On coupling resolved and unresolved physical processes in finite element discretisations of geophysical fluids

At the heart of modern numerical weather forecasting and climate modelling lie simulations of two geophysical fluids: the atmosphere and the ocean. These endeavours rely on numerically solving the equations that describe these fluids. A key challenge is that the fluids contain motions spanning a range of scales. As the small-scale processes (unresolved by the numerical model) affect the resolved motions, they need to be described in the model, which is known as parametrisation. One major class of methods for numerically solving such partial differential equations is the finite element method. This thesis focuses on the coupling of such parametrised processes to the resolved flow within finite element discretisations. Four sets of research are presented, falling under two main categories. The first is the development of a compatible finite element discretisation for use in numerical weather prediction models, so as to avoid the bottleneck in computational scalability associated with the convergence at the poles of latitude-longitude grids. We present a transport scheme for use with the lowest-order function spaces in such a compatible finite element method, which is motivated by the coupling of the resolved and unresolved processes within the model. This then facilitates the use of the lower-order spaces within Gusto, a toolkit for studying such compatible finite element discretisations. Then, we present a compatible finite element discretisation of the moist compressible Euler equations, parametrising the unresolved moist processes. This is a major step in the development of Gusto, extending it to describe its first unresolved processes. The second category with which this thesis is concerned is the stochastic variational framework presented by Holm [Variational principles for stochastic fluid dynamics, P. Roy. Soc. A-Math. Phy. 471 (2176), (2015)]. In this framework, the effect of the unresolved processes and their uncertainty is expressed through a stochastic component to the advecting velocity. This framework ensures the circulation theorem is preserved by the stochastic equations. We consider the application of this formulation to two simple geophysical fluid models. First, we discuss the statistical properties of an enstrophy-preserving finite element discretisation of the stochastic quasi-geostrophic equation. We find that the choice of discretisation and the properties that it preserves affects the statistics of the solution. The final research presented is a finite element discretisation of the stochastic Camassa-Holm equation, which is used to numerically investigate the formation of ‘peakons’ within this set-up, finding that they do still always form despite the noise’s presence.Open Acces

Simulation-based education within respiratory physiotherapy training:a scoping review

Objective The aim of this scoping review is to provide respiratory physiotherapists with guidance on the implementation of simulation-based education Introduction In recent years there has been a widespread rise in the adoption of simulation-based education. A scoping review was decided upon by the ACPRC Editorial Board to focus on any new evidence or guidance in the field. Inclusion criteria 1) Studies investigating the use of simulation-based education within respiratory physiotherapy 2) Meta-analyses, systematic reviews, scoping reviews, randomised controlled trials and observational studies. Methods A literature search was developed and refined through testing. Nine databases were searched between 01/01/2014 and 31/10/2022. Data regarding study design, population, intervention, comparator and control were extracted into a data extraction table. Results were grouped by study design, intervention or context. Results 141 sources were retrieved from the searches. After initial screening 27 sources were included and after full-text review, 25 were included. Sources included: meta-analyses and systematic review and studies considering pre-registration education, interprofessional learning, part-task trainers and postgraduate education. Conclusion There is increasing research output in the simulation-based education field for respiratory physiotherapy. The evidence continues to focus on learner experience. More resources and support are required to increase access to simulation-based education for respiratory physiotherapists

Cardiomyocyte tetrahydrobiopterin synthesis regulates fatty acid metabolism and susceptibility to ischaemia-reperfusion injury

New Findings What is the central question of this study? What are the physiological roles of cardiomyocyte-derived tetrahydrobiopterin (BH4) in cardiac metabolism and stress response? What is the main finding and its importance? Cardiomyocyte BH4 has a physiological role in cardiac metabolism. There was a shift of substrate preference from fatty acid to glucose in hearts with targeted deletion of BH4 synthesis. The changes in fatty-acid metabolic profile were associated with a protective effect in response to ischaemia–reperfusion (IR) injury, and reduced infarct size. Manipulating fatty acid metabolism via BH4 availability could play a therapeutic role in limiting IR injury. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthases in which its production of NO is crucial for cardiac function. However, non-canonical roles of BH4 have been discovered recently and the cell-specific role of cardiomyocyte BH4 in cardiac function and metabolism remains to be elucidated. Therefore, we developed a novel mouse model of cardiomyocyte BH4 deficiency, by cardiomyocyte-specific deletion of Gch1, which encodes guanosine triphosphate cyclohydrolase I, a required enzyme for de novo BH4 synthesis. Cardiomyocyte (cm)Gch1 mRNA expression and BH4 levels from cmGch1 KO mice were significantly reduced compared to Gch1flox/flox (WT) littermates. Transcriptomic analyses and protein assays revealed downregulation of genes involved in fatty acid oxidation in cmGch1 KO hearts compared with WT, accompanied by increased triacylglycerol concentration within the myocardium. Deletion of cardiomyocyte BH4 did not alter basal cardiac function. However, the recovery of left ventricle function was improved in cmGch1 KO hearts when subjected to ex vivo ischaemia–reperfusion (IR) injury, with reduced infarct size compared to WT hearts. Metabolomic analyses of cardiac tissue after IR revealed that long-chain fatty acids were increased in cmGch1 KO hearts compared to WT, whereas at 5 min reperfusion (post-35 min ischaemia) fatty acid metabolite levels were higher in WT compared to cmGch1 KO hearts. These results indicate a new role for BH4 in cardiomyocyte fatty acid metabolism, such that reduction of cardiomyocyte BH4 confers a protective effect in response to cardiac IR injury. Manipulating cardiac metabolism via BH4 could play a therapeutic role in limiting IR injury

Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2

Dlx2, Lymphoid Enhancer Factor (Lef-1) and Msx2 transcription factors are required for several developmental processes. To understand the control of gene expression by these factors, chromatin immunoprecipitation (ChIP) assays identified Msx2 as a downstream target of Dlx2 and Lef-1. Dlx2 activates the Msx2 promoter in several cell lines and binds DNA as a monomer and dimer. A Lef-1 β-catenin-dependent isoform minimally activates the Msx2 promoter and a Lef-1 β-catenin-independent isoform is inactive, however co-expression of Dlx2 and both Lef-1 isoforms synergistically activate the Msx2 promoter. Co-immunoprecipitation and protein pull-down experiments demonstrate Lef-1 physically interacts with Dlx2. Deletion analyses of the Lef-1 protein reveal specific regions required for synergism with Dlx2. The Lef-1 β-catenin binding domain (βDB) is not required for its interaction with Dlx2. Msx2 can auto-regulate its promoter and repress Dlx2 activation. Msx2 repression of Dlx2 activation is dose-specific and both bind a common DNA-binding element. These transcriptional mechanisms correlate with the temporal and spatial expression of these factors and may provide a mechanism for the control of several developmental processes. We demonstrate new transcriptional activities for Dlx2, Msx2 and Lef-1 through protein interactions and identification of downstream targets

Bruton's Tyrosine Kinase Is Required for Activation of Iκb Kinase and Nuclear Factor κb in Response to B Cell Receptor Engagement

Mutations in the gene encoding Bruton's tyrosine kinase (btk) cause the B cell deficiency diseases X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. In vivo and in vitro studies indicate that the BTK protein is essential for B cell survival, cell cycle progression, and proliferation in response to B cell antigen receptor (BCR) stimulation. BCR stimulation leads to the activation of transcription factor nuclear factor (NF)-κB, which in turn regulates genes controlling B cell growth. We now demonstrate that a null mutation in btk known to cause the xid phenotype prevents BCR-induced activation of NF-κB. This defect can be rescued by reconstitution with wild-type BTK. This mutation also interferes with BCR-directed activation of IκB kinase (IKK), which normally targets the NF-κB inhibitor IκBα for degradation. Taken together, these findings indicate that BTK couples IKK and NF-κB to the BCR. Interference with this coupling mechanism may contribute to the B cell deficiencies observed in XLA and xid

Simulations of idealised 3D atmospheric flows on terrestrial planets using LFRic-Atmosphere

We demonstrate that LFRic-Atmosphere, a model built using the Met Office's GungHo dynamical core, is able to reproduce idealised large-scale atmospheric circulation patterns specified by several widely-used benchmark recipes. This is motivated by the rapid rate of exoplanet discovery and the ever-growing need for numerical modelling and characterisation of their atmospheres. Here we present LFRic-Atmosphere's results for the idealised tests imitating circulation regimes commonly used in the exoplanet modelling community. The benchmarks include three analytic forcing cases: the standard Held-Suarez test, the Menou-Rauscher Earth-like test, and the Merlis-Schneider Tidally Locked Earth test. Qualitatively, LFRic-Atmosphere agrees well with other numerical models and shows excellent conservation properties in terms of total mass, angular momentum and kinetic energy. We then use LFRic-Atmosphere with a more realistic representation of physical processes (radiation, subgrid-scale mixing, convection, clouds) by configuring it for the four TRAPPIST-1 Habitable Atmosphere Intercomparison (THAI) scenarios. This is the first application of LFRic-Atmosphere to a possible climate of a confirmed terrestrial exoplanet. LFRic-Atmosphere reproduces the THAI scenarios within the spread of the existing models across a range of key climatic variables. Our work shows that LFRic-Atmosphere performs well in the seven benchmark tests for terrestrial atmospheres, justifying its use in future exoplanet climate studies.Comment: 34 pages, 9(12) figures; Submitted to Geoscientific Model Development; Comments are welcome (see Discussion tab on the journal's website: https://egusphere.copernicus.org/preprints/2023/egusphere-2023-647

Hepatitis E Virus Infection in Sheltered Homeless Persons, France

To determine the prevalence of hepatitis E virus (HEV) infection among sheltered homeless persons in Marseille, France, we retrospectively tested 490 such persons. A total of 11.6% had immunoglobulin (Ig) G and 2.5% had IgM against HEV; 1 person had HEV genotype 3f. Injection drug use was associated with IgG against HEV