Identification of functionally important domains of human cytomegalovirus gO that act after trimer binding to receptors.

Human cytomegalovirus (HCMV) entry involves trimer (gH/gL/gO) that interacts with PDGFRα in fibroblasts. Entry into epithelial and endothelial cells requires trimer, which binds unidentified receptors, and pentamer (gH/gL/UL128-131), which binds neuropilin-2. To identify functionally important domains in trimer, we screened an overlapping 20-mer gO peptide library and identified two sets of peptides: 19/20 (a.a. 235-267) and 32/33 (a.a. 404-436) that could block virus entry. Soluble trimer containing wild type gO blocked HCMV entry, whereas soluble trimers with the 19/20 or 32/33 sequences mutated did not block entry. Interestingly, the mutant trimers retained the capacity to bind to cellular receptors including PDGFRα. Peptide 19/20 and 32/33 sequences formed a lobe extending from the surface of gO and an adjacent concave structure, respectively. Neither of these sets of sequences contacted PDGFRα. Instead, our data support a model in which the 19/20 and 32/33 trimer sequences function downstream of receptor binding, e.g. trafficking of HCMV into endosomes or binding to gB for entry fusion. We also screened for peptides that bound antibodies (Abs) in human sera, observing that peptides 20 and 26 bound Abs. These peptides engendered neutralizing Abs (NAbs) after immunization of rabbits and could pull out NAbs from human sera. Peptides 20 and 26 sequences represent the first NAb epitopes identified in trimer. These studies describe two important surfaces on gO defined by: i) peptides 19/20 and 32/33, which apparently act downstream of receptor binding and ii) peptide 26 that interacts with PDGFRα. Both these surfaces are targets of NAbs.

Decisional Conflict Among Patients Newly Diagnosed With Clinical T1 Renal Masses: A Prospective Study.

PURPOSE: Because multiple management options exist for clinical T1 renal masses, patients may experience a state of uncertainty about the course of action to pursue (ie, decisional conflict). To better support patients, we examined patient, clinical, and decision-making factors associated with decisional conflict among patients newly diagnosed with clinical T1 renal masses suspicious for kidney cancer. MATERIALS AND METHODS: From a prospective clinical trial, participants completed the Decisional Conflict Scale (DCS), scored 0 to 100 with < 25 associated with implementing decisions, at 2 time points during the initial decision-making period. The trial further characterized patient demographics, health status, tumor burden, and patient-centered communication, while a subcohort completed additional questionnaires on decision-making. Associations of patient, clinical, and decision-making factors with DCS scores were evaluated using generalized estimating equations to account for repeated measures per patient. RESULTS: Of 274 enrollees, 250 completed a DCS survey; 74% had masses ≤ 4 cm in size, while 11% had high-complexity tumors. Model-based estimated mean DCS score across both time points was 17.6 (95% CI 16.0-19.3), though 50% reported a DCS score ≥ 25 at least once. On multivariable analysis, DCS scores increased with age (+2.64, 95% CI 1.04-4.23), high- vs low-complexity tumors (+6.50, 95% CI 0.35-12.65), and cystic vs solid masses (+9.78, 95% CI 5.27-14.28). Among decision-making factors, DCS scores decreased with higher self-efficacy (-3.31, 95% CI -5.77 to -0.86]) and information-seeking behavior (-4.44, 95% CI -7.32 to -1.56). DCS scores decreased with higher patient-centered communication scores (-8.89, 95% CI -11.85 to -5.94). CONCLUSIONS: In addition to patient and clinical factors, decision-making factors and patient-centered communication relate with decisional conflict, highlighting potential avenues to better support patient decision-making for clinical T1 renal masses.

HCMV trimer- and pentamer-specific antibodies synergize for virus neutralization but do not correlate with congenital transmission.

