Interpretative and predictive modelling of Joint European Torus collisionality scans

Transport modelling of Joint European Torus (JET) dimensionless collisionality scaling experiments in various operational scenarios is presented. Interpretative simulations at a fixed radial position are combined with predictive JETTO simulations of temperatures and densities, using the TGLF transport model. The model includes electromagnetic effects and collisions as well as □(→┬E ) X □(→┬B ) shear in Miller geometry. Focus is on particle transport and the role of the neutral beam injection (NBI) particle source for the density peaking. The experimental 3-point collisionality scans include L-mode, and H-mode (D and H and higher beta D plasma) plasmas in a total of 12 discharges. Experimental results presented in (Tala et al 2017 44th EPS Conf.) indicate that for the H-mode scans, the NBI particle source plays an important role for the density peaking, whereas for the L-mode scan, the influence of the particle source is small. In general, both the interpretative and predictive transport simulations support the experimental conclusions on the role of the NBI particle source for the 12 JET discharges

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

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

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Insights into the Cenozoic geology of North Beirut (harbour area): biostratigraphy, sedimentology and structural history

The biostratigraphy and sedimentology of the outcrops and bedrock recently exposed in archaeological excavations around the harbour area of Beirut (~5 km²) unlock the geological and structural history of that area, which in turn are key to understanding the hydrocarbon and hydrogeological potential of the region. A key location (Site 2) of a studied outcrop section and newly uncovered bedrock is on the northern foothill cliff of East Beirut (Achrafieh). The outcrop section of carbonates is of Eocene beds overlain by conformable Miocene beds. The excavation of the slope bordering the outcrop uncovered a bedrock section of an early Pliocene shoreline of carbonate/siliciclastic sands at its base and topped by a beach-rock structure. The early Pliocene age of the shoreline section is dated by an assemblage of planktonic foraminifera that includes Sphaeroidinellopsis subdehiscens, Sphaeroidinella dehiscens and Orbulina universa. The Eocene carbonates of Site 2 extend the coverage of the previously reported Eocene outcrops in the harbour area. They form a parasequence of thin-bedded, chalky white limestones that includes the youngest fossil fish deposits in Lebanon ( Bregmaceros filamentosus). The deposits are dated as early Priabonian by their association with the planktonic foraminiferal assemblage of Porticulasphaera tropicalis, Globigerinatheka barri, Dentoglobigerina venezuelana, Globigerina praebulloides, Turborotalia centralis and Borelis sp. The Middle Miocene carbonates that conformably overlie the early Priabonian, parasequence include a planktonic foraminiferal assemblage of Globigerinoides trilobus, Orbulina universa and Borelis melo. Elsewhere, in the harbour area, the preserved Eocene limestones are also overlain by conformable Miocene carbonate parasequences of Langhian–Serravallian age. Younger argillaceous limestone beds of the Mio/Pliocene age occur in the eastern central part of the harbour area and enclose an assemblage of Truncorotalia crassaformis, Globorotalia inflata and Orbulina universa. The three markers of old and recently raised structural blocks in the harbour area are a Lutetian/Bartonian marine terrace in the south west corner, a lower Pliocene shoreline carbonate section in the north east side and a Holocene raised beach of marine conglomerates in the north east corner of the area. The locations of these paleo-shorelines, less than 2 km apart, indicate a progressive platform narrowing of North Beirut since the Paleogene. This study underpins the geological complexity of the region and contributes to understanding the underlying geology, which will be needed for future regional archaeological, hydrocarbon and hydrogeological exploration

