Bronchoalveolar lavage (BAL) is becoming a common procedure for research into infectious disease immunology. Little is known about the clinical factors which influence the main outcomes of the ...procedure. In research participants who underwent BAL according to guidelines, the BAL volume yield, and cell yield, concentration, viability, pellet colour and differential count were analysed for association with important participant characteristics such as active tuberculosis (TB) disease, TB exposure, HIV infection and recent SARS-CoV-2 infection. In 337 participants, BAL volume and BAL cell count were correlated in those with active TB disease, and current smokers. The right middle lobe yielded the highest volume. BAL cell and volume yields were lower in older participants, who also had more neutrophils. Current smokers yielded lower volumes and higher numbers of all cell types, and usually had a black pellet. Active TB disease was associated with higher cell yields, but this declined at the end of treatment. HIV infection was associated with more bloody pellets, and recent SARS-CoV-2 infection with a higher proportion of lymphocytes. These results allow researchers to optimise their participant and end assay selection for projects involving lung immune cells.
Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, ...termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsiveness. We confirm that MDSC suppress non-specific T-cell activation. We also show that Sildenafil treatment fails to reverse the MDSC-mediated suppression of T-cell functions measured here, namely activation and proliferation. The impact of Sildenafil treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.
The need to integrate computation into the physics curriculum has long been established: using simulations and computational modeling can enhance students’ conceptual understanding, and the ...computational skills students acquire are both useful and necessary in their careers. However, making changes to an established physics course is a challenge on many fronts: instructors need to be comfortable with their own computational skills, they need time to find and adapt appropriate materials, and they may have questions about how to integrate computation into their course(s). The Partnership for Integration of Computation into Undergraduate Physics (PICUP) was organized to identify the barriers underlying these challenges, to document the current state of computation use in physics courses, and to explore avenues to reach and engage physics teachers.
We discuss the high temperature decay of isolated hills and saddle points on Si(001). Using in situ dark-field imaging in low energy electron microscopy, we track the movement of individual steps ...during high temperature annealing. We find different temperature dependent decay rates for the top of the hill compared to a saddle point with low step density that is present in the vicinity of the hill. The decay rate of the hill is always higher than the decay rate at the saddle. The two rates converge with increasing temperature and become equal at temperatures above 1060 °C. We also report an alternating fast and low decay rate for the layer-by-layer decay of the hills. This surprising finding is independent of temperature and is explained by macroscopic strain in the sample.
•Kinetic Monte Carlo approach to solving agent-based model of a financial market.•A market crash is observed, warning signs of impending crash observed long before crash occurs.•Simulation results ...provide insight into causes and ability to predict calamitous market events.
We use kinetic Monte Carlo simulations to produce solutions of an agent-based, rate equation model of an informationally efficient, closed financial market. The simulations produce a crash in the market that is forewarned through the observation of a market instability from which the market temporarily recovers. The market remained in a quasi-stable state for a relatively large amount of time between the warning and the crash, raising the prospect that some mitigating action can be taken in time to avert the impending crash. This result has strong ramifications for the future of predicting calamitous market events, especially if some observable aspect of financial markets can be positively identified and associated with simulation parameters.
We studied the self-assembly of wire-shaped Ag islands at high temperature with low energy electron microscopy and photoemission electron microscopy. A Au-faceted vicinal Si(001) surface was used as ...a substrate. The initial Ag deposit at 600–620°C induces a surface phase change from the (5×3.2) reconstruction of the Au-covered (001) terraces, to a (3×2) reconstruction, but leaves the structure of the Au-induced step bunches intact. Subsequent Ag growth produces two distinct types of 3D crystalline islands: compact and wire-like. The total Ag deposit is comprised mostly of compact islands, with only a small minority of wire-like islands. We attribute the wire formation to local step bunches that create the proper quasi-one-dimensional diffusion environment for the Ag islands to grow with a high aspect ratio.
We build on the developments in the application of statistical mechanics, notably the identity of the spin degree of freedom in the Ising model, to explain asset price dynamics in financial markets ...with a representative agent. Specifically, we consider the value of an individual spin to represent the proportional holdings in various assets. We use partial moment arguments to identify asymmetric reactions to information and develop an extension of a plunging and dumping model. This unique identification of the spin is a relaxation of the conventional discrete state limitation on an Ising spin to accommodate a new archetype in Ising model-finance applications wherein spin states may take on continuous values, and may evolve in time continuously, or discretely, depending on the values of the partial moments.
•Continuous spin Ising model.•Identification of fractional asset holding as spin degree of freedom.•Partial moments produce continuously or discretely varying spins.•Partial moments determined by Hamiltonian.
Purpose: The diagnosis of tuberculous meningitis (TBM) in children is often delayed due to diagnostic difficulties. New tools are urgently needed to improve the diagnosis of the disease in this ...vulnerable group. The present study aimed to validate the accuracy of recently identified host cerebrospinal (CSF) biomarkers as candidates for the diagnosis of TBM in children.
Materials and methods: We collected CSF samples from 87 children aged 3 months to 13 years, that were consecutively admitted at a tertiary hospital in Cape Town, South Africa, on suspicion of having TBM. We evaluated the concentrations of 67 selected host protein biomarkers using a multiplex platform.
Results: Previously identified 3-marker (VEGF-A + IFN-γ + MPO) and 4-marker (IFN-γ + MPO + ICAM-1 + IL-8) signatures diagnosed TBM with AUCs of 0.89 (95% CI, 0.81-0.97) and 0.87 (95% CI, 0.79-0.95) respectively; sensitivities of 80.6% (95% CI, 62.5-92.5%) and 81.6% (95% CI, 65.7-92.3%), and specificities of 86.8% (71.9-95.6%) and 83.7% (70.4-92.7%) respectively. Furthermore, a new combination between the analytes (CC4b + CC4 + procalcitonin + CCL1) showed promise, with an AUC of 0.98 (95% CI, 0.94-1.00).
Conclusions: We have shown that the accuracies of previously identified candidate CSF biomarkers for childhood TBM was reproducible. Our findings augur well for the future development of a simple bedside test for the rapid diagnosis of TBM in children.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In Bradley University's physics department, the author has developed an incremental approach to computational physics instruction. It interweaves modern computational techniques with traditional ...aspects of upper-level classical mechanics and thermodynamics courses, building from simple to more complex concepts and assignments. By directly programming and controlling all aspects of their computer applications, students can best grasp computational principles
Computational modeling has become a vital tool in many fields, including economics and finance. Realistic models have become increasingly complex, and this complexity, in turn, requires not only a ...computational approach, but also increasing levels of computational power. Simply using a more powerful computer to address the need for speed (higher CPU clock rate and more RAM) is not always sufficient to produce results in a practicable time frame. Most often, it is necessary to alter the entire structure of a computer model in order to maximize efficiency and lower computation time. The highperformance computing (HPC) community has worked for years to produce powerful techniques that can dramatically increase the speed and/or efficiency of a computational model. In this paper we describe how the implementation of some basic HPC techniques has dramatically increased the speed of an economic model of software utility in the console gaming market.
