Correlation between the Surface Undulation and Luminescence Characteristics in Semi-Polar 112¯2 InGaN/GaN Multi-Quantum Wells.

Surface undulation was formed while growing InGaN/GaN multi-quantum wells on a semi-polar m-plane (1-100) sapphire substrate. Two distinct facets, parallel to 112¯2 and 011¯1, were formed in the embedded multi-quantum wells (MQWs). The structural and luminescence characteristics of the two facets were investigated using transmission electron microscopy equipped with cathodoluminescence. Those well-defined quantum wells, parallel and slanted to the growth plane, showed distinct differences in indium incorporation from both the X-ray yield and the contrast difference in annular darkfield images. Quantitative measurements of concentration in 011¯1 MQWs show an approximately 4 at% higher indium incorporation compared to the corresponding 112¯2 when the MQWs were formed under the same growth condition.

Atomic Reconstruction and Oxygen Evolution Reaction of Mn3O4 Nanoparticles.

Understanding the chemical states of individual surface atoms and their arrangements is essential for addressing several current issues such as catalysis, energy stroage/conversion, and environmental protection. Here, we exploit a profile imaging technique to understand the correlation between surface atomic structures and the oxygen evolution reaction (OER) in Mn3O4 nanoparticles. We image surface structures of Mn3O4 nanoparticles and observe surface reconstructions in the (110) and (101) planes. Mn3+ ions at the surface, which are commonly considered as the active sites in OER, disappear from the reconstructed planes, whereas Mn3+ ions are still exposed at the edges of nanoparticles. Our observations suggest that surface reconstructions can deactivate low-index surfaces of Mn oxides in OER. These structural and chemical observations are further validated by density functional theory calculations. This work shows why atomic-scale characterization of surface structures is crucial for a molecular-level understanding of a chemical reaction in oxide nanoparticles.

In Situ TEM Study of Structural Changes in Na-ß″-Alumina Using Electron Beam Irradiation.

Real-time structural changes in Na-ß″-alumina were observed in situ using transmission electron microscopy (TEM) with electron beam irradiation. Na-ß″-alumina has been widely investigated as a solid electrolyte material for sodium-sulfur secondary batteries owing to its high ionic conductivity. This high conductivity is known to be due to the Na+ ions on the loosely packed conduction planes of Na-ß″-alumina. In the present study, we acquired real-time videos of the generation of spinel blocks caused by the conduction of Na+ ions. In addition, by observing Na extraction during electron beam irradiation, we experimentally confirmed that spinel block generation originates from the Na+ ion conduction, which has been a subject of recent debate.

Transarterial Infusion of Epirubicin and Cisplatin Combined With Systemic Infusion of 5-Flurouracil Versus Sorafenib for Hepatocellular Carcinoma With Refractoriness of Transarterial Chemoembolization Using Doxorubicin.

Transarterial chemoembolization using doxorubicin (TACE-DOX) is an effective therapy for advanced hepatocellular carcinoma (HCC). However, there are limited options for patients with TACE refractoriness. We compared the effectiveness between sorafenib and transarterial chemolipiodolization using epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil (5-FU; TACL-ECF) in patients with previous TACE-DOX refractoriness. We retrospectively analyzed 742 consecutively enrolled cohort patients who received TACE-DOX as the first-line therapy for HCC. Among the 94 patients who failed with TACE-DOX, 49 patients were treated with TACL-ECF and 45 patients were treated with sorafenib as a rescue therapy. The TACL-ECF regimen comprised transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-FU. Of the 94 patients, 22 and 72 patients were in Barcelona Clinic Liver Cancer stages B and C, respectively; 66% patients were classified as having Child-Pugh class A (CPC A). Overall survival (OS) after rescue therapy did not differ between the sorafenib and TACL-ECF groups (4.1 months vs 6.4 months, P = .355). Progression-free survival (PFS) did not differ between the sorafenib and TACL-ECF groups (2.8 months vs 3.5 months, P = .629). Adverse events of CTC grade 3/4 occurred more frequently in the sorafenib group than in the TACL-ECF group (P = .024). The present study showed that the OS and PFS did not differ between patients given rescue TACL-ECF therapy and those given sorafenib therapy. The TACL-ECF treatment was better tolerated than sorafenib. The TACL-ECF might be considered as an alternative therapy for the patients with TACE-DOX refractoriness, especially CPC B and sorafenib-intolerant patients.

Microstructural evolution of tantalum nitride thin films synthesized by inductively coupled plasma sputtering.

