Quantitative and Qualitative Analyses of Mass Spectra of OEL Materials by Artificial Neural Network and Interface Evaluation: Results from a VAMAS Interlaboratory Study.

Quantitative analysis of binary mixtures of tris(2-phenylpyridinato)iridium(III) (Ir(ppy)3) and tris(8-hydroxyquinolinato)aluminum (Alq3) by using an artificial neural network (ANN) system to mass spectra was attempted based on the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study (TW2 A31) to evaluate matrix-effect correction and to investigate interface determination. Monolayers of binary mixtures having different Ir(ppy)3 ratios (0, 0.25, 0.50, 0.75, and 1.00), and the multilayers containing these mixtures and pure samples were measured using time-of-flight secondary ion mass spectrometry (ToF-SIMS) with different primary ion beams, OrbiSIMS (SIMS with both Orbitrap and ToF mass spectrometers), laser desorption ionization (LDI), desorption/ionization induced by neutral clusters (DINeC), and X-ray photoelectron spectroscopy (XPS). The mass spectra were analyzed using a simple ANN with one hidden layer. The Ir(ppy)3 ratios of the unknown samples and the interfaces of the multilayers were predicted using the simple ANN system, even though the mass spectra of binary mixtures exhibited matrix effects. The Ir(ppy)3 ratios at the interfaces indicated by the simple ANN were consistent with the XPS results and the ToF-SIMS depth profiles. The simple ANN system not only provided quantitative information on unknown samples, but also indicated important mass peaks related to each molecule in the samples without a priori information. The important mass peaks indicated by the simple ANN depended on the ionization process. The simple ANN results of the spectra sets obtained by a softer ionization method, such as LDI and DINeC, suggested large ions such as trimers. From the first step of the investigation to build an ANN model for evaluating mixture samples influenced by matrix effects, it was indicated that the simple ANN method is useful for obtaining candidate mass peaks for identification and for assuming mixture conditions that are helpful for further analysis.

Near-Surface

Impurity spins in crystal matrices are promising components in quantum technologies, particularly if they can maintain their spin properties when close to surfaces and material interfaces. Here, we investigate an attractive candidate for microwave-domain applications, the spins of group-VI ^{125}Te^{+} donors implanted into natural Si at depths as shallow as 20 nm. We show that surface band bending can be used to ionize such near-surface Te to spin-active Te^{+} state, and that optical illumination can be used further to control the Te donor charge state. We examine spin activation yield, spin linewidth, and relaxation (T_{1}) and coherence times (T_{2}) and show how a zero-field 3.5 GHz "clock transition" extends spin coherence times to over 1 ms, which is about an order of magnitude longer than other near-surface spin systems.

How do we engage people in testing for COVID-19? A rapid qualitative evaluation of a testing programme in schools, GP surgeries and a university.

BACKGROUND: The UK Scientific Advisory Group for Emergencies (SAGE) emphasises the need for high levels of engagement with communities and individuals to ensure the effectiveness of any COVID-19 testing programme. A novel pilot health surveillance programme to assess the feasibility of weekly community RT-LAMP (Reverse transcription loop-mediated isothermal amplification) testing for the SARS-CoV-2 virus using saliva samples collected at home was developed and piloted by the University of Southampton and Southampton City Council. METHODS: Rapid qualitative evaluation was conducted to explore experiences of those who took part in the programme, of those who declined and of those in the educational and healthcare organisations involved in the pilot testing who were responsible for roll-out. This included 77 interviews and 20 focus groups with 223 staff, students, pupils and household members from four schools, one university, and one community healthcare NHS trust. The insights generated and informed the design and modification of the Southampton COVID-19 Saliva Testing Programme and the next phase of community-testing. RESULTS: Discussions revealed that high levels of communication, trust and convenience were necessary to ensure people's engagement with the programme. Participants felt reassured by and pride in taking part in this novel programme. They suggested modifications to reduce the programme's environmental impact and overcome cultural barriers to participation. CONCLUSIONS: Participants' and stakeholders' motivations, challenges and concerns need to be understood and these insights used to modify the programme in a continuous, real-time process to ensure and sustain engagement with testing over the extended period necessary. Community leaders and stakeholder organisations should be involved throughout programme development and implementation to optimise engagement.

Label-Free Time-of-Flight Secondary Ion Mass Spectrometry Imaging of Sulfur-Producing Enzymes inside Microglia Cells following Exposure to Silver Nanowires.

There are no methods sensitive enough to detect enzymes within cells, without the use of analyte labeling. Here we show that it is possible to detect protein ion signals of three different H2S-synthesizing enzymes inside microglia after pretreatment with silver nanowires (AgNW) using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Protein fragment ions, including the fragment of amino acid (C4H8N+ = 70 amu), fragments of the sulfur-producing cystathionine-containing enzymes, and the Ag+ ion signal could be detected without the use of any labels; the cells were mapped using the C4H8N+ amino acid fragment. Scanning electron microscopy imaging and energy-dispersive X-ray chemical analysis showed that the AgNWs were inside the same cells imaged by TOF-SIMS and transformed chemically into crystalline Ag2S within cells in which the sulfur-producing proteins were detected. The presence of these sulfur-producing cystathionine-containing enzymes within the cells was confirmed by Western blots and confocal microscopy images of fluorescently labeled antibodies against the sulfur-producing enzymes. Label-free TOF-SIMS is very promising for the label-free identification of H2S-contributing enzymes and their cellular localization in biological systems. The technique could in the future be used to identify which of these enzymes are most contributory.

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye.

Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5-20 µm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch's membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch's membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits.

Channels of oxygen diffusion in single crystal rubrene revealed.

Electronic devices made from organic materials have the potential to support a more ecologically friendly and affordable future. However, the ability to fabricate devices with well-defined and reproducible electrical and optical properties is hindered by the sensitivity to the presence of chemical impurities. Oxygen in particular is an impurity that can trap electrons and modify conductive properties of some organic materials. Until now the 3-dimensional profiling of oxygen species in organic semiconductors has been elusive and the effect of oxygen remains disputed. In this study we map out high-spatial resolution 3-dimensional distributions of oxygen inclusions near the surface of single crystal rubrene, using Time of Flight Secondary Ion Mass Spectroscopy (ToF-SIMS). Channels of diffused oxygen are found extending from uniform oxygen inclusion layers at the surface. These channels extend to depths in excess of 1.8 µm and act as an entry point for oxygen to diffuse along the ab-plane of the crystal with at least some of the diffused oxygen molecularly binding to rubrene. Our investigation of surfaces at different stages of evolution reveals the extent of oxygen inclusion, which affects rubrene's optical and transport properties, and is consequently of importance for the reliability and longevity of devices.

Bruch's Membrane Calcification in Pseudoxanthoma Elasticum: Comparing Histopathology and Clinical Imaging.

Purpose: To investigate the histology of Bruch's membrane (BM) calcification in pseudoxanthoma elasticum (PXE) and correlate this to clinical retinal imaging. Design: Experimental study with clinicopathological correlation. Subjects and Controls: Six postmortem eyes from 4 PXE patients and 1 comparison eye from an anonymous donor without PXE. One of the eyes had a multimodal clinical image set for comparison. Methods: Calcification was labeled with OsteSense 680RD, a fluorescent dye specific for hydroxyapatite, and visualized with confocal microscopy. Scanning electron microscopy coupled with energy-dispersive x-ray spectroscopy (SEM-EDX) and time-of-flight secondary ion mass spectrometry (TOF-SIMs) were used to analyze the elemental and ionic composition of different anatomical locations. Findings on cadaver tissues were compared with clinical imaging of 1 PXE patient. Main Outcome Measures: The characteristics and topographical distribution of hydroxyapatite in BM in eyes with PXE were compared with the clinical manifestations of the disease. Results: Analyses of whole-mount and sectioned PXE eyes revealed an extensive, confluent OsteoSense labeling in the central and midperipheral BM, transitioning to a speckled labeling in the midperiphery. These areas corresponded to hyperreflective and isoreflective zones on clinical imaging. Scanning electron microscopy coupled with energy-dispersive x-ray spectroscopy and TOF-SIMs analyses identified these calcifications as hydroxyapatite in BM of PXE eyes. The confluent fluorescent appearance originates from heavily calcified fibrous structures of both the collagen and the elastic layers of BM. Calcification was also detected in an aged comparison eye, but this was markedly different from PXE eyes and presented as small snowflake-like deposits in the posterior pole. Conclusions: Pseudoxanthoma elasticum eyes show extensive hydroxyapatite deposition in the inner and outer collagenous and elastic BM layers in the macula with a gradual change toward the midperiphery, which seems to correlate with the clinical phenotype. The snowflake-like calcification in BM of an aged comparison eye differed markedly from the extensive calcification in PXE. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Revealing surface oxidation on the organic semi-conducting single crystal rubrene with time of flight secondary ion mass spectroscopy.

To address the question of surface oxidation in organic electronics the chemical composition at the surface of single crystalline rubrene is spatially profiled and analyzed using Time of Flight - Secondary Ion Mass Spectroscopy (ToF-SIMS). It is seen that a uniform oxide (C42H28O) covers the surface while there is an increased concentration of peroxide (C42H28O2) located at crystallographic defects. By analyzing the effects of different primary ions, temperature and sputtering agents the technique of ToF-SIMS is developed as a valuable tool for the study of chemical composition variance both at and below the surface of organic single crystals. The primary ion beams C60(3+) and Bi3(+) are found to be most appropriate for mass spectroscopy and spatial profiling respectively. Depth profiling of the material is successfully undertaken maintaining the molecular integrity to a depth of ~5 µm using an Ar cluster ion source as the sputtering agent.

Toward Fabrication of Devices Based on Graphene/Oxide Multilayers.

Owing to its high electrical conductivity, low density, and flexibility, graphene has great potential for use as a building block in a wide range of applications from nanoelectronics to biosensing and high-frequency devices. For many device applications, it is required to deposit dielectric materials on graphene at high temperatures and in ambient oxygen. This has been proven to be highly challenging because these conditions cause significant degradation in graphene. In this work, we investigate the degradation of graphene at elevated temperatures in an oxygen atmosphere and possible protection mechanisms to enable the growth of oxide thin films on graphene at higher temperatures. We show that coating graphene with self-assembled monolayers of hexamethyldisilazane (HMDS) prior to a high-temperature deposition can significantly reduce the damage induced. Furthermore, a graphene sample treated with HMDS displayed a weaker doping effect due to weak interaction with oxygen species than bare graphene, and a much slower rate of electrical resistance degradation was exhibited during annealing. Thus, it is a promising approach that could enable the deposition of metal oxide materials on graphene at high temperatures without significant degradation in graphene quality, which is critical for a wide range of applications.

De novo phytosterol synthesis in animals.

Sterols are vital for nearly all eukaryotes. Their distribution differs in plants and animals, with phytosterols commonly found in plants whereas most animals are dominated by cholesterol. We show that sitosterol, a common sterol of plants, is the most abundant sterol in gutless marine annelids. Using multiomics, metabolite imaging, heterologous gene expression, and enzyme assays, we show that these animals synthesize sitosterol de novo using a noncanonical C-24 sterol methyltransferase (C24-SMT). This enzyme is essential for sitosterol synthesis in plants, but not known from most bilaterian animals. Our phylogenetic analyses revealed that C24-SMTs are present in representatives of at least five animal phyla, indicating that the synthesis of sterols common to plants is more widespread in animals than currently known.

Momentum-Space Imaging of Ultra-Thin Electron Liquids in δ-Doped Silicon.

Two-dimensional dopant layers (δ-layers) in semiconductors provide the high-mobility electron liquids (2DELs) needed for nanoscale quantum-electronic devices. Key parameters such as carrier densities, effective masses, and confinement thicknesses for 2DELs have traditionally been extracted from quantum magnetotransport. In principle, the parameters are immediately readable from the one-electron spectral function that can be measured by angle-resolved photoemission spectroscopy (ARPES). Here, buried 2DEL δ-layers in silicon are measured with soft X-ray (SX) ARPES to obtain detailed information about their filled conduction bands and extract device-relevant properties. This study takes advantage of the larger probing depth and photon energy range of SX-ARPES relative to vacuum ultraviolet (VUV) ARPES to accurately measure the δ-layer electronic confinement. The measurements are made on ambient-exposed samples and yield extremely thin (< 1 nm) and dense (≈1014  cm-2 ) 2DELs. Critically, this method is used to show that δ-layers of arsenic exhibit better electronic confinement than δ-layers of phosphorus fabricated under identical conditions.

