NMR study of the layered cobalt oxyphosphide Sr2Sc(Co1-xFex)PO3

We report the results of 31P-nuclear magnetic resonance (NMR) measurements on the layered cobalt oxyphosphide Sr2Sc(Co1−xFex)PO3 in order to investigate the magnetic properties at low temperatures from a microscopic view point. The 31P-Knight shifts measured at the resonance peak maximum of Sr2Sc(Co1−xFex)PO3 have positive values and are T-independent in an entire temperature range, and the absolute value decreases with increasing Fe content. Also, the nuclear spin-lattice relaxation rate 1/T1 is almost proportional to the temperature at low temperatures. The magnitude of 1/T1T decreases with increasing the Fe content, which suggests the decrease of the density of states around the Fermi level

Oxidation and reduction effects of successive superconducting transitions in ultra-fine YBa2Cu4O8 ceramics

We investigated the effects of oxidation and reduction on the successive superconducting transition in a ceramic material composed of YBa2Cu4O8 (Y124) submicron grains by linear and non-linear resistivity measurements. This material shows two-step superconducting transition and the lower one is identified as an inter-grain ordering. A sintering process fuses and joins the adjacent grains, so the lower transition was suppressed with increasing sintered time. Although Y124 is a stoichiometric ceramic, a reduction treatment suppressed the temperature of zero resistivity and broadened the non-linear resistivity peak. This suggests an oxygen vacancy was induced on the grain surface

Magnetic Field–Temperature Phase Diagram of Fine YBa2Cu3O7−δ Ceramics from Linear and Non-linear Resistivities

We performed linear and non-linear resistivity measurements for fine YBa2Cu3O7−δ ceramics under magnetic field. Successive superconducting transition was observed in the linear resistivity and the lower temperature part of the resistivity curve became convex upward at high fields. A non-linear resistivity peak was observed for this lower temperature region and its offset temperature Toffset and the onset temperature Tonest coincided with the temperature of zero resistivity and inflexion point in linear resistivity, respectively. At lower field, Tonset was less sensitive to the field than Toffset, which implies the existence of the peculiar inter-grain ordering phase at finite fields.2019 International Conference on Strongly Correlated Electron Systems (SCES2019), September 23-28, 2019, Okayama Convention Center in Okayama, Japa

Lecanemab in patients with early Alzheimer\u27s disease: Detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study

BACKGROUND: Lecanemab, a humanized IgG1 monoclonal antibody that targets soluble aggregated Aβ species (protofibrils), has demonstrated robust brain fibrillar amyloid reduction and slowing of clinical decline in early AD. The objective of this analysis is to report results from study 201 blinded period (core), the open-label extension (OLE), and gap period (between core and OLE) supporting the effectiveness of lecanemab. METHODS: The lecanemab study 201 core was a double-blind, randomized, placebo-controlled study of 856 patients randomized to one of five dose regimens or placebo. An OLE of study 201 was initiated to allow patients to receive open-label lecanemab 10mg/kg biweekly for up to 24 months, with an intervening off-treatment period (gap period) ranging from 9 to 59 months (mean 24 months). RESULTS: At 12 and 18 months of treatment in the core, lecanemab 10 mg/kg biweekly demonstrated dose-dependent reductions of brain amyloid measured PET and corresponding changes in plasma biomarkers and slowing of cognitive decline. The rates of clinical progression during the gap were similar in lecanemab and placebo subjects, with clinical treatment differences maintained after discontinued dosing over an average of 24 months in the gap period. During the gap, plasma Aβ42/40 ratio and p-tau181 levels began to return towards pre-randomization levels more quickly than amyloid PET. At OLE baseline, treatment differences vs placebo at 18 months in the randomized period were maintained across 3 clinical assessments. In the OLE, lecanemab 10 mg/kg biweekly treatment produced dose-dependent reductions in amyloid PET SUVr, improvements in plasma Aβ42/40 ratio, and reductions in plasma p-tau181. CONCLUSIONS: Lecanemab treatment resulted in significant reduction in amyloid plaques and a slowing of clinical decline. Data indicate that rapid and pronounced amyloid reduction correlates with clinical benefit and potential disease-modifying effects, as well as the potential to use plasma biomarkers to monitor for lecanemab treatment effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT01767311

