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Leptomeningeal metastases (LM) is a rare but devastating complication of advanced cancer. Advances in cancer treatment has markedly improved the survival, nonetheless, due to the poor penetration of these treatments beyond the blood-brain and blood-CSF barrier for most modalities, creating a sanctuary site in the CNS/CSF space for the disease, and reflecting as increased incidence of LM. Whereas the goal of LM treatment remains to be symptom palliation and not elongation of survival, the optimal treatment, and whom to treat remains to be somewhat controversial. Herein we review the advances in LM treatment focusing on the role of intrathecal chemotherapy.

Since its verification in 2019, there have been numerous high-profile papers reporting improved efficiency of lithium-mediated electrochemical nitrogen reduction to make ammonia. However, the literature lacks any coherent investigation systematically linking bulk electrolyte properties to electrochemical performance and Solid Electrolyte Interphase (SEI) properties. In this study, we discover that the salt concentration has a remarkable effect on electrolyte stability: at concentrations of 0.6 M LiClO4 and above the electrode potential is stable for at least 12 hours at an applied current density of −2 mA cm−2 at ambient temperature and pressure. Conversely, at the lower concentrations explored in prior studies, the potential required to maintain a given N2 reduction current increased by 8 V within a period of 1 hour under the same conditions. The behaviour is linked more coordination of the salt anion and cation with increasing salt concentration in the electrolyte observed via Raman spectroscopy. Time of flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy reveal a more inorganic, and therefore more stable, SEI layer is formed with increasing salt concentration. A drop in faradaic efficiency for nitrogen reduction is seen at concentrations higher than 0.6 M LiClO4, which is attributed to a combination of a decrease in nitrogen solubility and diffusivity as well as increased SEI conductivity as measured by electrochemical impedance spectroscopy.

Importance: Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients. Objective: To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient’s lifetime. Design, Setting, and Participants: Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months. Interventions: Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy. Main Outcomes and Measures: The primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient’s lifetime for the primary outcome and the secondary outcome of death from any cause. Results: A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival. Conclusions and Relevance: These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF. Trial registration: ClinicalTrials.gov Identifier: NCT03036124.

This paper reports the first T2K measurement of the transverse kinematic imbalance in the single-$\pi^+$ production channel of neutrino interactions. We measure the differential cross sections in the muon-neutrino charged-current interaction on hydrocarbon with a single $\pi^+$ and at least one proton in the final state, at the ND280 off-axis near detector of the T2K experiment. The extracted cross sections are compared to the predictions from different neutrino-nucleus interaction event generators. Overall, the results show a preference for models which have a more realistic treatment of nuclear medium effects including the initial nuclear state and final-state interactions.

Resumo Fundamento: A obesidade afeta a adolescência, podendo levar à síndrome metabólica (SM) e disfunção endotelial, um marcador precoce de risco cardiovascular. Apesar de a obesidade ser fortemente associada à síndrome da apneia obstrutiva do sono (SAOS), ainda não está claro o papel da SAOS na função endotelial em adolescentes obesos. Objetivo: Investigar se a obesidade durante a adolescência leva à SM e/ou SAOS e causa disfunção endotelial nesses indivíduos. Além disso, estudamos a possível associação dos fatores de risco para SM e do índice de apneia e hipopneia (IAH) com disfunção endotelial. Métodos: Estudamos 20 adolescentes obesos sedentários (AO; 14,2±1,6 anos, 100,9±20,3kg), e 10 adolescentes eutróficos (AE, 15,2±1,2 anos, 54,4±5,3kg) pareados por sexo. Avaliamos os fatores de risco para SM (critérios da Federação Internacional de Diabetes), função vascular (dilatação mediada pelo fluxo, DMF), capacidade funcional (VO2pico) e presença de SAOS (IAH > 1 evento/hora, pela polissonografia). Consideramos um p1event/h, by polysomnography). We considered statistically significant a P

We report measurements of the flux-integrated ν̅μ and ν̅μ + νμ charged-current cross-sections on water and hydrocarbon targets using the T2K anti-neutrino beam with a mean beam energy of 0.86 GeV. The signal is defined as the (anti-)neutrino charged-current interaction with one induced $\mu^\pm$ and no detected charged pion or proton. These measurements are performed using a new WAGASCI module recently added to the T2K setup in combination with the INGRID Proton Module. The phase space of muons is restricted to the high-detection efficiency region, $p_{\mu}>400~{\rm MeV}/c$ and $\theta_{\mu}200~{\rm MeV}/c$, $\theta_{\pi}600~{\rm MeV}/c$, $\theta_{\rm p}

The aim of this investigation is improvement of the performance of Darrieus-type hydraulic turbines operated in an open channel. Since the output power is very small in such a utilization of small hydropower, it is important to get more power for the cost reduction. In our previous experimental investigation, the performance of turbine runner installed near the side wall of the channel was better than that installed at the center of the channel. In order to enhance the output power, a flat guide was installed upstream of the runner on the opposite side of the side wall. In the present study, we parametrically investigate the effects of flow guiding angle and installation position of the guide on the turbine performance. Two-dimensional unsteady CFD simulations are carried out to qualitatively understand the flow mechanism leading to the better performance of turbine. As a result, it is found that the turbine performance can be significantly enhanced by the appropriately placed flow guide. This enhancement is found to be achieved by the improvement of turbine efficiency and the increase of the input power.

BackgroundIn clinical practice for systemic lupus erythematosus (SLE), the concept of “treat to target” has been introduced with an established goal of reducing glucocorticoid dose as much as possible while controlling disease activity. Although it has been shown that various personality characteristics of patients with SLE affect their disease activity and damage, it is not clear whether the personality characteristics of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait characterized by perseverance and passion for achieving long-term goals.ObjectivesThis study aims to evaluate the relationship between attending physicians’ grit personality characteristics and treatment goal achievements in patients with SLE.MethodsA cross-sectional study was conducted on 386 patients with SLE in five referral hospitals in Japan. The main exposure was the “perseverance” and “consistency” (scores 1-5) of the attending physicians, as measured by the Short Grit Scale, and the primary outcome was the achievement of the Lupus Low Disease Activity Score (LLDAS). Considering the clustering of achievement of LLDAS by each attending physician, the association between attending physician’s personality and LLDAS was analyzed by logistic regression with cluster robust variance estimation. Odds ratios to assess the relationship between perseverance and consistency and LLDAS were estimated with adjustment for confounders (age, sex, disease duration, hydroxychloroquine use, immunosuppressant use, and Systemic Lupus International Collaborating Clinics-Damage Index). We used multiple imputation to handle the uncertainty caused by missing values of potential confounders on the assumption of missing at random.ResultsThe median age of the patients was 45 years (interquartile range[IQR],36-56), 88% were female, and the median disease duration was 152 months(IQR, 80-240). Thirty-seven doctors were in charge of the patients (1-79 patients/each doctor). The median age of the attending physicians was 40 years (IQR, 35-43), and 19% were female. The median perseverance and consistency scores of attending physicians were 3.1 (IQR, 3.0-3.5) and 3.3 (IQR, 2.8-3.8), respectively. Of the enrolled patients, 154 (40%) had achieved LLDAS. The attending physicians with a lower consistency score of ConclusionThe grit personality characteristics of the attending physician may affect the achievement of treatment goals in patients with SLE.Disclosure of InterestsKEN-EI SADA Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., Grant/research support from: I received a research grant from Pfizer Inc., Yoshia Miyawaki: None declared, Kenta Shidahara: None declared, Shoichi Nawachi: None declared, Yu Katayama: None declared, Yosuke ASANO: None declared, Keigo Hayashi: None declared, Keiji Ohashi: None declared, Eri Katsuyama: None declared, Takayuki Katsuyama: None declared, Mariko Narazaki: None declared, Yoshinori Matsumoto: None declared, Nao Oguro: None declared, Yuichi Ishikawa: None declared, Natsuki Sakurai: None declared, Chiharu Hidekawa: None declared, Ryusuke Yoshimi: None declared, Takanori Ichikawa: None declared, Dai Kishida: None declared, Yasuhiro Shimojima: None declared, Noriaki Kurita: None declared, Nobuyuki Yajima: None declared

BackgroundThe minimally important difference (MID) required to interpret the magnitude of changes in lupus patient-reported outcome (LupusPRO), which is a widely used outcome measure of quality of life in SLE patients, remains unclear.ObjectivesWe report preliminary results of an ongoing prospective observational study that assesses the MID as the interpretability of emotional health (EH) domain in Japanese version of LupusPRO.MethodsWe recruited subjects at three university hospitals in Japan participating in an ongoing multidisciplinary cohort study (the Lupus registry of Nationwide institutions (LUNA). Of a total of 210 SLE patients enrolled during the 17-month recruitment period, patients with low disease activity, defined as SLE Disease Activity Index 2000 (SLEDAI-2K) ≤ 4, and who were seen at least twice of three months’ duration and responded to both the LupusPRO and health status change questions were included in this subcohort. The second questionnaire was given an allowance period of 30 days before or after the ​three months from starting date. Descriptive statistics were presented as means and standard deviations (SD) or counts and percentages (%). The emotional health score ranges from 0 to 100; a higher score indicates less frequent presence of symptoms. The change in health status was assessed using the 7-point Global Rating of Change 1), and the score = 0 and the score ≥ +1 were considered in the ‘unchanged’ and the minimal ‘improved’ category, respectively. MID was mainly estimated using the mean change of the groups with the score ≥ +1 as the anchor-based method, and the area under the curve (AUC) was also calculated as a sensitivity analysis to estimate MID thresholds 2) and 95% confidence intervals (CI) were constructed using 1000 bootstrapping.ResultsThe mean age of the 24 eligible patients was 48 (SD 14), and 88% were female. The glucocorticoid dose, SLEDAI-2K, and Systemic Lupus International Collaborating Clinics /American College of Rheumatology Damage Index were 3.4 (2.1) mg, 1.0 (1.1) and 1.1 (1.9), respectively. The mean EH score was 67.5 (30.3), five patients (21%) had the maximum EH score at baseline, 73.4 (25.0) after three months, 7.2 (18.0) for the change in EH. The correlation coefficient and the AUC for the change in health status and the EH were 0.23 and 0.60. The mean changes were 4.1 (18.4) of the groups with ‘unchanged’ health status and 12.3 (17.1) of the groups with ‘improved’ health status. The MID for improvement was estimated at 12.3 using the anchor-based method, and the cutoff point corresponded to 9.3 [95%CI -6.7 to 25.3]) of the EH change score by the receiver operating curve method.ConclusionIn this study, the MID (3 months) for the EH domain in the Japanese version of LupusPRO was estimated to be between 9 and 12, which was similar to the results of the previous cross-sectional study 3). The challenge in estimating the MID in our setting was the low correlation with external anchors, even though the study population was limited to patients with low disease activity, because disease activity at baseline can generally influence ‘improved’ health status.References[1]Kamper SJ, Maher CG, Mackay G. Global rating of change scales: a review of strengths and weaknesses and considerations for design. J Man Manip Ther. 2009;17(3):163.[2]Froud R, Abel G. Using ROC curves to choose minimally important change thresholds when sensitivity and specificity are valued equally: the forgotten lesson of pythagoras. theoretical considerations and an example application of change in health status. PLoS One. 2014;9(12):e114468.[3]Miyawaki Y, Shimizu S, Ogawa Y, et al. Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study. Arthritis Res Ther. 2021;23(1):79.AcknowledgementsThe authors thank Yuka Nakanou for her significant assistance in data management and Kikuko Miyazaki for her expert assistance on this topic.Disclosure of InterestsYoshia Miyawaki: None declared, Kenta Shidahara: None declared, Shoichi Nawachi: None declared, Yosuke ASANO: None declared, Yu Katayama: None declared, Keiji Ohashi: None declared, Eri Katsuyama: None declared, Takayuki Katsuyama: None declared, Mariko Narazaki: None declared, Yoshinori Matsumoto Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., KEN-EI SADA Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., Ryo Yanai: None declared, Nobuyuki Yajima: None declared, Ayuko Takatani: None declared, Kunihiro Ichinose: None declared, Jun Wada Speakers bureau: Jun Wada receives speaker honoraria from Astra Zeneca, Daiichi Sankyo, Novartis, Novo Nordisk Pharma, Tanabe Mitsubishi and receives grant support from Astellas, Baxter, Bayer, Chugai, Dainippon Sumitomo, Kyowa Kirin, Novo Nordisk Pharma, Ono, Otsuka, Tanabe Mitsubishi, and Teijin.

The aim of this investigation is to develop a nano-hydro turbine that can effectively utilize the wasted hydraulic energy in infrastructure such as agricultural and industrial canals and irrigation waterways. Up to this time, the utilization of such a small hydropower has not progressed owing to economic reasons. Therefore, we focus on the Savonius type, which has the advantages of low manufacturing cost and excellent maintainability because of its simple structure. Conventionally, the Savonius type has been developed and researched as a vertical axis wind turbine. In order to effectively utilize the water surface flow, which is particular to open channels, we place the turbine runner perpendicular to the water flow and horizontally on the channel bottom. In the present study, we experimentally investigated the effect of the parameters for the turbine installation and its operation, namely distance between a runner and the water surface and the rotation direction of the runner, on the performance at each water level. As a result, it was found that the suitable installation depth differs depending on the rotation direction of the turbine.

BackgroundThe metabolic syndrome (MetS) is an obesity-driven disorder with pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered autonomic regulation, are important components of MetS pathophysiology. We recently reported that galantamine, an acetylcholinesterase inhibitor and an FDA-approved drug (for Alzheimer’s disease) alleviates the inflammatory state in MetS subjects. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.MethodsThe effects of galantamine treatment, 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n=22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.ResultsGalantamine treatment significantly increased antioxidant enzyme activities, including SOD (+1.65 USOD/mg protein, [95% CI 0.39 to 2.92], P=0.004) and CAT (+0.93 nmol/mg, [95% CI 0.34 to 1.51], P=0.011), decreased lipid peroxidation (thiobarbituric acid reactive substances, -5.45 pmol/mg, [95% CI -10.97 to 0.067], P=0.053) and systemic nitrite levels (-0.05 nit/mg protein, [95% CI -0.21 to 0.10], P=0.038) compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.ConclusionLow-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with galantamine to ameliorate MetS pathophysiology.

The electron (anti-)neutrino component of the T2K neutrino beam constitutes the largest background in the measurement of electron (anti-)neutrino appearance at the far detector. The electron neutrino scattering is measured directly with the T2K off-axis near detector, ND280. The selection of the electron (anti-)neutrino events in the plastic scintillator target from both neutrino and anti-neutrino mode beams is discussed in this paper. The flux integrated single differential charged-current inclusive electron (anti-)neutrino cross-sections, dσ/dp and dσ/d cos(θ), and the total cross-sections in a limited phase-space in momentum and scattering angle (p > 300 MeV/c and θ ≤ 45°) are measured using a binned maximum likelihood fit and compared to the neutrino Monte Carlo generator predictions, resulting in good agreement., Journal of High Energy Physics, 2020 (10), ISSN:1126-6708, ISSN:1029-8479

