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Wagner, Brent

Publications and source records attributed to Wagner, Brent.

The safety of magnetic resonance imaging contrast agents

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.

59 BASIC BIOLOGICAL SCIENCES↗

The onset of rare earth metallosis begins with renal gadolinium-rich nanoparticles from magnetic resonance imaging contrast agent exposure

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal–ligand complexes, especially with repeated use, should be studied further.

36 MATERIALS SCIENCE↗

Effect of vaccination on the case fatality rate for COVID-19 infections 2020–2021: multivariate modelling of data from the US Department of Veterans Affairs

Objectives: To evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections. Design, setting and participants: The US Department of Veterans Affairs has 130 medical centres. We created multivariate models from these data—339 772 patients with COVID-19—as of 30 September 2021. Outcome measures: The primary outcome for all models was death within 60 days of the diagnosis. Logistic regression was used to derive adjusted ORs for vaccination and infection with Delta versus earlier variants. Models were adjusted for confounding factors, including demographics, comorbidity indices and novel parameters representing prior diagnoses, vital signs/baseline laboratory tests and outpatient treatments. Patients with a Delta infection were divided into eight cohorts based on the time from vaccination to diagnosis. A common model was used to estimate the odds of death associated with vaccination for each cohort relative to that of unvaccinated patients. Results: 9.1% of subjects were vaccinated. 21.5% had the Delta variant. 18 120 patients (5.33%) died within 60 days of their diagnoses. The adjusted OR for a Delta infection was 1.87±0.05, which corresponds to a relative risk (RR) of 1.78. The overall adjusted OR for prior vaccination was 0.280±0.011 corresponding to an RR of 0.291. Raw CFR rose steadily after 10–14 weeks. The OR for vaccination remained stable for 10–34 weeks. Conclusions: Our CFR model controls for the severity of confounding factors and priority of vaccination, rather than solely using the presence of comorbidities. Our results confirm that Delta was more lethal than earlier variants and that vaccination is an effective means of preventing death. After adjusting for major selection biases, we found no evidence that the benefits of vaccination on CFR declined over 34 weeks. We suggest that this model can be used to evaluate vaccines designed for emerging variants.

59 BASIC BIOLOGICAL SCIENCES↗

A neutron scintillator based on transparent nanocrystalline CaF{sub 2}:Eu glass ceramic

There are no efficient Eu{sup 2+} doped glass neutron scintillators reported due to low doping concentrations of Eu{sup 2+} and the amorphous nature of the glass matrix. In this work, an efficient CaF{sub 2}:Eu glass ceramic neutron scintillator was prepared by forming CaF{sub 2}:Eu nanocrystals in a {sup 6}Li-containing glass matrix. Through appropriate thermal treatments, the scintillation light yield of the transparent glass ceramic was increased by a factor of at least 46 compared to the as-cast amorphous glass. This improvement was attributed to more efficient energy transfer from the CaF{sub 2} crystals to the Eu{sup 2+} emitting centers. Further light yield improvement is expected if the refractive index of the glass matrix can be matched to the CaF{sub 2} crystal.

36 MATERIALS SCIENCE↗

High Extraction Phosphors for Solid State Lighting

We have developed high-index, high efficiency bulk luminescent materials and novel nano-sized phosphors for improved solid-state white LED lamps. These advances can potentially contribute to reducing the loss in luminous efficiencies due to scattering, re-absorption, and thermal quenching. The bulk and nanostructured luminescent materials investigated are index matched to GaN and have broad and size-tunable absorption bands, size and impurity tuned emission bands, size-driven elimination of scattering effects, and a separation between absorption and emission bands. These innovations were accomplished through the use of novel synthesis techniques suitable for high volume production for LED lamp applications. The program produced a full-color set of high quantum yield phosphors with high chemical stability. In the bulk phosphor study, the ZnSeS:Cu,Ag phosphor was optimized to achieve >91% efficiency using erbium (Er) and other activators as sensitizers. Detailed analysis of temperature quenching effects on a large number of ZnSeS:Cu,Ag,X and strontium- and calcium-thiogallate phosphors lead to a breakthrough in the understanding of the anti-quenching behavior and a physical bandgap model was developed of this phenomena. In a follow up to this study, optimized phosphor blends for high efficiency and color performance were developed and demonstrated a 2-component phosphor system with good white chromaticity, color temperature, and high color rendering. By extending the protocols of quantum dot synthesis, large nanocrystals, greater than 20 nm in diameter were synthesized and exhibited bulk-like behavior and blue light absorption. The optimization of ZnSe:Mn nanophosphors achieved ~85% QE The limitations of core-shell nanocrystal systems were addressed by investigating alternative deltadoped structures. To address the manufacturability of these systems, a one-pot manufacturing protocol was developed for ZnSe:Mn nanophosphors. To enhance the stability of these material systems, the encapsulation of ZnSeS particle phosphors and ZnSeS screens with Al 2 O 3 and TiO 2 using ALD was shown to improve the stability by >8X and also increased the luminescence efficiency due to improved surface passivation and optical coupling. A large-volume fluidized bed ALD system was designed that can be adapted to a commercial ALD or vapor deposition system. Throughout the program, optical simulations were developed to evaluate and optimize various phosphor mixtures and device configurations. For example, to define the scattering properties of nanophosphors in an LED device or in a stand-off screen geometry. Also this work significantly promoted and assisted in the implementation of realistic phosphor material models into commercial modeling programs.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