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t suitable for clinical application in individual patients. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES The mechanisms of attrition of the Fontan population have been poorly characterised and it is unclear whether some of the deaths are potentially preventable. We analysed the circumstances of late death in patients with a Fontan circulation, with a special focus on identifying lesions amenable to intervention that may have contributed to the decline of their circulation. METHODS Between 1975 and 2018, a total of 105 patients from a Bi-National Registry died beyond 1 year after Fontan completion, at a median age of 18.6 (IQR 13.8-26.0) years old, 12.7 (IQR 6.0-19.3) years after Fontan completion. RESULTS A total of 105 patients died-63 patients (60%) with an atriopulmonary (AP) Fontan, 21 patients (20%) with a lateral tunnel (LT) and 21 patients (20%) with an extracardiac conduit (ECC). 72 patients (69%) were reviewed within 2 years preceding death, with 32% (23/72) deemed to be clinically well. Fontan circulatory failure was the most common cause of death in 42 patients (45%). Other causes of death included sudden death/arrhythmia (19%), perioperative death (12%), neurological complication (7%) and thromboembolism (7%). All patients with an LT or ECC who died from Fontan failure had at least one surgical defect that was amenable to intervention at time of death. CONCLUSIONS Conventional clinical surveillance has been insensitive in detecting a significant proportion of patients at risk of late death. Fontan circulatory failure contributes to half of the late deaths. Patients with an LT or ECC Fontan who died with a clinical picture of circulation failure may have potentially correctable lesions. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To examine the association between age at period cessation and trajectories of anthropometry, blood pressure, lipids and glycated haemoglobin (HbA1c) from midlife to age 69 years. METHODS We used data from the UK Medical Research Council National Survey of Health and Development to examine the association between age at period cessation and trajectories of systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC) from 36 to 69 years and trajectories of triglyceride, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and HbA1c from 53 to 69 years. RESULTS We found no evidence that age at period cessation was associated with trajectories of log triglyceride, LDL-C and HDL-C from 53 to 69 years and trajectories of SBP or DBP from 36 to 69 years, regardless of whether period cessation occurred naturally or due to hysterectomy. Selleck SLF1081851 While we found some evidence of associations of age at period cessation with log BMI, log WC and log HbA1c, patterns were not consistent and differences were small at age 69 years, with confidence intervals that spanned the null value. CONCLUSION How and when women experience period cessation is unlikely to adversely affect conventional cardiovascular risk factors across mid and later life. Women and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impact over the long term is small. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Correct selection of the cell division axis is important for cell differentiation, tissue and organ morphogenesis, and homeostasis. Both integrins, which mediate interactions with extracellular matrix (ECM) components such as fibronectin, and cadherins, which mediate interactions between cells, are implicated in the determination of spindle orientation. We found that both cadherin- and integrin-based adhesion resulted in cell divisions parallel to the attachment plane and elicited identical spindle responses to spatial adhesive cues. This suggests that adhesion topology provides purely mechanical spatial cues that are independent of the molecular nature of the interaction or signaling from adhesion complexes. We also demonstrated that cortical integrin activation was indispensable for correct spindle orientation on both cadherin and fibronectin substrates. These data suggest that spindle orientation responses to adhesion topology are primarily a result of force anisotropy on the cell cortex and show that integrins play a central role in this process that is distinct from their role in cell-ECM interactions. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.The complex signaling dynamics of transcription factors can encode both qualitative and quantitative information about the extracellular environment, which increases the information transfer capacity and potentially supports accurate cellular decision-making. An important question is how these signaling dynamics patterns are translated into functionally appropriate gene regulation programs. To address this question for transcription factors of the nuclear factor κB (NF-κB) family, we profiled the single-cell dynamics of two major NF-κB subunits, RelA and c-Rel, induced by a panel of pathogen-derived stimuli in immune and nonimmune cellular contexts. Diverse NF-κB-activating ligands produced different patterns of RelA and c-Rel signaling dynamic features, such as variations in duration or time-integrated activity. Analysis of nascent transcripts delineated putative direct targets of NF-κB as compared to genes controlled by other transcriptional and posttranscriptional mechanisms and showed that the transcription of more than half of the induced genes was tightly linked to specific dynamic features of NF-κB signaling. Fibroblast and macrophage cell lines shared a cluster of such "NF-κB dynamics-decoding" genes, as well as cell type-specific decoding genes. Dissecting the subunit specificity of dynamics-decoding genes suggested that target genes were most often linked to both RelA and c-Rel or to RelA alone. Thus, our analysis reveals the cell type-specific interpretation of pathogenic information through the signaling dynamics of NF-κB. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.