bluuebunny/crossref_metadata_2025 huggingface dataset:
Life Time Performance Characterization of Solid Oxide Electrolysis Cells for Hydrogen Production
Authors: Sun Xiufu , Chen Ming , Liu Yi-Lin , Hendriksen Peter Vang
Published: July 2015

Solid oxide electrolysis cells (SOECs) offer a promising technological solution for efficient energy conversion and production of hydrogen or syngas. The commercialization of the SOEC technology can be promoted if SOECs can be operated at high current density with stable performance over ~5 years. In this work, long-term durability of Ni/yttria stabilized zirconia (YSZ) supported planar SOECs was investigated at 800 oC for electrolysis of steam at different current densities from 0 to -1.25 A/cm2. The SOEC cells are able to be operated at current density up to ~-1 A/cm2, with a predicted life time of 2 - 3 years (continuous operation, setting 1.5 V as the upper voltage defining “end of life”). The results provide technological input to future design of electrolysis plants for hydrogen production.
Assessment of Pressure Effects on High Temperature Steam Electrolysis Based on Solid Oxide Technology
Authors: Bernadet Lucile , Gousseau Georges , Chatroux André , Laurencin Jérôme , Mauvy Fabrice , Reytier Magali
Published: July 2015

To manage the grid with renewable electrical sources, hydrogen chains have to be considered. However, hydrogen must be pressurized before being used or stored. Why not performing the High Temperature Steam Electrolysis (HTSE) step directly under pressure? An experimental and modelling approach has been adopted in order to better understand the basic underlying mechanisms of pressurized steam electrolysis operation. Experiments were carried on two different single commercial cathode-supported Solid Oxide Electrolysis Cells (SOEC) at 800°C in the pressure range of 1 to 10 bars. According to the i-V curves, the Open Cell Voltage increases with increasing the pressure. Nevertheless, the limiting current density increases because of a better gas diffusion in through the thick porous cermet support, meaning that the hydrogen production can be improved depending on the voltage. The model, which has been calibrated on the experimental i-V curves recorded at the atmospheric conditions, has been validated for the pressurized operation.
Electrochemical Characterization of Ni/Y2O3-ZrO2 Hydrogen Electrode for Water Splitting in Solid Oxide Electrolysis Cells
Authors: Pan Weiping , Chen Kongfa , Ai Na , Lü Zhe , Jiang San Ping
Published: July 2015

Ni/Y2O3 stabilized ZrO2 (Ni/YSZ) cermet is a widely used hydrogen electrode for solid oxide fuel cells (SOECs), but detailed studies regarding the water splitting processes are scarce. Here we report the preliminary results on the variation of electrocatalytic activity of Ni/YSZ hydrogen electrodes as a function of operating temperature, water concentration and dc bias. The electrode activity for the water splitting reaction is strongly influenced by varying the water concentration and dc bias. The electrochemical performance for the water splitting reaction decreases with the increase of water concentration. The electrode polarization resistance increases gradually with the increase of dc bias regardless of the H2O content. The decrease of activity is particularly pronounced in the low frequency impedance process related to the H2O dissociative adsorption and diffusion processes. This study clearly demonstrates the reaction mechanism and kinetics of the H2O dissociation reaction.
Steam Electrolysis by Proton-Conducting Solid Oxide Electrolysis Cells (SOECs) with Chemically Stable BaZrO3-Based Electrolytes
Authors: Bi Lei , Traversa Enrico
Published: July 2015

BaZrO3-based material was applied as the electrolyte for proton-conducting solid oxide fuel cells (SOECs). Compared with the instability of BaCeO3-based proton-conductors, BaZrO3-based material could be a more promising candidate for proton-conducting SOECs due to its excellent chemical stability under H2O conditions, but few reports on this aspect has been made due to the processing difficulty for BaZrO3. Our recent pioneer work has demonstrated the feasibility of using BaZrO3-based electrolyte for SOECs and the fabricated cell achieves relatively high cell performance, which is comparable or even higher than that for BaCeO3-based SOECs and offers better chemical stability. Cell performance can be further improved by tailoring the electrolyte and electrode.
Steam and Co-Electrolysis Sensitivity Analysis on Ni-YSZ Supported Cells
Authors: Rinaldi Giorgio , Diethelm Stefan , Van herle Jan
Published: July 2015

The present paper investigates the variation in performances in steam electrolysis and co-electrolysis of steam/CO2 on SOEC single cells.In electrolysis mode, a sensitivity analysis was performed looking in particular at the effects of temperature (750°C and 800°C) and inlet gas flows (from 100 to 200 Nml/min) on the performances. I-V characterization and EIS measurements at different current densities were carried out for each sequence. As expected, the increase of temperature has a positive impact on the performances, while the change of fuel flow slightly affects them. In co-electrolysis mode CO2 and H2O content was varied, keeping constant the total molar flow and the hydrogen fraction. Resulting plots demonstrate different ongoing processes favored at high current densities and high inlet CO2 molar fraction. In particular, reverse water-gas-shift reaction plays an important role on the overall balance of the gas species, and it directly depends on temperature and inlet fuel composition.
Development of Medium-Temperature Solid Oxide Fuel Cells and CO2 and H2O Co-Electrolysis Cells in Estonia
Authors: Lust Enn , Tamm Kadi , Nurk Gunnar , Möller P , Kivi Indrek , Kanarbik Rait , Heinsaar Alar
Published: July 2015

