143174 research outputs found
Sort by
VALIDATE-PERIANAL: an international real-world multi-centre exploratory validation of the TOpClass definition of a radiologically healed fistula in perianal fistulising Crohn’s disease
No full textObjectives:
Radiological healing on MRI is the ultimate therapeutic goal in Class 2a perianal fistulising Crohn’s disease (pfCD). The TOpClass consortium recently defined radiological healing (TOpClass-RH) by the absence of T2 hyperintensity, a completely fibrotic fistula tract, and absence of contrast enhancement when used. This study aimed to validate TOpClass-RH in real-world clinical practice.
Methods:
VALIDATE-PERIANAL was a retrospective, multi-centre international study. Patients with pfCD with a baseline MRI scan showing active disease and follow-up MRI evidence of radiological fistula healing between 2021–2023 were identified. Paired scans were independently reviewed by three gastrointestinal radiologists using TOpClass-RH criteria, with consensus adjudication. A minimum of 12-months clinical follow-up was required. The primary outcome was sustained clinical remission; secondary outcomes included inter-rater reliability (Cohen’s kappa) and rates of proctectomy and stoma formation.
Results:
Of 977 patients screened, 40 with pfCD met inclusion criteria;14/40 (35%) fulfilled TOpClass-RH criteria. Sustained clinical remission was achieved in 93% of TOpClass-RH patients. Clinical recurrence occurred in 1/14 (7%) of TOpClass-RH patients versus 8/26 (30.8%) in the non-RH group (RR 4.3 [0.60–31.0], p=0.12), with a median follow-up of 28 months. Inter-rater reliability was excellent (κ 0.89–0.95). There was a trend toward lower rates of proctectomy and stoma formation in the TOpClass-RH group.
Conclusion:
TOpClass-RH was associated with sustained clinical remission, although the study was underpowered to detect statistically significant differences. The definition demonstrated excellent inter-rater reliability, supporting TOpClass-RH as a clinically meaningful radiological endpoint for trials and diagnostic stratification in pfCD. Larger prospective studies are required
μEd API: Towards a shared API for EdTech microservices
No full textPreprint versionLearning at scale often requires domain-specific automation such as assessment and feedback. An organization locked in to a general learning platform without these specialist automations limits its pedagogical offering. An ecosystem of interoperable, platformagnostic microservices for domain-specific automation would solve this problem. To develop an effective ecosystem , a standard interface (API) for education microservices is required. We propose an initial specification for a standard, platformindependent API for educational microservices, µEd. The API integrates functionality from existing systems in use at four institutions, which are adopting the new API. The API is initially specified for automation of feedback, assessment, and educational chatbots, with further service types envisaged in the future. The API specification provided here enables the development of an ecosystem of education microservices that will facilitate automation in more domains, to more users, providing a richer learning experience in a wide range of disciplines. CCS Concepts • General and reference → Computing standards, RFCs and guidelines; • Applied computing → Education
An investigation into the structure of extremophile membranes
No full textThe possibility that living organisms might exist in extraterrestrial environments, often referred to as extremophiles, has been one of the most controversial topics in space science. This research investigated the effects of high pressure on conditions relevant to the origin of extraterrestrial life. The primary objective of this study was the construction of a high-pressure system in the laboratory. The developed system was integrated with a phase-contrast microscope to measure the bending rigidity of Giant Unilamellar Vesicle (GUV) membranes with different degrees of lipid unsaturation (e.g., DOPC, POPC, and DMPC) under varying pressure conditions. Bending rigidity, which represents the energy required to deform membrane curvature, is a fundamental parameter for understanding many biophysical and biochemical behaviors of biological membranes. In addition, the high-pressure system was also integrated with a quartz cuvette to monitor and incubate deep-ocean bacteria under high-pressure conditions. Besides the simplified vesicle model experiments, bacterial experiments using marine microorganisms were designed as a complementary component of this study.Open Acces
A global evaluation of the use of faecal microbiota transplant (FMT)
No full textBackground: Faecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridioides difficile infection (CDI); its use is increasingly being investigated for other indications. Although regional surveys and national registries have provided insight into local practices, a comprehensive global overview of FMT access, implementation and governance is lacking.
Methods: A survey regarding key aspects related to FMT use was disseminated electronically to members of the World Gastroenterology organisation, European FMT Network, and International Society of Infectious Diseases. Responses were analysed both descriptively and using appropriate statistical methods.
Findings: 80 responses were obtained from 55 countries. FMT was available in significantly more Tier 1/2, than Tier 3/4, nations (24/28 vs 8/27; p<0.001). In countries lacking access to FMT reasons included: lack of expertise/infrastructure; financial constraints; regulatory uncertainty; and perceived lack of clinical need. Most countries using FMT employed both
upper and lower gastrointestinal administration routes; 18/32 (56%) used capsulised FMT.