Tantalum nitride (TaNx) thin films were grown utilizing an inductively coupled plasma (ICP) assisted direct current (DC) sputtering, and 20-100% improved microhardness values were obtained. The detailed microstructural changes of the TaNx films were characterized utilizing transmission electron microscopy (TEM), as a function of nitrogen gas fraction and ICP power. As nitrogen gas fraction increases from 0.05 to 0.15, the TaNx phase evolves from body-centered-cubic (b.c.c.) TaN0.1, to face-centered-cubic (f.c.c.) δ-TaN, to hexagonal-close-packing (h.c.p.) ε-TaN phase. By increasing ICP power from 100 W to 400 W, the f.c.c. δ- TaN phase becomes the main phase in all nitrogen fractions investigated. The higher ICP power enhances the mobility of Ta and N ions, which stabilizes the δ-TaN phase like a high-temperature regime and removes the micro-voids between the columnar grains in the TaNx film. The dense δ-TaN structure with reduced columnar grains and micro-voids increases the strength of the TaNx film.

A new corrosion-inhibiting strategy for biodegradable magnesium: reduced nicotinamide adenine dinucleotide (NADH).

Utilization of biodegradable metals in biomedical fields is emerging because it avoids high-risk and uneconomic secondary surgeries for removing implantable devices. Mg and its alloys are considered optimum materials for biodegradable implantable devices because of their high biocompatibility; however, their excessive and uncontrollable biodegradation is a difficult challenge to overcome. Here, we present a novel method of inhibiting Mg biodegradation by utilizing reduced nicotinamide adenine dinucleotide (NADH), an endogenous cofactor present in all living cells. Incorporating NADH significantly increases Mg corrosion resistance by promoting the formation of thick and dense protective layers. The unique mechanism by which NADH enables corrosion inhibition was discovered by combined microscopic and spectroscopic analyses. NADH is initially self-adsorbed onto the surface of Mg oxide layers, preventing Cl- ions from dissolving Mg oxides, and later recruits Ca2+ ions to form stable Ca-P protective layers. Furthermore, stability of NADH as a corrosion inhibitor of Mg under physiological conditions were confirmed using cell tests. Moreover, excellent cell adhesion and viability to Mg treated with NADH shows the feasibility of introduction of NADH to Mg-based implantable system. Our strategy using NADH suggests an interesting new way of delaying the degradation of Mg and demonstrates potential roles for biomolecules in the engineering the biodegradability of metals.

Sustained multiple organ ischaemia after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads) may enhance drug delivery to tumours and reduce systemic toxicity. TACE with DC beads leads to significantly fewer serious side-effects compared with conventional TACE. A 66-year-old man with hepatocellular carcinoma (HCC) complained of continuous abdominal pain 1 month after TACE with DC beads. At the time of TACE, angiography revealed severe stenosis of both hepatic arteries. The diagnostic work up on admission suggested severe bile duct injury with regional bile duct dilatation, segmental liver and spleen infarction, necrotizing pancreatitis, as well as gastric and duodenal ulcers. The pathology specimens of the duodenum contained DC beads that had passed through small vessels in the connective tissue. The patient's condition appeared to improve after 2 weeks of antibiotic treatment and supportive care, but new multifocal liver and spleen infarction subsequently developed. After 2 months, he was well enough to be discharged. His HCC partially responded to the TACE with DC beads but eventually progressed and he died after 11 months. The present case report highlights unexpected ongoing multiple organ ischaemia in a 66-year-old man treated for HCC using TACE with DC beads. The use of TACE with DC beads should be carefully considered in patients with vascular strictures or aberrant blood supply.

Surface-Modified Ta3N5 Nanocrystals with Boron for Enhanced Visible-Light-Driven Photoelectrochemical Water Splitting.

Photocatalysts for water splitting are the core of renewable energy technologies, such as hydrogen fuel cells. The development of photoelectrode materials with high efficiency and low corrosivity has great challenges. In this study, we report new strategy to improve performance of tantalum nitride (Ta3N5) nanocrystals as promising photoanode materials for visible-light-driven photoelectrochemical (PEC) water splitting cells. The surface of Ta3N5 nanocrystals was modified with boron whose content was controlled, with up to 30% substitution of Ta. X-ray photoelectron spectroscopy revealed that boron was mainly incorporated into the surface oxide layers of the Ta3N5 nanocrystals. The surface modification with boron increases significantly the solar energy conversion efficiency of the water-splitting PEC cells by shifting the onset potential cathodically and increasing the photocurrents. It reduces the interfacial charge-transfer resistance and increases the electrical conductivity, which could cause the higher photocurrents at lower potential. The onset potential shift of the PEC cell with the boron incorporation can be attributed to the negative shift of the flat band potential. We suggest that the boron-modified surface acts as a protection layer for the Ta3N5 nanocrystals, by catalyzing effectively the water splitting reaction.

