Impact Storytelling: the Ecosystem, the Evidence and Possible Futures

“Impact Storytelling: the Ecosystem, the Evidence and Possible Futures” is a ‘go-to’ report for storytellers, artivists, students, scholars and impact practitioners interested in impact storytelling (often referred to as "storytelling for social change"). This large study from UAL's AKO Storytelling Institute has been designed to help answer questions such as: what is 'impact storytelling'? What evidence is there that impact storytelling works? What is the history and current landscape of impact storytelling, in the UK and internationally? It maps the structure of the impact storytelling ecosystem, identifies its key players, listens to current live debates and questions how to better collaborate in an emerging space that is still fairly siloed. By bringing to the foreground some of the ecosystem's gaps and blind spots, it hopes to open a space for reflection and debate. The intention is to serve as a base towards cross-industry collaboration and cross-disciplinary consolidation

Innocent strategies as presheaves and interactive equivalences for CCS

Seeking a general framework for reasoning about and comparing programming languages, we derive a new view of Milner's CCS. We construct a category E of plays, and a subcategory V of views. We argue that presheaves on V adequately represent innocent strategies, in the sense of game semantics. We then equip innocent strategies with a simple notion of interaction. This results in an interpretation of CCS. Based on this, we propose a notion of interactive equivalence for innocent strategies, which is close in spirit to Beffara's interpretation of testing equivalences in concurrency theory. In this framework we prove that the analogues of fair and must testing equivalences coincide, while they differ in the standard setting.Comment: In Proceedings ICE 2011, arXiv:1108.014

Impact Storytelling: the Ecosystem, the Evidence and Possible Futures

“Impact Storytelling: the Ecosystem, the Evidence and Possible Futures” is a ‘go-to’ report for storytellers, artivists, students, scholars and impact practitioners interested in impact storytelling (often referred to as "storytelling for social change"). This large study from UAL's AKO Storytelling Institute has been designed to help answer questions such as: what is 'impact storytelling'? What evidence is there that impact storytelling works? What is the history and current landscape of impact storytelling, in the UK and internationally? It maps the structure of the impact storytelling ecosystem, identifies its key players, listens to current live debates and questions how to better collaborate in an emerging space that is still fairly siloed. By bringing to the foreground some of the ecosystem's gaps and blind spots, it hopes to open a space for reflection and debate. The intention is to serve as a base towards cross-industry collaboration and cross-disciplinary consolidation

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

Randomised controlled trial and economic evaluation of a targeted cancer awareness intervention for adults living in deprived areas of the UK

Background: Cancer outcomes are poor in socioeconomically deprived communities, with low symptom awareness contributing to prolonged help-seeking and advanced disease. Targeted cancer awareness interventions require evaluation. Methods: Randomised controlled trial involving adults aged 40+ recruited in community and healthcare settings in deprived areas of South Yorkshire and South-East Wales. Intervention: personalised behavioural advice facilitated by a trained lay advisor. Control: usual care. Follow-up at 2-weeks and 6-months post-randomisation. Primary outcome: total cancer symptom recognition score 2-weeks post-randomisation. Results: 234 participants were randomised. The difference in total symptom recognition at 2-weeks [adjusted mean difference (AMD) 0.6, 95% CI:-0.03, 1.17, p=0.06] was not statistically significant. Intervention participants reported increased symptom recognition (AMD 0.8, 95% CI:0.18, 1.37, p=0.01) and earlier intended presentation (AMD -2.0, 95% CI:-3.02, -0.91, p<0.001) at 6-months. “Lesser known” symptom recognition was higher in the intervention arm (2-weeks AMD 0.5, 95% CI:0.03, 0.97 and 6-months AMD 0.7, 95% CI:0.16, 1.17). Implementation cost per participant was £91.34, with no significant between-groups differences in healthcare resource use post-intervention. Conclusions: Improved symptom recognition and earlier anticipated presentation occurred at longer-term follow-up. The ABACus Health Check is a viable low-cost intervention to increase cancer awareness in socioeconomically deprived communities. Clinical Trial Registration: ISRCTN1687254

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype