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Background Rapid reduction of heart rate (HR) is the most evident physiological response of vagal nerve stimulation (VNS). Since HR reduction is the most potent factor to decrease myocardial oxygen consumption rate (MVO2), the appropriate VNS can exert cardio-protective effects. It is also known that VNS reduces inflammation, oxidative stress, and sympathetic overload. In addition, the VNS during ischemia-reperfusion is known to attenuate myocardial damage by studies in various animal species. Despite the presence of preclinical evidence of VNS benefits, the lack of the device has limited the translation of this technology to clinical practice. We have recently developed an intravenous VNS catheter (JOHAKU, Neuroceuticals Inc.) that can stimulate the right vagal nerve via superior vena cava (SVC) (Figure 1) on temporary basis. Purpose We aimed to confirm the feasibility of JOHAKU as a device to modulate heart rate and MVO2 rapidly by a canine experiment. Methods In eight beagle dogs, JOHAKU was inserted from the right femoral vein and placed at the SVC level. The stimulation intensity was adjusted to 10–20 V (20 Hz). We simultaneously recorded electrocardiogram and intraarterial blood pressure (BP). In three of eight dogs, we measured the left anterior descending coronary artery flow and oxygen saturations of arterial and coronary sinus blood to calculate MVO2. We compared HR, BP, and MVO2 during JOHAKU stimulation to ones at baseline. Results As shown in Figure 2, JOHAKU attenuated HR immediately after stimulation. Compared with baseline, JOHAKU significantly reduced HR (baseline: 135±13 vs. 5 min on stimulation: 107±13 bpm, p Conclusion JOHAKU rapidly attenuated cardiac metabolism burden via the rapid HR reduction. The controllability of HR by JOHAKU without affecting BP enables us to apply the VNS even for patients with hemodynamic instability, such as heart failure and acute myocardial infarction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical and Research Development

Oligometastatic prostate cancer (omPCa) is a novel intermediate disease state characterized by a limited volume of metastatic cells and specific locations. Accurate staging is paramount to unmask oligometastatic disease, as provided by prostate-specific membrane antigen-positron emission tomography. Driven by the results of prospective trials employing conventional and/or modern staging modalities, the treatment landscape of omPCa has rapidly evolved over the last years. Several treatment-related questions comprising the concept of precision strikes are under development. For example, beyond systemic therapy, cohort studies have found that cytoreductive radical prostatectomy (CRP) can confer a survival benefit in select patients with omPCa. More importantly, CRP has been consistently shown to improve long-term local symptoms when the tumor progresses across disease states due to resistance to systemic therapies. Metastasis-directed treatments have also emerged as a promising treatment option due to the visibility of oligometastatic disease and new technologies as well as treatment strategies to target the novel PCa colonies. Whether metastases are present at primary cancer diagnosis or detected upon biochemical recurrence after treatment with curative intent, targeted yet decisive elimination of disseminated tumor cell hotspots is thought to improve survival outcomes. One such strategy is salvage lymph node dissection in oligorecurrent PCa which can alter the natural history of progressive PCa. In this review, we will highlight how refinements in modern staging modalities change the classification and treatment of (oligo-)metastatic PCa. Further, we will also discuss the current role and future directions of precision surgery in omPCa.

