Early History of The Royal College of Physicians of Edinburgh

Factors that led to the award of the College’s Royal Charter . The definitive history of the College written in 1976 by Craig runs to over 1,100 pages, and that by Ritchie in 1899 is also substantial.1 It is unlikely therefore that this account could be other than a very brief chronology of the principal events associated with the Royal College of Physicians of Edinburgh between the early 17lh century and the present time. While the College eventually received its Royal Charter in 1681 this was only after three previous abortive attempts had been made in 1617, 1630 and again in 1656. These various attempts were each made by small groups of dedicated physicians, all of whom had received their medical training on the Continent. On returning to Edinburgh, they particularly wished to elevate the status of their city, and the standard of medical practice in Scotland, but particularly in Edinburgh and its surrounding area. They were certainly aware that the standard of medical practice was without question far lower than it was on the Continent and even in England at that time. The award of a Royal Charter would also undoubtedly elevate the status of the Physicians as a corporate entity from the others that practised medicine in the same area. The Physicians in Edinburgh also believed that they would be in a similar position to their clinical brethren in London who had received their Royal Charter in 1518. Considerable difficulties were encountered over the years, however, before the Edinburgh physicians successfully obtained their Royal Charter. These came from a number of quarters, but particularly from the Edinburgh Surgeons, from the Church, from factions within the Town Council and from the University

Two Diplomas Awarded to George Joseph Bell now in the Possession of the Royal Medical Society

The two earliest diplomas in the possession of the Royal Medical Society were both awarded to George Joseph Bell, BA Oxford. One of these diplomas was his Extraordinary Membership Diploma that was awarded to him on 5 April 1839. Very few of these Diplomas appear to have survived, and the critical introductory part of his Diploma is inscribed as follows:Ingenuus ornatissimusque Vir Georgius Jos. Bell dum socius nobis per tres annos interfuit, plurima eademque pulcherrima, hand minus ingenii f elicis, quam diligentiae insignis, animique ad optimum quodque parati, exempla in medium protulit. In quorum fidem has literas, meritis tantum concessus, manibus nostris sigilloque munitas, discedenti lubentissime donatus.2 Edinburgi 5 Aprilis 1839.

Peter David Handyside’s Diploma as Senior President of the Royal Medical Society

Over the last few years, the author of this article was fortunate to be offered and purchased two diplomas dating from the first half of the 19th century. Both were awarded to Peter David Handyside1 (1808-81). He had graduated in medicine in 1831 with the Edinburgh M.D. degree. Shortly after he graduated, he pursued his anatomical studies, initially in Paris and then in Heidelberg under the distinguished physician Friedrich (or Frederick) Tiedemann (1781-1861). It is believed that his earlier apprenticeship under James Syme (1799-1870) had stimulated his interest in both Anatomy and Surgery. He was awarded the FRCS Edin. (Fellowship of the Royal College of Surgeons of Edinburgh) diploma in August of 1833, and was for most of the rest of his career a practising surgeon. The subject of his probationary essay was Osteo-aneurism, and this was dedicated to Tiedemann. He commenced the teaching of Anatomy in Edinburgh in the summer of 1834, and was, on and off, for over 45 years a teacher of this subject at the Edinburgh Extra-mural School. He taught this subject until a few weeks before his death. While a medical student, he was elected Senior President of the Royal Medical Society during the Society’s 92nd Session (1828-29). He had also been awarded the Harveian Society medal in 1827, and was in 1837 appointed Secretary of the Harveian Society. During the same year, he was elected to a Fellowship of the Royal Society of Edinburgh, while in 1871 he was elected President  f the Medico-Chirurgical Society of Edinburgh

An engraving entitled: “Melbourne Place and Victoria Terrace from George IV Bridge"

I thought that the members of the Society might be interested in learning about an “engraving” that hangs rather inauspiciously on one of the walls of the Society’s Library in Bristo Place (figure 1). This item is of interest in several regards, but principally because no copy of it is available in the Reference Collection of the Royal Commission on Ancient and Historical Monuments of Scotland (RCAHMS) in Bernard Terrace, Edinburgh

Dependence of Hippocampal Function on ERRγ-Regulated Mitochondrial Metabolism

SummaryNeurons utilize mitochondrial oxidative phosphorylation (OxPhos) to generate energy essential for survival, function, and behavioral output. Unlike most cells that burn both fat and sugar, neurons only burn sugar. Despite its importance, how neurons meet the increased energy demands of complex behaviors such as learning and memory is poorly understood. Here we show that the estrogen-related receptor gamma (ERRγ) orchestrates the expression of a distinct neural gene network promoting mitochondrial oxidative metabolism that reflects the extraordinary neuronal dependence on glucose. ERRγ−/− neurons exhibit decreased metabolic capacity. Impairment of long-term potentiation (LTP) in ERRγ−/− hippocampal slices can be fully rescued by the mitochondrial OxPhos substrate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ in cerebral cortex and hippocampus exhibit defects in spatial learning and memory. These findings implicate neuronal ERRγ in the metabolic adaptations required for memory formation

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen

Background Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures