Microstructural origin of locally enhanced CO2 electroreduction activity on gold.

Understanding how the bulk structure of a material affects catalysis on its surface is critical to the development of actionable catalyst design principles. Bulk defects have been shown to affect electrocatalytic materials that are important for energy conversion systems, but the structural origins of these effects have not been fully elucidated. Here we use a combination of high-resolution scanning electrochemical cell microscopy and electron backscatter diffraction to visualize the potential-dependent electrocatalytic carbon dioxide [Formula: see text] electroreduction and hydrogen [Formula: see text] evolution activity on Au electrodes and probe the effects of bulk defects. Comparing colocated activity maps and videos to the underlying microstructure and lattice deformation supports a model in which CO2 electroreduction is selectively enhanced by surface-terminating dislocations, which can accumulate at grain boundaries and slip bands. Our results suggest that the deliberate introduction of dislocations into materials is a promising strategy for improving catalytic properties.

Hybrid scanning electrochemical cell microscopy-interference reflection microscopy (SECCM-IRM): tracking phase formation on surfaces in small volumes.

We describe the combination of scanning electrochemical cell microscopy (SECCM) and interference reflection microscopy (IRM) to produce a compelling technique for the study of interfacial processes and to track the SECCM meniscus status in real-time. SECCM allows reactions to be confined to well defined nm-to-µm-sized regions of a surface, and for experiments to be repeated quickly and easily at multiple locations. IRM is a highly surface-sensitive technique which reveals processes happening (very) close to a substrate with temporal and spatial resolution commensurate with typical electrochemical techniques. By using thin transparent conductive layers on glass as substrates, IRM can be coupled to SECCM, to allow real-time in situ optical monitoring of the SECCM meniscus and of processes that occur within it at the electrode/electrolyte interface. We first use the technique to assess the stability of the SECCM meniscus during voltammetry at an indium tin oxide (ITO) electrode at close to neutral pH, demonstrating that the meniscus contact area is rather stable over a large potential window and reproducible, varying by only ca. 5% over different SECCM approaches. At high cathodic potentials, subtle electrowetting is easily detected and quantified. We also look inside the meniscus to reveal surface changes at extreme cathodic potentials, assigned to the possible formation of indium nanoparticles. Finally, we examine the effect of meniscus size and driving potential on CaCO3 precipitation at the ITO electrode as a result of electrochemically-generated pH swings. We are able to track the number, spatial distribution and morphology of material with high spatiotemporal resolution and rationalise some of the observed deposition patterns with finite element method modelling of reactive-transport. Growth of solid phases on surfaces from solution is an important pathway to functional materials and SECCM-IRM provides a means for in situ or in operando visualisation and tracking of these processes with improved fidelity. We anticipate that this technique will be particularly powerful for the study of phase formation processes, especially as the high throughput nature of SECCM-IRM (where each spot is a separate experiment) will allow for the creation of large datasets, exploring a wide experimental parameter landscape.

Visualization of Ion Fluxes in Nanopipettes: Detection and Analysis of Electro-osmosis of the Second Kind.

Nanopipettes are finding increasing use as nano "test tubes", with reactions triggered through application of an electrochemical potential between electrodes in the nanopipette and a bathing solution (bath). Key to this application is an understanding of how the applied potential induces mixing of the reagents from the nanopipette and the bath. Here, we demonstrate a laser scanning confocal microscope (LSCM) approach to tracking the ingress of dye into a nanopipette (20-50 nm diameter end opening). We examine the case of dianionic fluorescein under alkaline conditions (pH 11) and large applied tip potentials (±10 V), with respect to the bath, and surprisingly find that dye ingress from the bath into the nanopipette is not observed under either sign of potential. Finite element method (FEM) simulations indicate this is due to the dominance of electro-osmosis in mass transport, with electro-osmotic flow in the conventional direction at +10 V and electro-osmosis of the second kind acting in the same direction at -10 V, caused by the formation of significant space charge in the center of the orifice. The results highlight the significant deviation in mass transport behavior that emerges at the nanoscale and the utility of the combined LSCM and FEM approach in deepening understanding, which in turn should promote new applications of nanopipettes.

Scanning Ion Conductance Microscopy: Surface Charge Effects on Electroosmotic Flow Delivery from a Nanopipette.

