Dirichlet spaces on H-convex sets in Wiener space

We consider the $(1,2)$-Sobolev space $W^{1,2}(U)$ on subsets $U$ in an abstract Wiener space, which is regarded as a canonical Dirichlet space on $U$. We prove that $W^{1,2}(U)$ has smooth cylindrical functions as a dense subset if $U$ is $H$-convex and $H$-open. For the proof, the relations between $H$-notions and quasi-notions are also studied.Comment: 18 pages, 1 figure. Erratum has been added, which was accepted for publication in Bull. Sci. Mat

Risk factors for lower limb lymphedema after lymph node dissection in patients with ovarian and uterine carcinoma

<p>Abstract</p> <p>Background</p> <p>Lymph node dissection has proven prognostic benefits for patients with ovarian or uterine carcinoma; however, one of the complications associated with this procedure is lymphedema. We aimed to identify the factors that are associated with the occurrence of lymphedema after lymph node dissection for the treatment of ovarian or uterine carcinoma.</p> <p>Methods</p> <p>A total of 694 patients with histologically confirmed ovarian (135 patients) or uterine cancer (258 with cervical cancer, 301 with endometrial cancer) who underwent lymph node dissection were studied retrospectively. Logistic regression analyses were used to identify the risk factors associated with occurrence of lymphedema.</p> <p>Results</p> <p>Among ovarian and uterine cancer patients who underwent pelvic lymph node dissection, post-operative radiotherapy (odds ratio: 1.79; 95% confidence interval: 1.20–2.67; p = 0.006) was statistically significantly associated with occurrence of lymphedema.</p> <p>Conclusion</p> <p>There was no relationship between any surgical procedure and occurrence of lymphedema among patients undergoing pelvic lymphadenectomy. Our findings are supported by a sound biological rationale because they suggest that limb lymphedema is caused by pelvic lymph node dissection.</p

Metabolomic correlation-network modules in Arabidopsis based on a graph-clustering approach

<p>Abstract</p> <p>Background</p> <p>Deciphering the metabolome is essential for a better understanding of the cellular metabolism as a system. Typical metabolomics data show a few but significant correlations among metabolite levels when data sampling is repeated across individuals grown under strictly controlled conditions. Although several studies have assessed topologies in metabolomic correlation networks, it remains unclear whether highly connected metabolites in these networks have specific functions in known tissue- and/or genotype-dependent biochemical pathways.</p> <p>Results</p> <p>In our study of metabolite profiles we subjected root tissues to gas chromatography-time-of-flight/mass spectrometry (GC-TOF/MS) and used published information on the aerial parts of 3 <it>Arabidopsis </it>genotypes, Col-0 wild-type, <it>methionine over-accumulation 1 </it>(<it>mto1</it>), and <it>transparent testa4 </it>(<it>tt4</it>) to compare systematically the metabolomic correlations in samples of roots and aerial parts. We then applied graph clustering to the constructed correlation networks to extract densely connected metabolites and evaluated the clusters by biochemical-pathway enrichment analysis. We found that the number of significant correlations varied by tissue and genotype and that the obtained clusters were significantly enriched for metabolites included in biochemical pathways.</p> <p>Conclusions</p> <p>We demonstrate that the graph-clustering approach identifies tissue- and/or genotype-dependent metabolomic clusters related to the biochemical pathway. Metabolomic correlations complement information about changes in mean metabolite levels and may help to elucidate the organization of metabolically functional modules.</p

Supercurrent Distribution in Real-Space and Anomalous Paramagnetic Response in a Superconducting Quasicrystal

We theoretically study the real-space distribution of the supercurrent that flows under a uniform vector potential in a two-dimensional quasiperiodic structure. This is done by considering the attractive Hubbard model on the quasiperiodic Ammann-Beenker structure and studying the superconducting phase within the Bogoliubov-de Gennes mean-field theory. Decomposing the local supercurrent into the paramagnetic and diamagnetic components, we numerically investigate their dependencies on average electron density, temperature, and the angle of the applied vector potential. We find that the diamagnetic current locally violates the current conservation law, necessitating compensation from the paramagnetic current, even at zero temperature. The paramagnetic current shows exotic behaviors in the quasiperiodic structure, such as local currents which are oriented transversally or reversely to that of the applied vector potential.Comment: 14 pages, 11 figure