A 2-D analysis of OFF-state breakdown characteristics of AlGaN/GaN HEMTs with a high- ${k}$ passivation layer is performed as a function of gate-to-drain distance ${L} _{\text {GD}}$ . The relative permittivity of the passivation layer $\varepsilon _{\text {r}}$ is changed from 1 to 60, and ${L} _{\text {GD}}$ is changed from 1.5 to $10~\mu \text{m}$ . It is shown that, in all cases with different ${L} _{\text {GD}}$ , the breakdown voltage ${V} _{\text {br}}$ increases as $\varepsilon _{\text {r}}$ increases. When a deep-acceptor density in an Fe-doped buffer layer ${N} _{\text {DA}}$ is $10^{{17}}$ cm $^{-{3}}$ and the gate length is $0.3~\mu \text{m}$ , ${V} _{\text {br}}$ is determined by buffer leakage current at $\varepsilon _{\text {r}} \ge30$ before impact ionization dominates. Hence, ${V} _{\text {br}}$ is similar at ${L} _{\text {GD}} =3$ – $10~\mu \text{m}$ , and the increase rate in ${V} _{\text {br}}$ from ${L} _{\text {GD}} = 1.5\,\,\mu \text{m}$ is about 50% even at $\varepsilon _{\text {r}} =60$ . However, when ${N} _{\text {DA}}$ is $2\times 10^{{17}}$ cm $^{-{3}}$ , ${V} _{\text {br}}$ is determined by impact ionization of carriers even at $\varepsilon _{\text {r}} \ge30$ because the buffer leakage current is reduced. ${V} _{\text {br}}$ becomes about 500, 930, 1360, and 1650 V for ${L} _{\text {GD}} =1.5$ , 3, 5, and $7~\mu $ m, respectively, at $\varepsilon _{\text {r}} =60$ . These voltages correspond to gate-to-drain average electric fields of about 3.3, 3.1, 2.7, and 2.3 MV/cm, respectively. Particularly, for short ${L} _{\text {GD}}$ , the electric field profiles between the gate and the drain are rather uniform. However, in the case of ${L} _{\text {GD}} = 10\,\,\mu \text{m}$ , ${V} _{\text {br}}$ is about the same as that (1650 V) of ${L} _{\text {GD}} = 7\,\,\mu \text{m}$ , suggesting that the electric field at the drain edge of the gate becomes a critical value before the high electric field region extends to the drain enough. This may be a limitation to increase ${V} _{\text {br}}$ by using a high- ${k}$ passivation layer in this case. However, it can be said that, to improve ${V} _{\text {br}}$ further at long ${L} _{\text {GD}}$ , such as $10~\mu \text{m}$ , the combination of field plate or using a higher $\varepsilon _{\text {r}}$ material may be effective because both of them decrease the electric field at the drain edge of the gate.

The electrochemical properties of the composite electrodes of LaNi0.6Fe0.4O3−δ-Ce0.9Gd0.1O1.95 in various compositions were measured by electrochemical impedance spectroscopy as a function of temperature and p(O2). The enhancement of area-specific conductivity, σE, was found higher than that of the single-phase porous LaNi0.6Fe0.4O3−δ electrode. σE greatly depends on their volume ratio, where σE increases with the increase of the volume fraction of Ce0.9Gd0.1O1.95 phase up to 50%. Above 50% of the volume ratio, σE decreases which could be due to the loss of its surface area density and connectivity between LaNi0.6Fe0.4O3−δ particles. The enhancement degree of σE was evaluated using the transmission line model for the porous-mixed ionic and electronic electrodes. The calculated model is close to the measured σE, showing that the enhancement of σE is not only because of the enhancement of ionic conducting pathways but also possibly due to the decrease of the surface reaction resistivity upon contact with the Ce0.9Gd0.1O1.95.

The electrochemical properties of LaNi0.6Co0.4O3-δ–Ce0.9Gd0.1O1.95 composite electrodes as a function of temperature and p(O2) were investigated by electrochemical impedance spectroscopy. The area-specific conductivity, σE, of the composite electrodes was found higher than the porous LaNi0.6Co0.4O3-δ electrode. The σE greatly depends on their volume ratios, where 70% LaNi0.6Co0.4O3-δ-30% Ce0.9Gd0.1O1.95 showed the highest σE among the compositions. The effective reaction length (lc) of the composite electrodes was estimated by taking the ratio of the calculated capacitance from the impedance analysis to the volume-specific chemical capacitance of LaNi0.6Co0.4O3-δ electrode. The lc is independent of the volume ratio of the composite electrode although the σE greatly depends on their volume ratios, meaning that the lc is independent to the enhancement of σE. Semi-quantitative analysis on the transport properties indicated that the enhancement of the ionic conducting pathway was not the only reason for the enhancement of the electrochemical properties, but also the surface reaction rate of LaNi0.6Co0.4O3-δ was expected to enhance upon contact with Ce0.9Gd0.1O1.95 phase.