Scanning ion conductance microscopy (SICM) is a powerful and versatile technique that allows an increasingly wide range of interfacial properties and processes to be studied. SICM employs a nanopipette tip that contains electrolyte solution and a quasi-reference counter electrode (QRCE), to which a potential is applied with respect to a QRCE in a bathing solution, in which the tip is placed. The work herein considers the potential-controlled delivery of uncharged electroactive molecules (solute) from an SICM tip to a working electrode substrate to determine the effect of the substrate on electroosmotic flow (EOF). Specifically, the local delivery of hydroquinone from the tip to a carbon fiber ultramicroelectrode (CF UME) provides a means of quantifying the rate of mass transport from the nanopipette and mapping electroactivity via the CF UME current response for hydroquinone oxidation to benzoquinone. EOF, and therefore species delivery, has a particularly strong dependence on the charge of the substrate surface at close nanopipette-substrate surface separations, with implications for retaining neutral solute within the tip predelivery and for the delivery process itself, both controlled via the applied tip potential. Finite element method (FEM) simulations of mass transport and reactivity are used to explain the experimental observations and identify the nature of EOF, including unusual flow patterns under certain conditions. The combination of experimental results with FEM simulations provides new insights on mass transport in SICM that will enhance quantitative applications and enable new possibilities for the use of nanopipettes for local delivery.

Survival of advanced melanoma patients treated with immunotherapy and targeted therapy: A real-world study.

INTRODUCTION: We aimed to examine the survival outcomes plus patient and treatment characteristics of advanced melanoma patients treated with first-line immunotherapy (IT), targeted therapy (TT), and chemotherapy (CTH) and compare findings with information from pivotal trials for each therapy. MATERIALS AND METHODS: We retrospectively reviewed the use of systematic IT, TT and CTH therapies in melanoma patients in four Queensland public hospitals. We estimated median duration of overall survival (OS) and survival rates (6 months, 1, and 2 years) using Kaplan-Meier methods. We compared our findings to those of clinical trials. RESULTS: Five hundred three patients who met the inclusion criteria were divided into three groups based on the first-line treatment: IT 232; TT 157; and CTH 114. OS was 18 months with IT (95% CI 13, 22); 12 months with TT (95% CI 8, 15); and 5 months with CTH (95% CI 5, 6). The demographic characteristics, treatment protocols, and durations for IT and TT were generally consistent with trials but fewer patients in our study had subsequent therapy than in the trials. The OS in our study was slightly lower than the OS reported in trials. CONCLUSION: The OS of novel cancer therapy in the real world was lower than seen in trials but is expected given these are patients who have a poorer prognosis. A future study could investigate the impact of prognostic factors on survival in the longer term. This study provides evidence that we can use routinely collected real-world data to evaluate the effectiveness of checkpoint and kinase inhibitors in patients with advanced melanoma.

Electrochemical Impedance Measurements in Scanning Ion Conductance Microscopy.

Electrochemical impedance spectroscopy (EIS) is a versatile tool for electrochemistry, particularly when applied locally to reveal the properties and dynamics of heterogeneous interfaces. A new method to generate local electrochemical impedance spectra is outlined, by applying a harmonic bias between a quasi-reference counter electrode (QRCE) placed in a nanopipet tip of a scanning ion conductance microscope (SICM) and a conductive (working electrode) substrate (two-electrode setup). The AC frequency can be tuned so that the magnitude of the impedance is sensitive to the tip-to-substrate distance, whereas the phase angle is broadly defined by the local capacitive response of the electrical double layer (EDL) of the working electrode. This development enables the surface topography and the local capacitance to be sensed reliably, and separately, in a single measurement. Further, self-referencing the probe impedance near the surface to that in the bulk solution allows the local capacitive response of the working electrode substrate in the overall AC signal to be determined, establishing a quantitative footing for the methodology. The spatial resolution of AC-SICM is an order of magnitude larger than the tip size (100 nm radius), for the studies herein, due to frequency dispersion. Comprehensive finite element method (FEM) modeling is undertaken to optimize the experimental conditions and minimize the experimental artifacts originating from the frequency dispersion phenomenon, and provides an avenue to explore the means by which the spatial resolution could be further improved.