Biochemical outcomes and predictive factors by risk group after permanent iodine-125 seed implantation: Prospective cohort study in 2,316 patients

Purpose: To evaluate the biochemical freedom from failure (bFFF) by risk group and treatment modality and the predictive factors of bFFF by risk group in patients with prostate cancer undergoing permanent seed implantation (PI) with or without external beam radiation therapy (EBRT) in a nationwide prospective cohort study (Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 [I-125] Seed Implantation) in Japan during the first 2 years. Methods and materials: The analyses included 2,316 participants in 42 institutions; bFFF was evaluated using the Phoenix definition and calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify the factors associated with bFFF. Results: Median followup period was 60.0 months. The 5-year bFFF rates in all patients, 1,028 low-risk patients, 1,114 intermediate-risk patients, and 133 high-risk patients were 93.6%, 94.9%, 92.7%, and 91.1%, respectively. The 5-year bFFF rates in the PI group and EBRT combination therapy group were 93.7% and 93.3%, respectively. In a multivariate analysis, younger age, higher Gleason score (GS), higher percent positive biopsies (%PB), and lower prostate V100 (p = 0.0012, 0.0030, 0.0026, and 0.0368) in all patients; younger age, higher pretreatment prostate-specific antigen, and lower prostate V100 (p = 0.0002, 0.0048, and 0.0012) in low-risk patients; higher GS, higher %PB, and no hormonal treatment (p = 0.0005, 0.0120, and 0.0022) in intermediate-risk patients; and higher GS and higher %PB (p = 0.0329 and 0.0120) in high-risk patients were significantly associated with bFFF. Conclusions: PI with or without EBRT resulted in excellent short-term biochemical outcomes in all risk groups, especially in high-risk patients. Age, pretreatment prostate-specific antigen, and prostate V100 in low-risk patients; GS, %PB, and hormonal treatment in intermediate-risk patients; and GS and %PB in high-risk patients were independently affected bFFF

Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

<p>Abstract</p> <p>Background</p> <p>In Japan, high incidences of interstitial lung disease (ILD) and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC). We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients.</p> <p>Findings</p> <p>We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0). ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%), of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD.</p> <p>Conclusion</p> <p>The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.</p

Frequency-dependent bifurcation point between field-cooled and zero-field-cooled dielectric constant of LiTaO3 nanoparticles embedded in amorphous SiO2

Splitting between the field-cooled dielectric constant and the zero-field-cooled dielectric constant was observed for a diluted system of LiTaO3 nanoparticles (diameter 30 Å) embedded in amorphous SiO2. At the applied field frequency of 100 kHz, the real part of the field-cooled dielectric constant diverged from that of the zero-field-cooled one at 380 °C. The bifurcation point of the history-dependent dielectric constant rose from 310 to 540 °C upon increasing the field frequency from 10 to 1000 kHz. Bulk LiTaO3 powders showed no splitting in the history-dependent dielectric constant and the maximum at 645 °C in the real part of the dielectric constant, despite the variation of frequency. Both the splitting of the history-dependent dielectric constant and the frequency dependence of the bifurcation point suggest that the LiTaO3 nanoparticles with a single-domain structure were in the superparaelectric state as a consequence of insignificant cooperative interactions among the nanoparticles in the diluted system. The energy barrier of 0.9 eV separating two (+p and –p) polarization states corroborated the potential of the LiTaO3 nanoparticle for ultrahigh-density recording media applications

Unbiased characterization of genotype-dependent metabolic regulations by metabolomic approach in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>Metabolites are not only the catalytic products of enzymatic reactions but also the active regulators or the ultimate phenotype of metabolic homeostasis in highly complex cellular processes. The modes of regulation at the metabolome level can be revealed by metabolic networks. We investigated the metabolic network between wild-type and 2 mutant (<it>methionine-over accumulation 1 </it>[<it>mto1</it>] and <it>transparent testa4 </it>[<it>tt4</it>]) plants regarding the alteration of metabolite accumulation in <it>Arabidopsis thaliana</it>.</p> <p>Results</p> <p>In the GC-TOF/MS analysis, we acquired quantitative information regarding over 170 metabolites, which has been analyzed by a novel score (ZMC, z-score of metabolite correlation) describing a characteristic metabolite in terms of correlation. Although the 2 mutants revealed no apparent morphological abnormalities, the overall correlation values in <it>mto1 </it>were much lower than those of the wild-type and <it>tt4 </it>plants, indicating the loss of overall network stability due to the uncontrolled accumulation of methionine. In the <it>tt4 </it>mutant, a new correlation between malate and sinapate was observed although the levels of malate, sinapate, and sinapoylmalate remain unchanged, suggesting an adaptive reconfiguration of the network. Gene-expression correlations presumably responsible for these metabolic networks were determined using the metabolite correlations as clues.</p> <p>Conclusion</p> <p>Two Arabidopsis mutants, <it>mto1 </it>and <it>tt4</it>, exhibited the following changes in entire metabolome networks: the overall loss of metabolic stability (<it>mto1</it>) or the generation of a metabolic network of a backup pathway for the lost physiological functions (<it>tt4</it>). The expansion of metabolite correlation to gene-expression correlation provides detailed insights into the systemic understanding of the plant cellular process regarding metabolome and transcriptome.</p

