Adverse outcomes and an immunosuppressed endotype in septic patients with reduced IFN-γ ELISpot

BACKGROUNDSepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting clinical outcomes and immunological endotyping of septic patients generally relies on using blood protein or mRNA biomarkers, or static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.METHODSAn ex vivo whole-blood enzyme-linked immunosorbent spot (ELISpot) assay for cellular production of interferon γ (IFN-γ) was evaluated in 107 septic and 68 nonseptic patients from 5 academic health centers using blood samples collected on days 1, 4, and 7 following ICU admission.RESULTSCompared with 46 healthy participants, unstimulated and stimulated whole-blood IFN-γ expression was either increased or unchanged, respectively, in septic and nonseptic ICU patients. However, in septic patients who did not survive 180 days, stimulated whole-blood IFN-γ expression was significantly reduced on ICU days 1, 4, and 7 (all P \u3c 0.05), due to both significant reductions in total number of IFN-γ-producing cells and amount of IFN-γ produced per cell (all P \u3c 0.05). Importantly, IFN-γ total expression on days 1 and 4 after admission could discriminate 180-day mortality better than absolute lymphocyte count (ALC), IL-6, and procalcitonin. Septic patients with low IFN-γ expression were older and had lower ALCs and higher soluble PD-L1 and IL-10 concentrations, consistent with an immunosuppressed endotype.CONCLUSIONSA whole-blood IFN-γ ELISpot assay can both identify septic patients at increased risk of late mortality and identify immunosuppressed septic patients.TRIAL REGISTRYN/A.FUNDINGThis prospective, observational, multicenter clinical study was directly supported by National Institute of General Medical Sciences grant R01 GM-139046, including a supplement (R01 GM-139046-03S1) from 2022 to 2024

P-West High Intensity Secondary Beam Area Design Report

This report gives the initial design parameters of a 1000 GeV High Intensity Superconducting Secondary Beam Laboratory to be situated in the Proton Area downstream of the existing Proton West experimental station. The area will provide Fermilab with a major capability for experimentation with pion and antiproton beams of intensities and of energies available at no other laboratory and with an electron beam with excellent spot size, intensity, and purity at energies far above that available at electron machines. Detailed beam design, area layouts, and cost estimates are presented, along with the design considerations

Earthquake Response of Connected and Unconnected Back-to-Back Geosynthetic-Reinforced Soil Walls

A two-dimensional finite-element analysis based on PLAXIS 2D was used to study the behavior of connected and unconnected back-to-back mechanically stabilized earth walls under earthquake loading. The numerical model was first validated with the results from the full-scale dynamic centrifuge tests on reinforced soil-retaining walls. The behavior of connected and closely spaced unconnected back-to-back mechanically stabilized earth walls (BBMSE) was compared in terms of tensile forces mobilized in geogrids, and the lateral earth pressures and maximum displacements of the wall. The total seismic earth thrusts at the end of the reinforced zone and at the facing of BBMSE walls and their points of application were presented. These results were compared with the widely used Mononobe-Okabe method. The connected walls were found to significantly reduce the dynamic loads on the walls compared with those on unconnected walls. © 2021 American Society of Civil Engineers

Formation and characterization of calcium silicate hydrate-hexadecyltrimethylammonium nanostructure

Results of an investigation of the interaction potential of synthetic and pre-treated C-S-H (with hexadecyltrimethylammonium (HDTMA)) are reported. It is inferred that the stability of C-S-H binders in concrete can be affected by a variation in nanostructure resulting from engineering variables such as curing temperature and use of chemical admixtures.On fait \ue9tat ici des r\ue9sultats d'une investigation du potentiel d'intercalation des hydrates de silicate de calcium (C-S-H) synth\ue9tiques et pr\ue9trait\ue9s (avec hexad\ue9cyltrim\ue9thylammonium [HDTMA]). Il est suppos\ue9 qu'une variation dans la nanostructure r\ue9sultant de variables d'ing\ue9nierie telles que la temp\ue9rature de la cure et l'emploi d'adjuvants chimiques peut influer sur la stabilit\ue9 des liants \ue0 base de C-S-H dans le b\ue9ton.Peer reviewed: YesNRC publication: Ye

Seismic Performance of Cantilever Retaining Walls with Tire Shreds as Compressible Inclusion