Almost all countries with access to FMT used it to treat CDI, albeit with different thresholds for the number of CDI episodes prior to use. There were many non-CDI indications for FMT in current use. Payment for stool donation was reported by 10 countries.
Interpretation: This is the first global overview of FMT availability and governance, highlighting substantial international inequities and considerable heterogeneity in regulation, clinical use, donor screening, and cost. Standardisation of practice and targeted support for lower income countries is needed to ensure equitable access and to promote safe, high quality delivery as FMT and microbiome-based therapeutics continue to evolve
From photons to phenotypes: decoding organoid biochemistry via deep learning-enhanced raman spectroscopy
No full textThree-dimensional neural organoids have emerged as powerful in vitro models for studying human brain development, disease and drug response. Yet their analysis remains constrained by standard imaging and characterisation techniques, which are invasive, require exogenous labelling and offer limited multiplexing. There is a pressing need for advanced analytical and imaging approaches that can interrogate spatial organisation and dynamics in intact organoid systems under physiologically relevant settings, without prior knowledge of specific molecular targets or the use of external labels.
To address this challenge, this thesis develops computational methods for non-invasive, label-free biochemical analysis using Raman spectroscopy (RS). First, it introduces RamanSPy – an open-source Python package for RS data analysis designed to improve standardisation, reproducibility, accessibility and interoperability. RamanSPy provides a comprehensive library of tools for spectroscopic analysis that supports day-to-day tasks, integrative analyses, method and protocol development, and the integration of advanced data analytics. Next, hyperspectral unmixing algorithms for RS based on autoencoder neural networks are developed and systematically validated using synthetic and experimental benchmark datasets. Unmixing autoencoders consistently outperform standard methods, achieving more accurate qualitative and quantitative analysis and enabling enhanced volumetric Raman imaging of a monocytic cell.
Building on these tools, a Raman imaging platform for unsupervised, spatially resolved biochemical analysis in neural organoids is established. This approach enables non-invasive, label-free mapping of cellular and subcellular structures in both cryosectioned and intact organoids. Using this platform, volumetric imaging of a neural rosette within a neural organoid is demonstrated. Furthermore, changes in biochemical composition during early developmental stages in intact neural organoids are interrogated, revealing spatiotemporal variations in lipids, proteins and nucleic acids.
Overall, this work expands the methodological and computational toolkit for RS chemometrics and establishes a versatile framework for high-content, label-free (bio)chemical phenotyping with broad applications in organoid research, cell biology, disease modelling and drug discovery.Open Acces
Nasopharyngeal microbiome composition and its clinical correlates in children hospitalized with severe pneumonia in East Africa
No full textBackground
Pneumonia remains the leading cause of infectious mortality in children under 5, with the highest burden in sub-Saharan Africa. Dysbiosis in nasopharyngeal (NP) microbiota may influence pneumonia susceptibility and progression, but little is known about its composition or clinical relevance in low- and middle-income countries. We characterized the NP microbiota of children hospitalized with severe pneumonia in East Africa and investigated associations with clinical outcomes.
Methods
We performed 16S rRNA partial gene sequencing of NP swabs collected at hospital admission from 876 children enrolled in the COAST trial across 5 sites in Kenya and Uganda. Clinical, demographic, and virological data were prospectively collected. Microbial profiles were analyzed using hierarchical clustering, nonmetric multidimensional scaling, and multivariable regression to assess associations with respiratory viral infections, sepsis, cyanosis, bacteremia, coma, HIV status, malnutrition, sickle cell disease, malaria, and mortality.
Results
The NP microbiome was structured in 6 distinct clusters, each dominated by different genera, including Staphylococcus, Streptococcus, Haemophilus, Dolosigranulum, Corynebacterium, and Moraxella. Multivariable models adjusting for study site and age showed a positive association between Corynebacterium and early mortality. Temporal analysis showed elevated Corynebacterium abundance in children who died within 48 hours of admission, then declined over longer 56 survival intervals, approaching levels observed in survivors. However, time-continuous models did not support this persistent association, suggesting a subgroup effect.
Conclusions
We provide one of the largest high-resolution surveys of the pediatric upper airway microbiome in Africa, identifying microbial patterns associated with viral infection, HIV status, early death, and bacteremia
ASPIRE-Med project: a study protocol on an Australian psychotropic medicines training programme for disability support workers
No full textIntroduction Overmedication of off-label use of psychotropic medicines to address behaviours of concern in people with intellectual and developmental disabilities is a major public health concern. Disability support workers (DSWs) play a pivotal role in supporting adults with intellectual and developmental disabilities who are prescribed psychotropic medicines. Therefore, there is an urgent need to train DSWs to help understand the appropriate use of these medicines. This paper describes the protocol of a project that aims to develop such a programme.