Relevant factors affecting an oxygen reduction reaction (ORR) in a heterostructure electrode comprising a Ce0.9Gd0.1O1.95 porous layer on LaNi0.6Fe0.4O3 − δ film electrode were evaluated using electrochemical impedance spectroscopy and isotope depth profile analyses. Despite the LaNi0.6Fe0.4O3 − δ film – porous Ce0.9Gd0.1O1.95 electrode having higher interfacial conductivity, σE, compared to a bare LaNi0.6Fe0.4O3 − δ film electrode, σE behavior as a function of p(O2) was similar to each measured temperature. This exhibits a good correlation with the isotopic oxygen depth profile analysis where the evaluated surface oxygen exchange coefficient, k*, showed enhancement compared to bare LaNi0.6Fe0.4O3 − δ film and exhibited the same behavior on p(O2). Based on the analyses, there are two plausible reasons for this enhancement: (a) the formation of triple phase boundaries at the junction of LaNi0.6Fe0.4O3 − δ film, porous Ce0.9Gd0.1O1.95, and gas phase, where the incorporation process during an ORR process takes place via the porous Ce0.9Gd0.1O1.95; and (b) a modification of the subsurface layer just below the film surface where the presence of diffused Ce and Gd appears to accelerate the ORR process.

In order to elucidate the electronic conduction mechanism and defect chemical model of LaNi 0.4 Fe 0.6 O 3 − δ at high temperatures, electrical conductivity ( σ ), Seebeck coefficient ( S ), and oxygen vacancy concentration ( δ ) of LaNi 0.4 Fe 0.6 O 3 − δ were measured as a function of oxygen partial pressure ( p (O 2 )) and temperature. Relatively large σ and small positive S values are observed, which indicates the contribution of ionic conduction is negligibly small to thermoelectric power and the major electronic carrier is a hole. From the analysis of σ and S , it is expected that the LaNi 0.4 Fe 0.6 O 3 − δ has small polaron hopping conduction mechanism where an electron is localized on the Fe. The slope of δ vs p (O 2 ) shows a minimum value near the stoichiometric composition and the δ increases as p (O 2 ) reduces and temperature increases. The relationship between δ vs. log p (O 2 ) is analyzed by a localized electron model and the behavior of the oxygen nonstoichiometry of LaNi 0.4 Fe 0.6 O 3 − δ can be explained.

Summary Background Given the unique phenotype of type 2 diabetes in Japanese patients, novel therapies such as oral semaglutide require evaluation in this population. PIONEER 9 aimed to assess the dose-response of oral semaglutide and to compare the efficacy and safety of oral semaglutide with placebo and a subcutaneous GLP-1 receptor agonist in a Japanese population. Methods PIONEER 9 was a 52-week, phase 2/3a, randomised, controlled trial done at 16 sites (clinics and university hospitals) in Japan. Japanese patients aged 20 years or older with uncontrolled type 2 diabetes managed by diet or exercise or with oral glucose-lowering drug monotherapy (washed out) were randomly assigned (1:1:1:1:1) to receive double-blind once-daily oral semaglutide (3 mg, 7 mg, or 14 mg) or placebo, or open-label subcutaneous once-daily liraglutide 0·9 mg. The primary endpoint was change in HbA1c from baseline to week 26 with the trial product (primary) estimand (which assumes all patients remained on trial product without rescue medication use) in all randomly assigned patients. This trial is registered with ClinicalTrials.gov , NCT03018028 . Findings Between Jan 10, and July 11, 2017, 243 patients were randomly assigned to oral semaglutide 3 mg (n=49), 7 mg (n=49), or 14 mg (n=48), or placebo (n=49), or to liraglutide 0·9 mg (n=48). Changes in HbA1c from baseline (mean 8·2%) to week 26 were dose-dependent with oral semaglutide (mean change −1·1% [SE 0·1] for oral semaglutide 3 mg, −1·5% [0·1] for 7 mg, and −1·7% [0·1] for 14 mg), −0·1% (0·1) with placebo, and −1·4% (0·1) with liraglutide 0·9 mg. Estimated treatment differences for change in HbA1c compared with placebo were −1·1 percentage points (95% CI −1·4 to −0·8; p Interpretation This study showed that oral semaglutide provides significant reductions in HbA1c compared with placebo in a dose-dependent manner in Japanese patients with type 2 diabetes, and has a safety profile consistent with that of GLP-1 receptor agonists. Funding Novo Nordisk.

