Promoters are DNA sequences that have an essential role in controlling gene expression. While recent whole cancer genome analyses have identified numerous hotspots of somatic point mutations within promoters, many have not yet been shown to perturb gene expression or drive cancer development. As such, positive selection alone may not adequately explain the frequency of promoter point mutations in cancer genomes. Here we show that increased mutation density at gene promoters can be linked to promoter activity and differential nucleotide excision repair (NER). By analysing 1,161 human cancer genomes across 14 cancer types, we find evidence for increased local density of somatic point mutations within the centres of DNase I-hypersensitive sites (DHSs) in gene promoters. Mutated DHSs were strongly associated with transcription initiation activity, in which active promoters but not enhancers of equal DNase I hypersensitivity were most mutated relative to their flanking regions. Notably, analysis of genome-wide maps of NER shows that NER is impaired within the DHS centre of active gene promoters, while XPC-deficient skin cancers do not show increased promoter mutation density, pinpointing differential NER as the underlying cause of these mutation hotspots. Consistent with this finding, we observe that melanomas with an ultraviolet-induced DNA damage mutation signature show greatest enrichment of promoter mutations, whereas cancers that are not highly dependent on NER, such as colon cancer, show no sign of such enrichment. Taken together, our analysis has uncovered the presence of a previously unknown mechanism linking transcription initiation and NER as a major contributor of somatic point mutation hotspots at active gene promoters in cancer genomes.

Elderly co-resident caregivers for stroke and dementia patients experience similar degrees of burden and high levels of psychological morbidity. Psychiatric aspects of chronic disability, rather than physical aspects, were found to be more stressful to caregivers. All assessments of the disabled elderly should include measures of caregiver burden and psychological distress.

Reproducible research is the bedrock of experimental science. To enable the deployment of large-scale proteomics, we assess the reproducibility of mass spectrometry (MS) over time and across instruments and develop computational methods for improving quantitative accuracy. We perform 1560 data independent acquisition (DIA)-MS runs of eight samples containing known proportions of ovarian and prostate cancer tissue and yeast, or control HEK293T cells. Replicates are run on six mass spectrometers operating continuously with varying maintenance schedules over four months, interspersed with~5000 other runs. We utilise negative controls and replicates to remove unwanted variation and enhance biological signal, outperforming existing methods. We also design a method for reducing missing values. Integrating these computational modules into a pipeline (ProNorM), we mitigate variation among instruments over time and accurately predict tissue proportions. We demonstrate how to improve the quantitative analysis of large-scale DIA-MS data, providing a pathway toward clinical proteomics.

Published evidence for the role of participatory art in supporting health and well‐being is growing. The Arts on Prescription model is one vehicle by which participatory art can be delivered. Much of the focus of Arts on Prescription has been on the provision of creative activities for people with mental health needs. This Arts on Prescription program, however, targeted community‐dwelling older people with a wide range of health and wellness needs. Older people were referred to the program by their healthcare practitioner. Professional artists led courses in visual arts, photography, dance and movement, drama, singing, or music. Classes were held weekly for 8–10 weeks, with six to eight participants per class, and culminated with a showing of work or a performance. Program evaluation involved pre‐ and postcourse questionnaires, and focus groups and individual interviews. Evaluation data on 127 participants aged 65 years and older were available for analysis. We found that Arts on Prescription had a positive impact on participants. Quantitative findings revealed a statistically significant improvement in the Warwick–Edinburgh Mental Well‐being Scale (WEMWBS) as well as a statistically significant increase in the level of self‐reported creativity and frequency of creative activities. Qualitative findings indicated that the program provided challenging artistic activities which created a sense of purpose and direction, enabled personal growth and achievement, and empowered participants, in a setting which fostered the development of meaningful relationships with others. This evaluation adds to the evidence base in support of Arts on Prescription by expanding the application of the model to older people with a diverse range of health and wellness needs.