Impact of electronic portal image quality on Elekta AQUA® collimator isocenter.

PURPOSE: The collimator radiation isocenter position determined in AQUA® v3.0 [Elekta AB, Stockholm, Sweden] software test "MLC Leaf and Jaw Position" was independently validated using an in-house MATLAB [Natick, MA: The MathWorks Inc.] script. METHODS: The AQUA test determines radiation isocenter using the mean field center of nine 4 cm × 4 cm electronic portal imager (EPID) exposures at equidistant collimator angles. Impact of EPID image quality on AQUA reported isocenter for thirteen Elekta linear accelerators with Agility MLC heads were evaluated. RESULTS: Of the thirteen, three had visually and quantitatively identifiable artifacts. For the ten good EPID's there was a systematic 0.25 mm offset of the MATLAB calculated mean field center relative to AQUA in the X-axis and Y-axis. This corresponds to one image pixel and was found to be due to differences in software co-ordinate convention. After subtracting this offset there was no significant difference in AQUA and MATLAB calculated isocenter. CONCLUSIONS: For the three machines with poor image quality there was a demonstrated variation in AQUA calculated field center and therefore radiation isocenter relative to MATLAB. Restricting the region of interest (ROI) in AQUA software to only the irradiated section of the EPID brought AQUA and MATLAB result for these three machines into agreement.

Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK.

Radioactive iodine is a highly effective treatment for thyroid cancer and has now been used in clinical practice for more than 80 years. In general, the treatment is well tolerated. However, it can be logistically quite complex for patients due to the need to reduce iodine intake and achieve high levels of thyroid-stimulating hormone prior to treatment. Radiation protection precautions must also be taken to protect others from unnecessary radiation exposure following treatment. It has been well documented by thyroid cancer patient support groups that there is significant variation in practice across the UK. It is clear that some patients are being asked to observe unnecessarily burdensome restrictions that make it more difficult for them to tolerate the treatment. At the instigation of these support groups, a multidisciplinary group was assembled to examine the evidence and generate guidance on best practice for the preparation of patients for this treatment and the management of subsequent radiation protection precautions, with a focus on personalising the advice given to individual patients. The guidance includes advice about managing particularly challenging situations, for example treating patients who require haemodialysis. We have also worked together to produce a patient information leaflet covering these issues. We hope that the guidance document and patient information leaflet will assist centres in improving our patients' experience of receiving radioactive iodine. The patient information sheet is available as Supplementary Material to this article.

Dealumination of small-pore zeolites through pore-opening migration process with the aid of pore-filler stabilization.

Small-pore zeolites are gaining increasing attention owing to their superior catalytic performance. Despite being critical for the catalytic activity and lifetime, postsynthetic tuning of bulk Si/Al ratios of small-pore zeolites has not been achieved with well-preserved crystallinity because of the limited mass transfer of aluminum species through narrow micropores. Here, we demonstrate a postsynthetic approach to tune the composition of small-pore zeolites using a previously unexplored strategy named pore-opening migration process (POMP). Acid treatment assisted by stabilization of the zeolite framework by organic cations in pores is proven to be successful for the removal of Al species from zeolite via POMP. Furthermore, the dealuminated AFX zeolite is treated via defect healing, which yields superior hydrothermal stability against severe steam conditions. Our findings could facilitate industrial applications of small-pore zeolites via aluminum content control and defect healing and could elucidate the structural reconstruction and arrangement processes for inorganic microporous materials.

Atomic-Level Changes during Electrochemical Cycling of Oriented LiMn2O4 Cathodic Thin Films.

Spinel LiMn2O4 is an attractive lithium-ion battery cathode material that undergoes a complex series of structural changes during electrochemical cycling that lead to rapid capacity fading, compromising its long-term performance. To gain insights into this behavior, in this report we analyze changes in epitaxial LiMn2O4 thin films during the first few charge-discharge cycles with atomic resolution and correlate them with changes in the electrochemical properties. Impedance spectroscopy and scanning transmission electron microscopy are used to show that defect-rich LiMn2O4 surfaces contribute greatly to the increased resistivity of the battery after only a single charge. Sequences of {111} stacking faults within the films were also observed upon charging, increasing in number with further cycling. The atomic structures of these stacking faults are reported for the first time, showing that Li deintercalation is accompanied by local oxygen loss and relaxation of Mn atoms onto previously unoccupied sites. The stacking faults have a more compressed structure than the spinel matrix and impede Li-ion migration, which explains the observed increase in thin-film resistivity as the number of cycles increases. These results are used to identify key factors contributing to conductivity degradation and capacity fading in LiMn2O4 cathodes, highlighting the need to develop techniques that minimize defect formation in spinel cathodes to improve cycle performance.

Oxide-ion diffusion in brownmillerite-type Ca2AlMnO5+δ from first-principles calculations.

Oxide-ion diffusion pathways in brownmillerite oxides Ca2AlMnO5 and Ca2AlMnO5.5 are systematically investigated using first-principles calculations. These structures reversibly transform into each other by oxidation and reduction. We examine oxide-ion migration in Ca2AlMnO5 and Ca2AlMnO5.5 using the nudged elastic band method. In the reduced structure (Ca2AlMnO5), oxide-ion migration through a vacancy channel is found to have the lowest migration energy barrier, at 0.58 eV. The migration energy barrier of the second-lowest energy path, perpendicular to the vacancy channel, is found to be 0.98 eV. In the oxidized structure (Ca2AlMnO5.5), oxide-ion migration within AlO6 layers has migration energy barriers of 0.55 eV and 0.56 eV in the [100] and [001] directions, respectively. Oxide-ion migration perpendicular to the AlO6 layer has a migration energy barrier of 1.33 eV, suggesting that oxide-ion diffusion in the [010] direction is difficult even at elevated temperature. These results indicate that diffusion in the reduced phase is predominantly one-dimensional whereas it is two-dimensional in the oxidized phase.

Quantitative prediction of grain boundary thermal conductivities from local atomic environments.

Quantifying the dependence of thermal conductivity on grain boundary (GB) structure is critical for controlling nanoscale thermal transport in many technologically important materials. A major obstacle to determining such a relationship is the lack of a robust and physically intuitive structure descriptor capable of distinguishing between disparate GB structures. We demonstrate that a microscopic structure metric, the local distortion factor, correlates well with atomically decomposed thermal conductivities obtained from perturbed molecular dynamics for a wide variety of MgO GBs. Based on this correlation, a model for accurately predicting thermal conductivity of GBs is constructed using machine learning techniques. The model reveals that small distortions to local atomic environments are sufficient to reduce overall thermal conductivity dramatically. The method developed should enable more precise design of next-generation thermal materials as it allows GB structures exhibiting the desired thermal transport behaviour to be identified with small computational overhead.

Characterisation of the temperature-dependent M1 to R phase transition in W-doped VO2 nanorod aggregates by Rietveld refinement and theoretical modelling.

Understanding the mechanism of the insulator-metal transition (IMT) in VO2 is a necessary step in optimising this material's properties for a range of functional applications. Here, Rietveld refinement of synchrotron X-ray powder diffraction patterns is performed on thermochromic V1-xWxO2 (0.0 ≤ x ≤ 0.02) nanorod aggregates over the temperature range 100 ≤ T ≤ 400 K to examine the effect of doping on the structure and properties of the insulating monoclinic (M1) phase and metallic rutile (R) phase. Precise measurement of the lattice constants of the M1 and R phases enabled the onset (Ton) and endset (Tend) temperatures of the IMT to be determined accurately for different dopant levels. First-principles calculations reveal that the observed decrease in both Ton and Tend with increasing W content is a result of Peierls type V-O-V dimers being replaced by linear W-O-V dimers with a narrowing of the band gap. The results are interpreted in terms of the bandwidth-controlled Mott-Hubbard IMT model, providing a more detailed understanding of the underlying physical mechanisms driving the IMT as well as a guide to optimising properties of VO2-based materials for specific applications.

Systematic analysis of electron energy-loss near-edge structures in Li-ion battery materials.

Electrical conductivity, state of charge and chemical stability of Li-ion battery materials all depend on the electronic states of their component atoms, and tools for measuring these reliably are needed for advanced materials analysis and design. Here we report a systematic investigation of electron energy-loss near-edge structures (ELNES) of Li-K and O-K edges for ten representative Li-ion battery electrodes and solid-state electrolytes obtained by performing transmission electron microscopy with a Wien-filter monochromator-equipped microscope. While the peaks of Li-K edges are positioned at about 62 eV for most of the materials examined, the peak positions of O-K edges vary within a range of about 530 to 540 eV, and the peaks can be categorised into three groups based on their characteristic edge shapes: (i) double peaks, (ii) single sharp peaks, and (iii) single broad peaks. The double peaks of group (i) are attributable to the d0 electronic configuration of their transition metal ions bonded to O atoms. The origin of the different peak shapes of groups (ii) and (iii) is more subtle but insights are gained using density functional theory methods to simulate O-K ELNES edges of group (ii) material LiCoO2 and group (iii) material LiFePO4. Comparison of their densities of states reveals that in LiCoO2 the Co-O hybrid orbitals are separated from Li-O hybrid orbitals, resulting in a sharp peak in the O-K edge, while Fe-O, Li-O and P-O hybrid orbitals in LiFePO4 partially overlap each other and produce a broad peak.

Microscopic mechanism of biphasic interface relaxation in lithium iron phosphate after delithiation.

Charge/discharge of lithium-ion battery cathode material LiFePO4 is mediated by the structure and properties of the interface between delithiated and lithiated phases. Direct observations of the interface in a partially delithiated single crystal as a function of time using scanning transmission electron microscopy and electron energy-loss spectroscopy help clarify these complex phenomena. At the nano-scale, the interface comprises a thin multiphase layer whose composition varies monotonically between those of the two end-member phases. After partial delithiation, the interface does not remain static, but changes gradually in terms of orientation, morphology and position, as Li ions from the crystal bulk diffuse back into the delithiated regions. First-principles calculations of a monoclinic crystal of composition Li2/3FePO4 suggest that the interface exhibits higher electronic conductivity than either of the end-member phases. These observations highlight the importance of the interface in enabling LiFePO4 particles to retain structural integrity during high-rate charging and discharging.

Quantifying Anharmonic Vibrations in Thermoelectric Layered Cobaltites and Their Role in Suppressing Thermal Conductivity.

Optimizing multiple materials properties which are simultaneously in competition with each other is one of the chief challenges in thermoelectric materials research. Introducing greater anharmonicity to vibrational modes is one strategy for suppressing phonon thermal transport in crystalline oxides without detrimentally affecting electronic conductivity, so that the overall thermoelectric efficiency can be improved. Based on perturbed molecular dynamics and associated numerical analyses, we show that CoO2 layers in layered cobaltite thermoelectrics NaxCoO2 and Ca3Co4O9 are responsible for most of the in-plane heat transport in these materials, and that the non-conducting intermediate layers in the two materials exhibit different kinds of anharmonicity. More importantly, thermal conduction is shown to be altered by modifying the structure of the intermediate layers. The simulation methods developed to quantify the effect of anharmonic atomic vibrations on thermal conductivity provide a new tool for the rational design of thermoelectric materials, and the insights gained should hasten the attainment of higher conversion efficiencies so that thermoelectrics can be put to widespread practical use.

Density functional study of the phase stability and Raman spectra of Yb2O3, Yb2SiO5 and Yb2Si2O7 under pressure.