Methods and analysis A participatory action framework will underscore the programme and follow a Universal Design for Learning approach. It will be a co-production involving all stakeholders, including people with intellectual and developmental disabilities, their families, members of the disability workforce, healthcare professionals and educational designers. The programme will be developed using the following steps: (a) development of a consumer advisory committee and expert panel groups, (b) an online survey of learning needs analysis, (c) a rapid umbrella review of the relevant literature, (d) focus groups involving participants from different parts of Australia, (e) co-design events in four Australian cities, (f) field testing on 6–12 DSWs to determine any practical difficulties of implementing the programme, (g) a feasibility trial involving at least 1200 DSWs using a train-the-trainer model and online resources and (h) a mixed-method process evaluation using interviews of a purposive sample of trainees and online questionnaire survey.
Ethics and dissemination Ethics approval will be sought at each stage of the co-design process. Each step of the project will include an academic language paper and Easy Read report developed. The training programme will be shared across Australia, with DSWs able to complete the project for free. We expect the training will help improve DSWs’ knowledge of appropriate psychotropic medicine prescribing in people with intellectual and developmental disabilities, confidence in effectively communicating with health professionals and using non-pharmacological approaches to support behaviours of concern, promote shared decision-making with clients, advocate for psychotropic medicine reviews by healthcare professionals, encourage positive interactions with people with intellectual and developmental disabilities and their families and self-reflection on their own behaviour and attitude can influence their client and behaviours of concern
Heterogeneous iron-doped covalent triazine framework for the efficient photocatalytic upcycling of polystyrene waste to valuable aromatics under ambient conditions
No full textPolystyrene (PS), a widely used commodity plastic, has a persistently low recycling rate, making it a major contributor to plastic pollution. Selective PS upcycling under ambient conditions remains challenging due to its chemically inert structure, characterized by stable Csingle bondC and Csingle bondH bonds. As a consequence, efficient PS degradation typically requires energy-intensive pyrolysis or harsh oxidizing conditions. Existing homogeneous photocatalysts, such as strong acids or metal salts, are unsustainable long-term solutions for PS waste management due to their lack of reusability and complex separation requirements. Although covalent organic frameworks (COFs) and covalent triazine frameworks (CTFs) have previously been explored as general photocatalysts, their use in selective PS upcycling remains underexplored. Here, we report an iron-doped CTF for the efficient photocatalytic upcycling of PS under ambient conditions. By harnessing the framework's porous character and tunable electronic and photophysical properties, the catalyst incorporates less than 3 wt% iron and offers a sustainable alternative to photocatalysts with higher metal content. Synthesized via solvent-free mechanochemical Friedel-Crafts alkylation of trichlorotriazine and phenothiazine, the CTF forms a porous, p-type semiconductor with FeCl4− ions cross-linking 2D CTF polymer sheets to form an [FeCl4]@CTF heterogeneous photocatalyst. The disclosed [FeCl4]@CTF photocatalyst achieves 100% degradation of commercial and post-consumer PS under ambient conditions, yielding approximately 70% of valuable aromatic compounds with high selectivity. The scalable mechanochemical synthesis of the CTF, coupled with its reduced reliance on high metal loadings provides a sustainable blueprint for organocatalyst-driven plastic waste management using earth-abundant metals
Search for the inert doublet model in a final state with two leptons at the CMS experiment
No full textThis thesis describes two searches for neutral scalars of the Inert Doublet Model (IDM)
in the dilepton final state. The first search is performed using proton-proton
collision data collected from 2016-2022 with the CMS detector at centre of mass
energies of TeV and TeV, corresponding
to a total integrated luminosity of 172.2 fb. No significant excess above the SM
prediction is found. 95\% CL upper limits are
placed on the masses of the two neutral IDM scalars, and , resulting in
a maximum exclusion up to 108 GeV at a mass splitting of approximately GeV.
The second search is a projection study looking at the
sensitivity to the IDM at the Future Circular Collider with electron-positron
collisions at GeV and GeV, corresponding to 10.8
ab and 2.7 ab of integrated luminosity, respectively. Using
solely simulated events and a simplified detector model, expected limits are
derived for the two neutral IDM scalars, resulting in an expected exclusion of
nearly the entire kinematically-allowed parameter space.
In addition, a study is presented on the performance of
graph neural networks (GNNs) for electron and photon identification versus
pileup, carried out in the context of the High-Luminosity LHC CMS endcap
upgrade. Utilising only the raw energy deposits in the detector, the GNN is
capable of automatically extracting meaningful features from the data, and is
shown to outperform current methods based on boosted decision trees.Open Acces