47011 research outputs found
Sort by
High-resolution mass spectrometry imaging reveals metabolic signatures of Staphylococcus epidermidis in host defense against influenza A virus
No full textBackground: The commensal nasal microbiota Staphylococcus epidermidis (S. epidermidis) can suppress influenza A virus (IAV) activity in the host lung by modulating the microcellular environment. However, the metabolic mechanisms underlying this antiviral effect remain unclear. This study employs a novel combination of atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) and Orbitrap secondary ion mass spectrometry (OrbiSIMS) imaging to investigate the metabolic interactions between nasal microbiota and IAV infection in mouse lung tissue. Results: By utilizing this high-resolution dual-platform MS imaging (MSI) approach, we achieved high spatial resolution mapping of metabolic alterations, revealing polyamine metabolism as a key pathway mediating the antiviral effects of S. epidermidis. Our findings demonstrate that S. epidermidis inoculation downregulates polyamine metabolism, significantly suppressing IAV replication, a mechanism confirmed through targeted polyamine supplementation. Additionally, sulfate/sulfite metabolism was identified as a crucial metabolic pathway modulated in IAV-infected and S. epidermidis-treated lungs. Significance: This study represents the first application of integrated AP-MALDI and OrbiSIMS MSI to antiviral metabolomic analysis, providing critical insights into host-microbiota interactions in respiratory infections. Our results provide a foundation for utilizing spatial metabolomics to explore novel therapeutic targets for viral infections and highlight the potential of nasal microbiota in respiratory defense. These findings could advance MS-based biomarker discovery and antiviral drug development
Between-country differences in the psychosocial profiles of British cattle farmers
Full text linkBackground: Psychosocial factors are important for the uptake of livestock disease control measures by farmers and can differ by region, which would have implications for disease control nationally. Methods: We investigated altruism, trust, psychological proximity and the COM-B behaviour change framework in a survey of 475 British cattle farmers in 2020. Using regression models, we studied associations between the country farmers lived in and psychosocial and behaviour change factors. Results: There were many between-country differences in farmers' psychosocial and COM-B profiles. Accounting for multiple tests, Scottish cattle farmers reported higher trust in governmental judgements for disease control and greater social opportunity to control disease than English cattle farmers. Limitations: There were relatively low numbers of respondents from Scotland and Wales. As such,the results should be interpreted with caution. Northern Irish farmers could not be included in the analyses as there were too few responses. Conclusion: Cattle farmers differed in their psychosocial profiles by country. Our sample of Scottish farmers reported higher trust in, and felt better supported by, government in the context of disease control than the English farmers, which could be due to different disease control approaches between devolved governments. Understanding between-country differences in farmer psychosocial attributes has implications for animal health governance and approaches to disease control
Phased Variant–Supported Circulating Tumor DNA as a Prognostic Biomarker After First-Line Treatment in Large B-Cell Lymphoma: Findings From the DIRECT Study
No full textPurposeCirculating tumor DNA (ctDNA) is emerging as a promising tool to monitor treatment response in large B-cell lymphoma (LBCL). Tracking tumor-specific phased variants (PVs) allows ultrasensitive detection of minimal residual disease (MRD) that may enhance the accuracy of response assessment. Previous studies have been constrained by small cohort size, retrospective design, or assays limited to a single commercial provider.Patients and MethodsDIRECT was a prospective, multisite study evaluating the utility of ctDNA in patients with LBCL. We developed a lymphoma-customized, open-source, ctDNA assay and pipeline that captured hundreds of PVs per patient. Using landmark analysis, we evaluated the prognostic impact of PV-supported MRD at the end of first-line therapy (EoT).ResultsEoT PV-MRD status was available for 155 patients. After a median of 24.5 months, 2-year time to tumor progression (TTP) for patients with detectable versus undetectable PV-MRD was 42% versus 95%, respectively (P < .001; hazard ratio [HR], 13.7). When restricted to patients receiving full-dose anthracycline-based immunochemotherapy, 2-year TTP was 45% versus 96%, respectively (P < .001; HR, 15.4), outperforming conventional radiological response assessment (HRs, 6.9 for positron emission tomography v 16.9 for PV-MRD). The limit of detection with 95% confidence (LoD95) varied by more than two orders of magnitude across patients, underscoring the need to report patient-specific LoD95. Persistent PV-MRD in the absence of relapse was noted, including three of four patients with transformed follicular lymphoma, highlighting a potential caveat when interpreting positive PV-MRD.ConclusionEoT PV-MRD enables sensitive and clinically meaningful response assessment in LBCL. It provides independent prognostic information, enhancing EoT response assessment beyond conventional radiologic assessment. Our findings support the incorporation of PV-MRD into clinical trials and routine management of diffuse LBCL