Human cytomegalovirus (HCMV) causes substantial disease in transplant patients and harms the development of the nervous system in babies infected in utero. Thus, there is a major focus on developing safe and effective HCMV vaccines. Evidence has been presented that a major target of neutralizing antibodies (NAbs) is the HCMV pentamer glycoprotein gH/gL/UL128-131. In some studies, most of the NAbs in animal or human sera were found to recognize the pentamer, which mediates HCMV entry into endothelial and epithelial cells. It was also reported that pentamer-specific antibodies correlate with protection against transmission from mothers to babies. One problem with the studies on pentamer-specific NAbs to date has been that the studies did not compare the pentamer to the other major form of gH/gL, the gH/gL/gO trimer, which is essential for entry into all cell types. Here, we demonstrate that both trimer and pentamer NAbs are frequently found in human transplant patients' and pregnant mothers' sera. Depletion of human sera with trimer caused reductions in NAbs similar to that observed following depletion with the pentamer. The trimer- and pentamer-specific antibodies acted in a synergistic fashion to neutralize HCMV and also to prevent virus cell-to-cell spread. Importantly, there was no correlation between the titers of trimer- and pentamer-specific NAbs and transmission of HCMV from mothers to babies. Therefore, both the trimer and pentamer are important targets of NAbs. Nevertheless, these antibodies do not protect against transmission of HCMV from mothers to babies.

Impacts of seasonality and operating conditions on algal-dual osmosis membrane system for potable water reuse: Part 2.

This study investigated the impact of seasonal variation and operating conditions on recovery of potable quality water from municipal wastewater effluent using an integrated algal treatment process with a dual forward osmosis (FO)-reverse osmosis (RO) membrane system. Pilot study of the algal process treating primary effluent validated the technical viability and seasonal performance during warm weather (May to October, 25-55 °C) using an extremophilic algal strain Galdieria sulphuraria, and during cold weather (November to April, 4-17 °C) using polyculture strains of algae and bacteria. Algal effluents from both seasons were used as the feed solution for the laboratory FO-RO study. In addition, pilot-scale FO-RO experiments were conducted to compare the system performance during treatment of algal effluent and secondary effluent from the conventional treatment facility. At 90% water recovery, the FO-RO achieved over 90% overall rejection of major ions and organic matter using the bench-scale system and over 99% rejection of all contaminants in pilot-scale studies. Detailed water quality analysis indicated that the product water from the integrated system met both the primary and secondary drinking water standards. This study demonstrated that the FO-RO system can be engineered as a viable alternative to treat algal effluent and secondary effluent for potable water reuse independent of seasonal variations and operating conditions.

Impacts of seasonality and operating conditions on water quality of algal versus conventional wastewater treatment: Part 1.

Municipal wastewater is a reliable source from which water, renewable energy, and nutrients could be recovered for beneficial use. Our previous efforts have documented that an innovative algal-based wastewater treatment (WWT) system could recover energy and nutrients from wastewater while having a lower energy footprint than conventional WWT processes. As a biological treatment process, the algal WWT can be affected by algal species, operating conditions, and meteorological factors. This study aimed to identify suitable algal cultures to treat municipal wastewater during warm and cold weather. The algal system achieved the secondary effluent discharge standards for biochemical oxygen demand and nutrients within 2-3 days during warm weather (May to October, 25-55 °C) using an extremophilic algal strain Galdieria sulphuraria; and within 1-2 days in winter (November to April, 4-17 °C) using polyculture strains of algae with bacteria. The impact of seasonal variation and operating conditions on the water quality of pilot-scale algal bioreactors was compared with a full-scale conventional WWT system. The treatment performance of the algal system (NH4-N: 1.3 ± 1.25 mg/L in winter and not detected in summer and conventional system; PO4-P: 0.89 ± 0.6 mg/L in winter, 0.02 ± 0.03 mg/L in summer and, 5.93 ± 1.32 mg/L in conventional system) was comparable or better than that of the conventional WWT in nutrients removal and other contaminants were below the discharge standards. This study indicates that the algal system can be engineered for reliable wastewater treatment independent of seasonal variations.

Characterization of the Herpes Simplex Virus (HSV) Tegument Proteins That Bind to gE/gI and US9, Which Promote Assembly of HSV and Transport into Neuronal Axons.

