Search for Ultralight Dark Matter from Long-Term Frequency Comparisons of Optical and Microwave Atomic Clocks.

We search for ultralight scalar dark matter candidates that induce oscillations of the fine structure constant, the electron and quark masses, and the quantum chromodynamics energy scale with frequency comparison data between a ^{171}Yb optical lattice clock and a ^{133}Cs fountain microwave clock that span 298 days with an uptime of 15.4%. New limits on the couplings of the scalar dark matter to electrons and gluons in the mass range from 10^{-22} to 10^{-20} eV/c^{2} are set, assuming that each of these couplings is the dominant source of the modulation in the frequency ratio. The absolute frequency of the ^{171}Yb clock transition is also determined as 518 295 836 590 863.69(28) Hz, which is one of the important contributions toward a redefinition of the second in the International System of Units.

Quadriplegia after ECMO therapy with sluggish recovery in a COVID-19 patient: A case report with a 14-month follow-up.

COVID-19 patients often develop neuromuscular complications, and critically ill patients often develop ICU-acquired weakness. We report a COVID-19 patient who developed flaccid quadriplegia after ECMO therapy and achieved a slow but consistent recovery during a 14-month period of sustained holistic rehabilitation including early mobilization to an outdoor environment.

Endoscopic resection using an over-the-scope clip for duodenal neuroendocrine tumors.

Background and study aims Endoscopic resection of duodenal neuroendocrine tumors (DNETs) remains controversial, and its indications are still unclear. This study aimed to evaluate short-term outcomes of a newly developed endoscopic muscularis resection (EMR) method that utilizes an over-the-scope clip (OTSC), termed EMRO, for treating DNETs. Patients and methods In total, 13 consecutive patients with 14 small (≤ 10 mm) DNETs who underwent EMRO from September 2017 to March 2020 were retrospectively enrolled. EMRO was performed by a single experienced endoscopist. Patients' characteristics and treatment outcomes were assessed. Results The En bloc and R0 resection rates were 100 % (14/14) and 92.9 % (13/14), respectively. The median pathological resected specimen size was 10 mm, with a median pathological resected tumor size of 6 mm. During the EMRO procedure, there was no occurrence of misplacement of the OTSC to the target lesion. With respect to the pathological resection depth, nine cases (64.3 %) and five cases (35.7 %) were categorized as deep submucosal resection and muscularis resection, respectively, whereas no case was categorized as full-thickness resection. There were no intraoperative or delayed perforations. However, delayed bleeding occurred in two cases. At a median follow-up of 12 months (range 7-36) after EMRO, there was no incidence of local recurrence. At the first follow-up endoscopy performed at 6 months after EMRO, the OTSC was retained in place in two of 14 DNETs (14.3 %). Conclusions EMRO can be performed safely, by an experienced endoscopist, for small (≤ 10 mm) DNETs.

Comparison of Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Biopsy Device for Lymphadenopathy.

BACKGROUND: Accurate diagnosis of benign and malignant lymphadenopathy is important for determining the appropriate treatment and prognosis. This study evaluated the diagnostic accuracy and usefulness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with a conventional needle compared to endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) with a Franseen needle for diagnosing lymphadenopathy. METHODS: Patients who underwent EUS-FNA or EUS-FNB for mediastinal or abdominal lymphadenopathy between July 2013 and August 2020 were enrolled in the study. The outcomes between EUS-FNA patients (July 2013 to January 2017; 22-gauge conventional needle; Group A) and EUS-FNB patients (February 2017 to August 2020; 22-gauge Franseen needle; Group B) were compared. RESULTS: A total of 154 patients (Group A: 83; Group B: 71) were analyzed. The diagnostic accuracy (differentiating between malignant and benign lesions) was 88.0% (95% confidence interval [CI], 79.2-93.3%) in Group A and 95.8% (95% CI, 88.3-98.8%) in Group B. Group B had high diagnostic accuracy, but there was no difference between the groups (p = 0.14). Group B had significantly fewer passes (median 2, interquartile range (IQR): 2-4) than Group A (median 3, IQR: 3-4) (p < 0.001). No procedural adverse events occurred in either group. CONCLUSIONS: Although the diagnostic accuracy between the groups was not statistically significant, EUS-FNB with a Franseen needle provided high diagnostic accuracy and required fewer passes to establish a diagnosis. Thus, EUS-FNB is useful for diagnosing lymphadenopathy.

Diagnosis of Biliary Strictures Using Probe-Based Confocal Laser Endomicroscopy under the Direct View of Peroral Cholangioscopy: Results of a Prospective Study (with Video).