Estonian solid oxide fuel cell (SOFC) and solid oxide electrolysis cell (SOEC) programs started in 2001 and 2012, respectively. Solid oxide fuel and co-electrolysis cell single cells based on Ni-Ce0.9Gd0.1O2-
d or Ni-Zr0.92Y0.08O2-
d supporting anodes/cathodes, bi-layered Zr0.92Y0.08O2-
d | Ce0.9Gd0.1O2-
d or Zr0.94Sc0.06O2-
d | Ce0.9Gd0.1O2-
d electrolytes and micro-meso-porous La0.6Sr0.4CoO3-
d, Gd0.6Sr0.4CoO3-
d or Pr0.6Sr0.4CoO3-
d cathodes/anodes, respectively, prepared from nano-microporous powders at different sintering temperatures and pore former additions in the raw cathode and anode pastes have been studied. Ni-free anodes/cathodes have been also synthesized and tested at temperatures from 550 to 800 °C. Different physical (FIB-TOF-SIMS, XRD, high-temperature XRD under electrochemical working conditions, FIB-SEM-EDX, AFM, gas chromatography-mass spectrometry, BET) and electrochemical (cyclic voltammetry, chronoamperometry and electrochemical impedance) methods have been applied. Influence of the anode and cathode porosity, depending on the electrode preparation methods, and also of the bi-layered electrolyte properties (chemical composition, thickness, etc.) on the power density of the SOFC and SOEC single cells has been shown and discussed. The synchrotron radiation based X-ray absorption spectroscopy under electrochemical polarization and different fuel feeding and temperature cyclation conditions has been applied for chemical analysis of surface composition of the SOFC anodes.
Electrochemical Impedance Spectroscopy Data from Solid Oxide Cells Undergoing Co-Electrolysis: The Influence of Rig Inductance
Authors: Thompson Alison R , Call Ann V , Cumming Denis J , Sinclair Derek C , Elder Rachael H
Published: July 2015

High temperature solid oxide cells (SOCs) are used for co-electrolysis of carbon dioxide and steam for the production of synthetic fuels. SOC rate-limiting processes can be investigated using Electrochemical Impedance Spectroscopy (EIS), but first, test rig contributions must be subtracted: inductance in particular. Here we illustrate the effect of inductance correction L on interpretation methods, including: impedance Z* and electric modulus M* formalisms, the Analysis of Differences in Impedance Spectra (ADIS) and the determination of Distribution of Relaxation Times (DRT). For inductances in the range ~10-7 H, results were sensitive to small changes in L, giving a significant change in high frequency Z* and M* data. This causes underestimation of the SOC polarisation resistance. ADIS results are less affected, due to the nature of the subtraction method, whereas DRT is highly sensitive to inductance, hence care must be taken to optimise inductance correction, to obtain accurate results.
Carbon Deposition during CO2 Electrolysis in Ni-Based Solid-Oxide-Cell Electrodes
Authors: Skafte Theis Løye , Graves Christopher , Blennow Peter , Hjelm Johan
Published: July 2015

The carbon formation threshold in an operating cell was investigated during electrolysis of an idealized reactant atmosphere of CO and CO2. The electrolysis current was gradually increased in steps until the cell voltage spontaneously increased, thereby indicating cell degradation and possibly the onset of carbon deposition. The outlet gas composition at each current step was estimated based on the inlet gas composition and the reactant conversion using Faraday's law. The increase in voltage was observed at lower outlet pCO/pCO2 ratios than that corresponding to the expected thermodynamic threshold for carbon formation. The degradation observed was related to the fuel electrode, as confirmed by electrochemical impedance spectroscopy. Mitigation of the degradation mechanism was attempted by infiltrating gadolinium doped ceria. The onset of carbon deposition was largely unaffected, but the polarization resistance of the electrode during electrolysis was significantly decreased.
Carbon Tolerant Electrodes for SOFC and Reversible SOFC (RSOFC) Cells Operating on Carbon Containing Fuels
Authors: Niakolas Dimitrios K. , Neofytides Charalampos , Neophytides Stylianos G. , Tsiplakides Dimitrios , Papazisi Kalliopi-Maria , Balomenou Stella
Published: July 2015

A challenging barrier for the broad, successful implementation of SOFC/SOEC technologies, remains the long term stability by the effective control and minimization of degradation resulting from carbon built up. A class of Au-modified commercially available NiO/GDC and NiO/YSZ cermet powders has been developed and studied for their performance and tolerance to carbon deposition, employed as SOFC anodes for CH4 steam reforming, as well as bi-functional electrodes in a Regenerative SOFC operating on the CO2 cycle (SOEC: CO2 electrolysis, SOFC: power generation through the electrochemical reaction of CO and oxygen). In-situ HT-XRD tests revealed that the presence of Au, in an optimum nominal loading of 3wt%, affects the Ni crystal phase and has a significant positive effect in inhibiting carbon deposition. Cell testing in the temperature range of 800-1000° under carbon forming conditions, showed promising stable performance of the modified electrodes.
Effects of Current Collector Materials on Performances of Micro-Tubular Solid Oxide Electrolysers for Splitting CO2
Authors: Kleiminger Lisa , Kelsall Geoff H. , Li Tao , Li Kang
Published: July 2015

Specific surface areas of micro-tubular solid oxide electrolysers (MT-SOEs) increase with the reciprocal of their lumen diameters. However, this benefit over planar counterparts may be offset by difficulties in fabricating effective current collectors for < 1 mm diameter inner electrodes, causing significant potential losses, decreasing their performance. Hence, the effects were investigated of different current collector materials for the inner cathodes of such SOEs for splitting CO2. Ohmic area-specific resistances were lowest for silver wire-based compared to nickel wire-based current collectors, due to silver’s higher electronic conductivity. However, silver’s lower mechanical strength required addition of silver paste for effective connections, but the paste interfered with the electrode process, increasing the area-specific electrode polarization at 1.5 V by > 300% at 700 and 800 °C. Microstructural analysis suggested the silver paste caused partial blockage of surface pores. MT-SOEs with only nickel wire current collectors achieved 1 A cm-2 at 1.5 V.
Development of Electrochemical Methanation Reactor with Co-Electrolysis of Humidified CO2
Authors: Yamaguchi Toshiaki , Shimada Hiroyuki , Honda U , Kishimoto Haruo , Ishiyama Tomohiro , Fujishiro Yoshinobu
Published: July 2015

We have been developing a tubular electrochemical cell composed of Ni-cermet support/YSZ/GDC/LSCF-GDC or Ni-cermet support/GDC/LSCF-GDC in order to synthesize energy-carrier chemicals (methane etc.) via co-electrolysis of H2O-CO2 mixed gas. In this report, we will show effects of (1) the cell fabrication processes, (2) the cell microstructure and (3) methanation ability of two types of SOECs at 400 ºC.
Methane Synthesis Characteristics of H2O/CO2 Co-Electrolysis in Tubular Solid Oxide Electrolysis Cells
Authors: Luo Yu , Li Wenying , Shi Yixiang , Ye Xiaofeng , Wang Shaorong , Cai Ningsheng
Published: July 2015

Producing methane by H2O/CO2 co-electrolysis through solid oxide electrolysis cell (SOEC) is a promising method to store unstable renewable power and reduce CO2 emission simultaneously. In this paper, CH4 synthesis characteristics in tubular SOEC (TSOEC) is studied in the temperature range of 550-650oC by combining experiment and simulation. Experiments demonstrates adding H2 increases the CH4 production ratio from 0 to 4.01% at 600oC. Besides, electricity significantly promotes CH4 production, especially when H2 is added. The voltage of 1.5 V just increases CH4 production ratio by <0.04% in the absence of H2. But when 20% H2 is fed in cathode, a voltage of 1.5 V can increase CH4 production ratio by 3-4%. Finally, chemical reactions, thermal distribution and optimal operating condition are simulated by a well validated thermal model. A reasonable thermal distribution created by operating TSOEC in counter-flow mode and lower inlet steam partial pressure can dramatically improve CH4 production.
Fabrication and Performance Evaluation of Solid Oxide Electrolysis Cell Integrated with Metal Interconnect by Joining Process
Authors: Yoo Young-Sung , Choi Mihwa , Yang Seugran , Jin Hyun-Jin , Park Min-Ah , Kim Eui-Hyun
Published: July 2015

Fuel-electrode supported solid oxide cell (SOC) integrated with metal interconnect was fabricated and its electrochemical performance was investigated under both fuel cell and coelectrolysis (steam and CO2) mode at 750~850°C. The single cell performances under fuel cell (FC) and co-electrolysis (Co-EC) modes are compared with those of conventional fuel-electrode supported SOC by analyzing AC impedance spectra and product gas composition with gas chromatography (GC). Fairly stable long-term performance in co-electrolysis mode under the constant current density of 800 mA/cm2 is obtained at 800°C using wet and carbon dioxide (CO2) mixed gas condition.
9000 Hours Operation of a 25 Solid Oxide Cells Stack in Steam Electrolysis Mode
Authors: Corre Gaël , Brisse Annabelle
Published: July 2015

The operation of 25 solid oxide cells stacks in steam electrolysis mode over 9000 hours is reported. The stack has been operated at current densities of 0.57 and 0.72 A/cm2, using a 50% steam conversion, in the 750-780°C temperature range. Performance degradation rates of 2.30%/ kh are reported, with some non-homogeneity in the stack repeat units behavior observed. Stack repeat units located at the bottom of the stack feature degradation rates below 2%/kh. The possibility to use the operating temperature as a buffer to counter the performance degradation is highlighted. The stack performance was not affected by incidents that occurred during the test.
Performance and Degradation of Solid Oxide Electrolysis Cells in Stack
Authors: Fang Qingping , Blum Ludger , Menzler Norbert H.
Published: July 2015

A Solid Oxide Electrolysis (SOE) short stack consisting of anode-supported cells (ASCs in fuel cell mode) was assembled in JÜLICH’s F10-design. ASCs are based on Ni/8YSZ (8 mol-% yttria-stabilized zirconia) with an LSCF air electrode (La0.58Sr0.4Co0.2Fe0.8O3-δ) and 8YSZ electrolyte. A gadolinium-doped ceria (GDC) (Ce0.8Gd0.2O1.9) barrier layer was deposited between 8YSZ and LSCF by means of physical vapor deposition (PVD). The stack was mainly characterized in a furnace environment in both fuel cell and electrolysis modes, with 50% humidified H2 at 700 and 800 °C. An endothermic long-term electrolysis operation was carried out at 800 °C with a current density of -0.5 Acm-2 and steam conversion rate of 50%. After 2300 h of operation, the stack showed an average voltage degradation rate of 0.7%/kh. Electrochemical impedance spectroscopy (EIS) and analysis of the distribution function of relaxation times (DRT) showed that the degradation was primarily due to the increase in ohmic resistance.
Development of a Tubular Solid Oxide Cell for Co-Electrolysis of H2O and CO2 for Syngas Production
Authors: Tanaka Yohei , Kato Tohru , Nagata Susumu , Negishi Akira
Published: July 2015

