The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource

CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset.MethodsFour real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies.ResultsOf 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10% to 60% and was not improved through harmonisation. ConclusionsCombining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration

Evaluating a Smartphone-Based Symptom Self-Monitoring App for Psychosis in China (YouXin): a Non-Randomised Validity and Feasibility Study with a Mixed-Methods Design

Background: Psychosis causes significant burden globally, including in China, where limited mental health resources hinder access to care. Smartphone-based remote monitoring offers a promising solution. This study aimed to assess validity, feasibility, acceptability, and safety of a symptom self-monitoring smartphone app, YouXin, for people with psychosis in China. Methods: A pre-registered non-randomised validity and feasibility study with a mixed-methods design. Participants with psychosis were recruited from a major tertiary psychiatric hospital in Beijing, China. Participants utilised the YouXin app to self-monitor psychosis and mood symptoms for four weeks. Feasibility outcomes were recruitment, retention and outcome measures completeness. Active symptom monitoring (ASM) validity was tested against corresponding clinical assessments (PANSS and CDS) using Spearman correlation. Ten participants completed qualitative interviews at study end to explore acceptability of the app and trial procedures. Results: Feasibility parameters were met. The target recruitment sample of 40 participants was met, with 82.5% completing outcome measures, 60% achieving acceptable ASM engagement (completing &gt;33% of all prompts), and 33% recording sufficient passive monitoring data to extract mobility indicators. Five ASM domains (hallucinations, suspiciousness, guilt feelings, delusions, grandiosity) achieved moderate correlation with clinical assessment. Both quantitative and qualitative evaluation showed high acceptability of YouXin. Clinical measurements indicated no symptom and functional deterioration. No adverse events were reported, suggesting YouXin is safe to use in this clinical population. Conclusions: The trial feasibility, acceptability and safety parameters were met and a powered efficacy study is indicated. However, refinements are needed to improve ASM validity and increase passive monitoring data completeness. <br/

Production, Analysis and Identification of Crystal By-products in C₃F₇CN Mixtures

This paper examines the production, analysis and identification of crystal by-products, such as perfluoroisobutanamide (C3F7CONH2) and metal complexes from perfluoroisobutyronitrile (C3F7CN), produced under different environmental conditions, examined by a suite of mass spectroscopy instruments, Fourier transform infrared and Raman spectroscopy techniques

Development and validation of an efficient and safe loud music exposure paradigm

Purpose: To develop a time-efficient music exposure and testing paradigm, that safely creates temporary cochlear dysfunction that could be used in future temporary threshold shift (TTS) studies. Method: A 30-min audio compilation of pop-rock music tracks was created. Adult volunteers with normal hearing were then exposed to this music material monaurally through headphones for 30 min at 97 dB A or 15 min at 100 dB A. Levels were measured from the ear of a manikin and are considered to provide an equivalent daily noise dose based on a 3-dB exchange. We assessed the changes in their hearing, by means of distortion product otoacoustic emission (DPOAE) testing, and standard and extended high-frequency pure-tone audiometry before and after exposure. There were 17 volunteers in total. In a first trial, eight volunteers [four females; median age = 31 years (IQR = 4.25)] were included. Although TTS was observed in all eight participants for at least one frequency, a large variation in affected frequencies was observed. To address this issue, the audio material was further remastered to adjust levels across the different frequency bands. Fourteen adults [nine newly recruited and five from the first trial; seven females; median age = 31 years (IQR = 5)] were exposed to the new material. Results: All but 2 out of 17 participants presented clinically significant TTS or decrease in DPOAE amplitude in at least one frequency. Statistically significant average TTS of 7.43 dB was observed at 6kHz. There were statistically significant average DPOAE amplitude shifts of -2.55 dB at 4 kHz, -4.97 dB at 6 kHz, and -3.14 dB at 8 kHz. No participant presented permanent threshold shift.Conclusions: A monaural music paradigm was developed and shown to induce statistically significant TTS and DPOAE amplitude shifts, without evidence of permanent loss. This realistic and time-efficient paradigm may be considered a viable option for experimental studies of temporary music-induced hearing loss

