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The conjunctive use of surface water and groundwater is practiced worldwide as a measure to address water supply uncertainty. This paper focuses on a scenario in which an aquifer is open to multiple users and examines the impact of such an open-access environment on the stabilization function of conjunctive management. We construct a non-cooperative stochastic dynamic game model where multiple users utilize groundwater intake from a common aquifer as a complement to fluctuating surface water. We also propose a simpler baseline applicable to dynamic environments to compute the benefits of the stabilization function when users are unable to adjust groundwater intake to surface water uncertainties. We then apply the model to the real-world case of the water supply environment of the Cao'e River in China. Simulation results show that open access leads to diminishing stabilization values as higher pumping costs due to declining stocks lead to a weakening of users' incentive to utilize groundwater flexibly. Furthermore, the stabilization function itself is destabilized as the number of users increases. This is because greater groundwater intake and a decline in stocks amplify variations in pumping costs caused by different patterns of surface-water fluctuation. [ABSTRACT FROM AUTHOR]

We have developed a new and compact β-nuclear magnetic resonance (NMR) system using beta-radioactive nuclei. By using a Halbach array permanent magnet to create a static magnetic field, and a scintillating fiber as a detector, we succeeded in significantly reducing the size and weight of the entire system. The performance of the new spectrometer was tested and evaluated by observing an NMR spectrum of 19O (T1/2 = 26.9 s, I = 5/2) in TiO2. [ABSTRACT FROM AUTHOR]

The spin-lattice relaxation times T1 of an unstable nucleus 19O (T1/2 = 26.9 s, I = 5/2) implanted into Y2O3 stabilized ZrO2 (YSZ), which is a solid oxide fuel cell material, were measured at T = 278 − 333 K by means of the β-NMR technique, using a highly spin polarized 19O beam produced via the heavy ion reaction. The motional correlation times τc for oxygen motion derived from the T1 data are on the same straight line on the Arrhenius plot as those derived from the previous 17O-NMR data at above the room temperature. This indicates that 19O ions implanted into YSZ from outside seem to exhibit the same behavior as oxygen ions in the host YSZ material. [ABSTRACT FROM AUTHOR]

The optical navigation camera telescope (ONC-T) is a telescopic framing camera with seven colors onboard the Hayabusa2 spacecraft launched on December 3, 2014. The main objectives of this instrument are to optically navigate the spacecraft to asteroid Ryugu and to conduct multi-band mapping the asteroid. We conducted performance tests of the instrument before its installation on the spacecraft. We evaluated the dark current and bias level, obtained data on the dependency of the dark current on the temperature of the charge-coupled device (CCD). The bias level depends strongly on the temperature of the electronics package but only weakly on the CCD temperature. The dark-reference data, which is obtained simultaneously with observation data, can be used for estimation of the dark current and bias level. A long front hood is used for ONC-T to reduce the stray light at the expense of flatness in the peripheral area of the field of view (FOV). The central area in FOV has a flat sensitivity, and the limb darkening has been measured with an integrating sphere. The ONC-T has a wheel with seven bandpass filters and a panchromatic glass window. We measured the spectral sensitivity using an integrating sphere and obtained the sensitivity of all the pixels. We also measured the point-spread function using a star simulator. Measurement results indicate that the full width at half maximum is less than two pixels for all the bandpass filters and in the temperature range expected in the mission phase except for short periods of time during touchdowns. [ABSTRACT FROM AUTHOR]

A liquid He target system was successfully developed for experimental studies of the anti-kaon interaction with a nucleon at the J-PARC hadron facility. Pumped liquid He with the temperature of 1.4 K is used to condense gaseous He with a total volume of 400 L at atmospheric pressure and 21 °C. A circulation of the liquid between a heat exchanger and a target cell works well for an effective heat transfer between them. The target system was stably operated in the first experiment at the K1.8BR beam line in May 2013. [ABSTRACT FROM AUTHOR]

We compared the expected medical costs of empirical and preemptive treatment strategies for invasive fungal infection in neutropenic patients with hematological diseases. Based on the results of two clinical trials with different backgrounds reported by Oshima et al. [J Antimicrob Chemother 60(2):350-355; Oshima study] and Cordonnier et al. [Clin Infect Dis 48(8):1042-1051; PREVERT study], we developed a decision tree model that represented the outcomes of empirical and preemptive treatment strategies, and estimated the expected medical costs of medications and examinations in the two strategies. We assumed that micafungin was started in the empirical group at 5 days after fever had developed, while voriconazole was started in the preemptive group only when certain criteria, such as positive test results of imaging studies and/or serum markers, were fulfilled. When we used an incidence of positive test results of 6.7 % based on the Oshima study, the expected medical costs of the empirical and preemptive groups were 288,198 and 150,280 yen, respectively. Even in the case of the PREVERT study, in which the incidence of positive test results was 32.9 %, the expected medical costs in the empirical and preemptive groups were 291,871 and 284,944 yen, respectively. A sensitivity analysis indicated that the expected medical costs in the preemptive group would exceed those in the empirical group when the incidence of positive test results in the former was over 34.4 %. These results suggest that a preemptive treatment strategy can be expected to reduce medical costs compared with empirical therapy in most clinical settings. [ABSTRACT FROM AUTHOR]

Background/Objectives:Although adipokines and insulin resistance are known to be correlated with body fatness, it is unclear whether they are independently related to weight gain experience. We examined the associations of serum adipokines and marker of insulin resistance with past weight gain during adulthood by taking the degree of attained body mass index (BMI) level into consideration.Subjects/Methods:Subjects were 399 Japanese municipal employees, aged ⩾30 years, who participated in a health survey. Serum adipokines were measured using a Luminex suspension bead-based multiplexed array. Weight change during adulthood was calculated as the difference between measured current weight and recalled weight at the age of 20 years. Multiple regression was performed to calculate mean adipokine levels and homeostasis model assessment of insulin resistance (HOMA-IR) according to weight gain (<5 kg, 5-9.9 kg, or ⩾10 kg) with adjustment for current BMI.Results:Weight gain from the age of 20 years was significantly and positively associated with leptin levels even after adjustment for current BMI (P for trend <0.001), whereas it was significantly and inversely associated with adiponectin levels in a BMI-adjusted model among subjects aged ⩾40 years (P for trend=0.03). Weight gain was associated with HOMA-IR in a BMI-unadjusted model (P for trend <0.001), but this association was largely attenuated after adjustment for BMI. Resistin, plasminogen activator inhibitor-1 and visfatin were not associated with past weight gain.Conclusions:Results suggest that a large weight gain during adulthood is associated with higher leptin and lower adiponectin levels independently of the degree of attained BMI level. [ABSTRACT FROM AUTHOR]

Numerous studies support a role of phosphatase and tensin homolog deleted from chromosome 10 (Pten) as a tumor suppressor gene that controls epithelial cell homeostasis to prevent tumor formation. Mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen and provides a unique model for analyzing homeostasis of stratified squamous epithelia. We analyzed vaginal epithelium-specific Pten conditional knockout (CKO) mice to provide new insights into Pten/phosphoinositide-3-kinase (PI3K)/Akt function. The vaginal epithelium of ovariectomized (OVX) mice (control) was composed of 1-2 layers of cuboidal cells, whereas OVX CKO mice exhibited epithelial hyperplasia in the suprabasal cells with increased cell mass and mucin production. This is possibly due to misactivation of mammalian target of rapamycin and mitogen-activated protein kinase. Intriguingly, estrogen administration to OVX Pten CKO mice induced stratification and keratinized differentiation in the vaginal epithelium, as in estrogen-treated controls. We found that Pten is exclusively expressed in the suprabasal cells in the absence of estrogens, whereas estrogen administration induced Pten expression in the basal cells. This suggests that Pten acts to prevent excessive cell proliferation as in the case of other squamous tissues. Thus, Pten exhibits a dual role on the control of vaginal homeostasis, depending on whether estrogens are present or absent. Our results provide new insights into how Pten functions in tissue homeostasis. [ABSTRACT FROM AUTHOR]

We are preparing for an ultra-high resolution X-ray spectroscopy of kaonic atoms using an X-ray spectrometer based on an array of superconducting transition-edge-sensor microcalorimeters developed by NIST. The instrument has excellent energy resolutions of 2-3 eV (FWHM) at 6 keV and a large collecting area of about 20 mm $$^2$$ . This will open new door to investigate kaon-nucleus strong interaction and provide new accurate charged-kaon mass value. [ABSTRACT FROM AUTHOR]

We previously reported that the baseline C-reactive protein level did not predict infectious events after hematopoietic cell transplantation (HCT). Procalcitonin (PCT) has recently emerged as a powerful biomarker for the early diagnosis of bacterial infection. We evaluated the ability of the baseline PCT level to predict early infectious events after HCT in 79 recipients who received HCT between 2008 and 2012. The high-PCT group (0.07 ng/mL, n=27) frequently experienced documented infection (DI) (21.2% vs 44.4% at day 30, P=0.038) and bloodstream infection (BSI) (15.4% vs 37.0% at day 30, P=0.035). In a multivariate analysis, however, the baseline PCT level was not significantly associated with DI (HR 2.01, P=0.089) or BSI (HR 2.28, P=0.084). Localized infection, such as anal canal problems, before the start of conditioning was seen in 26 patients. When we stratified the patients according to the presence of elevated PCT and localized infection, the group with elevated PCT and localized infection (n=17) was significantly associated with increased DI (HR 3.40, P=0.0074) and BSI (HR 3.59 P=0.0078) after HCT. A larger prospective observation is warranted to confirm the impact of the baseline PCT level and clinical features on the outcome of HCT. [ABSTRACT FROM AUTHOR]

Background:Interleukin-6 (IL-6) has an important role in cancer progression, and high levels of plasma IL-6 are correlated with a poor prognosis in a variety of cancers. It has also been reported that tumour stromal fibroblasts are necessary for steps in cancer progression, such as angiogenesis. There have been few reports of a correlation between fibroblast actions and IL-6 levels. In this study, we examined the correlation between cancer stromal fibroblasts and IL-6 and the utility of IL-6 as a therapeutic target in human colon cancer.Methods:The expression levels of IL-6 and VEGF of fibroblasts and cancer cell lines were evaluated using real-time PCR and ELISA. The anti-angiogenic effect of inhibiting IL-6 signalling was measured in an angiogenesis model and animal experiment.Results:We demonstrate that stromal fibroblasts isolated from colon cancer produced significant amounts of IL-6 and that colon cancer cells enhanced IL-6 production by stromal fibroblasts. Moreover, IL-6 enhanced VEGF production by fibroblasts, thereby inducing angiogenesis. In vivo, anti-IL6 receptor antibody targeting stromal tissue showed greater anti-tumour activity than did anti-IL6 receptor antibody targeting xenografted cancer cells.Conclusion:Cancer stromal fibroblasts were an important source of IL-6 in colon cancer. IL-6 produced by activated fibroblasts induced tumour angiogenesis by stimulating adjacent stromal fibroblasts. The relationship between IL-6 and stromal fibroblasts offers new approaches to cancer therapy. [ABSTRACT FROM AUTHOR]

