Sir Robert Cecil and Elizabethan Intelligencing, 1590-1603

Much scholarly attention has been given to the development of Sir Francis Walsingham’s intelligence-gathering network and how it played an important role in Elizabethan foreign and domestic politics during the 1580s, but little has been attempted for the 1590s. This thesis will argue that the practices and methods that Walsingham laid down did not completely dissipate after his death but in fact continued to be adhered to, most notably in the person of Sir Robert Cecil. It was Cecil who, more than any other Elizabethan in high authority, looked to create his own intelligence-gathering network as he foresaw the benefits of doing so. However, this transition was by no means straightforward, and in fact it can be seen as disjointed. The thesis will also show that the rise of Cecil’s intelligence-gathering network became intertwined with the rise of his political career. It was not until he became principal secretary in July 1596 that the creation of his own network could really proceed apace. The make-up and construction of his intelligence-gathering network will be discussed, as will the backgrounds of the people who worked for Cecil: his secretaries, his agents and message carriers. In sum, it will be shown that Sir Robert Cecil created by 1603 an effective intelligence-gathering network that was put to good use in the final years of Elizabeth’s reign and continued into that of James I

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Signaling from the Secretory Granule to the Nucleus: Uhmk1 and PAM

Neurons and endocrine cells package peptides in secretory granules (large dense-core vesicles) for storage and stimulated release. Studies of peptidylglycine α-amidating monooxygenase (PAM), an essential secretory granule membrane enzyme, revealed a pathway that can relay information from secretory granules to the nucleus, resulting in alterations in gene expression. The cytosolic domain (CD) of PAM, a type 1 membrane enzyme essential for the production of amidated peptides, is basally phosphorylated by U2AF homology motif kinase 1 (Uhmk1) and other Ser/Thr kinases. Proopiomelanocortin processing in AtT-20 corticotrope tumor cells was increased when Uhmk1 expression was reduced. Uhmk1 was concentrated in the nucleus, but cycled rapidly between nucleus and cytosol. Endoproteolytic cleavage of PAM releases a soluble CD fragment that localizes to the nucleus. Localization of PAM-CD to the nucleus was decreased when PAM-CD with phosphomimetic mutations was examined and when active Uhmk1 was simultaneously overexpressed. Membrane-tethering Uhmk1 did not eliminate its ability to exclude PAM-CD from the nucleus, suggesting that cytosolic Uhmk1 could cause this response. Microarray analysis demonstrated the ability of PAM to increase expression of a small subset of genes, including aquaporin 1 (Aqp1) in AtT-20 cells. Aqp1 mRNA levels were higher in wild-type mice than in mice heterozygous for PAM, indicating that a similar relationship occurs in vivo. Expression of PAM-CD also increased Aqp1 levels whereas expression of Uhmk1 diminished Aqp1 expression. The outlines of a pathway that ties secretory granule metabolism to the transcriptome are thus apparent

35th IMAC, A Conference and Exposition on Structural Dynamics 2017

Nonlinear Dynamics, Volume 1: Proceedings of the 35th IMAC, A Conference and Exposition on Structural Dynamics, 2017, the first volume of ten from the Conference brings together contributions to this important area of research and engineering. The collection presents early findings and case studies on fundamental and applied aspects of Nonlinear Dynamics, including papers on: Nonlinear System Identification Nonlinear Modeling &amp; Simulation Nonlinear Reduced-order Modeling Nonlinearity in Practice Nonlinearity in Aerospace Systems Nonlinearity in Multi-Physics Systems Nonlinear Modes and Modal Interactions Experimental Nonlinear Dynamics.Special Topics in Structural Dynamics, Volume 6: Proceedings of the 35th IMAC, A Conference and Exposition on Structural Dynamics, 2017, the sixth volume of ten from the Conference brings together contributions to this important area of research and engineering. The collection presents early findings and case studies on fundamental and applied aspects of Structural Dynamics, including papers on: Experimental Methods Analytical Methods General Dynamics & Modal Analysis General Dynamics & System Identification Damage Detection .Structural Health Monitoring & Damage Detection, Volume 7: Proceedings of the 35th IMAC, A Conference and Exposition on Structural Dynamics, 2017, the seventh volume of ten from the Conference brings together contributions to this important area of research and engineering. The collection presents early findings and case studies on fundamental and applied aspects of Structural Health Monitoring & Damage Detection, including papers on: Structural Health Monitoring Damage Detection System Identification Active Controls.Rotating Machinery, Hybrid Testing, Vibro-Acoustics & Laser Vibrometry, Volume 8: Proceedings of the 35th IMAC, A Conference and Exposition on Structural Dynamics, 2017, the eighth volume of ten from the Conference brings together contributions to this important area of research and engineering. The collection presents early findings and case studies on fundamental and applied aspects of Rotating Machinery, Hybrid Testing, Vibro-Acoustics & Laser Vibrometry, including papers on: Rotating Machinery Vibro-Acoustics Experimental Techniques Advances in Wind Energy Scanning Laser Doppler Vibrometry Methods Hybrid Test Methods.Topics in Modal Analysis & Testing, Volume 10: Proceedings of the 35th IMAC, A Conference and Exposition on Structural Dynamics, 2017, the tenth volume of ten from the Conference brings together contributions to this important area of research and engineering. The collection presents early findings and case studies on fundamental and applied aspects of Modal Analysis, including papers on: Operational Modal & Modal Analysis Applications Experimental Techniques Modal Analysis, Measurements & Parameter Estimation Modal Vectors & Modeling Basics of Modal Analysis Additive Manufacturing & Modal Testing of Printed Parts