Nanoscale kinetics of amorphous calcium carbonate precipitation in H2O and D2O.

Calcium carbonate (CaCO3) is one of the most well-studied and abundant natural materials on Earth. Crystallisation of CaCO3 is often observed to proceed via an amorphous calcium carbonate (ACC) phase, as a precursor to more stable crystalline polymorphs such as vaterite and calcite. Despite its importance, the kinetics of ACC formation have proved difficult to study, in part due to rapid precipitation at moderate supersaturations, and the instability of ACC with respect to all other polymorphs. However, ACC can be stabilised under confinement conditions, such as those provided by a nanopipette. This paper demonstrates electrochemical mixing of a Ca2+ salt (CaCl2) and a HCO3- salt (NaHCO3) in a nanopipette to repeatedly and reversibly precipitate nanoparticles of ACC under confined conditions, as confirmed by scanning transmission electron microscopy (STEM). Measuring the current as a function of applied potential across the end of the nanopipette and time provides millisecond-resolved measurements of the induction time for ACC precipitation. We demonstrate that under conditions of electrochemical mixing, ACC precipitation is extremely fast, and highly pH sensitive with an apparent third order dependence on CO32- concentration. Furthermore, the rate is very similar for the equivalent CO32- concentrations in D2O, suggesting that neither ion dehydration nor HCO3- deprotonation represent significant energetic barriers to the formation of ACC. Finite element method simulations of the electrochemical mixing process enable the supersaturation to be estimated for all conditions and accurately predict the location of precipitation.

Bortezomib use and outcomes for the treatment of multiple myeloma.

BACKGROUND: The public subsidy in Australia of bortezomib (Velcade) for untreated non-transplant multiple myeloma patients was based on the VISTA trial. AIMS: To ascertain the health outcomes of bortezomib in 'real world' transplant-ineligible elderly patients, compared to trial data. METHODS: Patient and treatment data were extracted from an oncology information system, laboratory information system and medical chart audits for three Queensland public hospitals. RESULTS: We identified 74 patients; the median age was 75 years. Our cohort comprised 47% patients who were International Staging System stage III, 45% at stage II and 8% at stage I. Patients who had comorbidities, such as cardiac disease (41%), pulmonary disease (14%), diabetes (22%), peripheral neuropathy (14%) and other comorbidities (41%) at baseline were included. The common regimens prescribed were VMP, CVD and VD, and most patients (n = 73) received bortezomib on a once-weekly or twice-a-week basis. The overall response rate was 81%. Half (53%) of the patients did not complete their planned therapy due to toxicity (30%), suboptimal response or disease progression (15%), or death on treatment (8%). Overall survival was 40.7 months and progression free survival was 17.7 months. CONCLUSIONS: Our patients were older, had worse disease characteristics and more comorbidities than patients in the VISTA trial. While response rates were similar, survival outcomes appeared worse. Bortezomib-based treatment in the real world setting still carries a high risk of toxicity in the elderly population.

Electric Field-Controlled Synthesis and Characterisation of Single Metal-Organic-Framework (MOF) Nanoparticles.

Achieving control over the size distribution of metal-organic-framework (MOF) nanoparticles is key to biomedical applications and seeding techniques. Electrochemical control over the nanoparticle synthesis of the MOF, HKUST-1, is achieved using a nanopipette injection method to locally mix Cu2+ salt precursor and benzene-1,3,5-tricarboxylate (BTC3- ) ligand reagents, to form MOF nanocrystals, and collect and characterise them on a TEM grid. In situ analysis of the size and translocation frequency of HKUST-1 nanoparticles is demonstrated, using the nanopipette to detect resistive pulses as nanoparticles form. Complementary modelling of mass transport in the electric field, enables particle size to be estimated and explains the feasibility of particular reaction conditions, including inhibitory effects of excess BTC3- . These new methods should be applicable to a variety of MOFs, and scaling up synthesis possible via arrays of nanoscale reaction centres, for example using nanopore membranes.

Systemic anticancer therapy in the last 30 days of life: Retrospective audit from an Australian Regional Cancer Centre.

