Stabilization of cycles with stochastic prediction-based and target-oriented control

We stabilize a prescribed cycle or an equilibrium of a difference equation using pulsed stochastic control. Our technique, inspired by Kolmogorov's law of large numbers, activates a stabilizing effect of stochastic perturbation and allows for stabilization using a much wider range for the control parameter than would be possible in the absence of noise. Our main general result applies to both prediction-based and target-oriented controls. This analysis is the first to make use of the stabilizing effects of noise for prediction-based control; the stochastic version has previously been examined in the literature, but only the destabilizing effect of noise was demonstrated. A stochastic variant of target-oriented control has never been considered, to the best of our knowledge, and we propose a specific form that uses a point equilibrium or one point on a cycle as a target. We illustrate our results numerically on the logistic, Ricker, and Maynard Smith models from population biology

Paediatric acute hepatitis of unknown aetiology : a national investigation and adenoviraemia case-control study in the UK

Funding Information: This work was undertaken as part of a national enhanced incident by UK public health agencies. We thank the parents and guardians of the children who gave up their valuable time to speak to the public health investigation teams; without their support we could not have been able to undertake a thorough investigation. We are grateful to the many paediatricians and liver specialists who reported cases to us and responded to follow-up with further information. We also thank Ezra Linley and Simon Tonge of the UK Health Security Agency Seroepidemiology Unit for rapidly providing serum samples for testing. We would like to thank the Incident Management Teams of the UK nations, members of the incident cells, epidemiology, laboratory, and local Health Protection Teams who supported the investigations, in particular: Katy Sinka, Mike Gent, Suzanna Howes, Eileen Gallagher, Selene Corsini, Eleanor Clarke, Rajani Raghu, Kelsey Mowat, Iain Hayden, Matt Hibbert, Skye Firminger, Catriona Angel, Donna Haskins, Kay Ratcliffe, Hannah Emmett, Alex Elliot, Helen Hughes, Sarah Deeny, Sarah Garner, Sarah Gerver, Flora Stevens, Paula Blomquist, Gabriel Gurmail Kauffman, Kristine Cooper, Hannah Taylor, Giovanni Leonardi, Michelle Dickinson and Michelle Watson from England; Kimberly Marsh, Michael Lockhart, David Yirrell, Sandra Currie, Kate Templeton, Samantha Shepherd, Roisin Ure, Jim McMenamin, Rachel Tayler, Louisa Pollock, Antonia Ho, Chris Cunningham and Hayley Peacock from Scotland; and Katie Binley and Meg Wallace from Northern Ireland.Peer reviewe

Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Adaptive timestepping strategies for nonlinear stochastic systems

We introduce a class of adaptive timestepping strategies for stochastic differential equations with non-Lipschitz drift coefficients. These strategies work by controlling potential unbounded growth in solutions of a numerical scheme due to the drift. We prove that the Euler-Maruyama scheme with an adaptive timestepping strategy in this class is strongly convergent. Specific strategies falling into this class are presented and demonstrated on a selection of numerical test problems. We observe that this approach is broadly applicable, can provide more dynamically accurate solutions than a drift-tamed scheme with fixed stepsize, and can improve MLMC simulations