Purpose To characterize the preoperative use of alpha-1 adrenergic receptor (AR) blockers and investigate its impact on the outcome of single-session extracorporeal shock wave lithotripsy (SWL) for a ureteral calculus in male patients. Methods We conducted a retrospective single-center cohort study involving 193 patients who underwent SWL for a single ureteral calculus between 2006 and 2016. We reviewed their medical records to obtain the data on the preoperative use of alpha-1 AR blocker and, if any, the reason for the prescription. The primary outcome was treatment success after single-session SWL, defined as complete stone clearance or residual fragments

A hydrogen membrane fuel cell (HMFC) consisting of a Pd solid anode, 1 μm thick BaCe0.8Y0.2O3−δ thin-film electrolyte, and La0.6Sr0.4Co0.2Fe0.8O3 cathode was examined. A single-phase BaCe0.8Y0.2O3−δ thin film was successfully deposited by radio frequency cosputtering with BaCe0.8Y0.2O3 and Ce0.9Y0.1O2 double targets, as checked by X-ray diffraction, transmission electron microscopy, and wavelength dispersive X-ray analysis. The maximum power density reached 1.05 W cm–2 at 600 °C, and this value was higher than the champion data of the recently reported proton-conducting ceramic fuel cells (PCFCs). Electrochemical impedance analysis was performed to characterize the anode and cathode polarization behavior. The impedance responses of HMFC were explicable with an equivalent circuit built by a series connection of cathode charge-transfer elements and anode mass-transfer elements. The contribution of the mass transfer in Pd bulk was found to be relatively small in comparison to cathode polarization and ohmic l...

Dense film electrodes of La 0.6 Sr 0.4 CoO 3 were formed on ceria based solid electrolytes by pulsed laser deposition. The oxygen exchange reaction rate on the surface was evaluated by impedance spectroscopy, and the effect of coexistence of LaSrCoO 4 phase on the surface was investigated. The tendency of Sr segregation on the surface of La 0.6 Sr 0.4 CoO 3 was mitigated by addition of porous LaSrCoO 4 layer, which reduced the activation energy of oxygen exchange reaction and enhanced the reaction rate.

Goose feather and down is a renewable natural product valued for its peculiar quality properties. This material is largely obtained after the slaughter of waterfowl and on a smaller scale by harves...

The aim of this study was to analyze the impact of dementia with differential levels of locomotive function on heavier care burden. A cross-sectional study was conducted to analyze 10,150 persons aged 65 years or older (male, 33.6%) with officially certified care necessity during April 2009 and March 2014 in a suburban city in Japan. Heavier care burden was defined as estimated duration of daily care requirement 70 minutes or longer. Dementia was judged based on the standardized physicians’ classification II or greater, which was validated by a comparison with neuropsychiatrists’ diagnoses defined by the International Psychogeriatric Association. Locomotive function of each study participant was evaluated based on one’s ability to stand-up, walk, sit, and roll over on a bed. Those high discrimination abilities were confirmed by item-response theory analyses, and we could divide their mobility into four categories: higher, high, low, and lower. The proportion of dementia among persons who were certified care necessity was 30.3%. Using logistic regression analyses with stratified by the locomotive function group, calculated sex- and age-adjusted odds ratios of dementia for heavier care burden in higher, high, low, and lower mobility group were 9.4 (95% confidential intervals: 6.2–14.0), 5.3 (3.8–7.5), 4.1 (3.5–4.7), 8.5 (5.8–12.4), respectively, compared to no dementia. Heavy care burden of dementia, which requires communicational assistance more than physical assistance generally, was observed among the elderly with physically independent as well as bed-bound with/without high medical needs.