Cellular immunity is important for the control of CMV infection after allogeneic hematopoietic cell transplantation (Allo-HCT). However, the actual in vivo dynamics of CMV-specific cytotoxic T cell (CMV-CTL) clones are still unclear. We conducted clone monitoring of tetramer+ CMV-CTLs in HLA-A*2402-positive donor-patient pairs, using a direct single-cell analysis that enabled the simultaneous identification and quantification of CTL clones. Clone dynamics were assessed in three cases with or without CMV reactivation. In Case-1 without CMV reactivation, despite the long-term use of systemic steroid, dominant clones of Donor-1 persisted and remained dominant. The CMV-CTLs at 1 year after Allo-HCT included a high proportion of CD45RA+CCR7− effector and CD27−CD57+mature T cells. On the other hand, in Cases-2 and -3 with CMV reactivation, novel clones appeared and became dominant during the follow-up. Their CMV-CTLs included more CD27+ immature T cells at 1 year after Allo-HCT. With regard to clonotypes, HLA-A*2402-restricted CMV-CTLs tended to select BV7 and BJ1-1 genes for complementarity-determining region 3 (CDR3) of T-cell receptor (TCR)-β. Specific amino-acid sequences of CDR3 of TCR-β were found in each case. Patterns of clone reconstitution and phenotype would be different according to CMV reactivation. In vivo clone monitoring of CMV-CTLs could provide insight into the mechanism of immunological reconstitution following Allo-HCT. [ABSTRACT FROM AUTHOR]

Although dorsal and caudal fin deformities (curvature), abnormal body color patterns, and fluctuating asymmetry of meristic characters have been previously reported for white-spotted charr ( Salvelinus leucomaenis), the incidence of skeletally deformed individuals in the wild are extremely rare. Here, we report on skeletally deformed individuals of white-spotted charr with extremely truncated upper jaw, in a headwater reach of the Yoneshiro River, northern Honshu, Japan. In this study, we examined the genetic diversity of deformed and non-deformed populations of white-spotted charr using polymorphic microsatellite DNA markers. We also compared individual growth histories of deformed individuals with normal individuals using a back-calculation of fish lengths at previous ages from otolith annuli. We collected 41 and 100 individuals from the below- and above-waterfall sites, respectively. Of these, two individuals from the above-waterfall site were skeletally deformed, whereas the other individuals had a normal morphology. Microsatellite DNA genetic diversities of the above-waterfall population were notably lower than those of the just below-waterfall population. Individuals of the above-waterfall population had significantly higher internal relatedness and lower standardized heterozygosity values compared with those of the below-waterfall population, indicating higher inbreeding situation of the above-waterfall individuals compared with individuals in the below-waterfall site. Back-calculation of individual growth using otoliths revealed that deformed individuals grew significantly slower than sympatric normal individuals. Although incidence of deformed individuals in the wild might be related with accumulated inbreeding as suggested for other fishes, mechanisms for their long-term persistence in the wild remain unclear. [ABSTRACT FROM AUTHOR]

We observed the motion of an organelle transported by motor proteins in cells using fluorescence microscopy. Particularly, among organelles, the mitochondria in PC12 cells were studied. A mitochondrion was dragged at a constant speed for several seconds without pausing. We investigated the fluctuation dissipation theorem for this constant drag motion by comparing it with the motion of Brownian beads that were incorporated into the cells by an electroporation method. We estimated the viscosity value inside cells from the diffusion coefficients of the beads. Then the viscosity value obtained by using the beads was found to be slightly lower than that obtained from the diffusion coefficient for the organelle motion via the Einstein relation. This discrepancy indicates the violation of the Einstein relation for the organelle motion. Graphical abstract: [ABSTRACT FROM AUTHOR]

Study design:A cross-sectional analysis.Objective:To examine whether intramedullary stress is related to the appearance of symptoms in cervical spondylotic myelopathy (CSM).Setting:Japan.Methods:Thirty-three consecutive patients with CSM and 30 consecutive patients without CSM were enrolled. A total of 99 disc levels from C3 to C6 in 33 patients with CSM were divided into two groups: 33 disc levels with high signal intensity (HSI) on T2-weighted magnetic resonance image (HSI group) and 66 disc levels without HSI (Non-HSI group). Ninety disc levels from C3 to C6 in patients without CSM were set up in a control group. Intramedullary stress value at each level was analyzed using the finite element method. Stress was compared among the three groups. A cutoff value of stress to present HSI was investigated from receiver operator characteristics (ROC) curve.Results:In all the patients with CSM, the disc level with HSI presented the highest stress among the three disc levels evaluated. The stress was 3.16±0.86 kPa (mean±s.d.) in the HSI group, 1.81±0.72 kPa in the Non-HSI group and 1.01±0.37 kPa in the control group. The stress differed significantly among the three groups (P<0.0001). The qualified cutoff value derived from the ROC curve was 2.30 kPa (sensitivity 78.8%, specificity 91.9%). None of the disc levels in the control group exceeded 2.30 kPa.Conclusion:HSI was strongly associated with intramedullary stress. Threshold of intramedullary stress to present HSI that related closely to the symptoms of myelopathy was revealed. [ABSTRACT FROM AUTHOR]

Background/objectives:Vitamin B6 is suggested to have a protective role against depression. However, the association between vitamin B6 intake and depression remains inconclusive, and few studies have examined the relationship between circulating vitamin B6 concentrations and depressive symptoms. Here, we investigated the cross-sectional and prospective associations between serum pyridoxal concentrations and depressive symptoms among Japanese workers. Subjects/methods: Participants were 422 municipal employees (aged 21-67 years) who participated in a baseline survey in 2006 for cross-sectional analysis, and 210 subjects without depressive symptoms at baseline (2006) who completed both baseline and follow-up (2009) surveys for prospective analysis. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Logistic regression analysis was used to estimate the odds ratio of depressive symptoms (CES-D scale of ≥19) according to tertile of serum pyridoxal with adjustment for potential confounding variables. Results:In the cross-sectional analysis, serum pyridoxal concentrations were significantly associated with a decreased prevalence of depressive symptoms (P for trend=0.03); the multivariable-adjusted odds ratio of depressive symptoms for the highest tertile of pyridoxal was 0.54 (95% confidence interval 0.30-0.96) compared with the lowest tertile. In longitudinal analyses, higher serum pyridoxal concentrations at baseline were associated with a trend toward reduced depressive symptoms after 3 years; the multivariable-adjusted odds ratio of depressive symptoms for the highest versus the lowest tertile of pyridoxal concentration was 0.55 (95% confidence interval 0.13-2.32).Conclusions:A higher vitamin B6 status may be associated with a decreased risk of depressive symptoms in Japanese. [ABSTRACT FROM AUTHOR]