Preferred diffusion paths for copper electromigration by in situ transmission electron microscopy.

Ionic transport in the reverse direction of an electric field is caused by momentum transfer from free electrons to metal ions, i.e., electromigration (EM), which is a critical factor leading to copper (Cu) interconnect failure in integrated circuits under extreme operating conditions. We investigated Cu self-diffusion paths under electrical bias using in situ transmission electron microscopy (TEM). An electric current was applied to multigrain Cu lines in the TEM instrument for durations of up to the order of 104s to trace EM-induced Cu movement around voids and hillocks. Combining this approach with scanning nanobeam diffraction, we observed that high-angle grain boundaries exposed to the free surface are the most favored paths for Cu EM, rather than a specific orientation within the grain. On hillocks of accumulated Cu atoms, we directly observed grain growth, accompanied by the formation of Σ7 high-mobile and Σ3 twin coincidence site lattice boundaries for effective growth. This study provides insight into the EM mechanism to improve the reliability of metal interconnect design.

Microscopic Evidence for Strong Interaction between Pd and Graphene Oxide that Results in Metal-Decoration-Induced Reduction of Graphene Oxide.

Graphene oxide (GO) is reduced spontaneously when palladium nanoparticles are decorated on the surface. The oxygen functional groups at the GO surface near the nanoparticles are absorbed to the palladium to produce a palladium oxide interlayer. Palladium therefore grows on the GO with preferred orientations, resulting in unique microstructural and electrical properties.

The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma.

BACKGROUND & AIMS: Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient's mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. METHODS: We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n=1461) accrued from Europe, the United States and Asia. RESULTS: Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection (p<0.001), transarterial chemoembolization (p<0.001) and sorafenib (p<0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study (p<0.001). CONCLUSIONS: In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. LAY SUMMARY: Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC.

A predictive model of the tensile strength of twisted carbon nanotube yarns.

Due to the outstanding mechanical properties of individual carbon nanotubes (CNTs) at the nanoscale, CNT yarns are expected to demonstrate high strength at the macroscale. In this study, a predictable model was developed to predict the tensile strength of twisted CNT yarns. First, the failure mechanism of twisted CNT yarns was investigated using in situ tensile tests and ex situ observations. It was revealed that CNT bundles, which are groups of CNTs that are tightly bound together, formed during tensile loading, leaving some voids around the bundles. Failure of the CNT yarns occurred as the CNT bundles were pulled out of the yarns. Two stresses that determined the tensile strength of the CNT yarns were identified: interfacial shear and frictional stresses originating from van der Waals interactions, and the lateral pressure generated by the twisted yarn structure. Molecular dynamics and yarn mechanics were used to calculate these two stresses. Finally, the tensile strength of CNT yarns was predicted and compared with experimental data, showing reasonable agreement.

Bond strength of individual carbon nanotubes grown directly on carbon fibers.

The performance of carbon nanotube (CNT)-based devices strongly depends on the adhesion of CNTs to the substrate on which they were directly grown. We report on the bond strength of CNTs grown on a carbon fiber (T700SC Toray), measured via in situ pulling of individual CNTs inside a transmission electron microscope. The bond strength of an individual CNT, obtained from the measured pulling force and CNT cross-section, was very high (∼200 MPa), 8-10 times higher than that of an adhesion model assuming only van der Waals interactions (25 MPa), presumably due to carbon-carbon interactions between the CNT (its bottom atoms) and the carbon substrate.

Prognostic sub-classification of intermediate-stage hepatocellular carcinoma: a multicenter cohort study with propensity score analysis.

