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Kazuki Hashimoto, Takuro Nii, Hitoshi Sumitani, Masashi Yokoyama, Satoshi Miyamoto, Yasuhiro Mihashi, Yuka Nagata, Takanori Matsuki, Kazuyuki Tsujino, Keisuke Miki, Hiroshi Kida Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Osaka, JapanCorrespondence: Takuro Nii, Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka, Osaka, 560-8552, Japan, Tel +81-6-6853-2001, Fax +81-6-6853-3127, Email nii.takuro.kw@mail.hosp.go.jpAbstract: Amikacin liposome inhalation suspension (ALIS) is a key drug for the treatment of refractory Mycobacterium avium complex pulmonary disease (MAC-PD). Although cases of drug-induced interstitial lung disease (DIILD) by ALIS have been reported, its diagnosis is challenging due to overlapping existing pulmonary shadows, airway bleeding, exacerbation of underlying conditions, and the potential for various concurrent infections. A 72-year-old woman started treatment with ALIS for refractory MAC-PD. Three weeks later, she had a fever, cough, and appetite loss. She was hospitalized because multiple infiltrative opacities were observed on chest X-ray and chest computed tomography. Because the opacities worsened after empiric antibiotic therapy with broad-spectrum antibiotics, we initiated corticosteroid therapy, suspecting DIILD caused by ALIS, although drug lymphocyte stimulation tests for ALIS and amikacin were negative. Three days later, we found signs of improvement and quickly tapered the corticosteroids. After obtaining informed consent, we performed a drug provocation test of ALIS. Seven days later, she exhibited fever, an increased peripheral white blood cell count, and elevated serum C-reactive protein level, all of which returned to baseline 4 days after stopping ALIS, leading to a diagnosis of DIILD caused by ALIS in this patient. DIILD caused by ALIS is rare but should be carefully diagnosed to ensure that patients with refractory MAC-PD do not miss the opportunity to receive ALIS treatment.Keywords: amikacin liposome inhalation suspension, Mycobacterium avium complex pulmonary disease, drug-induced interstitial lung disease, drug provocation test, paradoxical response

Masahiro Shinoda,1 Osamu Hataji,2 Motohiko Miura,3 Masaharu Kinoshita,4 Akira Mizoo,5 Kazunori Tobino,6 Toru Soutome,7 Takanobu Nishi,7 Takeo Ishii,7 Bruce E Miller,8 Ruth Tal-Singer,8 Ryan Tomlinson,8 Taizo Matsuki,7 Paul W Jones,9 Yoko Shibata10 1Department of Respiratory Medicine, Tokyo Shinagawa Hospital, Shinagawa, Tokyo, Japan; 2Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Mie, Japan; 3Department of Respiratory Medicine, Tohoku Rosai Hospital, Sendai, Miyagi, Japan; 4Department of Respiratory Medicine, Nagata Hospital, Yanagawa, Fukuoka, Japan; 5Department of Pulmonary Medicine Japan, Japan Community Healthcare Organization Tokyo Shinjuku Medical Center, Shinjuku, Tokyo, Japan; 6Department of Respiratory Medicine, Iizuka Hospital, Iizuka, Fukuoka, Japan; 7Japan Medical & Development, GSK K.K, Minato-Ku, Tokyo, Japan; 8GSK Pharma R&D, Collegeville, PA, USA; 9General Medicine, GSK, Brentford, Middlesex, UK; 10Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, JapanCorrespondence: Taizo Matsuki, Value Evidence Outcomes, Japan Medical & Development, GSK K.K, Akasaka Intercity AIR 1-8-1 Akasaka, Minato-Ku, Tokyo, 107-0052, Japan, Tel +81-8036928935, Email taizo.2.matsuki@gsk.comBackground: Telemedicine may help the detection of symptom worsening in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in improved outcomes. This study aimed to determine the feasibility and acceptability of telemedicine among patients with COPD and physicians and facility staff in Japan.Methods: This was a 52-week multicenter, prospective, single-arm, feasibility and acceptability cohort study of Japanese patients ≥ 40 years of age with COPD or asthma-COPD overlap. Participants underwent training to use YaDoc, a telemedicine smartphone App, which included seven daily symptom questions and weekly COPD Assessment Test (CAT) questions. The primary endpoint was participant compliance for required question completion. The secondary endpoint was participant and physician/facility staff acceptability of YaDoc based on questionnaires completed at Week 52. The impact of the Japanese COVID-19 pandemic state of emergency on results was also assessed.Results: Of the 84 participants enrolled (mean age: 68.7 years, 88% male), 72 participants completed the study. Completion was high in the first six months but fell after that. Median (interquartile range [IQR]) compliance for daily questionnaire entry was 66.6% (31.0– 91.8) and 81.0% (45.3– 94.3) for weekly CAT entry. Positive participant responses to the exit questionnaire were highest regarding YaDoc ease of use (83.8%), positive impact on managing health (58.8%), and overall satisfaction (53.8%). Of the 26 physicians and facility staff enrolled, 24 completed the study. Of these, the majority (66.7%) responded positively regarding app facilitation of communication between physicians and participants to manage disease. Compliance was similar before and after the first COVID-19 state of emergency in Japan.Conclusion: Daily telemedicine monitoring is potentially feasible and acceptable to both patients and physicians in the management of COPD. These results may inform potential use of telemedicine in clinical practice and design of future studies.Clinical Trial Registration: JapicCTI-194916.Keywords: Japan, patient-reported outcome measure, feasibility, acceptability, telemonitoring, smartphone

