Bilateral Ocular Myositis Associated with Whipple's Disease

Purpose: To describe the clinical features of a Caucasian female patient with a history of treated gastrointestinal Whipple's disease (WD) who developed new-onset diplopia, with a description of the histopathological features of the extraocular muscle biopsies. Methods: A previously fit 38-year-old Caucasian female presented with acute-onset diplopia after being on a sustained medication regime for biopsy-proven gastrointestinal WD. A magnetic resonance imaging scan of her orbits with gadolinium revealed diffuse enhancement of the bellies of the extraocular muscles bilaterally, particularly the medial rectus, superior rectus, and superior oblique muscles, consistent with an infiltrative myositis. She underwent unilateral extraocular muscle biopsies. Results: The extraocular muscle biopsies contained macrophages between the muscle fibres. These contained periodic acid-Schiff-positive cytoplasmic granules. Immunohistochemistry with an antibody raised to Tropheryma whipplei showed positive staining of the same macrophages. Transmission electron microscopy confirmed the presence of effete T. whipplei cell membranes in lysosomes. Conclusion: This case describes bilateral WD-associated extraocular muscle myositis. The exact mechanism for this unusual presentation is unclear, but both a WD-associated immune reconstitution inflammatory syndrome and treatment failure are possibilities, with a good response observed to antibiotic therapy and adjunctive corticosteroids

Reflections on the Diverse Voices speaker series

The impacts of extreme weather and climate change will, and are, affecting a diversity of people in many different ways. Yet the UK field of weather and climate appears to be generally un-diverse. Besides its importance for innovation in any field, having a diversity of voices in this field is especially vital, given the often unequal impacts of weather and climate. In 2024, the Royal Meteorological Society supported the set-up of the Diverse Voices speaker series, aimed at improving representation and elevating role models. Here we reflect on the series so far and its outlook for the future

Assessing the Spurious Impacts of Ice-Constraining Methods on the Climate Response to Sea-Ice Loss using an Idealised Aquaplanet GCM

Coupled climate model simulations designed to isolate the effects of Arctic sea-ice loss often apply artificial heating, either directly to the ice or through modification of the surface albedo, to constrain sea ice in the absence of other forcings. Recent work has shown that this approach may lead to an overestimation of the climate response to sea-ice loss. In this study, we assess the spurious impacts of ice-constraining methods on the climate of an idealised aquaplanet general circulation model (GCM) with thermodynamic sea ice. The true effect of sea-ice loss in this model is isolated by inducing ice loss through reduction of the freezing point of water, which does not require additional energy input. We compare results from freezing point modification experiments with experiments where sea-ice loss is induced using traditional ice-constraining methods, and confirm the result of previous work that traditional methods induce spurious additional warming. Furthermore, additional warming leads to an overestimation of the circulation response to sea-ice loss, which involves a weakening of the zonal wind and storm track activity in midlatitudes. Our results suggest that coupled model simulations with constrained sea ice should be treated with caution, especially in boreal summer, where the true effect of sea-ice loss is weakest but we find the largest spurious response. Given that our results may be sensitive to the simplicity of the model we use, we suggest that devising methods to quantify the spurious effects of ice-constraining methods in more sophisticated models should be an urgent priority for future work

Electrical and Magnetic Properties of 3D Printed Integrated Conductive Biodegradable Polymer Nanocomposites for Sustainable Electronics Development

This article reports research on the development and implementation of new methods for structurally integrated and recyclable polymer based electronic products via multi-head fused deposition modelling (FDM) 3D printing. The focus of this research is to propose an efficient FDM-3D printing process utilising multiple filaments with no interruption of the process to ensure the multi-material electronic product achieved is structurally integrated. Such research is an attempt towards development of recyclable rigid electronic structures via multi-material 3D printing, i.e., multiple conductive nanomaterial embedded thermoplastic and non-conductive thermoplastic layers (in coil forms, herein). Six radio frequency identification (RFID) tag coil geometries were selected for the study. The thermoplastic polymer used in this research was polylactic acid (PLA), and the conductive filament was carbon black nanoparticle embedded PLA at approx. 21wt.%. The nozzle and filaments diameters examined were 1.75 mm. A MakerBot Replicator 2X 3D printer was partially disassembled to be equipped with a dual head, for our examinations. The research investigated the major challenges ahead of the proposed development, mainly, on the deteriorating effects on the quality of the integrated product (structural integrity, electric and magnetic properties) induced by the 3D printing process parameters (e.g., temperature). The most efficient nozzle and bed temperatures to prevent visible defects were found to be higher than the supplier’s recommendation, attributed to the uncertainties associated with the multi-material composition, and were found to require 248°C and 100°C for reliable and continued FDM printing, respectively. The measurements on the electric and magnetic properties, using 4-wire resistance and Hall effect method respectively, were conducted to quantify process induced deteriorating effects, quantitatively. It has been examined whether the multi-material electronic structure can be achieved via uninterrupted (continuous) processing of polymer nanocomposite-based identification systems for recyclability purpose whilst maintaining the electromagnetic properties of it, a promising technology for reducing landfill. Recommendations were identified for best practices behind such development