The development of a facile growth method of gold nanocrystals with a controlled shape is of crucial importance to expand the potential applications of gold nanoarchitectures which have various unique and useful physicochemical properties. Here, we report the site-preferential formation of gold nanostructures with various shapes on Si substrates. When a Si wafer covered with cetyltrimethylammonium bromide (CTAB, an organic salt) is immersed in Au(OH)4− aqueous solution and immediately photoirradiated, dendritic gold nanostructures grow on the surface of the Si wafer. Interestingly, the gold nanodendrites preferentially grow on scratched portions drawn by using a pen-type diamond glass cutter on the Si wafer. The shape of gold nanocrystals depends on the structure of both quaternary alkylammonium cations and halide anions, which are components of the organic salt film, and gold nanostructures with various shapes are successfully obtained at the scratched portions. It is revealed that concerted mechanisms of photoreduction of Au3+ ions and a new type of galvanic displacement reaction between Si and Au(OH)4− cause the site-preferential growth of gold nanoarchitectures.

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (ω-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. −12%, p = 0.06, ES = 0.9; and +23 vs. −22%, p = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (−4 vs. +45%, p = 0.04, ES = −0.9) and tumor necrosis factor (−13 vs. +0.3%, p = 0.04, ES = −0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p = 0.1, ES = −0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.

In this chapter we describe several techniques to study endothelial function in humans. Specifically, intravascular ultrasound, peripheral arterial tonometry, and blood biomarkers are discussed and illustrated. Technical aspects, limitations, and clinical applicabilities are extensively analyzed. Finally a comparison of advantages and limitations of all methods is presented. These methods allow identification of endothelial dysfunction is several clinical conditions including atherosclerosis, arterial hypertension, and diabetes.

Background/aims The matrix of intercellular lipids (ICL) of stratum corneum (SC) plays an important role in the barrier function of SC. It is important to understand the structure of the ICL matrix for dermatology and cosmetic science. Several methods exist for the analysis of the structure; however, it is difficult to conduct these analyses noninvasively. Methods We have developed a method for the analysis of the lateral packing of ICL using Raman spectroscopy. As a proof-of-principle experiment, we prepared a human SC sheet sample and analyzed its structure by the proposed method and by a conventional method involving X-ray diffraction. We compared the results of both methods. In addition, we applied the proposed method to living human skin, and we analyzed the lateral packing of ICL of SC taken from three separate body sites. Results The results of our method corresponded to those of the conventional method. We detected regional differences of ICL lateral packing using our method in vivo. The results indicated that the packing of ICL in SC taken from the forearm and upper arm are more ordered than that taken from the cheek. Conclusion The results verify that our developed method allows the evaluation of the lateral packing of ICL inside the SC layer of the skin in vivo. Using this method, we can detect regional differences of SC samples taken from various body sites.

Introduction: Lamotrigine is widely used for mood disorders including bipolar disorder and major depression, but its therapeutic levels have yet to be determined. This study was conducted to investigate the hypothesis that lamotrigine may have a therapeutic window for mood disorders. Methods: 25 patients with mood disorders received lamotrigine for more than one year during which time plasma lamotrigine levels were measured at least once. Their mental state was retrospectively and regularly but blindly assessed using the Clinical Global Impression–Severity (CGI-S) scale. In order to investigate our hypothesis, we depicted the relationship between the last lamotrigine levels and the last CGI scores in 25 patients. If any, the potential therapeutic window was further investigated. Results: The relationship between the last lamotrigine levels and the last CGI scores in the 25 patients indicated the presence of a therapeutic window of lamotrigine from 5 to 11 μg/mL. The repeated measures of ANOVA reached a significant tendency of the effects of lamotrigine levels within 5–11 μg/mL on better CGI-S scores, and the CGI-S scores at the last observation of the 15 patients whose lamotrigine levels were within 5–11 μg/mL were significantly better than those of 10 patients whose lamotrigine levels were not within 5–11 μg/mL. Conclusion: These findings suggest that lamotrigine may have a therapeutic window for patients with mood disorder from 5 to 11 μg/mL.

Bone marrow derived mononuclear cell (MNC) transplantation is a potential therapy for ischemic stroke. Here, we hypothesized that valproic acid (VPA) would modulate transplantation effects of MNCs in a rat ischemic stroke model. Male Sprague-Dawley rats were subjected to transient 90min middle cerebral artery occlusion. Infarct volume, neurological outcome, and immunohistological assessments were performed 7 days after ischemia. MNCs injected 6 or 24h but not 48 or 72h after ischemia significantly reduced infarct volume and improved neurological deficits. We then tested whether the therapeutic window of MNC transplantation could be expanded through combination therapy with VPA. MNC transplantation at 48h combined with VPA injection three times at 47, 53, and 72h after ischemia significantly ameliorated infarct volume and neurological deficits compared to a vehicle group. Combination therapy reduced the number of myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1-positive cells, tumor necrosis factor-α-positive cells, and von Willebrand factor-positive cells in the ischemic boundary zone. The number of engrafted MNCs that were fluorescently labeled with PKH 26, on day 7, was significantly higher after combination therapy than after that MNC transplantation alone. Our results demonstrated that combination therapy with VPA enhanced the anti-inflammatory and vasculo-protective effects against endothelial damage following ischemia, and increased the survival of transplanted cells, leading to expansion of the therapeutic time window for MNC transplantation. Together, these findings suggest that VPA may be an appropriate partner for cell-based treatment of ischemic stroke.

A high current gain cutoff frequency (fT ) of 90 GHz and a peak maximum oscillation frequency (f MAX) as high as 150 GHz are reported for a rectangular-shaped gate AlGaN/GaN high-electron mobility transistor (HEMT) on a high resistive silicon (HR-Si) substrate. The combined high fT /f MAX values for 100 nm unpassivated gate device demonstrate the high-quality heterostructure on silicon substrate. The reported high-performance RF device characteristics are comparable and even superior to the existing passivated AlGaN/GaN HEMTs of similar gate length. In addition, good DC characteristics have been recorded with the drain current density and an extrinsic transconductance of 0.6 A/mm and 157 mS/mm, respectively.

ITER toroidal field coil (TFC) structures are large welding structures composed of coil case and support structures made of heavy thick high strength and high toughness stainless steels. Japan Atomic Energy Agency plans to apply narrow gap Tungsten Inert Gas (TIG) welding with FMYJJ1 (0.03C–10Mn–12Cr–14Ni–5Mo–0.13N) which is full austenitic stainless filler material. In order to evaluate effect of base material thickness and combinations of base material on tensile properties, tensile tests were performed at room temperature, 77 K and 4 K by using tensile specimens taken from 200 mm thickness welded joints of two combinations of base materials and 40 mm thickness welded joints of four combinations of base materials. As the results, it was confirmed that there were no large distribution of yield and tensile strength along the thickness of welded joints of 200 mm thickness and yield and tensile strengths of welded joints were decreased with decreasing of C + N contents of base material.

The broad organization of information related to the transportation time and the quality of ready-mixed concrete at acceptance is considered to not only contribute to the grasp of actual conditions of concrete in general but also to be of use for various studies. This report presents the results of (1) investigations of the transportation time and the time until placing completion, (2) the average values and standard deviations for each product, and (3) the relationship between fresh properties and compressive strength based on the survey on the actual conditions of ready-mixed concrete for building construction.運搬時間や受入時のレディーミクストコンクリートの品質に関わる情報を広く整理することは，一般的なコンクリートの実態の把握に繋がるだけでなく，様々な検討に有効に活用できるものと考えられる。本報告では，建築工事用レディーミクストコンクリートの実態調査を実施し，①運搬時間および打込終了までの時間に関する検討，②製品ごとの品質の平均値および標準偏差に関する検討および③フレッシュ性状と圧縮強度との関係に関する検討の結果について紹介する。