The precision of GPS/acoustic seafloor positioning was improved by introducing a hull-mounted onboard system in March 2008, which allows us to conduct acoustic ranging measurements with the vessel sailing along the pre-determined track lines, while the early system before 2008 could only adopt the uncontrollable drifting observation. The continuity of the positioning results due to the transition was first confirmed through the comparison between results from sailing and drifting observations conducted in parallel. Using the data acquired for about 3 years since 2008, the repeatability of the determined position for the sailing observation was evaluated to be about 2 cm in root mean squares in the horizontal component, significantly better than that for the early drifting observation. The improvement of positioning precision probably resulted from the improvement of geometric distribution of acoustic ranging data by controlling the track lines. It was also shown that the sailing observation allows to obtain reliable results with a smaller amount of data. Comparison between the results in different sea regions suggests that positioning precision is better in the region along the Nankai Trough than in the region along the Japan Trench, probably because of the complicated acoustic velocity structure of seawater often observed in the latter. Furthermore, the precision of height determination was also improved, which leads us to expect that vertical crustal movement will be detectable in the future through accumulation of data as well as further technology development. [ABSTRACT FROM AUTHOR]

KRAS mutations are one of the most common driver mutations in non-small-cell lung cancer (NSCLC) and finding druggable target molecules to inhibit oncogenic KRAS signaling is a significant challenge in NSCLC therapy. We recently identified epiregulin (EREG) as one of several putative transcriptional targets of oncogenic KRAS signaling in both KRAS-mutant NSCLC cells and immortalized bronchial epithelial cells expressing ectopic mutant KRAS. In the current study, we found that EREG is overexpressed in NSCLCs harboring KRAS, BRAF or EGFR mutations compared with NSCLCs with wild-type KRAS/BRAF/EGFR. Small interfering RNAs (siRNAs) targeting mutant KRAS, but not an siRNA targeting wild-type KRAS, significantly reduced EREG expression in KRAS-mutant and EREG-overexpressing NSCLC cell lines. In these cell lines, EREG expression was downregulated by MEK and ERK inhibitors. Importantly, EREG expression significantly correlated with KRAS expression or KRAS copy number in KRAS-mutant NSCLC cell lines. Further expression analysis using 89 NSCLC specimens showed that EREG was predominantly expressed in NSCLCs with pleural involvement, lymphatic permeation or vascular invasion and in KRAS-mutant adenocarcinomas. In addition, multivariate analysis revealed that EREG expression is an independent prognostic marker and EREG overexpression in combination with KRAS mutations was associated with an unfavorable prognosis for lung adenocarcinoma patients. In KRAS-mutant and EREG overexpressing NSCLC cells, siRNA-mediated EREG silencing inhibited anchorage-dependent and -independent growth and induced apoptosis. Our findings suggest that oncogenic KRAS-induced EREG overexpression contributes to an aggressive phenotype and could be a promising therapeutic target in oncogenic KRAS-driven NSCLC. [ABSTRACT FROM AUTHOR]

Various biomarkers have been investigated with regard to their ability to predict the outcome of allogeneic hematopoietic SCT (HSCT). In this study, we retrospectively reviewed 90 recipients who received HSCT between 2007 and 2011 in our institution, and evaluated the predictive value of the baseline serum C-reactive protein (CRP) levels just before the initiation of conditioning for transplant-related complications after allogeneic HSCT. A receiver-operating characteristic curve revealed that the baseline serum CRP levels had an excellent predictive value for non-relapse mortality (NRM), with an area under the curve of 0.83. The sensitivity and specificity for NRM were 80% and 87%, respectively, with a cutoff of 0.6 mg/dL. With this cutoff value, multivariate analyses revealed that a higher baseline CRP level was an independent risk factor for NRM (HR 6.21, P<0.01), grade III-IV acute GVHD (HR 3.91, P=0.03) and poor overall survival (HR 3.27, P=0.0018). On the other hand, the baseline CRP level did not predict infectious events. These findings suggested that CRP levels before conditioning may be a useful predictive biomarker for poor survival. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR) has an essential role in multiple signaling pathways, including cell proliferation and migration, through extracellular ligand binding and subsequent activation of its intracellular tyrosine kinase (TK) domain. The non-small cell lung cancer (NSCLC)-associated EGFR mutants, L858R and G719S, are constitutively active and oncogenic. They display sensitivity to TK inhibitors, including gefitinib and erlotinib. In contrast, the secondary mutation of the gatekeeper residue, T790M, reportedly confers inhibitor resistance on the oncogenic EGFR mutants. In this study, our biochemical analyses revealed that the introduction of the T790M mutation confers gefitinib resistance on the G719S mutant. The G719S/T790M double mutant has enhanced activity and retains high gefitinib-binding affinity. The T790M mutation increases the ATP affinity of the G719S mutant, explaining the acquired drug resistance of the double mutant. Structural analyses of the G719S/T790M double mutant, as well as the wild type and the G719S and L858R mutants, revealed that the T790M mutation stabilizes the hydrophobic spine of the active EGFR-TK conformation. The Met790 side chain of the G719S/T790M double mutant, in the apo form and gefitinib- and AMPPNP-bound forms, adopts different conformations that explain the accommodation of these ligands. In the L858R mutant structure, the active-site cleft is expanded by the repositioning of Phe723 within the P-loop. Notably, the introduction of the F723A mutation greatly enhanced the gefitinib sensitivity of the wild-type EGFR in vivo, supporting our hypothesis that the expansion of the active-site cleft results in enhanced gefitinib sensitivity. Taken together, our results provide a structural basis for the altered drug sensitivities caused by distinct NSCLC-associated EGFR mutations. [ABSTRACT FROM AUTHOR]

