Upper Extremity Nerve Transfers for Treatment of Nerve Injury After Cervical Spine Surgery: A Single-Center Retrospective Review.

PURPOSE: Nerve transfers to restore or augment function after spinal cord injury is an expanding field. There is a paucity of information, however, on the use of nerve transfers for patients having undergone spine surgery. The incidence of neurologic deficit after spine surgery is rare but extremely debilitating. The purpose of this study was to describe the functional benefit after upper extremity nerve transfers in the setting of nerve injury after cervical spine surgery. METHODS: A single-center retrospective review of all patients who underwent nerve transfers after cervical spine surgery was completed. Patient demographics, injury features, spine surgery procedure, nerve conduction and electromyography study results, time to referral to nerve surgeon, time to surgery, surgical technique and number of nerve transfers performed, complications, postoperative muscle testing, and subjective outcomes were reviewed. RESULTS: Fourteen nerve transfers were performed in 6 patients after cervical spine surgery. Nerve transfer procedures consisted of a transfer between a median nerve branch of flexor digitorum superficialis into a biceps nerve branch, an ulnar nerve branch of flexor carpi ulnaris into a brachialis nerve branch, a radial nerve branch of triceps muscle into the axillary nerve, and the anterior interosseous nerve into the ulnar motor nerve. Average patient age was 55 years; all patients were male and underwent surgery on their left upper extremity. Average referral time was 7 months, average time to nerve transfer was 9 months, and average follow-up was 21 months. Average preoperative muscle grading was 0.9 of 5, and average postoperative muscle grading was 4.1 of 5 ( P < 0.00001). CONCLUSIONS: Upper extremity peripheral nerve transfers can significantly help patients regain muscle function from deficits secondary to cervical spine procedures. The morbidity of the nerve transfers is minimal with measurable improvements in muscle function.

Molecular-Scale Visualization of Steric Effects of Ligand Binding to Reconstructed Au(111) Surfaces.

Direct imaging of single molecules at nanostructured interfaces is a grand challenge with potential to enable new, precise material architectures and technologies. Of particular interest are the structural morphology and spectroscopic signatures of the adsorbed molecule, where modern probes are only now being developed with the necessary spatial and energetic resolution to provide detailed information at the molecule-surface interface. Here, we directly characterize the adsorption of individual m-terphenyl isocyanide ligands on a reconstructed Au(111) surface through scanning tunneling microscopy and inelastic electron tunneling spectroscopy. The site-dependent steric pressure of the various surface features alters the vibrational fingerprints of the m-terphenyl isocyanides, which are characterized with single-molecule precision through joint experimental and theoretical approaches. This study provides molecular-level insights into the steric-pressure-enabled surface binding selectivity as well as its effect on the chemical properties of individual surface-binding ligands.

Optically Transparent Lead Halide Perovskite Polycrystalline Ceramics.

We utilize room-temperature uniaxial pressing at applied loads achievable with low-cost, laboratory-scale presses to fabricate freestanding CH3NH3PbX3 (X- = Br-, Cl-) polycrystalline ceramics with millimeter thicknesses and optical transparency up to ∼70% in the infrared. As-fabricated perovskite ceramics can be produced with desirable form factors (i.e., size, shape, and thickness) and high-quality surfaces without any postprocessing (e.g., cutting or polishing). This method should be broadly applicable to a large swath of metal halide perovskites, not just the compositions shown here. In addition to fabrication, we analyze microstructure-optical property relationships through detailed experiments (e.g., transmission measurements, electron microscopy, X-ray tomography, optical profilometry, etc.) as well as modeling based on Mie theory. The optical, electrical, and mechanical properties of perovskite polycrystalline ceramics are benchmarked against those of single-crystalline analogues through spectroscopic ellipsometry, Hall measurements, and nanoindentation. Finally, γ-ray scintillation from a transparent MAPbBr3 ceramic is demonstrated under irradiation from a 137Cs source. From a broader perspective, scalable methods to produce freestanding polycrystalline lead halide perovskites with comparable properties to their single-crystal counterparts could enable key advancements in the commercial production of perovskite-based technologies (e.g., direct X-ray/γ-ray detectors, scintillators, and nonlinear optics).

Scientific Review of the Proarrhythmic Risks of Oligonucleotide Therapeutics: Are Dedicated ICH S7B/E14 Studies Needed for Low-Risk Modalities?

Oligonucleotide therapeutics (ONTs) represent a new modality with unique pharmacological and chemical properties that modulate gene expression with a high degree of target specificity mediated by complementary Watson-Crick base pair hybridization. To date, the proarrhythmic assessment of ONTs has been influenced by International Conference on Harmonization (ICH) E14 and S7B guidance. To document current hERG/QTc evaluation practices, we reviewed US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Approval Packages (source: PharmaPendium.com) and collated preclinical and clinical studies for 17 marketed ONTs. In addition, clinical QTc data from 12 investigational ONTs were obtained from the literature. Of the marketed ONTs, eight were tested in the hERG assay with no inhibitory effect identified at the top concentration (range: 34-3,000 µM) tested. Fourteen of the ONTs were evaluated in nonhuman primate cardiovascular studies with 11 of them in dedicated telemetry studies. No effect on QTc intervals were observed (at high exposure multiples) in all studies. Clinically, four ONTs were evaluated in TQT studies; an additional six ONTs were assessed by concentration-QTc interval analysis, and six by routine safety electrocardiogram monitoring. None of the clinical studies identified a QTc prolongation risk; the same was true for the 12 investigational ONTs. A search of the FDA Adverse Event Database indicated no association between approved ONTs and proarrhythmias. Overall, the collective weight of evidence from 29 ONTs demonstrate no clinical proarrhythmic risk based on data obtained from ICH S7B/E14 studies. Thus, new ONTs may benefit from reduced testing strategies because they have no proarrhythmic risk, a similar cardiac safety profile as monoclonal antibodies, proteins, and peptides.

Switchable Optical Properties of Dyes and Nanoparticles in Electrowetting Devices.

The optical properties of light-absorbing materials in optical shutter devices are critical to the use of such platforms for optical applications. We demonstrate switchable optical properties of dyes and nanoparticles in liquid-based electrowetting-on-dielectric (EWOD) devices. Our work uses narrow-band-absorbing dyes and nanoparticles, which are appealing for spectral-filtering applications targeting specific wavelengths while maintaining device transparency at other wavelengths. Low-voltage actuation of boron dipyromethene (BODIPY) dyes and nanoparticles (Ag and CdSe) was demonstrated without degradation of the light-absorbing materials. Three BODIPY dyes were used, namely Abs 503 nm, 535 nm and 560 nm for dye 1 (BODIPY-core), 2 (I2BODIPY) and 3 (BODIPY-TMS), respectively. Reversible and low-voltage (≤20 V) switching of dye optical properties was observed as a function of device pixel dimensions (300 × 900, 200 × 600 and 150 × 450 µm). Low-voltage and reversible switching was also demonstrated for plasmonic and semiconductor nanoparticles, such as CdSe nanotetrapods (abs 508 nm), CdSe nanoplatelets (Abs 461 and 432 nm) and Ag nanoparticles (Abs 430 nm). Nanoparticle-based devices showed minimal hysteresis as well as faster relaxation times. The study presented can thus be extended to a variety of nanomaterials and dyes having the desired optical properties.

Partially Ion-Paired Solvation Structure Design for Lithium-Sulfur Batteries under Extreme Operating Conditions.

Achieving increased energy density under extreme operating conditions remains a major challenge in rechargeable batteries. Herein, we demonstrate an all-fluorinated ester-based electrolyte comprising partially fluorinated carboxylate and carbonate esters. This electrolyte exhibits temperature-resilient physicochemical properties and moderate ion-paired solvation, leading to a half solvent-separated and half contact-ion pair in a sole electrolyte. As a result, facile desolvation and preferential reduction of anions/fluorinated co-solvents for LiF-dominated interphases are achieved without compromising ionic conductivity (>1 mS cm-1 even at -40 °C). These advantageous features were found to apply to both lithium metal and sulfur-based electrodes even under extreme operating conditions, allowing stable cycling of Li || sulfurized polyacrylonitrile (SPAN) full cells with high SPAN loading (>3.5 mAh cm-2 ) and thin Li anode (50 µm) at -40, 23 and 50 °C. This work offers a promising path for designing temperature-resilient electrolytes to support high energy density Li metal batteries operating in extreme conditions.

Toward a quantitative interfacial description of solvation for Li metal battery operation under extreme conditions.

