Report of the panel on earth structure and dynamics, section 6

The panel identified problems related to the dynamics of the core and mantle that should be addressed by NASA programs. They include investigating the geodynamo based on observations of the Earth's magnetic field, determining the rheology of the mantle from geodetic observations of post-glacial vertical motions and changes in the gravity field, and determining the coupling between plate motions and mantle flow from geodetic observations of plate deformation. Also emphasized is the importance of support for interdisciplinary research to combine various data sets with models which couple rheology, structure and dynamics

Size effects in ion-neutral complex-mediated alkane eliminations from ionized aliphatic ethers

AbstractThe effects of the size of the ionic and neutral partners on ion-neutral complex-mediated alkane eliminations from ionized aliphatic ethers were determined by obtaining metastable decomposition spectra and photoionization ionization efficiency curves. Increasing the size of the ionic partner decreases the competitiveness of alkane elimination with alkyl loss. This is attributed to decreasing attraction between the partners with increasing distance between the neutral partner and the center of charge in the associated ion. Increasing the size of the neutral partner lowers the threshold for alkane elimination relative to that for simple dissociation when the first threshold is above ΔHf(products). This is attributed to increasing attraction between the partners with increasing polarizability of the radical in the complex. Adding a CH2 to the radical in a complex seems to increase the attraction between the partners by about 24 kJ mol−1

Mean Dynamic Topography of the Arctic Ocean

ICESat and Envisat altimetry data provide measurements of the instantaneous sea surface height (SSH) across the Arctic Ocean, using lead and open water elevation within the sea ice pack. First, these data were used to derive two independent mean sea surface (MSS) models by stacking and averaging along-track SSH profiles gathered between 2003 and 2009. The ICESat and Envisat MSS data were combined to construct the high-resolution ICEn MSS. Second, we estimate the 5.5-year mean dynamic topography (MDT) of the Arctic Ocean by differencing the ICEn MSS with the new GOCO02S geoid model, derived from GRACE and GOCE gravity. Using these satellite-only data we map the major features of Arctic Ocean dynamical height that are consistent with in situ observations, including the topographical highs and lows of the Beaufort and Greenland Gyres, respectively. Smaller-scale MDT structures remain largely unresolved due to uncertainties in the geoid at short wavelengths

Omicron neutralising antibodies after COVID-19 vaccination in haemodialysis patients.

Funder: Kidney Research U

Morphology of late Quaternary submarine landslides along the U.S. Atlantic continental margin

This paper is not subject to U.S. copyright. The definitive version was published in Marine Geology 264 (2009): 4-15, doi:10.1016/j.margeo.2009.01.009.The nearly complete coverage of the U.S. Atlantic continental slope and rise by multibeam bathymetry and backscatter imagery provides an opportunity to reevaluate the distribution of submarine landslides along the margin and reassess the controls on their formation. Landslides can be divided into two categories based on their source areas: those sourced in submarine canyons and those sourced on the open continental slope and rise. Landslide distribution is in part controlled by the Quaternary history of the margin. They cover 33% of the continental slope and rise of the glacially influenced New England margin, 16% of the sea floor offshore of the fluvially dominated Middle Atlantic margin, and 13% of the sea floor south of Cape Hatteras. The headwall scarps of open-slope sourced landslides occur mostly on the lower slope and upper rise while they occur mostly on the upper slope in the canyon-sourced ones. The deposits from both landslide categories are generally thin (mostly 20–40 m thick) and comprised primarily of Quaternary material, but the volumes of the open-slope sourced landslide deposits can be larger (1–392 km3) than the canyon-sourced ones (1–10 km3). The largest failures are located seaward of shelf-edge deltas along the southern New England margin and near salt domes that breach the sea floor south of Cape Hatteras. The spatial distribution of landslides indicates that earthquakes associated with rebound of the glaciated part of the margin or earthquakes associated with salt domes were probably the primary triggering mechanism although other processes may have pre-conditioned sediments for failure. The largest failures and those that have the potential to generate the largest tsunamis are the open-slope sourced landslides.The U.S. Nuclear Regulatory Commission and the U.S. Geological Survey are acknowledged for their support of this research.Work was funded by US Nuclear Regulatory Commission grant N6480 Physical study of tsunami sources

Risk Factors for Severe Outcomes in Patients With Systemic Vasculitis and COVID‐19: A Binational, Registry‐Based Cohort Study

Funder: Vifor Pharma; Id: http://dx.doi.org/10.13039/501100006484Objective: COVID‐19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID‐19. We undertook this study to establish the risk factors for severe COVID‐19 outcomes in these patients, including the impact of immunosuppressive therapies. Methods: A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID‐19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death. Results: The cohort included 65 patients with systemic vasculitis who developed COVID‐19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1–14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9–38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes. Conclusion: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID‐19. These data can inform clinical decision‐making relating to the risk of severe COVID‐19 in this vulnerable patient group

Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death

Funder: The Sidharth Burman endowmentEnd-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte–endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders