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We present the measured spin correlation coefficient C y , y for p- 3 He elastic scattering at 100 MeV at the angles θ c. m. = 46. 9 ∘ – 149. 2 ∘ in the center of mass system. The experiment was performed using a 100 MeV polarized proton beam in conjunction with the polarized 3 He target. Proton beams were injected to the target, and scattered protons were detected by using E- Δ E detectors which consisted of plastic and NaI(Tl) scintillators. The data are compared with rigorous numerical calculations based on realistic NN potentials as well as with the Δ -isobar excitation. The obtained results indicate that the C y , y expands the knowledge of the nuclear interactions with Δ -isobar or those including 3NFs that are masked in nucleon-deuteron elastic scattering. [ABSTRACT FROM AUTHOR]

The sub- and picosecond optical response dynamics of the metal–dielectric metasurface based on gold nanospheres placed in a layer of bismuth-substituted yttrium iron garnet has been studied via the pump–probe femtosecond spectroscopy with time resolution. It is shown that the plasmon modes of the metasurface demonstrate bulk gold dynamics, while the observed relaxation of the polariton mode is slowed down by several picoseconds. The difference arise because of the detection of different processes at the wavelengths of the plasmon and polariton modes by the probe beam. [ABSTRACT FROM AUTHOR]

Bright, energetic, and directional electron bunches are generated through efficient energy transfer of relativistic intense (~ 1019 W/cm2), 30 femtosecond, 800 nm high contrast laser pulses to grating targets (500 lines/mm and 1000 lines/mm), under surface plasmon resonance (SPR) conditions. Bi-directional relativistic electron bunches (at 40° and 150°) are observed exiting from the 500 lines/mm grating target at the SPR conditions. The surface plasmon excited grating target enhances the electron flux and temperature by factor of 6.0 and 3.6, respectively, compared to that of the plane substrate. Particle-in-Cell simulations indicate that fast electrons are emitted in different directions at different stages of the laser interaction, which are related to the resultant surface magnetic field evolution. This study suggests that the SPR mechanism can be used to generate multiple, bright, ultrafast relativistic electron bunches for a variety of applications. [ABSTRACT FROM AUTHOR]

Background: Evidence of the association between chronic low-grade inflammation, as reflected by C-reactive protein (CRP) measurements, and cancer risk is equivocal. Specifically, few studies have examined this in uncommon cancers and Asian populations.Methods: We utilised a case-cohort design consisting of multi-types of cancer (N = 3608), and a random subcohort (N = 4432) in a Japanese large population-based study, with a median follow-up time of 15.6 years, and measured baseline plasma CRP using high sensitivity assay. The hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods.Results: The multivariable-adjusted HR (95% confidence interval) for the top quartile of CRP was 1.28 (1.11‒1.48) (Ptrend < 0.001) for overall cancer compared to the bottom quartile of CRP. Among site-specific cancers, higher CRP levels were associated with an increased risk of colorectal, lung, breast, biliary tract, and kidney cancer, and leukaemia. These positive associations remained among participants after >3 years' follow-up. Furthermore, subgroup analyses for overall cancer robustly showed a positive association with CRP levels, regardless of sex and obesity.Conclusion: Our consistent findings suggested that chronic low-grade inflammation measured by CRP is associated with the risk of cancer. [ABSTRACT FROM AUTHOR]

We present a precise measurement of 3 He analyzing powers for p- 3 He elastic scattering with the polarized 3 He target at 50, 65, 70, and 100 MeV. The data at 65 and 70 MeV are compared with the theoretical predictions based on the modern nucleon-nucleon potentials. Large discrepancies between the data and the predictions are clearly seen at the angles where the 3 He analyzing power takes the minimum and maximum values, which are not explained by Δ -isobar effects. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. Methods: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. Results: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. Conclusion: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs. [ABSTRACT FROM AUTHOR]

International Ocean Discovery Program (IODP) Expedition 359 cored sediments from eight borehole locations in the carbonate platform of the Maldives in the Indian Ocean. The expedition set out to unravel the timing of Neogene climate changes, in particular the evolution of the South Asian monsoon and fluctuations of the sea level. The timing of these changes are assessed by dating resultant sedimentary alterations that mark stratigraphic turning points in the Neogene Maldives platform system. The first four turning points during the early and middle Miocene are related to sea-level changes. These are reliably recorded in the stratigraphy of the carbonate sequences in which sequence boundaries provide the ages of the sea-level lowstand. Phases of aggradational platform growth give precise age brackets of long-term sea-level high stands during the early Miocene and the early to middle Miocene Climate Optimum that is dated here between 17 to 15.1 Ma. The subsequent middle Miocene cooling coincident with the eastern Antarctic ice sheet expansion resulted in a long-term lowering of sea level that is reflected by a progradational platform growth. The change in platform architecture from aggradation to progradation marks this turning point at 15.1 Ma. An abrupt change in sedimentation pattern is recognized across the entire archipelago at a sequence boundary dated as 12.9-13 Ma. At this turning point, the platform sedimentation switched to a current-controlled mode when the monsoon-wind-driven circulation started in the Indian Ocean. The similar age of the onset of drift deposition from monsoon-wind-driven circulation across the entire archipelago indicates an abrupt onset of monsoon winds in the Indian Ocean. Ten unconformities dissect the drift sequences, attesting changes in current strength or direction that are likely caused by the combined product of changes in the monsoon-wind intensity and sea level fluctuations in the last 13 Ma. A major shift in the drift packages is dated with 3.8 Ma that coincides with the end of stepwise platform drowning and a reduction of the oxygen minimum zone in the Inner Sea. The strata of the Maldives platform provides a detailed record of the extrinsic controlling factors on carbonate platform growth through time. This potential of carbonate platforms for dating the Neogene climate and current changes has been exploited in other platforms drilled by the Ocean Drilling Program. For example, Great Bahama Bank, the Queensland Plateau, and the platforms on the Marion Plateau show similar histories with sediment architectures driven by sea level in their early history (early to middle Miocene) replaced by current-driven drowning or partial drowning during their later history (Late Miocene). In all three platform systems, the influence of currents on sedimentations is reported between 11 and 13 Ma. [ABSTRACT FROM AUTHOR]

