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Advanced preclinical testing of a design-optimized ceramic bearing for a cervical total disc replacement
Get PDFObjective: Arthroplasty in the cervical spine is performed using Total Disc Replacement (TDR) implants. This study investigates the safety and tribology of a design-optimized ceramic TDR bearing. Methods: Samples of an optimized bearing geometry were manufactured from the bioceramic BIOLOX®delta (CeramTec GmbH, Germany) and tested in a six degree of freedom universal joint simulator in diluted calf serum at body temperature. The investigated load and motion profiles simulated movements of daily living; three pure rotations under static load and three rotations coupled under sinusoidal load as well as adverse events (three subluxation test conditions). Results: Dynamic coefficients of friction during flexion/extension and lateral bending were µ = 0.16 ± 0.011 and µ = 0.16 ± 0.070, respectively. Friction factors during flexion/extension and lateral bending were f = 0.14 ± 0.0092 and f = 0.13 ± 0.063, whereas the friction factor in axial rotation was f = 0.033 ± 0.0028 and for three coupled rotations under sinusoidal load, it was f = 0.13 ± 0.028. The design demonstrated a sufficient resistance against subluxation, with subluxation forces more than 3.5-fold the 20N that are typically required as acceptance criteria in FDA safety and effectiveness data. Conclusion: Friction values were found to be comparable to or higher than those typically reported for ceramic-on-ceramic hip replacements. Furthermore, the results indicated that the optimized bearing design is sufficiently resistant to subluxation. Significance: Test protocols to investigate safety and tribology of cervical TDRs are proposed and their results are reported for a design-optimized ceramic TDR bearing
Microbiome research in practice:priorities for clinical translation and impact
Get PDFBackgroundRapid advances in microbiome science have sparked clinical and commercial enthusiasm for interventions, yet translation into practice risks outpacing both mechanistic understanding and the infrastructure required for safe adoption.ObjectivesTo outline a coordinated research, clinical, social, and policy agenda for advancing safe, effective, and equitable microbiome-based interventions.SourcesWe convened an interdisciplinary Royal Society-funded expert workshop (Leeds, UK, October 2024) with international leaders in microbiome science, clinical trials, regulation, and social science. Thematic analysis of workshop discussions and written contributions identified priority domains for translation.ContentThree intersecting priorities emerged: scientific credibility, practical viability, and stakeholder engagement. Scientific credibility demands investment in multiomic and strain-level characterization of host-microbiome interactions on a large scale, benchmarking of clinical and microbiological endpoints, and harmonization of trial conduct and reporting. Clinical adoption requires fit-for-purpose regulation, diversified investment to address funding bottlenecks, and coordinated capacity building. Meaningful stakeholder engagement with clinicians, patients, policymakers, and the public is essential to foster confidence, develop clinically relevant research questions, and ensure equitable implementation of any new technology.ImplicationsTo realize the clinical impact of microbiome interventions, sustained collaboration across disciplines is essential. This review offers a translational roadmap and actionable priorities to accelerate safe, effective, and equitable microbiome-based interventions—ensuring the field fulfils its clinical potential and delivers real-world impact.</div
Parents’ experiences of the time preceding infant admission to hospital within 4 weeks of birth:a qualitative interview study
Get PDFProblem Infant readmissions within the first 28 days of life have risen significantly over the past decade. Background Postnatal care is often described as under-resourced, with many women reporting a lack of sufficient support after birth. Objective To explore parents’ experiences in the lead-up to infant readmission within the first four weeks of life. Methods Twenty-eight parents of 18 infants unexpectedly admitted to a large urban paediatric referral hospital in England within four weeks of birth were interviewed face to face. Data were analysed using thematic analysis. Findings Parents valued being united in their role as protectors. Mothers struggling with breastfeeding often felt intense responsibility, being their baby’s sole source of nutrition. When concerns arose, some parents were unsure who to contact. Seeking advice from family sometimes delayed professional help. Others felt dismissed by health professionals