Residual Stresses Characterisation of Hard Ceramic Coating (SiC-5wt%Al2O3) Using X-Ray Diffraction Technique

The aim of this study is to measure residual stresses, specifically in wear protection coating, using the sin2ψ based on the X-ray diffraction technique. The combination of silicon carbide substrate and aluminium oxide (SiC-5wt.% Al2O3) is used as the wear protection coating, and AlNi alloy represents the bond coat, which is formed by the flame spraying method on the mild steel substrate. This in turn has enabled to reduce the thermal expansion constant between the substrate and composite ceramic layer. The diffraction angle, 2θ, is measured experimentally, and the lattice spacing is calculated using Bragg's Law using the measured diffraction angle and the known X-ray wavelength. Interestingly, stress calculations for the samples demonstrate a linear relationship of a slop proportionate to stress same as to homogenous isotropic samples in a bi-axial stress. Thus, the relationship between dspacing and sin2ψ is demonstrated as a straight line with a slope proportional to stress. However, the oscillatory trend showed the existence of in-homogeneous stress distribution. To resolve this challenge, X-ray elastic parameters are deployed instead of Poisson ratio (ν) and Young's modulus (E) values. The value of the residual stresses for these coatings calculated is compressive residual stresses of (-594.029 MPa)

Alternatives to project-specific consent for access to personal information for health research: Insights from a public dialogue

<p>Abstract</p> <p>Background</p> <p>The role of consent for research use of health information is contentious. Most discussion has focused on when project-specific consent may be waived but, recently, a broader range of consent options has been entertained, including broad opt-in for multiple studies with restrictions and notification with opt-out. We sought to elicit public values in this matter and to work toward an agreement about a common approach to consent for use of personal information for health research through deliberative public dialogues.</p> <p>Methods</p> <p>We conducted seven day-long public dialogues, involving 98 participants across Canada. Immediately before and after each dialogue, participants completed a fixed-response questionnaire rating individuals' support for 3 approaches to consent in the abstract and their consent choices for 5 health research scenarios using personal information. They also rated how confident different safeguards made them feel that their information was being used responsibly.</p> <p>Results</p> <p>Broad opt-in consent for use of personal information garnered the greatest support in the abstract. When presented with specific research scenarios, no one approach to consent predominated. When profit was introduced into the scenarios, consent choices shifted toward greater control over use. Despite lively and constructive dialogues, and considerable shifting in opinion at the individual level, at the end of the day, there was no substantive aggregate movement in opinion. Personal controls were among the most commonly cited approaches to improving people's confidence in the responsible use of their information for research.</p> <p>Conclusion</p> <p>Because no one approach to consent satisfied even a simple majority of dialogue participants and the importance placed on personal controls, a mechanism should be developed for documenting consent choice for different types of research, including ways for individuals to check who has accessed their medical record for purposes other than clinical care. This could be done, for example, through a web-based patient portal to their electronic health record. Researchers and policy makers should continue to engage the public to promote greater public understanding of the research process and to look for feasible alternatives to existing approaches to project-specific consent for observational research.</p

Nomograms including the UBC® Rapid test to detect primary bladder cancer based on a multicentre dataset

Objectives: To evaluate the clinical utility of the urinary bladder cancer antigen test UBC Rapid for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high risk of primary BC. Patients and Methods: Data from 1787 patients from 13 participating centres, who were tested between 2012 and 2020, including 763 patients with BC, were analysed. Urine samples were analysed with the UBC Rapid test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC Rapid test was evaluated using receiver-operating characteristic curve analysis. Brier scores and calibration curves were chosen for the validation. Biopsy-proven BC was predicted using multivariate logistic regression. Results: The sensitivity, specificity, and area under the curve for the UBC Rapid test were 46.4%, 75.5% and 0.61 (95% confidence interval [CI] 0.58–0.64) for low-grade (LG) BC, and 70.5%, 75.5% and 0.73 (95% CI 0.70–0.76) for high-grade (HG) BC, respectively. Age, UBC Rapid test results, smoking status and haematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in areas under the curve of 0.79 (95% CI 0.72–0.87) and 0.95 (95% CI: 0.92–0.98) for predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC Rapid test alone for low and medium risk levels in decision curve analysis. The R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index.net. Conclusion: The UBC Rapid test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status and haematuria provides a fast, highly accurate and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC

International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

BACKGROUND: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. METHODS: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined. RESULTS: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006). CONCLUSIONS: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies