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Tomoko Betsuyaku,1 Motokazu Kato,2 Keisaku Fujimoto,3 Akihiro Kobayashi,4 Tomoyuki Hayamizu,4 Hideki Hitosugi,4 Gerald Hagan,5 Mark H James,6 Paul W Jones6 1Division of Pulmonary Medicine, Department of Medicine, Keio University, Tokyo, Japan; 2Chest Disease Clinical and Research Institute, Kishiwada City Hospital, Kishiwada, Japan; 3Department of Clinical Laboratory Sciences, Shinshu University, Matsumoto, Japan; 4GSK K.K., MA, Respiratory, Tokyo, Japan; 5Respiratory Science Consultant, Marbella, Spain; 6GSK, Respiratory Franchise Medical, GSK House, Brentford, Middlesex, UK Background: The Global initiative for chronic Obstructive Lung Disease strategy document for COPD recommends treatment changes according to the persistence of symptoms or exacerbations. This study assessed the feasibility and outcomes of a structured step-up/step-down treatment approach in a randomized controlled clinical trial setting. Methods: Japanese patients with moderate-to-severe COPD were randomized to blinded, double-dummy treatment with twice-daily fluticasone propionate/salmeterol (FP/SAL) 250/50 µg or once-daily tiotropium bromide (TIO) 18 µg for 24 weeks (dual bronchodilator was not available). At 4-weekly intervals, patients remaining symptomatic (COPD Assessment Test score >10) or experiencing an exacerbation were offered the option to use triple therapy. Primary endpoint was the proportion of patients remaining on randomized therapy. Results: In total, 406 patients participated (mean FEV1 59%±13% predicted; COPD Assessment Test 12±6). Of these, 204 and 201 patients were included in the FP/SAL and TIO groups, respectively, of whom 67% and 63% continued treatment throughout the study; this difference was not statistically significant. Time to first therapy switch was longer with FP/SAL, but not significantly (P=0.21). More patients in Global initiative for chronic Obstructive Lung Disease (2011 criteria) groups C/D switched (FP/SAL 55%, TIO 63%) than in groups A/B (FP/SAL 27%, TIO 27%). Conclusion: Given the choice, patients with more symptoms or those experiencing an exacerbation will agree to step-up therapy. Effectiveness of disease management pathways can be tested using double-blind studies. Keywords: COPD management, fluticasone propionate/salmeterol, tiotropium

The Centaur (60558) Echeclus was discovered on 2000 March 03, orbiting between the orbits of Jupiter and Uranus. After exhibiting frequent outbursts, it also received a comet designation, 174P. If the ejected material can be a source of debris to form additional structures, studying the surroundings of an active body like Echeclus can provide clues about the formation scenarios of rings, jets, or dusty shells around small bodies. Stellar occultation is a handy technique for this kind of investigation, as it can, from Earth-based observations, detect small structures with low opacity around these objects. Stellar occultation by Echeclus was predicted and observed in 2019, 2020, and 2021. We obtain upper detection limits of rings with widths larger than 0.5 km and optical depth of τ = 0.02. These values are smaller than those of Chariklo's main ring; in other words, a Chariklo-like ring would have been detected. The occultation observed in 2020 provided two positive chords used to derive the triaxial dimensions of Echeclus based on a 3D model and pole orientation available in the literature. We obtained a  = 37.0 ± 0.6 km, b  = 28.4 ± 0.5 km, and c  = 24.9 ± 0.4 km, resulting in an area-equivalent radius of 30.0 ± 0.5 km. Using the projected limb at the occultation epoch and the available absolute magnitude (⁠|$\rm {H}_{\rm {v}} = 9.971 \pm 0.031$|⁠), we calculate an albedo of p v = 0.050 ± 0.003. Constraints on the object's density and internal friction are also proposed. [ABSTRACT FROM AUTHOR]

Tomotaka Kawayama,1 Takashi Kinoshita,1 Kazuko Matsunaga,2 Akihiro Kobayashi,3 Tomoyuki Hayamizu,4 Malcolm Johnson,5 Tomoaki Hoshino11Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, 2Department of Respiratory Medicine, Fukuoka Sanno Hospital, Fukuoka, 3Biomedical Data Science Department, 4Medical Affairs Respiratory Department, GlaxoSmithKline, Shibuya-ku, Tokyo, Japan; 5Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UKPurpose: To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC).Patients and methods: This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation.Results: In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P

Takefumi Saito,1 Akinori Takeda,2 Katsuji Hashimoto,3 Akihiro Kobayashi,4 Tomoyuki Hayamizu,5 Gerald W Hagan6 1Department of Respiratory Medicine, Ibarakihigashi National Hospital, Naka, Ibaraki, 2Center for Pulmonary Medicine, Asahikawa Medical Center, Asahikawa, Hokkaido, 3AMC Nishiumeda Clinic, Osaka, 4Biomedical Science Department, 5Medical Affairs Respiratory Department, GlaxoSmithKline KK, Tokyo, Japan; 6Independent Consultant, Marbella, Spain Purpose: Triple therapy using salmeterol/fluticasone propionate (FP) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease (COPD), but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients. The effects of of salmeterol/fluticasone propionate 50/250 µg (SFC250) twice daily plus tiotropium 18 µg (TIO) once daily and individual treatments on lung function were compared. Patients and methods: Fifty three Japanese COPD patients participated in this randomized, double-blind, double-dummy, Williams square design crossover study. Lung function was assessed by plethysmography and spirometry. Results: The primary endpoint of postdose specific airway conductance area under the curve (AUC0–4h) on day 28 was significantly higher following SFC250 + TIO (0.854) compared with TIO (0.737, 15.8%) and SFC250 (0.663, 28.8%) alone. SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO (0.161 L, P