The future application of Li metal batteries (LMBs) at scale demands electrolytes that endow improved performance under fast-charging and low-temperature operating conditions. Recent works indicate that desolvation kinetics of Li+ plays a crucial role in enabling such behavior. However, the modulation of this process has typically been achieved through inducing qualitative degrees of ion pairing into the system. In this work, we find that a more quantitative control of the ion pairing is crucial to minimizing the desolvation penalty at the electrified interface and thus the reversibility of the Li metal anode under kinetic strain. This effect is demonstrated in localized electrolytes based on strongly and weakly bound ether solvents that allow for the deconvolution of solvation chemistry and structure. Unexpectedly, we find that maximum degrees of ion pairing are suboptimal for ultralow temperature and high-rate operation and that reversibility is substantially improved via slight local dilution away from the saturation point. Further, we find that at the optimum degree of ion pairing for each system, weakly bound solvents still produce superior behavior. The impact of these structure and chemistry effects on charge transfer are then explicitly resolved via experimental and computational analyses. Lastly, we demonstrate that the locally optimized diethyl ether-based localized-high-concentration electrolytes supports kinetic strained operating conditions, including cycling down to -60 °C and 20-min fast charging in LMB full cells. This work demonstrates that explicit, quantitative optimization of the Li+ solvation state is necessary for developing LMB electrolytes capable of low-temperature and high-rate operation.

Locally Saturated Ether-Based Electrolytes With Oxidative Stability For Li Metal Batteries Based on Li-Rich Cathodes.

Li metal batteries applying Li-rich, Mn-rich (LMR) layered oxide cathodes present an opportunity to achieve high-energy density at reduced cell cost. However, the intense oxidizing and reducing potentials associated with LMR cathodes and Li anodes present considerable design challenges for prospective electrolytes. Herein, we demonstrate that, somewhat surprisingly, a properly designed localized-high-concentration electrolyte (LHCE) based on ether solvents is capable of providing reversible performance for Li||LMR cells. Specifically, the oxidative stability of the LHCE was found to heavily rely on the ratio between salt and solvating solvent, where local-saturation was necessary to stabilize performance. Through molecular dynamics (MD) simulations, this behavior was found to be a result of aggregated solvation structures of Li+/anion pairs. This LHCE system was found to produce significantly improved LMR cycling (95.8% capacity retention after 100 cycles) relative to a carbonate control as a result of improved cathode-electrolyte interphase (CEI) chemistry from X-ray photoelectron spectroscopy (XPS), and cryogenic transmission electron microscopy (cryo-TEM). Leveraging this stability, 4 mAh cm-2 LMR||2× Li full cells were demonstrated, retaining 87% capacity after 80 cycles in LHCE, whereas the control electrolyte produced rapid failure. This work uncovers the benefits, design requirements, and performance origins of LHCE electrolytes for high-voltage Li||LMR batteries.

Agglomeration Drives the Reversed Fractionation of Aqueous Carbonate and Bicarbonate at the Air-Water Interface.

In the course of our investigations of the adsorption of ions to the air-water interface, we previously reported the surprising result that doubly charged carbonate anions exhibit a stronger surface affinity than singly charged bicarbonate anions. In contrast to monovalent, weakly hydrated anions, which generally show enhanced concentrations in the interfacial region, multivalent (and strongly hydrated) anions are expected to show a much weaker surface propensity. In the present work, we use resonantly enhanced deep-UV second-harmonic generation spectroscopy to measure the Gibbs free energy of adsorption of both carbonate (CO32-) and bicarbonate (HCO3-) anions to the air-water interface. Contrasting the predictions of classical electrostatic theory and in support of our previous findings from X-ray photoelectron spectroscopy, we find that carbonate anions do indeed exhibit much stronger surface affinity than do the bicarbonate anions. Extensive computer simulations reveal that strong ion pairing of CO32- with the Na+ countercation in the interfacial region results in the formation of near-neutral agglomerate clusters, consistent with a theory of interfacial ion adsorption based on hydration free energy and capillary waves. Simulated X-ray photoelectron spectra predict a 1 eV shift in the carbonate spectra compared to that of bicarbonate, further confirming our experiments. These findings not only advance our fundamental understanding of ion adsorption chemistry but also impact important practical processes such as ocean acidification, sea-spray aerosol chemistry, and mammalian respiration physiology.