Yuji Yamamoto, Keisuke Miki, Takanori Matsuki, Kiyoharu Fukushima, Yohei Oshitani, Hiroyuki Kagawa, Kazuyuki Tsujino, Kenji Yoshimura, Mari Miki, Hiroshi Kida Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Osaka, JapanCorrespondence: Keisuke MikiDepartment of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka, Osaka 560-8552, JapanTel +81-6-6853-2001Fax +81-6-6853-3127Email miki.keisuke.pu@mail.hosp.go.jpBackground: Oscillometry is a tool to measure respiratory impedance that requires minimal patients’ effort. In patients with chronic obstructive pulmonary disease (COPD), the correlation of respiratory impedance at rest with exertional ventilatory parameters, including exercise tolerance, has scarcely been reported. In addition, the utility of oscillometric parameters might differ between the inspiratory and expiratory phases due to airflow obstruction during expiration, but the hypothesis had not been validated. The aim of the present study was to investigate whether oscillometric parameters are associated with exertional ventilatory parameters in patients with COPD.Methods: Fifty-five subjects with COPD who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center performed spirometry, oscillometry, and cardiopulmonary exercise testing (CPET) within 2 weeks. The correlations between parameters of spirometry, oscillometry, and CPET were analyzed using Spearman’s rank correlation coefficient, univariate, and multivariate analyses.Results: Respiratory reactance had better correlations with the CPET parameters than respiratory resistance. Moreover, inspiratory reactance at rest correlated with the CPET parameters stronger than expiratory reactance. In particular, inspiratory resonant frequency (Fres-ins) correlated with peak oxygen uptake (rS=− 0.549, p< 0.01) and dead space to tidal volume ratio at peak exercise (rS=0.677, p< 0.01) and the best predicted expiratory tidal volume (VT ex) at peak exercise of all the oscillometric parameters (rS=− 0.679, p< 0.01). However, the correlation between Fres-ins and VT ex at peak exercise became weak in subjects with severe and very severe COPD during exercise.Conclusion: Measurement of respiratory reactance is useful for the effortless evaluation of not only exertional ventilatory parameters but exercise tolerance in patients with COPD. The correlation of respiratory impedance with exertional ventilatory parameters can become weak in patients with advanced COPD; thus, the measurement of oscillometry might not be appropriate for evaluating exertional ventilatory parameters of patients with advanced COPD.Keywords: dyspnea, dynamic hyperinflation, airflow obstruction, resonant frequency, tidal volume