The use of recycled tire shreds as a compressible inclusion behind cantilever retaining wall is an effective method to reduce the seismic earth pressures acting on the wall. A two-dimensional finite element analysis based on PLAXIS 2D was developed to analyze the response of a typical cantilever retaining wall, consisting of compressible tire shreds (CTS) as a cushion, under earthquake ground motion applied at the wall base. The numerical model was first validated against experimental shake table test results available in the literature. To quantify the benefit of CTS cushion, a comparison was made in the behavior of wall without and with cushion in terms of horizontal displacement and rotation, the maximum shear force and bending moment, the seismic earth thrust and its point of application on the wall. The results from the analysis indicate that the dynamic earth thrust against the wall reduced considerably due to the presence of cushion made up of compressible tire shreds. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG

Formation and properties of C-S-H -PEG nano-structures

Results of an investigation of the intercalation potential of polyethylene glycol (PEG) with synthetic and pre-treated C-S-H are reported. The partial intercalation of PEG molecules in the interlayer of C-S-H is discussed. The effective and strong interaction of PEG molecules with the C-S-H surface was shown using XRD, 13C CP and 29Si MAS NMR, and DTGA. The position and character of the 002 low angle XRD peak of C-S-H are affected by drying procedures and concomitant chemical treatment preceding intercalation and the reaction temperature. Recovery of the initial 002 position after severe drying and intercalation with distilled water or PEG is incomplete but is accompanied by an increase in intensity. It is inferred that the stability of C-S-H binders in concrete can be impacted by a variation in nanostructure dependent on curing temperature and use of chemical admixtures.Ce document d\ue9crit les caract\ue9ristiques d?acoustique et de milieu sonore de 27 salles de classe traditionnelles, de forme rectangulaire, parmi les 41 salles ayant \ue9t\ue9 mesur\ue9es. Le but de ces travaux \ue9tait de permettre de mieux comprendre comment am\ue9liorer la communication de la parole entre enseignants et \ue9l\ue8ves. L?\ue9tude a r\ue9v\ue9l\ue9 les valeurs moyennes suivantes, durant les classes, du point de vue des \ue9l\ue8ves : niveaux sonores de la parole \ue9mise par l?enseignant de 60,4 dBA, niveaux de bruit de 49,1 dB, et rapport signal vocal/bruit moyen de 11 dBA. Le temps de r\ue9verb\ue9ration moyen dans les salles de classe occup\ue9es \ue9tait de 0,41 s, soit 10 % de moins que dans les salles inoccup\ue9es. On a utilis\ue9 les mesures des temps de r\ue9verb\ue9ration pour d\ue9terminer la valeur d?absorption moyenne qu?ajoutait la pr\ue9sence de chaque \ue9l\ue8ve. Les analyses d\ue9taill\ue9es des sons conversationnels \ue0 arriv\ue9e imm\ue9diate et de ceux \ue0 arriv\ue9e tardive ont r\ue9v\ue9l\ue9 que ces niveaux sonores pouvaient \ueatre pr\ue9dits avec assez de pr\ue9cision. Ces analyses font entrevoir des approches am\ue9lior\ue9es au probl\ue8me de la conception de l?acoustique des salles.Peer reviewed: YesNRC publication: Ye

Immune Adjuvant Therapy With Interleukin-7 in a Lymphopenic Patient With Aplastic Anemia and Mucormycosis

BACKGROUND:. We report the case of a patient with aplastic anemia and pancytopenia on immune-suppressive therapy who developed invasive pulmonary infection with mucormycosis and was treated with immune adjuvant therapy. CASE SUMMARY:. Given the patient’s profound lymphopenia and progressive invasive mucor despite dual antifungal drug therapy, interleukin (IL)-7, a cytokine that induces lymphocyte activation and proliferation, was instituted and resulted in normalization of absolute lymphocyte counts and was temporally associated with clearance of fungal pathogens and resolution of clinical symptoms. CONCLUSION:. Patients with life-threatening fungal infections are frequently immune suppressed and immune adjuvant therapies should be considered in patients who are not responding to antifungal drugs and source control. Well-designed, double-blind, placebo-controlled trials are needed to advance the field. Although a number of immune adjuvants may be beneficial in fungal sepsis, IL-7 is a particularly attractive immune adjuvant because of its broad immunologic effects on key immunologic pathways that mediate enhanced antifungal immune system activity