Optimizing Hot Electron Harvesting at Planar Metal-Semiconductor Interfaces with Titanium Oxynitride Thin Films.

Understanding metal-semiconductor interfaces is critical to the advancement of photocatalysis and sub-bandgap solar energy harvesting where electrons in the metal can be excited by sub-bandgap photons and extracted into the semiconductor. In this work, we compare the electron extraction efficiency across Au/TiO2 and titanium oxynitride (TiON)/TiO2-x interfaces, where in the latter case the spontaneously forming oxide layer (TiO2-x) creates a metal-semiconductor contact. Time-resolved pump-probe spectroscopy is used to study the electron recombination rates in both cases. Unlike the nanosecond recombination lifetimes in Au/TiO2, we find a bottleneck in the electron relaxation in the TiON system, which we explain using a trap-mediated recombination model. Using this model, we investigate the tunability of the relaxation dynamics with oxygen content in the parent film. The optimized film (TiO0.5N0.5) exhibits the highest carrier extraction efficiency (NFC ≈ 2.8 × 1019 m-3), slowest trapping, and an appreciable hot electron population reaching the surface oxide (NHE ≈ 1.6 × 1018 m-3). Our results demonstrate the productive role oxygen can play in enhancing electron harvesting and prolonging electron lifetimes, providing an optimized metal-semiconductor interface using only the native oxide of titanium oxynitride.

Determination of proton- and oxide ion tracer diffusion in lanthanum tungstate (La/W = 5.6) by means of ToF-SIMS.

Tracer diffusion of protons and oxide ions, as well as chemical diffusion of water, have been determined for the high temperature proton conductor lanthanum tungstate by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS). The oxygen tracer diffusion and surface exchange coefficients, D(O)* and k(O)*, were measured after exchange anneals in water vapor enriched in H(2)(18)O between 350 and 620 °C, and the apparent activation energies were 176 and 82 kJ mol(-1), respectively. The hydrogen tracer diffusion coefficient (D(H)*) was measured between 220 and 320 °C after exchange anneals in D(2)O-containing atmospheres, and the apparent activation energy was 63 kJ mol(-1). The extracted D(H)* agrees with the results of transient conductivity- and TG-measurements. Chemical diffusion and surface exchange coefficients, D(H)δ and k(H)δ, were measured at 250 and 400 °C, and the result confirms that the material is hydrated by ambipolar sluggish transport of protons and oxide ions. The surface exchange coefficients were compared to the result of TG relaxation, suggesting that access to oxygen vacancies limits the overall surface exchange reaction under incorporation of water and oxygen.

The Causes and Impact of Crisis for People with Parkinson's Disease: A Patient and Carer Perspective.

BACKGROUND: The reasons for acute hospital admissions among people with Parkinson's disease are well documented. However, understanding of crises that are managed in the community is comparatively lacking. Most existing literature on the causes of crisis for people with Parkinson's disease (PwP) uses hospital data and excludes the individual's own perspective on the crisis trigger and the impact of the crisis on their care needs. OBJECTIVE: To identify the causes and impact of crises in both community and hospital settings, from a patient and carer perspective. METHODS: A total of 550 UK-based PwP and carers completed a survey on (a) their own personal experiences of crisis, and (b) their general awareness of potential crisis triggers for PwP. RESULTS: In addition to well-recognised causes of crisis such as falls, events less widely associated with crisis were identified, including difficulties with activities of daily living and carer absence. The less-recognised crisis triggers tended to be managed more frequently in the community. Many of these community-based crises had a greater impact on care needs than the better-known causes of crisis that more frequently required hospital care. PwP and carer responses indicated a good general knowledge of potential crisis triggers. PwP were more aware of mental health issues and carers were more aware of cognitive impairment and issues with medications. CONCLUSION: These findings could improve care of Parkinson's by increasing understanding of crisis events from the patient and carer perspective, identifying under-recognised crisis triggers, and informing strategies for best recording symptoms from PwP and carers.

Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium-Basal Lamina Space in Aged Human Eyes.