There is significant heterogeneity in the clinicopathological characteristics of intermediate hepatocellular carcinoma (IHCC). This also translates to treatment as transarterial chemoembolization (TACE) is used as first-line therapy for patients with IHCC; however, in Asia liver resection (LR) is preferred. Prognostic tools are required to help guide clinicians in deciding treatment options. This study evaluates the prognostic impact of the Intermediate Stage Score (ISS) on overall survival (OS) in a large, multicenter cohort study of patients with IHCC treated with TACE or surgery LR. Consecutive patients from centers in Japan, Korea, Italy and the United Kingdom who underwent TACE or LR between 2001 and 2015 were enrolled. Propensity score (PS) adjustment was used to remove residual confounding and applied to LR (n = 162) and TACE (n = 449) to determine the prognostic significance of ISS. Among 611 patients, 75 % were men and 25 % women, with a mean age of 70 years. ISS is a valid prognostic tool in the BCLC-B population with a median OS ISS 1-51, 2-38.3, 3-24.3, 4-15.6, 5-16 months (p < 0.0001). ISS was analyzed within each treatment modality, and this was a valid prognostic score among those treated with TACE and LR (p < 0.001 vs. p = 0.008). In the PS-adjusted model, ISS retained its prognostic utility in TACE and LR groups (p < 0.001 vs. p = 0.007). ISS optimizes prognostic prediction in IHCC, reducing clinical heterogeneity, and is a useful tool for patients treated for TACE or LR.

Combined sequential use of HAP and ART scores to predict survival outcome and treatment failure following chemoembolization in hepatocellular carcinoma: a multi-center comparative study.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is variable, despite a myriad of prognostic markers. We compared and integrated the established prognostic models, HAP and ART scores, for their accuracy of overall survival (OS) prediction. RESULTS: In both training and validation sets, HAP and ART scores emerged as independent predictors of OS (p<0.01) with HAP achieving better prognostic accuracy (c-index: 0.68) over ART (0.57). We tested both scores in combination to evaluate their combined ability to predict OS. Subgroup analysis of BCLC-C patients revealed favorable HAP stage (p<0.001) and radiological response after initial TACE (p<0.001) as positive prognostic factors. PATIENTS AND METHODS: Prognostic scores were studied using multivariable Cox regression and c-index analysis in 83 subjects with Barcelona Clinic Liver Cancer (BCLC) A/B stage from UK and Italy (training set), and 660 from Korea and Japan (validation set), all treated with conventional TACE. Scores were further validated in an separate analysis of patients with BCLC-C stage disease (n=63) receiving initial TACE. CONCLUSION: ART and HAP scores are validated indices in patients with intermediate stage HCC undergoing TACE. The HAP score is best suited for screening patients prior to initial TACE, whilst sequential ART assessment improves early detection of chemoembolization failure. BCLC-C patients with low HAP stage may be a subgroup where TACE should be explored in clinical studies.

CoSe2 and NiSe2 Nanocrystals as Superior Bifunctional Catalysts for Electrochemical and Photoelectrochemical Water Splitting.

Catalysts for oxygen evolution reactions (OER) and hydrogen evolution reactions (HER) are central to key renewable energy technologies, including fuel cells and water splitting. Despite tremendous effort, the development of low-cost electrode catalysts with high activity remains a great challenge. In this study, we report the synthesis of CoSe2 and NiSe2 nanocrystals (NCs) as excellent bifunctional catalysts for simultaneous generation of H2 and O2 in water-splitting reactions. NiSe2 NCs exhibit superior electrocatalytic efficiency in OER, with a Tafel slope (b) of 38 mV dec(-1) (in 1 M KOH), and HER, with b = 44 mV dec(-1) (in 0.5 M H2SO4). In comparison, CoSe2 NCs are less efficient for OER (b = 50 mV dec(-1)), but more efficient for HER (b = 40 mV dec(-1)). It was found that CoSe2 NCs contained more metallic metal ions than NiSe2, which could be responsible for their improved performance in HER. Robust evidence for surface oxidation suggests that the surface oxide layers are the actual active sites for OER, and that CoSe2 (or NiSe2) under the surface act as good conductive layers. The higher catalytic activity of NiSe2 is attributed to their oxide layers being more active than those of CoSe2. Furthermore, we fabricated a Si-based photoanode by depositing NiSe2 NCs onto an n-type Si nanowire array, which showed efficient photoelectrochemical water oxidation with a low onset potential (0.7 V versus reversible hydrogen electrode) and high durability. The remarkable catalytic activity, low cost, and scalability of NiSe2 make it a promising candidate for practical water-splitting solar cells.

The usefulness of C-reactive protein and neutrophil-to-lymphocyte ratio for predicting the outcome in hospitalized patients with liver cirrhosis.