Background/objectives: Epidemiologic evidence on the relationship between antioxidant vitamin intake and stroke is limited. We aimed to investigate the association between dietary intake of antioxidant vitamins and the incidence of total stroke and ischemic stroke.Subjects/methods: The subjects were 82 044 Japanese men and women aged 45-74 years under the Japan Public Health Center-based Prospective Cohort Study. Between 1995 and 1997, dietary assessment was done using a food frequency questionnaire. During 983 857 person-years of follow-up until the end of 2009 we documented 3541 incident total strokes and 2138 ischemic strokes.Results: Dietary intakes of α-carotene, β-carotene, α-tocopherol and vitamin C were not inversely associated with the incidence of total stroke and ischemic stroke adjustment for cardiovascular risk factors and selected lifestyle variables. When stratified by current smoking status, the inverse association between dietary vitamin C intake and incidence of total stroke observed among non-smokers but not smokers, with respective multivariable hazard ratios for the highest versus lowest quintiles of vitamin C of 0.81 (95% confidence interval (CI), 0.68-0.96; P-trend=0.03) among non-smokers; and 1.03 (0.84-1.25; P-trend=0.55) among smokers. As for ischemic stroke, the corresponding multivariable hazard ratios were 0.76 (0.60-0.96; P-trend=0.02) among non-smokers; and 1.00 (0.78-1.28; P-trend=0.61) among smokers.Conclusions: Dietary vitamin C intake was inversely associated with the incidence of total stroke and ischemic stroke among non-smokers. [ABSTRACT FROM AUTHOR]

Sleep problems are common in patients with systemic lupus erythematosus (SLE). This study aimed to examine the following: (1) predictors of sleep quality and (2) fluctuations in sleep quality in patients with SLE. Patients with SLE were recruited from three rheumatology centers in Japan. We collected demographic and clinical data and data on sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI), the Medical Outcome Study Short Form-12, and the Lupus Patient Reported Outcome Tool (LupusPRO). Fluctuations in sleep quality were examined by administering the PSQI a second time after a 2-week interval. We used multiple linear regression analysis to predict sleep quality. Of 205 patients who completed the survey, 62.9% showed poor sleep quality. The largest fluctuation in sleep quality was for 'waking in the middle of the night or early morning.' 'LupusPRO pain/vitality' was a major predictor of poor sleep. The other significant predictors were mostly LupusPRO subscales and clinical variables and SF-12 subscales were mostly non-predictive. The majority of the participants had poor sleep quality. A lupus-specific QoL scale is important for understanding poor sleep quality in SLE patients. Symptom management appeared to play a key role in improving sleep quality. [ABSTRACT FROM AUTHOR]

Lichen symbiosis is a successful nutritional strategy that drives lichen distributions in high Arctic ecosystems. However, the in situ effects of fungal partners (mycobionts) on water availability for the photosynthetic partners (photobionts) and their necessity for survival remain unclear. We investigated the factors creating differences in water availability in high Arctic lichen assemblages using observational and experimental analyses of substrates and thallus morphology in the high Arctic, near Ny-Ålesund, Svalbard (79°N) during the snow-free season. We used five lichen species found on five substrate types: moss litter, vascular plant litter, mixed litter, biological soil crust (BSC) and gravel. BSC had significantly higher water content than the other substrates; although it had high levels of surface evaporation, BSC took up more ground water. Moreover, the structure of BSC supported greater water retention than the four other substrates in our study, providing the moistest environment for lichens. In fact, 60 % of the surface area of the crustose lichen Ochrolechia frigida, which was mainly distributed on BSC, was in contact with the substrate. In contrast, the four fruticose lichens had larger surface areas than Och frig and roughly 90 % air exposure. Initial rates of absorption and evaporation increased with greater thallus surface area, suggesting that water availability for photobionts is strongly affected by both morphological characteristics and substrate water properties, both of which depend on mycobionts. We conclude that lichens show preferences for both morphologies and substrates that promote autotrophic nutrition in the water-limited glacier foreland of the high Arctic region. [ABSTRACT FROM AUTHOR]

Background/objectives: Although vitamin D has been experimentally reported to inhibit tumorigenesis, cell growth and prostate cancer invasion, epidemiologic data regarding prostate cancer risk are inconsistent, and some studies have suggested positive but nonsignificant associations. Further, the impact of vitamin D on prostate cancer between Western and Japanese populations may differ due to different plasma vitamin D levels.Subjects/methods: We performed a nested case-control study within the Japan Public Health Center-based Prospective (JPHC) Study in 14,203 men (40-69 years) who answered a self-administered questionnaire at baseline (1990-1994) and gave blood samples, and were followed until 2005. We identified 201 prostate cancers which are newly diagnosed during follow-up (mean 12.8 years). We selected two matched controls for each case from the cohort. We used a conditional logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer with respect to levels of 25-hydroxy vitamin D (25(OH)D) in plasma.Results: We did not observe statistically significant association between 25(OH)D level and total prostate cancer (multivariate OR=1.13 (95%CI=0.66-1.94, Ptrend=0.94) for the highest versus lowest tertile) However, 25(OH) levels were slightly positively associated with advanced cancer. The results remained substantially unchanged after stratification by intake of fish or calcium intake.Conclusions: 25(OH)D level showed no association with overall prostate cancer among Japanese men in this large cohort. [ABSTRACT FROM AUTHOR]

Purpose: Binimetinib is a potent, selective MEK1/2 inhibitor with demonstrated efficacy against BRAF- and RAS-mutant tumors. Retinal adverse events associated with MEK inhibitors have been reported in some cases. The aim of this study was to assess single-agent binimetinib, with detailed ophthalmologic monitoring, in Japanese patients with advanced solid tumors. Methods: This was an open-label phase I dose-escalation and dose-expansion study (NCT01469130). Adult patients with histologically confirmed, evaluable, advanced solid tumors were enrolled and treated with binimetinib 30 or 45 mg twice daily (BID). The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of single-agent binimetinib in Japanese patients. Results: Twenty-one patients were enrolled; 3 and 8 patients had documented BRAF and KRAS mutations, respectively. Two of 6 patients (33 %) receiving binimetinib 45 mg BID in dose-escalation experienced recurrent grade 2 retinal adverse events (AEs) which were reversible, and this dose was declared the MTD and RP2D. All patients experienced ≥1 AE suspected to be treatment related; the most common (>50 %) were blood creatine phosphokinase increase (76 %), retinal detachment and aspartate aminotransferase increase (62 % each), and diarrhea (52 %). There were no complete or partial responses; 14 patients (67 %) had stable disease, which lasted >180 days in 5 patients. Expression of phospho-ERK decreased in the skin following binimetinib treatment at both dose levels, indicating target inhibition. Conclusions: Binimetinib demonstrated efficacy and acceptable safety in Japanese patients with solid tumors, supporting the 45 mg BID dose of binimetinib as the RP2D. [ABSTRACT FROM AUTHOR]

The outcome of 55 children with severe aplastic anemia (SAA) who received a second hematopoietic stem cell transplantation (HSCT) was retrospectively analyzed using the registration data of the Japanese Society for Hematopoietic Cell Transplantation. The 5-year overall survival (OS) and failure-free survival (FFS) after the second transplantation were 82.9% (95% confidence interval (CI), 69.7-90.8)) and 81.2% (95% CI, 67.8-89.4), respectively. FFS was significantly better when the interval between the first and second transplantation was >60 days (88.9%; 95% CI, 73.0-95.7) than when it was ⩽60 days (61.4%; 95% CI, 33.3-80.5; P=0.026). All 12 patients who were conditioned with regimens containing fludarabine and melphalan were alive with hematopoietic recovery. These findings justify the recommendation of a second HSCT for children with SAA who have experienced graft failure after first HSCT. [ABSTRACT FROM AUTHOR]

Purpose: The current study aimed to verify the usefulness of preoperative ultrasonographic evaluation of contralateral patent processus vaginalis (PPV) at the level of the internal inguinal ring. Methods: This was a prospective study of patients undergoing unilateral inguinal hernia repair at two institutions during 2010-2011. The sex, age at initial operation, birth weight, initial operation side, and the preoperative diameter of the contralateral PPV as determined using ultrasonography (US) were recorded. We analyzed the incidence of contralateral inguinal hernia, risk factors, and the usefulness of the preoperative major diameter of the contralateral PPV. The follow-up period was 36 months. Results: All 105 patients who underwent unilateral hernia repair completed 36 months of follow-up, during which 11 patients (10.5 %) developed a contralateral hernia. The following covariates were not associated with contralateral hernia development: sex ( p = 0.350), age ( p = 0.185), birth weight ( p = 0.939), and initial operation side ( p = 0.350). The preoperative major diameter of the contralateral PPV determined using US was significantly wider among patients with a contralateral hernia than those without a contralateral hernia ( p = 0.001). When the 105 patients were divided into two groups according to cut-off values of the preoperative major diameter of the contralateral PPV (wide group, >2.0 mm; narrow group, ≤2.0 mm), a significant association was observed between the preoperative major diameter of the contralateral PPV and patient outcomes ( p = 0.001). Conclusions: We used US and confirmed the usefulness of a preoperative evaluation of the major diameter of the contralateral PPV at the level of the internal inguinal ring in pediatric patients with unilateral inguinal hernias. [ABSTRACT FROM AUTHOR]

Far-upstream element-binding protein-interacting repressor (FIR) is a transcription factor that inhibits c-Myc expression and has been shown to have antitumor effects in some malignancies. Here, we evaluated the antitumor effects of FIR using fusion gene-deleted Sendai virus (SeV/ΔF) as a nontransmissible vector against head and neck squamous cell carcinoma (HNSCC). Using in vitro and in vivo xenograft mouse models, we observed efficient expression of green fluorescent protein (GFP) following transduction with the SeV/ΔF vector encoding GFP (GFP-SeV/ΔF) into HNSCC cells. In vitro and in vivo studies revealed that administration of the FIR-encoded SeV/ΔF (FIR-SeV/ΔF) vector exerted significant antitumor effects, suppressed c-Myc expression and induced apoptosis in HNSCC. Additionally, the antitumor effects of FIR or the expression of GFP following administration of the FIR- or GFP-SeV/ΔF vector, respectively, were dependent on the multiplicity of infection or titer. Furthermore, the SeV/ΔF vector itself had no cytotoxic effects. Therefore, the SeV/ΔF vector may be safe and useful for the treatment of HNSCC, allowing for high-titer SeV/ΔF vector administration for anticancer gene therapy. In addition, SeV/ΔF vector-mediated FIR gene therapy demonstrated effective tumor suppression in HNSCC, suggesting that this therapy may have the potential for clinical use as a novel strategy for HNSCC treatment. [ABSTRACT FROM AUTHOR]

Lateral and temporal profiles for concentrations of Cs and Cs were examined in marine sediments obtained from coastal and offshore areas on the Sea of Japan-side of central Honshu. In 2013, concentrations declined sharply from an estuarine (30 Bq/kg-dry for Cs) to offshore areas. In the offshore Sado Basin, the concentration of short-lived Cs, which was not detected (<0.3 Bq/kg-dry) in 2010, was 1-15 Bq/kg-dry in 2011-2013. Discharged riverine materials affected by radiocesium derived from the Fukushima Dai-ichi Nuclear Power Plant have been delivered to this offshore basin. [ABSTRACT FROM AUTHOR]

We analyzed a total of 25 seawater samples collected from 2 columns within the Sea of Japan for Ra (half life 1,600 years) and Ra (half life 5.75 years) by employing low-background γ-spectrometry. The Ra activity level in the deep proper water (DPW) (~0.13 mBq/L) was found to be higher than that of deep waters from the Pacific and Atlantic Oceans (<0.1 mBq/L), indicating its continuous delivery to the DPW by active water circulation before complete radioactive decay. Using a steady state box model of Ra and Ra, the turn-over time in the DPW was calculated to be ~80 years. [ABSTRACT FROM AUTHOR]

Background: In the tumor microenvironment, factors inhibiting the targeting of cancer cells by activated T cells have recently been noted. B7-H3 belongs to the B7 superfamily of immune regulatory ligands and plays an important role in the adaptive immune response of co-inhibitory/stimulatory factors in regulating T cells. However, the degree to which B7-H3 directly affects tumor immune evasion mechanisms remains unclear, particularly in patients with breast cancer. Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The present study demonstrated that expression of B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment independently affected prognosis in breast cancer patients. Methods: We immunohistochemically investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in pathological specimens from 90 patients with breast cancer. Results: Positive B7-H3 expression was associated with shorter recurrence-free survival (RFS) ( p = 0.014). A higher percentage of Foxp3-positive cells also correlated with shorter RFS ( p = 0.039). Multivariate analysis showed B7-H3 as an independent factor on RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated significantly with larger tumor size (>2 cm), expression of human epidermal growth factor receptor 2 (HER2), and higher nuclear grade ( p = 0.003, p < 0.001, p = 0.001, respectively). No correlation was identified between expression of B7-H3 and the percentage of Foxp3-positive TILs. Conclusions: B7-H3 and Foxp3 can be regarded as markers of poor prognosis in breast cancer. These expressions were not correlated, suggesting that B7-H3 expression plays an independent role in tumor immune evasion, regardless of Tregs. [ABSTRACT FROM AUTHOR]