Engineered porosity for tissue-integrating, bioresorbable lifetime-based phosphorescent oxygen sensors.

Versatile silk protein-based material formats were studied to demonstrate bioresorbable, implantable optical oxygen sensors that can integrate with the surrounding tissues. The ability to continuously monitor tissue oxygenation in vivo is desired for a range of medical applications. Silk was chosen as the matrix material due to its excellent biocompatibility, its unique chemistry that facilitates interactions with chromophores, and the potential to tune degradation time without altering chemical composition. A phosphorescent Pd (II) benzoporphyrin chromophore was incorporated to impart oxygen sensitivity. Organic solvent-based processing methods using 1,1,1,3,3,3-hexafluoro-2-propanol were used to fabricate: 1) silk-chromophore films with varied thickness and 2) silk-chromophore sponges with interconnected porosity. All compositions were biocompatible and exhibited photophysical properties with oxygen sensitivities (i.e., Stern-Volmer quenching rate constants of 2.7-3.2 × 104 M-1) useful for monitoring physiological tissue oxygen levels and for detecting deviations from normal behavior (e.g., hyperoxia). The potential to tune degradation time without significantly impacting photophysical properties was successfully demonstrated. Furthermore, the ability to consistently monitor tissue oxygenation in vivo was established via a multi-week rodent study. Histological assessments indicated successful tissue integration for the sponges, and this material format responded more quickly to various oxygen challenges than the film samples.

Goldilocks Energy Minimum: Peptide-Based Reversible Aggregation and Biosensing.

Colorimetric biosensors based on gold nanoparticle (AuNP) aggregation are often challenged by matrix interference in biofluids, poor specificity, and limited utility with clinical samples. Here, we propose a peptide-driven nanoscale disassembly approach, where AuNP aggregates induced by electrostatic attractions are dissociated in response to proteolytic cleavage. Initially, citrate-coated AuNPs were assembled via a short cationic peptide (RRK) and characterized by experiments and simulations. The dissociation peptides were then used to reversibly dissociate the AuNP aggregates as a function of target protease detection, i.e., main protease (Mpro), a biomarker for severe acute respiratory syndrome coronavirus 2. The dissociation propensity depends on peptide length, hydrophilicity, charge, and ligand architecture. Finally, our dissociation strategy provides a rapid and distinct optical signal through Mpro cleavage with a detection limit of 12.3 nM in saliva. Our dissociation peptide effectively dissociates plasmonic assemblies in diverse matrices including 100% human saliva, urine, plasma, and seawater, as well as other types of plasmonic nanoparticles such as silver. Our peptide-enabled dissociation platform provides a simple, matrix-insensitive, and versatile method for protease sensing.

Unravelling Ultrafast Li Ion Transport in Functionalized Metal-Organic Framework-Based Battery Electrolytes.

Nonaqueous fluidic transport and ion solvation properties under nanoscale confinement are poorly understood, especially in ion conduction for energy storage and conversion systems. Herein, metal-organic frameworks (MOFs) and aprotic electrolytes are studied as a robust platform for molecular-level insights into electrolyte behaviors in confined spaces. By employing computer simulations, along with spectroscopic and electrochemical measurements, we demonstrate several phenomena that deviate from the bulk, including modulated solvent molecular configurations, aggregated solvation structures, and tunable transport mechanisms from quasi-solid to quasi-liquid in functionalized MOFs. Technologically, taking advantage of confinement effects may prove useful for addressing stability concerns associated with volatile organic electrolytes while simultaneously endowing ultrafast transport of solvates, resulting in improved battery performance, even at extreme temperatures. The molecular-level insights presented here further our understanding of structure-property relationships of complex fluids at the nanoscale, information that can be exploited for the predictive design of more efficient electrochemical systems.

A Comparative Study of 2-Corner, 3-Corner, and 4-Corner Arthrodesis for Midcarpal Arthritis.

