James I and the performance and representation of royalty

This thesis explores how James I performed and represented his royalty in two key areas. The first is his engagement with the European tradition of magnificence, which was a central aspect of Renaissance court culture, in such areas as public appearance and liberality. The second is his self-representation in his writings. James prioritised verbal over visual forms of self-representation and portrayed himself as a Writer-King, and these are amongst the most distinctive aspects of his kingship. The thesis examines a range of primary sources, principally James’s writings but also contemporary responses to the king’s self-representation, such as letters and ambassadorial reports, and engages with other critical and historical studies. The gaps and misapprehensions in accounts of James that this thesis contributes towards rectifying derive from several general tendencies. There has been an over-reliance on the early historiography of James, a lack of work on the Scottish and European contexts for his self-representation in England, and little attention paid to his writings. This thesis combines the close reading of the ‘literary’ approach with the attention to context of the ‘historical’ approach, placing the discussion of James’s self-representation within the cultural and political contexts of Scotland and England, and considering his cultural and political engagement with continental Europe. It has four main chapters, one on James’s background in Scotland, one on his performance of the role of magnificent king in England, and two on the writings he wrote or republished in England. The discussion reveals that in Scotland James developed tendencies, strategies, and anxieties that would continue into his English reign, and argues that negative perceptions of him in England derived largely from a clash between the style he had developed and the expectations of his new subjects. It examines James’s attempts to combine authorship and authority and reveals their problematic relationship. The discussion suggests that James was aware of the importance of effective self-representation, but his style, the clash of expectations, and problems inherent in the representation of royalty, meant that his attempts to reinforce his image risked undermining and demystifying the king

Routine resite of peripheral intravenous devices every 3 days did not reduce complications compared with clinically indicated resite: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Peripheral intravenous device (IVD) complications were traditionally thought to be reduced by limiting dwell time. Current recommendations are to resite IVDs by 96 hours with the exception of children and patients with poor veins. Recent evidence suggests routine resite is unnecessary, at least if devices are inserted by a specialised IV team. The aim of this study was to compare the impact of peripheral IVD 'routine resite' with 'removal on clinical indication' on IVD complications in a general hospital without an IV team.</p> <p>Methods</p> <p>A randomised, controlled trial was conducted in a regional teaching hospital. After ethics approval, 362 patients (603 IVDs) were randomised to have IVDs replaced on clinical indication (185 patients) or routine change every 3 days (177 patients). IVDs were inserted and managed by the general hospital medical and nursing staff; there was no IV team. The primary endpoint was a composite of IVD complications: phlebitis, infiltration, occlusion, accidental removal, local infection, and device-related bloodstream infection.</p> <p>Results</p> <p>IVD complication rates were 68 per 1,000 IVD days (clinically indicated) and 66 per 1,000 IVD days (routine replacement) (<it>P </it>= 0.86; HR 1.03; 95% CI, 0.74-1.43). Time to first complication per patient did not differ between groups (KM with log rank, <it>P </it>= 0.53). There were no local infections or IVD-related bloodstream infections in either group. IV therapy duration did not differ between groups (<it>P </it>= 0.22), but more (<it>P </it>= 0.004) IVDs were placed per patient in the routine replacement (mean, 1.8) than the clinical indication group (mean, 1.5), with significantly higher hospital costs per patient (<it>P </it>< 0.001).</p> <p>Conclusions</p> <p>Resite on clinical indication would allow one in two patients to have a single cannula per course of IV treatment, as opposed to one in five patients managed with routine resite; overall complication rates appear similar. Clinically indicated resite would achieve savings in equipment, staff time and patient discomfort. There is growing evidence to support the extended use of peripheral IVDs with removal only on clinical indication.</p> <p>Registration number</p> <p>Australian New Zealand Clinical Trials Registry (ANZCTR) Number ACTRN12608000421336.</p