Summary: This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. Introduction: Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. Methods: Baseline studies were conducted in 1993-1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40-69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. Results: The 10-year cumulative incidence of vertebral fractures was 0.67 %. Those who engaged in strenuous physical activity of <1 h/day had a significantly lower incidence of vertebral fractures than those who did not engage in such activity (RR = 0.52, 95 % CI 0.28-0.97), while those engaged in such activity ≥1 h/day did not (RR = 0.82, 95 % CI 0.58-1.14). Long-duration sedentary activity was associated with a low incidence of vertebral fractures ( P for trend = 0.0002), but the frequencies of sports activities and metabolic equivalents were not ( P for trend = 0.0729 and 0.4341, respectively). Conclusions: Strenuous activity and sedentary activity are associated with the incidence of vertebral fractures, although the association may not be linear. The pattern of association between physical activity and vertebral fractures appears to be different from that of hip fractures. [ABSTRACT FROM AUTHOR]

The mitotic spindle is assembled by the coordinated action of centrosomes and kinetochore microtubules. An evolutionally conserved protein family, transforming acidic coiled-coil (TACC), has been shown to be involved in this process. In humans, TACC3 is aberrantly expressed in a variety of human cancers, but its biological significance remains to be elucidated. Here, using a novel compound targeting TACC3, spindlactone (SPL), we show that the perturbation of TACC3 selectively inhibited the nucleation of centrosome microtubules in ovarian cancer cells. In contrast to centrosome microtubules, the kinetochore microtubules were robustly assembled, forming ectopic spindle poles that resulted in multipolar spindles. Interestingly, the extensive inhibition of TACC3 partially suppressed the nucleation of kinetochore microtubules. These dose-dependent effects of SPL were consistent with the results observed by the depletion of TACC3 and its binding partner, colonic and hepatic tumor overexpressed gene protein (TOGp). Although these proteins both have roles in the assembly of centrosome and kinetochore microtubules, their contributions were spatiotemporally different. Notably, SPL did not affect spindle assembly in normal cells. Furthermore, the oral administration of SPL significantly suppressed tumor growth in vivo. The unique mechanism of action of SPL not only enables it to be used as a tool to dissect the molecular basis of spindle assembly but also to provide a rationale for the use of TACC3 as a molecular target for cancer treatment. This rationale offers an opportunity to develop new strategies for cancer chemotherapy that overcome the limitations of microtubule toxins and expand their scope and clinical efficacy. [ABSTRACT FROM AUTHOR]

Purpose: Morphological assessment of human blastocysts has been effective for selecting embryos with high potential. However, they often show repeated shrinkage and expansion toward their hatching. Here we assessed whether capturing morphological changes over time of vitrified-warmed blastocysts could lead to a better selection of viable embryos from shrunken blastocysts. Methods: The implantation rates of vitrified-warmed blastocysts that were shrunken or expanded (developing) at the time of loading for transfer were compared among 2,729 cycles that were subjected to single blastocyst transfer. Vitrified (107) and fresh blastocysts (17) were donated for the experimental study. To assess the relationship between morphology (expanded vs. shrunken) and the mitochondrial respiration of blastocysts, the oxygen consumption rate (OCR) was analyzed for 55 specimens using an uncoupler of oxidative phosphorylation. The remaining 69 blastocysts were used for recording morphological changes every 15 min for 48 h after warming. Results: Because there were no surplus embryos, 7 % of the vitrified-warmed blastocysts were shrunken and transferred. The shrunken embryos had sufficient implantation ability (40 %). The OCR of the shrunken embryos was significantly lower than that of their expanded counterparts. Upon exposure to the uncoupler, the OCR of some shrunken embryos increased to levels similar to the expanded specimens. Time-lapse images revealed some shrunken embryos which formed blastocoel by 5 h following warming exhibited developmental competence to the hatched stage. Conclusions: Data of the present study suggest a group of shrunken blastocysts contains many viable and clinically available embryos and time-lapse observation of vitrified-warmed blastocysts is a potential method to distinguish viable embryos from shrunken blastocysts. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the images created in a model eye during simulated cataract surgery.Patients and methodsThis study was conducted as a laboratory investigation and interventional case series. An artificial opaque lens, a clear intraocular lens (IOL), or an irrigation/aspiration (I/A) tip was inserted into the 'anterior chamber' of a model eye with the frosted posterior surface corresponding to the retina. Video images were recorded of the posterior surface of the model eye from the rear during simulated cataract surgery. The video clips were shown to 20 patients before cataract surgery, and the similarity of their visual perceptions to these images was evaluated postoperatively.ResultsThe images of the moving lens fragments and I/A tip and the insertion of the IOL were seen from the rear. The image through the opaque lens and the IOL without moving objects was the light of the surgical microscope from the rear. However, when the microscope light was turned off after IOL insertion, the images of the microscope and operating room were observed by the room illumination from the rear. Seventy percent of the patients answered that the visual perceptions of moving lens fragments were similar to the video clips and 55% reported similarity with the IOL insertion. Eighty percent of the patients recommended that patients watch the video clip before their scheduled cataract surgery.ConclusionsThe patients' visual perceptions during cataract surgery can be reproduced in the model eye. Watching the video images preoperatively may help relax the patients during surgery. [ABSTRACT FROM AUTHOR]