BACKGROUND: The accurate diagnosis of biliary strictures remains problematic. The aim of the present study was to prospectively evaluate the clinical utility of probe-based confocal laser endomicroscopy (pCLE) under the direct view of peroral cholangioscopy (POCS) for the diagnosis of biliary strictures. METHODS: Consecutive patients with biliary strictures were included. We investigated sensitivity, specificity, and accuracy to diagnose malignancy for (1) ERCP alone, (2) POCS, (3) pCLE under the direct view of POCS, and (4) tissue sampling under the direct view of POCS. RESULTS: A total of 30 patients (17 with malignant lesions) were prospectively enrolled. (1) ERCP alone showed 88.2% sensitivity, 46.2% specificity, and 70% (95% confidence interval (CI), 52.1%-83.3%) accuracy. (2) POCS showed 100% sensitivity, 76.9% specificity, and 90% (95% CI, 74.4%-96.5%) accuracy. (3) pCLE under the direct view of POCS showed 94.1% sensitivity, 92.3% specificity, and 93.3% (95% CI, 78.7%-98.8%) accuracy. (4) Tissue sampling under the direct view of POCS showed 82.4% sensitivity, 100% specificity, and 90% (95% CI, 74.4%-96.5%) accuracy. CONCLUSIONS: pCLE under the direct view of POCS provided highly accurate and sensitive characterization of biliary strictures and showed the potential for more diagnostic reliability and reduction of delays in diagnosis. This trial was registered at UMIN (registration number: UMIN000033801).

Development of 8-branch Er:fiber frequency comb for Sr and Yb optical lattice clocks.

We demonstrate an 8-branch Er:fiber frequency comb with seven application ports, which can be individually optimized for applications with different wavelengths. The beat between the comb and a cw laser has a signal-to-noise ratio exceeding 30 dB at a resolution bandwidth of 300 kHz. The 8-branch frequency comb is used to perform frequency locking for four repumping and lattice lasers, and the frequency measurement of two clock lasers of strontium and ytterbium optical lattice clocks. We have achieved reliable optical lattice clock operation, thanks to the stable frequency locking and measurement obtained by using the 8-branch frequency comb. The developed frequency comb is a powerful experimental tool for various applications, including not only optical lattice clocks, but also research on quantum optics that use many frequency-stabilized lasers.

Clinical and neuropathologic analysis of intracerebral hemorrhage in patients with cerebral amyloid angiopathy.

OBJECTIVE: To evaluate the clinical and histopathological features of elderly patients with subcortical intracerebral hemorrhage (ICH), and to analyze the presence of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) type pathologic changes using amyloid beta (Aß) and tau immunohistochemistry. PATIENTS AND METHODS: We retrospectively analyzed cases satisfying the Boston criteria for CAA among patients with subcortical hemorrhage who underwent surgical removal by craniotomy at our hospital. Surgical specimens were subjected to hematoxylin and eosin (HE) staining as well as immunostaining. RESULTS: A total of 54 patients were included in this study, with a mean age of 74.5 years (range: 72.5-76.5 years, 95% confidence interval [CI]; 51% female). Of these 54 patients, 31 (57%) were hypertensive, 18 (33%) were undergoing antithrombotic therapy, and 12 (22%) had dementia. Strong immunoreactivity for Aß40 in the cerebral vessels was observed in 30 patients (55.6%), and among these, 27 patients (90%) also showed strong immunoreactivity for Aß42. Among the 54 patients, 25 (46%) exhibited AD characteristics, including Aß-positive senile plaques and AT8-positive neurons. Multivariate analysis revealed that strong Aß40 immunoreactivity in the cerebral vessels was associated with older patients, females, lack of high blood pressure, and the presence of AT8-positive neurons. CONCLUSION: CAA patients with strong Aß40 deposition in the cerebral vessels were associated with subcortical hemorrhage in our cohort. Future studies should investigate the pathomechanism of ICH in individuals with CAA.

Potential for improving the local realization of coordinated universal time with a convolutional neural network.

The time difference between coordinated universal time (UTC) and a hydrogen maser, which is a master oscillator for the local realization of UTC at the National Metrology Institute of Japan (NMIJ), has been predicted by using one of the deep learning techniques called a one-dimensional convolutional neural network (1D-CNN). Regarding the prediction result obtained by the 1D-CNN, we have observed improvement in the accuracy of prediction compared with that obtained by the Kalman filter. Although more investigations are required to conclude that the 1D-CNN can work as a good predictor, the present results suggest that the computational approach based on the deep learning technique may become a versatile method for improving the synchronous accuracy of UTC(NMIJ) relative to UTC.

Uncertainty Evaluation of an 171Yb Optical Lattice Clock at NMIJ.