Inter-grain Phase Transitions in Superconducting Ceramic YBa2Cu3O7−δ under Low Magnetic Fields

We investigated the magnetic field dependence of inter-grain phase transitions in the ceramic YBa2Cu3O7−δ. To this end, we measured the temperature dependences of the nonlinear magnetic responses and the current–voltage characteristics under low magnetic fields. We then estimated the inter-grain temperatures of the glass and superconducting transitions. The field–temperature phase diagram of the inter-grain ordering was similar to that of YBa2Cu4O8 ceramic. The results imply the occurrence of chiral-glass ordering in ceramic cuprate superconductors under low magnetic fields.2019 International Conference on Strongly Correlated Electron Systems (SCES2019), September 23-28, 2019, Okayama Convention Center in Okayama, Japa

Measurement of the X-ray spectrum of a free electron laser with a wide-range high-resolution single-shot spectrometer

We developed a single-shot X-ray spectrometer for wide-range high-resolution measurements of Self-Amplified Spontaneous Emission (SASE) X-ray Free Electron Laser (XFEL) pulses. The spectrometer consists of a multi-layer elliptical mirror for producing a large divergence of 22 mrad around 9070 eV and a silicon (553) analyzer crystal. We achieved a wide energy range of 55 eV with a fine spectral resolution of 80 meV, which enabled the observation of a whole SASE-XFEL spectrum with fully-resolved spike structures. We found that a SASE-XFEL pulse has around 60 longitudinal modes with a pulse duration of 7.7 ± 1.1 fs.Inubushi, Y.; Inoue, I.; Kim, J.; Nishihara, A.; Matsuyama, S.; Yumoto, H.; Koyama, T.; Tono, K.; Ohashi, H.; Yamauchi, K.; Yabashi, M. Measurement of the X-ray Spectrum of a Free Electron Laser with a Wide-Range High-Resolution Single-Shot Spectrometer. Appl. Sci. 2017, 7, 584. https://doi.org/10.3390/app7060584

Scanning Differential-Phase-Contrast Hard X-Ray Microscopy with Wedge Absorber Detector

A new and simple idea for scanning differential-phase-contrast (S-DPC) hard X-ray microscopy has been proposed. It only uses a wedge absorber coupled with two intensity detectors, and is much more sensitive to sample structures than absorption contrast. It can also extract pure quantitative one-dimensional phase gradient given by a sample without an effect of sample absorption. The S-DPC microscope has been constructed at BL24XU of SPring-8, and its feasibility has been successfully demonstrated at the photon energy of 10 keV by clearly visualizing structures of samples. Further, the experimental phase gradient profile agrees well with simulation. By integrating the resultant phase gradient, the corresponding phase shift distribution could be also imaged. There are two main types in X-ray microscopes, one is an imaging type and the other is a scanning type. 1) The former provides direct magnification and shorter exposure time, while the latter provides digitally stored images with minimal radiation exposure to samples. 1) Recently, phasecontrast X-ray microscopy has rapidly grown in the hard Xray region since the advent of the 3 rd generation synchrotron radiation facilities. It is based on the fact that phase-shift cross section is almost a thousand times larger than absorption one for light elements as expected from a comparison between real and imaginary parts of the refractive index. 2,3) In the imaging type, the phase-contrast microscopy has been demonstrated by the Zernike's method 6) Further, we have recently demonstrated the novel imaging phase-contrast microscopy using a micro-interferometer consisting of a twin zone plate. 7) On the other hand, in the scanning type, the phase-contrast microscopy has been demonstrated by the configured 8) or segmented 9) detectors, the CCD-camera image-detections, 10-12) the diffracting aperture based method 13) and the dark-field imaging. 14,15) The former two require the highly sophisticated X-ray detector of electronic devises. The CCD-camera imagedetection must take diffraction images of a microbeam for all pixels, thus need a huge memory and the stored dataset must be processed later with an appropriate numerical calculation for image reconstruction. The diffracting aperture based method and the dark-field imaging are simple methods to realize the scanning phase-contrast microscopy, but phase information was not evaluated quantitatively. Here, we propose a new idea for S-DPC hard X-ray microscopy. It is a very simple way to purely extract quantitative one-dimensional phase gradient given by a sample to be imaged removing an effect of sample absorption by only adding a wedge absorber coupled with two intensity detectors into the normal scheme of the scanning microscopy. In this paper, the concept of the S-DPC hard X-ray microscopy is described and the feasibility test is presented. The principle of the S-DPC microscopy is illustrated i