Purpose: Previously, we established a pre-operative risk scoring system to predict contralateral inguinal hernia in children with unilateral inguinal hernias. The current study aimed to verify the usefulness of our pre-operative scoring system. Methods: This was a prospective study of patients undergoing unilateral inguinal hernia repair from 2006 to 2009 at a single institution. Gender, age at initial operation, birth weight, initial operation side, and the pre-operative risk score were recorded. We analyzed the incidence of contralateral inguinal hernia, risk factors, and the usefulness of our pre-operative risk scoring system. The follow-up period was 36 months. We used forward multiple logistic regression analysis to predict contralateral hernia. Results: Of the 372 patients who underwent unilateral hernia repair, 357 (96.0 %) were completely followed-up for 36 months, and 23 patients (6.4 %) developed a contralateral hernia. Left-sided hernia (OR = 5.5, 95 %, CI = 1.3-24.3, p = 0.023) was associated with an increased risk of contralateral hernia. The following covariates were not associated with contralateral hernia development: gender ( p = 0.702), age ( p = 0.215), and birth weight ( p = 0.301). The pre-operative risk score (cut-off point = 4.5) of the patients with a contralateral hernia was significantly higher, compared with the patients without a contralateral hernia using the area under the receiver operating characteristic curve ( p = 0.024). Conclusions: Using multivariate analysis, we confirmed usefulness of our pre-operative scoring system and initial side of the inguinal hernia, together, for the prediction of contralateral inguinal hernia in children. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) incidence rate increased rapidly in Japan between the 1950s and 1990s. We examined the association between rice intake and CRC risk in comparison with bread, noodles and cereal among Japanese adults enrolled in the Japan Public Health Center-based prospective Study.Methods: A total of 73,501 Japanese men and women were followed-up from 1995 to 1999 until the end of 2008 for an average of 11 years. During 801,937 person-years of follow-up, we identified 1276 incident cases of CRC. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC for rice, noodle, bread and cereal intake were calculated by Cox proportional hazards model.Results: Overall, no significant association was observed for the highest quartile of rice intake compared with the lowest and the risk of CRC and its subsites in men (HR, 0.77; 95% CI, 0.56-1.07) and women (HR, 1.10; 95% CI, 0.71-1.68). However, a non-significant inverse trend was observed between rice intake and rectal cancer in men. No clear patterns of association were observed in bread, noodle and cereal intake.Conclusion: Our findings suggest that the consumption of rice does not have a substantial impact on the risk of CRC in the Japanese population. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the functional outcomes of patients with polypoidal choroidal vasculopathy (PCV) who underwent intravitreal ranibizumab (IVR) treatment, compared with photodynamic therapy (PDT), after at least 2 years.MethodsWe retrospectively studied all the treatment-naïve patients with PCV who were scheduled to undergo IVR or PDT between August 2005 and June 2010. All the patients who had a 2-year or longer follow-up period were included in the study. The best-corrected visual acuity (BCVA) in the two groups was compared before treatment and at 3, 6, 12, 18 and 24 months after the initial treatment. The regression of the polyps was also assessed using indocyanine green angiography.ResultsA total of 77 patients were included in this study. Thirty-three eyes were treated with IVR, and 44 eyes were treated with PDT. Although no significant differences between the two groups were observed at baseline or at 3, 6, and 12 months after treatment, a significantly better BCVA was seen in the IVR group, compared with the PDT group, at 18 and 24 months after treatment (P=0.035 and P=0.021, respectively). No significant difference in the rate of polyp regression was observed between the two groups (P=0.092).ConclusionIVR was well tolerated and maintained or improved the vision of patients with PCV, compared with PDT, as evaluated at 2-year follow-up examinations. PDT for the treatment of PCV might result in unfavorable outcomes, with no superiority to achieving the involution of polyps. [ABSTRACT FROM AUTHOR]

Primary graft failure (pGF) is associated with considerable morbidity and mortality. Salvage hematopoietic SCT (HSCT) can rescue pGF patients; however, the optimal preconditioning regimen and stem cell source are yet to be determined, particularly in children. In this study, we retrospectively analyzed 102 pediatric patients who received salvage allogeneic HSCT for pGF. Salvage HSCT from matched or one-Ag-mismatched related donors (rMM01) provided superior OS compared with that from two- or three-Ags-mismatched related donors (rMM23) or cord blood transplantation (CBT). CBT showed a trend toward a slightly lower engraftment rate and late engraftment achievement compared with rMM23; however, the OS rate was similar between the two groups (47.6±7.7% for rMM23 and 45.7±8.6% for CBT, at 1 year after salvage HSCT). Multivariate analysis showed that preconditioning regimens with fludarabine or irradiation were associated with a higher engraftment rate and those with alkylating agents were associated with better OS. In conclusion, our results showed that rMM01 was the most suitable donor for salvage HSCT for pediatric pGF, and that CBT was an equally important option compared with rMM23 for patients without rMM01. [ABSTRACT FROM AUTHOR]

In lotic systems, the hyporheic zone has been suggested as a potential refuge for aquatic organisms during disturbances (hyporheic refuge hypothesis). However, the supporting evidence is unclear, especially regarding the survival of hyporheic refugees and their contribution to the recovery of post-disturbance populations. Moreover, few studies have focused on the importance of the hyporheic refuge for aquatic vertebrates such as fish. In this study, we present evidence that the hyporheic zone acts as a refuge for a small benthic fish ( Cobitis shikokuensis) following surface drying in an intermittent river. We examined its survival during and recolonization after dry periods by direct hyporheic sampling and mark-and-recapture surveys. When the streambed dried, hyporheic sampling was conducted 58 times across 33 locations in the intermittent reach and 31 individuals of C. shikokuensis were captured from extracted hyporheic water. Mark-and-recapture surveys revealed that recolonizers after re-wetting included C. shikokuensis individuals that had survived dry periods in the hyporheic refuge. The condition factor of C. shikokuensis significantly declined after dry periods, suggesting that most recolonizers suffered from physiological stress, probably within the hyporheic refuge. These results clearly support the long-debated, hyporheic refuge hypothesis, and provide a striking example of the critical role of the hyporheic zone in population maintenance of lotic organisms. [ABSTRACT FROM AUTHOR]