offering false reassurance. Many were comforted upon arriving at the hospital and receiving a diagnosis, which validated their concerns and reinforced their protective instincts. Discussion This study highlights parents’ need to be together post-birth, their decision-making when their baby became unwell, and their interactions with health professionals during readmission. Conclusion Services should support shared caregiving early on by improving partner access to postnatal wards and enhancing community support for families returning home. The care pathway for unwell infants is often unclear and should be made more accessible to avoid unnecessary emergency visits. Health professionals must prioritise women’s emotional wellbeing, especially during breastfeeding challenges, and respond seriously to parental concerns with clear escalation routes
Reply to Comment on “Cost Comparisons in NICE Technology Appraisals:An External Assessment Group Perspective”
No full textKey Protective Factors that Mitigate the Impact of Childhood Trauma on Poor Mental Health in Adulthood:A Scoping Review Protocol
No full textIntroduction: A significant proportion of adults in England and Wales report experiencing childhood trauma, which is often associated with poor health and negative social outcomes including a significant increase in the risk of poor mental health outcomes in adulthood1. This proposed scoping review adopts a broad definition of childhood trauma and applies both a salutogenic framework and ecological systems theory to explore how protective factors at five ecological levels can support mental wellbeing. The review will also examine how protective factors varies across different population groups and contexts. Methods and analysis: The scoping review will follow the Joanna Briggs Institute (JBI) protocol for scoping reviews. The databases that will be searched are Embase, PubMed, Web of Science, PsycINFO, CINAHL and Medline. Studies will be included if they include protective factors and involve adults aged 18 and over who have experienced childhood trauma, whether self-identified, retrospectively self-reported or measured using a validated instrument Studies will be excluded if they focus on participants under the age of 18. All search results will be uploaded to Covidence, duplicates removed, and titles/abstracts screened by at least two reviewers based on inclusion criteria. Full texts of potentially relevant sources will be imported into EndNote 21. Reasons for exclusions will be documented and disagreements resolved through discussion or a third reviewer. The full process will be reported using a PRISMA flow diagram2. Data will be extracted by at least two reviewers using a tool developed by the team based on the JBI guidance3. A best-fit framework analysis will be used, using a matrix developed by the researchers including the four salutogenic domains and the five levels of the ecological framework. Ethics and dissemination: Formal ethical approval is not necessary for this scoping review as it does not involve the collection of primary data. The outcomes of this study will be disseminated through peer-reviewed journal articles, conference/seminar presentations, and developed into resources for stakeholders and collaborators. Study registration: Open Science Framework (DOI 10.17605/OSF.IO/CJRUY
New Perspectives:Four Unsung Heroes of Diabetes Research
No full textThis article explores four little-known stories about research into, and treatment for, diabetes. Progressing in order from the participant about whose story we know the most to those about whom we know the least demonstrates that clinical research and therapeutic development are collaborative enterprises and that often key innovations and discoveries happen outside the laboratory setting. The role of unlikely individuals and collectives in reforming diabetes care is revealed, to nudge researchers into new and fruitful pathways. Further, this article shows how with a historical approach we can find the right stories of discovery to help both patients and researchers gain new insights into the prevention, management, and treatment of diabetes in all its forms.</p
Articulation in Motion:Prior-free Part Mobility Analysis for Articulated Objects By Dynamic-Static Disentanglement