BACKGROUND: Cessation of chemotherapy at an appropriate time is an important component of good quality palliative care. Published studies looking at administration of chemotherapy at the end of life vary widely. OBJECTIVE: To retrospectively determine the rate of death occurring within 14 and 30 days of chemotherapy and use this to benchmark against other cancer centres as a quality of care measure. METHOD: All adult patients who received systemic anticancer therapy for solid tumours and haematological malignancies at an Australian Regional Cancer Centre between 2011 and 2015 were included. RESULTS: Over a five-year period, 1215 patients received systemic anticancer therapy. Of these, 23 (1.89%) died within 14 days following systemic anticancer therapy and 68 (5.60%) within 30 days. All patients who died had been treated with palliative intent. Mean time to death was 17.7 days. The majority were female (61.8%) and the mean age was 62.3 years. The most common cause of death was disease progression (80.9%). Nearly half died at the Regional Cancer Centre, including 30.9% who lived in rural or remote localities. CONCLUSION: The rate of death observed in this study is at the lower end of the range seen in published studies for both the last 14 and 30 days post-systemic anticancer therapy. It is important to routinely collect data to enable benchmarking against other institutions, determine factors potentially associated with higher risks of mortality at the end of life and improve clinical decision making.

The Feasibility of Electrochemical Ammonia Synthesis in Molten LiCl-KCl Eutectics.

Molten LiCl and related eutectic electrolytes are known to permit direct electrochemical reduction of N2 to N3- with high efficiency. It had been proposed that this could be coupled with H2 oxidation in an electrolytic cell to produce NH3 at ambient pressure. Here, this proposal is tested in a LiCl-KCl-Li3 N cell and is found not to be the case, as the previous assumption of the direct electrochemical oxidation of N3- to NH3 is grossly over-simplified. We find that Li3 N added to the molten electrolyte promotes the spontaneous and simultaneous chemical disproportionation of H2 (H oxidation state 0) into H- (H oxidation state -1) and H+ in the form of NH2- /NH2 - /NH3 (H oxidation state +1) in the absence of applied current, resulting in non-Faradaic release of NH3 . It is further observed that NH2- and NH2 - possess their own redox chemistry. However, these spontaneous reactions allow us to propose an alternative, truly catalytic cycle. By adding LiH, rather than Li3 N, N2 can be reduced to N3- while stoichiometric amounts of H- are oxidised to H2 . The H2 can then react spontaneously with N3- to form NH3 , regenerating H- and closing the catalytic cycle. Initial tests show a peak NH3 synthesis rate of 2.4×10-8  mol cm-2 s-1 at a maximum current efficiency of 4.2 %. Isotopic labelling with 15 N2 confirms the resulting NH3 is from catalytic N2 reduction.

Efficient Non-dissociative Activation of Dinitrogen to Ammonia over Lithium-Promoted Ruthenium Nanoparticles at Low Pressure.

There is an exciting possibility to decentralize ammonia synthesis for fertilizer production or energy storage without carbon emission from H2 obtained from renewables at small units operated at lower pressure. However, no suitable catalyst has yet been developed. Ru catalysts are known to be promoted by heavier alkali dopants. Instead of using heavy alkali metals, Li is herein shown to give the highest rate through surface polarisation despite its poorest electron donating ability. This exceptional promotion rate makes Ru-Li catalysts suitable for ammonia synthesis, which outclasses industrial Fe counterparts by at least 195 fold. Akin to enzyme catalysis, it is for the first time shown that Ru-Li catalysts hydrogenate end-on adsorbed N2 stabilized by Li+ on Ru terrace sites to ammonia in a stepwise manner, in contrast to typical N2 dissociation on stepped sites adopted by Ru-Cs counterparts, giving new insights in activating N2 by metallic catalysts.

Adsorbed Intermediates in Oxygen Reduction on Platinum Nanoparticles Observed by In†Situ IR Spectroscopy.

The sluggish kinetics of oxygen reduction to water remains a significant limitation in the viability of proton-exchange-membrane fuel cells, yet details of the four-electron oxygen reduction reaction remain elusive. Herein, we apply in situ infrared spectroscopy to probe the surface chemistry of a commercial carbon-supported Pt nanoparticle catalyst during oxygen reduction. The IR spectra show potential-dependent appearance of adsorbed superoxide and hydroperoxide intermediates on Pt. This strongly supports an associative pathway for oxygen reduction. Analysis of the adsorbates alongside the catalytic current suggests that another pathway must also be in operation, consistent with a parallel dissociative pathway.