Background/objective:Dietary patterns in Western populations have been linked to type 2 diabetes, but the association of distinctive dietary patterns of Japanese population remains unclear. We prospectively investigated the association between dietary patterns and risk of developing type 2 diabetes among Japanese adults.Subjects/methods:Participants were 27 816 men and 36 889 women aged 45-74 years who participated in the second survey of the Japan Public Health Center-based prospective study and had no history of diabetes. Dietary patterns were derived by using principal component analysis of the consumption of 134 food and beverage items ascertained by a food frequency questionnaire. Odds ratios of self-reported physician-diagnosed type 2 diabetes over 5 year were estimated using logistic regression analysis.Results:A total of 1194 new cases (692 men and 502 women) of type 2 diabetes were self-reported. We identified three dietary patterns: prudent, westernized and traditional Japanese patterns. Any dietary pattern was not significantly associated with type 2 diabetes risk after adjustment for covariates in both men and women. The multivariate-adjusted odds ratios (95% confidence interval) for type 2 diabetes for the highest versus lowest quartile of each dietary pattern score in men and women, respectively, were 0.93 (0.74-1.16) and 0.90 (0.69-1.16) for the prudent pattern, 1.15 (0.90-1.46) and 0.81 (0.61-1.08) for the westernized pattern, and 0.97 (0.74-1.27) and 0.87 (0.66-1.15) for the traditional pattern.Conclusions:Although a small protective effect of the prudent dietary pattern cannot be excluded, dietary patterns may not be appreciably associated with type 2 diabetes risk in Japanese. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively investigate the short-term therapeutic effects and adverse effects associated with the use of miriplatin-lipiodol suspension for transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC), using TACE with cisplatin-lipiodol suspension as the historical control.Materials and Methods: The study was conducted on 48 and 50 consecutive patients with HCC who underwent TACE with miriplatin-lipiodol suspension and cisplatin-lipiodol suspension, respectively. Therapeutic effect was evaluated by mRECIST. Adverse effects were graded by CTCAE, version 4.0. The therapeutic and adverse effects were compared using Fisher's exact test and multivariate logistic regression.Results: Complete remission, partial response, stable disease and progressive disease were observed in 37.5, 18.8, 33.3 and 10.4 % of patients in the miriplatin group, with the corresponding percentages being 54.0, 32.0, 14.0 and 0.0 %, respectively, in the cisplatin group. The short-term therapeutic effects were statistically significantly worse in the miriplatin group than in the cisplatin group, even after adjustment for tumor size and Child-Pugh class. The rates of nausea and serum creatinine elevation were statistically significantly lower in the miriplatin group (p < 0.05).Conclusion: TACE using miriplatin-lipiodol suspension yielded worse short-term responses than cisplatin-lipiodol suspension; however, the rates of adverse events were significantly lower in the miriplatin group. [ABSTRACT FROM AUTHOR]

A second SCT is generally accepted as the only potentially curative approach for ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL is not fully understood. We performed a retrospective analysis of 171 pediatric patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2 years was 29.4±3.7%, the cumulative incidence of relapse was 44.1±4.0% and non-relapse mortality was 18.8±3.5%. Relapse occurred faster after the second SCT than after the first SCT (117 days vs 164 days, P=0.04). Younger age (9 years or less), late relapse (180 days or more after first SCT), CR at the second SCT, and myeloablative conditioning were found to be related to longer survival. Neither acute GVHD nor the type of donor influenced the outcome of second SCT. Multivariate analysis showed that younger age and late relapse were associated with better outcomes. Our analysis suggests that second SCT for relapsed pediatric ALL is an appropriate treatment option for patients that have achieved CR, which is associated with late relapse after the first SCT. [ABSTRACT FROM AUTHOR]

Background:Recently developed detection system for circulating tumour cells (CTCs) using a telomerase-specific replicative adenovirus generated nonspecific green fluorescent protein (GFP) signals because of the co-presence of white blood cells (WBCs) nonspecifically infected by viruses. Here, we established a unique detection system for CTCs that completely excludes nonspecific signals.Methods:Blood obtained from the patients was subjected to haemolytic processes to eliminate red blood cells. The cell pellets were then infected with OBP-401, fixed, incubated with fluorescence-labelled anti-CD45 antibody to mark white blood WBCs, and examined on slides under a microscope.Results:Preparatory experiments with cancer cells artificially added to healthy donor samples confirmed that CD45 labelling could distinguish GFP-positive cancer cells from WBCs. In 53 patients with gynaecological cancers, CTCs were detected in 21 patients (39.6%) when CD45-positive cells were excluded as WBCs among GFP-positive cells. No CTCs were detected in samples from healthy volunteers. There was no significant correlation between CTC counts and known clinicopathological factors. The CTCs rapidly vanished after surgery or chemotherapy in most patients whose treatments were effective. In contrast, the persistence of CTCs even after treatments was tightly associated with poor response to the treatments (P<0.005).Conclusion:The presence of CTCs in our system may potentially be a novel therapeutic marker in gynaecological cancers. [ABSTRACT FROM AUTHOR]

Background:Epithelial cells of endometriotic tissues are difficult to propagate in vitro as experimental material is scarce owing to their limited life span. However, there is an increasing concern regarding their malignant transformation in ovaries. The present study sought to generate their stable culture system.Methods and results:Purified epithelial cells isolated from ovarian endometriomas using microscopic manipulation were successfully immortalised by combinatorial transfection of human cyclinD1, cdk4 and human telomerase reverse transcriptase (hTERT) genes, whereas the introduction of hTERT alone, or together with cdk4, was insufficient for immortalisation, leading to cellular senescence. We confirmed stable cytokeratin expression in the immortalised cells, proving their epithelial origin. These cells expressed progesterone receptor B and showed significant growth inhibition by various progestins. Oestrogen receptor (ER) expression was detected in these cells, albeit at low levels. Additional overexpression of ERα generated stable cells with oestrogen-dependent growth activation. Soft-agar colony formation assay and nude mice xenograft experiments demonstrated that these cells, even those with additional inactivation of p53, did not have transformed phenotypes.Conclusion:We for the first time generated immortalised epithelial cells from ovarian endometrioma that retained sex steroid responsiveness. These cells are invaluable tools not only for the consistent in vitro work but also for the study of molecular pathogenesis or carcinogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Background: For the treatment of chronic hepatitis C, a combination of pegylated interferon-α (PEG-IFNα) and ribavirin has been widely used as a standard of care. Enhancement of immune response against hepatitis C virus (HCV) is known to be involved in the efficacy of the combination therapy. Our aim was to elucidate whether or not the frequency or function of blood cells is related to the outcome of the therapy.Methods: Sixty-seven chronic hepatitis C patients with high viral load of HCV genotype 1 infection who underwent 48 weeks of PEG-IFNα2b and ribavirin therapy were examined. During the treatment, frequencies of myeloid or plasmacytoid dendritic cells, Th1, Th2 cells, NK cells, and regulatory T cells were phenotypically determined.Results: Among the patients enrolled, 29 showed a sustained virological response (SVR), 18 a transient response (TR) and 17 no response (NR). The clinical and immunological markers were compared between the SVR and non-SVR patients, including TR and NR. Based on clinical, histological, immunological parameters, and cumulative dosage of PEG-IFNα2b and ribavirin, multivariate analyses revealed that higher platelet counts and higher regulatory T cell frequency at week 12 are indicative of SVR. Even in patients who attained complete early virological response at week 12, multivariate analyses disclosed that higher platelet counts and higher plasmacytoid dendritic cell frequency are indicative of SVR.Conclusions: In PEG-IFNα and ribavirin combination therapy for chronic hepatitis C patients, the increments of regulatory T cells and plasmacytoid dendritic cell frequency are independently related to favorable virological response to the therapy. [ABSTRACT FROM AUTHOR]