The phase stability and Raman spectra of Yb2O3, Yb2SiO5 and Yb2Si2O7 under hydrostatic pressure are investigated using density functional theory calculations. The calculated energies of polymorphs of each compound show that the stable phases at zero pressure, viz., C-type Yb2O3, X2-Yb2SiO5 and ß-Yb2Si2O7, exhibit a pressure-induced phase transition as compressive pressure increases, which is consistent with available experimental data. The theoretical Raman spectra at zero pressure are in good agreement with experimental results for the stable phases and can be used to identify each polymorph. Although the calculated pressure dependence of Raman peak positions of C-type Yb2O3 is overestimated compared to available experimental data, piezospectroscopic coefficients extracted from Raman peaks of X2-Yb2SiO5 and ß-Yb2Si2O7 suggest that Raman spectroscopy can be used to measure stresses and strains in Yb silicates. Normal mode analyses reveal that characteristic Raman peaks of Yb silicates at frequencies above 600 cm-1 are strongly associated with vibrations of Si-O bonds in SixOy tetrahedral units.

Two Contrasting Failure Modes of Enteric Coated Beads.

This study aimed to elucidate the mechanisms and kinetics of coating failure for enteric coated beads exposed to high-humidity conditions at different storage temperatures. Enteric coated beads were placed on high-humidity conditions (75 to 98% relative humidity (RH)) in the temperature range of 5 to 40°C. These stability samples of beads were tested for acid dissolution and water activity and also analyzed with SEM, X-ray CT, and DMA. Exposure of enteric coated beads to high humidity led to increased gastric release of drug which eventually failed the dissolution specification. SEM showed visible cracks on the surface of beads exposed to 5°C/high humidity and fusion of enteric beads into agglomerates at 40°C/high humidity. In a non-destructive time elapse study, X-ray CT demonstrated swelling of microcrystalline cellulose cores, crack initiation, and propagation through the API layer within days under 5°C/98% RH storage conditions and ultimately fracture through the enteric coating. DMA data showed a marked reduction in Tg of the enteric coating materials after exposure to humidity. At 5°C/high humidity, the hygroscopic microcrystalline cellulose core absorbed moisture leading to core swelling and consequent fracture through the brittle API and enteric layers. At 40°C (high humidity) which is above the Tg of the enteric polymer, enteric coated beads coalesced into agglomerates due to melt flow of the enteric coating. We believe it is the first report on two distinct failure models of enteric coated dosage forms.

Quantitative analysis of Li distributions in battery material Li1-xFePO4 using Fe M2,3-edge and valence electron energy loss spectra.

The spatial distribution of Li ions in a lithium iron phosphate (Li1-xFePO4) single crystal after chemical delithiation is quantitatively investigated using Fe M2,3-edge and valence electron energy loss (EEL) spectroscopy techniques. Li contents between those of end-member compositions LiFePO4 and FePO4 are found to correspond to reproducible changes in Fe M2,3-edge and valence EEL spectra across an interface between LiFePO4 and FePO4 regions. Quantitative analysis of these changes is used to estimate the local valence states of Fe ions, from which the Li concentration in the intermediate phase can be deduced. The faster recording time for valence EEL spectra than Fe M2,3-edge spectra makes measurement of the former a more efficient and reproducible means of estimating Li distributions.

Advanced electron holography techniques for in situ observation of solid-state lithium ion conductors.

Advanced techniques for overcoming problems encountered during in situ electron holography experiments in which a voltage is applied to an ionic conductor are reported. The three major problems encountered were 1) electric-field leakage from the specimen and its effect on phase images, 2) high electron conductivity of damage layers formed by the focused ion beam method, and 3) chemical reaction of the specimen with air. The first problem was overcome by comparing experimental phase distributions with simulated images in which three-dimensional leakage fields were taken into account, the second by removing the damage layers using a low-energy narrow Ar ion beam, and the third by developing an air-tight biasing specimen holder.

IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes.

Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-γ inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses. IFI16 is also required for the cGAMP-induced activation of STING, and interacts with STING to promote STING phosphorylation and translocation. We propose that the two DNA sensors IFI16 and cGAS cooperate to prevent the spurious activation of the type I interferon response.

