The Production and Consumption of Medical Knowledge in Seventeenth-Century Russia: The Apothecary Chancery

This thesis explores the importance of Western knowledge at the Russian court from the 1620s to the 1700s. After the disorder of the Time of Troubles the Russian court, under pressure from ambitious neighbours, sought to use elements of Western European learning and skill to further reconstruction. Reconstruction developed into an expansion of state powers over Russian life, facilitated by the growing system of courtly departments that were partly staffed by foreign experts. Consequently, this thesis engages with debates concerning how Russians related to Westerners and Western ideas. Here these debates will be reassessed through an examination of the reports and other texts Western experts produced for the court. Foreign influence was especially significant in shaping medicine: the court medical department – the Apothecary Chancery – was staffed with foreign medical practitioners overseen by Russian officials. The Apothecary Chancery medical practitioners produced reports on a range of subjects linked to medicine: medicaments, patient examinations and autopsies. Reports were commonly linked to the wider concerns of the court, such as autopsies on politically or diplomatically important people. The Apothecary Chancery also produced texts aimed at affecting the lives of Muscovites outside the court, such as reports on witchcraft and the sale of medicines, as well as medical recipe books aimed at educating Russians. This dissertation examines the production and consumption of these reports and medical recipe books by the Russian court. It studies the intellectual context and sources that guided the foreign medical practitioners in fashioning their reports. It also scrutinises the purposes for which the Russian court commissioned such texts, and the modifications of the medical practitioners’ views to suit their purposes. This thesis shows Russian interaction with Western ideas to have been selective and critical

Complete bilayer adsorption of C16TAB on the surface of mica using neutron reflection.

We present neutron reflection data from an alkylammonium surfactant (C16TAB) at the mica/water interface. The system is studied in situ in a noninvasive manner and indicates the formation of a complete adsorbed bilayer with little evidence of defects. A detailed analysis suggests that the data are not consistent with some other previously reported adsorbed structures, such as micelles or cylinders.BPThis is the accepted manuscript. The final version is available at http://pubs.acs.org/doi/full/10.1021/acs.jpcb.5b00397

Secondary structure in the core of amyloid fibrils formed from human βm and its truncated variant Δn6

Amyloid fibrils formed from initially soluble proteins with diverse sequences are associated with an array of human diseases. In the human disorder, dialysis-related amyloidosis (DRA), fibrils contain two major constituents, full-length human β-microglobulin (hβm) and a truncation variant, ΔN6 which lacks the N-terminal six amino acids. These fibrils are assembled from initially natively folded proteins with an all antiparallel β-stranded structure. Here, backbone conformations of wild-type hβm and ΔN6 in their amyloid forms have been determined using a combination of dilute isotopic labeling strategies and multidimensional magic angle spinning (MAS) NMR techniques at high magnetic fields, providing valuable structural information at the atomic-level about the fibril architecture. The secondary structures of both fibril types, determined by the assignment of ∼80% of the backbone resonances of these 100- and 94-residue proteins, respectively, reveal substantial backbone rearrangement compared with the location of β-strands in their native immunoglobulin folds. The identification of seven β-strands in hβm fibrils indicates that approximately 70 residues are in a β-strand conformation in the fibril core. By contrast, nine β-strands comprise the fibrils formed from ΔN6, indicating a more extensive core. The precise location and length of β-strands in the two fibril forms also differ. The results indicate fibrils of ΔN6 and hβm have an extensive core architecture involving the majority of residues in the polypeptide sequence. The common elements of the backbone structure of the two proteins likely facilitates their ability to copolymerize during amyloid fibril assembly

A randomized control trial evaluating fluorescent ink versus dark ink tattoos for breast radiotherapy.

OBJECTIVE: The purpose of this UK study was to evaluate interfraction reproducibility and body image score when using ultraviolet (UV) tattoos (not visible in ambient lighting) for external references during breast/chest wall radiotherapy and compare with conventional dark ink. METHODS: In this non-blinded, single-centre, parallel group, randomized control trial, patients were allocated to receive either conventional dark ink or UV ink tattoos using computer-generated random blocks. Participant assignment was not masked. Systematic (∑) and random (σ) setup errors were determined using electronic portal images. Body image questionnaires were completed at pre-treatment, 1 month and 6 months to determine the impact of tattoo type on body image. The primary end point was to determine that UV tattoo random error (σsetup) was no less accurate than with conventional dark ink tattoos, i.e. <2.8 mm. RESULTS: 46 patients were randomized to receive conventional dark or UV ink tattoos. 45 patients completed treatment (UV: n = 23, dark: n = 22). σsetup for the UV tattoo group was <2.8 mm in the u and v directions (p = 0.001 and p = 0.009, respectively). A larger proportion of patients reported improvement in body image score in the UV tattoo group compared with the dark ink group at 1 month [56% (13/23) vs 14% (3/22), respectively] and 6 months [52% (11/21) vs 38% (8/21), respectively]. CONCLUSION: UV tattoos were associated with interfraction setup reproducibility comparable with conventional dark ink. Patients reported a more favourable change in body image score up to 6 months following treatment. Advances in knowledge: This study is the first to evaluate UV tattoo external references in a randomized control trial

Transglutaminase 2 limits the extravasation and the resultant myocardial fibrosis associated with factor XIII-A deficiency

