from United Kingdom TYA survivors between 13 and 24 years of age. TYA survivors were stratified into those on (n = 67) and off (n = 135) treatment. Linear regression analyses were used with HRQOL as the dependent variable to investigate potential associations. Fatigue and sleep were entered separately and together in the same model. Age at survey and diagnosis, gender, and ethnicity were included as covariates.Results: 85.07% of TYAs on and 62.69% of TYAs off treatment had sleep quality scores suggestive of clinically significant sleep disorders. 56.72% of TYAs on and 26.67% of TYAs off treatment reported clinically significant levels of fatigue. Strong independent associations between sleep (B = 0.05, 95% confidence intervals [CI] = 0.03–0.07, p < 0.001), fatigue (B = 0.02, 95% CI = 0.01–0.03, p < 0.001), and HRQOL were observed among TYA survivors on treatment. TYAs off treatment showed moderate to strong associations between sleep (B = 0.04, 95% CI = 0.02–0.05, p < 0.001) and fatigue (B = 0.02, 95% CI = 0.01–0.02, p < 0.001), and HRQOL, when examined separately. Sleep was not independently associated with HRQOL among TYAs off treatment (B = 0.01, 95% CI = −0.01 to 0.02, p = 0.296).Conclusion: The significant associations reported suggest that sleep quality and fatigue are potential modifiable factors associated with HRQOL. Further research is warranted to understand the direction of associations

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment

Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia

In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. We show that long-lived CAR-T cells developed a CD4/CD8 double-negative phenotype with an exhausted-like memory state and distinct transcriptional signature. This persistence signature was dominant among circulating CAR-T cells in all children with a long-lived treatment response for which sequencing data were sufficient (4/4, 100%). The signature was also present across T cell subsets and clonotypes, indicating that persisting CAR-T cells converge transcriptionally. This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists

Reporting the whole story : Analysis of the 'out-of-scope' questions from the James Lind Alliance Teenage and Young Adult Cancer Priority Setting Partnership Survey

OBJECTIVE: We conducted a UK-wide survey to identify the top 10 research questions for young people's cancer. We conducted secondary analysis of questions submitted, which were 'out-of-scope' of the original survey aim. We sought to disseminate these questions, to inform practice, policy and the development of potential interventions to support young people with cancer. DESIGN: James Lind Alliance Priority Setting Partnership. PARTICIPANTS: Young people aged 13-24 with a current/previous cancer diagnosis, their families/friends/partners and professionals who work with this population. METHODS: Eight hundred and fifty-five potential research questions were submitted, and 326 were classified as 'out-of-scope'. These questions, along with 49 'free-text' comments, were analysed using thematic analysis. RESULTS: The 375 out-of-scope questions and comments were submitted by: 68 young people, 81 family members/partners/friends and 42 professionals. Ten overarching themes were identified: diagnostic experience; communication; coordination of care; information needs and lack of information; service provision; long-term effects and aftercare support; family support; financial impact; end-of life care; and research methods and current research. CONCLUSIONS: The need to tailor services, information and communication is a striking thread evidenced across the 'out-of-scope' questions. Gaps in information highlight implications for practice in revisiting information needs throughout the cancer trajectory. We must advocate for specialist care for young people and promote the research priorities and these findings to funding bodies, charities, young people and health and social care policymakers, in order to generate an evidence base to inform effective interventions across the cancer trajectory and improve outcomes. PATIENT/PUBLIC CONTRIBUTIONS: Patients and carers were equal stakeholders throughout

Predictors of recovery following allogeneic CD34+-selected cell infusion without conditioning to correct poor graft function

Poor graft function is a serious complication following allogeneic hematopoietic stem cell transplantation. Infusion of CD34+-selected stem cells without pre-conditioning has been used to correct poor graft function, but predictors of recovery are unclear. We report the outcome of 62 consecutive patients who had primary or secondary poor graft function who underwent a CD34+-selected stem cell infusion from the same donor without further conditioning. Forty-seven of 62 patients showed hematological improvement and became permanently transfusion and growth factor-independent. In multivariate analysis, parameters significantly associated with recovery were shared CMV seronegative status for recipient/donor, the absence of active infection and matched recipient/donor sex. Recovery was similar in patients with mixed and full donor chimerism. Five -year overall survival was 74.4% (95% CI 59-89) in patients demonstrating complete recovery, 16.7% (95% CI 3-46) in patients with partial recovery and 22.2% (CI 95% 5-47) in patients with no response. In patients with count recovery, those with poor graft function in 1-2 lineages had superior 5-year overall survival (93.8%, 95% CI 82-99) than those with tri-lineage failure (53%, 95% CI 34-88). New strategies including cytokine or agonist support, or second transplant need to be investigated in patients who do not recover

Research priorities for young people with cancer : a UK priority setting partnership with the James Lind Alliance

OBJECTIVES: To conduct a UK-wide survey of young people who have experienced cancer, carers and professionals, to identify and prioritise research questions to inform decisions of research funders and support the case for research with this unique cancer population. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative and partner organisations were recruited. Unanswered questions were collected in an online survey. Evidence searching verified uncertainties. An interim survey was used to rank questions prior to a final prioritisation workshop. PARTICIPANTS: Young people aged 13-24 years with a current or previous cancer diagnosis, their families, friends, partners and professionals who work with this population. RESULTS: Two hundred and ninety-two respondents submitted 855 potential questions. Following a refining process and removal of 'out of scope' questions, 208 unique questions remained. Systematic evidence checking identified seven answered questions and 16 were the subject of ongoing studies. The interim survey was completed by 174 participants. The top 30 questions were prioritised at a workshop attended by 25 young people, parents and multidisciplinary professionals. The top three priorities are: (1) What psychological support package improves psychological well-being, social functioning and mental health during and after treatment? (2) What interventions, including self-care, can reduce or reverse adverse short-term and long-term effects of cancer treatment? (3) What are the best strategies to improve access to clinical trials? The remaining questions reflect the complete cancer pathway: new therapies, life after cancer, support, education/employment, relapse and end-of-life care. CONCLUSIONS: We have identified shared research priorities for young people with cancer using a rigorous, person-centred approach involving stakeholders typically not involved in setting the research agenda. The breadth of priorities suggest future research should focus on holistic and psychosocial care delivery as well as traditional drug/biology research