Evolution of electronic and ionic structure of Mg-clusters with the growth cluster size

The optimized structure and electronic properties of neutral and singly charged magnesium clusters have been investigated using ab initio theoretical methods based on density-functional theory and systematic post-Hartree-Fock many-body perturbation theory accounting for all electrons in the system. We have systematically calculated the optimized geometries of neutral and singly charged magnesium clusters consisting of up to 21 atoms, electronic shell closures, binding energies per atom, ionization potentials and the gap between the highest occupied and the lowest unoccupied molecular orbitals. We have investigated the transition to the hcp structure and metallic evolution of the magnesium clusters, as well as the stability of linear chains and rings of magnesium atoms. The results obtained are compared with the available experimental data and the results of other theoretical works.Comment: 30 pages, 10 figures, 3 table

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

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

A multi-proxy study of Holocene lake development, lake settlement and vegetation history in central Ireland

Stratigraphical investigations, geomorphological mapping, and diatom, plant macrofossil and pollen analyses were undertaken in and around two lakes in central Ireland to establish correlations between changes in lake conditions and catchment vegetation throughout the Holocene. Similar investigations of an adjacent mire reveal early Holocene changes in lake level and area. The palaeoecological data show high correlations related to variations in lake depth and area, catchment vegetation type, organic inputs and trophic status. Catchment-scale deforestation is gradual and occurs through the Bronze and the Iron Ages, and the construction of a crannog in the early Medieval period (seventh century AD) appears to be associated with a widespread increase in deforestation and mixed agriculture in the catchment. Both pollen and plant macrofossils suggest that one of the crannogs was used for crop storage in addition to domestic and any other activities. In the early to middle Holocene similarities in the proxy-data appear to be climatically driven through changing lake levels and areal extent whereas the later Holocene record is clearly dominated by anthropogenic changes within the catchment and the construction of crannogs in the lakes. The advantages of combining multi-proxy indicators of lake hydroecology with the vegetation record are illustrated

Multi-proxy study of Holocene environmental change and human activity in the Central Apennine Mountains, Italy

This paper describes a multi-proxy palaeoecological investigation undertaken in conjunction with an archaeological survey of the Upper Sangro Valley in the Abruzzo National Park, Central Italy. Despite being a biodiversity hotspot and regarded as a near-pristine area, the pollen, spore and diatom data all show major changes in the vegetation extending to over 2000 m a.s.l. during the mid to late Holocene. Although there are changes in ecological composition earlier in the Holocene they are different in type and magnitude from the changes which began about 800 cal a BC. The pollen and diatom evidence do not correlate well with regional palaeoclimate data, or on-site isotopic evidence, but do appear to be related to Samnite (later Iron Age) clearance and upland grazing associated with transhumance and later annexation (and centuriation) of the lower slopes by Roman surveyors. The greatest change in vegetation was during the period c. AD 500–600 and corresponds with the Byzantine–Gothic Wars, and Lombard–Carolingian settlement reorganization into nucleated hilltop settlements which managed upland grazing. This pattern of intensive land use at all altitudes persisted until the early 20th century and only changed following rural depopulation after World War II. These data illustrate how cultural factors had a profound effect on this mountainous region which, in this case, far outweighed the effects of climatic fluctuations which are known to have occurred from both this study area and the region

A sediment-based multiproxy palaeoecological approach to the environmental archaeology of lake dwellings (crannogs), Central Ireland

A multiproxy study of Ballywillin Crannog, Lough Kinale, central Ireland is presented. The methodology used reveals the wealth of information that a multiproxy approach can contribute in lake settlement studies. Plant macrofossils, pollen and spores, diatoms, chironomids and Coleoptera from a lake core are used to reconstruct local and regional vegetation change and lake history to establish the age and function of the crannog. The palaeoecological evidence suggests that Ballywillin Crannog was constructed around AD620, with its most intensive period of occupation after AD1150. Cereals and a range of gathered fruits and nuts were brought onto and cooked on the crannog, and cereal grains were possibly stored there

The effect of using fecal testing after a negative sigmoidoscopy on the risk of death from colorectal cancer.

To examine whether receiving a fecal occult blood test after a negative sigmoidoscopy reduced mortality from colorectal cancer. We used a nested case-control design with incidence-density matching in historical cohorts of 1,877,740 50-90-year-old persons during 2006-2012, in an integrated health-system setting. We selected 1758 average risk patients who died from colorectal cancer and 3503 matched colorectal cancer-free persons. Colorectal cancer-specific death was ascertained from cancer and mortality registries. Screening histories were determined from electronic and chart-audit clinical data in the 5- to 10-year period prior to the reference date. We evaluated receipt of subsequent fecal occult blood test within five years of the reference date among patients with negative sigmoidoscopy two to six years before the reference date. Of the 5261 patients, 831 patients (204 colorectal cancer deaths/627 controls) had either negative sigmoidoscopy only (n = 592) or negative sigmoidoscopy with subsequent screening fecal occult blood test (n = 239). Fifty-six (27.5%) of the 204 patients dying of colorectal cancer and 183 (29.2%) of the 627 colorectal cancer-free patients received fecal occult blood test following a negative sigmoidoscopy. Conditional regressions found no significant association between fecal occult blood test receipt and colorectal cancer death risk, overall (adjusted odds ratio = 0.93, confidence interval: 0.65-1.33), or for right (odds ratio = 1.02, confidence interval: 0.65-1.60) or left-colon/rectum (odds ratio = 0.77, confidence interval: 0.39-1.52) cancers. Similar results were obtained in sensitivity analyses with alternative exposure ascertainment windows or timing of fecal occult blood test. Our results suggest that receipt of at least one fecal occult blood test during the several years after a negative sigmoidoscopy did not substantially reduce mortality from colorectal cancer