Long-term probability distribution of fixed offshore structuralresponse using animproved version of finite memory nonlinear system procedure

Offshore structures are exposed to random wave loading in the ocean environment and hence the probability distribution of the extreme values of their response to wave loading is required for their safe and economical design. Due to nonlinearity of the drag component of Morison’s wave loading and also due to intermittency of wave loading on members in the splash zone, the response is often non-Gaussian [1-2]; therefore, simple techniques for derivation of the probability distribution of extreme responses are not available. However, it has recently been shown that the short-term response of an offshore structure exposed to Morison wave loading can be approximated by the response of an equivalent finite-memory nonlinear system (FMNS) [3]. Previous investigation shows that the developed FMNS models reduce the computational effort but the predictions are not very good for low intensity sea states. Therefore, to overcome this deficiency, a modified version of FMNS models is referred to as MFMNS models is used to determine the extreme response values which improves the accuracy but is computationally less efficient than FMNS models. In this paper, the 100-year responses derived from the long-term probability distribution of the extreme responses from MFMNS and FMNS models are compared with corresponding distributions from the CTS method is investigated with the effect of current to establish their level of accuracy. The methodology for derivation of the long-term distribution of extreme responses (and the evaluation of 100-year responses) is discussed. The accuracy of the predictions of the 100- year responses from MFMNS and FMNS models will then be investigated

Comparison of the extreme responses from different methods of simulating wave kinematics

Linear random wave theory (LRWT) is frequently used to simulate water particle kinematics at different nodes of an offshore structure from a reference surface elevation record. However, it is well known that LRWT leads to water particle kinematics with exaggerated high-frequency components in the vicinity of mean water level (MWL). Methods have been introduced to overcome this problem of high kinematics above the MWL consists of using linear wave theory (such as Wheeler, vertical stretching, effective node elevation and effective water depth methods) can be used to provide a more realistic representation of near- surface wave kinematics. There is promising as there is some evidence that the water particle kinematics from the Wheeler method are underestimated and that those from the vertical stretching method are somewhat exaggerated. In this paper, the comparisons of the probability distributions of extreme values from different methods of simulation wave kinematics are investigated by using Monte Carlo simulation procedure

The effect of wave in-deck in conventional pushover analysis

Subsidence is not a local settlement and one of the phenomena that may be experiencing by the offshore platform throughout the platform life. Compaction of the reservoir can cause it due to pressure reduction resulted to vertical movement of soils from the reservoir to mudline. The impact of subsidence on platforms will lead to a gradually reduces wave crest to deck air gap (insufficient air gap) and causing the Wave-in-Deck (WID) on platform deck. The WID load can cause a major consequence damage to the deck structures and potential to the collapse of the entire platform. The aim of this study is to investigate the impact of WID (with and without load) on structure response for fixed offshore structure. The usual run of pushover analysis only considering the base 100-years design crest height for the ultimate collapse. Thus, by calculating the wave height at collapse using a limit state equation for probabilistic model can give a significant result for WID. It is crucial to ensure that the Reserve Strength Ratio (RSR) is not overly estimated hence giving a false impression of the value. This study is performed in order to quantify the WID load effect on producing the new revised RSR. Finally, a parametric study on the probability of failure (POF) of the platform will be performed. As part of the analysis, the USFOS Software (Non-linear) and wave-in-deck calculation as suggested by ISO 19902 as practice in the industry are used in order to complete the study. It is expected that the new revised RSR with the inclusion of WID load will be lower hence increases the POF of the platform. The accuracy and effectiveness of this method will assist the industry, especially operators, for the purpose of decision-making and, ore specifically, for their outlining of action items as part of their business risk management

Design and fabrication of densely integrated silicon quantum dots using a VLSI compatible hydrogen silsesquioxane electron beam lithography process

Hydrogen silsesquioxane (HSQ) is a high resolution negative-tone electron beam resist allowing for direct transfer of nanostructures into silicon-on-insulator. Using this resist for electron beam lithography, we fabricate high density lithographically defined Silicon double quantum dot (QD) transistors. We show that our approach is compatible with very large scale integration, allowing for parallel fabrication of up to 144 scalable devices. HSQ process optimisation allowed for realisation of reproducible QD dimensions of 50 nm and tunnel junction down to 25 nm. We observed that 80% of the fabricated devices had dimensional variations of less than 5 nm. These are the smallest high density double QD transistors achieved to date. Single electron simulations combined with preliminary electrical characterisations justify the reliability of our device and process

Gravitational collapse of a Hagedorn fluid in Vaidya geometry

The gravitational collapse of a high-density null charged matter fluid, satisfying the Hagedorn equation of state, is considered in the framework of the Vaidya geometry. The general solution of the gravitational field equations can be obtained in an exact parametric form. The conditions for the formation of a naked singularity, as a result of the collapse of the compact object, are also investigated. For an appropriate choice of the arbitrary integration functions the null radial outgoing geodesic, originating from the shell focussing central singularity, admits one or more positive roots. Hence a collapsing Hagedorn fluid could end either as a black hole, or as a naked singularity. A possible astrophysical application of the model, to describe the energy source of gamma-ray bursts, is also considered.Comment: 14 pages, 2 figures, to appear in Phys. Rev.

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

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