Background/Objectives:There has been no study with regard to the association between dietary fibers and the incidence of stroke and coronary heart disease (CHD) in Asia. We investigated the association between dietary fiber and the risk of cardiovascular disease (CVD), which we defined as stroke or CHD, in a Japanese population.Subjects/Methods:We studied 86 387 Japanese subjects (age 45-65 years, without CVD or cancer in 1995 as Cohort I and in 1998 as Cohort II) and used a self-administered questionnaire to follow-up the participants until the end of 2004. Dietary fiber intake was estimated from food-frequency questionnaires comprising 138 food items.Results:After 899 141 person-years of follow-up, we documented the incidence of 2553 strokes and 684 cases of CHD. Multivariable-adjusted hazard ratios (95% confidence intervals (CIs)) of CVD for the third to fifth quintiles of total fiber were 0.79 (0.63-0.99), 0.70 (0.54-0.89) and 0.65 (0.48-0.87) in women, respectively, compared with the lowest quintile. Total fiber intake was inversely associated with the incidence of stroke, either cerebral infarction or intracerebral hemorrhage in women. The results for insoluble fiber in women were similar to those for total fiber, whereas those for soluble fiber were weak. An inverse association of total fiber with CVD was observed primarily in non-smokers (P for trend=0.045 and 0.001) and not in smokers (probability values for interaction between total fiber and smoking were 0.06 and 0.01 in men and women, respectively).Conclusions:Higher total dietary fiber was associated with reduced risk of CVD in Japanese non-smokers. [ABSTRACT FROM AUTHOR]

IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLA-matched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P=0.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI, 0.75-45.72; P=0.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P=0.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD. [ABSTRACT FROM AUTHOR]

The interaction of linearly polarized light with photonic crystals based on bulk and thin-film synthetic opals is studied. Experimental transmission spectra and spectra showing the polarization state of light transmitted through opals are discussed. A change in polarization is found for waves experiencing Bragg diffraction from systems of crystallographic planes of the opal lattice. It is shown that the polarization plane of the incident linearly polarized wave at the exit from photonic crystals can be considerably rotated. In addition, incident linearly polarized light can be transformed to elliptically polarized light with the turned major axis of the polarization ellipse. Analysis of polarization states of transmitted light by using the transfer-matrix theory and homogenization theory revealed good agreement between calculated and experimental spectra. [ABSTRACT FROM AUTHOR]

Fcγ receptor type IIIA (FCGR3A) has a functional single-nucleotide polymorphism (rs396991), at which a G-to T-point mutation results in an amino acid substitution at position 158 (valine to phenylalanine; V158F). This study examined the effect of the FCGR3A polymorphism in donors and recipients on the clinical outcomes in unrelated HLA fully matched myeloablative BMT. The FCGR3A-V158F genotype was retrospectively analyzed in a total of 99 recipients with myeloid malignancies, and their unrelated donors. The presence of the 158V genotype in recipients showed a statistically better OS (adjusted hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.26-0.93; P=0.03) and TRM (HR 0.30; 95% CI 0.14-0.67; P=0.003) without significant influence on the relapse rate. The recipient 158V genotype was also associated with a significantly reduced risk of chronic GVHD (HR 0.45; 95% CI 0.20-0.99; P=0.049) and a trend toward a reduced risk of grade II-IV acute GVHD (HR 0.55; 95% CI 0.27-1.10; P=0.09), leading to a significantly reduced GVHD-related mortality (HR 0.22; 95% CI 0.06-0.77; P=0.02). The donor FCGR3A polymorphism did not have any effect on the transplant outcomes. These results suggest an association between the recipient FCGR3A genotype and the clinical outcomes after BMT. [ABSTRACT FROM AUTHOR]

Objective:The Japan Public Health Center-based prospective Study examined the association of body mass index (BMI) and weight change with incident stroke in Japanese individuals, for whom BMI levels are generally low.Methods:We used initial data from 1990 to 1994 and 5-year follow-up surveys from 1995 to 1999. We calculated weight change over a 5-year period for 32 847 men and 38 875 women, aged 45-74 years, with no history of cardiovascular disease or cancer. Subjects were followed from the 1995-1999 survey to the end of 2005, and hazard ratios of self-reported BMI levels and weight change for incident stroke were estimated using Cox's proportional hazard models adjusted for potential confounders.Results:During the follow-up period (median 7.9 years) there were 2019 incident strokes, including subtypes. Multivariable-adjusted hazard ratios for all stroke events by BMI levels of 27.0-29.9 and 30 kg m-2 versus 23.0-24.9 kg m-2 were 1.09 (95% confidence interval 0.88, 1.36) and 1.25 (0.86, 1.84) in men (P for trend=0.22), and 1.29 (1.01, 1.65) and 2.16 (1.60, 2.93) in women (P for trend <0.001), respectively. A weight change of 10% in the previous 5 years was associated with total strokes and ischemic strokes in women.Conclusion:Higher BMI levels and a weight gain of 10% over 5 years were associated with an increased risk of stroke in women, whereas this association was weak in men. [ABSTRACT FROM AUTHOR]

Background: Identification of tumour-associated antigens (TAAs) that induce cytotoxic T lymphocytes (CTLs) specific to cancer cells is critical for the development of anticancer immunotherapy. In this study, we aimed at identifying a novel TAA of pancreatic cancer for immunotherapy.Methods: On the basis of the genome-wide cDNA microarray analysis, we focused on KIF20A (also known as RAB6KIFL/MKlp2) as a candidate TAA in pancreatic cancer cells. The HLA-A2 (A*02:01)-restricted CTL epitopes of KIF20A were identified using HLA-A2 transgenic mice (Tgm) and the peptides were examined to check whether they could generate human CTLs exhibiting cytotoxic responses against KIF20A(+), HLA-A2(+) tumour cells in vitro.Results: KIF20A was overexpressed in pancreatic cancer and in some other malignancies, but not in their non-cancerous counterparts and many normal adult tissues. We found that KIF20A-2 (p12-20, LLSDDDVVV), KIF20A-8 (p809-817, CIAEQYHTV), and KIF20A-28 (p284-293, AQPDTAPLPV) peptides could induce HLA-A2-restricted CTLs in HLA-A2 Tgm without causing autoimmunity. Peptide-reactive human CTLs were generated from peripheral blood mononuclear cells of HLA-A2(+) healthy donors by in vitro stimulation with the three peptides, and those CTLs successfully exhibited cytotoxic responses to cancer cells expressing both KIF20A and HLA-A2.Conclusion: KIF20A is a novel promising candidate for anticancer immunotherapeutic target for pancreatic cancers. [ABSTRACT FROM AUTHOR]