Assessing impact of ICT intercultural work

This article reports on a school-based ICT initiative, called Dissolving Boundaries (DB) which links primary, (students aged 5-11), post-primary (students aged 12-18) and special schools (students aged 5-18) in partnerships across the border between Northern Ireland and the Republic of Ireland. The aim of the research was to investigate if participation in DB was associated with an increased awareness and understanding of life on the other side of the border. The ICT skills of students were also probed. Two cohorts of students were used in the study, one which had taken part in the Dissolving Boundaries program during an academic year and another cohort of similar age in the same schools, which had not taken part. Findings suggest that participation in the program contributed to students’ knowledge and awareness in general of the other jurisdiction. In terms of collaborative work, a large majority of DB students agreed that they could learn something new from working with another school. Participating students in the DB program showed much higher competence in those ICT skills associated with communication and collaboration than their non-participant peers

A self-consistent, multi-variate method for the determination of gas phase rate coefficients, applied to reactions of atmospheric VOCs and the hydroxyl radical

Gas-phase rate coefficients are fundamental to understanding atmospheric chemistry, yet experimental data are not available for the oxidation reactions of many of the thousands of volatile organic compounds (VOCs) observed in the troposphere. Here a new experimental method is reported for the simultaneous study of reactions between multiple different VOCs and OH, the most important daytime atmospheric radical oxidant. This technique is based upon established relative rate concepts but has the advantage of a much higher throughput of target VOCs. By evaluating multiple VOCs in each experiment, and through measurement of the depletion in each VOC after reaction with OH, the OH + VOC reaction rate coefficients can be derived. Results from experiments conducted under controlled laboratory conditions were in good agreement with the available literature for the reaction of nineteen VOCs, prepared in synthetic gas mixtures, with OH. This approach was used to determine a rate coefficient for the reaction of OH with 2,3-dimethylpent-1-ene for the first time; k = 5.7 (±0.3) × 10–11–cm3 molecule−1 s−1. In addition, a further seven VOCs had only two, or fewer, individual OH rate coefficient measurements available in the literature. The results from this work were in good agreement with those measurements. A similar dataset, at an elevated temperature of 323 (±10) K, was used to determine new OH rate coefficients for twelve aromatic, five alkane, five alkene and three monoterpene VOC + OH reactions. In OH relative reactivity experiments that used ambient air at the University of York, a large number of different VOCs were observed, of which 23 were positively identified. 19 OH rate coefficients were derived from these ambient air samples, including ten reactions for which data was previously unavailable at the elevated reaction temperature of T = 323 (±10) K

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Comparison between first and second wave of COVID-19 outbreak in older people. The COPE multicentre European observational cohort study

Background: Effective shielding measures and virus mutations have progressively modified the disease between the waves, likewise health care systems have adapted to the outbreak. Our aim was to compare clinical outcomes for older people with COVID-19 in Wave 1 (W1) and 2 (W2). Methods: All data, including the Clinical Frailty Scale (CFS), were collected for COVID-19 consecutive patients, aged ≥65, from thirteen hospitals, in W1 (February-June 2020) and W2 (October 2020-March 2021). The primary outcome was mortality (time to mortality and 28-day mortality). Data were analysed with multilevel Cox proportional hazards, linear and logistic regression models, adjusted for wave baseline demographic and clinical characteristics. Results: Data from 611 people admitted in W2 were added to and compared with data collected during W1 (N = 1340). Patients admitted in W2 were of similar age, median [IQR], W2 = 79 [73-84]; W1 = 80 [74-86]; had a greater proportion of men (59.4% vs 53.0%); had lower 28-day mortality (29.1% vs 40.0%), compared to W1. For combined W1-W2 sample, W2 was independently associated with improved survival: time-to-mortality aHR= 0.78 (95%CI 0.65-0.93), 28-day mortality aOR = 0.80 (95%CI 0.62-1.03). W2 was associated with increased length of hospital stay aHR = 0.69 (95%CI 0.59-0.81). Patients in W2 were less frail, CFS (adjusted mean difference [aMD]=-0.50, 95%CI -0.81, -0.18), as well as presented with lower CRP (aMD=-22.52, 95%CI -32.00, -13.04). Conclusions: COVID-19 older adults in W2 were less likely to die than during W1. Patients presented to hospital during W2 were less frail and with lower disease severity and less likely to have renal decline

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication