Kinetics of Ordering in Fluctuation-Driven First-Order Transitions: Simulations and Dynamical Renormalization

Many systems where interactions compete with each other or with constraints are well described by a model first introduced by Brazovskii. Such systems include block copolymers, alloys with modulated phases, Rayleigh-Benard Cells and type-I superconductors. The hallmark of this model is that the fluctuation spectrum is isotropic and has a minimum at a nonzero wave vector represented by the surface of a d-dimensional hyper-sphere. It was shown by Brazovskii that the fluctuations change the free energy structure from a $\phi ^{4}$ to a $\phi ^{6}$ form with the disordered state metastable for all quench depths. The transition from the disordered to the periodic, lamellar structure changes from second order to first order and suggests that the dynamics is governed by nucleation. Using numerical simulations we have confirmed that the equilibrium free energy function is indeed of a $\phi ^{6}$ form. A study of the dynamics, however, shows that, following a deep quench, the dynamics is described by unstable growth rather than nucleation. A dynamical calculation, based on a generalization of the Brazovskii calculations shows that the disordered state can remain unstable for a long time following the quench.Comment: 18 pages, 15 figures submitted to PR

Middle to late Pleistocene palaeoecological reconstructions and palaeotemperature estimates for cold/cool stage deposits at Whittlesey, eastern England

Fossiliferous beds in a complex sequence of late Middle to Late Pleistocene deposits at Whittlesey, eastern England, provided a rare opportunity for a multidisciplinary study of the palaeoecology of cool/cold stage deposits from different glacial stages. The fossiliferous sediments investigated form part of the River Nene 1st Terrace. Three of the four fossil assemblages investigated pre-date the last interglacial stage (Ipswichian/Eemian/marine oxygen isotope stage (MIS) 5e), whereas the other dates to part of the MIS 3 interstadial complex (Middle Devensian/Weichselian). Pollen, plant macrofossil, molluscan, coleopteran, ostracod, foraminifera and vertebrate data are available to a greater or lesser extent for each cool/cold stage assemblage, and they broadly present the same ecological picture for each one: a continuum from low-energy permanent to non-permanent aquatic habitats through marshland with associated waterside taxa, together with flood influxes of fluvial, riparian and ruderal taxa. Although each fossil assemblage records cool/cold climatic conditions, to a greater or lesser extent, these conditions are more apparent in the insect and ostracod faunas. In comparison with results published for the Last Glacial Maximum (LGM) stadial in The Netherlands, palaeotemperature estimates based on ranges of mutual agreement between independent coleopteran and ostracod methods for the three pre-Ipswichian/Eemian assemblages indicate minimum mean July air temperatures that are from +1° to +3 °C warmer, but January values that embrace the −8 °C estimate for the LGM. There is, however, a disparity between the coleopteran and ostracod palaeotemperature estimates for the Middle Devensian/Weichselian fossil assemblage, which are based on two different sample stratigraphic levels; the lower, coleopteran assemblage is indicative of very cool, continental climates, whereas the stratigraphically slightly higher ostracod assemblage suggests a climatic amelioration. Lack of numerical age-estimates prevents a robust stratigraphical interpretation, but the youngest pre-Ipswichian/Eemian fossil assemblage could date to the MIS 7–6 transition, at a time when cooling possibly preceded glacially driven sea-level fall. It is apparent from the rich coleopteran data that some continental cold-indicator taxa also appeared in pre-Ipswichian/Eemian cold stages and therefore assignment of continental cold-indicator taxa to particular Devensian/Weichselian intervals should be undertaken with care

Spinodal decomposition in multicomponent fluid mixtures: A molecular dynamics study

We have investigated the effect of the number p of components on the dynamics of phase separation in two-dimensional symmetric multicomponent fluids. In contrast to concentrated two-dimensional binary fluids, where the growth dynamics is controlled by the coupling of the velocity held to the order parameter, leading to large growth-exponent values, the dynamics in multicomponent fluids (p = 3, 4) is found to follow a t(1/3) growth law, where t is time, which we relate to a long-wavelength evaporation-condensation process. These findings, which are proposed to be consequences of the compact domain structure persisting in multicomponent fluids, imply that hydrodynamic modes do not affect the dynamics of the phase separation in these systems

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury

Long COVID and cardiovascular disease: a prospective cohort study

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

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