Magnetostratigraphy of the Lower Triassic beds from Chaohu(China) and its implications for the Induan–Olenekian stage boundary.

A magnetostratigraphic study was performed on the lower 44 m of the West Pingdingshan section near Chaohu city, (Anhui province, China) in order to provide a magnetic polarity scale for the early Triassic. Data from 295 paleomagnetic samples is integrated with a detailed biostratigraphy and lithostratigraphy. The tilt-corrected mean direction from the West Pingdingshan section, passes the reversal and fold tests. The overall mean direction after tilt correction is D=299.9º, I=18.3º (κ=305.2, α95=1.9, N=19). The inferred paleolatitude of the sampling sites (31.6ºN, 117.8ºE) is about 9.4º, consistent with the stable South China block (SCB), though the declinations indicate some 101o counter-clockwise rotations with respect to the stable SCB since the Early Triassic. Low-field anisotropy of magnetic susceptibility indicates evidence of weak strain. The lower part of the Yinkeng Formation is dominated by reversed polarity, with four normal polarity magnetozones (WP2n to WP5n), with evidence of some thinner (<0.5 m thick) normal magnetozones. The continuous magnetostratigraphy from the Yinkeng Formation, provides additional high-resolution details of the polarity pattern through the later parts of the Induan into the lowest Olenekian. The magnetostratigraphic and biostratigraphic data shows the conodont marker for the base of the Olenekian (first presence of Neospathodus waageni) is shortly prior to the base of normal magnetozone WP5n. This provides a secondary marker for mapping the base of the Olenekian into successions without conodonts. This section provides the only well-integrated study from a Tethyan section across this boundary, but problems remain in definitively relating this boundary into Boreal sections with magnetostratigraphy

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

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Magnetostratigraphy of the Lower Triassic beds from Chaohu(China) and its implications for the Induan–Olenekian stage boundary.

A magnetostratigraphic study was performed on the lower 44 m of the West Pingdingshan section near Chaohu city, (Anhui province, China) in order to provide a magnetic polarity scale for the early Triassic. Data from 295 paleomagnetic samples is integrated with a detailed biostratigraphy and lithostratigraphy. The tilt-corrected mean direction from the West Pingdingshan section, passes the reversal and fold tests. The overall mean direction after tilt correction is D=299.9º, I=18.3º (κ=305.2, α95=1.9, N=19). The inferred paleolatitude of the sampling sites (31.6ºN, 117.8ºE) is about 9.4º, consistent with the stable South China block (SCB), though the declinations indicate some 101o counter-clockwise rotations with respect to the stable SCB since the Early Triassic. Low-field anisotropy of magnetic susceptibility indicates evidence of weak strain. The lower part of the Yinkeng Formation is dominated by reversed polarity, with four normal polarity magnetozones (WP2n to WP5n), with evidence of some thinner (<0.5 m thick) normal magnetozones. The continuous magnetostratigraphy from the Yinkeng Formation, provides additional high-resolution details of the polarity pattern through the later parts of the Induan into the lowest Olenekian. The magnetostratigraphic and biostratigraphic data shows the conodont marker for the base of the Olenekian (first presence of Neospathodus waageni) is shortly prior to the base of normal magnetozone WP5n. This provides a secondary marker for mapping the base of the Olenekian into successions without conodonts. This section provides the only well-integrated study from a Tethyan section across this boundary, but problems remain in definitively relating this boundary into Boreal sections with magnetostratigraphy

EC97-2506 A Place in the Country: The Acreage Owner\u27s Guide

A special place in the country is often a long-awaited dream. For many it communicates freedom, open space, clean air and unique opportunities to enjoy hobbies, nature and quiet living at its best. Making this a reality not only requires a major financial investment, it also requires careful planning and assessment of the existing property or new homesite under consideration. This extension circular helps you as an acreage owner make the right decisions when living in the country

Elder Abuse and Adult Safeguarding in UK

This chapter will provide an overview of elder abuse, with a particular focus on the UK. The issues and developments that have occurred globally will be briefly explored. Over the last ten years, there has been increasing global recognition of the abuse and neglect of older adults as a social problem in need of attention. The UK was one of the earliest of European countries to undertake work in this area. However, the identification of abuse remains somewhat problematic and defining abuse remains difficult, perhaps even more so when the abuse occurs within an institutional setting. Techniques of intervention with victims of abuse and those who abuse are in comparatively early stages of development, although in recent years there has been progress in the production of policies and procedures for healthcare and social care professionals. A number of national and international organisations have been established to respond to abuse and abusive situations; there are differences between different nations of the UK in how abuse is responded to. Various research initiatives are underway. Education and training for professionals is taking place concerning recognition and awareness of abuse and intervention skills. This chapter aims to examine some of the pertinent issues from a UK context. Responses to the problem of elder abuse will be explored with a concentration on techniques of intervention from a UK perspective, together with some exploration of a number of prevention strategies. Possible future developments and the potential for international action to resolve this problem will be considered

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

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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