BACKGROUND: Four-corner fusion (4CF) is a common treatment for midcarpal arthritis; however, alternatives including 2-corner fusion (2CF) and 3-corner fusion (3CF) have been described. Limited literature suggests 2CF and 3CF may improve range of motion but have higher complication rates. Our objective is to compare function and patient-reported outcomes following 4CF, 3CF, and 2CF at our institution. METHODS: Adult patients undergoing 4CF, 3CF, and 2CF from 2011 to 2021 who attended at least one follow-up were included. Four-corner fusion patients were compared with those who underwent either 3CF or 2CF using staple fixation. Outcomes include nonunion rate, reoperation rate, progression to wrist fusion, range of motion, and patient-reported pain, satisfaction, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. RESULTS: A total of 58 patients met inclusion criteria. There were 49 4CF and 9 2CF or 3CF patients. Nonunion rates, progression to wrist fusion, and repeat surgery for any indication were not significantly different among groups. Range of motion (flexion-extension, radial-ulnar deviation) and grip strength at postoperative visits were not significantly different. Significantly more 4CF patients required bone grafting. Pain, overall satisfaction, and DASH scores were similar. CONCLUSIONS: Although prior studies suggest increased risk of nonunion and hardware migration after 2CF/3CF, we did not observe higher complication rates compared with 4CF. Range of motion, strength, and patient-reported outcomes were similar. While 4CF is traditionally the procedure of choice for midcarpal fusion, we found that when using a staple fixation technique, 2CF and 3CF have comparable clinical and patient-reported outcomes yet decrease the need for autologous bone grafting.

Probing lithium mobility at a solid electrolyte surface.

Solid-state electrolytes overcome many challenges of present-day lithium ion batteries, such as safety hazards and dendrite formation1,2. However, detailed understanding of the involved lithium dynamics is missing due to a lack of in operando measurements with chemical and interfacial specificity. Here we investigate a prototypical solid-state electrolyte using linear and nonlinear extreme-ultraviolet spectroscopies. Leveraging the surface sensitivity of extreme-ultraviolet-second-harmonic-generation spectroscopy, we obtained a direct spectral signature of surface lithium ions, showing a distinct blueshift relative to bulk absorption spectra. First-principles simulations attributed the shift to transitions from the lithium 1 s state to hybridized Li-s/Ti-d orbitals at the surface. Our calculations further suggest a reduction in lithium interfacial mobility due to suppressed low-frequency rattling modes, which is the fundamental origin of the large interfacial resistance in this material. Our findings pave the way for new optimization strategies to develop these electrochemical devices via interfacial engineering of lithium ions.

Electronic signatures of Lorentzian dynamics and charge fluctuations in lithiated graphite structures.

Lithium graphite intercalation compounds (Li-GICs) are essential materials for modern day portable electronics and obtaining insights into their atomic structure and thermodynamics is of fundamental interest. Here we explore the electronic and atomic states of Li-GICs at varying degrees of Lithium loading (i.e., "staging") by means of ab-initio molecular dynamics simulations and simulated X-ray adsorption spectroscopy (XAS). We analyze the atomic correlation functions and shows that the enhancements of the Li-ion entropy with increased staging result from Lorentzian lithium-ion dynamics and charge fluctuations, which activate low-energy phonon modes. The associated electronic signatures are modulations of the unoccupied π*/σ* orbital energy levels and unambiguous fingerprints in Carbon K-edge XAS spectra. Thus, we extend the canonical view of XAS, establishing that these "static" measurements in fact encode the signature of the thermodynamic response and relaxation dynamics of the system. This causal link between atomic structure, spectroscopy, thermodynamics, and information theory can be generally exploited to better understand stability in solid-state electrochemical systems.

Do The Twist: Efficient Heavy-Atom-Free Visible Light Polymerization Facilitated by Spin-Orbit Charge Transfer Inter-system Crossing.

The use of visible light to drive polymerizations with spatiotemporal control offers a mild alternative to contemporary UV-light-based production of soft materials. In this spectral region, photoredox catalysis represents the most efficient polymerization method, yet it relies on the use of heavy-atoms, such as precious metals or toxic halogens. Herein, spin-orbit charge transfer intersystem crossing from boron dipyrromethene (BODIPY) dyads bearing twisted aromatic groups is shown to enable efficient visible light polymerizations in the absence of heavy-atoms. A ≈5-15× increase in polymerization rate and improved photostability was achieved for twisted BODIPYs relative to controls. Furthermore, monomer polarity had a distinct effect on polymerization rate, which was attributed to charge transfer stabilization based on ultrafast transient absorption and phosphorescence spectroscopies. Finally, rapid and high-resolution 3D printing with a green LED was demonstrated using the present photosystem.

