First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset

This prespecified subanalysis of the global, randomized controlled phase Ill KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression-free survival by independent central review (data cut-off date, 10 July 2017) was 0.25 (95% confidence interval [CI], 0.10-0.64; one-sided, nominal P = .001). The HR for overall survival (data cut-off date, 15 February 2019) was 0.39 (95% CI, 0.17-0.91; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFRIALK alterations and a PD-L1 tumor proportion score of 50% or greater

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset

This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD‐L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (four to six cycles). The primary end‐point was progression‐free survival; secondary end‐points included overall survival and safety. Of 305 patients randomized in KEYNOTE‐024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression‐free survival was 41.4 (95% confidence interval [CI], 4.2‐42.5) months with pembrolizumab and 4.1 (95% CI, 2.8‐8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11‐0.65]; one‐sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9‒NR) and 21.5 (95% CI, 5.2‐35.0) months, respectively (HR, 0.39 [95% CI, 0.17‐0.91]; one‐sided, nominal P = .012). Treatment‐related adverse events occurred in 21/21 (100%) pembrolizumab‐treated and 18/19 (95%) chemotherapy‐treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3‐5 events. Immune‐mediated adverse events and infusion reactions occurred in 11 pembrolizumab‐treated patients (52%) and four chemotherapy‐treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3‐5 events. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738

環境影響評価の現場観測：海底資源開発に向けて

海底熱水鉱床開発に伴う環境影響評価についての法制度や標準的手法については、国際的にも議論が続いている。一方で深海での現場観測は多大な経費を必要とするが，商業レベルではいかにしてデータ品質を落とすことなく経済性・効率性を兼ね備えた調査観測を実施できるのかを求められている。SIP次世代海洋資源調査技術プロジェクト（以下，SIP プロジェクト）では，最新の調査技術と研究成果を導入した実用的な手法開発および経済性・効率性を兼ね備えた戦略的な評価手順の構築を目指した。深海生物群集を解析する手法として，微小生物（メイオファウナ）を対象とした画像解析による迅速検査法を開発し，遺伝子情報との組み合わせによる統合解析を検討した。海底での長期観測技術として、国内メーカーが深海底における長期モニタリング用機器として開発した「江戸っ子１号」による海底近傍の長期観測を実用化に取り組んだ。SIP プロジェクトで製作されたホバリング型AUV「ほばりん」による海底マッピング調査を行い，海底の詳細地形や中型?大型生物の生息状況といった環境情報を効率的に取得した。開発に伴う濁質水の拡散を精度よく予測するための基礎データとして重要な乱流観測に取り組み，深海乱流の直接計測のプロトコルを作成した。SIP プロジェクトではこれらの新たな知見に基づいた技術開発と手法改良を進めたが，さらに資源探査の段階から効率的に事前調査を実施する環境影響評価のプロトコルを考案した。これは近年環境省が推奨している「戦略的環境アセスメント」の考え方を適用した技術で，開発の早い段階から環境の状況を解析することで，より戦略的に，海域条件を考慮した鉱区設定および適切な環境保全と影響緩和策の立案ができると考えている。今後においては，SIP プロジェクトでの成果と経験が民間企業に実装されることが，国際競争力のある海洋産業の発展につながると考える

A LONGITUDINAL STUDY OF FACIAL GROWTH IN RELATION TO GENERAL BODY HEIGHT DURING ADOLESCENCE

A roentgenographic cephalometric study using 24 boys and 27 girls have carried out for about 10 years duration of longitudinal examination. For a craniofacial criterion, sella-gnathion length was selected as a representative dimension in the structures. The boys group showed relatively superior level in the amount of the annual increment covering the whole period of the study. Both the average circum-puberal growth peak of the body height and sella-gnathion length in boys were synchronized and each of them was found in between 12 and 13 years of age. On the other hand, in the girls group, the most of the cases indicate that the peaks of the sella-gnathion incremental maximum were synchronized or followed after the onset of the body height peak of the maximum. At conclusion, the annual increment rate of the body height may be able to apply as a prediction tool of the craniofacial growth changes especially in the girls group

Glycerol dialkyl glycerol tetraethers and TEX86 index in sinking particles in the western North Pacific

