Raman Spectroscopy of Liquid-Based Cervical Smear Samples as a Triage to Stratify Women Who Are HPV-Positive on Screening

Persistent high-risk human papillomavirus (HPV) infection can lead to cervical precancer and cancer. Recently, HPV testing has been introduced for primary cervical screening, but the HPV DNA test cannot distinguish between transient and persistent HPV infection. Thus, there is an unmet clinical need to develop a new test to identify women with a high-risk persistent HPV infection. Raman spectra were recorded from cervical smear samples (n = 60) and, on the basis of HPV DNA and HPV mRNA test results, a classifier was developed to identify persistent HPV infection. A further blinded independent test set (n = 14) was used to validate the model, and sensitivity of 90% and specificity of 100% were achieved. Improved triage would allow women with a high-risk persistent HPV infection to be referred for immediate treatment, while women with a low-risk transient infection could avoid overtreatment

The histone chaperones Vps75 and Nap1 form ring-like, tetrameric structures in solution

NAP-1 fold histone chaperones play an important role in escorting histones to and from sites of nucleosome assembly and disassembly. The two NAP-1 fold histone chaperones in budding yeast, Vps75 and Nap1, have previously been crystalized in a characteristic homodimeric conformation. In this study, a combination of small angle X-ray scattering, multi angle light scattering and pulsed electron–electron double resonance approaches were used to show that both Vps75 and Nap1 adopt ring-shaped tetrameric conformations in solution. This suggests that the formation of homotetramers is a common feature of NAP-1 fold histone chaperones. The tetramerisation of NAP-1 fold histone chaperones may act to shield acidic surfaces in the absence of histone cargo thus providing a ‘self-chaperoning’ type mechanism

Real world hospital costs following stress echocardiography in the UK: a costing study from the EVAREST/BSE-NSTEP multi-entre study

Background: Stress echocardiography is widely used to detect coronary artery disease, but little evidence on downstream hospital costs in real-world practice is available. We examined how stress echocardiography accuracy and downstream hospital costs vary across NHS hospitals and identifed key factors that afect costs to help inform future clinical planning and guidelines. Methods: Data on 7636 patients recruited from 31 NHS hospitals within the UK between 2014 and 2020 as part of EVAREST/BSE-NSTEP clinical study, were used. Data included all diagnostic tests, procedures, and hospital admissions for 12 months after a stress echocardiogram and were costed using the NHS national unit costs. A decision tree was built to illustrate the clinical pathway and estimate average downstream hospital costs. Multi-level regression analysis was performed to identify variation in accuracy and costs at both patient, procedural, and hospital level. Linear regression and extrapolation were used to estimate annual hospital cost-savings associated with increasing predictive accuracy at hospital and national level. Results: Stress echocardiography accuracy varied with patient, hospital and operator characteristics. Hypertension, presence of wall motion abnormalities and higher number of hospital cardiology outpatient attendances annually reduced accuracy, adjusted odds ratio of 0.78 (95% CI 0.65 to 0.93), 0.27 (95% CI 0.15 to 0.48), 0.99 (95% CI 0.98 to 0.99) respectively, whereas a prior myocardial infarction, angiotensin receptor blocker medication, and greater operator experience increased accuracy, adjusted odds ratio of 1.77 (95% CI 1.34 to 2.33), 1.64 (95% CI 1.22 to 2.22), and 1.06 (95% CI 1.02 to 1.09) respectively. Average downstream costs were £646 per patient (SD 1796) with signifcant variation across hospitals. The average downstream costs between the 31 hospitals varied from £384–1730 per patient. False positive and false negative tests were associated with average downstream costs of £1446 (SD £601) and £4192 (SD 3332) respectively, driven by increased non-elective hospital admissions, adjusted odds ratio 2.48 (95% CI 1.08 to 5.66), 21.06 (95% CI 10.41 to 42.59) respectively. We estimated that an increase in accuracy by 1 percentage point could save the NHS in the UK £3.2 million annually. Conclusion: This study provides real-world evidence of downstream costs associated with stress echocardiography practice in the UK and estimates how improvements in accuracy could impact healthcare expenditure in the NHS. A real-world downstream costing approach could be adopted more widely in evaluation of imaging tests and interventions to refect actual value for money and support realistic planning

The histone chaperones Vps75 and Nap1 form ring-like, tetrameric structures in solution

MRC [G1100021]; Wellcome Senior Fellowship [095062]. Source of open access funding: The Wellcome Trust [094090].NAP-1 fold histone chaperones play an important role in escorting histones to and from sites of nucleosome assembly and disassembly. The two NAP-1 fold histone chaperones in budding yeast, Vps75 and Nap1, have previously been crystalized in a characteristic homodimeric conformation. In this study, a combination of small angle X-ray scattering, multi angle light scattering and pulsed electron-electron double resonance approaches were used to show that both Vps75 and Nap1 adopt ring-shaped tetrameric conformations in solution. This suggests that the formation of homotetramers is a common feature of NAP-1 fold histone chaperones. The tetramerisation of NAP-1 fold histone chaperones may act to shield acidic surfaces in the absence of histone cargo thus providing a 'self-chaperoning' type mechanism.Publisher PDFPeer reviewe

