SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

The quaternary geology of the Buddon Ness area of Tayside, Scotland

1.25SIGLELD:7520.335(IGS-R--81/1). / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Lithostratigraphy of the late Devonian and early Carboniferous rocks in the Midland Valley of Scotland

2.75SIGLEAvailable from British Library Document Supply Centre- DSC:1947.5903(BGS-R--18(pt.3)) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The impact of the presence of autoantibodies against citrullinated, carbamylated and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis:an observational cohort study

Background: A range of anti-modified protein antibodies (AMPAs) are associated with rheumatoid arthritis. We aimed to assess the relationship between AMPA profiles and radiographic progression in patients with new-onset rheumatoid arthritis. Methods: In this cohort study, we obtained samples and data from the Scottish Early Rheumatoid Arthritis (SERA) inception cohort and biobank, which recruited patients with new-onset rheumatoid arthritis or undifferentiated arthritis who had at least one swollen joint from 20 hospitals across Scotland. AMPAs in plasma samples were measured by ELISAs at baseline. Paired radiographs of the hands and feet were taken at baseline and at 1 year and were scored with the Sharp-van der Heijde (SvH) method. We calculated differences in radiographic progression using estimated marginal mean changes between baseline and 1 year, with the baseline values of radiographic variables, rheumatoid factor, sex, age at recruitment, symptom duration, and Disease Activity Score 28 with C-reactive protein included as covariates. Findings: Between March 1, 2011, and April, 30, 2015, 1073 patients were recruited to the SERA study. 362 patients with rheumatoid arthritis were included in our study and had their AMPA profiles determined. Patients were grouped into four main autoantibody profiles by reactivities to post-translational modifications: single positivity for anti-citrullinated peptide antibodies (ACPAs; 73 [20%]); double positivity for ACPAs and anti-acetylated peptide antibodies (AAPAs; 45 [12%]); triple positivity for ACPAs, AAPAs, and anti-carbamylated peptide antibodies (151 [42%]); and AMPA negativity (74 [20%]). 19 (5%) patients were in one of the minor autoantibody groups. Of the 233 patients with both antibody data and radiographs of sufficient quality, triple-positive patients had more radiographic progression between baseline and 12 months (estimated mean change in total SvH score 1·8, 95% CI 0·9–2·6, SE 0·4) than did single-positive patients (0·5, 0·1–1·0, 0·2; estimated mean difference in the total change in SvH score 1·2, 95% CI 0·1–2·4, SE 0·5). There was no difference in radiographic progression between single positive patients and AMPA negative patients (estimated mean change in total SvH score 0·7, 95% CI 0·1–1·4, SE 0·3; estimated mean difference in the total change in SvH score −0·2, 95% CI −1·1 to 0·7, SE 0·4). Interpretation: This study suggests that the optimal prediction of future rates of radiographic progression in patients with rheumatoid arthritis will require an assessment of autoantibodies against multiple post-translationally modified proteins or peptides. Funding: The EU FP7 HEALTH programme, the Scottish Translational Medicine Research Collaboration, and the Chief Scientist Office Scotland

The impact of the presence of autoantibodies against citrullinated, carbamylated and acetylated peptides on radiographic progression in patients with new onset rheumatoid arthritis: an observational study

Background: A range of anti-modified peptide autoantibodies (AMPA) are associated with rheumatoid arthritis (RA). We assessed the relationship between AMPA profiles and radiographic progression in new onset RA. Methods: AMPAs (targeting citrullinated, carbamylated and acetylated peptides) were measured by ELISA in 362 patients with new onset RA from the Scottish Early Rheumatoid Arthritis Inception Cohort and Biobank (SERA). Radiographic progression in hands and feet was determined using the Sharp-van der Heijde (SvH) method. 233 patients with RA had AMPA status and radiographic progression scores after quality control. Differences in radiographic progression between groups were determined using least square means changes with baseline value of radiographic variable, rheumatoid factor, gender, age of onset of disease, symptom duration and baseline DAS28-CRP included as covariates. Findings: Four main autoantibody groupings by class of modification were identified in RA patients (n=362) with reactivities against modified peptides as follows: citrullinated only (n=73, 20%), citrullinated and acetylated (n=45, 12%), citrullinated, carbamylated and acetylated (n=151, 42%) and AMPA negative (n=74, 20%). In RA patients with both antibody and radiographic data, those with antibodies against all three post-translational modifications (least square mean 1&#xB7;7, n=97) had greater radiographic progression over 12 months compared to those with anti-citrullinated peptide antibodies (ACPA) only (least square mean 0&#xB7;5, n=48) (least square mean difference of total SvH score of 1&#xB7;2, 95% CI 0&#xB7;05-2.40). There was no difference in progression comparing ACPA only with seronegative patients (least square mean 0.7, n=47) (least square mean difference -0.2, 95% CI -1&#xB7;09-0&#xB7;67). Interpretation: RA patients with all three classes of AMPA have more rapid radiographic progression over 12 months than those with ACPA alone. Patients with ACPA alone had similar radiographic progression over 12 months to AMPA negative patients.</p

The anatomy of an early Dinantian terraced floodplain: palaeoenvironment and early diagenesis

The lowermost Carboniferous rocks in the Cockburnspath area of east Berwickshire (southern Scotland) are interpreted as coastal floodplain sediments. A lower mudstone-dominated unit is composed of silty mudstones and shales with subordinate sandstones and argillaceous ferroan dolomites (cementstones). These are interpreted as distal floodplain sediments with periodic crevasse-splay deposition. The dark grey colour of the mudrocks suggests deposition in reducing conditions, probably in floodplain lakes. Most of the cementstones are concretionary, some with septarian cracks, suggesting an early diagenetic origin. An immature palaeosol suggests periodic pedogenesis under improved drainage. A synsedimentary erosion surface indicates incision of a valley into the floodplain, presumably in response to base-level lowering. An upper sandstone-dominated unit starts with fine-grained rippled sandstones, cut by small channel sandstones. These are interpreted as floodplain lake deposits fed by crevasse channels. A distinctive conglomerate with cementstone clasts, wood fragments and fish remains is interpreted as a major overbank deposit, dumped into a pre-existing floodplain lake. A bivalve fauna was established in the overlying mudstones, followed by a thin limestone with a restricted marine fossil assemblage, showing that seawater flooding of the lakes occurred at times. Mudrocks throughout the sequence contain no pyrite, except for the marine band which has an organic-carbon/sulphur ratio and degree of pyritization value typical of marine sediments. The concretionary cementstones have d13C values around —4 to —6%0/00 PDB which are interpreted as indicative of anaerobic oxidation of organic matter. The combined geochemical data suggest a significant involvement of iron reduction in cementstone formation, although the d13C values are ambiguous in assessing the relative involvement of methanogenesis and methane oxidation. Limited seawater inundation of the floodplains might have supplied magnesium and calcium ions for dolomite formation assuming that any H2S derived as a result of sulphate reduction was oxidized by iron reduction. Alternatively a weathering source for solutes might have been involved