Unemployment and health 1975-1987 : A case study in the relationship between research and policy debate.

SIGLEAvailable from British Library Document Supply Centre- DSC:D87556 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Is chemical zonation in plutonic rocks driven by changes in source magma composition or shallow-crustal differentiation?

Lithologic and magnetic-susceptibility mapping of the western Half Dome Granodiorite of the Tuolumne Intrusive Suite of California reveals seven km-scale lithologic cycles, each of which is bounded by a sharp west-dipping contact that is subparallel to the external contact of the pluton. Crosscutting relations indicate that the cycles become younger to the east. Each cycle is inferred to have been a zone of partial melt in which an eastern melt-depleted base grades westward to a melt-rich top now preserved as a leucocratic facies of the Half Dome Granodiorite. Sharp contacts between cycles may record freezing episodes when the rate of heat input into the growing pluton dropped below that required to maintain interstitial melt. Thus, the interstitial melt zone migrated with time and its size at any given time need not have differed greatly from the ~1km thickness of the cycles. Cycles occur on the outer, older margins of the suite, and disappear toward the interior, younger intrusions. Inward disappearance of cycles likely reflects thermal maturation of the system such that melt was continuously present until the final migration of the solidus through the intrusive suite. Although the cycles span the compositional range from granodiorite to leucogranite, trace-element trends preserved in the cycles differ dramatically from those of both the Tuolumne Intrusive Suite and other Cretaceous zoned plutons of the eastern Sierra Nevada batholith. We suggest that (1) the compositional variations of the intrusive suite and the batholith reflect a signal from the source of the magmas, and (2) the geochemistry within the km-scale cycles reflects in situ crystal/liquid separation

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

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

The persisting effect of unemployment on health and social well-being in men early in working life

In our studies of the effects of unemployment in the early working life of men in a British national birth cohort we have shown elsewhere that this experience was part of a longer term accumulation of social and health disadvantage. This present study asks whether men's unemployment also inflicted potential longterm damage to future socio-economic chances and health. We therefore constructed indicators of socio-economic circumstances and health at 33 years from factors already shown to be associated with health in later life. For the socio-economic indicator we used a combination of income, occupational status and home ownership and described this as socio-economic capital. For the health indicator we combined scores of body mass index, leisure time exercise, frequency of eating fresh fruit and of smoking, and described this as health capital. After controlling for pre-labour market socio-economic and health factors, prolonged unemployment is shown here to reduce significantly both socio-economic and health capital by age 33 years. We conclude that the experience of prolonged unemployment early in the working life of this population of young men looks likely to have a persisting effect on their future health and socio-economic circumstances.Unemployment Socio-economic capital Health capital National Child Development Study (NCDS) Britain

Geother evaluation and improvement: A progress report including test cases for two-dimensional BWIP (Basalt Waste Isolation Project) analysis

The objective of the work is to evaluate the GEOTHER code and peform necessary improvements to make it specifically suitable for predicting the environmental conditions of the waste package for the Basalt Waste Isolation Project (BWIP); and to perform resaturation analyses, that is, the analyses of steam formation and condensation, for the repository and waste package using the improved GEOTHER code. This is a progress report to BWIP documenting the status of GEOTHER code testing, evaluation, and improvements. The computational results documented in this report reflect the current condition of the code and the condition before code improvements. The test cases used are intended for examining the code features in sufficient detail and are not intended to be taken as final conclusions for BWIP applications