Concurrent Change in Serum Cholinesterase Activity and Midregional-Proadrennomedullin Level Could Predict Patient Outcome following Liver Transplantation.

BACKGROUND: After liver transplantation (LTX), patients are susceptible to opportunistic infections resulting in reduced outcomes within the early post-transplantation period. The postoperative monitoring of LTX patients has gained much importance in recent years. However, reliable plasmatic markers predicting 90-day outcomes are still lacking. METHODS: In the post hoc analysis of a prospective, observational study, butyrylcholinesterase (BChE), mid-regional proadrenomedullin (MR-proADM), as well as conventional inflammatory markers (procalcitonin, C-reactive protein) were evaluated in 93 patients at seven consecutive timepoints within the first 28 days following LTX. RESULTS: Persistently reduced activity of BChE and elevated MR-proADM levels indicated reduced 90-day survival following LTX. Furthermore, reduced BChE and increased MR-proADM activity could indicate early post-transplantation bacterial infections, whereas conventional inflammatory biomarkers showed no diagnostic efficacy within the observation period. CONCLUSION: Concurrent assessment of BChE and MR-proADM activity might serve as a bedside diagnostic tool for early bacterial infections following liver transplantation. Thus, a combined utilization of the two biomarkers may be a useful tool in the risk evaluation of patients following liver transplantation.

Metallic technetium sequestration in nickel core/shell microstructure during Fe(OH)2 transformation with Ni doping.

This study investigates the impacts of Ni doping on technetium-99 (Tc) sequestration in aqueous solutions through transformation of Fe(OH)2(s) to iron spinel (magnetite) under alkaline conditions. Extensive solid characterization was performed for the mineral phases produced, as well as the Tc/Ni speciation and distribution within these phases. X-ray diffraction results show that iron spinel was the dominant mineral product without detectable Ni incorporation. The doped Ni ions mainly precipitated as fine Fe/Ni oxide/hydroxide particles, including strongly reduced nanometer-sized spheroidal Ni-rich and metallic Ni phases. High-resolution analytical scanning transmission electron microscopy using energy dispersive X-ray spectroscopy and electron energy loss spectroscopy on the produced solid samples (focused ion beam-prepared specimens) revealed three Tc distribution domains dominated by nanocrystals and, especially, a Tc-rich metallic phase. Instances of metallic Tc were specifically found in spheroidal, Ni-rich and metallic nanoparticles exhibiting a core/shell microstructure that suggests strong reduction and sequential precipitation of Ni-Tc-Ni. Mass balance analysis showed nearly 100% Tc removal from the 4.8 × 10-4 M Tc solutions. The finding of the metallic Tc encapsulation indicates that Tc sequestration through Ni-doped Fe(OH)2(s)-to-iron spinel transformation process likely provides an alternative treatment pathway for Tc removal and could be combined into further waste treatment approaches.

Machine Learning Enabled Models to Predict Sulfur Solubility in Nuclear Waste Glasses.

The U.S. Department of Energy is considering implementing the direct feed approach for the vitrification of low-activity waste (LAW) and high-level waste (HLW) at the Hanford site in Washington state. If implemented, the nuclear waste with a higher concentration of alkali/alkaline-earth sulfates (than expected under the previously proposed vitrification scheme) will be sent to the vitrification facility. It will be difficult for the existing empirical models to predict sulfate solubility in these glasses or design glass formulations with enhanced sulfate loadings in such a scenario. Further, the existing models are unable to produce reliable predictions when applied to HLW glasses whose composition falls outside of the range encompassed by the database used to develop/calibrate the models. Accordingly, this study harnesses the power of artificial intelligence (machine learning, ML) with a goal to address the limitations of the existing models. Toward this, three ML models have been trained using a large database; comprising >1000 LAW and HLW glasses and encompassing a wide range of glass compositions and processing variables. Next, the ML model with the best prediction performance has been used to quantitatively assess and rank the influence (i.e., importance) of glasses' compositional/processing variables on the SO3 solubility in the glasses. Finally, on the premise of such understanding of influential and inconsequential variables, two closed-form analytical models─with disparate degrees of complexity (one highly parametrized and one with fewer input variables)─have been developed. Results show that both analytical models produce predictions of SO3 solubility in LAW and HLW glasses with an accuracy analogous to ML models and substantially higher than the analytical models that represent the current state-of-the-art. Overall, this study's outcomes present a roadmap─informed by data and channeled by artificial intelligence─that can be leveraged in the future to design nuclear waste glasses with unprecedented sulfur loadings.

