Tenure, gender and household structure

Starting with a review of recent literature on gender and housing, this paper goes on to develop a new theory of household structure, in which concepts of gender and generation play a key role. The utility of this theory is then demonstrated in the analysis of data from a survey of households in the City of Salford

Estimating overdiagnosis in giant cell arteritis diagnostic pathways using genetic data: genetic association study

Objectives GCA can be confirmed by temporal artery biopsy (TAB) but false negatives can occur. GCA may be overdiagnosed in TAB-negative cases, or if neither TAB nor imaging is done. We used HLA genetic association of TAB-positive GCA as an ‘unbiased umpire’ test to estimate historic overdiagnosis of GCA. Methods Patients diagnosed with GCA between 1990 and 2014 were genotyped. During this era, vascular imaging alone was rarely used to diagnose GCA. HLA region variants were jointly imputed from genome-wide genotypic data of cases and controls. Per-allele frequencies across all HLA variants with P < 1.0 × 10−5 were compared with population control data to estimate overdiagnosis rates in cases without a positive TAB. Results Genetic data from 663 GCA patients were compared with data from 2619 population controls. TAB-negative GCA (n = 147) and GCA without TAB result (n = 160) had variant frequencies intermediate between TAB-positive GCA (n = 356) and population controls. For example, the allele frequency of HLA-DRB1*04 was 32% for TAB-positive GCA, 29% for GCA without TAB result, 27% for TAB-negative GCA and 20% in population controls. Making several strong assumptions, we estimated that around two-thirds of TAB-negative cases and one-third of cases without TAB result may have been overdiagnosed. From these data, TAB sensitivity is estimated as 88%. Conclusions Conservatively assuming 95% specificity, TAB has a negative likelihood ratio of around 0.12. Our method for utilizing standard genotyping data as an ‘unbiased umpire’ might be used as a way of comparing the accuracy of different diagnostic pathways

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

Tumor necrosis factor-α polymorphism, bone strength phenotypes, and the risk of fracture in older women

10.1210/jc.2004-2235Journal of Clinical Endocrinology and Metabolism9063491-349

Isolated housewives and complex maternal worlds: the significance of social contacts between women with young children in industrial societies.

This article reconsiders the picture of the mother of young children in industrialised societies as the 'isolated housewife', suggesting this notion is by no means straightforward. We suggest there is considerable evidence for the existence of mothers' social contacts and their significance both as 'work' and 'friendship' in industrial societies. A pre-occupation with the notion of the 'isolation' of 'housewives' has led social researchers to neglect sustained examination of the social relationships within which many/most mothers are involved on a day-to-day basis. Complexities of interpretation, for example what 'isolation' can actually mean, need to be drawn out from the existing literature. Evidence presented from two recent ethnographic studies shows patterned opportunities/constraints occurring in relation to mothers' social contacts within localised settings, whether through organised groups or other personal ties. The complex nature of individual women's social contacts is thus brought out. Some key questions are raised for the importance to sociology, anthropology and social policy of these apparently insignificant or invisible women's networks