Kohei Fujita

Predictors of 5-year mortality in pulmonary Mycobacterium avium-intracellulare complex disease.

SETTING Kyoto, Japan. OBJECTIVE To determine predictors of 5-year mortality in pulmonary Mycobacterium avium-intracellulare complex (MAC) disease. DESIGN Retrospective study of 164 patients diagnosed with pulmonary MAC disease between 1999 and 2005 and followed for 5 years. RESULTS Overall 5-year mortality was 28.0%. Among 117 patients with microbiological outcomes, 54 were treated (treated MAC patients) and 24 were not treated and did not experience sputum culture conversion during follow-up (untreated chronic MAC patients); 39 patients were not treated and experienced sputum culture conversion. Five-year all-cause overall mortality among the 78 patients with definite MAC disease (including treated and untreated chronic MAC patients) was 25.6%. The mortality rate was 33.3% for untreated chronic MAC patients only vs. 22.2% for treated MAC patients (P = 0.30). After adjustment for clinical, microbiological and radiological confounders, independent factors for 5-year mortality were a high Charlson comorbidity index in cases with definite MAC disease (hazard ratio [HR] 1.76) and untreated chronic MAC (HR 3.08), and presence of cavitary lesions in cases with definite MAC disease (HR 1.82) and treated MAC patients (HR 3.91). CONCLUSION Patients with cavitary lesions require immediate treatment for sputum culture conversion and to improve their chances of survival.

Optimal placement of viscoelastic dampers and supporting members under variable critical excitations

The concept of performance-based design has recently been introduced and is well accepted in the current structural design practice of buildings. In earthquake-prone countries, the philosophy of earthquake-resistant design to resist ground shaking with sufficient stiffness and strength of a building itself has also been accepted as a relevant structural design concept for many years. On the other hand, a new strategy based on the concept of active and passive structural control has been introduced rather recently in order to provide structural designers with powerful tools for performance-based design.

Environmental Risk Factors for Pulmonary Mycobacterium avium-intracellulare Complex Disease

BACKGROUND Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous pathogen found in soil and water. Environmental exposure is the primary route for MAC infection. However, specific environmental risk factors have been poorly determined in immunocompetent patients with pulmonary MAC disease. METHODS A case-control study was performed with 106 patients with pulmonary MAC disease (men [women], 23 [83]; age, 64.3 ± 9.2 years) and 53 age-matched control patients with bronchiectasis but not pulmonary MAC infection (men [women], 7[46]; age, 63.0 ± 11.0 years). All participants completed a standardized questionnaire that included questions about medical history, smoking history, alcohol usage, age at menopause, and environment exposures. Environment exposures included soil exposure from farming or gardening; water exposure from bathing, showering, hot tub use, dishwashing, swimming, and drinking water; and pet exposure. RESULTS No differences were identified in the patient characteristics and underlying diseases. More case patients experienced high soil exposure (≥ 2 per week) than control patients (23.6% vs 9.4%, P = .032); this remained significant after multivariate analysis (OR, 5.9; 95% CI, 1.4-24.7; P = .015). There were no significant differences in other environmental exposures. Case patients with high soil exposure were significantly older than those with low soil exposure (67.3 ± 7.3 years vs 64.3 ± 9.5 years, P = .037). Other characteristics, underlying diseases, and mycobacterial species did not differ between the two groups. CONCLUSIONS Patients with pulmonary MAC disease had significantly more soil exposure than noninfected control patients, which suggests that environmental soil exposure is a likely risk factor for the development of pulmonary MAC disease.

Decreased Lectin-Like Oxidized LDL Receptor 1 (LOX-1) and Low Nrf2 Activation in Placenta Are Involved in Preeclampsia

CONTEXT Serum concentration of oxidized low-density lipoprotein (oxLDL) is higher in women with preeclampsia than in normal pregnant woman. Lectin-like oxLDL receptor-1 (LOX-1) is one of the scavenger receptors for oxLDL and is abundantly expressed in placenta. It is well known that oxLDL activates nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant and cytoprotective genes such as heme oxygenase-1 (HO-1), which play an important role in preeclampsia. However, it has yet to be elucidated whether LOX-1, along with Nrf2, participates in the pathology of preeclampsia. OBJECTIVE The objective of the study was to assess LOX-1 expression and Nrf2 activation in preeclamptic placentas and to manifest their physiological roles in preeclampsia. METHODS Expression and regulation of LOX-1, HO-1, and Nrf2 were evaluated by real-time quantitative RT-PCR and Western blotting. The functions of LOX-1 and Nrf2 were examined using an anti-LOX-1 antibody and Nrf2 activator in JAR, a choriocarcinoma cell line, and placental explants. RESULTS Both LOX-1 expression and Nrf2 activation were significantly decreased in preeclamptic placentas compared with normal controls. A significant decrease in LOX-1 mRNA was found in placental explant cultures under hypoxic conditions. Activation of Nrf2 up-regulated HO-1 in both the JAR cells and placental explants. Furthermore, oxLDL increased HO-1 mRNA, whereas the blockade of LOX-1 inhibited the increase of HO-1 mRNA in JAR cells. CONCLUSION Decreasing LOX-1 expression in preeclamptic placenta may contribute to high oxLDL concentration, low Nrf2 activation, and low HO-1 expression. These findings provide novel insights into the crucial role of LOX-1 and Nrf2 in the pathogenesis of preeclampsia.

Physics-based urban earthquake simulation enhanced by 10.7 BlnDOF × 30 K time-step unstructured FE non-linear seismic wave simulation

With the aim of dramatically improving the reliability of urban earthquake response analyses, we developed an unstructured 3-D finite-element-based MPI-OpenMP hybrid seismic wave amplification simulation code, GAMERA. On the K computer, GAMERA was able to achieve a size-up efficiency of 87.1% up to the full K computer. Next, we applied GAMERA to a physics-based urban earthquake response analysis for Tokyo. Using 294,912 CPU cores of the K computer for 11 h, 32 min, we analyzed the 3-D non-linear ground motion of a 10.7 BlnDOF problem with 30 K time steps. Finally, we analyzed the stochastic response of 13,275 building structures in the domain considering uncertainty in structural parameters using 3 h, 56 min of 80,000 CPU cores of the K computer. Although a large amount of computer resources is needed presently, such analyses can change the quality of disaster estimations and are expected to become standard in the future.

Differential expression and the anti-apoptotic effect of human placental neurotrophins and their receptors

Neurotrophin (NT) is important in the survival, maintenance and differentiation of neuronal tissue, and functions in follicle maturation, tumor growth, angiogenesis and immunomodulation; however, the expression of NT and its receptors (NTR) in human placenta and their influence on fetal growth are unclear. Here we investigated the correlation of NT and NTR in human placenta with uterine environment and fetal growth. TrkB, a NTR, mRNA was expressed on decidual and villous tissue and increased with gestational age, localizing in the trophoblast layer and endothelium by immunohistochemistry. Villous TrkB mRNA was significantly increased in preeclampsia (PE) than in controls and was higher in the normotensive small for gestational age (SGA) placenta, although it was not significant. It was also significantly increased in the small twin of discordant twin pregnancies. Brain-derived neurotrophic factor (BDNF), the main ligand of TrkB, was expressed in membranous chorion and villous tissue and was significantly higher in maternal plasma in normotensive SGA and PE than in controls. TrkB mRNA expression was up-regulated on cultured villous tissue explants and on JEG-3, a choriocarcinoma cell line, by H(2)O(2) treatment. BDNF decreased apoptotic cells in H(2)O(2)-treated JEG-3, indicating that BDNF/TrkB signaling had anti-apoptotic effects against oxidative stress in JEG-3, suggesting a protective role of BDNF/TrkB in human villous tissue under unfavorable conditions in utero.