Holy sites of Serindia (Altishahr) in the 11th and 21st centuries

This essay offers an experiment in chronological boundary crossing as way of addressing questions about continuity and change in Central Eurasia. It analyzes the violent transformations of holy sites in Altishahr (Eastern Turkistan or Xinjiang), examining the 11th-century transition from Buddhist to Muslim rule alongside the 21st century efforts of the People’s Republic of China to transform sacred Islamic sites into nationalist showpieces for “Silk Road” tourism. This juxtaposition calls into question prevailing understandings of the 11th -century transition as a simple refashioning of existing Buddhist sites into Islamic manifestations, while placing current Chinese restrictions on Islamic holy sites in a broader historical perspective. Together, the two examples show that shrines act as cultural arbiters, establishing routes by which change has entered Altishahr and stubbornly preserving not just older meanings, but also older ways of knowing. At the same time, they are places where the dynamics of continuous meaning creation come into clear view, where cultural change itself becomes an explicit part of the narratives that bind people together in supposedly stable identity groups such as religions and nations

Chimeric Antigen Receptor T-Cell Therapy: A New Emerging Landscape in Autoimmune Rheumatic Diseases

Chimeric antigen receptor T-cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionised the treatment landscape of haematological malignancies. The past two years have witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis, and anti-synthetase syndrome. In comparison to existing B-cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promising results necessitate validation through long-term, large-sample, randomized controlled studies. Corroborating the role of CAR-T therapy in refractory rheumatological disorders and affirming safety, efficacy and durability of responses are the aims of future clinical studies. Optimising the engineering strategies and better patient selection are also critical to further refining the successful clinical implementation of CAR-T therapy

Multinationals’ Value Chain Configuration for Product Diversification in Emerging Markets: Western Firms in China

Purpose – This study aims to analyse how MNCs organise value chain activities to penetrate new market segments. It contributes by expanding traditional decisions regarding the vertical fine-slicing of value chain activities (whether performed internally or externally) and the consideration of resource sharing decisions (integration or separation) for each value chain function. Design/methodology/approach – We draw on primary data collected from two case study firms operating in the large emerging Chinese market: Volvo Construction Equipment AB and Epiroc AB. Indepth cases illustrate how foreign MNCs expand into new market segments and simultaneously target both the lower-priced mid-market and the premium segments in the Chinese mining and construction industry. Findings – The results reveal that product diversification creates challenges for managers who must oversee new (vertical) value chains, often simultaneously. Beyond geography and modes of governance, managers must decide whether to integrate or separate value chain activities for the new product lines. The study identifies four main strategic options for firms to address this complexity, focusing on the decision to internalise or externalise (i.e. within or across organisational boundaries) and integrate or separate value chain activities between different product lines. Originality/value – This study builds upon the Internalisation theory and recent IB contributions that focus on value chain configurations to explain MNCs’ product diversification as a growth strategy in a host emerging market. It also sheds light on the choice of conducting new activities in-house or externally and elucidates firms’ managerial decisions to operationally integrate or separate individual value chain activities. The study provides insights into the drivers explaining managerial decisions to configure value chain activities across product lines and contributes to the growing body of literature on MNC activities in emerging economies by highlighting that product diversification impacts entry mode diversity and resource sharing across units

Polyhydroxyalkanoates production: A challenge for the plastic industry.

The accumulation of petroleum-based plastics in the environment has heightened the necessity of finding alternative materials with similar properties and lower environmental impact. Polyhydroxyalkanoates (PHAs) are a group of naturally occurring polyesters that have been investigated for several decades as potential substitutes of commonly used plastics. PHAs are biodegradable and biocompatible polymers derived from renewable resources. From this point of view, their industrial implementation represents an attractive strategy to reduce plastic pollution and petroleum dependency. Nevertheless, the high production costs related to these materials have considerably hindered their broader use and commercialization. In this regard, several approaches have been proposed to turn their production competitive from a commercial perspective. For instance, several studies have scrutinized the different production steps of PHAs in terms of economic viability. Reported strategies include optimization of fermentation processes, selection, isolation, and genetic modification of microbial strains, selection of low-cost renewable raw materials, and more efficient separation processes of the produced PHAs. This review summarizes the main advantages and disadvantages of different strategies proposed to improve the competitiveness of PHAs production; potential applications of PHAs manufactured by these different methods, as well as the main challenges to be overcome to develop economically viable industrial processes, are discussed in detail

Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People with Rheumatic Diseases:A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry

Background: Approximately one-third of individuals worldwide have not received a COVID-19 vaccine. While studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases, we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern.Methods: Patients with rheumatic disease and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, rheumatic disease activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; sub-analyses stratified patients according to rheumatic disease types. Results: Among 19,256 unvaccinated people with rheumatic disease and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell depleting therapy were associated with worse outcomes. In those with connective tissue disease or vasculitis, B-cell depleting therapy was associated with worse outcomes.Conclusions: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with rheumatic disease. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.<br/