Thin films of the perovskite-type oxide La1-χSrχCoO3-δ were deposited onto Ce0.9Gd0.1O1.95, SiO2 and single crystal MgO (100) substrates surface by a pulsed laser deposition (PLD) using a XeCl excimer laser to study the difference of the electronic properties and nonstoichiometry. It was shown that the oxygen nonstoichiometry of thin film is smaller than that of bulk for La1-χSrχCoO3-δ. The conductivity of the films were measured by a DC four probe method in 10-4-1 bar O2 gas at temperatures of 25-800{degree sign}C. The activation energy of the conductivity for thin films strongly depends on substrates due to the mismatch of the thermal expansion coefficient between the thin film and the substrate. Although the temperature coefficient of conductivity of La1-χSrχCoO3-δ bulk was negative for χ≥0.4 and was positive for 0≤χ≤0.3, that of thin film was positive irrespective of χ. At the condition with the Co mean valence of 3.0 for χ=0.4, 0.5, the conductivity shows large values for bulk, on the other hand, the conductivity is close to 0 for thin film. These facts suggest the electron hole in bulk is delocalized and metal like, while that in thin film is localized on cobalt ion.

The electronic structure of the protonic conductor Y-doped BaCeO 3 (BaCe 0.90 Y 0.10 O 3− δ ) has been studied by soft-X-ray spectroscopy. The valence band of H 2 -annealed BaCe 0.90 Y 0.10 O 3− δ , which consists of the O 2 p states hybridized with Ce 4 f states, shifts to the higher binding energy side by approximately 0.4 eV. In the air-annealed BaCe 0.90 Y 0.10 O 3− δ , holes and acceptor levels are observed at the top of the valence band and just above E F , respectively. Their intensities are lower in H 2 -annealed BaCe 0.90 Y 0.10 O 3− δ . These findings indicate directly that hydrogen doping compensates for the presence of the holes.

The electronic structure of protonic conductor SrZr 1– x M x O 3– δ (M = Y 3+ , Sc 3+ ) has been studied by soft-X-ray spectroscopy. The valence band is mainly composed of O 2 p state. The conduction band is composed of Zr 4 d state. The holes and the acceptor level are observed at the top of valence band and just above the Fermi level ( E F ), respectively. In H 2 -annealed SrZr 1– x M x O 3– δ (M = Y 3+ , Sc 3+ ), their intensities decrease and the hydrogen-induced level is created at just below E F . The energy separation between the bottom of the hydrogen-induced level and the top of valence band agrees with the activation energy estimated from the electrical conductivity.

EMF of the hydrogen isotope cell has been applied to the sensing of hydrogen isotopes. In this paper, the atomic hydrogen isotope composition and the total pressure of the hydrogen isotopes were determined simultaneously by use of two electrochemical cells with different kind of proton-conducting electrolytes. Among the several proton conductors, CaZr0.9In0.1O3−α and SrCe0.95Yb0.05O3−α were chosen for the sensor. The difference in EMFs of the two proton conductor cells was independent of the total pressure of hydrogen isotopes and, thus, served to determine the atomic hydrogen isotope compositions in gases.

Nonstoichiometry of the fluorite-type oxide solid solutions Ce 1− X Y X O 2−0.5 X − δ ( X =0.1, 0.2) was measured as a function of temperature ( T =973–1373 K) and oxygen partial pressure ( P (O 2 )=10 −2 –10 −24 atm) by means of thermogravimetry. The result shows that the nonstoichiometry of Ce 1− X Y X O 2−0.5 X − δ ( X =0.1, 0.2) is not explained by a simple point defect model, therefore, defect association models are suggested. From the calculation, it is found that (Ce Ce ′V O Ce Ce ′) x is the major defect association not only in Ce 1− X Y X O 2−0.5 X − δ ( X =0.1, 0.2), but also in pure CeO 2 for nonstoichiometries less than 0.10. It is also found that the defect association (Ce Ce ′V O Ce Ce ′) x is dominating at lower temperature and smaller X composition.