Genetic relatedness of Mycobacterium avium‐intracellulare complex isolates from patients with pulmonary MAC disease and their residential soils

Mycobacterium avium-intracellulare complex (MAC) strains were recovered from 48.9% of residential soil samples (agricultural farms (n = 7), residential yards (n = 79), and planting pots (n = 49)) of 100 pulmonary MAC patients and 35 non-infected control patients. The frequency of MAC recovery did not differ among soil types or among patients regardless of the presence of pulmonary MAC disease, infecting MAC species or period of soil exposure. Variable numbers of tandem repeats (VNTR) analysis for MAC clinical and soil isolates revealed 78 different patterns in 47 M. avium clinical isolates and 41 soil isolates, and 53 different patterns in 18 M. intracellulare clinical isolates and 37 soil isolates. Six clinical and corresponding soil isolate pairs with an identical VNTR genotype were from case patients with high soil exposure (≥2 h per week, 37.5% (6/16) with high exposure compared with 0.0% (0/19) with low or no exposure, p <0.01), suggesting that residential soils are a likely source of pulmonary MAC infection.

Critical earthquake loads for SDOF inelastic structures considering evolution of seismic waves

The damage of structures induced by earthquake ground motions depends primarily on three parameters: (1) the characteristics of earthquake source properties and ground motions (magnitude, epicentral distance, duration, frequency content, amplitude and local soil type), (2) the properties of the structure (natural frequencies, mode shapes, damping properties, material of construction, structural system and ductility capacity), and (3) how close the structure’s fundamental natural frequency to the dominant frequency of the ground motion. The 2011 off the Pacific coast of Tohoku earthquake has demonstrated these facts clearly. In general, the ground motion characteristics involve large inherent uncertainties and cannot be controlled while the structure’s properties have smaller variability and can be managed to some extent in general. For instance, the material and members of construction can be selected and the seismic-resistance of the structure can be improved to fairly high levels through member detailing for enhancement of ductility capacity.

Implicit nonlinear wave simulation with 1.08T DOF and 0.270T unstructured finite elements to enhance comprehensive earthquake simulation

This paper presents a new heroic computing method for unstructured, low-order, finite-element, implicit nonlinear wave simulation: 1.97 PFLOPS (18.6% of peak) was attained on the full K computer when solving a 1.08T degrees-of-freedom (DOF) and 0.270T-element problem. This is 40.1 times more DOF and elements, a 2.68-fold improvement in peak performance, and 3.67 times faster in time-to-solution compared to the SC14 Gordon Bell finalists state-of-the-art simulation. The method scales up to the full K computer with 663,552 CPU cores with 96.6% sizeup efficiency, enabling solving of a 1.08T DOF problem in 29.7 s per time step. Using such heroic computing, we solved a practical problem involving an area 23.7 times larger than the state-of-the-art, and conducted a comprehensive earthquake simulation by combining earthquake wave propagation analysis and evacuation analysis. Application at such scale is a groundbreaking accomplishment and is expected to change the quality of earthquake disaster estimation and contribute to society.

Piezoelectric dynamic strain monitoring for detecting local seismic damage in steel buildings

This research presents a methodology for damage detection along with a sensing system for monitoring seismic damage in steel buildings. The system extracts the location and extent of local damage, such as fracture at a beam‐column connection, from changes in the bending moment distribution in a steel moment-resisting frame. We developed a dynamic strain-based sensing system utilizing piezoelectric film sensors and wireless sensing techniques to estimate the bending moments resisted by individual structural members under small amplitude loadings such as ambient vibrations and minor earthquakes. We introduce a new damage index that extracts local damage information from the comparative study of the dynamic strain responses of the structural members before and after a large earthquake event. The damage detection scheme was examined both analytically and numerically using a simple frame example. Then, the entire local damage detection scheme was verified through a series of vibration tests using a one-quarter-scale steel testbed that simulated seismic damage at member ends. (Some figures may appear in colour only in the online journal)