Clogging the machinery: the BBC's experiment in science coordination, 1949–1953

In 1949, physicist Mark Oliphant criticised the BBC’s handling of science in a letter to the Director General William Haley. It initiated a chain of events which led to the experimental appointment of a science adviser, Henry Dale, to improve the ‘coordination’ of science broadcasts. The experiment failed, but the episode revealed conflicting views of the BBC’s responsibility towards science held by scientists and BBC staff. For the scientists, science had a special status, both as knowledge and as an activity, which in their view obligated the BBC to make special arrangements for it. BBC staff, however, had their own professional procedures which they were unwilling to abandon. The events unfolded within a few years of the end of the Second World War, when social attitudes to science had been coloured by the recent conflict, and when the BBC itself was under scrutiny from the William Beveridge’s Committee. The BBC was also embarking on new initiatives, notably the revival of adult education. These contextual factors bear on the story, which is about the relationship between a public service broadcaster and the external constituencies it relies on, but must appear to remain independent from. The article therefore extends earlier studies showing how external bodies have attempted to manipulate the inner workings of the BBC to their own advantage (e.g. those by Doctor and Karpf) by looking at the little-researched area of science broadcasting. The article is largely based on unpublished archive documents

Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision

Background Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1–2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84–99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group. Methods Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed. Findings Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67–80] vs 65 years [61–71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6–12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups. Interpretation The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery. Funding Cancer Research UK

Rare genetic variants underlie outlying levels of DNA methylation and gene-expression

Testing the effect of rare variants on phenotypic variation is difficult due to the need for extremely large cohorts to identify associated variants given expected effect sizes. An alternative approach is to investigate the effect of rare genetic variants on DNA methylation (DNAm) as effect sizes are expected to be larger for molecular traits compared to complex traits. Here, we investigate DNAm in healthy ageing populations—the Lothian Birth Cohorts of 1921 and 1936 and identify both transient and stable outlying DNAm levels across the genome. We find an enrichment of rare genetic single nucleotide polymorphisms (SNPs) within 1 kb of DNAm sites in individuals with stable outlying DNAm, implying genetic control of this extreme variation. Using a family-based cohort, the Brisbane Systems Genetics Study, we observed increased sharing of DNAm outliers among more closely related individuals, consistent with these outliers being driven by rare genetic variation. We demonstrated that outlying DNAm levels have a functional consequence on gene expression levels, with extreme levels of DNAm being associated with gene expression levels towards the tails of the population distribution. This study demonstrates the role of rare SNPs in the phenotypic variation of DNAm, and the effect of extreme levels of DNAm on gene expression