The isothermal thermogravimetry was performed on the system of Ce 0.9 Gd 0.1 O 2− δ (CGO10) to determine the oxygen nonstoichiometry, δ , in the temperature range between 1073 and 1173 K and the oxygen partial pressure range of 10 −22 –1 bar. In addition, chemical diffusion coefficients, D chem , and surface reaction rate constants, k , were obtained in CO–CO 2 and H 2 –H 2 O atmospheres through the analysis of a weight relaxation process. The values of obtained chemical diffusion coefficients were consistent with those estimated from partial conductivity and oxygen nonstoichiometry through the P O 2 regions from predominant ionic conduction to predominant electronic conduction. Surface reaction rate constants are not directly related with oxygen partial pressure but depend on the gas species and the composition. The isotope exchange depth profiling with secondary ion mass spectrometry (SIMS) was done to examine the relationship between k and surface exchange coefficients, k s . It was shown that the hydrogen partial pressure dependence of k s converted from k was the same, although the absolute value was about 1 over 30 of those from SIMS analysis.

Internet of Things has inhibited many parts of our modern day lifestyles impacting the simplest to the most complex of our daily activities. Ranging from smart homes, smart water and even smart living, now even farming have been made easier by the intervention of technology. By focusing on pest control in smart farming, we apply the usage of sound alarms, passive infrared sensor, light dependent resistor sensor and Bluetooth connectivity to enhance the performance of pest control farmers have currently. The research deploys a sequential mix mode to collect primary data and experimental validation.

We previously found that ziram, a carbamate fungicide, significantly induced apoptosis and necrosis in human NK-92MI, a natural killer cell line. To investigate whether other carbamate pesticides also induce apoptosis and necrosis in human natural killer cell, we conducted further experiments with NK-92CI, a human natural killer cell line using a more sensitive assay. NK-92CI cells were treated with ziram, thiram, maneb or carbaryl at 0.031-40 microM for 2-24 h in the present study. Apoptosis and necrosis were determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspases 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that ziram and thiram also induced apoptosis and necrosis in a time- and dose-dependent manner; however, maneb and carbaryl induced apoptosis and necrosis only at higher doses in NK-92CI cells. The strength of the apoptosis-inducing effect differed among the pesticides, and the order was as follows: thiramziram greater than maneb greater than carbaryl. NK-92CI was more sensitive to ziram than NK-92MI. Moreover, ziram and thiram significantly increased the intracellular level of active caspase 3 in NK-92CI and caspase inhibitor significantly inhibited the apoptosis. Ziram and thiram significantly caused mitochondrial cytochrome-c release in NK-92CI. These findings indicate that carbamate pesticides can induce apoptosis in natural killer cells, and the apoptosis is mediated by both the caspase-cascade and mitochondrial cytochrome-c pathways.

Oxygen reaction kinetics was investigated with a dense film of (La,Sr)CoO3−δ on ceria based electrolytes. The rate determining step for a highly Sr doped sample was confirmed to be the surface reaction that included at least two series processes, i.e. oxygen adsorption from the gas phase and oxygen transfer across the sub surface layer of the electrode. The reaction rates of those processes were determined separately by using a porous oxygen sensor (POS) which measures the surface oxygen potential on the working electrode. Empirical equations and the kinetic parameters were obtained. The sub surface oxygen transfer process had higher activation energy, and became important in lower temperature applications.

The additive effects of a diblock copolymer of polypropylene and ethylene–propylene rubber PP- b -EPR(50–50) on the morphology and mechanical properties of PP/EPR(50/50) blends were investigated. It was found from an electron microscopy study that the block copolymer is compatible with the PP phase but incompatible with the EPR phase. Dynamic mechanical spectra showed that the PP- b -EPR block copolymers are incorporated into the PP phase, and consequently, the EPR portions of the block are trapped into the interlamellae of PP.