THE OPERATIVE TREATMENT OF TUBERCULOUS GLANDS OF THE NECK

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Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible

Necroptosis, a Potential Therapeutic Target for Neurological Disorders

Necrosis is considered to be an unregulated and chaotic cell death. However, recent advances in cell death strategies support necroptosis as a form of regulated programmed necrotic cell death. In response to TNF-a or Fas ligands, necroptosis can be induced by cell death receptors in multiple cell lines in the presence of a caspase inhibitor z-VAD; necroptotic cell death has been found to play an important role in normal development, immunity, inflammation, cancer, and human diseases. In this chapter, the molecular mechanisms governing necroptosis, recent findings about the upstream and downstream schema of necroptosis, and potential therapeutic targets in neurological disorders are discussed. After being activated by TNF-a (or Fas ligands) and death receptors, receptor-interacting proteins 1 and 3 (RIP1 and RIP3) form a complex, which play a central role in the induction of necroptosis. RIP3 phosphorylates and activates mitochondrial proteins mixed lineage kinase domain-like protein (MLKL) and PGAM5, resulting in the execution of necroptosis by dynamin-related protein 1, the GTPase that controls mitochondrial fission. Some small molecules such as necrostain-1 and necrosulfonamide target different steps of necroptosis and impede the progress of necroptosis. FADD, caspase-8, CLIP, and CYLD positively or negatively regulate RIP1-/RIP3-dependent necroptosis by different mechanisms. Recent studies demonstrate the involvement of necroptosis in many neurological disorders including stroke, trauma, neonatal hypoxic-ischemic encephalopathy, and Huntington\u27s disease. As a potential therapeutic target, the understanding of necroptotic mechanisms will provide new insights to develop more potent neuroprotectants and specific therapeutic strategies for clinical treatments of neurological disorders

Application of Gaussian process regression to plasma turbulent transport model validation via integrated modelling

This paper outlines an approach towards improved rigour in tokamak turbulence transport model validation within integrated modelling. Gaussian process regression (GPR) techniques were applied for profile fitting during the preparation of integrated modelling simulations allowing for rigourous sensitivity tests of prescribed initial and boundary conditions as both fit and derivative uncertainties are provided. This was demonstrated by a JETTO integrated modelling simulation of the JET ITER-like-wall H-mode baseline discharge #92436 with the QuaLiKiz quasilinear turbulent transport model, which is the subject of extrapolation towards a deuterium-tritium plasma. The simulation simultaneously evaluates the time evolution of heat, particle, and momentum fluxes over similar to 10 confinement times, with a simulation boundary condition at rho(tor) = 0.85. Routine inclusion of momentum transport prediction in multi-channel flux-driven transport modelling is not standard and is facilitated here by recent developments within the QuaLiKiz model. Excellent agreement was achieved between the fitted and simulated profiles for n(e), T-e, T-i, and Omega(tor) within 2 sigma, but the simulation underpredicts the mid-radius Ti and overpredicts the core n(e) and T-e profiles for this discharge. Despite this, it was shown that this approach is capable of deriving reasonable inputs, including derivative quantities, to tokamak models from experimental data. Furthermore, multiple figures-of-merit were defined to quantitatively assess the agreement of integrated modelling predictions to experimental data within the GPR profile fitting framework

EDGE2D-EIRENE simulations of the influence of isotope effects and anomalous transport coefficients on near scrape-off layer radial electric field

EDGE2D-EIRENE (the 'code') simulations show that radial electric field, Er, in the near scrape-off layer (SOL) of tokamaks can have large variations leading to a strong local E x B shear greatly exceeding that in the core region. This was pointed out in simulations of JET plasmas with varying divertor geometry, where the magnetic configuration with larger predicted near SOL E-r was found to have lower H-mode power threshold, suggesting that turbulence suppression in the SOL by local E. x. B shear can be a player in the L-H transition physics (Delabie et al 2015 42nd EPS Conf. on Plasma Physics (Lisbon, Portugal, 22-26 June 2015) paper O3.113 (http://ocs.ciemat.es/EPS2015PAP/pdf/O3.113.pdf), Chankin et al 2017 Nucl. Mater. Energy 12 273). Further code modeling of JET plasmas by changing hydrogen isotopes (H-D-T) showed that the magnitude of the near SOL E-r is lower in H cases in which the H-mode threshold power is higher (Chankin et al 2017 Plasma Phys. Control. Fusion 59 045012). From the experiment it is also known that hydrogen plasmas have poorer particle and energy confinement than deuterium plasmas, consistent with the code simulation results showing larger particle diffusion coefficients at the plasma edge, including SOL, in hydrogen plasmas (Maggi et al 2018 Plasma Phys. Control. Fusion 60 014045). All these experimental observations and code results support the hypothesis that the near SOL E x B shear can have an impact on the plasma confinement. The present work analyzes neutral ionization patterns of JET plasmas with different hydrogen isotopes in L-mode cases with fixed input power and gas puffing rate, and its impact on target electron temperature, T-e, and SOL E-r. The possibility of a self-feeding mechanism for the increase in the SOL E-r via the interplay between poloidal E x B drift and target T-e is discussed. It is also shown that reducing anomalous turbulent transport coefficients, particle diffusion and electron and ion heat conductivities, leads to higher peak target T-e and larger E-r, suggesting the possibility of a positive feedback loop, under an implicitly made assumption that the E x B shear in the SOL is capable of suppressing turbulence