The herpes simplex virus (HSV) heterodimer gE/gI and another membrane protein, US9, which has neuron-specific effects, promote the anterograde transport of virus particles in neuronal axons. Deletion of both HSV gE and US9 blocks the assembly of enveloped particles in the neuronal cytoplasm, which explains why HSV virions do not enter axons. Cytoplasmic envelopment depends upon interactions between viral membrane proteins and tegument proteins that encrust capsids. We report that tegument protein UL16 is unstable, i.e., rapidly degraded, in neurons infected with a gE-/US9- double mutant. Immunoprecipitation experiments with lysates of HSV-infected neurons showed that UL16 and three other tegument proteins, namely, VP22, UL11, and UL21, bound either to gE or gI. All four of these tegument proteins were also pulled down with US9. In neurons transfected with tegument proteins and gE/gI or US9, there was good evidence that VP22 and UL16 bound directly to US9 and gE/gI. However, there were lower quantities of these tegument proteins that coprecipitated with gE/gI and US9 from transfected cells than those of infected cells. This apparently relates to a matrix of several different tegument proteins formed in infected cells that bind to gE/gI and US9. In cells transfected with individual tegument proteins, this matrix is less prevalent. Similarly, coprecipitation of gE/gI and US9 was observed in HSV-infected cells but not in transfected cells, which argued against direct US9-gE/gI interactions. These studies suggest that gE/gI and US9 binding to these tegument proteins has neuron-specific effects on virus HSV assembly, a process required for axonal transport of enveloped particles.IMPORTANCE Herpes simplex viruses 1 and 2 and varicella-zoster virus cause significant morbidity and mortality. One basic property of these viruses is the capacity to establish latency in the sensory neurons and to reactivate from latency and then cause disease in peripheral tissues, such as skin and mucosal epithelia. The transport of nascent HSV particles from neuron cell bodies into axons and along axons to axon tips in the periphery is an important component of this reactivation and reinfection. Two HSV membrane proteins, gE/gI and US9, play an essential role in these processes. Our studies help elucidate how HSV gE/gI and US9 promote the assembly of virus particles and sorting of these virions into neuronal axons.

Predicting Pathological Tumor Size in Prostate Cancer Based on Multiparametric Prostate Magnetic Resonance Imaging and Preoperative Findings.

PURPOSE: Oncologic efficacy of focal therapies in prostate cancer depends heavily on accurate tumor size estimation. We aim to evaluate the agreement between radiologic tumor size and pathological tumor size, and identify predictors of pathological tumor size. MATERIALS AND METHODS: This single arm study cohort included all consecutive patients with biopsy proven prostate cancer and a corresponding PI-RADS®v2 3 or greater index tumor on multiparametric magnetic resonance imaging who subsequently underwent radical prostatectomy. Radiologic tumor size was defined as maximum tumor diameter on multiparametric magnetic resonance imaging and compared to whole mount histopathology tumor correlates. The difference between radiologic tumor size and pathological tumor size was assessed, and clinical, pathological and radiographic predictors of pathological tumor size were examined. RESULTS: A total of 461 consecutive lesions in 441 men were included for statistical analysis. Mean radiologic tumor size and pathological tumor size was 1.57 and 2.37 cm, respectively (p <0.001). Radiologic tumor size consistently underestimated pathological tumor size regardless of the preoperative covariates, and the degree of underestimation increased with smaller radiologic tumor size and lower PI-RADSv2 scores. Pathological tumor size was significantly larger for biopsy Gleason Grade Group (GG) 5 compared to GG1 (mean change 0.37 cm, p=0.014), PI-RADSv2 5 lesions compared to PI-RADSv2 4 (mean change 0.26, p=0.006) and higher prostate specific antigen density. The correlations between radiologic tumor size vs pathological tumor size according to biopsy GG and radiologic covariates were generally low with correlation coefficients ranging between 0.1 and 0.65. CONCLUSIONS: Multiparametric magnetic resonance imaging frequently underestimates pathological tumor size and the degree of underestimation increases with smaller radiologic tumor size and lower PI-RADSv2 scores. Therefore, a larger ablation margin may be required for smaller tumors and lesions with lower PI-RADSv2 scores. These variables must be considered when estimating treatment margins in focal therapy.

Substituent Effects in the Synthesis of Heterostructures.