Reproduction of melting behavior for vitrified hillforts based on amphibolite, granite, and basalt lithologies.

European Bronze and Iron Age vitrified hillforts have been known since the 1700s, but archaeological interpretations regarding their function and use are still debated. We carried out a series of experiments to constrain conditions that led to the vitrification of the inner wall rocks in the hillfort at Broborg, Sweden. Potential source rocks were collected locally and heat treated in the laboratory, varying maximum temperature, cooling rate, and starting particle size. Crystalline and amorphous phases were quantified using X-ray diffraction both in situ, during heating and cooling, and ex situ, after heating and quenching. Textures, phases, and glass compositions obtained were compared with those for rock samples from the vitrified part of the wall, as well as with equilibrium crystallization calculations. 'Dark glass' and its associated minerals formed from amphibolite or dolerite rocks melted at 1000-1200 °C under reducing atmosphere then slow cooled. 'Clear glass' formed from non-equilibrium partial melting of feldspar in granitoid rocks. This study aids archaeological forensic investigation of vitrified hillforts and interpretation of source rock material by mapping mineralogical changes and glass production under various heating conditions.

Impact of Cr and Co on 99Tc retention in magnetite: A combined study of ab initio molecular dynamics and experiments.

The effect of co-mingled dopants, Co(II) and Cr(III), on Tc(IV) incorporation and retention in magnetite under varying temperatures (75-700 °C) was explored using ab initio molecular dynamics simulations, batch experiments, and solid phase characterization. Tc(IV) stabilization was achieved with a magnetite surface oversaturated with or containing an equal number of Tc and Cr. Under oversaturation conditions, the forced formation of a Cr2O3 phase on the magnetite surface may help prevent Tc release. Upon Co addition, and depending on the relative concentration of Tc, Cr, and Co at the magnetite surface, Co was found to preferentially stabilize Cr rather than Tc and suppress the formation of the protective Cr2O3 surface phase. Only systems with similar Cr/Co concentrations or relatively high Cr concentrations stabilized Tc within magnetite. As such, the relative concentration of Tc, Cr, and Co was identified as a critical parameter for maximizing dopant efficacy towards Tc stabilization in magnetite.

New approaches for the detection of invasive fungal diseases in patients following liver transplantation-results of an observational clinical pilot study.

PURPOSE: Despite antifungal prophylaxis following liver transplantation (LTX), patients are at risk for the development of subsequent opportunistic infections, such as an invasive fungal disease (IFD). However, culture-based diagnostic procedures are associated with relevant weaknesses. METHODS: Culture and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of ß-D-glucan (BDG), galactomannan (GM), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A and mid-regional proadrenomedullin (MR-proADM) were evaluated in 93 patients at 6 consecutive time points within 28 days following LTX. RESULTS: A NGS-based diagnostic approach was shown to be suitable for the early identification of fungal pathogens in patients following LTX. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with an IFD. CONCLUSION: Plasma measurements of MR-proADM and IL-17A as well as a NGS-based diagnostic approach were shown to be attractive methodologies to attenuate the weaknesses of routinely used culture-based diagnostic procedures for the determination of an IFD in patients following LTX. However, an additional confirmation within a larger multicenter trial needs to be recommended. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00005480 .

Silver-functionalized silica aerogels and their application in the removal of iodine from aqueous environments.

One of the key challenges for radioactive waste management is the efficient capture and immobilization of radioiodine, because of its radiotoxicity, high mobility in the environment, and long half-life (t1/2 = 1.57 × 107 years). Silver-functionalized silica aerogel (AgAero) represents a strong candidate for safe sequestration of radioiodine from various nuclear waste streams and subsurface environments. Batch sorption experiments up to 10 days long were carried out in oxic and anoxic conditions in both deionized water (DIW) and various Hanford Site Waste Treatment Plant (WTP) off-gas condensate simulants containing from 5 to 10 ppm of iodide (I-) or iodate (IO3-). Also tested was the selectivity of AgAero towards I- in the presence of other halide anions. AgAero exhibited fast and complete removal of I- from DIW, slower but complete removal of I- from WTP off-gas simulants, preferred removal of I- over Br- and Cl-, and it demonstrated ability to remove IO3- through reduction to I-.

Synthesis of ABBV-168, a 2'-Bromouridine for the Treatment of Hepatitis C.

ABBV-168 is a dihalogenated nucleotide under investigation for the treatment of hepatitis C virus. Three synthetic routes aimed at achieving the stereoselective installation of the C2' gem-Br,F substitution and subsequent Vorbruggen glycosylation were explored to prepare the penultimate nucleoside intermediate. Development culminated in a route to ABBV-168 featuring a de novo chromatography-free furanose synthesis, protecting group-directed Vorbruggen glycosylation, and highly selective phosphoramidation to furnish the API.

99Tc immobilization from off-gas waste streams using nickel-doped iron spinel.

Technetium-99 (99Tc) incorporation within stable spinel phases is a novel method for 99Tc removal and immobilization from waste streams. In this study, transformation of Ni-doped Fe(OH)2(s) to spinel minerals, e.g. trevorite (NiFe2O4), is explored as a method for removing 99Tc from Hanford Waste Treatment and Immobilization Plant (WTP) primary off-gas waste stream simulant. The Fe(OH)2(s) transformation process was found to reduce 99Tc(VII) to 99Tc(IV) and incorporate reduced Tc(VI) into the produced spinel simultaneously. Nickel doping was applied in the mineral transformation to inhibit potential reoxidation of 99Tc(IV). Solid phase characterization by XRD and XANES confirmed the formation of nickel substituted ferric-spinel, and suggest incorporation of 99Tc(IV) in the final spinel. Furthermore, in the primary off-gas stream, which contains both redox-sensitive contaminants Cr(VI) and 99Tc(VII), results from solution analysis and solid digestion indicate that nearly 100% Cr and over 80% 99Tc can be simultaneously removed by adding Fe(OH)2(s) to solution with a solid to solution ratio of 5 g/L under near neutral and alkaline conditions. The 99Tc removal approach developed herein provides an alternative treatment method to eliminate the proposed recycle process of the off-gas waste stream, which ultimately can reduce WTP mission cost and operation time.

Cr(VI) Effect on Tc-99 Removal from Hanford Low-Activity Waste Simulant by Ferrous Hydroxide.

Here, Cr(VI) effects on Tc-immobilization by Fe(OH)2(s) are investigated while assessing Fe(OH)2(s) as a potential treatment method for Hanford low-activity waste destined for vitrification. Batch studies using simulated low-activity waste indicate that Tc(VII) and Cr(VI) removal is contingent on reduction to Tc(IV) and Cr(III). Furthermore, complete removal of both Cr and Tc depends on the amount of Fe(OH)2(s) present, where complete Cr and Tc removal requires more Fe(OH)2(s) (∼200 g/L of simulant), than removing Cr alone (∼50 g/L of simulant). XRD analysis suggests that Fe(OH)2(s) reaction and transformation in the simulant produces mostly goethite (α-FeOOH), where Fe(OH)2(s) transformation to goethite rather than magnetite is likely due to the simulant chemistry, which includes high levels of nitrite and other constituents. Once reduced, a fraction of Cr(III) and Tc(IV) substitute for octahedral Fe(III) within the goethite crystal lattice as supported by XPS, XANES, and/or EXAFS results. The remaining Cr(III) forms oxide and/or hydroxide phases, whereas Tc(IV) not fully incorporated into goethite persists as either adsorbed or partially incorporated Tc(IV)-oxide species. As such, to fully incorporate Tc(IV) into the goethite crystal structure, additional Fe(OH)2(s) (>200 g/L of simulant) may be required.