Hyperbilirubinemia in the early phase after allogeneic hematopoietic SCT (HSCT) is due to various causes. One of the most important causes of hyperbilirubinemia is veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS). However, the prognosis of patients who are clinically diagnosed as SOS varies. We retrospectively evaluated 82 patients who underwent their first allogeneic HSCT. GVHD prophylaxis was a combination of short-term MTX and CsA (n=77) or tacrolimus (n=5). Thirty-three patients developed hyperbilirubinemia, with a bilirubin level of at least 2 mg/dL, within 20 days after HSCT. Of these patients, 24 were diagnosed as VOD/SOS using the modified Seattle criteria. Twenty-six recovered to a bilirubin level of <2 mg/dL. We focused on the serum alkaline phosphatase/total bilirubin ratio (ALP/TB) at the onset of hyperbilirubinemia and found that it significantly predicted the recovery from hyperbilirubinemia. OS was significantly higher in patients with a lower ALP/TB ratio (P=0.00056). In addition, a lower ALP/TB ratio was associated with better survival even in patients who were clinically diagnosed as SOS (P<0.001). The ALP/TB ratio at the onset of hyperbilirubinemia may be a useful predictor for the prognosis of hyperbilirubinemia and SOS early after HSCT. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of transcatheter arterial chemoembolization (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5-furuorouracil: Multi group) with TACE using epirubicin (EP group) for hepatocellular carcinoma (HCC). Materials and Methods: The study design was a single-center, prospective, randomized controlled trial. Patients with unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation, were assigned to the Multi group or the EP group. We assessed radiographic response as the primary endpoint; secondary endpoints were progression-free survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage or mild vessel wall irregularity; Grade II, overt stenosis; Grade III, occlusion; Grades II and III indicated significant hepatic artery damage). A total of 51 patients were enrolled: 24 in the Multi group vs. 27 in the EP group. Results: No significant difference in HCC patient background was found between the groups. Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs. EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and 76%, respectively, with no significant difference. Significantly greater Grade 3 transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery abnormality was observed in 34% of the Multi group and in 17.1% of the EP group (p = 0.019). Conclusion: TACE with multiple anti-cancer drugs was tolerable but appeared not to contribute to an increase in radiographic response or PFS, and caused significantly more hepatic arterial abnormalities compared with TACE with epirubicin alone. [ABSTRACT FROM AUTHOR]

Background/Objectives:The association between vitamin D status and insulin resistance (IR) has been less studied among Asians, and it remains elusive whether calcium could modify such an association. We examined the association of serum 25-hydroxyvitamin D (25(OH)D) concentrations with IR markers and the potential effect modification by calcium intake among a Japanese population.Subjects/Methods:The authors analyzed data (n=494) from a cross-sectional survey conducted in 2009 among a Japanese working population aged 20-68 years. Fasting serum 25(OH)D and insulin, as well as fasting plasma glucose were determined, and homeostatic model assessment of IR (HOMA-IR) was calculated. Calcium intake was assessed using a validated diet history questionnaire. Multiple linear regression was done with adjustment of potential confounding variables.Results:Fasting insulin and HOMA-IR were significantly inversely associated with 25(OH)D concentration across quartiles of 25(OH)D after fully adjusting for covariates (Ptrend=0.04 and 0.02, respectively). Across clinically relevant categories of 25(OH)D, compared with participants in the vitamin D sufficiency group, those in the vitamin D insufficiency group had a 5% higher HOMA-IR score, and those in the hypovitaminosis D group had an 18% higher HOMA-IR score (Ptrend=0.01). In an analysis by calcium intake, the HOMA-IR score was highest among participants with both a low calcium intake and lowest 25(OH)D concentrations, with significant inverse trend being observed in the group with lower calcium intake (Ptrend=0.02).Conclusions:Our findings suggest that low vitamin D status is associated with IR among Japanese adults. [ABSTRACT FROM AUTHOR]

Summary: This study aims to determine the relationship between advanced glycation end-product (AGE) accumulation in skin tissue and bone strength, assessed by quantitative ultrasound, among healthy adult Japanese men. The results of the study suggest that men with higher AGE accumulation in skin tissue have a lower osteo-sono assessment index. Introduction: AGE accumulate in bone collagen with age and diabetes and decrease the mechanical properties of bone. Although increased AGE levels are associated with fractures among diabetic patients and elderly women, it is unclear whether a relationship between increased AGE levels and bone strength is present in apparently healthy adult males. The aim of this study was to determine the relationship between AGE accumulation in tissue and the mechanical properties of bone among adult Japanese men, using quantitative ultrasound as a surrogate measure of the latter. Methods: Skin autofluorescence (AF), which is a noninvasive method for measuring tissue AGEs, and osteo-sono assessment index (OSI), which is determined by quantitative ultrasound, were measured in 193 adult Japanese men (median age 43 years; interquartile range 37.0-55.0 years). Results: Adjusted for age, BMI, calcium intake, physical activity, smoking status, and education level, log-transformed skin AF had a negative association with log-transformed OSI ( β = −0.218, P < 0.01). Adjusted geometric means (95% CI) for OSI across the tertiles of skin AF were 2.81 (2.75-2.87) for the lowest tertile, 2.81 (2.74-2.87) for the middle tertile, and 2.66 (2.61-2.73) for the highest tertile; thus, OSI for the highest skin AF appeared to be 5.0% lower than that for the lowest and middle skin AF tertiles ( P < 0.01). Conclusion: Among apparently healthy adult Japanese men, those with higher skin AF had a lower OSI, indicating a relationship between AGE accumulation and bone strength. A long-term prospective study is required to clarify the causality. [ABSTRACT FROM AUTHOR]