We report an uncertainty evaluation of an 171Yb optical lattice clock with a total fractional uncertainty of 3.6×10-16 , which is mainly limited by the lattice-induced light shift and the blackbody radiation shift. Our evaluation of the lattice-induced light shift, the density shift, and the second-order Zeeman shift is based on an interleaved measurement where we measure the frequency shift using the alternating stabilization of a clock laser to the 6s2 1S0-6s6p 3P0 clock transition with two different experimental parameters. In the present evaluation, the uncertainties of two sensitivity coefficients for the lattice-induced hyperpolarizability shift d incorporated in a widely used light shift model by RIKEN and the second-order Zeeman shift aZ are improved compared with the uncertainties of previous coefficients. The hyperpolarizability coefficient d is determined by investigating the trap potential depth and the light shifts at the lattice frequencies near the two-photon transitions 6s6p3P0-6s8p3P0, 6s8p3P2, and 6s5f3F2. The obtained values are d=-1.1(4) µ Hz and aZ=-6.6(3) Hz/mT2. These improved coefficients should reduce the total systematic uncertainties of Yb lattice clocks at other institutes.

Dual-Mode Operation of an Optical Lattice Clock Using Strontium and Ytterbium Atoms.

We have developed an optical lattice clock that can operate in dual modes: a strontium (Sr) clock mode and an ytterbium (Yb) clock mode. Dual-mode operation of the Sr-Yb optical lattice clock is achieved by alternately cooling and trapping 87Sr and 171Yb atoms inside the vacuum chamber of the clock. Optical lattices for Sr and Yb atoms were arranged with horizontal and vertical configurations, respectively, resulting in a small distance of the order of between the trapped Sr and Yb atoms. The 1S0-3P0 clock transitions in the trapped atoms were interrogated in turn and the clock lasers were stabilized to the transitions. We demonstrated the frequency ratio measurement of the Sr and Yb clock transitions by using the dual-mode operation of the Sr-Yb optical lattice clock. The dual-mode operation can reduce the uncertainty of the blackbody radiation shift in the frequency ratio measurement, because both Sr and Yb atoms share the same blackbody radiation.

[Three Cases of High-Grade Malignant Cancer of Unknown Primary with a Long-Term Survival].

We report 3unusual cases of cancer of unknown primary(CUP)with a long-term survival after chemotherapy. A 56-yearold man was diagnosed as having CUP with invasion of an enlarged carcinoma 20 cm in size to the pancreas and peritoneal dissemination. He received chemotherapy with paclitaxel, carboplatin, and gemcitabine. After the chemotherapy, CT scan and PET-CT revealed no evidence of disease, so tumor resection was performed. The subsequent pathological findings revealed no cancer and a complete pathological response. The patient is currently alive 4 years after the first surgery, without evidence of recurrence and adjuvant chemotherapy. A 60-year-old man was diagnosed as having CUP with an undifferentiated carcinoma and lymph node metastasis. He received chemotherapy with paclitaxel, carboplatin, and gemcitabine. However, unanticipated adverse events(finger ulcer)occurred. Thus, the chemotherapy was changed to paclitaxel, carboplatin, and etoposide. The patient is currently alive 4.2 years after the first chemotherapy, without evidence of recurrence. A 59-year-old man was diagnosed as having CUP with neuroendocrine carcinoma(NEC)and lymph node metastasis. He received chemotherapy with irinotecan and cisplatin. The lymph node metastases disappeared, but bone metastasis was found. The chemotherapy was changed to paclitaxel, carboplatin, and etoposide. The patient is currently alive 3.5 years after the first chemotherapy, without evidence of recurrence. We report 3rare cases of high-grade malignant CUP with complete pathological response, partial response, stable disease, and long-term survival after chemotherapy.

Second harmonic generation at 399 nm resonant on the 1S0-1P1 transition of ytterbium using a periodically poled LiNbO3 waveguide.

We demonstrate a compact and robust method for generating a 399-nm light resonant on the 1S0 - 1P1 transition in ytterbium using a single-pass periodically poled LiNbO3 waveguide for second harmonic generation (SHG). The obtained output power at 399 nm was 25 mW when a 798-nm fundamental power of 380 mW was coupled to the waveguide. We observed no degradation of the SHG power for 13 hours with a low power of 6 mW. The obtained SHG light has been used as a seed light for injection locking, which provides sufficient power for laser cooling ytterbium.

Compact iodine-stabilized laser operating at 531 nm with stability at the 10(-12) level and using a coin-sized laser module.

We demonstrate a compact iodine-stabilized laser operating at 531 nm using a coin-sized light source consisting of a 1062-nm distributed-feedback diode laser and a frequency-doubling element. A hyperfine transition of molecular iodine is observed using the light source with saturated absorption spectroscopy. The light source is frequency stabilized to the observed iodine transition and achieves frequency stability at the 10(-12) level. The absolute frequency of the compact laser stabilized to the a(1) hyperfine component of the R(36)32 - 0 transition is determined as 564074632419(8) kHz with a relative uncertainty of 1.4×10(-11). The iodine-stabilized laser can be used for various applications including interferometric measurements.

