The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials.

SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.

Synchrotron radiation X-ray diffraction computed tomography (XRDCT): a new tool in cultural heritage and stone conservation for 3D non-destructive probing and phase analysis of inorganic re-treatments.

The issue of preserving carbonatic stones of cultural heritage (CH) restored in the past that have undergone new decay phenomena is strongly emerging and conservation science has not yet found a reliable solution. In this paper, we propose the application of synchrotron radiation X-ray diffraction computed tomography (XRDCT) to explore the effects of using inorganic-mineral products (ammonium oxalate; ammonium phosphate) in sequence as a novel, compatible and effective re-treatment approach to consolidate decayed carbonatic stones already treated with inorganic-mineral treatments. High-quality XRDCT datasets were used to qualitatively/quantitatively investigate and 3D localize the complex mixture of crystalline phases formed after the conservation re-treatments within a porous carbonatic stone substrate. The XRDCT reconstruction images and the structural refinements of XRD patterns with the Rietveld methods showed that the phase composition of reaction products, their volume distribution, and weight fraction vary as a function of the treatment sequence and penetration depth. The high potential of XRDCT allows (i) assessment of peculiar trends of each treatment/treatment sequence; (ii) exploration of the reaction steps of the sequential treatments and (iii) demonstration of the consolidating effect of inorganic re-treatments, non-destructively and at the micron scale. Above all, our study (i) provides new analytical tools to support the conservation choices, (ii) showcases new analytical possibilities for XRDCT in conservation science, including in investigations of CH materials and decay processes, and (iii) opens up new perspectives in analytical chemistry and material characterisation for the non-destructive and non-invasive analysis of reactions within heterogeneous polycrystalline systems.

Cardiovascular Disease in Anti-neutrophil Cytoplasm Antibody-Associated Vasculitis.

PURPOSE OF REVIEW: Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare, multisystem, autoimmune disease characterised by microvascular inflammation. Over the past 20 years, advances in immunological management have improved short-term patient outcomes. Longer-term patient outcomes remain poor with cardiovascular disease now the leading cause of death in AAV. Here, we examine the potential pathways that contribute to the increased risk of cardiovascular disease in AAV and the current evidence to manage this risk. RECENT FINDINGS: The incidence of cardiovascular disease in AAV exceeds that expected by traditional risk factors alone, suggesting a contribution from disease-specific factors. Similarly, it is unclear how different immunosuppressive therapies contribute to and modify cardiovascular risk, and there is a paucity of data examining the efficacy of traditional cardioprotective medications in AAV. There is a lack of evidence-based cardiovascular risk assessment tools and cardioprotective therapies in patients with AAV which should be addressed to improve long-term outcomes.

Progress Toward Measles Elimination - African Region, 2017-2021.

Worldwide, measles remains a major cause of disease and death; the highest incidence is in the World Health Organization African Region (AFR). In 2011, the 46 AFR member states established a goal of regional measles elimination by 2020; this report describes progress during 2017-2021. Regional coverage with a first dose of measles-containing vaccine (MCV) decreased from 70% in 2017 to 68% in 2021, and the number of countries with ≥95% coverage decreased from six (13%) to two (4%). The number of countries providing a second MCV dose increased from 27 (57%) to 38 (81%), and second-dose coverage increased from 25% to 41%. Approximately 341 million persons were vaccinated in supplementary immunization activities, and an estimated 4.5 million deaths were averted by vaccination. However, the number of countries meeting measles surveillance performance indicators declined from 26 (62%) to nine (22%). Measles incidence increased from 69.2 per 1 million population in 2017 to 81.9 in 2021. The number of estimated annual measles cases and deaths increased 22% and 8%, respectively. By December 2021, no country in AFR had received verification of measles elimination. To achieve a renewed regional goal of measles elimination in at least 80% of countries by 2030, intensified efforts are needed to recover and surpass levels of surveillance performance and coverage with 2 MCV doses achieved before the COVID-19 pandemic.

Correction: 5D total scattering computed tomography reveals the full reaction mechanism of a bismuth vanadate lithium ion battery anode.

Correction for '5D total scattering computed tomography reveals the full reaction mechanism of a bismuth vanadate lithium ion battery anode' by Jonas Sottmann et al., Phys. Chem. Chem. Phys., 2022, 24, 27075-27085, https://doi.org/10.1039/D2CP03892G.