Trimethylphosphine-Assisted Surface Fingerprinting of Metal Oxide Nanoparticle by (31)P Solid-State NMR: A Zinc Oxide Case Study.

Nano metal oxides are becoming widely used in industrial, commercial and personal products (semiconductors, optics, solar cells, catalysts, paints, cosmetics, sun-cream lotions, etc.). However, the relationship of surface features (exposed planes, defects and chemical functionalities) with physiochemical properties is not well studied primarily due to lack of a simple technique for their characterization. In this study, solid state (31)P MAS NMR is used to map surfaces on various ZnO samples with the assistance of trimethylphosphine (TMP) as a chemical probe. As similar to XRD giving structural information on a crystal, it is demonstrated that this new surface-fingerprint technique not only provides qualitative (chemical shift) but also quantitative (peak intensity) information on the concentration and distribution of cations and anions, oxygen vacancies and hydroxyl groups on various facets from a single deconvoluted (31)P NMR spectrum. On the basis of this technique, a new mechanism for photocatalytic •OH radical generation from direct surface-OH oxidation is revealed, which has important implications regarding the safety of using nano oxides in personal care products.

Synchrotron-Based Infrared Microanalysis of Biological Redox Processes under Electrochemical Control.

We describe a method for addressing redox enzymes adsorbed on a carbon electrode using synchrotron infrared microspectroscopy combined with protein film electrochemistry. Redox enzymes have high turnover frequencies, typically 10-1000 s(-1), and therefore, fast experimental triggers are needed in order to study subturnover kinetics and identify the involvement of transient species important to their catalytic mechanism. In an electrochemical experiment, this equates to the use of microelectrodes to lower the electrochemical cell constant and enable changes in potential to be applied very rapidly. We use a biological cofactor, flavin mononucleotide, to demonstrate the power of synchrotron infrared microspectroscopy relative to conventional infrared methods and show that vibrational spectra with good signal-to-noise ratios can be collected for adsorbed species with low surface coverages on microelectrodes with a geometric area of 25 × 25 µm(2). We then demonstrate the applicability of synchrotron infrared microspectroscopy to adsorbed proteins by reporting potential-induced changes in the flavin mononucleotide active site of a flavoenzyme. The method we describe will allow time-resolved spectroscopic studies of chemical and structural changes at redox sites within a variety of proteins under precise electrochemical control.

Effect of a Standardized Ginger Root Powder Regimen on Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial.

BACKGROUND: There is substantial interest in the role of ginger as an adjuvant therapy for chemotherapy-induced nausea and vomiting (CINV). However, available evidence lacks robust methodology. OBJECTIVE: To assess the effect of adjuvant ginger compared with placebo on chemotherapy-induced nausea-related quality of life (QoL) and CINV-related outcomes. DESIGN: A parallel, double-blind, placebo-controlled randomized trial with 1:1 allocation was conducted. PARTICIPANTS/SETTING: One hundred three chemotherapy-naïve adults scheduled to receive moderately to highly emetogenic chemotherapy at two hospitals in Australia were enrolled and analyzed. INTERVENTION: Four standardized ginger capsules (totaling 84 mg/day active gingerols/shogaols), or placebo, were administered commencing the day of chemotherapy and continuing for 5 days for chemotherapy cycles 1 through 3. MAIN OUTCOME MEASURES: The primary outcome was chemotherapy-induced nausea-related QoL. Secondary outcomes were vomiting- and CINV-related QoL; anticipatory, acute, and delayed nausea and vomiting; fatigue; nutritional status; depression and anxiety; health-related QoL; and adverse events. STATISTICAL ANALYSES PERFORMED: Intention-to-treat analysis was performed. Mixed analysis of variance with repeated measures determined differences between groups. The null hypothesis was no difference between groups. After applying a Bonferroni multiple testing correction, evidence against the null hypothesis was considered at P= 0.003. RESULTS: One hundred three participants (ginger: n = 52; placebo: n = 51) were enrolled and analyzed. There was clinically relevant evidence against the null hypothesis, favoring ginger, in change scores for nausea-related QoL (F[df] = 9.34[1,101]; P = 0.003; partial η2 = 0.09), overall CINV-related QoL (F[df] = 12.26[1,101]; P < 0.001; partial η2 = 0.11), delayed nausea severity (F[df] = 9.46[1,101]; P = 0.003; partial η2 = 0.09), and fatigue (F[df] = 10.11[1,101]; P = 0.002; partial η2 = 0.09). There was a clinically meaningful lower incidence of delayed nausea and vomiting in the ginger group at Cycle 2 (53% vs 75%; P = 0.020 and 4% vs 27%; P = 0.001, respectively) and Cycle 3 (49% vs 79%; P = 0.002 and 2% vs 23%; P = 0.001, respectively). There was a clinically meaningful lower incidence of malnutrition in the ginger group at Cycle 3 (18% vs. 41%; P = 0.032) and in change scores for Patient-Generated Subjective Global Assessment (F[df)] = 4.32[1,100]; P = 0.040; partial η2 = 0.04). Change scores between groups favored ginger for vomiting-related QoL and number of vomiting episodes; however, findings were not clinically meaningful. There was no effect of ginger on anticipatory or acute CINV, health-related QoL, anxiety, or depression. No serious adverse events were reported. CONCLUSIONS: Ginger supplementation was a safe adjuvant to antiemetic medications for CINV that enhanced QoL during chemotherapy treatment. Future trials are needed to examine dose-dependent responses to verify optimal dosing regimens.

