47 research outputs found
Inhibition of protein breakdown in cultured cells is a consistent response to growth factors
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Structural Ceramics by Fused Deposition of Ceramics
Fused Deposition of Ceramics (FDC) is a SFF technique, based on FDMTM technology, for
fabrication of advanced structural ceramics from powderlbinder filaments. In this study, in-situ
reinforced (ISR) Si3N4 powder and polymer/wax based binder systems were used as filament
material for FDC processing using a commercially available FDMTM system, 3D Modeler.
Powderlbinder feedstocks were mixed using a torque rheometer and filaments were fabricated
using a capillary rheometer and twin screw extruder. Green FDC components were built from
these filaments and then characterized for inter-road and inter-layer bonding. Binder removal
procedures were established for FDC green components to yield brown parts without distortion or
shape change. Brown FDC parts were characterized for carbon residue, pore distribution and
dimensional changes. Brown FDC parts were then sintered and the sintered density,
microstructure, and shrinkage anisotropy were studied.Mechanical Engineerin
Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
Peer reviewe
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Balance conditions in variational data assimilation for a high-resolution forecast model
This paper explores the role of balance relationships for background error covariance modelling as the model's grid box decreases to convective-scales. Data assimilation (DA) analyses are examined from a simplified convective-scale model and DA system (called ABC-DA) with a grid box size of 1.5km in a 2D 540km (longitude), 15km (height) domain. The DA experiments are performed with background error covariance matrices B modelled and calibrated by switching on/off linear balance (LB) and hydrostatic balance (HB), and by observing a subset of the ABC variables, namely v, meridional wind, r', scaled density (a pressure-like variable), and b', buoyancy (a temperature-like variable). Calibration data are sourced from two methods of generating proxies of forecast errors. One uses forecasts from different latitude slices of a 3D parent model (here called the `latitude slice method'), and the other uses sets of differences between forecasts of different lengths but valid at the same time (the National Meteorological Center method).
Root-mean-squared errors computed over the domain from identical twin DA experiments suggest that there is no combination of LB/HB switches that give the best analysis for all model quantities. It is frequently found though that the B-matrices modelled with both LB and HB do perform the best. A clearer picture emerges when the errors are examined at different spatial scales. In particular it is shown that switching on HB in B mostly has a neutral/positive effect on the DA accuracy at `large' scales, and switching off the HB has a neutral/positive effect at `small' scales. The division between `large' and `small' scales is between 10 and 100km. Furthermore, one hour forecast error correlations computed between control parameters find that correlations are small at large scales when balances are enforced, and at small scales when balances are not enforced (ideal control parameters have zero cross correlations). This points the way to modelling B with scale-dependent balances
Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study
Background:
Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea.
Methods:
CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107).
Findings:
2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect.
Interpretation:
Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition.
Funding:
UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council
SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript
Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease
One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials
Accelarated immune ageing is associated with COVID-19 disease severity
Background
The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls.
Results
We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity (
= 0.174, p = 0.043), with a major influence being disease severity (
= 0.188, p = 0.01).
Conclusions
Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease
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Preoperational radiation surveillance of the WIPP Project by EEG for the years 1993 - 1995
Average {sup 241}Am, {sup 239+240}Pu and {sup 238}Pu concentrations measured in ambient air near the Waste Isolation Pilot Plant (WIPP) site during 1993, 1994 and 1995 are consistent with similar data reported by the U.S. Environmental Protection Agency (EPA) and Los Alamos National Laboratory (LANL) for Espanola, Pojoaque and Santa Fe, New Mexico. Through the use of replicate analyses of matrix blanks minimum detectable activity (MDA), minimum detectable concentration (MDC) and action levels (ACTL) were established for the Environmental Evaluation Group (EEG) measurement system. Using MDA data from fixed air sampler (FAS) filters and conservative assumptions applied in the National Council on Radiation Protection and Measurements (NCRP) Report 123 (NCRP 1996), it is shown that the EEG sampling and measurement methodology is capable of detecting effluent air emissions which would produce a dose that is approximately 1000 times below the 40 CFR 191 Subpart A limit of 2.5E{sup -4} Sv/y (25 mrem/y). A similar calculation using the NCRP worksheet with storm water effluent MDCs found the EEG measurement program capable of detecting actinide emissions which would result in a dose that is approximately 10 times below the dose limits in 40 CFR 191 Subpart A and 40 CFR 61 Subpart H
Object Recognition and Tracking in Video Sequences: A New Integrated Methodology
This paper describes a methodology that integrates recognition and segmentation, simultaneously with image tracking in a cooperative manner, for recognition of objects (or parts of them) in image sequences. A probabilistic general approach at pixel level is depicted together with a practical heuristic simplification in which pixels’ class probabilities are approximated by a finite small set of class possibility values. These possibility values are updated iteratively along the image sequence for each class and each pixel taking into account both the prior tracking information and the spot-based object recognition results provided by a trained neural network. A further segmentation of the class possibility images allows the tracking of each object of interest in the sequence. The good experimental results obtained so far show the viability of the approach under certain conditions.Postprint (published version