Understanding failure mechanisms in composite injection overmoulded components through multi-scale imaging during pull-off testing
Full text linkThe structural integrity of composite injection overmoulded components is critically dependent on the bond between the overmoulded rib and the thermoplastic organosheet. However, the mechanisms by which these bonded regions fail remain poorly understood, limiting broader industrial adoption. This study investigates the failure behaviour of carbon-fibre poly-ether-ether-ketone (CF-PEEK) ribs injection overmoulded onto carbon-fibre low-melting point poly-aryl-ether-ketone (CF-LM-PAEK) organosheets using real-time, multi-scale imaging during pull-off testing.Results reveal that failure mode is strongly influenced by proximity to the injection gate. Near the gate, elevated thermal energy during moulding promotes strong interfacial bonding. Here, the interfacial bond exceeds the organosheet's interlaminar strength and the failure mode is via delamination within the substrate. This delamination is driven by inherent porosity in the organosheet, likely introduced during deconsolidation and initial compaction.Conversely, in regions farther (10 cm) from the injection point, reduced melt temperatures result in weaker interfacial bonds. Here, failure preferentially occurs at the interface, governed by process-induced porosity arising from polymer shrinkage during cooling.Importantly, this study demonstrates that pull-off testing does not yield a singular "interfacial strength" value. Instead, it serves as a diagnostic tool for assessing local manufacturing quality in injection overmoulded thermoplastic composites, identifying whether the interface or the organosheet is the limiting factor in structural performance. These insights are essential for developing predictive models and refining manufacturing protocols for thermoplastic composite structures
Implementation and stability analysis of speed-adaptive full-order observer based on multistep discretization method in speed-sensorless induction machine drives
No full textThe discretization of a speed-adaptive full-order observer (AFO) is essential for digital control in speed-sensorless induction machine (IM) drives. However, traditional approximate discretization methods, such as forward Euler(FE) and backward Euler (BE), hardly balance stability, computational burden, and accuracy. This study proposes a multistep discretization method for AFO. Unlike conventional methods, the proposed multistep discretization method ensures stability in the high-speed range with relatively low computational burden and high accuracy, which is suitable for most applications. Furthermore, the proposed method utilizes the information known within the past multiple steps to estimate the current state quantity, demonstrating its flexibility and easy implementation. The effectiveness and correctness of the proposed method are verified through theoretical analysis and experimental results from the IM drive platform for an industrial washing machine
Framework for Insulation Thickness Calculation in PD-Free E-Machines for Automotive & Aerospace
Full text linkThis paper presents a framework for optimizing insulation thickness (IT) in electrical machines (EMs), ensuring reliability and efficiency for a fixed copper diameter and slot geometry. A validated, model-based software, grounded in the streamer inception criterion (SIC), calculates optimal IT for turn-to-turn windings in automotive and aerospace applications, incorporating enhancement factors (EFs) from IEC 60034-18-41. IT is evaluated for automotive systems (1000 mbar) across five temperatures (20°C-180°C) and four inverter DC bus voltages (1-1.6 kV). Aerospace analysis considers three air pressures (600, 400, 200 mbar) at altitudes of 13.8k-38.6k ft, the same temperature range, and four voltage levels (0.7-1 kV). The framework is applicable to all winding topologies and evaluates IT under worst-case conditions (non-impregnated insulation) and varying partial discharge inception probabilities (PDIPs). Trends in partial discharge inception voltage (PDIV) vs. IT are analyzed, with sensitivity to voltage variations examined across air pressures and temperatures. These findings support the design of reliable, high-performance insulation systems for electric transport
A XRISM/Resolve View of the Dynamics in the Hot Gaseous Atmosphere of M87
No full textThe XRISM/Resolve microcalorimeter directly measured the gas velocities in the core of the Virgo Cluster, the closest example of AGN feedback in a cluster. This proximity allows us to resolve the kinematic impact of feedback on scales down to 5 kpc. Our spectral analysis reveals a high velocity dispersion of σ v = 262 +45 −38 km/s near the AGN, which steeply declines to ∼60 km/s between 5 and 25 kpc in the northwest direction. The observed line-of-sight bulk velocity in all regions is broadly consistent with the central galaxy, M87, with a mild trend toward blueshifted motions at larger radii. Systematic uncertainties have been carefully assessed and do not affect the measurements. The central velocities, if attributed entirely to isotropic turbulence, correspond to a transonic ICM at sub-6 kpc scales with three-dimensional Mach number 0.69 +0.14 −0.11 and a non-thermal pressure fraction of 21 +7 −5 %. Simple models of weak shocks and sound waves and calculations assuming isotropic turbulence both support the hypothesis that the velocity field reflects a mix of shock-driven expansion and turbulence. Compared to other clusters observed by XRISM to date, M87's central region stands out as the most kinematically disturbed, exhibiting both the highest velocity dispersion and the largest 3D Mach number, concentrated at the smallest physical scales