Frequency ratio measurement of 171Yb and 87Sr optical lattice clocks.

The frequency ratio of the (1)S(0)(F = 1/2)-(3)P(0)(F = 1/2) clock transition in (171)Yb and the (1)S(0)(F = 9/2)-(3)P(0)(F = 9/2) clock transition in (87)Sr is measured by an optical-optical direct frequency link between two optical lattice clocks. We determined the ratio (ν(Yb)/ν(Sr)) to be 1.207 507 039 343 341 2(17) fractional standard uncertainty of 1.4 × 10(-15) [corrected]. The measurement uncertainty of the frequency ratio is smaller than that obtained from absolute frequency measurements using the International Atomic Time (TAI) link. The measured ratio agrees well with that derived from the absolute frequency measurement results obtained at NIST and JILA, Boulder, CO using their Cs-fountain clock. Our measurement enables the first international comparison of the frequency ratios of optical clocks. The measured frequency ratio will be reported to the International Committee for Weights and Measures for a discussion related to the redefinition of the second.

Errata: Frequency ratio measurement of 171Yb and 87Sr optical lattice clocks.

We correct the errors in the uncertainty budget. The determined ratio (νYb/νSr) is corrected to be 1.207 507 039 343 341 2(17) with a fractional standard uncertainty of 1.4 × 10-15.

Spectroscopy of 171Yb in an optical lattice based on laser linewidth transfer using a narrow linewidth frequency comb.

We propose a novel, high-performance, and practical laser source system for optical clocks. The laser linewidth of a fiber-based frequency comb is reduced by phase locking a comb mode to an ultrastable master laser at 1064 nm with a broad servo bandwidth. A slave laser at 578 nm is successively phase locked to a comb mode at 578 nm with a broad servo bandwidth without any pre-stabilization. Laser frequency characteristics such as spectral linewidth and frequency stability are transferred to the 578-nm slave laser from the 1064-nm master laser. Using the slave laser, we have succeeded in observing the clock transition of (171)Yb atoms confined in an optical lattice with a 20-Hz spectral linewidth.

Narrow linewidth laser system realized by linewidth transfer using a fiber-based frequency comb for the magneto-optical trapping of strontium.

A narrow linewidth diode laser system at 689 nm is realized by phase-locking an extended cavity diode laser to one tooth of a narrow linewidth optical frequency comb. The optical frequency comb is phase-locked to a narrow linewidth laser at 1064 nm, which is frequency stabilized to a high-finesse optical cavity. We demonstrate the magneto-optical trapping of Sr using an intercombination transition with the developed laser system.

A compact light source at 461 nm using a periodically poled LiNbO3 waveguide for strontium magneto-optical trapping.

We have developed a compact light source at 461 nm using a single-pass periodically poled LiNbO3 waveguide for second-harmonic (SH) generation. The obtained optical power at 461 nm is 76 mW when the power of the 922-nm fundamental light coupled into the waveguide is 248 mW. Although a narrowing of the phase-matching temperature acceptance bandwidth is observed at a high SH power, stable overnight operation is realized by carefully controlling the device temperature within an uncertainty of 0.01 °C.

Evaluation of the clock laser for an Yb lattice clock using an optic fiber comb.

A light source to drive the (1)S0-(3)P0 transition in Yb atoms is generated by 2 solid state lasers: a Nd:YAG laser and an Yb:YAG laser, using a sum-frequency generation (SFG) scheme. With a ridge waveguide (WG) periodically poled lithium niobate (PPLN) device, SFG power of about 150 mW is obtained at the required frequency. The zero-expansion temperature of a Fabry-Pérot etalon was determined by using a home-made fiber-based optical frequency comb running continuously for weeks. Frequency stabilization of the clock laser system was also evaluated by the optical frequency comb.

A multi-branch, fiber-based frequency comb with millihertz-level relative linewidths using an intra-cavity electro-optic modulator.

We demonstrate that fiber-based frequency combs with multi-branch configurations can transfer both linewidth and frequency stability to another wavelength at the millihertz level. An intra-cavity electro-optic modulator is employed to obtain a broad servo bandwidth for repetition rate control. We investigate the relative linewidths between two combs using a stable continuous-wave laser as a common reference to stabilize the repetition rate frequencies in both combs. The achieved energy concentration to the carrier of the out-of-loop beat between the two combs was 99% and 30% at a bandwidth of 1 kHz and 7.6 mHz, respectively. The frequency instability of the comb was 3.7x10(-16) for a 1 s averaging time, improving to 5-8x10(-19) for 10000 s. We show that the frequency noise in the out-of-loop beat originates mainly from phase noise in branched optical fibers.