Active States During the Reduction of CO2 by a MoS2 Electrocatalyst.

Transition-metal dichalcogenides (TMDCs) such as MoS2 are Earth-abundant catalysts that are attractive for many chemical processes, including the carbon dioxide reduction reaction (CO2RR). While many studies have correlated synthetic preparation and architectures with macroscopic electrocatalytic performance, not much is known about the state of MoS2 under functional conditions, particularly its interactions with target molecules like CO2. Here, we combine operando Mo K- and S K-edge X-ray absorption spectroscopy (XAS) with first-principles simulations to track changes in the electronic structure of MoS2 nanosheets during CO2RR. Comparison of the simulated and measured XAS discerned the existence of Mo-CO2 binding in the active state. This state perturbs hybridized Mo 4d-S 3p states and is critically mediated by sulfur vacancies induced electrochemically. The study sheds new light on the underpinnings of the excellent performance of MoS2 in CO2RR. The electronic signatures we reveal could be a screening criterion toward further gains in activity and selectivity of TMDCs in general.

Decoupling Planarizing and Steric Energetics to Accurately Model the Rigidity of π-Conjugated Polymers.

The π-conjugated backbone of semiconducting polymers gives rise to both their electronic properties and structural rigidity. However, current computational methods for understanding the rigidity of polymer chains fail in one crucial way. Namely, standard torsional scan (TS) methods do not satisfactorily capture the behavior of polymers exhibiting a high degree of steric hindrance. This deficiency in part stems from the method by which torsional scans decouple energy related to electron delocalization from that related to nonbonded interactions. These methods do so by applying classical corrections of the nonbonded energy to the quantum mechanical (QM) torsional profile for polymers that are highly sterically hindered. These large corrections to the energy from nonbonded interactions can substantially skew the calculated QM energies related to torsion, resulting in an inaccurate or imprecise estimation of the rigidity of a polymer. As a consequence, simulations of the morphology of a highly sterically hindered polymer using the TS method can be highly inaccurate. Here, we describe an alternative, generalizable method by which the delocalization energy can be decoupled from the energy associated with nonbonded interactions─the "isolation of delocalization energy" (DE) method. From torsional energy calculations, we find that the relative accuracy of the DE method is similar to the TS method (within 1 kJ/mol) for two model polymers (P3HT, PTB7) when compared to quantum mechanical calculations. However, the DE method significantly increased the relative accuracy for simulations of PNDI-T, a highly sterically hindered polymer (8.16 kJ/mol). Likewise, we show that comparison of the planarization energy (i.e., backbone rigidity) from torsional parameters is significantly more precise for both PTB7 and PNDI-T when using the DE method as opposed to the TS method. These differences affect the simulated morphology, with the DE method predicting a significantly more planar configuration of PNDI-T.

Investigation of local distortion effects on X-ray absorption of ferroelectric perovskites from first principles simulations.

Understanding the role of ferroelectric polarization in modulating the electronic and structural properties of crystals is critical for advancing these materials for overcoming various technological and scientific challenges. However, due to difficulties in performing experimental methods with the required resolution, or in interpreting the results of methods therein, the nanoscale morphology and response of these surfaces to external electric fields has not been properly elaborated. In this work we investigate the effect of ferroelectric polarization and local distortions in a BaTiO3 perovskite, using two widely used computational approaches which treat the many-body nature of X-ray excitations using different philosophies, namely the many-body, delta-self-consistent-field determinant (mb-ΔSCF) and the Bethe-Salpeter equation (BSE) approaches. We show that in agreement with our experiments, both approaches consistently predict higher excitations of the main peak in the O-K edge for the surface with upward polarization. However, the mb-ΔSCF approach mostly fails to capture the L2,3 separations at the Ti-L edge, due to the absence of spin-orbit coupling in Kohn-Sham density functional theory (KS-DFT) at the generalized gradient approximation level. On the other hand, and most promising, we show that application of the GW/BSE approach successfully reproduces the experimental XAS, both the relative peak intensities as well as the L2,3 separations at the Ti-L edges upon ferroelectric switching. Thus simulated XAS is shown to be a powerful method for capturing the nanoscale structure of complex materials, and we underscore the need for many-body perturbation approaches, with explicit consideration of core-hole and multiplet effects, for capturing the essential physics in these systems.