Relativistic Models for Binary Neutron Stars with Arbitrary Spins

We introduce a new numerical scheme for solving the initial value problem for quasiequilibrium binary neutron stars allowing for arbitrary spins. The coupled Einstein field equations and equations of relativistic hydrodynamics are solved in the Wilson-Mathews conformal thin sandwich formalism. We construct sequences of circular-orbit binaries of varying separation, keeping the rest mass and circulation constant along each sequence. Solutions are presented for configurations obeying an n=1 polytropic equation of state and spinning parallel and antiparallel to the orbital angular momentum. We treat stars with moderate compaction ((m/R) = 0.14) and high compaction ((m/R) = 0.19). For all but the highest circulation sequences, the spins of the neutron stars increase as the binary separation decreases. Our zero-circulation cases approximate irrotational sequences, for which the spin angular frequencies of the stars increases by 13% (11%) of the orbital frequency for (m/R) = 0.14 ((m/R) = 0.19) by the time the innermost circular orbit is reached. In addition to leaving an imprint on the inspiral gravitational waveform, this spin effect is measurable in the electromagnetic signal if one of the stars is a pulsar visible from Earth.Comment: 21 pages, 14 figures. A few explanatory sentences added and some typos corrected. Accepted for publication in Phys. Rev.

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

Involvement of BAG3 and HSPB7 loci in various etiologies of systolic heart failure: Results of a European collaboration assembling more than 2000 patients

International audienceHeart failure (HF), a major public health burden affecting 2% of industrialized populations, is a syndrome resulting from structural or functional myocardial impairment leading to inadequate cardiac output to meet the body's metabolic demands [1]. Half of HF patients present systolic dysfunction (systolic-HF), also called reduced ejection fraction (HF-REF), a disease related to various causes including idiopathic Dilated Cardiomyopathy (DCM) and Coronary Artery Diseases (CAD) (ischemic-HF). HF is usually a multifactorial disease but the genetic variants contributing to its susceptibility or its severity may be different according to its underlying causes [2] and their identification is only beginning.[...

Author Correction: Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals (Nature Communications, (2020), 11, 1, (2523), 10.1038/s41467-019-10717-9)

10.1038/s41467-021-21052-3Nature Communications12183

Publisher Correction: LifeTime and improving European healthcare through cell-based interceptive medicine (Nature, (2020), 587, 7834, (377-386), 10.1038/s41586-020-2715-9)

10.1038/s41586-021-03287-8Nature592785

LifeTime and improving European healthcare through cell-based interceptive medicine

LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.We would like to acknowledge all participants that have attended and contributed to LifeTime meetings and workshops through many exciting presentations and discussions. We thank Johannes Richers for artwork. LifeTime has received funding from the European Unionʼs Horizon 2020 research and innovation framework programme under Grant agreement 820431