A tubular Ni-8YSZ/SSZ/GDC/SSC (Strontium-doped Samarium Cobaltite) cell was prepared for high temperature co-electrolysis of H2O and CO2. This cell enhanced a current density at 750ºC by two-fold compared to a previous type of our cell. Measurements of voltage-current density (V-J) curves revealed that 0.55 A/cm2 was attained at 750ºC and a thermoneutral voltage (1.33 V). The V-J curves were not influenced by change of H2/C (= 2-4) or flow-rate ratio (= 1-4) of positive electrode to negative one. In addition, V-J curve measurement at constant 80% utilization of H2O and CO2 clarified that 0.41 A/cm2 was achieved at the thermoneutral voltage and 750ºC. It was observed by precise gas analyses that gas composition changed in proportion to J and utilization of H2O and CO2. Simultaneously, cross gas-leakages were detected from one electrode to the other.
Possibility of Methane Production from Steam and Carbon Dioxide by Using Solid Oxide Electrolysis Cells
Authors: Kato Tohru , Nagata Susumu , Honda Takeo , Negishi Akira , Tanaka Yohei , Momma Akihiko
Published: July 2015

Performances of an SOEC methane production system and a conventional methane production system consisting of a water electrolyzer and a methanator are investigated. At first operating condition at which each system can be operate without carbon deposition is estimated by equilibrium calculation. Next, under obtained operating condition, dependences of reactant composition and system efficiency of the each system on operating conditions, are calculated and compared with each other. From the result of the analysis, advantage of SOEC methane production system is clarified.
A Packaged and Efficient SOEC System Demonstrator
Authors: Chatroux André , Reytier Magali , Di Iorio Stéphane , Bernard Charlotte , Roux Guilhem , Petitjean Marie , Mougin Julie
Published: July 2015

High Temperature Steam Electrolysis, based on solid oxide electrolysis cells (SOEC) is a promising way to produce hydrogen with high efficiencies. The balance of plant (BoP) is a key point for that technology because the heat management of the system has to be optimized to effectively reach the expected high electrical efficiency. For that purpose, the CEA-LITEN has designed and tested a packaged SOEC system demonstrator. It is based on a single 25-cell-stack and the required auxiliaries, including a steam generator at 150°C and high temperature exchangers to superheat the inlet steam flow thanks to the heat recovered in the exhaust gases. At 700°C, the system produces 1.2 Nm3/h of H2 with a total electrical consumption of 3.9 kWh/Nm3, achieving 91% of efficiency, this efficiency corresponding to the higher heating value (HHV) of the produced hydrogen vs the electrical consumption of the system.
Influence of Ni-YSZ Electrode Thickness on the Behaviour of Commercial Solid Oxide Electrolysis Cells by Mean of Electrochemical Impedance Spectroscopy
Authors: Nechache Aziz , Cassir Michel , Ringuede Armelle
Published: July 2015

Electrochemical Impedance Spectroscopy (EIS) is used here in a two-electrode configuration to acquire a deeper comprehension of high-temperature solid oxide electrolysis cells (SOEC), distinguishing different phenomena related to electrochemical and degradation processes. Such approach is applicable to any kind of electrochemical cell. In the present study, chronopotentiometry and EIS are combined in order to analyze the influence of Ni-YSZ electrode thickness on the behavior of two commercial SOECs.
Understanding of CO2 Electrochemical Reduction Reaction Process via High Temperature Solid Oxide Electrolysers
Authors: Yue Xiangling , Irvine John T. S.
Published: July 2015

The CO2 electrochemical reduction via SOEC was studied at a range of cathode materials in various operational conditions. The influences of the fuel gas composition, operating potential and temperature on cathode behavior were discussed and compared on different cathodes. The dissociative adsorption and surface diffusion of active species from CO2 reduction reaction was found to contributed dominantly to the LSCM-based cathode working in CO2-CO mixtures. Efforts were also made to obtain a high performance and durable cathode for high temperature CO2 electrolyser by employing a gradient LSCM-YSZ cathode and by adopting wet impregnation in cathode preparation. The latter was to more effective in enhancing the cathode electro-catalytic activity. A competitive cathode to Ni-YSZ cermet was fabricated by infiltrating 0.5wt% Pd and GDC into porous LSCM and YSZ layers.
Systematic Parameter Study on the Influence of Humidification and Current Density on SOEC Degradation
Authors: Hoerlein Michael P. , Schiller Guenter , Tietz Frank , Friedrich K. Andreas
Published: July 2015

Within a joint project of German Aerospace Center (DLR) and Forschungszentrum JÜLICH solid oxide fuel cells have been electrochemically characterized and the influence of the current density and fuel gas humidity on the long-term stability of electrolysis operation have been investigated. In order to observe the time- dependent change in electrochemical behaviour of the fuel electrode supported cells, in-situ analysis with a special focus on impedance spectroscopy was utilized. DRT-analysis was applied to validate assumptions made for equivalent circuit fitting and to improve fitting quality and reliability. Four rate limiting processes (electrolyte, cathode, anode and mass transport) could be separated and it was possible to track their development during the 1000 h experiments, showing their individual degradation behaviour under the applied operating conditions. This information was used for a dependence study, while additionally post mortem analysis methods were applied.
Challenges of Solid Oxide Electrolysis for Production of Fuel and Oxygen from Mars Atmospheric CO2
Authors: Hartvigsen Joseph J , Elangovan S , Larsen Dennis , Elwell Jessica , Bokil Mukul , Frost Lyman J , Clark Laurie M.
Published: July 2015

A new field of application for solid oxide electrolysis producing fuels from CO2 is emerging in the area of human exploration of Mars. The Martian atmosphere is 96% CO2, making it a prime resource for extraction of oxygen that will be needed by human explorers and for production of the fuel that will be needed for the ascent vehicle to return them to earth. The fundamental operating principles and materials of the Mars in-situ resource utilization (ISRU) application are no different than the hydrogen and synfuel applications developed in past decades. However there are circumstances of the ISRU application that place challenging constraints on the design and performance that have not been previously encountered in our SOEC development efforts. These issues are outlined and the approaches to address them are presented. Ceramatec is designing and building the SOEC (aka SOXE) stack for the MOXIE instrument on the Mars 2020 mission.
Sleep, death, and the heart
Authors: Mansukhani Meghna P. , Wang Shihan , Somers Virend K.
Published: July 2015

Obstructive and central sleep apnea have been associated with increased risk of adverse cardiovascular events and mortality. Sympathetic dysregulation occurring as a result of the respiratory disturbance is thought to play a role in this increased risk. Sleep apnea increases the risk of arrhythmias, myocardial ischemia/infarction, stroke, and heart failure, all of which may increase mortality risk. A higher incidence of nocturnal arrhythmias, cardiac ischemia, and sudden death has been noted in subjects with sleep-disordered breathing (SDB). In this review, the association between SDB and each of these conditions is discussed, as well as the potential mechanisms underlying these risks and the effects of treatment of SDB. Particular emphasis is placed on the relationship between SDB and nocturnal atrial and ventricular arrhythmias, myocardial ischemia/infarction and sudden death.
Passive leg movement-induced vasodilation in women: the impact of age
Authors: Groot H. Jonathan , Rossman Matthew J. , Trinity Joel D. , Layec Gwenael , Ives Stephen J. , Richardson Russell S.
Published: July 2015

Passive leg movement (PLM), an assessment of predominantly nitric oxide-dependent vasodilation, is decreased with age and cannot be augmented by posture-induced increases in femoral perfusion pressure in older men. However, this novel method of assessing vascular function has yet to be used to evaluate alterations in nitric oxide-dependent vasodilation with age in females. PLM was performed in 10 young (20 ± 1 yr) and 10 old (73 ± 2 yr) women in both the supine and upright-seated postures, whereas central and peripheral hemodynamic measurements were acquired second by second using noninvasive techniques (finger photoplethysmography and Doppler ultrasound, respectively). The heart rate response to PLM was attenuated in the old compared with the young in both the supine (young, 10 ± 1; and old, 5 ± 1 beats/min; P < 0.05) and upright-seated posture (young, 10 ± 2; and old, 5 ± 1 beats/min; P < 0.05), leading to a blunted cardiac output response in the old in the upright-seated posture (young, 1.0 ± 0.2; and old, 0.3 ± 0.1 l/min; P < 0.05). The PLM-induced peak change in leg vascular conductance was lower in the old compared with the young in both postures (young supine, 5.7 ± 0.5; old supine, 2.6 ± 0.3; young upright, 9.2 ± 0.7; and old upright, 2.2 ± 0.4 ml·min−1·mmHg−1; P < 0.05) and was significantly augmented by the upright-seated posture in the young only, revealing a vasodilatory reserve capacity in the young (3.5 ± 0.6 ml·min−1·mmHg−1, P < 0.05) that was absent in the old (−0.5 ± 0.3 ml·min−1·mmHg−1, P = 0.18). These data support previous literature demonstrating attenuated PLM-induced vasodilation with age and extend these findings to include the female population, thus bolstering the utility of PLM as a novel assessment of vascular function across the life span in humans.
Lost after translation: insights from pulmonary surfactant for understanding the role of alveolar epithelial dysfunction and cellular quality control in fibrotic lung disease
Authors: Mulugeta Surafel , Nureki Shin-Ichi , Beers Michael F.
Published: July 2015

Dating back nearly 35 years ago to the Witschi hypothesis, epithelial cell dysfunction and abnormal wound healing have reemerged as central concepts in the pathophysiology of idiopathic pulmonary fibrosis (IPF) in adults and in interstitial lung disease in children. Alveolar type 2 (AT2) cells represent a metabolically active compartment in the distal air spaces responsible for pulmonary surfactant biosynthesis and function as a progenitor population required for maintenance of alveolar integrity. Rare mutations in surfactant system components have provided new clues to understanding broader questions regarding the role of AT2 cell dysfunction in the pathophysiology of fibrotic lung diseases. Drawing on data generated from a variety of model systems expressing disease-related surfactant component mutations [surfactant proteins A and C (SP-A and SP-C); the lipid transporter ABCA3], this review will examine the concept of epithelial dysfunction in fibrotic lung disease, provide an update on AT2 cell and surfactant biology, summarize cellular responses to mutant surfactant components [including endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and intrinsic apoptosis], and examine quality control pathways (unfolded protein response, the ubiquitin-proteasome system, macroautophagy) that can be utilized to restore AT2 homeostasis. This integrated response and its derangement will be placed in the context of cell stress and quality control signatures found in patients with familial or sporadic IPF as well as non-surfactant-related AT2 cell dysfunction syndromes associated with a fibrotic lung phenotype. Finally, the need for targeted therapeutic strategies for pulmonary fibrosis that address epithelial ER stress, its downstream signaling, and cell quality control are discussed.
Defining Effective Combinations of Immune Checkpoint Blockade and Oncolytic Virotherapy
Authors: Rojas Juan J. , Sampath Padma , Hou Weizhou , Thorne Steve H.
Published: July 2015

Purpose: Recent data from randomized clinical trials with oncolytic viral therapies and with cancer immunotherapies have finally recapitulated the promise these platforms demonstrated in preclinical models. Perhaps the greatest advance with oncolytic virotherapy has been the appreciation of the importance of activation of the immune response in therapeutic activity. Meanwhile, the understanding that blockade of immune checkpoints (with antibodies that block the binding of PD1 to PDL1 or CTLA4 to B7-2) is critical for an effective antitumor immune response has revitalized the field of immunotherapy. The combination of immune activation using an oncolytic virus and blockade of immune checkpoints is therefore a logical next step.