There have been a number of surprising reports of unexpected products when preparing heterostructures of Bi2Se3 with other 2D layers. These reports prompted us to explore the formation of metastable heterostructures containing Bi2Se3 using X-ray diffraction techniques to follow the reaction pathway. We discovered that the products formed depend on the electronic properties of the second constituent. Bi|Se layers deposited in a 2:3 ratio with enough atoms to make a single five-plane layer evolved to form thermodynamically stable Bi2Se3 as expected from the phase diagram. When the same Bi|Se layers were sequentially deposited with M|Se layers that form semiconductor layers (PbSe and 2H-MoSe2), Bi2Se3-containing heterostructures formed. When the same Bi|Se layers were deposited with M|Se layers that form metallic layers (TiSe2, VSe2, and 1T-MoSe2), BiSe-containing heterostructures formed. The amount of excess Se in the precursor controls whether [(Bi2Se3)1+δ]1[(MoSe2)]1 or [(BiSe)1+γ]1[(MoSe2)]1 forms. XPS data indicates that a mixture of both metallic 1T and semiconducting 2H-MoSe2 is present in [(BiSe)1+γ]1[(MoSe2)]1, while only semiconducting 2H-MoSe2 is present when layered with Bi2Se3. The electronic structure of adjacent layers impacts the formation of different structures from layers with similar local compositions. This provides an important additional parameter to consider when designing the synthesis of heterostructures, similar to substituent effects in molecular chemistry.

Enhanced Low-Temperature Thermoelectric Performance in (PbSe)1+δ(VSe2)1 Heterostructures due to Highly Correlated Electrons in Charge Density Waves.

We explore the effect of charge density wave (CDW) on the in-plane thermoelectric transport properties of (PbSe)1+δ(VSe2)1 and (PbSe)1+δ(VSe2)2 heterostructures. In (PbSe)1+δ(VSe2)1 we observe an abrupt 86% increase in the Seebeck coefficient, 245% increase in the power factor, and a slight decrease in resistivity over the CDW transition. This behavior is not observed in (PbSe)1+δ(VSe2)2 and is rather unusual compared to the general trend observed in other materials. The abrupt transition causes a deviation from the Mott relationship through correlated electron states. Raman spectra of the (PbSe)1+δ(VSe2)1 material show the emergence of additional peaks below the CDW transition temperature associated with VSe2 material. Temperature-dependent in-plane X-ray diffraction (XRD) spectra show a change in the in-plane thermal expansion of VSe2 in (PbSe)1+δ(VSe2)1 due to lattice distortion. The increase in the power factor and decrease in the resistivity due to CDW suggest a potential mechanism for enhancing the thermoelectric performance at the low temperature region.

Controlling the Self-Assembly of New Metastable Tin Vanadium Selenides Using Composition and Nanoarchitecture of Precursors.

In solid-state chemistry, the direct reaction of elements at low temperatures is limited by low solid-state interdiffusion rates. This and the limited number of processing parameters often prevent the synthesis of metastable compounds. Precisely controlling the number of atoms and nanoarchitecture of layered elemental precursors enabled the selective synthesis of two closely related metastable tin vanadium selenides via near-diffusionless reactions at low temperatures. Although the nanoarchitectures of the precursors required to form [(SnSe2)0.80]1(VSe2)1 and [(SnSe)1.15]1(VSe2)1 are very similar, controlling the local composition of the Sn|Se layers in the precursors enables the selective synthesis of either compound. The metastable alloy SnxV1-xSe2 was preferentially formed over [(SnSe2)0.80]1(VSe2)1, which has the identical composition, by modifying the nanoarchitecture of the precursor. Ex situ in-plane X-ray diffraction and X-ray reflectivity collected as a function of annealing temperature provided information on lateral and perpendicular growth of [(SnSe2)0.80]1(VSe2)1. The presence of Laue oscillations throughout the self-assembly provided atomic-scale information on the thickness of the [(SnSe2)0.80]1(VSe2)1 domains, giving insights into the self-assembly process. A reaction mechanism is proposed and used to rationalize how composition and nanoarchitecture control the reaction pathway through the free energy landscape.

Subclonal TP53 copy number is associated with prognosis in multiple myeloma.

Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts (P < .001) and increased lactate dehydrogenase (P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) (P = .002) or del(1p) (P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.

Longitudinal Associations Between Healthcare Resources, Policy, and Firearm-Related Suicide and Homicide from 2012 to 2016.