Pre-viking Swedish hillfort glass: A prospective long-term alteration analogue for vitrified nuclear waste.

Models for long-term glass alteration are required to satisfy performance predictions of vitrified nuclear waste in various disposal scenarios. Durability parameters are usually extracted from short-term laboratory tests, and sometimes checked with long-term natural experiments on glasses, termed analogues. In this paper, a unique potential ancient glass analogue from Sweden is discussed. The hillfort glass found at Broborg represents a unique case study as a vitrified waste glass analogue to compare to Low Activity Waste glass to be emplaced in near surface conditions at Hanford (USA). Glasses at Broborg have similar and dissimilar compositions to LAW glasses, allowing the testing of long-term alteration of different glass chemistries. In addition, the environmental history of the site is reasonably well documented. Initial investigations on previously collected samples established methodologies for handling and characterizing these artifacts by laboratory methods while preserving their alteration layers and cultural context. Evidence of possible biologically influenced glass alteration, and differential alteration in the 2 types of glass found at the Broborg site is presented.

Reduction and Simultaneous Removal of 99Tc and Cr by Fe(OH)2(s) Mineral Transformation.

Technetium (Tc) remains a priority remediation concern due to persistent challenges, including mobilization due to rapid reoxidation of immobilized Tc, and competing comingled contaminants, e.g., Cr(VI), that inhibit Tc(VII) reduction and incorporation into stable mineral phases. Here Fe(OH)2(s) is investigated as a comprehensive solution for overcoming these challenges, by serving as both the reductant, (Fe(II)), and the immobilization agent to form Tc-incorporated magnetite (Fe3O4). Trace metal analysis suggests removal of Tc(VII) and Cr(VI) from solution occurs simultaneously; however, complete removal and reduction of Cr(VI) is achieved earlier than the removal/reduction of comingled Tc(VII). Bulk oxidation state analysis of the final magnetite solid phase by XANES shows that the majority of Tc is Tc(IV), which is corroborated by XPS measurements. Furthermore, EXAFS results show successful, albeit partial, Tc(IV) incorporation into magnetite octahedral sites. Cr XPS analysis indicates reduction to Cr(III) and the formation of a Cr-incorporated spinel, Cr2O3, and Cr(OH)3 phases. Spinel (modeled as Fe3O4), goethite (α-FeOOH), and feroxyhyte (δ-FeOOH) are detected in all reacted final solid phase samples analyzed by XRD. Incorporation of Tc(IV) has little effect on the spinel lattice structure. Reaction of Fe(OH)2(s) in the presence of Cr(III) results in the formation of a spinel phase that is a solid solution between magnetite (Fe3O4) and chromite (FeCr2O4).

Chemical Trends in Solid Alkali Pertechnetates.

Insight into the solid-state chemistry of pure technetium-99 (99Tc) oxides is required in the development of a robust immobilization and disposal system for nuclear waste stemming from the radiopharmaceutical industry, from the production of nuclear weapons, and from spent nuclear fuel. However, because of its radiotoxicity and the subsequent requirement of special facilities and handling procedures for research, only a few studies have been completed, many of which are over 20 years old. In this study, we report the synthesis of pure alkali pertechnetates (sodium, potassium, rubidium, and cesium) and analysis of these compounds by Raman spectroscopy, X-ray absorption spectroscopy (XANES and EXAFS), solid-state nuclear magnetic resonance (static and magic angle spinning), and neutron diffraction. The structures and spectral signatures of these compounds will aid in refining the understanding of 99Tc incorporation into and release from nuclear waste glasses. NaTcO4 shows aspects of the relatively higher electronegativity of the Na atom, resulting in large distortions of the pertechnetate tetrahedron and deshielding of the 99Tc nucleus relative to the aqueous TcO4-. At the other extreme, the large Cs and Rb atoms interact only weakly with the pertechnetate, have closer to perfect tetrahedral symmetry at the Tc atom, and have very similar vibrational spectra, even though the crystal structure of CsTcO4 is orthorhombic while that of RbTcO4 is tetragonal. Further trends are observed in the cell volume and quadrupolar coupling constant.