Experimental Design: Here, we explore such combinations and demonstrate their potential to produce enhanced responses in mouse tumor models. Different combinations and regimens were explored in immunocompetent mouse models of renal and colorectal cancer. Bioluminescence imaging and immune assays were used to determine the mechanisms mediating synergistic or antagonistic combinations.

Results: Interaction between immune checkpoint inhibitors and oncolytic virotherapy was found to be complex, with correct selection of viral strain, antibody, and timing of the combination being critical for synergistic effects. Indeed, some combinations produced antagonistic effects and loss of therapeutic activity. A period of oncolytic viral replication and directed targeting of the immune response against the tumor were required for the most beneficial effects, with CD8+ and NK, but not CD4+ cells mediating the effects.

Conclusions: These considerations will be critical in the design of the inevitable clinical translation of these combination approaches. Clin Cancer Res; 21(24); 5543–51. ©2015 AACR.

See related commentary by Slaney and Darcy, p. 5417
A Phase I Trial of Combined Ridaforolimus and MK-2206 in Patients with Advanced Malignancies
Authors: Gupta Shilpa , Argilés Guillem , Munster Pamela N. , Hollebecque Antoine , Dajani Olav , Cheng Jonathan D. , Wang Ruixue , Swift Ann , Tosolini Alessandra , Piha-Paul Sarina A.
Published: July 2015

Purpose: The PI3K/Akt/mTOR signaling pathway is aberrantly activated in many cancers. Combining ridaforolimus, an mTOR inhibitor, with MK-2206, an Akt inhibitor, may more completely block the PI3K pathway and inhibit tumor growth.

Experimental Design: This phase I study assessed dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of oral ridaforolimus plus oral MK-2206 in patients with advanced solid tumors. Efficacy was evaluated in patients with biomarker-identified estrogen receptor–positive breast cancer (low RAS gene signature and high Ki67 index) or castration-resistant prostate cancer (PTEN deficiency) with PI3K pathway addiction.

Results: Thirty-five patients were enrolled: 11 patients in part A (three breast cancer) and 24 biomarker-eligible patients in part B (16 breast cancer, eight prostate cancer). One patient with breast cancer from part A was also found to be biomarker-eligible when tested after she had clinical response. The MTD was 10 mg/d ridaforolimus 5 d/wk + 90 mg/wk MK-2206; 1 of 17 patients experienced DLT (grade 3 rash) at this dose. The most common adverse events at MTD were rash (44.4%), stomatitis (38.9%), diarrhea (27.8%), and decreased appetite (27.8%). By investigator assessment, 2 of 16 (12.5%) evaluable patients with breast cancer had partial response; by central assessment, 2 of 14 (14.3%) evaluable patients had complete response. Two patients had durable stable disease (SD) for 416 and 285 days, respectively. No patients with prostate cancer responded; one patient had SD for ≥6 months.

Conclusions: Combination ridaforolimus and MK-2206 showed promising activity and good tolerability in heavily pretreated patients with hormone-positive and -negative breast cancer exhibiting PI3K pathway dependence. Clin Cancer Res; 21(23); 5235–44. ©2015 AACR.
Analysis of Molecular Markers by Anatomic Tumor Site in Stage III Colon Carcinomas from Adjuvant Chemotherapy Trial NCCTG N0147 (Alliance)
Authors: Sinicrope Frank A. , Mahoney Michelle R. , Yoon Harry H. , Smyrk Thomas C. , Thibodeau Stephen N. , Goldberg Richard M. , Nelson Garth D. , Sargent Daniel J. , Alberts Steven R.
Published: July 2015

Purpose: To determine the frequency and prognostic association of molecular markers by anatomic tumor site in patients with stage III colon carcinomas.

Experimental Design: In a randomized trial of adjuvant FOLFOX ± cetuximab, BRAFV600E and KRAS (exon 2) mutations and DNA mismatch repair (MMR) proteins were analyzed in tumors (N = 3,018) in relationship to tumor location, including subsite. Cox models were used to assess clinical outcome, including overall survival (OS).

Results: KRAS codon 12 mutations were most frequent at the splenic flexure and cecum; codon 13 mutations were evenly distributed. BRAF mutation frequency sharply increased from transverse colon to cecum in parallel with deficient (d) MMR. Nonmutated BRAF and KRAS tumors progressively decreased from sigmoid to transverse (all P < 0.0001). Significantly, poorer OS was found for mutant KRAS in distal [HR, 1.98; 95% confidence interval (CI), 1.49–2.63; P < 0.0001] versus proximal (1.25; 95% CI, 0.97–1.60; P = 0.079) cancers. BRAF status and outcome were not significantly associated with tumor site. Proximal versus distal dMMR tumors had significantly better outcome. An interaction test was significant for tumor site by KRAS (Padjusted = 0.043) and MMR (Padjusted = 0.010) for OS. Significant prognostic differences for biomarkers by tumor site were maintained in the FOLFOX arm. Tumor site was independently prognostic with a stepwise improvement from cecum to sigmoid (OS: Padjusted = 0.001).