Lithium salts as "redox active" p-type dopants for organic semiconductors and their impact in solid-state dye-sensitized solar cells.

Lithium salts have been shown to dramatically increase the conductivity in a broad range of polymeric and small molecule organic semiconductors (OSs). Here we demonstrate and identify the mechanism by which Li(+) p-dopes OSs in the presence of oxygen. After we established the lithium doping mechanism, we re-evaluate the role of lithium bis(trifluoromethylsulfonyl)-imide (Li-TFSI) in 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenyl-amine)9,9'-Spirobifluorene (Spiro-OMeTAD) based solid-state dye-sensitized solar cells (ss-DSSCs). The doping mechanism consumes Li(+) during the device operation, which poses a problem, since the lithium salt is required at the dye-sensitized heterojunction to enhance charge generation. This compromise highlights that new additives are required to maximize the performance and the long-term stability of ss-DSSCs.

Multiscale Electrochemistry of Lithium Manganese Oxide (LiMn2O4): From Single Particles to Ensembles and Degrees of Electrolyte Wetting.

Scanning electrochemical cell microscopy (SECCM) facilitates single particle measurements of battery materials using voltammetry at fast scan rates (1 V s-1), providing detailed insight into intrinsic particle kinetics, otherwise obscured by matrix effects. Here, we elucidate the electrochemistry of lithium manganese oxide (LiMn2O4) particles, using a series of SECCM probes of graded size to determine the evolution of electrochemical characteristics from the single particle to ensemble level. Nanometer scale control over the SECCM meniscus cell position and height further allows the study of variable particle/substrate electrolyte wetting, including comparison of fully wetted particles (where contact is also made with the underlying glassy carbon substrate electrode) vs partly wetted particles. We find ensembles of LiMn2O4 particles show voltammograms with much larger peak separations than those of single particles. In addition, if the SECCM meniscus is brought into contact with the substrate electrode, such that the particle-support contact changes from dry to wet, a further dramatic increase in peak separation is observed. Finite element method modeling of the system reveals the importance of finite electronic conductivity of the particles, contact resistance, surface kinetics, particle size, and contact area with the electrode surface in determining the voltammetric waveshape at fast scan rates, while the responses are relatively insensitive to Li+ diffusion coefficients over a range of typical values. The simulation results explain the variability in voltammetric responses seen at the single particle level and reveal some of the key factors responsible for the evolution of the response, from ensemble, contact, and wetting perspectives. The variables and considerations explored herein are applicable to any single entity (nanoscale) electrochemical study involving low conductivity materials and should serve as a useful guide for further investigations of this type. Overall, this study highlights the potential of multiscale measurements, where wetting, electronic contact, and ionic contact can be varied independently, to inform the design of practical composite electrodes.