BACKGROUND: The role of clinical parameters such as systemic inflammatory response syndrome (SIRS) criteria in predicting the infection remains unclear in cirrhosis patients. The aim was to evaluate the usefulness of inflammatory markers including C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) for diagnosis of infection and predicting the outcomes in hospitalized cirrhotic patients. METHODS: The study included 184 cirrhotic patients consecutively hospitalized from 2011 to 2012. The presence of overt infection and survival was evaluated. CRP concentration, NLR, Model for End-Stage Liver Disease (MELD) score and the presence of SIRS were assessed. RESULTS: The main cause of admission was uncontrolled ascites (36.4 %), followed by varix bleeding (23.9 %), and hepatic encephalopathy (13.6 %). Fifty-eight patients (31.5 %) had overt infection during hospitalization and thirty-two patients (17.4 %) expired during the follow up period (median 38 months). Ninety-two patients (52.2 %) fulfilled the SIRS criteria and among them, only 32 patients (38.5 %) had the overt infection. For diagnose of the infection, baseline CRP concentration was a significant factor compared to the presence of SIRS (odds ratio 1.202, P = 0.003). For predicting one-month short-term survival, MELD score, NLR and WBC count were significant factors but in Child-Pugh class C patients, NLR was only an independent factor. CONCLUSIONS: CRP was a significant indicator of infection in hospitalized cirrhotic patients and a NLR was a useful predictor of 1-month survival, particularly in Child-Pugh class C patients. This study suggests that the inflammatory markers such as CRP and NLR can help identify cirrhotic patients at risk of unfavorable outcomes.

Reactivation of hepatitis B virus in HBsAg-negative patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Despite increasing attention to hepatitis B virus (HBV) reactivation in hematologic settings, information on reactivation in hepatitis B surface (HBsAg)-negative patients with hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE). METHODS: A total of 109 HBsAg-negative patients with HCC were consecutively recruited for this study and treated with either mono- (n = 75), combination-drug TACE (n = 20), or combination-drug TACE plus radiotherapy (n = 14). With serial monitoring of virological markers every 2-3 months, patients were observed for HBV reactivation (defined as the reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with control subjects with HBsAg-negative cirrhosis (n = 16) or HBsAg loss (n = 46). RESULTS: During the study period, HBV reactivation occurred in 12 (11.0%) and 1 (1.6%) patients in the TACE and control groups, respectively. The median level of HBV DNA at reactivation was 5,174 copies/ml (range: 216-116,058). Of the 12 patients with HBV reactivation, four (33.3%) developed clinical hepatitis, including one patient who suffered from decompensation. All antiviral-treated patients achieved undetectable HBV DNA or HBsAg loss after commencement of antiviral drugs. TACE was significantly correlated with a high incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment. On multivariate analysis, treatment intensity and a prior history of chronic hepatitis B remained independently predictive of reactivation. CONCLUSIONS: TACE can reactivate HBV replication in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. Patients with prior chronic HBV infection who are to undergo intensive TACE should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation.

Short Term Virologic Efficacies of Telbivudine versus Entecavir against Hepatitis B-Related Hepatocellular Carcinoma.

Telbivudine has been reported to be more effective than lamivudine. However, because of the resistance rate to telbivudine (TLV), the current guidelines recommend entecavir (ETV) or tenofovir (TNV) as the first-line therapy for chronic hepatitis B. We investigated the short term virologic efficacy of TLV in comparison with ETV as the first-line agent of HBV suppression in HBV-related advanced HCC patients. A total of 86 consecutive patients with HBV-related HCC for whom antiviral treatment was initiated in Incheon St. Mary's Hospital between 2010 and 2013 were analyzed. Virologic responses were investigated on the 4th, 12th, and 24th weeks of the antiviral therapies. In patients with advanced TNM stage cancer (stage 3 or 4) and poor liver function (Child-Pugh class B or C), the virologic response rates at weeks 12 and 24 were 25% (1/4) and 42.8% (3/7) in the TLV group and 33.3% (1/3) and 33.3% (1/3) in the ETV group, respectively (P = 0.424, P = 0.800). The short term efficacy of TLV was similar to that of ETV. Since TLV is highly cost-effective, it should be considered as a first-line antiviral agent in patients with advanced HCC, poor liver function, and short life expectancies.

Design and application of a novel in situ nano-manipulation stage for transmission electron microscopy.

A novel nano-scale manipulator capable of handling low-dimensional materials with three-dimensional linear motion, gripping action, and push-pull action of the gripper was developed for an in situ experiment in transmission electron microscopy. X-Y-Z positioning and push-pull action were accomplished by a piezotubing system, combined with a specially designed assembly stage that consisted of a lever-action gripping tip backed by a push-pull piezostack. The gripper tip consisted of tungsten wire fabricated by electrochemical etching followed by a focused ion beam process. Performance of the nano-scale manipulator was demonstrated in a grab-and-pick test of a single silver nanowire and in an in situ tensile test of a pearlitic steel sample with a specific orientation.