Conclusions: Mutation in BRAF or KRAS codon 12 was enriched in proximal cancers whereas nonmutated BRAF/KRAS was increased in distal tumors. Significant differences in outcome for KRAS mutations and dMMR were found by tumor site, indicating that their interpretation should occur in the context of tumor location. Clin Cancer Res; 21(23); 5294–304. ©2015 AACR.
A Cluster-Randomized, Controlled Trial of a Simplified Multifaceted Management Program for Individuals at High Cardiovascular Risk (SimCard Trial) in Rural Tibet, China, and Haryana, India
Authors: Tian Maoyi , Ajay Vamadevan S. , Dunzhu Danzeng , Hameed Safraj S. , Li Xian , Liu Zhong , Li Cong , Chen Hao , Cho KaWing , Li Ruilai , Zhao Xingshan , Jindal Devraj , Rawal Ishita , Ali Mohammed K. , Peterson Eric D. , Ji Jiachao , Amarchand Ritvik , Krishnan Anand , Tandon Nikhil , Xu Li-Qun , Wu Yangfeng , Prabhakaran Dorairaj , Yan Lijing L.
Published: July 2015

Background—

In rural areas in China and India, the cardiovascular disease burden is high but economic and healthcare resources are limited. This study (the Simplified Cardiovascular Management Study [SimCard]) aims to develop and evaluate a simplified cardiovascular management program delivered by community health workers with the aid of a smartphone-based electronic decision support system.

Methods and Results—

The SimCard study was a yearlong cluster-randomized, controlled trial conducted in 47 villages (27 in China and 20 in India). Recruited for the study were 2086 individuals with high cardiovascular risk (aged ≥40 years with self-reported history of coronary heart disease, stroke, diabetes mellitus, and/or measured systolic blood pressure ≥160 mm Hg). Participants in the intervention villages were managed by community health workers through an Android-powered app on a monthly basis focusing on 2 medication use and 2 lifestyle modifications. In comparison with the control group, the intervention group had a 25.5% (
P
<0.001) higher net increase in the primary outcome of the proportion of patient-reported antihypertensive medication use pre- and post-intervention. There were also significant differences in certain secondary outcomes: aspirin use (net difference: 17.1%;
P
<0.001) and systolic blood pressure (–2.7 mm Hg;
P
=0.04). However, no significant changes were observed in the lifestyle factors. The intervention was culturally tailored, and country-specific results revealed important differences between the regions.

Conclusions—

The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in resource-poor settings in China and India. Larger trials in more places are needed to ascertain the potential impacts on mortality and morbidity outcomes.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01503814.
Stroke and Bleeding Risk Associated With Antithrombotic Therapy for Patients With Nonvalvular Atrial Fibrillation in Clinical Practice
Authors: An JaeJin , Niu Fang , Lang Daniel T. , Jazdzewski Kristin P. , Le Paul T. , Rashid Nazia , Meissner Brian , Mendes Robert , Dills Diana G. , Aranda Gustavus , Bruno Amanda
Published: July 2015

Background

The quality of antithrombotic therapy for patients with nonvalvular atrial fibrillation during routine medical care is often suboptimal. Evidence linking stroke and bleeding risk with antithrombotic treatment is limited. The purpose of this study was to evaluate the associations between antithrombotic treatment episodes and outcomes.

Methods and Results

A retrospective longitudinal observational cohort study was conducted using patients newly diagnosed with nonvalvular atrial fibrillation with 1 or more stroke risk factors (
CHADS
2
≥1) in Kaiser Permanente Southern California between January 1, 2006 and December 31, 2011. A total of 1782 stroke and systemic embolism (
SE
) and 3528 major bleed events were identified from 23 297 patients during the 60 021 person‐years of follow‐up. The lowest stroke/
SE
rates and major bleed rates were observed in warfarin time in therapeutic range (
TTR
) ≥55% episodes (stroke/
SE
: 0.87 [0.71 to 1.04]; major bleed: 4.91 [4.53 to 5.28] per 100 person‐years), which was similar to the bleed rate in aspirin episodes (4.95 [4.58 to 5.32] per 100 person‐years). The warfarin
TTR
≥55% episodes were associated with a 77% lower risk of stroke/
SE
(relative risk=0.23 [0.18 to 0.28]) compared to never on therapy; and the warfarin
TTR
<55% and on‐aspirin episodes were associated with a 20% lower and with a 26% lower risk of stroke/
SE
compared to never on therapy, respectively. The warfarin
TTR
<55% episodes were associated with nearly double the risk of a major bleed compared to never on therapy (relative risk=1.93 [1.74 to 2.14]).