Arterial hypertension is frequently associated to glucose and lipid metabolism abnormalities. The purpose of this study was to determine if antioxidants (fruit extract) supplementation interfere with glucose and lipid metabolism in overweight hypertensive patients. A randomized clinical trial was conducted with 30 individuals, 23 hypertensive patients (group A) and 7 normotensive controls (group B). They were randomized to take 3 capsules of different fruits extract a day (blueberry, cranberry and pomegranate) or placebo for 4 weeks. This is a crossover study, which started with placebo changed to capsules and vice versa. Blood samples were collected after 12 hours fasting for biochemical tests (glucose, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), anthropometric assessment (weight, height, and body mass index), systolic BP, diastolic BP and heart rate were evaluated at baseline, after 4, and 8 weeks. The comparisons between groups were held with the GLM repeated measures. Twenty three hypertensive patients (age 47 years, 14 females) and 7 normotensive controls (age 40 years, 7 females) were evaluated. BMI, blood pressure, heart and lipid profile did not differ between groups. HOMAir decreased significantly in both groups. See results in table 1. Values are expressed as medians (±SD) In these preliminary results a 4-weeks supplementation of antioxidants (fruit extract) improved insulin resistance in overweight hypertensive and normotensive subjects. Financial support: FAPESP 2014/25808-3

Introduction: Lamotrigine is one of several mood stabilizers and its effects for the treatment and prevention of depressive episodes, particularly in bipolar disorder, are generally accepted. Although the findings about a therapeutic window of lamotrigine are yet to be determined, it seems important to obtain information on individual pharmacokinetic peculiarities. This study was conducted to formulate the predictive model of plasma lamotrigine levels. Methods: Using the data of 47 patients whose lamotrigine levels, liver function, and renal function were measured, predictive models of lamotrigine levels were formulated by stepwise multiple regression analyses. The predictive power of the models was compared using another dataset of 25 patients. Results: Two models were created using stepwise multiple regression. The first model was: plasma lamotrigine level (μg/mL)=2.308+0.019×lamotrigine dose (mg/day). The second model was: plasma lamotrigine level (μg/mL)=0.08+0.024×lamotrigine dose (mg/day)+4.088×valproate combination (no=0, yes=1). The predictive power of the second model was better than that of the first model. Discussion: The present study proposes a prompt and relatively accurate equation to predict lamotrigine levels.

The friction stir welding (FSW) has been used widely in the field of industry. Numerical analysis models for FSW also have been developed and there are many papers about it. In these papers, the most frequently used method is finite element method or finite difference method. However, by employing these methods, it is difficult or troublesome to calculate the advective term both for momentum and temperature. It is also difficult to calculate the big deformation of the material. Moreover, complex process is required to analyse the dissimilar joining with respect to dealing with substance transfer. In this paper, to avoid these difficulties or troublesome processes, particle method is adopted for dissimilar FSW simulation. In particle method, advective term, substance transfer and surface deformation are calculated automatically mainly because that Lagrangian approach is used. Performing some of analysis for FSW, the effectivity of this method is verified.

Long-term WT1 peptide vaccination for patients with acute myeloid leukemia with minimal residual disease

The aim of this study is to evaluate the influence of antenatal magnesium sulfate (MgSO(4)) treatment on the clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis and on that of symptomatic patent ductus arteriosus (sPDA) to indomethacin treatment in premature neonates.This is a retrospective study of 160 consecutively admitted neonates with a gestational age of28 weeks (41 MgSO(4) exposed and 119 controls) who received indomethacin prophylaxis.Incidence of early closure of the ductus arteriosus was lower in the MgSO(4)-exposed neonates than in the control group (59 vs 84%, respectively; P=0.002), whereas incidence of an sPDA was higher (46 vs 24%, respectively; P=0.006). Response to indomethacin treatment was similar between the two groups. Logistic regression analysis indicated increased risk of failure of early ductus arteriosus closure following antenatal MgSO(4) treatment (odds ratio, 4.03; P=0.002).In extremely preterm neonates, antenatal MgSO(4) treatment reduces clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis but not that of sPDA to indomethacin treatment.