We retrospectively audited the performance of the commercial kit in use in our laboratory for the detection of Mycobacterium tuberculosis complex (MTBC) and found the sensitivity to be unacceptably low at 69% (52/75). We developed an in-house end-point polymerase chain reaction (PCR) detecting IS6110, an IS-like element of MTBC, and achieved a sensitivity of 90% (66/73) with the same DNA samples, re-emphasising the poor performance of the commercial kit. In order to avoid specificity issues surrounding gel-based PCR, we developed a probe-based real-time PCR assay with an internal control and achieved a sensitivity of 84%, specificity of 97% and diagnostic odds ratio (DOR) of 207. The evaluation was performed on clinically requested samples, so we expect the performance of the assay in real life to match the data from this evaluation. Centers for Disease Control and Prevention (CDC) guidelines recommending nucleic acid tests for the investigation of possible cases of tuberculosis are expected to promote the use of molecular assays. It is important that clinical laboratories do not assume that assays, in-house or commercial, will perform well or that they will continue to perform well. Audit at regular intervals is necessary to maintain confidence and to demonstrate that the assay works to specification in the real test population. [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]

We report characterization of ZnO thin-film transistors (TFTs) on glass substrates fabricated by pulsed laser deposition (PLD). ZnO films were characterized by X-ray diffraction (XRD), atomic force microscopy and Hall effect measurements. The XRD results showed high c-axis-oriented ZnO(0002) diffraction corresponding to the wurtzite phase. Moreover, the crystallization and the electrical properties of ZnO thin films grown at room temperature are controllable by PLD growth conditions such as oxygen gas pressure. The ZnO films are very smooth, with a root-mean-square roughness of 1 nm. From the Hall effect measurements, we have succeeded in fabricating ZnO films on glass substrates with an electron mobility of 21.7 cm/V s. By using the ZnO thin film grown by two-step PLD and a HfO high- k gate insulator, a transconductance of 24.1 mS/mm, a drain current on/off ratio of 4.4×10 and a subthreshold gate swing of 0.26 V/decade were obtained for the ZnO TFT. [ABSTRACT FROM AUTHOR]

This study examined the association between magnesium intake and type II diabetes risk among Japanese adults. Participants were 25 872 men and 33 919 women aged 45-75 years who had no history of diabetes. Magnesium intake was ascertained using a 147-item food frequency questionnaire. Odds ratio of self-reported physician-diagnosed type II diabetes over 5 years was estimated using logistic regression analysis. A total of 1114 new cases of type II diabetes were self-reported. Magnesium intake was not significantly associated with type II diabetes in either men or women. The multivariable-adjusted odds ratios (95% confidence intervals) of type II diabetes for the highest versus lowest quintile of magnesium intake were 0.86 (0.63-1.16) and 0.92 (0.66-1.28) for men and women, respectively. Although a small effect cannot be excluded in men, magnesium intake may not be appreciably associated with risk of type II diabetes for Japanese adults. [ABSTRACT FROM AUTHOR]

The evolution of the phase-structure state of Fe-ZrN films grown by RF magnetron sputtering and annealed at T = 200-650°C has been studied by transmission electron microscopy, high-resolution electron microscopy, and X-ray diffraction analysis. It has been found that the initial state of the film contains 1- to 5-nm crystallites of α-Fe-based solid solution supersaturated with nitrogen. The number of such crystallites increases, the concentration of nitrogen in them decreases and 2- to 10-nm nanocrystallites of ZrN and Fe2N nitride phases appear after annealing. The formation of zirconium nitride at the first stage (200-500°C) is associated with a decrease in the degree of supersaturation of the α-Fe lattice with nitrogen. At a higher annealing temperature (650°C), a decrease in the nitrogen concentration in the lattices of both the bcc Fe and zirconium nitride phase leads to the formation of iron nitride crystallites. [ABSTRACT FROM AUTHOR]

Background: Disabled phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase signalling is involved in endometrial carcinogenesis, and there is evidence that expression of epidermal growth factor receptor (EGFR) family members has a role in such intracellular signalling pathways. This study analysed the prognostic impact of EGFR family expression in endometrial cancer in relation to PI3K-AKT and MAPK-ERK signalling, as well as drug sensitivity.Methods and Results: Immunohistochemical analysis using 63 surgical specimens of endometrioid-type endometrial cancers revealed that EGFR, human epidermal growth factor receptor (HER)-2 and HER-4 were expressed in 25 (39.7%) of 63, 26 (41.3%) of 63 and 31 (49.2%) of 63 tumours, respectively. Gene amplification of HER-2 was observed in 2 of 26 patients with high HER-2 expression. Kaplan-Meier analysis revealed that high HER-2 expression was a factor that negatively influenced the progression-free and overall survival rate (P<0.05), and multivariate analysis showed high HER-2 expression to be an independent prognostic factor. Subsequently, we performed in vitro knockdown analysis to investigate the linkage between HER-2 expression and PI3K-AKT pathways. Short interfering RNA (siRNA)-based knockdown of HER-2 in endometrial cancer cells led to a significant reduction in phosphorylated AKT (p-AKT) expression, indicating the existence of a HER-2/PI3K-AKT axis. As the PI3K-AKT pathway is known to have crucial roles in anticancer drug sensitivity, we examined the involvement of HER-2 in sensitivity to paclitaxel. Short interfering RNA-based knockdown of HER-2 conferred increased sensitivity to paclitaxel in endometrial cancer cells, attenuating the induction of p-AKT on paclitaxel stimulation, which was cancelled by inactivating AKT by the introduction of a dominant-negative form.Conclusion: HER-2 is a significant prognostic factor of endometrioid-type endometrial cancer, as well as a key molecule that affects paclitaxel sensitivity by HER-2 interaction with the PI3K-AKT pathway. [ABSTRACT FROM AUTHOR]