Conclusions

Continuation of antithrombotic therapy as well as maintaining an adequate level of
TTR
is beneficial to prevent strokes while minimizing bleeding events.
Mobilizing a Market
Authors: Yenkey Christopher B.
Published: July 2015

This study examines how actors from diverse and competing social groups can come to identify as members of a common market rather than as agents of their discrete social groups. Using data on new-investor recruitment into Kenya’s nascent capital market, the Nairobi Securities Exchange, from 2005 through 2008, I identified mechanisms driving social segmentation as well as integration of disparate groups. The empirical context is characterized by weak formal institutions and high levels of inter-ethnic distrust, a novel but productive setting for studying how potential adopters use social identities to resolve uncertainty around expected gains of participating in a new market. Results show that instead of exhibiting blanket influence by homophilous peers, potential investors were positively influenced by profits earned by proximate coethnic peers primarily when their own exposure to corrupt financial organizations was higher but were negatively influenced by the profits of ethnic outsiders when the market was identified with distrusted political rivals. Several mechanisms moderated this pattern of distrust, including inter-ethnic residential and religious integration but especially the use of national language rather than ethnic language advertising campaigns, which reframed the market as a shared social identity. Findings indicate that the negative effects of social segmentation, including the distorting influences of dissimilar peers and environmental factors such as political tensions and distrust in institutions, can be reversed when potential investors learn about new market opportunities from neutral third parties or when policy makers frame such practices in socially neutral language.
Facing Morbid Obesity
Authors: Ricci Maria Anastasia , De Vuono Stefano , Scavizzi Matteo , Gentili Alessandra , Lupattelli Graziana
Published: July 2015

Obesity is a major public health problem, with a prevalence of 10% to 20% in Western Europe. Morbid obesity, characterized by body mass index >40 kg/m2, showed an increased prevalence in the last 30 years. Obesity is associated with reduced economic and social opportunities, reduced quality of life, and is a determinant of several “intermediate risk factors,” leading to an increased mortality and a loss in life expectancy. The rising prevalence of morbid obesity increased the demand for bariatric surgery, also called “metabolic surgery”: after these interventions, there is a decrease in metabolic comorbidities, cardiovascular (CV) risk, and total mortality. In this review, we update the evaluation of morbid obese patients from the physical examination to the metabolic, CV and respiratory assessments in order to correctly stratify the CV risk and provide the best treatment. To obtain these achievements, multidisciplinary work has to be carried out with a team involving several experts with different skills.
Critical appraisal in the practice of laboratory medicine
Authors: Price Christopher P , Christenson Robert H
Published: July 2015

Critical appraisal is a key skill employed across the spectrum of laboratory medicine practice. It underpins the use of information that is relevant, of good quality and is meaningful. Relevance is answering the right question for the right patient at the right time, with quality ensuring provision of the right information. Meaningful is making the right decisions in order to deliver the right outcomes. Critical appraisal is about minimizing the risk of bias or ‘departures from trueness’ in all of the facets of laboratory medicine practice. It can be summarized in four steps: (i) a clear understanding and articulation of the problem being addressed – whether it be an analytical challenge, individual patient care or policymaking; (ii) verifying the methodological approach employed; (iii) assuring the reliability of the results and (iv) ensuring the applicability and implications of the results. Reference is made to a number of checklists that can be used to assist in the process of critical appraisal.
Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry-recommended reference measurement procedure and reference materials for glycated albumin determination
Authors: Takei Izumi , Hoshino Tadao , Tominaga Makoto , Ishibashi Midori , Kuwa Katsuhiko , Umemoto Masao , Tani Wataru , Okahashi Mikiko , Yasukawa Keiko , Kohzuma Takuji , Sato Asako
Published: July 2015

Background

Glycated albumin is an intermediate glycaemic control marker for which there are several measurement procedures with entirely different reference intervals. We have developed a reference measurement procedure for the purpose of standardizing glycated albumin measurements.

Methods

The isotope dilution liquid chromatography/tandem mass spectrometry method was developed as a reference measurement procedure for glycated albumin. The stable isotopes of lysine and fructosyl-lysine, which serve as an internal standard, were added to albumin isolated from serum, followed by hydrogenation. After hydrolysis of albumin with hot hydrochloric acid, the liberated lysine and fructosyl-lysine were measured by liquid chromatography/tandem mass spectrometry, and their concentrations were determined from each isotope ratio. The reference materials (JCCRM611) for determining of glycated albumin were prepared from pooled patient blood samples.

Results

The isotope dilution–tandem mass spectrometry calibration curve of fructosyl-lysine and lysine showed good linearity (r = 0.999). The inter-assay and intra-assay coefficient of variation values of glycated albumin measurement were 1.2 and 1.4%, respectively. The glycated albumin values of serum in patients with diabetes assessed through the use of this method showed a good relationship with routine measurement procedures (r = 0.997). The relationship of glycated albumin values of the reference material (JCCRM611) between these two methods was the same as the relationship with the patient serum samples.

Conclusion

The Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry recommends the isotope dilution liquid chromatography/tandem mass spectrometry method as a reference measurement procedure, and JCCRM611 as a certified reference material for glycated albumin measurement. In addition, we recommend the traceability system for glycated albumin measurement.
Multidisciplinary Pediatric Obesity Clinic via Telemedicine Within the Los Angeles Metropolitan Area
Authors: Slusser Wendy , Whitley Margaret , Izadpanah Nilufar , Kim Sion L. , Ponturo Don
Published: July 2015

Telemedicine has been shown to be effective for rural populations, but little is reported on pediatric obesity care via telemedicine in urban settings. This study aims to assess feasibility and acceptability of multidisciplinary pediatric obesity care via telemedicine within the same metropolitan area in terms of information technology, coordination, patient care, and clinical outcomes. All project notes and communications were reviewed to extract key lessons from implementation. Patient and Provider Satisfaction Questionnaires were conducted to assess overall satisfaction; baseline and follow-up information were collected from chart reviews to evaluate clinical outcomes. Based on the questionnaires, 93% of responding patients (n = 28) and 88.3% of referring providers (n = 17) felt satisfied with the appointment. Chart review indicated a trend for decreased or stabilized body mass index and blood pressure (n = 32). Implementation of telemedicine for tertiary multidisciplinary pediatric obesity care in urban settings is both feasible and acceptable to patients and health care providers.