We clarified that the superior parietal lobule (SPL) in the right hemisphere involves the perceptual reversal of an ambiguous figure using repetitive transcranial magnetic stimulation (rTMS). The aim of this study was to investigate what effect the stimulus frequency and number of pulses of rTMS had on the Inter-reversal time (IRT) of perceptual reversal on the right SPL. Spinning wheel illusions were used as the ambiguous figures for stimulation in this study. To investigate what effect rTMS had over the right SPL during perceptual reversal, a 0.25 Hz 60-pulse, a 0.25Hz 120-pulse, a 0.5Hz 120-pulse and a 1Hz 120-pulse biphasic rTMS at 90% of the resting motor threshold was applied over the right SPL and right posterior temporal lobe (PTL), respectively. As a control, a no-TMS trial was also conducted. We found that the 60-pulse rTMS at 0.25Hz applied over the right SPL caused shorter IRT. However, there was no significant difference in the 120-pulse rTMS at 0.25Hz, 0.5Hz and 1Hz applied over the right SPL. Moreover, we compared this study to a previous study. Therefore, the application of rTMS over the right SPL suggested that the IRT of perceptual reversal was changed by rTMS conditions such as the number of pulses.

β-FeOOH thin film was prepared on the surface of a foamed Ni substrate by liquid phase deposition (LPD) method with a chemical equilibrium reaction between metal-fluoro complex and oxyhydroxide to make a low-cost and environmentally friendly positive electrode for high-power batteries. The new film electrode, with a thickness of 316 nm, was found out to give a large discharge capacity of 260 mAh g −1 at 0.05 C rate even without an electro-conductive material. Furthermore, the electrode also showed good discharge performance with the retention of 69.9% at 10–0.05 C current rate, which means a promising positive active material for high-power use.

Electrochemical performance of β-FeOOH thin film has been investigated for a low-cost and environmentally friendly negative electrode with a large capacity. The electrode was found out to give an initial large discharge capacity of 864 mAh g−1 and good cycleability with a constant value around 700 mAh g−1 at subsequent cycles. In the first charge process, one electron change reaction proceeded from the initial rest potential of 3.04–1.65 V vs. Li/Li+, resulting in the formation of divalent product FeOOHLi. Further charging caused the surface film formation like solid electrolyte interface (SEI) between 1.65 V and 1.18 V vs. Li/Li+ together with the reduction of Fe compound from divalent to partially zero-valent, followed by its film growth from 1.18 V to 0.07 V vs. Li/Li+.

The nitriding performance of low power electron beam excited plasma is investigated by characterizing the surface of nitrided low alloy Cr–Mo steels. In this research, a particular attention was given to the effect of the acceleration voltage and processing time on the composition and hardness of the processed samples. In an attempt to maximize the dissociation of N 2 , the acceleration voltages applied in our experiments were set within a range that corresponds to the maximum dissociation cross-section of N 2 . The results show that the peak intensity of the alpha Fe observed for the unprocessed sample decreases as the acceleration voltage increases. Moreover, the peak intensities depicting the formation of the nitride compound layers, Fe 4 N and Fe 3 N phases, increases with the acceleration voltage of the electron beam. Consequently, the surface hardness of the treated low alloy steel was increased by more than two times that of the unprocessed specimen.

Based on the NEGF and tight-binding approaches, the bias-induced energy of the metallic CNT is accounted for by the capacitance or inductance in the proposed equivalent circuit model, from which we get an excellent agreement with the semi-classical treatments. The kinetic energy of the electrons in the subband for a FETCNT is modelled as an additional quantum capacitance, which suggests a modified circuit model. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)