Recent studies suggest that one or more genes on chromosome 5q21 are important for the development of colorectal cancers, particularly those associated with familial adenomatous polyposis (FAP). To facilitate the identification of genes from this locus, a portion of the region that is tightly linked to FAP was cloned. Six contiguous stretches of sequence (contigs) containing approximately 5.5 Mb of DNA were isolated. Subclones from these contigs were used to identify and position six genes, all of which were expressed in normal colonic mucosa. Two of these genes (APC and MCC) are likely to contribute to colorectal tumorigenesis. The MCC gene had previously been identified by virtue of its mutation in human colorectal tumors. The APC gene was identified in a contig initiated from the MCC gene and was found to encode an unusually large protein. These two closely spaced genes encode proteins predicted to contain coiled-coil regions. Both genes were also expressed in a wide variety of tissues. Further studies of MCC and APC and their potential interaction should prove useful for understanding colorectal neoplasia.

With mass covid-19 vaccination efforts under way in many countries, including the UK, we need to understand and redress the disparities in its uptake. Data to 14 February 2021 show that over 90% of adults in Britain have received or would be likely to accept the covid-19 vaccine if offered. 1 However, surveys have indicated much greater vaccine hesitancy among people from some ethnic minorities. 2-4 In a UK survey in December 2020, vaccine hesitancy was highest among black (odds ratio 12.96, 95% confidence interval 7.34 to 22.89), Bangladeshi, and Pakistani (both 2.31, 1.55 to 3.44) populations compared with people from a white ethnic background. 5 Even more worryingly, data up to 15 January 2021 show substantially lower rates of covid-19 vaccinations among over 80s in ethnic minority (white people 42.5%, black people 20.5%) and deprived communities (least deprived 44.7%, most deprived 37.9%) in England. 6 Similarly, data from an NHS trust show lower covid-19 vaccination rates among ethnic minority healthcare workers (70.9% in white workers v 58.5% in South Asian and 36.8% in black workers; P<0.001 for both). 7

We have developed a method whereby a single TaqMan™ probe can be used for many PCR reactions. We demonstrate its application as an integrated system for the direct measurement of allele-specific amplicon generation coupled to the suppression of primer-dimer accumulation in PCR. The system uses a 5′-exonuclease assay of amplicon annealed fluorogenic probes that operates in conjunction with the Amplification Refractory Mutation System, whereby relative changes in reporter fluorescent emission are monitored in real-time using an analytical thermal cycler. We have called this system Three-STAR, and it is universal in that it can either use a single probe for the detection of any one target DNA sequence or a single pair of probes for genotyping any bi-allelic polymorphism. Three-STAR is, therefore, particularly useful for the single-tube genotype analysis of a variety of human DNA polymorphisms and mutations.

Despite their brief and often jocular nature, #TipsForNewDocs tweets provided meaningful advice for newcomers to the profession, often focusing on tacit learning and professional socialisation. Hashtag-driven enquiries can be a valuable and time-efficient way of accessing and sharing tacitly held knowledge. Social media content analysis can provide valuable insights into key educational issues.

Introduction cardiovascular disease (CVD) and chronic inflammation are implicated in the development of frailty. Longitudinal analyses of inflammatory markers, biomarkers of cardiac dysfunction and incidence of frailty are limited. Methods in the British Regional Heart Study, 1,225 robust or pre-frail men aged 71–92 years underwent a baseline examination, with questionnaire-based frailty assessment after 3 years. Frailty definitions were based on the Fried phenotype. Associations between incident frailty and biomarkers of cardiac dysfunction (high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP)) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) were examined, by tertile, with the lowest as reference. Results follow-up data were available for 981 men. Ninety one became frail. Adjusted for age, pre-frailty, prevalent and incident CVD, comorbidity, polypharmacy and socioeconomic status, IL-6 (third tertile OR 2.36, 95% CI 1.07–5.17) and hs-cTnT (third tertile OR 2.24, 95% CI 1.03–4.90) were associated with increased odds of frailty. CRP (third tertile OR 1.83, 95% CI 0.97–4.08) and NT-proBNP (second tertile OR 0.48, 95% CI 0.23–1.01) showed no significant association with incident frailty. The top tertiles of CRP, IL-6, hscTnT and NT-proBNP were strongly associated with mortality prior to follow-up. Conclusion IL-6 is associated with incident frailty, supporting the prevailing argument that inflammation is involved in the pathogenesis of frailty. Cardiomyocyte injury may be associated with frailty risk. Associations between elevated CRP and frailty cannot be fully discounted; NT-proBNP may have a non-linear relationship with incident frailty. CRP, IL-6, hs-cTnT and NT-proBNP are vulnerable to survivorship bias.