BACKGROUND: Firearm-related violence is a leading cause of mortality in the United States (US). Prior research suggests that public policy plays a role in firearm mortality, but the role of healthcare resources (physicians, insurance coverage) within the US policy context has not yet been studied. OBJECTIVE: To examine how healthcare resources and social/firearm policy affect firearm-related suicide and homicide rates in the US. DESIGN: Longitudinal, ecological study. SETTING: US. PARTICIPANTS: US states from 2012 to 2016 (N = 242). MEASUREMENT: The outcome variables were age-adjusted, firearm-related suicide and homicide rates. Predictor variables were healthcare resources (physicians, Medicaid benefits generosity) and policy context (social policy, firearm policy) with covariates for sociodemographic factors. RESULTS: Healthcare provider variables did not have significant associations to firearm-related suicide or homicide. In fully saturated models, more worker protection laws, greater average population density, more alcohol regulation, and more firearm prohibition policies were associated with fewer firearm-related suicides. Higher generosity of Medicaid benefits was associated with fewer firearm-related homicides. Poverty rate was a predictor of both outcomes. LIMITATIONS: This state-level study cannot make individual-level inferences. Only proxy variables were available for measuring gun ownership and actual gun ownership rates may not have been ideally captured at the state level. CONCLUSIONS: At the state level, there are protective associations of certain social, healthcare, and firearm policies to firearm-related suicide and homicide rates. Healthcare resources play a role in population-level firearm outcomes but alone are not sufficient to decrease firearm-related homicide or suicide.

Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.

BACKGROUND: While genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS). RESULTS: GWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80-491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus. CONCLUSIONS: Our findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.

Synthesis of Metastable Inorganic Solids with Extended Structures.

The number of known inorganic compounds is dramatically less than predicted due to synthetic challenges, which often constrains products to only the thermodynamically most stable compounds. Consequently, a mechanism-based approach to inorganic solids with designed structures is the holy grail of solid state synthesis. This article discusses a number of synthetic approaches using the concept of an energy landscape, which describes the complex relationship between the energy of different atomic configurations as a function of a variety of parameters such as initial structure, temperature, pressure, and composition. Nucleation limited synthesis approaches with high diffusion rates are contrasted with diffusion limited synthesis approaches. One challenge to the synthesis of new compounds is the inability to accurately predict what structures might be local free energy minima in the free energy landscape. Approaches to this challenge include predicting potentially stable compounds thorough the use of structural homologies and/or theoretical calculations. A second challenge to the synthesis of metastable inorganic solids is developing approaches to move across the energy landscape to a desired local free energy minimum while avoiding deeper free energy minima, such as stable binary compounds, as reaction intermediates. An approach using amorphous intermediates is presented, where local composition can be used to prepare metastable compounds. Designed nanoarchitecture built into a precursor can be preserved at low reaction temperatures and used to direct the reaction to specific structural homologs.

Using spatial tracking with magnetic resonance imaging/ultrasound-guided biopsy to identify unilateral prostate cancer.

OBJECTIVES: To create reliable predictive metrics of unilateral disease using spatial tracking from a fusion device, thereby improving patient selection for hemi-gland ablation of prostate cancer. PATIENTS AND METHODS: We identified patients who received magnetic resonance imaging (MRI)/ultrasound-guided biopsy and radical prostatectomy at a single institution between 2011 and 2018. In addition to standard clinical features, we extracted quantitative features related to biopsy core and MRI target locations predictive of tumour unilaterality. Classification and Regression Tree (CART) analysis was used to create a decision tree (DT) for identifying cancer laterality. We evaluated concordance of model-determined laterality with final surgical pathology. RESULTS: A total of 173 patients were identified with biopsy coordinates and surgical pathology available. Based on CART analysis, in addition to biopsy- and MRI-confirmed disease unilaterality, patients should be further screened for cancer detected within 7 mm of midline in a 40 mL prostate, which equates to the central third of any-sized prostate by radius. The area under the curve for this DT was 0.82. Standard diagnostics and the DT correctly identified disease laterality in 73% and 80% of patients, respectively (P = 0.13). Of the patients identified as unilateral by standard diagnostics, 47% had undetected contralateral disease or were otherwise incorrectly identified. This error rate was reduced to 17% (P = 0.01) with the DT. CONCLUSION: Using spatial tracking from fusion devices, a DT was more reliable for identifying laterality of prostate cancer compared to standard diagnostics. Patients with cancer detected within the central third of the prostate by radius are poor hemi-gland ablation candidates due to the risk of midline extension of tumour.

