Frequency ratios of Sr, Yb and Hg based optical lattice clocks and their applications

This article describes the recent progress of optical lattice clocks with neutral strontium ($^{87}$Sr), ytterbium ($^{171}$Yb) and mercury ($^{199}$Hg) atoms. In particular, we present frequency comparison between the clocks locally via an optical frequency comb and between two Sr clocks at remote sites using a phase-stabilized fibre link. We first review cryogenic Sr optical lattice clocks that reduce the room-temperature blackbody radiation shift by two orders of magnitude and serve as a reference in the following clock comparisons. Similar physical properties of Sr and Yb atoms, such as transition wavelengths and vapour pressure, have allowed our development of a compatible clock for both species. A cryogenic Yb clock is evaluated by referencing a Sr clock. We also report on a Hg clock, which shows one order of magnitude less sensitivity to blackbody radiation, while its large nuclear charge makes the clock sensitive to the variation of fine-structure constant. Connecting all three types of clocks by an optical frequency comb, the ratios of the clock frequencies are determined with uncertainties smaller than possible through absolute frequency measurements. Finally, we describe a synchronous frequency comparison between two Sr-based remote clocks over a distance of 15 km between RIKEN and the University of Tokyo, as a step towards relativistic geodesy.Comment: 11 pages, 5 figures, invited review article in Comptes Rendus de Physique 201

Direct Comparison of Distant Optical Lattice Clocks at the 10−1610^{-16} Uncertainty

Fiber-based remote comparison of $^{87}$Sr lattice clocks in 24 km distant laboratories is demonstrated. The instability of the comparison reaches $5\times10^{-16}$ over an averaging time of 1000 s, which is two orders of magnitude shorter than that of conventional satellite links and is limited by the instabilities of the optical clocks. By correcting the systematic shifts that are predominated by the differential gravitational redshift, the residual fractional difference is found to be $(1.0\pm7.3)\times10^{-16}$, confirming the coincidence between the two clocks. The accurate and speedy comparison of distant optical clocks paves the way for a future optical redefinition of the second

A Case of Metastatic Urachal Cancer Including a Neuroendocrine Component Treated with Gemcitabine, Cisplatin and Paclitaxel Combination Chemotherapy

The present case report describes a case of recurrent and advanced urachal carcinoma including neuroendocrine features with iliac bone metastasis after partial cystectomy and adjuvant chemotherapy consisting of irinotecan and cisplatin in a 32-year-old man. He received gemcitabine/cisplatin/ paclitaxel (GCP) combination chemotherapy, consisting of gemcitabin (1,000mg/m2) on day 1, 8, cisplatin (70mg/m2) on day 1, and paclitaxel (80mg/m2) on day 1 and 8. After three cycles of chemotherapy, PET-CT showed complete regression of the disease. So the patient underwent total cystourethrectomy, and histological examination showed an almost complete pathological response. External beam radiation therapy was also given to the ileac bone metastasis regions. However, PET-CT taken 17 months after the external beam radiation showed multiple lung metastases. He received GCP chemotherapy again, which resulted in a complete response again after three cycles of chemotherapy. This is the first report on GCP chemotherapy used not only as a salvage chemotherapy but also as a rechallenge regimen for metastatic urachal cancer including a neuroendocrine component

All-optical link for direct comparison of distant optical clocks

We developed an all-optical link system for making remote comparisons of two distant ultra-stable optical clocks. An optical carrier transfer system based on a fiber interferometer was employed to compensate the phase noise accumulated during the propagation through a fiber link. Transfer stabilities of $2\times10^{-15}$ at 1 second and $4\times10^{-18}$ at 1000 seconds were achieved in a 90-km link. An active polarization control system was additionally introduced to maintain the transmitted light in an adequate polarization, and consequently, a stable and reliable comparison was accomplished. The instabilities of the all-optical link system, including those of the erbium doped fiber amplifiers (EDFAs) which are free from phase-noise compensation, were below $2\times10^{-15}$ at 1 second and $7\times10^{-17}$ at 1000 seconds. The system was available for the direct comparison of two distant $^{87}$Sr lattice clocks via an urban fiber link of 60 km. This technique will be essential for the measuring the reproducibility of optical frequency standards

Stability Transfer between Two Clock Lasers Operating at Different Wavelengths for Absolute Frequency Measurement of Clock Transition in 87Sr

We demonstrated transferring the stability of one highly stable clock laser operating at 729 nm to another less stable laser operating at 698 nm. The two different wavelengths were bridged using an optical frequency comb. The improved stability of the clock laser at 698 nm enabled us to evaluate the systematic frequency shifts of the Sr optical lattice clock with shorter averaging time. We determined the absolute frequency of the clock transition 1S0 - 3P0 in 87Sr to be 429 228 004 229 873.9 (1.4) Hz referenced to the SI second on the geoid via International Atomic Time (TAI)

A Combination Therapy of Partial Nephrectomy and Cryoablation Achieved Good Cancer Control and Renal Function in Bilateral Synchronous Renal Cell Carcinoma

We report the case of a 58-year-old Japanese man with bilateral synchronous renal cell carcinoma (RCC). The diameters of the right and left tumors were 56 and 69 mm, respectively. Both tumors were endophytic. Cryoablation with prophylactic embolization was performed for the left tumor, and 1 month later, a right open partial nephrectomy was performed. No recurrence was observed during a 16-month follow-up, and the serum creatinine level has been stable. The prognosis of bilateral synchronous RCC is better than that of dialysis patients. The novel approach of combining cryoablation and partial nephrectomy can achieve good cancer control and renal function in bilateral RCC

Testosterone Recovery after Neoadjuvant Gonadotropin-Releasing Hormone Antagonist versus Agonist on Permanent Iodine-125 Seed Brachytherapy in Prostate Cancer Patients: A Propensity Score Analysis

Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients’ prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients

A Case of Metastatic Fumarate Hydratase-Deficient–like Renal Cell Carcinoma Successfully Managed by Ipilimumab plus Nivolumab

We report a 62-year-old male with metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) without fumarate hydratase (FH) mutation (FH-deficient–like RCC). The International Metastatic RCC Database Consortium risk score was intermediate, and immunotherapy with nivolumab and ipilimumab (Ipi/ Nivo) was initiated. Four cycles of Ipi/Nivo and 5 cycles of nivolumab resulted in a complete response of the metastases. Hypophysitis occurred as an immune-related adverse event after four cycles of Ipi/Nivo. The prognosis of patients with FH-deficient RCC is generally poor. Few reports of FH-deficient RCC successfully treated with Ipi/Nivo have been published. Ipi/Nivo can be effective for treating FH-deficient RCC