Discovery of mechanisms that impede the aggressive and metastatic phenotype of human basal triple-negative-type breast cancers (BTNBCs) could provide novel targets for therapy for this form of breast cancer that has a relatively poor prognosis. Previous studies have demonstrated that expression of GATA3, the master transcriptional regulator of mammary luminal differentiation, can reduce the tumorigenicity and metastatic propensity of the human BTNBC MDA-MB-231 cell line (MB231), although the mechanism for reduced metastases was not elucidated. We demonstrate through gene expression profiling that GATA3 expression in 231 cells resulted in the dramatic reduction in the expression of lysyl oxidase (LOX), a metastasis-promoting, matrix-remodeling protein, in part, through methylation of the LOX promoter. Suppression of LOX expression by GATA3 was further confirmed in the BTNBC Hs578T cell line. Conversely, reduction of GATA3 expression by small interfering RNA in luminal BT474 cells increased LOX expression. Reconstitution of LOX expression in 231-GATA3 cells restored metastatic propensity. A strong inverse association between LOX and GATA3 expression was confirmed in a panel of 51 human breast cancer cell lines. Similarly, human breast cancer microarray data demonstrated that high LOX/low GATA3 expression is associated with the BTNBC subtype of breast cancer and poor patient prognosis. Expression of GATA3 reprograms BTNBCs to a less aggressive phenotype and inhibits a major mechanism of metastasis through inhibition of LOX. Induction of GATA3 in BTNBC cells or novel approaches that inhibit LOX expression or activity could be important strategies for treating BTNBCs. [ABSTRACT FROM AUTHOR]

The lattice parameters of a Nd 1111 Fe-pnictide superconductor, NdFeAsOF, were accurately measured using X-ray diffraction between 20 K and 280 K. A very small change in the lattice parameter could be detected in the superconducting phase. This change can be attributed to a spontaneous strain generated in the superconducting phase by the coupling between a superconducting order parameter and the strain. The present results are compared with the thermal expansion coefficients of Ba (FeCo)As, in addition to the previous lattice parameter measurements of YBaCuO, MgB, LaSrCuO, and BaKBiO. [ABSTRACT FROM AUTHOR]

Objectives: Reported rates of major complications and mortality of radiofrequency ablation (RFA), microwave ablation (MWA) and percutaneous ethanol injection (PEI) for the treatment of liver tumours were substantially heterogeneous among studies. The aim was to analyse the mortality and major complication rates of percutaneous RFA, PEI and MWA.Methods: MEDLINE and EMBASE search from January 1982 to August 2010. Randomised clinical trials and observational studies, age >18, more than 50 patients for each technique analysed, studies reporting mortality and major complications were included. Random effects model was performed, with assessment for heterogeneity and publication bias.Results: Thirty-four studies including 9531, 1185, and 1442 patients for RFA, MWA, and PEI, respectively were included. For all ablative techniques pooled proportion mortality rate was 0.16% (95% confidence interval [CI], 0.10-0.24). Pooled mortality rate associated with RFA, PEI and MWA was 0.15% (0.08-0.23), 0.59% (0.14-1.3) and 0.23% (0.0-0.58) respectively. Pooled proportion of major complications was 3.29% (2.43-4.28). Major complication rates associated with RFA, MWA, and PEI was 4.1% (3.3-5.1), 4.6% (0.7-11.8) and 2.7% (0.28-7.4) respectively.Conclusions: Percutaneous RFA, PEI and MWA can be considered safe techniques for the treatment of liver tumours. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to clarify the effect of the interval between transcatheter hepatic arterial embolization (TAE) with Lipiodol plus gelatin sponge particles and radiofrequency (RF) ablation on the extent of ablation.Materials and Methods: Eight healthy swine were divided into four groups: RF ablation (ablation only), RF ablation immediately after TAE (immediate ablation), RF ablation 3 days after TAE (3-day ablation), and RF ablation 6 days after TAE (6-day ablation). Five ablated lesions were created in each swine (10 per group). A 2-cm expandable LeVeen needle electrode was used for RF ablation. Ablated lesions are composed of an outer reddish zone and an inner whitish zone.Results: The average longest length of the major, intermediate, and minor axes and the volume in the immediate ablation, 3-day ablation, and 6-day ablation groups were significant longer and greater (1.52 and 1.52, 1.46 and 1.50, and 1.37 and 1.35 times greater in the red zone and the whitish area, respectively) than those in the ablation-only group (P < 0.05/3). Accumulation of Lipiodol was still noted in the hepatic sinusoids in the 3-day and 6-day ablation groups.Conclusion: RF ablation delayed to 6 days following TAE produced larger ablation volumes than did RF ablation alone. [ABSTRACT FROM AUTHOR]

The authors have demonstrated an optical parametric chirped-pulse amplification (OPCPA)/Yb:YAG ceramic thin disk hybrid laser system having hundred mJ level pulse energy sub-picosecond pulse duration with high temporal contrast. At an input chirped-pulse energy of 3.8 mJ from an OPCPA preamplifier an output energy of 130 mJ has been generated from multipass diode-pumped Yb:YAG ceramic thin disk amplifier. A recompressed pulse duration of 450 fs with a contrast level of less than 7.2×10 at −150 ps before the main pulse has been obtained. The contrast level is the highest value achieved in Yb:YAG chirped-pulse amplification (CPA) laser system at 100 mJ level. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic SCT (ASCT) has been investigated as salvage therapy for refractory systemic lupus erythematosus (SLE). Although immune recovery after ASCT with in vitro purging of lymphocytes has been extensively studied, little information is available about immune recovery after ASCT without in vitro purging. Therefore, we analyzed the immune recovery of a patient who successfully underwent ASCT without in vitro purging for refractory SLE. In addition to the numbers of PBL subsets, T-cell receptor rearrangement excision circles (TRECs) and the T-cell receptor repertoire diversity of both CD4+ and CD8+ T cells were sequentially analyzed. All SLE-related symptoms disappeared within 3 months after ASCT and the serum anti-dsDNA Ab became undetectable. The number of CD4+CD45RO+ memory T cells remained lower than that in healthy adult controls, but the number of CD4+CD45RA+ naïve T cells showed a rapid increase after ASCT. TRECs of both CD4+ and CD8+ T cells were strongly suppressed before ASCT, but consistently increased after ASCT. The T-cell receptor repertoire of CD8+ T cells was skewed before ASCT, but the diversity recovered after ASCT. ASCT with the reinfusion of a large number of autologous T cells did not impair the recovery of naive T cells or resetting of the immune system. [ABSTRACT FROM AUTHOR]