The association between N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, and clinical outcomes in patients undergoing robotic-assisted radical cystectomy.

PURPOSE: To assess the impact of N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, on the post-operative recovery of patients undergoing robotic-assisted radical cystectomy for bladder cancer. METHODS: We retrospectively reviewed patients undergoing robotic-assisted radical cystectomy by a single surgeon (KC) prior to (control group) and after (treatment group) the routine use of N-methylnaltrexone. Kaplan-Meier curves and the log-rank test were used to quantify time to flatus, bowel movement, and discharge. Daily mean opioid use, daily pain assessment rating, and episodes of severe pain (7-10/10) were compared. Gastrointestinal-related complications, including ileus, emesis, and/or need for post-op nasogastric tube placement, and 30-day readmissions were also compared between groups. Charge capture data were compared between groups to analyze cost impact. RESULTS: 29 patients each in the control and treatment group met inclusion criteria. Patients receiving N-methylnaltrexone had reduced length of stay compared with no N-methylnaltrexone (median 4 vs. 7 days, p < 0.01). Time to flatus and bowel movement, however, were similar. In a multivariable analysis controlling for possible confounders, however, the improvement in length of stay associated with N-methylnaltrexone use did not reach statistical significance (p = 0.11). Episodes of severe pain and composite gastrointestinal-related complications were reduced in the N-methylnaltrexone group (44.8% vs. 10.3%, p < 0.01). The reduction in length of stay was associated with approximately $10,500 in cost savings per patient. CONCLUSIONS: In this study, N-methylnaltrexone was associated with reduced length of stay, fewer episodes of severe pain, and reduced costs. These results provide the impetus for further study.

Investigating the Formation of MoSe2 and TiSe2 Films from Artificially Layered Precursors.

The reaction of ultrathin layers of Mo and Ti with Se was investigated, and significantly different reaction pathways were found. However, in both systems postdeposition annealing results in smooth dichalcogenide films with specific thicknesses determined by the precursor. X-ray diffraction (XRD) patterns of as-deposited Mo|Se films around a 1:2 ratio of Mo to Se contain weak, broad reflections from small and isolated MoSe2 crystallites that nucleated during deposition and a sharper intensity maximum resulting from the composition modulation created from the alternating deposition of Mo and Se layers. In contrast, as-deposited Ti|Se films around a 1:2 ratio of Ti to Se contain narrow and intense 00l reflections from TiSe2 crystallites and do not contain a Bragg reflection from the sequence of deposited Ti|Se layers. The as-deposited TiSe2 crystallites have a larger c-axis lattice parameter than was previously reported for TiSe2, however, which suggests a poor vertical interlayer registry and/or high defect densities including interstitial atoms. In-plane XRD patterns show the nucleation of both TiSe2 and Ti2Se during deposition, with the Ti2Se at the substrate. For both systems, annealing the precursors decreases the peak width and increases the intensity of reflections from crystalline TiSe2 and MoSe2. Optimized films consist of a single phase after the annealing and show clear Laue oscillations in the specular XRD patterns, which can only occur if a majority of the diffracting crystallites in the film consist of the same number of unit cells. The highest quality films was obtained when an excess of ∼10% Se was deposited in the precursor, which presumably acts as a flux to facilitate diffusion of metal atoms to crystallite growth fronts and compensates for Se loss to the open system during annealing.

Synthesis and Characterization of [(PbSe)1+δ]4[TiSe2]4 Isomers.

This work presents the preparation of a series of [(PbSe)1+δ]4[TiSe2]4 isomers via a low temperature synthesis approach that exploits precursor nanoarchitecture to direct formation of specific isomers. The targeted isomers formed even when the precursors did not have the correct amount of each element to make a unit cell from each repeating sequence of elemental layers deposited. This suggests that the exact composition of the precursors is less important than the nanoarchitecture in directing the formation of the compounds. The as-deposited diffraction data show that the isomers begin to form during the deposition, and Ti2Se, in addition to PbSe and TiSe2, are present in the specular diffraction patterns. HAADF-STEM images reveal impurity layers above and below an integer number of targeted isomer unit cells. The structural data suggest that Ti2Se forms as Se is deposited on the initial Ti layers and remains throughout isomer self-assembly. During growth, the isomers deplete the local supply of Ti and Pb, creating diffusion gradients that drive additional cations toward the growth front, which leaves surface impurity layers of TiSe2 and TiO2 after the supply of Pb is exhausted. The deposited stacking sequences direct formation of the targeted isomers, but fewer repeating units form than intended due to the lack of material per layer in the precursor and formation of impurity layers. All isomers have negative Hall and Seebeck coefficients, indicating that electrons are the majority carrier. The carrier concentration and conductivity of the isomers increase with the number of interfaces in the unit cell, resulting from charge donation between adjacent layers. The opposite variation of the carrier concentration and mobility with temperature result in minima in the resistivity between 50 and 100 K. The very weak temperature dependence of the carrier concentration likely results from changes in the amount of charge transfer between the layers with temperature.

