'Death and Doctor Hornbook' by Robert Burns: A view from medical history

Robert Burns's poem, Death and Doctor Hornbook, 1785, tells of the drunken narrator's late night encounter with Death. The Grim Reaper is annoyed that ‘Dr Hornbook’, a local schoolteacher who has taken to selling medications and giving medical advice, is successfully thwarting his efforts to gather victims. The poet fears that the local gravedigger will be unemployed but Death reassures him that this will not be the case since Hornbook kills more than he cures. Previous commentators have regarded the poem as a simple satire on amateur doctoring. However, it is here argued that, if interpreted in the light of the exoteric and inclusive character of 18th century medical knowledge and practice, the poem is revealed to have a much broader reference as well as being more subtle and morally ambiguous. It is a satire on 18th century medicine as a whole

Community concepts in plant ecology: from Humboldtian plant geography to the superorganism and beyond

The paper seeks to provide an introduction to, and review of, the history of concepts of the plant community. Eighteenth-century naturalists recognised that vegetation was distributed geographically and that different species of plants and animals were interconnected in what would later be called ecological relationships. It was not, however, until the early nineteenth century that the study of vegetation became a distinctive and autonomous form of scientific inquiry. Humboldt was the first to call communities of plants ‘associations’. His programme for the empirical study of plant communities was extended by many European and North American botanists, throughout the nineteenth and into the twentieth century. There developed an almost complete consensus among ecologists that vegetation was made up of natural communities, discrete entities with real boundaries. However, there was little agreement about the nature of the putative unit or how it should be classified. Gleason advanced the alternative view that vegetation was an assemblage of individual plants with each species being distributed according to its own physiological requirements and competitive interactions. This debate was never wholly resolved and the divergent opinions can be discerned within early ecosystem theory

The baboon endogenous virus genome. II. Provirus sequence variations in baboon cell DNA

Restriction analysis of the approximately 100 integrated baboon endogenous virus (BaEV) proviruses in baboon cells and tissues has revealed two major sequence variations, both in the gag gene region of the genome. One, a 150 nucleotide pair insert, is present in a small proportion of the proviral DNAs of some baboons, but is present in the majority of the proviral DNAs of other baboons. The second, a Bam HI recognition sequence located 2.25 kb from the proviral 5' end, is missing or modified in approximately one-half of the integrated genomes. We consider the possibility that accumulation of proviruses not containing the 0.15 kb insert is correlated with viral activation and expression since it is this form that is a replication intermediate in freshly infected permissive cells. It is evident from these initial studies that the organization of the multiple BaEV proviruses in baboon DNA has undergone modification during evolution

Baboon endogenous virus genome. I. Restriction enzyme map of the unintegrated DNA genome of a primate retrovirus

A detailed restriction map was deduced for the genome of an endogenous retrovirus of a higher primate, that of baboon. The cleavage sites for 12 restriction enzymes were mapped. The unintegrated linear viral DNA intermediate that is produced by infection of permissive cells with baboon endogenous virus was isolated. Hybridization with a strong-stop complementary DNA probe demonstrated presence of a terminal repetition in the linear viral DNA. The positions of restriction sites for two particular enzymes, SmaI and XhoI, near each end were consistent with this result and indicated that the length of the repetition is 0.55 +/- 0.01 kilobase. The linear viral DNA had a unique restriction map indicating that it is not a set of random circular permutations of the RNA genome. From hybridization with a 3'-specific probe, the DNA restriction map was aligned relative to the 5'-to-3' orientation of the viral RNA. We observed a minor heterogeneity in a BamHI recognition site 1.95 kilobases from the right end of the linear map

Baboon endogenous virus genome: Molecular cloning and structural characterization of nondefective viral genomes from DNA of a baboon cell strain

Several heterogeneities in the baboon endogenous virus (BaEV) genomes that are present in the DNA of normal baboon tissues and the baboon cell strain BEF-3 have been described previously. To study these genomes, we cloned BaEV proviruses from BEF-3 cellular DNA into the vector Charon 4A. Of the four full-length clones isolated, one was nondefective as determined by transfection. The sequence of a portion of this clone was found to code for amino acids 61-91 in the p30 region of the gag gene. This identification allowed us to align the restriction map with the BaEV genetic map. One heterogeneity, a BamHI site 2.4 kilobases (kb) from the proviral 5' end, was located close to the gag-pol junction; another, a BamHI site 1.4 kb from the 5' end of the genome, corresponded to the gag p30 coding sequence for amino acids 32-34; and a third, a Xho I site, was near the 3' end of the pol gene. To select the nondefective BaEV genomes from BEF-3 cells, we infected permissive cells with virus produced by BEF-3 cells and also transfected BEF-3 cellular DNA into permissive cells. The BaEV genomes in the permissive recipient cultures were then analyzed by restriction enzyme analysis. These nondefective genomes were found to be heterogeneous with respect to the gag-pol BamHI site and the Xho I site, but all were found to contain the BamHI site 1.4 kb from the 5' end of the genome

Tailored emails prompt electric vehicle owners to engage with tariff switching information

The carbon intensity of the electricity used to charge an electric vehicle (EV) is dependent on when in the day charging occurs. However, persuading EV owners to adopt incentives to charge during off-peak hours is challenging. Here we show that governments could exploit the ‘window of opportunity’ created when people purchase their first EV to promote time-of-use tariffs. Email recipients (n = 7,038 EV owners) were more likely to click-through to an information webpage when the email emphasized specific reductions in home-charging costs versus general bill savings. However, the ‘window of opportunity’ for maximizing potential adoption is short; email open rates declined from over 70% immediately after purchase to 40% for recipients owning their EV for over three months. These results demonstrate the potential of prompts to change behaviours for which opt-out enrolment (where enrolment is automatic unless people explicitly opt out) would be unethical or less effective

PD-L1 testing for lung cancer in the UK: recognizing the challenges for implementation.

A new approach to the management of non-small-cell lung cancer (NSCLC) has recently emerged that works by manipulating the immune checkpoint controlled by programmed death receptor 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Several drugs targeting PD-1 (pembrolizumab and nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved or are in the late stages of development. Inevitably, the introduction of these drugs will put pressure on healthcare systems, and there is a need to stratify patients to identify those who are most likely to benefit from such treatment. There is evidence that responsiveness to PD-1 inhibitors may be predicted by expression of PD-L1 on neoplastic cells. Hence, there is considerable interest in using PD-L1 immunohistochemical staining to guide the use of PD-1-targeted treatments in patients with NSCLC. This article reviews the current knowledge about PD-L1 testing, and identifies current research requirements. Key factors to consider include the source and timing of sample collection, pre-analytical steps (sample tracking, fixation, tissue processing, sectioning, and tissue prioritization), analytical decisions (choice of biomarker assay/kit and automated staining platform, with verification of standardized assays or validation of laboratory-devised techniques, internal and external quality assurance, and audit), and reporting and interpretation of the results. This review addresses the need for integration of PD-L1 immunohistochemistry with other tests as part of locally agreed pathways and protocols. There remain areas of uncertainty, and guidance should be updated regularly as new information becomes available