Middle Neolithic pits and a burial at West Amesbury, Wiltshire

Excavations on the south-eastern slopes of King Barrow Ridge, 1.5 km east of Stonehenge, revealed five pits, a grave and other features of Middle Neolithic date. Analysis of the pit assemblages and the partial inhumation interred in the grave has provided insights into lifeways in this landscape in the late fourth millennium cal BC. Evidence suggests that the area was visited by a pastoralist, mobile community on a semi-regular basis for a significant period, in late autumn or winter. Selected remnants of craft-working and consumption were deposited in pits, before deliberate infilling. These depositions repeatedly memorialised activity on the hillside at a time of contemporary activity elsewhere on King Barrow Ridge and at the future site of Stonehenge. Middle Neolithic pits are present in significant numbers across King Barrow Ridge, and alongside pits in the Durrington area, form one of the densest concentrations of such activity in the region. Long distance mobility is suggested by the possible Irish origins of the inhumation, the first Middle Neolithic individual excavated in the environs of Stonehenge. Whilst of significance for understanding the Middle Neolithic in the WHS and the region, this research also hints at the roots of Late Neolithic monumentalisation of this landscape

Function and failure of the fetal membrane : modelling the mechanics of the chorion and amnion

The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally occurs at term, preterm rupture can result in increased risk of fetal mortality and morbidity, as well as danger of infection in the mother. Although structural changes have been observed in the membrane in such cases, the mechanical behaviour of the human fetal membrane in vivo remains poorly understood and is challenging to investigate experimentally. Therefore, the objective of this study was to develop simplified finite element models to investigate the mechanical behaviour and rupture of the fetal membrane, particularly its constituent layers, under various physiological conditions. It was found that modelling the chorion and amnion as a single layer predicts remarkably different behaviour compared with a more anatomically-accurate bilayer, significantly underestimating stress in the amnion and under-predicting the risk of membrane rupture. Additionally, reductions in chorion-amnion interface lubrication and chorion thickness (reported in cases of preterm rupture) both resulted in increased membrane stress. Interestingly, the inclusion of a weak zone in the fetal membrane that has been observed to develop overlying the cervix would likely cause it to fail at term, during labour. Finally, these findings support the theory that the amnion is the dominant structural component of the fetal membrane and is required to maintain its integrity. The results provide a novel insight into the mechanical effect of structural changes in the chorion and amnion, in cases of both normal and preterm rupture

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Improving entity disambiguation with a vector space semantic tagger

This note describes a few suggestions for improving entity disambiguation using a vector-based semantic tagger, trained using the Skipgram model. The suggestions include assuming non uniform distributions for the probability distribution of the entity, different ways of building vectors for the document, and using a neural network architecture. We exemplify the suggestions on a running example: the disambiguation of entity Boston, which may be referring to the famous city in Massachusetts US, or a town in Lincolnshire UK, or as we will see in the examples below, a few other places in the US and UK

Coral bioerosion on the marginal reefs of northeastern Arabia

© Copyright © 2019 AEHMS. The maintenance of coral reef framework results from a balance between skeletal accretion and bioerosion, and this balance can be disrupted by environmental stress and disturbance. Coral reefs in northeastern Arabia exist in extreme environmental conditions and have experienced severe disturbances in recent years. This study assessed the intensity of macrobioerosion in two regionally common species, Platygyra daedalea and Cyphastrea microphthalma, at three sites within the southern Persian/Arabian Gulf and at one site in the Sea of Oman. On average, bioeroders removed 9.2 ± 1.6% of the skeletal surface area in P. daedalea and 26.4 ± 1.6% in C. microphthalma, with variation between species attributed to differences in colony morphology. Bioerosion intensity varied among sites in each species. Within the southern Arabian Gulf, both P. daedalea and C. microphthalma showed the highest bioerosion intensity at Delma, in the western region, compared with that of Saadiyat or Ras Ghanada to the east, with the elevated bioerosion at Delma consistent with a history of more extreme environmental conditions and bleaching-related disturbances. The highest bioerosion in P. daedalea occurred at Fujairah in the Sea of Oman, and this site was amongst the highest in C. microphthalma. Although this site is characterized by more benign environmental conditions, reefs in this area experienced mass coral mortality due to anoxia during a large-scale harmful algal bloom in 2008/9 and the high bioerosion in Fujairah likely represents a long-term signature of this disturbance. The intensity of macrobioerosion observed here is high compared with other regions, suggesting that that chronic exposure to long-term environmental stress and a history of disturbance may lead enhanced loss of reef framework

Prediction of tool-wear in turning of medical grade cobalt chromium molybdenum alloy (ASTM F75) using non-parametric Bayesian models

We present a novel approach to estimating the effect of control parameters on tool wear rates and related changes in the three force components in turning of medical grade Co-Cr-Mo (ASTM F75) alloy. Co-Cr-Mo is known to be a difficult to cut material which, due to a combination of mechanical and physical properties, is used for the critical structural components of implantable medical prosthetics. We run a designed experiment which enables us to estimate tool wear from feed rate and cutting speed, and constrain them using a Bayesian hierarchical Gaussian Process model which enables prediction of tool wear rates for untried experimental settings. However, the predicted tool wear rates are non-linear and, using our models, we can identify experimental settings which optimise the life of the tool. This approach has potential in the future for realtime application of data analytics to machining processes.Enterprise IrelandDePuy SynthesUpdate embargo when doing check date report - MEL 01/09/201