Analysis of guideline recommended use of renal mass biopsy and association with treatment.

INTRODUCTION: Renal mass biopsy (RMB) may not be indicated when the results are unlikely to impact management, such as in young and/or healthy patients and in elderly and/or frail patients. We analyzed the utility of RMB in three patient cohorts stratified by age-adjusted Charlson comorbidity index score (ACCI). MATERIALS AND METHODS: We identified patients with cT1a renal tumors in the National Cancer Database from 2004-2014. We combined age and Charlson-Deyo scores to identify young and/or healthy patients ('healthy-ACCI'), elderly and/or frail patients ('frail-ACCI'), and a reference cohort. We performed multivariable logistic regression to identify predictors of RMB and treatment. We evaluated the impact of RMB on management by analyzing the proportion of high-grade disease on final pathology as a surrogate for risk stratification. RESULTS: We identified 36,720 healthy-ACCI, 2,516 frail-ACCI, and 18,989 reference-ACCI patients. Healthy-ACCI patients were less likely to undergo RMB (7.5% versus 10.8%; p < 0.001) while frail-ACCI patients underwent RMB at similar rates (11.8% versus 10.8%; p = 0.14) compared with reference-ACCI patients. On multivariable logistic regression, in both healthy-ACCI and frail-ACCI patients, RMB was associated with decreased odds of surgical treatment, and increased odds of ablation and surveillance (all p < 0.01). In the frail-ACCI patients, higher grade disease at surgery was identified in the RMB cohort (32.9% versus 23.5%, p = 0.05). CONCLUSIONS: RMB is performed less frequently in healthy-ACCI patients compared with the reference cohort. RMB is associated with decreased odds of surgical treatment and increased odds of surveillance and ablation in all cohorts. In frail-ACCI patients who underwent surgery, RMB may provide additional risk stratification as these patients had lower rates of low-grade disease.

Kinetics of the Topochemical Transformation of (PbSe) m(TiSe2) n(SnSe2) m(TiSe2) n to (Pb0.5Sn0.5Se) m(TiSe2) n.

Solid-state reaction kinetics on atomic length scales have not been heavily investigated due to the long times, high reaction temperatures, and small reaction volumes at interfaces in solid-state reactions. All of these conditions present significant analytical challenges in following reaction pathways. Herein we use in situ and ex situ X-ray diffraction, in situ X-ray reflectivity, high-angle annular dark field scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy to investigate the mechanistic pathways for the formation of a layered (Pb0.5Sn0.5Se)1+δ(TiSe2) m heterostructure, where m is the varying number of TiSe2 layers in the repeating structure. Thin film precursors were vapor deposited as elemental-modulated layers into an artificial superlattice with Pb and Sn in independent layers, creating a repeating unit with twice the size of the final structure. At low temperatures, the precursor undergoes only a crystallization event to form an intermediate (SnSe2)1+γ(TiSe2) m(PbSe)1+δ(TiSe2) m superstructure. At higher temperatures, this superstructure transforms into a (Pb0.5Sn0.5Se)1+δ(TiSe2) m alloyed structure. The rate of decay of superlattice reflections of the (SnSe2)1+γ(TiSe2) m(PbSe)1+δ(TiSe2) m superstructure was used as the indicator of the progress of the reaction. We show that increasing the number of TiSe2 layers does not decrease the rate at which the SnSe2 and PbSe layers alloy, suggesting that at these temperatures it is reduction of the SnSe2 to SnSe and Se that is rate limiting in the formation of the alloy and not the associated diffusion of Sn and Pb through the TiSe2 layers.