Pancreatic arteriovenous malformation (PAVM) is rare and is mainly reported from Asian countries. We incidentally encountered an asymptomatic, early-stage PAVM in a patient who presented with portal venous distention, Child B liver cirrhosis, and hepatoma. The PAVM had multiple feeding arteries and drainage into the portal vein and varices. Because surgery was not indicated, after considering the risks and bene-fits the patient chose treatment with 40 Gy of conformal radiotherapy for 4 weeks. Computed tomography performed 6 months later revealed reduction in the size of the PAVM. Treatment had lasting effects for 18 months without significant toxicity. As observed in many reports of radiotherapy for various AVMs, the radiotherapy may stall self-augmenting growth of the AVM. Conventional fractionated radiotherapy of 40 Gy may be a useful choice for early-stage PAVM. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to compare the strength among bone marrow nails created to treat long bone fractures using interventional procedures. Methods: Twelve resected intact tibiae of healthy swine were used. A circumferential bone fracture was made in nine tibiae and restored with the following created bone marrow nails: acrylic cement alone (ACA) (n=3), acrylic-cement-filled bare metallic stent (AC-FBMS) (n=3), and acrylic-cement-filled covered metallic (AC-FCMS) stent (n=3). The remaining intact tibiae (n=3) were used as controls. Results: A bone marrow nail was successfully achieved within 30 min in all swine. The maximum injection volume of acrylic cement for creating ACA, AC-FBMS, and AC-FCMS was 1.7±0.3, 3.2±0.4, and 2.9±0.4 mL, respectively. The thickness of bone marrow nail created in the ACA, AC-FBMS, and AC-FCMS groups was 3.6±1.0, 10.3±0.26, and 9.6±0.32 mm, respectively (AC-FBMS group versus AC-FCMS group, p=0.038), probably because of leakage of acrylic cement surrounding the interstices. The maximum bending power (kilonewton) and bending strength (newton/mm2) in the normal long bone, ACA, AC-FBMS, and AC-FCMS groups were: 1.70±0.25 and 79.2±16.1; 0.21±0.11 and 8.8±2.8; 0.46±0.06 and 18.2±1.6; and 0.18±0.04 and 7.8±2.7, respectively. Conclusions: Although the maximum bending power and bending strength of AC-FBMS were not satisfactory, it was the most robust of the three marrow nails for restoring fractured long bone. [ABSTRACT FROM AUTHOR]

Objectives:This study examines the gender differences in the association between maternal smoking during pregnancy and later growth in childhood.Design:Ongoing prospective cohort study, which is called 'the Project Koshu', initiated in the foetal stage to the age of 9-10 years.Setting:Koshu City which was in Japanese rural areaParticipants:The study population comprised children born between 1 April 1991 and 31 March 1999 in Koshu City, Japan, and their mothers. Maternal smoking during early pregnancy was the exposure studied.Main outcome measures:Childhood body mass index (BMI) and BMI z-score trajectories of the children born to the smoking and non-smoking mothers by gender. Multilevel analysis that includes both individual and age as different-level variables was used for statistical analyses.Results:The participating mothers delivered 1619 babies during the study period. Birth weight and anthropometric data were collected from 1603 (at birth, 99.0%), 1358 (at age 3, 83.9%), 1248 (at age 5, 77.1%), 1270 (at age 7-8, 78.4%) and 1274 (at age 9-10, 78.7%) of these children. The mean birth weight of both the male and female children whose mothers had smoked during pregnancy was significantly low compared with those born to non-smoking mothers (P<0.01). However, the childhood BMI at each subsequent checkup age significantly increased only among the male children born to the smoking mothers. Moreover, this increase was continuously observed after 3 years of age. The results of BMI z-score analysis were also similar to these of BMI analysis.Conclusions:Smoking by pregnant women decreases the infant birth weight irrespective of gender but increases childhood weight gain especially by male children. The results might be valuable to explore the mechanism of fetal programming. [ABSTRACT FROM AUTHOR]

Since we reported the first successful case of allogeneic hematopoietic SCT (allo-HSCT), we have performed allo-HSCT for 29 patients with chronic active EBV infection (CAEBV), using either myeloablative conditioning (MAC) allo-HSCT (MAST) or reduced-intensity conditioning (RIC) allo-HSCT (RIST). In this retrospective analysis we compared the outcomes after MAST and RIST to identify the optimal conditioning for patients with CAEBV. Of 29 patients, 11 underwent allo-HSCT with MAC, consisting of TBI (12 Gy), etoposide (900 mg/m2) and CY (120 mg/kg) or melphalan (210 mg/m2), and the remaining 18 patients received allo-HSCT after RIC, consisting of fludarabine (∼180 mg/m2) and melphalan (140 mg/m2) or CY (120 mg/kg), with/without antithymocyte globulin and low-dose irradiation. Donor sources were 8 related BM, 2 related peripheral blood, 5 CD34 selected cells from HLA-haploidentical donors, 8 unrelated BM and 8 unrelated cord blood. The 3-year-EFS rate was 54.5±15.0% for MAST group and 85.0±8.0% for RIST group, and the 3-year OS rate was 54.5±15.0% for MAST group and 95.0±4.9% for RIST group (P=0.016). Allo-HSCT after RIC seems to be a promising approach for the treatment of CAEBV. [ABSTRACT FROM AUTHOR]