Global evolution and paleogeographic distribution of mid-Cretaceous orbitolinids

Members of the Larger Benthic Foraminiferal (LBF) family Orbitolinidae occured from the Cretaceous to the Paleogene, however, they were most diverse during the mid-Cretaceous, and dominated the agglutinated LBF assemblages described from limestones of that period. Various orbitolinid species have been used to zone and date lithologies formed in the shallow, warm waters of the Aptian to the Early Cenomanian, and many, sometimes inaccurate, generic and sub-generic nomenclatures have been proposed to differentiate the often subtle morphological changes that orbitolinids exhibit over time. Until now, it has not been possible to develop an effective global overview of their evolution and environmental development because descriptions of specimens from Asia have been relatively rare. Following our recent study of over 1800 orbitolinid-rich thin sections of material from 13 outcrops of the Langshan Limestone, from the Southern Tibetan Plateau, and from the Barito Basin, South Kalimantan, Indonesia, it has been possible to compare the stratigraphic ranges of these orbitolinids with previously described Tethyan and American forms, based on the use of a planktonic zonal (PZ) scheme, itself tied to the most recent chronostratigraphic scale. This has allowed the reconstruction of the phylogenetic and paleogeographic evolution of the orbitolinids from their Valanginian origin in the Tethys. Although Tethys remained the paleogeographic focus for the orbitolinids, it is inferred here for the first time that a bi-directional paleogeographic migration of some orbitolinid genera occurred from Tethys to the Americas and also to the Western Pacific region. Our observations and dating confirm that global marine regressions in the Aptian were coincident with, and may well have facilitated, these orbitolinid transoceanic migrations. However, migration stopped after rising sea-level in the Early Albian appears to have again isolated these provinces from each other. Tectonic forces associated with the subduction of the Farallon Plate and further sea-level raises led to the opening of the Western Interior Seaway in the North America, which correlates with, and may have been the cause of, the Middle Albian (top of PZ Albian 2) extinction of the American orbitolinids. The extinction of the orbitolinids revealed that the Western Pacific province was split into two sub-provinces, with extinction occurring at the end of the Early Albian (top of PZ Albian 1) in the Northwest Pacific sub-province, and at the end of the Albian (top of PZ Albian 4) in the sub-province that is today South East Asia (on the margins and west of the Wallace Line). The final virtual extinction of the orbitolinids occurred at the end of the Cenomanian in the Tethyan province, which coincides with, and may have been caused by, global anoxic oceanic events that correlate with a near-peak Mesozoic eustatic sea-level high-stand that led to the overall global collapse of the paleotropical reef ecosystem at that time

First principles and integrated modelling achievements towards trustful fusion power predictions for JET and ITER

Predictability of burning plasmas is a key issue for designing and building credible future fusion devices. In this context, an important effort of physics understanding and guidance is being carried out in parallel to JET experimental campaigns in H and D by performing analyses and modelling towards an improvement of the understanding of DT physics for the optimization of the JET-DT neutron yield and fusion born alpha particle physics. Extrapolations to JET-DT from recent experiments using the maximum power available have been performed including some of the most sophisticated codes and a broad selection of models. There is a general agreement that 11-15 MW of fusion power can be expected in DT for the hybrid and baseline scenarios. On the other hand, in high beta, torque and fast ion fraction conditions, isotope effects could be favourable leading to higher fusion yield. It is shown that alpha particles related physics, such as TAE destabilization or fusion power electron heating, could be studied in ITER relevant JET-DT plasmas

A new mechanism for increasing density peaking in tokamaks: improvement of the inward particle pinch with edge E x B shearing

Developing successful tokamak operation scenarios, as well as confident extrapolation of present-day knowledge requires a rigorous understanding of plasma turbulence, which largely determines the quality of the confinement. In particular, accurate particle transport predictions are essential due to the strong dependence of fusion power or bootstrap current on the particle density details. Here, gyrokinetic turbulence simulations are performed with physics inputs taken from a JET power scan, for which a relatively weak degradation of energy confinement and a significant density peaking is obtained with increasing input power. This way physics parameters that lead to such increase in the density peaking shall be elucidated. While well-known candidates, such as the collisionality, previously found in other studies are also recovered in this study, it is furthermore found that edge E x B shearing may adopt a crucial role by enhancing the inward pinch. These results may indicate that a plasma with rotational shear could develop a stronger density peaking as compared to a non-rotating one, because its inward convection is increased compared to the outward diffusive particle flux as long as this rotation has a significant on E x B flow shear stabilization. The possibly significant implications for future devices, which will exhibit much less torque compared to present day experiments, are discussed