Vacancy-fluorine complexes in metal-oxide semiconductors (MOS) with high-k gate dielectrics were studied using a positron annihilation technique. F+ ions were implanted into Si substrates before the deposition of gate dielectrics (HfSiON). The shift of threshold voltage (Vth) in MOS capacitors and an increase in Fermi level position below the HfSiON/Si interface were observed after F+ implantation. Doppler broadening spectra of the annihilation radiation and positron lifetimes were measured before and after HfSiON fabrication processes. From a comparison between Doppler broadening spectra and those obtained by first-principles calculation, the major defect species in Si substrates after annealing treatment (1050 °C, 5 s) was identified as vacancy-fluorine complexes (V3F2). The origin of the Vth shift in the MOS capacitors was attributed to V3F2 located in channel regions. [ABSTRACT FROM AUTHOR]

We have found experimentally an anomalous thermoelectric characteristic of an n-type Si nanowire micro thermoelectric generator (μTEG). The μTEG is fabricated on a silicon-on-insulator wafer by electron beam lithography and dry etching, and its surface is covered with a thermally grown silicon dioxide film. The observed thermoelectric current is opposite to what is expected from the Seebeck coefficient of n-type Si. The result is understandable by considering a potential barrier in the nanowire. Upon the application of the temperature gradient across the nanowire, the potential barrier impedes the diffusion of thermally activated majority carriers into the nanowire, and it rather stimulates the injection of thermally generated minority carriers. The most plausible origin of the potential barrier is negative charges trapped at the interface between the Si nanowire and the oxide film. We practically confirmed that the normal Seebeck coefficient of the n-type Si nanowire is recovered after the hydrogen forming gas annealing. This implies that the interface traps are diminished by the hydrogen termination of bonding defects. The present results show the importance of the surface inactivation treatment of μTEGs to suppress the potential barrier and unfavorable contribution of minority carriers. [ABSTRACT FROM AUTHOR]

In this paper, we propose an LMI-based design method of a decentralised variable gain robust controller for large-scale interconnected systems with mismatched uncertainties. The mismatched uncertainties under consideration are composed of the matched part and the mismatched one, and the proposed decentralised robust controller consists of a state feedback with a fixed gain and one with a variable gain tuned by parameter adjustment laws. Sufficient conditions for the existence of the proposed decentralised variable gain robust controller are given in terms of linear matrix inequalities (LMIs). Finally, a numerical example is illustrated to validate the proposed design procedure. [ABSTRACT FROM AUTHOR]

Orexins are bioactive peptides, which have been shown to play a pivotal role in vigilance state transitions: the loss of orexin-producing neurons (orexin neurons) leads to narcolepsy with cataplexy in the human. However, the effect of the need for sleep (i.e., sleep pressure) on orexin neurons remains largely unknown. Here, we found that immunostaining intensities of the α1 subunit of the GABA A receptor and neuroligin 2, which is involved in inhibitory synapse specialization, on orexin neurons of mouse brain were significantly increased by 6-h sleep deprivation. In contrast, we noted that immunostaining intensities of the α2, γ2, and β2/3 subunits of the GABA A receptor and Huntingtin-associated protein 1, which is involved in GABA A R trafficking, were not changed by 6-h sleep deprivation. Using a slice patch recording, orexin neurons demonstrated increased sensitivity to a GABA A receptor agonist together with synaptic plasticity changes after sleep deprivation when compared with an ad lib sleep condition. In summary, the GABAergic input property of orexin neurons responds rapidly to sleep deprivation. This molecular response of orexin neurons may thus play a role in the changes that accompany the need for sleep following prolonged wakefulness, in particular the decreased probability of a transition to wakefulness once recovery sleep has begun. [ABSTRACT FROM AUTHOR]