Purpose: Micrometer-sized spherules formed of hydroxyapatite or whitlockite were identified within extracellular deposits that accumulate in the space between the basal lamina (BL) of retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch's membrane (sub-RPE-BL space). This investigation aimed to characterize the morphologic features, structure, and distribution of these spherules in aged human eyes with and without clinical indications of age-related macular degeneration (AMD). Design: Experimental study. Participants: Five human eyes with varying degrees of sub-RPE-BL deposits were obtained from the University College London Institute of Ophthalmology and Moorfield's Eye Hospital Tissue Repository or the Advancing Sight Network. Two eyes were reported as having clinical indications of AMD (age, 76-87 years), whereas 3 were considered healthy (age, 69-91 years). Methods: Cadaveric eyes with sub-RPE-BL deposits were embedded in paraffin wax and sectioned to a thickness of 4-10 µm. Spherules were identified and characterized using high-resolution scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy, and time-of-flight secondary ion mass spectroscopy. Main Outcome Measures: High-resolution scanning electron micrographs of spherules, the size-frequency distribution of spherules including average diameter, and the distribution of particles across the central-peripheral axis. Elemental maps and time-of-flight secondary ion mass spectra also were obtained. Results: The precipitation of spherules is ubiquitous across the central, mid-peripheral, and far-peripheral axis in aged human eyes. No significant difference was found in the frequency of spherules along this axis. However, statistical analysis indicated that spherules exhibited significantly different sizes in these regions. In-depth analysis revealed that spherules in the sub-RPE-BL space of eyes with clinical signs of AMD were significantly larger (median diameter, 1.64 µm) than those in healthy aged eyes (median diameter, 1.16 µm). Finally, spherules showed great variation in surface topography and internal structure. Conclusions: The precipitation of spherules in the sub-RPE-BL space is ubiquitous across the central-peripheral axis in aged human eyes. However, a marked difference exists in the size and frequency of spherules in eyes with clinical signs of AMD compared to those without, suggesting that the size and frequency of spherules may be associated with AMD.

Improved accuracy in multicomponent surface complexation models using surface-sensitive analytical techniques: Adsorption of arsenic onto a TiO2/Fe2O3 multifunctional sorbent.

Novel composite materials are increasingly developed for water treatment applications with the aim of achieving multifunctional behaviour, e.g. combining adsorption with light-driven remediation. The application of surface complexation models (SCM) is important to understand how adsorption changes as a function of pH, ionic strength and the presence of competitor ions. Component additive (CA) models describe composite sorbents using a combination of single-phase reference materials. However, predictive adsorption modelling using the CA-SCM approach remains unreliable, due to challenges in the quantitative determination of surface composition. In this study, we test the hypothesis that characterisation of the outermost surface using low energy ion scattering (LEIS) improves CA-SCM accuracy. We consider the TiO2/Fe2O3 photocatalyst-sorbents that are increasingly investigated for arsenic remediation. Due to an iron oxide surface coating that was not captured by bulk analysis, LEIS significantly improves the accuracy of our component additive predictions for monolayer surface processes: adsorption of arsenic(V) and surface acidity. We also demonstrate non-component additivity in multilayer arsenic(III) adsorption, due to changes in surface morphology/porosity. Our results demonstrate how surface-sensitive analytical techniques will improve adsorption models for the next generation of composite sorbents.

Surface Restructuring of Thin-Film Electrodes Based on Thermal History and Its Significance for the Catalytic Activity and Stability at the Gas/Solid and Solid/Solid Interfaces.

Electrodes in solid-state energy devices are subjected to a variety of thermal treatments, from film processing to device operation at high temperatures. All these treatments influence the chemical activity and stability of the films, as the thermally induced chemical restructuring shapes the microstructure and the morphology. Here, we investigate the correlation between the oxygen reduction reaction (ORR) activity and thermal history in complex transition metal oxides, in particular, La0.6Sr0.4CoO3-δ (LSC64) thin films deposited by pulsed laser deposition. To this end, three ∼200 nm thick LSC64 films with different processing and thermal histories were studied. A variety of surface-sensitive elemental characterization techniques (i.e., low-energy ion scattering, X-ray photoelectron spectroscopy, and secondary ion mass spectrometry) were employed to thoroughly investigate the cationic distribution from the outermost surface to the film/substrate interface. Moreover, electrochemical impedance spectroscopy was used to study the activity and the stability of the films. Our investigations revealed that, despite the initial comparable ORR activity at 600 °C, the degradation rates of the films differed by twofold in the long-term stability tests at 500 °C. Here, we emphasize the importance of processing and thermal history in the elemental surface distribution, especially for the stability of LSC64 electrodes and propose that they should be considered as among the main pillars in the design of active surfaces.