A Randomized, Double-Blind, Phase 2b Proof-of-Concept Clinical Trial in Early Alzheimer’s Disease With Lecanemab, an Anti-aβ Protofibril Antibody

Background: Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer’s disease, mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia. Methods: BAN2401-G000-201 aimed to establish the effective dose 90% (ED90), defined as the simplest dose that achieves ≥90% of the maximum treatment effect. The primary endpoint was Bayesian analysis of 12-month clinical change on the Alzheimer’s Disease Composite Score (ADCOMS) for the ED90 dose, which required an 80% probability of ≥25% clinical reduction in decline versus placebo. Key secondary endpoints included 18-month Bayesian and frequentist analyses of brain amyloid reduction using positron emission tomography; clinical decline on ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14); changes in CSF core biomarkers; and total hippocampal volume (HV) using volumetric magnetic resonance imaging. Results: A total of 854 randomized subjects were treated (lecanemab, 609; placebo, 245). At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (−0.306 SUVr units) while showing a drug-placebo difference in favor of active treatment by 27% and 30% on ADCOMS, 56% and 47% on ADAS-Cog14, and 33% and 26% on CDR-SB versus placebo according to Bayesian and frequentist analyses, respectively. CSF biomarkers were supportive of a treatment effect. Lecanemab was well-tolerated with 9.9% incidence of amyloid-related imaging abnormalities-edema/effusion at 10 mg/kg biweekly. Conclusions: BAN2401-G000-201 did not meet the 12-month primary endpoint. However, prespecified 18-month Bayesian and frequentist analyses demonstrated reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints. A phase 3 study (Clarity AD) in early Alzheimer’s disease is underway. Trial registration: Clinical Trials.govNCT01767311

Effect of exacerbations on health status in subjects with chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Acute exacerbations may cause deteriorations in the health status of subjects with chronic obstructive pulmonary disease (COPD). The present study prospectively evaluated the effects of such exacerbations on the health status and pulmonary function of subjects with COPD over a 6-month period, and examined whether those subjects showed a steeper decline in their health status versus those subjects without exacerbations.</p> <p>Methods</p> <p>A total of 156 subjects with COPD (mean age 71.4 ± 6.3 years) were included in the analysis. At baseline and after 6 months, their pulmonary function and health status were evaluated using the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ). An acute exacerbation was defined as a worsening of respiratory symptoms requiring the administration of systemic corticosteroids or antibiotics, or both.</p> <p>Results</p> <p>Forty-eight subjects experienced one or more exacerbations during the 6-month study period, and showed a statistically and clinically significant decline in Symptom scores on the SGRQ, whereas subjects without exacerbations did not show a clinically significant decline. Logistic multiple regression analyses confirmed that the exacerbations significantly influenced the Fatigue and Mastery domains of the CRQ, and the Symptoms in the SGRQ. Twelve subjects with frequent exacerbations demonstrated a more apparent decline in health status.</p> <p>Conclusion</p> <p>Although pulmonary function did not significantly decline during the 6-month period, acute exacerbations were responsible for a decline in health status. To minimize deteriorations in health status, one must prevent recurrent acute exacerbations and reduce the exacerbation frequencies in COPD subjects.</p