欠測を含む二値の経時データにおける経験尤度法を用いた多重頑健重み付き一般化推定方程式

京都大学新制・論文博士博士(社会健康医学)乙第13612号論社医博第18号京都大学大学院医学研究科社会健康医学系専攻(主査)教授 森田 智視, 教授 古川 壽亮, 教授 今中 雄一学位規則第4条第2項該当Doctor of Public HealthKyoto UniversityDFA

Early Cardiogenesis in the Newt Embryo

The migration of cardiogenic cells and the formation of a tubular heart in newt embryos were examined mainly by scanning electron microscopy (SEM). Cardiogenic cells are known to localize at the border region of lateral mesoderm migrating in the space between the ectoderm and the endoderm. They initially (before stage 20 or mid-neurula) appeared to attach to the basal surface of the ectoderm, whereas later (after stage 22 or late neurula) they changed their scaffold to the endoderm. On the scaffold cell surface, very fine fibrils of extracellular matrix (ECM) were found. These fibrils were proved to be composed partly of fibronectin by the immunofluorescence method as well as by immunoSEM using latex bead-labeled antibody, suggesting their seemingly important role in migration of cardiogenic cells. At stage 26 or the early tail bud stage, when the tips of bilateral cardiogenic areas begin to fuse under the foregut, several free vasoformative cells are seen there and the mesodermal sheet itself splits into two layers to produce a coelomic cavity. The splanchnic wall of the coelomic or pericardial cavity was recognized to form a trough consisting of cobblestone-like myocardial cells not yet covered with the epicardium

Seasonal cycles of ozone and oxidized nitrogen species in northeast Asia - 2:A model analysis of the roles of chemistry and transport

[1] The dominant factors controlling the seasonal variations of ozone (O-3) and three major oxidized nitrogen species, peroxyacetyl nitrate (PAN), nitrogen oxides (NOx), and nitric acid (HNO3), in northeast Asia are investigated by using a three-dimensional global chemical transport model to analyze surface observations made at Rishiri Island, a remote island in northern Japan. The model was evaluated by comparing with observed seasonal variations, and with the relationships between O-3, CO, and PAN. We show that the model reproduces the chemical environment at Rishiri Island reasonably well, and that the seasonal cycles of O-3, CO, NOy species, and VOCs are well predicted. The impact of local emissions on some of these constituents is significant, but is not the dominant factor affecting the seasonal cycles. The seasonal roles of chemistry and transport in controlling O-3 and PAN are revealed by examining production/ destruction and import/ export/deposition fluxes in the boundary layer over the Rishiri region. For O-3, transport plays a key role throughout the year, and the regional photochemical contribution is at most 10% in summer. For PAN, in contrast, transport dominates in winter, while in-situ chemistry contributes as much as 75% in summer. It is suggested that the relative contribution of transport and in-situ chemistry is significantly different for O-3 and PAN, but that the wintertime dominance of transport due to the long chemical lifetimes of these species is sufficient to drive the seasonal cycles of springtime maximum and summertime minimum characteristic of remote sites

Nemolizumab plus topical agents in patients with atopic dermatitis (AD) and moderate‐to‐severe pruritus provide improvement in pruritus and signs of AD for up to 68 weeks: results from two phase III, long‐term studies

[Background] Interleukin (IL)-31 affects the inflammatory response, is involved in epidermal barrier disruption in atopic dermatitis (AD) and plays a key role in pruritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administration period. [Objectives] To examine the long-term effectiveness and safety of nemolizumab in patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus. [Methods] In two long-term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concomitantly with topical treatments. Study-JP01 patients received double-blind nemolizumab or placebo for 16 weeks, and then entered a 52-week extension period in which all patients received nemolizumab (nemolizumab/nemolizumab and placebo/nemolizumab groups). Study-JP02 patients received nemolizumab for 52 weeks. Both studies included an 8-week follow-up period. [Results] Study-JP01 nemolizumab/nemolizumab and placebo/nemolizumab, and Study-JP02 nemolizumab groups comprised 143, 72 and 88 patients, respectively. In the nemolizumab/nemolizumab group, there were clinically meaningful improvements from the start of treatment to week 68 in the pruritus visual analogue scale (66% decrease) and Eczema Area and Severity Index (78% decrease). Quality of life (QoL) indicators improved after the first nemolizumab dose; improvements were maintained during the follow-up period. The long-term safety profile was consistent with previous studies, with no unexpected late-onset adverse events. [Conclusions] Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate-to-severe pruritus produced a continuous improvement in pruritus, signs of AD, and QoL for up to 68 weeks, with a favourable safety profile