Mapping the structural trends in zinc aluminosilicate glasses.

The structure of zinc aluminosilicate glasses with the composition (ZnO)x(Al2O3)y(SiO2)1-x-y, where 0 ≤ x < 1, 0 ≤ y < 1, and x + y < 1, was investigated over a wide composition range by combining neutron and high-energy x-ray diffraction with 27Al magic angle spinning nuclear magnetic resonance spectroscopy. The results were interpreted using an analytical model for the composition-dependent structure in which the zinc ions do not act as network formers. Four-coordinated aluminum atoms were found to be in the majority for all the investigated glasses, with five-coordinated aluminum atoms as the main minority species. Mean Al-O bond distances of 1.764(5) and 1.855(5) Å were obtained for the four- and five-coordinated aluminum atoms, respectively. The coordination environment of zinc was not observed to be invariant. Instead, it is dependent on whether zinc plays a predominantly network-modifying or charge-compensating role and, therefore, varies systematically with the glass composition. The Zn-O coordination number and bond distance were found to be 4.36(9) and 2.00(1) Å, respectively, for the network-modifying role vs 5.96(10) and 2.08(1) Å, respectively, for the charge-compensating role. The more open coordination environment of the charge-compensator is related to an enhanced probability of zinc finding bridging oxygen atoms as nearest-neighbors, reflecting a change in the connectivity of the glass network comprising four-coordinated silicon and aluminum atoms as the alumina content is increased.

Past as Prologue-Use of Rubella Vaccination Program Lessons to Inform COVID-19 Vaccination.

The rapid rollout of vaccines against COVID-19 as a key mitigation strategy to end the global pandemic might be informed by lessons learned from rubella vaccine implementation in response to the global rubella epidemic of 1963-1965. That rubella epidemic led to the development of a rubella vaccine that has been introduced in all but 21 countries worldwide and has led to elimination of rubella in 93 countries. Although widespread introduction and use of rubella vaccines was slower than that for COVID-19 vaccines, the process can provide valuable insights for the continued battle against COVID-19. Experiences from the rubella disease control program highlight the critical and evolving elements of a vaccination program, including clearly delineated goals and strategies, regular data-driven revisions to the program based on disease and vaccine safety surveillance, and evaluations to identify the vaccine most capable of achieving disease control targets.

Utility of interval kidney biopsy in ANCA-associated vasculitis.

OBJECTIVES: ANCA-associated vasculitis (AAV) is a rare autoimmune disorder that commonly involves the kidney. Early identification of kidney involvement, assessing treatment-response and predicting outcome are important clinical challenges. Here, we assessed the potential utility of interval kidney biopsy in AAV. METHODS: In a tertiary referral centre with a dedicated vasculitis service, we identified patients with AAV who had undergone interval kidney biopsy, defined as a repeat kidney biopsy (following an initial biopsy showing active AAV) undertaken to determine the histological response in the kidney following induction immunosuppression. We analysed biochemical, histological and outcome data, including times to kidney failure and death for all patients. RESULTS: We identified 57 patients with AAV who underwent at least one interval kidney biopsy (59 interval biopsies in total; median time to interval biopsy ∼130 days). Of the 59 interval biopsies performed, 24 (41%) patients had clinically suspected active disease at time of biopsy which was confirmed histologically in only 42% of cases; 35 (59%) patients were in clinical disease-remission, and this was correct in 97% of cases. The clinician's impression was incorrect in one in four patients. Hematuria at interval biopsy did not correlate with histological activity. Interval biopsy showed fewer acute lesions and more chronic damage compared with initial biopsy and led to immunosuppressive treatment-change in 75% (44/59) of patients. Clinical risk prediction tools tended to operate better using interval biopsy data. CONCLUSION: Interval kidney biopsy is useful for determining treatment-response and subsequent disease management in AAV. It may provide better prognostic information than initial kidney biopsy and should be considered for inclusion into future clinical trials and treatment protocols for patients with AAV.

Quantum Spin-1/2 Dimers in a Low-Dimensional Tetrabromocuprate Magnet.

This work describes a homometallic spin- 1 / 2 tetrabromocuprate adopting a bilayer structure. Magnetic-susceptibility measurements show a broad maximum centred near 70 K, with fits to this data using a Heisenberg model consistent with strong antiferromagnetic coupling between neighbouring copper atoms in different layers of the bilayer. There are further weak intralayer ferromagnetic interactions between copper cations in neighbouring dimers. First-principles calculations are consistent with this, but suggest there is only significant magnetic coupling within one direction of a layer; this would suggest the presence of a spin ladder within the bilayer with antiferromagnetic rung and weaker ferromagnetic rail couplings.

Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination - Worldwide, 2012-2020.

Rubella virus is a leading cause of vaccine-preventable birth defects and can cause epidemics. Although rubella virus infection usually produces a mild febrile rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or an infant born with a constellation of birth defects known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine (RCV) can provide lifelong protection against rubella (1). The Global Vaccine Action Plan 2011-2020 (GVAP) included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions* by 2020 (2), and WHO recommends capitalizing on the accelerated measles elimination activities as an opportunity to introduce RCV (1). This report updates a previous report (3) and summarizes global progress toward control and elimination of rubella and CRS from 2012, when accelerated rubella control activities were initiated, through 2020. Among 194 WHO Member States, the number with RCV in their immunization schedules has increased from 132 (68%) in 2012 to 173 (89%) in 2020; 70% of the world's infants were vaccinated against rubella in 2020. Reported rubella cases declined by 48%, from 94,277 in 2012 to 49,136 in 2019, and decreased further to 10,194 in 2020. Rubella elimination has been verified in 93 (48%) of 194 countries including the entire Region of the Americas (AMR). To increase the equity of protection and make further progress to eliminate rubella, it is important that the 21 countries that have not yet done so should introduce RCV. Likewise, countries that have introduced RCV can achieve and maintain rubella elimination with high vaccination coverage and surveillance for rubella and CRS. Four of six WHO regions have established rubella elimination goals; the two WHO regions that have not yet established an elimination goal (the African [AFR] and Eastern Mediterranean [EMR] regions) have expressed a commitment to rubella elimination and should consider establishing a goal.

Magnetic Phase Separation in the Oxypnictide Sr2Cr1.85Mn1.15As2O2.

Layered Sr2M3As2O2-type oxypnictides are composed of tetrahedral M2Pn2 and square planar MO2 layers, the building blocks of iron-based and cuprate superconductors. To further expand our understanding of the chemical and magnetic properties of the Sr2Cr3-xMnxAs2O2 solid solution, Sr2Cr2MnAs2O2 has been synthesized. The compound crystallizes in the I4/mmm tetragonal space group with a refined stoichiometry of Sr2Cr1.85Mn1.15As2O2. The M(2) site within the M2Pn2 slab is occupied by 42.7% Cr and 57.3% Mn, and the magnetic moments order antiferromagnetically below TN(M2) = 540 K with a C-type antiferromagnetic structure. The M(1) site within the MO2 layers is fully occupied by Cr, and antiferromagnetic order is observed below TN(M1) = 200 K. Along c, there are two possible interplanar arrangements: ferromagnetic with the (1/2, 1/2, 0) propagation vector and antiferromagnetic with the (1/2, 1/2, 1/2) propagation vector. Magnetic phase separation arises so that both propagation vectors are observed below 200 K. Such magnetic phase separation has not been previously observed in Sr2M3As2O2 phases (M = Cr, Mn) and shows that there are several competing magnetic structures present in these compounds.

Localized Spin Dimers and Structural Distortions in the Hexagonal Perovskite Ba3CaMo2O9.

Extended solid-state materials based on the hexagonal perovskite framework are typified by close competition between localized magnetic interactions and quasi-molecular electronic states. Here, we report the structural and magnetic properties of the new six-layer hexagonal perovskite Ba3CaMo2O9. Neutron diffraction experiments, combined with magnetic susceptibility measurements, show that the Mo2O9 dimers retain localized character down to 5 K and adopt nonmagnetic spin-singlet ground states. This is in contrast to the recently reported Ba3SrMo2O9 analogue, in which the Mo2O9 dimers spontaneously separate into a mixture of localized and quasi-molecular ground states. Structural distortions in both Ba3CaMo2O9 and Ba3SrMo2O9 have been studied with the aid of distortion mode analyses to elucidate the coupling between the crystal lattice and electronic interactions in 6H Mo5+ hexagonal perovskites.

Site-Selective d10/d0 Substitution in an S = 1/2 Spin Ladder Ba2CuTe1-xWxO6 (0 ≤ x ≤ 0.3).