Ratio of von Willebrand factor propeptide to ADAMTS13 is associated with severity of sepsis.

Von Willebrand factor (VWF)-cleaving protease (ADAMTS13) cleaves ultralarge VWF (ULVWF) secreted from endothelium and by which is regulating its physiologic function. An imbalance between ULVWF secretion and ADAMTS13 level occurs in sepsis and may cause multiple organ dysfunction. We evaluated the association between the VWF-propeptide (VWF-pp)/ADAMTS13 ratio and disease severity in patients with severe sepsis or septic shock. In 27 patients with severe sepsis or septic shock and platelet count less than 120,000/μL, we measured plasma VWF, VWF-pp, and ADAMTS13 levels on hospital days 1, 3, 5, and 7. The VWF-pp/ADAMTS13 ratio was increased greater than 12-fold in patients with severe sepsis or septic shock on day 1 and remained markedly high on days 3, 5, and 7 compared with normal control subjects. The VWF-pp/ADAMTS13 ratio significantly correlated with Acute Physiology and Chronic Health Evaluation II score on days 1 and 5; Sepsis-related Organ Failure Assessment score on days 1, 3, and 5; maximum Sepsis-related Organ Failure Assessment score and tumor necrosis factor α level on days 1, 3, 5, and 7; and creatinine level on days 1, 5, and 7. Patients with greater than stage 1 acute kidney injury had significantly higher VWF-pp/ADAMTS13 ratio than patients without acute kidney injury. In summary, the VWF-pp/ADAMTS13 ratio was associated with disease severity in patients with severe sepsis or septic shock and may help identify patients at risk for multiple organ dysfunction by detecting severe imbalance between ULVWF secretion and ADAMTS13 level.博士（医学）・乙第1318号・平成25年7月22

The Global academic research organization network: Data sharing to cure diseases and enable learning health systems.

Introduction:Global data sharing is essential. This is the premise of the Academic Research Organization (ARO) Council, which was initiated in Japan in 2013 and has since been expanding throughout Asia and into Europe and the United States. The volume of data is growing exponentially, providing not only challenges but also the clear opportunity to understand and treat diseases in ways not previously considered. Harnessing the knowledge within the data in a successful way can provide researchers and clinicians with new ideas for therapies while avoiding repeats of failed experiments. This knowledge transfer from research into clinical care is at the heart of a learning health system. Methods:The ARO Council wishes to form a worldwide complementary system for the benefit of all patients and investigators, catalyzing more efficient and innovative medical research processes. Thus, they have organized Global ARO Network Workshops to bring interested parties together, focusing on the aspects necessary to make such a global effort successful. One such workshop was held in Austin, Texas, in November 2017. Representatives from Japan, Taiwan, Singapore, Europe, and the United States reported on their efforts to encourage data sharing and to use research to inform care through learning health systems. Results:This experience report summarizes presentations and discussions at the Global ARO Network Workshop held in November 2017 in Austin, TX, with representatives from Japan, Korea, Singapore, Taiwan, Europe, and the United States. Themes and recommendations to progress their efforts are explored. Standardization and harmonization are at the heart of these discussions to enable data sharing. In addition, the transformation of clinical research processes through disruptive innovation, while ensuring integrity and ethics, will be key to achieving the ARO Council goal to overcome diseases such that people not only live longer but also are healthier and happier as they age. Conclusions:The achievement of global learning health systems will require further exploration, consensus-building, funding aligned with incentives for data sharing, standardization, harmonization, and actions that support global interests for the benefit of patients