Removal of Pertechnetate-Related Oxyanions from Solution Using Functionalized Hierarchical Porous Frameworks.

Efficient and cost-effective removal of radioactive pertechnetate anions from nuclear waste is a key challenge to mitigate long-term nuclear waste storage issues. Traditional materials such as resins and layered double hydroxides (LDHs) were evaluated for their pertechnetate or perrhenate (the non-radioactive surrogate) removal capacity, but there is room for improvement in terms of capacity, selectivity and kinetics. A series of functionalized hierarchical porous frameworks were evaluated for their perrhenate removal capacity in the presence of other competing anions.

Zirconium-Based Metal-Organic Framework for Removal of Perrhenate from Water.

The efficient removal of pertechnetate (TcO4(-)) anions from liquid waste or melter off-gas solution for an alternative treatment is one of the promising options to manage (99)Tc in legacy nuclear waste. Safe immobilization of (99)Tc is of major importance because of its long half-life (t1/2 = 2.13 × 10(5) yrs) and environmental mobility. Different types of inorganic and solid-state ion-exchange materials have been shown to absorb TcO4(-) anions from water. However, both high capacity and selectivity have yet to be achieved in a single material. Herein, we show that a protonated version of an ultrastable zirconium-based metal-organic framework can adsorb perrhenate (ReO4(-)) anions, a nonradioactive surrogate for TcO4(-), from water even in the presence of other common anions. Synchrotron-based powder X-ray diffraction and molecular simulations were used to identify the position of the adsorbed ReO4(-) (surrogate for TcO4(-)) molecule within the framework.

Impeding (99)Tc(IV) mobility in novel waste forms.

Technetium ((99)Tc) is an abundant, long-lived radioactive fission product whose mobility in the subsurface is largely governed by its oxidation state. Tc immobilization is crucial for radioactive waste management and environmental remediation. Tc(IV) incorporation in spinels has been proposed as a novel method to increase Tc retention in glass waste forms during vitrification. However, experiments under high-temperature and oxic conditions show reoxidation of Tc(IV) to volatile pertechnetate, Tc(VII). Here we examine this problem with ab initio molecular dynamics simulations and propose that, at elevated temperatures, doping with first row transition metal can significantly enhance Tc retention in magnetite in the order Co>Zn>Ni. Experiments with doped spinels at 700 °C provide quantitative confirmation of the theoretical predictions in the same order. This work highlights the power of modern, state-of-the-art simulations to provide essential insights and generate theory-inspired design criteria of complex materials at elevated temperatures.

Computational Investigation of Technetium(IV) Incorporation into Inverse Spinels: Magnetite (Fe3O4) and Trevorite (NiFe2O4).

Iron oxides and oxyhydroxides play an important role in minimizing the mobility of redox-sensitive elements in engineered and natural environments. For the radionuclide technetium-99 (Tc), these phases hold promise as primary hosts for increasing Tc loading into glass waste form matrices, or as secondary sinks during the long-term storage of nuclear materials. Recent experiments show that the inverse spinel, magnetite [Fe(II)Fe(III)2O4], can incorporate Tc(IV) into its octahedral sublattice. In that same class of materials, trevorite [Ni(II)Fe(III)2O4] is also being investigated for its ability to host Tc(IV). However, questions remain regarding the most energetically favorable charge-compensation mechanism for Tc(IV) incorporation in each structure, which will affect Tc behavior under changing waste processing or storage conditions. Here, quantum-mechanical methods were used to evaluate incorporation energies and optimized lattice bonding environments for three different, charge-balanced Tc(IV) incorporation mechanisms in magnetite and trevorite (∼5 wt % Tc). For both phases, the removal of two octahedral Fe(II) or Ni(II) ions upon the addition of Tc(IV) in an octahedral site is the most stable mechanism, relative to the creation of octahedral Fe(III) defects or increasing octahedral Fe(II) content. Following hydration-energy corrections, Tc(IV) incorporation into magnetite is energetically favorable while an energy barrier exists for trevorite.