Isovalent nonmagnetic d10 and d0 B″ cations have proven to be a powerful tool for tuning the magnetic interactions between magnetic B' cations in A2B'B″O6 double perovskites. Tuning is facilitated by the changes in orbital hybridization that favor different superexchange pathways. This can produce alternative magnetic structures when B″ is d10 or d0. Furthermore, the competition generated by introducing mixtures of d10 and d0 cations can drive the material into the realms of exotic quantum magnetism. Here, Te6+ d10 was substituted by W6+ d0 in the hexagonal perovskite Ba2CuTeO6, which possesses a spin ladder geometry of Cu2+ cations, creating a Ba2CuTe1-xWxO6 solid solution (x = 0-0.3). We find W6+ is almost exclusively substituted for Te6+ on the corner-sharing site within the spin ladder, in preference to the face-sharing site between ladders. The site-selective doping directly tunes the intraladder, Jrung and Jleg, interactions. Modeling the magnetic susceptibility data shows the d0 orbitals modify the relative intraladder interaction strength (Jrung/Jleg) so the system changes from a spin ladder to isolated spin chains as W6+ increases. This further demonstrates the utility of d10 and d0 dopants as a tool for tuning magnetic interactions in a wide range of perovskites and perovskite-derived structures.

5D total scattering computed tomography reveals the full reaction mechanism of a bismuth vanadate lithium ion battery anode.

We have used operando 5D synchrotron total scattering computed tomography (TSCT) to understand the cycling and possible long term deactivation mechanisms of the lithium-ion battery anode bismuth vanadate. This anode material functions via a combined conversion/alloying mechanism in which nanocrystals of lithium-bismuth alloy are protected by an amorphous matrix of lithium vanadate. This composite is formed in situ during the first lithiation of the anode. The operando TSCT data were analyzed and mapped using both pair distribution function and Rietveld methods. We can follow the lithium-bismuth alloying reaction at all stages, gaining real structural insight including variations in nanoparticle sizes, lattice parameters and bond lengths, even when the material is completely amorphous. We also observe for the first time structural changes related to the cycling of lithium ions in the lithium vanadate matrix, which displays no interactions beyond the first shell of V-O bonds. The first 3D operando mapping of the distribution of different materials in an amorphous anode reveals a decline in coverage caused by either agglomeration or partial dissolution of the active material, hinting at the mechanism of long term deactivation. The observations from the operando experiment are backed up by post mortem transmission electron microscope (TEM) studies and theoretical calculations to provide a complete picture of an exceptionally complex cycling mechanism across a range of length scales.

The Application of HEXS and HERFD XANES for Accurate Structural Characterisation of Actinide Nanomaterials: The Case of ThO2.

The structural characterisation of actinide nanoparticles (NPs) is of primary importance and hard to achieve, especially for non-homogeneous samples with NPs less than 3 nm. By combining high-energy X-ray scattering (HEXS) and high-energy-resolution fluorescence-detected X-ray absorption near-edge structure (HERFD XANES) analysis, we have characterised for the first time both the short- and medium-range order of ThO2 NPs obtained by chemical precipitation. By using this methodology, a novel insight into the structures of NPs at different stages of their formation has been achieved. The pair distribution function revealed a high concentration of ThO2 small units similar to thorium hexamer clusters mixed with 1 nm ThO2 NPs in the initial steps of formation. Drying the precipitates at around 150 °C promoted the recrystallisation of the smallest units into more thermodynamically stable ThO2 NPs. HERFD XANES analysis at the thorium M4 edge, a direct probe for f states, showed variations that we have correlated with the breakdown of the local symmetry around the thorium atoms, which most likely concerns surface atoms. Together, HEXS and HERFD XANES are a powerful methodology for investigating actinide NPs and their formation mechanism.

The Application of HEXS and HERFD XANES for Accurate Structural Characterisation of Actinide Nanomaterials: The Case of ThO2.

Invited for the cover of this issue is Lucia Amidani and co-workers from the The European Synchrotron, Helmholtz Zentrum Dresden-Rossendorf, Lomonosov Moscow State University, Kurchatov Institute, and the Université Grenoble Alpes. The image depicts the atomic structure of the sample being viewed through "atomic googles", which represent the X-ray techniques used in this work. Read the full text of the article at 10.1002/chem.202003360.

Prevalence and Medication Treatment of Opioid Use Disorder Among Primary Care Patients with Hepatitis C and HIV.