Characteristics and 12-month outcomes of clinically referred children and young people at risk of bipolar disorder
Full text linkIntroductionBipolar disorder is uncommon in children and young people (CYP), but those at risk are likely to be clinically referred. However, the characteristics and outcomes of CYP at risk of bipolar disorder referred to UK Child and Adolescent Mental Health Services (CAMHS) remain understudied.MethodsParticipants were 305 CYP aged 11–17 years, with emotional difficulties, referred to CAMHS. CYP and/or parent/carers self-completed the Development and Wellbeing Assessment (DAWBA, including the mania section) at baseline, and follow-up measures at 12 months.ResultsA computerised algorithm categorised 9 (3.0 %, 95 % CI [1.4 %, 5.5 %]) CYP as ‘possible’, 66 as ‘uncertain’, and 230 as ‘unlikely’ for bipolar disorder, using symptom and impact scores. CYP in the ‘possible’ bipolar disorder subgroup were young (mean age = 13 years) and of high socioeconomic status. These CYP were likely to have their CAMHS referral accepted (89 %) and treatment/intervention offered (67 %) and started (56 %) within 12 months of referral. They had high levels of self-harm thoughts and behaviours at baseline and follow-up. The diagnostic algorithm indicated that they had social phobia, generalised anxiety disorder, and/or depression. A third of them were diagnosed with these disorders or obsessive-compulsive disorder by clinicians within 12 months, but not bipolar disorder.LimitationsOur categories of likelihood subgroups were conservative as some participants only had DAWBAs completed by one informant. Subgroups were not compared statistically.ConclusionCYP in the ‘possible’ bipolar disorder subgroup were more likely to receive CAMHS input. They have high self-harm risk. Comorbid emotional disorders among these CYP should be considered
Willingness to wait covaries with endogenous variation in cortisol
No full textStress is a normal part of our everyday lives, alerting us to changes in our environment and working as an early warning system. However, when stress is prolonged, it can become harmful. The deleterious effects of stress on brain function are well established: chronic stress significantly impairs cognitive function, reducing our ability to solve problems and regulate behavior. Therefore, it may lead to more challenges that can further exacerbate stress. An important class of decisions made under stress includes those between rewards delivered immediately and those delivered in the future. Not considering or devaluing future outcomes (delay discounting) can result in adverse outcomes, such as not buying health insurance, gambling, or drug use. To date, however, little is known about how chronic stress influences economic decisions that differ in the timing of outcome delivery. A handful of studies suggest that increased stress may lead to more impulsive choices in subjects of average socioeconomic status and stress levels. In this study, we addressed this gap by using a multi-session design to determine whether chronic stress measures (via questionnaires, saliva, and hair samples) are associated with economic choices across different time scales within subject (N = 34). We found that the degree to which people think it is worth waiting, i.e., an individual's discount factor, varied reliably over seconds but not over days in response to endogenous stress. These results are crucial for understanding the impact of stress in various contexts. For instance, fluctuations in individual stress responses to the environment may help explain variations in consumer behaviors, such as impulse purchases, even among healthy adults
A mixed methods investigation into GP attitudes and experiences of using social prescribing in their practice
Full text linkAimSocial prescribing (SP) enables clinicians to signpost patients to non-medical services in the community in order to support their psycho-social needs. SP has been promoted as a positive service delivery model for primary and community care; however, there are few data on the views of doctors working in this area on the effectiveness of SP and its implementation.Subject and methodsThis study used a mixed methods approach to examine attitudes and experiences of general practitioners (GPs) on their use of SP. GPs completed an online survey (n = 102), provided narrative written responses (n = 55) and took part in semi-structured interviews on the topic (n = 8).ResultsPrincipal component analysis (PCA) showed that 90% of respondents use SP in their practice, with significant factor loadings on six separate components. Thematic analysis revealed three main themes, which were then combined with the PCA components to derive overarching themes that underpin effective implementation of SP: (1) perceptions of effectiveness and efficacy of SP, (2) training and awareness, and (3) structure and operational delivery.ConclusionThis study is one of the first to explore attitudes of doctors to SP. Whilst data shows that most respondents are supportive of SP in principle, the analysis also reveals that there are specific barriers that need to be overcome to enable effective implementation
Access Repository Dashboard
Do you manage Open Research Online? Become a CORE Member to access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard! 👇