Predicting Solar Power and Energy Production Over the Course of a Full Day

The majority of air and ground vehicle systems are reliant on specialized diesel fuel. This reliance increases the likelihood that operations may be operating in an energy constrained or contested environment given the state of international relations between global energy providers and consumers. Such a vulnerability has the potential to reduce operational effectiveness or efficiency if logistical supply chains were interrupted or impeded. The most effective and efficient methodology to reduce reliance on specialized diesel fuel is to hybridize our energy and power (E&P) systems, and support more diverse E&P solutions including renewable energy generation (photovoltaic (PV) arrays, wind generation, wave energy converters), nuclear, or decaying isotopes. In this paper/presentation, we present our advances in developing a set of predictive artificial intelligence and machine learning (AI/ML) algorithms that forecast E&P capabilities of a photovoltaic array indirectly and directly. These milestones are a product of two separate types of AI/ML approaches: (1) developing AI/ML based algorithms that predict ambient and panel temperature from various atmosphericbased sensor data which can then be used in combination with an irradiance profile and a MATLAB Simulink model to predict the E&P capabilities of the PV array (indirect method), and (2) developing AI/ML which predicts the resulting E&P capabilities of the PV array, using various atmospheric-based sensor data (direct method)

Development and Validation of a Raman Spectroscopic Classification Model for Cervical Intraepithelial Neoplasia (CIN)

The mortality associated with cervical cancer can be reduced if detected at the precancer stage, but current methods are limited in terms of subjectivity, cost and time. Optical spectroscopic methods such as Raman spectroscopy can provide a rapid, label-free and nondestructive measurement of the biochemical fingerprint of a cell, tissue or biofluid. Previous studies have shown the potential of Raman spectroscopy for cervical cancer diagnosis, but most were pilot studies with small sample sizes. The aim of this study is to show the clinical utility of Raman spectroscopy for identifying cervical precancer in a large sample set with validation in an independent test set. Liquid-based cervical cytology samples (n = 662) (326 negative, 200 cervical intraepithelial neoplasia (CIN)1 and 136 CIN2+) were obtained as a training set. Raman spectra were recorded from single-cell nuclei and subjected to a partial least squares discriminant analysis (PLSDA). In addition, the PLSDA classification model was validated using a blinded independent test set (n = 69). A classification accuracy of 91.3% was achieved with only six of the blinded samples misclassified. This study showed the potential clinical utility of Raman spectroscopy with a good classification of negative, CIN1 and CIN2+ achieved in an independent test set

Novel use of nanofiltered hyposaline water to control sea lice (Lepeophtheirus salmonis and Caligus elongatus) and amoebic gill disease, on a commercial Atlantic salmon (Salmo salar) farm

Infestations by the salmon louse (Lepeophtheirus salmonis) and amoebic gill disease (AGD) are currently significant disease concerns facing the Atlantic salmon aquaculture industry in Ireland. Increasing seawater temperatures, and the move away from chemotherapeutants has prompted a new approach to researching areas of host-parasite life histories and using the physiology and behaviour of the parasites to develop novel control methods. Freshwater, with a low ionic concentration can be used to control sea lice and AGD but this may not always be available. Alternative treatments with hydrogen peroxide can prove toxic at the higher summer water temperatures experienced at this latitude. The aim of this study was to determine the efficacy of using nano-filtered hyposaline water as a non-medicinal method to reduce sea lice (L. salmonis and Caligus elongatus) infestation levels and amoebic gill disease under commercial conditions on an Atlantic salmon farm. To achieve this salmon were bathed in a tarpaulin filled with 5 ppt hyposaline water for 4.5 h and a regime of prophylactic bath treatments put in place to follow the production cycle. The nano-filtration unit consistently produced low saline water and resulted in a significant reduction of sea lice levels and AGD following routine 4.5 h baths. A 4.5 h bioassay of detached salmon lice confirmed both hyposaline and freshwater were equally effective against L. salmonis in the absence of the host

Marking out the pitch: a historiography and taxonomy of football fiction

Football, or soccer as it is more commonly referred to in Australia and the US, is arguably the world’s most popular sport. It generates a proportionate volume of related writing. Within this landscape, works of novel-length fiction are seemingly rare. This paper establishes and maps a substantial body of football fiction works, explores elements and qualities exhibited individually and collectively. In bringing together current, limited surveys of the field, it presents the first rigorous definition of football fiction and captures the first historiography of the corpus. Drawing on distant reading methods developed in conjunction with closer textual analyses, the historiography and subsequent taxonomy represent the first articulation of relationships across the body of work, identify growth areas and establish a number of movements and trends. In advancing the understanding of football fiction as a collective body, the paper lays foundations for further research and consideration of the works in generic terms