Purpose: We compared the accuracy of magnetic resonance imaging (MRI) measurements of pulsatile flow velocity in a small tube phantom using different spatial factors versus those obtained by intraluminal Doppler guidewire examination (as reference).Materials and Methods: We generated pulsatile flow velocities averaging about 20-290 cm/sec in a tube of 4 mm diameter; we performed phase-contrast cine MRI on pixels measuring 1.00(2)-2.50(2) mm(2). We quantified spatial peak flow velocities of a single pixel and a cluster of five pixels and spatial mean velocities within regions of interest enclosing the entire lumen in the phantom's cross-section. Finally, we compared the measurements of temporally mean and maximum flow velocity with the Doppler measurements.Results: Linear correlation was excellent between both measurements of spatial peak flow velocities in one pixel. The highest spatial resolution using spatial peak flow velocities of a single pixel allowed the most accurate MRI measurements of both temporally mean and maximum pulsatile flow velocity (r = 0.97 and 0.99, respectively: MRI measurement = 0.95x + 8.9 and 0.88x + 24.0 cm/s, respectively). Otherwise, MRI measurements were significantly underestimated at lower spatial resolutions.Conclusion: High spatial resolution allowed accurate MRI measurement of temporally mean and maximum pulsatile flow velocity at spatial peak velocities of one pixel. [ABSTRACT FROM AUTHOR]

Accessory breast is synonymous with polymastia or supernumerary breast tissue. An accessory breast without a nipple or areola is rare. We report a case of fibroadenoma of an accessory breast with no nipple or areola in a 41-year-old woman who presented with a right axillary mass associated with five small nodules in the normally situated breast. Magnetic resonance imaging (MRI) showed the accessory breast surrounding the tumor. We ignored the presence of the component surrounding the mass and made a preoperative diagnosis of an axillary mass of possible metastases from multiple breast cancers or breast cancer of unknown origin associated with multiple breast fibroadenomas. From a retrospective view, based on the histological results, MRI and dynamic MRI demonstrated a tiny component of breast-like tissue surrounding the axillary mass and an enhancement pattern typical of fibroadenoma for the axillary mass. For the later diagnosis of the axillary mass, the interpretation of whether the component of breast tissue surrounding the axillary mass was present is crucial. If the component exists, a tumor that originated from the accessory breast should be foremost in the differential diagnosis. Dynamic MRI appears to contribute to the diagnosis of fibroadenoma of an accessory breast before biopsy or surgical resection. [ABSTRACT FROM AUTHOR]

Objective:Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese.Methods:Subjects were 521 municipal employees (309 men and 212 women), aged 21–67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D 16) with adjustment for potential confounding variables.Results:We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62–1.59) and 0.44 (0.25–0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms.Conclusions:Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status. [ABSTRACT FROM AUTHOR]

Background/Objectives:In spite of the much evidence for the beneficial effects of probiotics, their anti-obesity effects have not been well examined. We evaluated the effects of the probiotic Lactobacillus gasseri SBT2055 (LG2055) on abdominal adiposity, body weight and other body measures in adults with obese tendencies.Subjects/Methods:We conducted a multicenter, double-blind, randomized, placebo-controlled intervention trial. Subjects (n=87) with higher body mass index (BMI) (24.2–30.7 kg/m2) and abdominal visceral fat area (81.2–178.5 cm2) were randomly assigned to receive either fermented milk (FM) containing LG2055 (active FM; n=43) or FM without LG2055 (control FM; n=44), and were asked to consume 200 g/day of FM for 12 weeks. Abdominal fat area was determined by computed tomography.Results:In the active FM group, abdominal visceral and subcutaneous fat areas significantly (P<0.01) decreased from baseline by an average of 4.6% (mean (confidence interval): −5.8 (−10.0, −1.7) cm2) and 3.3% (−7.4 (−11.6, −3.1) cm2), respectively. Body weight and other measures also decreased significantly (P<0.001) as follows: body weight, 1.4% (−1.1 (−1.5, −0.7) kg); BMI, 1.5% (−0.4 (−0.5, −0.2) kg/m2); waist, 1.8% (−1.7 (−2.1, −1.4) cm); hip, 1.5% (−1.5 (−1.8, −1.1) cm). In the control group, by contrast, none of these parameters decreased significantly. High-molecular weight adiponectin in serum increased significantly (P<0.01) in the active and control groups by 12.7% (0.17 (0.07, 0.26) μg/ml) and 13.6% (0.23 (0.07, 0.38) μg/ml), respectively.Conclusion:The probiotic LG2055 showed lowering effects on abdominal adiposity, body weight and other measures, suggesting its beneficial influence on metabolic disorders. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the safety and short-term efficacy of transcatheter arterial chemoembolization (TACE) using cisplatin-Lipiodol suspension (CP/Lp) with that using epirubicin-Lipiodol emulsion (EP/Lp) in patients with recurrent hepatocellular carcinoma (HCC).Materials and Methods: A total of 28 HCC patients were enrolled prospectively and assigned to the CP/Lp group or EP/Lp group. Adverse effects related to TACE were graded; and the treatment effect (TE) on HCC nodules at 3 months and overall tumor response at 6 months were assessed as the endpoint.Results: No significant difference was observed between the groups regarding the frequency of adverse effects of grade 3 or less. The TE rates for 100% necrosis plus >50% necrosis in 62 HCC nodules in the CP/Lp group and 75 HCC nodules in the EP/Lp group were 72.6% and 66.7%, respectively (P = 0.894). Overall tumor response revealed that six patients (50.0%) in the CP/Lp group and six patients (37.5%) in the EP/Lp group had a partial response plus a complete response, with no significant difference (P = 0.615). TACE-free control curves for both groups revealed no significant difference (P = 0.513).Conclusion: No significant difference was found with regard to adverse effects, the treatment effect on HCC nodules, or overall tumor response between the CP/Lp and EP/Lp groups. [ABSTRACT FROM AUTHOR]