Atomic-Scale Patterning of Arsenic in Silicon by Scanning Tunneling Microscopy.

Over the past two decades, prototype devices for future classical and quantum computing technologies have been fabricated by using scanning tunneling microscopy and hydrogen resist lithography to position phosphorus atoms in silicon with atomic-scale precision. Despite these successes, phosphine remains the only donor precursor molecule to have been demonstrated as compatible with the hydrogen resist lithography technique. The potential benefits of atomic-scale placement of alternative dopant species have, until now, remained unexplored. In this work, we demonstrate the successful fabrication of atomic-scale structures of arsenic-in-silicon. Using a scanning tunneling microscope tip, we pattern a monolayer hydrogen mask to selectively place arsenic atoms on the Si(001) surface using arsine as the precursor molecule. We fully elucidate the surface chemistry and reaction pathways of arsine on Si(001), revealing significant differences to phosphine. We explain how these differences result in enhanced surface immobilization and in-plane confinement of arsenic compared to phosphorus, and a dose-rate independent arsenic saturation density of 0.24 ± 0.04 monolayers. We demonstrate the successful encapsulation of arsenic delta-layers using silicon molecular beam epitaxy, and find electrical characteristics that are competitive with equivalent structures fabricated with phosphorus. Arsenic delta-layers are also found to offer confinement as good as similarly prepared phosphorus layers, while still retaining >80% carrier activation and sheet resistances of <2 kΩ/square. These excellent characteristics of arsenic represent opportunities to enhance existing capabilities of atomic-scale fabrication of dopant structures in silicon, and may be important for three-dimensional devices, where vertical control of the position of device components is critical.

Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration.

Drusen are lipid-, mineral-, and protein-containing extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium (RPE) and Bruch's membrane (BrM) of the human eye. They are a defining feature of age-related macular degeneration (AMD), a common sight-threatening disease of older adults. The appearance of heterogeneous internal reflectivity within drusen (HIRD) on optical coherence tomography (OCT) images has been suggested to indicate an increased risk of progression to advanced AMD. Here, in a cohort of patients with AMD and drusen, we show that HIRD indicated an increased risk of developing advanced AMD within 1 year. Using multimodal imaging in an independent cohort, we demonstrate that progression to AMD was associated with increasing degeneration of the RPE overlying HIRD. Morphological analysis of clinically imaged cadaveric human eye samples revealed that HIRD was formed by multilobular nodules. Nanoanalytical methods showed that nodules were composed of hydroxyapatite and that they differed from spherules and BrM plaques, other refractile features also found in the retinas of patients with AMD. These findings suggest that hydroxyapatite nodules may be indicators of progression to advanced AMD and that using multimodal clinical imaging to determine the composition of macular calcifications may help to direct therapeutic strategies and outcome measures in AMD.

Processing Solvent-Dependent Electronic and Structural Properties of Cesium Lead Triiodide Thin Films.

Cesium lead triiodide (CsPbI3) is an attractive material for photovoltaic applications due to its appropriate band gap, strong optical absorption, and high thermal stability. However, the perovskite phase suffers from moisture induced structural instability. Previous studies have utilized a range of solvent systems to establish the role of solvent choice in structural instabilities. Despite this, effects of different solvents on the electronic structure of this material have not been compared. We report substantial chemical and compositional differences in thin films of CsPbI3 prepared from a range of solvent systems. We confirm via X-ray diffraction thin films formed from DMF, DMSO, and a mixture of these solvent systems share the same crystal structure. However, secondary ion mass spectrometry, X-ray photoelectron spectroscopy, and low energy ion scattering measurements reveal significant differences between films processed via different solvent systems. Our findings reveal the critical impact solvents have upon compositional stoichiometry and thin-film morphology.