Background and aims Transglutaminase (TG) 2 and Factor (F) XIII-A have both been implicated in cardiovascular protection and repair. This study was designed to differentiate between two competing hypotheses: that TG2 and FXIII-A mediate these functions in mice by fulfilling separate roles, or that they act redundantly in this respect. Methods Atherosclerosis was assessed in brachiocephalic artery plaques of fat-fed mixed strain apolipoprotein (Apo)e deficient mice that lacked either or both transglutaminases. Cardiac fibrosis was assessed both in the mixed strain mice and also in C57BL/6J Apoe expressing mice lacking either or both transglutaminases. Results No difference was found in the density of buried fibrous caps within brachiocephalic plaques from mice expressing or lacking these transglutaminases. Cardiac fibrosis developed in both Apoe/F13a1 double knockout and F13a1 single knockout mice, but not in Tgm2 knockout mice. However, concomitant Tgm2 knockout markedly increased fibrosis, as apparent in both Apoe/Tgm2/F13a1 knockout and Tgm2/F13a1 knockout mice. Amongst F13a1 knockout and Tgm2/F13a1 knockout mice, the extent of fibrosis correlated with hemosiderin deposition, suggesting that TG2 limits the extravasation of blood in the myocardium, which in turn reduces the pro-fibrotic stimulus. The resulting fibrosis was interstitial in nature and caused only minor changes in cardiac function. Conclusions These studies confirm that FXIII-A and TG2 fulfil different roles in the mouse myocardium. FXIII-A protects against vascular leakage while TG2 contributes to the stability or repair of the vasculature. The protective function of TG2 must be considered when designing clinical anti-fibrotic therapies based upon FXIII-A or TG2 inhibition

Correction: External validation of risk prediction models for incident colorectal cancer using UK Biobank.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Patient experience of NHS health checks: a systematic review and qualitative synthesis

$\textbf{Objective:}$ To review the experiences of patients attending NHS Health Checks in England. $\textbf{Design:}$ A systematic review of quantitative and qualitative studies with a thematic synthesis of qualitative studies. $\textbf{Data sources:}$ An electronic literature search of Medline, Embase, Health Management Information Consortium, Cumulative Index of Nursing and Allied Health Literature, Global Health, PsycInfo, Web of Science, OpenGrey, the Cochrane Library, National Health Service (NHS) Evidence, Google Scholar, Google, Clinical Trials.gov and the ISRCTN registry to 09/11/16 with no language restriction and manual screening of reference lists of all included papers. $\textbf{Inclusion criteria:}$ Primary research reporting experiences of patients who have attended NHS Health Checks. $\textbf{Results:}$ 20 studies met the inclusion criteria, 9 reporting quantitative data and 15 qualitative data. There were consistently high levels of reported satisfaction in surveys, with over 80% feeling that they had benefited from an NHS Health Check. Data from qualitative studies showed that the NHS Health Check had been perceived to act as a wake-up call for many who reported having gone on to make substantial lifestyle changes which they attributed to the NHS Health Check. However, some had been left with a feeling of unmet expectations, were confused about or unable to remember their risk scores, found the lifestyle advice too simplistic and non-personalised or were confused about follow-up. $\textbf{Conclusions:}$ While participants were generally very supportive of the NHS Health Check programme and examples of behaviour change were reported, there are a number of areas where improvements could be made. These include greater clarity around the aims of the programme within the promotional material, more proactive support for lifestyle change and greater appreciation of the challenges of communicating risk and the limitations of relying on the risk score alone as a trigger for facilitating behaviour change.This work was funded by a grant from Public Health England. JUS was funded by an NIHR Clinical Lectureship and FW by an NIHR Clinician Scientist award

Human cryptochrome exhibits light-dependent magnetosensitivity

Humans are not believed to have a magnetic sense, even though many animals use the Earth's magnetic field for orientation and navigation. One model of magnetosensing in animals proposes that geomagnetic fields are perceived by light-sensitive chemical reactions involving the flavoprotein cryptochrome (CRY). Here we show using a transgenic approach that human CRY2, which is heavily expressed in the retina, can function as a magnetosensor in the magnetoreception system of Drosophila and that it does so in a light-dependent manner. The results show that human CRY2 has the molecular capability to function as a light-sensitive magnetosensor and reopen an area of sensory biology that is ready for further exploration in humans

Delivery and impact of the NHS Health Check in the first 8 years: a systematic review

Background: Since 2009, all eligible persons in England have been entitled to an NHS Health Check. Uncertainty remains about who attends, and the health-related impacts. Aim: To review quantitative evidence on coverage (the proportion of eligible individuals who attend), uptake (proportion of invitees who attend), and impact of NHS Health Checks. Design and setting: A systematic review and quantitative data synthesis. Included were studies or data reporting coverage or uptake and studies reporting any health-related impact that used an appropriate comparison group or before- and-after study design. Method: Eleven databases and additional internet sources were searched to November 2016. Results: Twenty-six observational studies and one additional dataset were included. Since 2013, 45.6% of eligible individuals have received a health check. Coverage is higher among older people, those with a family history of coronary heart disease, those living in the most deprived areas, and some ethnic minority groups. Just under half (48.2%) of those invited have taken up the invitation. Data on uptake and impact (especially regarding health-related behaviours) are limited. Uptake is higher in older people and females, but lower in those living in the most deprived areas. Attendance is associated with small increases in disease detection, decreases in modelled cardiovascular disease risk, and increased statin and antihypertensive prescribing. Conclusion: Published attendance, uptake, and prescribing rates are all lower than originally anticipated, and data on impact are limited, with very few studies reporting the effect of attendance on health-related behaviours. High-quality studies comparing matched attendees and non-attendees and health economic analyses are required