Seasonal and depth variation in the flux of glycerol dialkyl glycerol tetraethers (GDGTs) and TEX86 (TEXH86 and TEXL86) values in sinking particles was examined by conducting a 21 month time-series sediment trap experiment at a mooring station (WCT-2, 39°N, 147°E) in the mid-latitude NW Pacific. The aim was to understand the sinking process of GDGTs in the water column and the preservation of the TEX86 signal in the water column and sediment surface. In the shallow trap, the sinking flux of GDGTs showed maxima from May 1998 to February 1999. The maximal peaks in sinking flux corresponded to peaks in the sinking flux of organic carbon, opal and lithogenic material. GDGT concentration in the total fine fraction and the caldarchaeol/crenarchaeol ratio at three depths (ca. 1300–4800 m) varied synchronously, implying rapid vertical transport of GDGTs to deeper water with a sinking velocity >260 m day−1 below ca. 1300 m. The changes in TEX86-based temperature were different from those in contemporary sea surface temperature (SST). The former was lower than the SST from May to December and corresponded to the temperature at the thermocline, whereas it was higher than the SST from December to May. The annual average sinking flux of the GDGTs decreased with depth. The GDGT half-depth, the depth range over which half of the GDGT is lost, was calculated to be 3108–3349 m, implying that GDGTs were well preserved during sinking. The flux-weighted average TEX86-based temperature was constant with depth and corresponded roughly to mean annual SST. The findings support a previous hypothesis that the GDGTs produced in surface water are preferentially delivered to the deeper water column via grazing and repackaging in larger particles. The constant TEX86 at different depths indicates that it was not affected by degradation in the water column. The preservation efficiency of GDGTs was 1.0–1.3% at the water–sediment interface. Despite significant GDGT degradation, there was a small difference in TEX86 values between sinking particles and surface sediment

Seasonal and depth variations in molecular and isotopic alkenone composition of sinking particles from the western North Pacific

Seasonal and depth variations in alkenone flux and molecular and isotopic composition of sinking particles were examined using a 21-month time-series sediment trap experiment at a mooring station WCT-2 (39°N, 147°E) in the mid-latitude NW Pacific to assess the influences of seasonality, production depth, and degradation in the water column on the alkenone unsaturation index UK′37. Analysis of the underlying sediments was also conducted to evaluate the effects of alkenone degradation at the water–sediment interface on UK′37. Alkenone sinking flux and UK′37-based temperature showed strong seasonal variability. Alkenone fluxes were higher from spring to fall than they were from fall to spring. During periods of high alkenone flux, the UK′37-based temperatures were lower than the contemporary sea-surface temperatures (SSTs), suggesting alkenone production in a well-developed thermocline (shallower than 30 m). During low alkenone flux periods, the UK′37-based temperatures were nearly constant and were higher than the contemporary SSTs. The nearly constant carbon isotopic ratios of C37:2 and C38:2 alkenones suggest that alkenones produced in early fall were suspended in the surface water until sinking. The alkenone sinking flux decreased exponentially with increasing depth. The decreasing trend was enhanced during the periods of high alkenone flux, suggesting that fresh and labile particles sank from spring to fall, while old and stable particles sank from fall to spring. The UK′37-based temperature usually increased with increasing depth. The preservation efficiency of alkenones was 2.7–5.2% at the water–sediment interface. Despite the significant degradation of the alkenones, there was little difference in UK′37 levels between sinking particles and the surface sediment

Alchemy in the Art of Traditional Japanese Ceramics: Microstructure and Formation Mechanism of Gold-Colored Bizen Stoneware

The microstructure and formation process of the golden color on traditional Japanese Bizen stoneware was investigated through model experiments. The current compositional and structural research of pottery fragments has revealed that the golden color comes from Fe oxide consisting of approximately 100 nm thick agglomerates of Al-substituted hematite (α-(Fe_1–<i>x</i>Al_<i>x</i>)₂O₃, <i>x</i> ≈ 0.05). The color is reproducible in the laboratory by sequential heat treatments of Bizen clay pellets under oxidizing and reducing atmospheres with an amount of potassium supplied as a melting point depressant. Lustrous colors such as silver and gold in Bizen stoneware have generally been attributed to the optical interference in superficial carbon films produced by burning wood fuel. Here, we show that the golden color is caused by the formation of Al-substituted hematite, not by the formation of carbon