Advanced electron holography techniques for in situ observation of solid-state lithium ion conductors.

Advanced techniques for overcoming problems encountered during in situ electron holography experiments in which a voltage is applied to an ionic conductor are reported. The three major problems encountered were 1) electric-field leakage from the specimen and its effect on phase images, 2) high electron conductivity of damage layers formed by the focused ion beam method, and 3) chemical reaction of the specimen with air. The first problem was overcome by comparing experimental phase distributions with simulated images in which three-dimensional leakage fields were taken into account, the second by removing the damage layers using a low-energy narrow Ar ion beam, and the third by developing an air-tight biasing specimen holder.

In situ electron holography of electric potentials inside a solid-state electrolyte: Effect of electric-field leakage.

In situ electron holography is used to observe changes of electric-potential distributions in an amorphous lithium phosphorus oxynitride (LiPON) solid-state electrolyte when different voltages are applied. 2D phase images are simulated by integrating the 3D potential distribution along the electron trajectory through a thin Cu/LiPON/Cu region. Good agreement between experimental and simulated phase distributions is obtained when the influence of the external electric field is taken into account using the 3D boundary-charge method. Based on the precise potential changes, the lithium-ion and lithium-vacancy distributions inside the LiPON layer and electric double layers (EDLs) are inferred. The gradients of the phase drops at the interfaces in relation to EDL widths are discussed.

Determination of the Degradation Chemistry of the Antitumor Agent Pemetrexed Disodium.

Stress-testing (forced degradation) studies have been conducted on pemetrexed disodium heptahydrate (1) (LY231514·2Na·7H2O) drug substance in order to identify its likely degradation products and establish its degradation pathways. Solid samples of the drug substance were stressed under various conditions of heat, humidity, and light, and solutions of the drug substance were stressed under various conditions of heat, light, oxidation, and over a wide pH range (1-13). The stressed samples were analyzed using a gradient elution reversed-phase HPLC method. The 7 major degradation products detected in the stress-testing studies were isolated, and the structures were elucidated via spectroscopic characterization. The structures of the degradation products and their proposed mechanisms of formation indicate that 1 degrades via 2 main pathways: oxidation and hydrolysis. Of the 7 identified degradation products, 6 are proposed to result from oxidation and 1 from hydrolysis.

Atomic-Scale Observations of (010) LiFePO4 Surfaces Before and After Chemical Delithiation.

The ability to view directly the surface structures of battery materials with atomic resolution promises to dramatically improve our understanding of lithium (de)intercalation and related processes. Here we report the use of state-of-the-art scanning transmission electron microscopy techniques to probe the (010) surface of commercially important material LiFePO4 and compare the results with theoretical models. The surface structure is noticeably different depending on whether Li ions are present in the topmost surface layer or not. Li ions are also found to migrate back to surface regions from within the crystal relatively quickly after partial delithiation, demonstrating the facile nature of Li transport in the [010] direction. The results are consistent with phase transformation models involving metastable phase formation and relaxation, providing atomic-level insights into these fundamental processes.

Particle shapes and surface structures of olivine NaFePO4 in comparison to LiFePO4.

The expansion of batteries into electric vehicle and grid storage applications has driven the development of new battery materials and chemistries, such as olivine phosphate cathodes and sodium-ion batteries. Here we present atomistic simulations of the surfaces of olivine-structured NaFePO4 as a sodium-ion battery cathode, and discuss differences in its morphology compared to the lithium analogue LiFePO4. The calculated equilibrium morphology is mostly isometric in appearance, with (010), (201) and (011) faces dominant. Exposure of the (010) surface is vital because it is normal to the one-dimensional ion-conduction pathway. Platelet and cube-like shapes observed by previous microscopy studies are reproduced by adjusting surface energies. The results indicate that a variety of (nano)particle morphologies can be achieved by tuning surface stabilities, which depend on synthesis methods and solvent conditions, and will be important in optimising electrochemical performance.