Get PDFArticulated objects are ubiquitous in daily life. Our goal is to achieve a high- quality reconstruction, segmentation of independent moving parts, and analysis of articulation. Recent methods analyze two different articulation states and perform per-point part segmentation, optimizing per-part articulation using cross-state cor- respondences, given a priori knowledge of the number of parts. Such assump- tions greatly limit their applications and performance. Their robustness is reduced when objects cannot be clearly visible in both states. To address these issues, in this paper, we present a novel framework, Articulation in Motion (AiM). We infer part-level decomposition, articulation kinematics, and reconstruct an interactive 3D digital replica from a user–object interaction video and a start-state scan. We propose a dual-Gaussian scene representation that is learned from an initial 3DGS scan of the object and a video that shows the movement of separate parts. It uses motion cues to segment the object into parts and assign articulation joints. Subsequently, a robust, sequential RANSAC is employed to achieve part mobility analysis without any part-level structural priors, which clusters moving primitives into rigid parts and estimates kinematics while automatically determining the number of parts. The proposed approach separates the object into parts, each represented as a 3D Gaussian set, enabling high-quality rendering. Our approach yields higher quality part segmentation than all previous methods, without prior knowledge. Extensive experimental analysis on both simple and complex objects validate the effectiveness and strong generalization ability of our approach. Code and implementation details will be made publicly available
Comparing Cognitive and Psychological Factors in Virtual Reality and Real Environments:A Cave Automatic Virtual Environment Experimental Study
Get PDFThe emergence of Building Information Modelling, Internet of Things, and Cave Automatic Virtual Environments (CAVEs) has created new opportunities for remote monitoring and decision-making in the operational built environment, yet empirical evidence supporting their use as alternatives to on-site observation remains limited. This study evaluates task and human performance in a controlled experiment comparing a CAVE with a real-world setting (n = 26). Situation awareness, workload, anxiety, presence, usability, and user experience were measured across conditions. Participants in the CAVE demonstrated substantially higher situation awareness (M = 92.1%) than those in the real-world condition (M = 56.8%), alongside significantly lower overall workload (NASA-TLX weighted workload = 38.3 vs. 53.8). Anxiety remained consistently low in the CAVE (ΔSTAI = –1.0), whereas participants in the real-world condition exhibited higher baseline anxiety followed by a large reduction during task execution (ΔSTAI = –13.2). The CAVE also elicited high levels of spatial presence, involvement, and realism relative to comparable projection-based systems, while usability ratings (SUS) were above industry benchmarks (M = 74.2). Together, these findings indicate that controlled immersive representations of built environments can support sensemaking and reduce extraneous cognitive load relative to live, uncontrolled on-site observation, with important implications for remote facilities management and operational decision-making
Neutralizing nanobodies against SARS-CoV-2 recognizing highly conserved epitopes at the Spike's S2 subunit
Get PDFThe formation of a six-helix bundle between the conserved heptad-repeat regions 1 and 2 (HR1 and HR2) in SARS-CoV-2 Spike's S2 subunit is essential for membrane fusion and represents a promising therapeutic target. Previously, we reported recombinant proteins named CoVS-HR1, which mimic the HR1 region and block its interaction with HR2, inhibiting viral fusion. Moreover, they are recognized by plasma antibodies from COVID-19 convalescent patients. In this work, we generated camelid heavy-chain-only antibody fragments (VHHs), also named nanobodies (NBs), against a CoVS-HR1 variant mimicking the full HR1 region. A first generation of selected NBs bound HR1 with high affinity and competed with HR2. Notably, this set of NBs exclusively recognized the C-terminal half of HR1, and two of them showed mild neutralizing activity in cell infection assays. Using a truncated CoVS-HR1 variant (N2C), we selected a second generation of NBs targeting specifically the N-terminal half of HR1. However, these NBs did not demonstrate neutralizing activity, possibly due to their low binding affinities. Several NB epitopes were delineated by hydrogen‑deuterium exchange and mass spectrometry analysis, and the crystal structure of a ternary complex between an HR1-mimetic protein and two NBs was determined, confirming competition with HR2. Intriguingly, we found cooperative binding effects between NBs targeting each half of HR1, but these did not result in detectable inhibitory synergy. These findings demonstrate the existence of neutralizing epitopes in the S2 HR1 region and provide a foundation for future development of enhanced neutralizing NBs focused on specific epitopes using HR1-mimetic proteins.</p
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