BACKGROUND: Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. OBJECTIVE: To describe the prevalence of documented OUD, as well as receipt of office-based medication treatment, among primary care patients with HCV or HIV. DESIGN: Retrospective observational cohort study using electronic health record and insurance data. PARTICIPANTS: Adults ≥ 18 years with ≥ 2 visits to primary care during the study (2014-2016) at 6 healthcare systems across five states (CO, CA, OR, WA, and MN). MAIN MEASURES: The primary outcome was the diagnosis of OUD; the secondary outcome was OUD treatment with buprenorphine or oral/injectable naltrexone. Prevalence of OUD and OUD treatment was calculated across four groups: HCV only; HIV only; HCV and HIV; and neither HCV nor HIV. In addition, adjusted odds ratios (AOR) of OUD treatment associated with HCV and HIV (separately) were estimated, adjusting for age, gender, race/ethnicity, and site. KEY RESULTS: The sample included 1,368,604 persons, of whom 10,042 had HCV, 5821 HIV, and 422 both. The prevalence of diagnosed OUD varied across groups: 11.9% (95% CI: 11.3%, 12.5%) for those with HCV; 1.6% (1.3%, 2.0%) for those with HIV; 8.8% (6.2%, 11.9%) for those with both; and 0.92% (0.91%, 0.94%) among those with neither. Among those with diagnosed OUD, the prevalence of OUD medication treatment was 20.9%, 16.0%, 10.8%, and 22.3%, for those with HCV, HIV, both, and neither, respectively. HCV was not associated with OUD treatment (AOR = 1.03; 0.88, 1.21), whereas patients with HIV had a lower probability of OUD treatment (AOR = 0.43; 0.26, 0.72). CONCLUSIONS: Among patients receiving primary care, those diagnosed with HCV and HIV were more likely to have documented OUD than those without. Patients with HIV were less likely to have documented medication treatment for OUD.

Electrolyte/Dye/TiO2 Interfacial Structures of Dye-Sensitized Solar Cells Revealed by In Situ Neutron Reflectometry with Contrast Matching.

The nature of an interfacial structure buried within a device assembly is often critical to its function. For example, the dye/TiO2 interfacial structure that comprises the working electrode of a dye-sensitized solar cell (DSC) governs its photovoltaic output. These structures have been determined outside of the DSC device, using ex situ characterization methods; yet, they really should be probed while held within a DSC since they are modulated by the device environment. Dye/TiO2 structures will be particularly influenced by a layer of electrolyte ions that lies above the dye self-assembly. We show that electrolyte/dye/TiO2 interfacial structures can be resolved using in situ neutron reflectometry with contrast matching. We find that electrolyte constituents ingress into the self-assembled monolayer of dye molecules that anchor onto TiO2. Some dye/TiO2 anchoring configurations are modulated by the formation of electrolyte/dye intermolecular interactions. These electrolyte-influencing structural changes will affect dye-regeneration and electron-injection DSC operational processes. This underpins the importance of this in situ structural determination of electrolyte/dye/TiO2 interfaces within representative DSC device environments.

Effect of thermal treatment on the stability of Na-Mn-W/SiO2 catalyst for the oxidative coupling of methane.

In this study, we investigate the effect of thermal treatment/calcination on the stability and activity of a Na-Mn-W/SiO2 catalyst for the oxidative coupling of methane. The catalyst performance and characterisation measurements suggest that the W species are directly involved in the catalyst active site responsible for CH4 conversion. Under operating conditions, the active components, present in the form of a Na-W-O-Mn molten state, are highly mobile and volatile. By varying the parameters of the calcination protocol, it was shown that these molten components can be partially stabilised, resulting in a catalyst with lower activity (due to loss of surface area) but higher stability even for long duration OCM reaction experiments.

ID15A at the ESRF - a beamline for high speed operando X-ray diffraction, diffraction tomography and total scattering.

ID15A is a newly refurbished beamline at the ESRF devoted to operando and time-resolved diffraction and imaging, total scattering and diffraction computed tomography. The beamline is optimized for rapid alternation between the different techniques during a single operando experiment in order to collect complementary data on working systems. The high available energy (up to 120 keV) means that even bulky and highly absorbing systems may be studied. The beamline is equipped with optimized focusing optics and a photon-counting CdTe pixel detector, allowing for both unprecedented data quality at high energy and for very rapid triggered experiments. A large choice of imaging detectors and ancillary probes and sample environments is also available.