Removal of TcO4(-) ions from solution: materials and future outlook.

Technetium mainly forms during artificial nuclear fission; it exists primarily as TcO4(-) in nuclear waste, and it is among the most hazardous radiation-derived contaminants because of its long half-life (t1/2 = 2.13 × 10(5) years) and environmental mobility. The high water solubility of TcO4(-) (11.3 mol L(-1) at 20 °C) and its ability to readily migrate within the upper layer of the Earth's crust make it particularly hazardous. Several types of materials, namely resins, molecular complexes, layered double hydroxides, and pure inorganic and metal-organic materials, have been shown to be capable of capturing TcO4(-) (or other oxoanions) from solution. In this review, we give a brief description about the types of materials that have been used to capture TcO4(-) and closely related oxyanions so far and discuss the possibility of using metal-organic frameworks (MOFs) as next-generation ion-exchange materials for the stated application. In particular, with the advent of ultra-stable MOF materials, in conjunction with their chemical tunability, MOFs can be applied to capture these oxyanions under real-life conditions.

Technetium Incorporation into Goethite (α-FeOOH): An Atomic-Scale Investigation.

During the processing of low-activity radioactive waste to generate solid waste forms (e.g., glass), technetium-99 (Tc) is of concern because of its volatility. A variety of materials are under consideration to capture Tc from waste streams, including the iron oxyhydroxide, goethite (α-FeOOH), which was experimentally shown to sequester Tc(IV). This material could ultimately be incorporated into glass or alternative low-temperature waste form matrices. However, questions remain regarding the incorporation mechanism for Tc(IV) in goethite, which has implications for predicting the long-term stability of Tc in waste forms under changing conditions. Here, quantum-mechanical calculations were used to evaluate the energy of five different charge-compensated Tc(IV) incorporation scenarios in goethite. The two most stable incorporation mechanisms involve direct substitution of Tc(IV) onto Fe(III) lattice sites and charge balancing either by removing one nearby H(+) (i.e., within 5 Å) or by creating an Fe(III) vacancy when substituting 3 Tc(IV) for 4 Fe(III), with the former being preferred over the latter relative to gas-phase ions. When corrections for hydrated references phases are applied, the Fe(III)-vacancy mechanism becomes more energetically competitive. Calculated incorporation energies and optimized bond lengths are presented. Proton movement is observed to satisfy undercoordinated bonds surrounding Fe(III)-vacancies in the goethite structure.

Rhenium solubility in borosilicate nuclear waste glass: implications for the processing and immobilization of technetium-99.

The immobilization of technetium-99 ((99)Tc) in a suitable host matrix has proven to be a challenging task for researchers in the nuclear waste community around the world. In this context, the present work reports on the solubility and retention of rhenium, a nonradioactive surrogate for (99)Tc, in a sodium borosilicate glass. Glasses containing target Re concentrations from 0 to 10,000 ppm [by mass, added as KReO(4) (Re(7+))] were synthesized in vacuum-sealed quartz ampules to minimize the loss of Re from volatilization during melting at 1000 °C. The rhenium was found as Re(7+) in all of the glasses as observed by X-ray absorption near-edge structure. The solubility of Re in borosilicate glasses was determined to be ~3000 ppm (by mass) using inductively coupled plasma optical emission spectroscopy. At higher rhenium concentrations, additional rhenium was retained in the glasses as crystalline inclusions of alkali perrhenates detected with X-ray diffraction. Since (99)Tc concentrations in a glass waste form are predicted to be <10 ppm (by mass), these Re results implied that the solubility should not be a limiting factor in processing radioactive wastes, assuming Tc as Tc(7+) and similarities between Re(7+) and Tc(7+) behavior in this glass system.