Saito T, Takeda A, Hashimoto K, et al. Int J Chron Obstruct Pulmon Dis. 2015;10:2393–2404.On page 2395, right column, line 3, “Philadelphia, PA, USA” should have read “Hoechberg, Germany”.On page 2396, Figure 2 was incorrect. The corrected figure is shown.On page 2396, right column, line 1, “although FEV1 and FVC were not log transformed prior to analysis” should have read “although sRaw and sGaw were log transformed prior to analysis”.On page 2397, right column, Lung volumes section, line 5, “Statistical significance was observed for postdose RV immediately after dosing (time =0) on day 28 for SFC250 + TIO compared to TIO and SFC250 (Tables S3, S4). Improvements on day 28 were also seen in postdose TGV, IC, and TLC following treatment with SFC250 + TIO compared to each component, but none were significant (Table S4). Improvements were seen for all parameters for their adjusted mean values on day 1, but none were significant (Table S3).” Should have read “Statistical significance was observed for trough RV (time =0) on day 28 for SFC250 + TIO compared to TIO and SFC250 (Table S3). Improvements on day 28 were also seen in postdose TGV, IC, and TLC following treatment with SFC250 + TIO compared to each component, but statistical treatment differences were not observed, except for after dosing (240 min) IC at day 28 (Table S3). Improvements were seen for all parameters for their adjusted mean values on day 1, but statistical treatment differences were not observed, except for SFC250 after dosing (240 min) TGV at day 1 (Table S3).”On page 2398, Figure 3 was incorrect. The corrected figure is shown.On page 2398, Table 3, TGV (L) row, SFC250 + TIO vs TIO (n=50): 97.5% CI column, “-0.029” should have read “0.029”.On page 2398, Table 3, TGV (L) row, SFC250 + TIO vs SFC250 (n=50): 97.5% CI column, “-0.028” should have read “0.028”.On page 2398, Table 3, Note section, “Difference” should have read “Adjusted mean difference”.On page 2402, Table S2, figure caption, “Postdose raw mean (standard deviation log) values of sGaw and sRaw (mITT population)” should have read “Postdose raw geometric mean (standard deviation log) values of sGaw and sRaw (mITT population)”.On page 2402, Table S2, Time (minutes) column, sGaw, third line down, “SFC250 + TIO” should have read “SFC250”.On page 2402, Table S2, Time (minutes) column, sRaw, third line down, “SFC250 + TIO” should have read “SFC250”.Read the original article

Nobuhisa Ishikawa,1 Noboru Hattori,2 Nobuoki Kohno,2 Akihiro Kobayashi,3 Tomoyuki Hayamizu,4 Malcolm Johnson5 1Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan; 2Department of Molecular and Internal Medicine, Hiroshima University, Hiroshima, Japan; 3Biomedical Data Science Department, 4Medical Affairs Respiratory Department, GlaxoSmithKline Shibuya-ku, Tokyo, Japan; 5Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UK Purpose: To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups.Patients and methods: This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures.Results: The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P

The search for the electric-dipole moment (EDM) of laser-cooled francium (Fr) atoms could lead to a measurement for the electron EDM. It is predicted that the electron EDM would be enhanced by approximately three orders of magnitude in heavy atoms such as Fr. Laser-cooling and trapping techniques are expected to suppress statistical and systematic errors in precision measurements. The magneto-optical trap was achieved using stable rubidium in a developing factory of laser-cooled radioactive atoms. In light of the results from the rubidium experiments, we found that an upgrade of each apparatus is preferred for Fr trapping.

For the measurement of the electron electric dipole moment using Fr atoms, a Fr ion-atom conversion is one of the most critical process. An ion-atom converter based on the “orthotropic” type of Fr source has been developed. This converter is able to convert a few keV Fr ion beam to a thermal atomic beam using a cycle of the surface ionization and neutralization. In this article, the development of the converter is reported.

We plan to measure the permanent electric dipole moment (EDM) of the electron, which has the sensitivity to the CP violation in theories beyond the standard model by using the laser-cooled francium (Fr) atom. This paper reports the present status of the EDM measurement system. A high voltage application system was constructed in order to produce the strong electric field (100 kV/cm) needed for the experiment. After conditioning, the leakage current was 10 pA when a high voltage of 43 kV was applied. Also, a drift of an environmental field was measured at the planned location of the Fr-EDM experiment. The drift is suppressed at present down to the level of 10 pT by installing a 4-layermagnetic shield. Improvements are still needed to reach the required field stability of 1 fT.