Evolution of mixing state of black carbon particles: Aircraft measurements over the western Pacific in March 2004

We report the evolution of the mixing state of black carbon (BC) particles in urban plumes measured by an airborne single particle soot photometer. The aircraft observations were conducted over the ocean near the coast of Japan in March 2004. The number fiaction of coated BC particles with a core diameter of 180 mn increased from 0.35 to 0.63 within 12 hours (h), namely 2.3% h-1, after being emitted from the Nagoya urban area in Japan. BC particles with a core diameter of 250 nm increased at the slower rate of 1.0% h-1. The increase in coated BC particles was associated with increases in non-sea salt sulfate and water-soluble organic carbon by a factor of approximately two, indicating that these compounds contributed to the coating on the BC particles. These results give direct evidence that BC particles become internally mixed on a time scale of 12 h in urban plumes. Copyright 2007 by the American Geophysical Union

Resistance of autotetraploids of grapevine rootstock cultivars to phylloxera (Daktulosphaira vitifoliae FITCH)

Resistance of colchicine-induced autotetraploids of four grapevine rootstock cultivars (Riparia Gloire de Montpellier, Rupestris St. George, Couderc 3309 and Kober 5BB) to phylloxera (Daktulosphaira vitifoliae FITCH) was evaluated using the aseptic co-culture technique of root segments and phylloxera in a petri dish, and compared with those of the original diploid and Cabernet Franc (Vitis vinifera L.). None or very few phylloxera nymphs grew to adults on the root of the rootstock cultivars and their autotetrapolids whereas 26.8 % of the eggs grew to adults on the roots of Cabernet Franc. Resistance of Riparia Gloire de Mont-pellier, Rupestris St. George, Couderc 3309 and their autotetraploids to phylloxera was also tested by planting in a phylloxera-infested vineyard and compared with that of Kyoho, a tetraploid table grape cultivar (V. vinifera x V. labrusca Bailey). The formation of galls on the root tips of tetraploid rootstock cultivars was not increased significantly as compared to that on their original diploid plants whereas galls were formed on 52.9% of Kyoho root tips examined. These results show that the autotetraploid rootstock cultivars used in this study had high resistance to phylloxera, thus they were not different from the original diploids.

Seasonal variations of atmospheric C2-C7 nonmethane hydrocarbons in Tokyo

Eighteen C2-C7 NMHCs (nonmethane hydrocarbons) were measured hourly during the Integrated Measurement Program for Aerosol and Oxidant Chemistry in Tokyo (IMPACT) measurement campaigns conducted in central Tokyo during four different periods (summer/autumn of 2003 and winter/summer of 2004). The ambient atmospheric concentrations of NMHCs showed an inverse correlation with wind speed and mixing height and were significantly affected by mesoscale weather conditions. The mixing ratio of isoprene tightly correlated with solar flux and temperature in summer, as it was dominantly emitted by the local vegetation. All the observed NMHCs except isoprene showed high correlation with each other in winter (r2 > 0.5), suggesting concurrent accumulation under stagnant condition and common sources. Emission ratios were calculated on the basis of the correlation with carbon monoxide and ethyne. Compared to the typical winter NMEC composition, during summer there was a significant increase (up to 7 times higher than wintertime) of C4-C5 alkanes from ftiel evaporation; of C2-C3 alkenes, n-hexane and benzene from chemical industry; and of toluene from local manufacturers, reflecting the temperature dependence of these evaporative emissions. In addition to the online measurements in Tokyo, canister sampling at a suburban site (Kisai) followed by multidimensional GC analyses was conducted during the summer campaign in 2004. The atmospheric concentrations of longer-lived compounds (≥ several days) at Kisai showed the buildup under sea breeze circulation. The average ambient, concentration of toluene was 2 times higher than that in central Tokyo, likely because of substantial emissions from local industries as reported in the prefectural statistics. Copyright 2007 by the American Geophysical Union