Synchronized source of indistinguishable photons for quantum networks.

We present a source of indistinguishable photons at telecom wavelength, synchronized to an external clock, for the use in distributed quantum networks. We characterize the indistinguishability of photons generated in independent parametric down-conversion events using a Hong-Ou-Mandel interferometer, and show non-classical interference with coalescence, C = 0.83(5). We also demonstrate the synchronization to an external clock within sub-picosecond timing jitter, which is significantly shorter than the single-photon wavepacket duration of ≈ 35 ps. Our source enables scalable quantum protocols over multi-node, long-distance optical networks using network-based clock recovery systems.

Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide.

BACKGROUND: Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary end points were evaluated. RESULTS: The median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy. Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P = 0.003). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy. The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).

Synchronization and coexistence in quantum networks.

We investigate the coexistence of clock synchronization protocols with quantum signals in a common single-mode optical fiber. By measuring optical noise between 1500 nm to 1620 nm we demonstrate a potential for up to 100 quantum, 100 GHz wide channels coexisting with the classical synchronization signals. Both "White Rabbit" and pulsed laser-based synchronization protocols were characterized and compared. We establish a theoretical limit of the fiber link length for coexisting quantum and classical channels. The maximal fiber length is below approximately 100 km for off-the-shelf optical transceivers and can be significantly improved by taking advantage of quantum receivers.

New Series of Red-Light Phosphor Ca9-xZnxGd0.9(PO4)7:0.1Eu3+ (x = 0-1).

In this study, a new series of phosphors, Ca9−xZnxGd0.9(PO4)7:0.1Eu3+ (x = 0.00−1.00, step dx 0.05), was synthesized, consisting of centro- and non-centrosymmetric phases with ß-Ca3(PO4)2-type structure. Crystal structures with space groups R3c (0.00 ≤ x < 0.35) and R3¯c (x > 0.8) were determined using X-ray powder diffraction and the method of optical second harmonic generation. In the region 0.35 ≤ x ≤ 0.75, phases R3c and R3¯c were present simultaneously. Refinement of the Ca8ZnGd(PO4)7 crystal structure with the Rietveld method showed that 71% of Gd3+ ions are in M3 sites and 29% are in M1 sites. A luminescent spectroscopy study of Ca9−xZnxGd0.9(PO4)7:0.1Eu3+ indicated the energy transfer from the crystalline host to the Gd3+ and Eu3+ luminescent centers. The maximum Eu3+ luminescence intensity corresponds to the composition with x = 1.

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer.

BACKGROUND: Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic, castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned in a 2:1 ratio to receive darolutamide (600 mg [two 300-mg tablets] twice daily) or placebo while continuing androgen-deprivation therapy. The primary end point was metastasis-free survival, with the presence of metastasis determined by independent central review of radiographic imaging every 16 weeks. RESULTS: In total, 1509 patients underwent randomization (955 to the darolutamide group and 554 to the placebo group). In the planned primary analysis, which was performed after 437 primary end-point events had occurred, the median metastasis-free survival was 40.4 months with darolutamide, as compared with 18.4 months with placebo (hazard ratio for metastasis or death in the darolutamide group, 0.41; 95% confidence interval, 0.34 to 0.50; P<0.001). Darolutamide was also associated with benefits with regard to all secondary end points, including overall survival, time to pain progression, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event. The incidence of adverse events that occurred or worsened during the treatment period and had a frequency of 5% or more or were of grade 3 or higher was similar in the two groups; all such events except fatigue occurred in less than 10% of patients in either group. The percentage of patients who discontinued the assigned regimen because of adverse events was 8.9% in the darolutamide group and 8.7% in the placebo group. Darolutamide was not associated with a higher incidence of seizures, falls, fractures, cognitive disorder, or hypertension than placebo. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, metastasis-free survival was significantly longer with darolutamide than with placebo. The incidence of adverse events was similar for darolutamide and placebo. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).

Experimental Shot-by-Shot Estimation of Quantum Measurement Confidence.

We demonstrate the single-shot confidence estimation for individual quantum measurement outcomes using the continuous measurement theory of the quantum counting process applied to the quantum state identification problem. We experimentally obtain single-shot and average confidences for quantum measurements and show that they favorably compare to that of the idealized classical measurement. Finally, we demonstrate that single-shot confidence estimations correctly represent observed experimental outcomes for a large ensemble of measurements.

In Situ Flow Cytometer Calibration and Single-Molecule Resolution via Quantum Measurement.

Fluorescent biomarkers are used to detect target molecules within inhomogeneous populations of cells. When these biomarkers are found in trace amounts it becomes extremely challenging to detect their presence in a flow cytometer. Here, we present a framework to draw a detection baseline for single emitters and enable absolute calibration of a flow cytometer based on quantum measurements. We used single-photon detection and found the second-order autocorrelation function of fluorescent light. We computed the success of rare-event detection for different signal-to-noise ratios (SNR). We showed high-accuracy identification of the events with occurrence rates below 10-5 even at modest SNR levels, enabling early disease diagnostics and post-disease monitoring.

Coherent optical processes with an all-optical atomic simulator.

We show how novel photonic devices such as broadband quantum memory and efficient quantum frequency transduction can be implemented using three-wave mixing processes in a 1D array of nonlinear waveguides evanescently coupled to nearest neighbors. We do this using an analogy of an atom interacting with an external optical field using both classical and quantum models of the optical fields and adapting well-known coherent processes from atomic optics, such as electromagnetically induced transparency and stimulated Raman adiabatic passage to design. This approach allows the implementation of devices that are very difficult or impossible to implement by conventional techniques.

Simple autocorrelation method for thoroughly characterizing single-photon detectors.

We introduce and demonstrate a simple and highly sensitive method for characterizing single-photon detectors. This method is based on analyzing multi-order correlations among time-tagged detection events from a device under calibrated continuous-wave illumination. First- and second-order properties such as detection efficiency, dark count rate, afterpulse probability, dead time, and reset behavior are measured with high accuracy from a single data set, as well as higher-order properties such as higher-order afterpulse effects. While the technique is applicable to any type of click/no-click detector, we apply it to two different single-photon avalanche diodes, and we find that it reveals a heretofore unreported afterpulse effect due to detection events that occur during the device reset.

Quantum frequency bridge: high-accuracy characterization of a nearly-noiseless parametric frequency converter.

We demonstrate an efficient and inherently ultra-low noise frequency conversion via a parametric sum frequency generation. Due to the wide separation between the input and pump frequencies and the low pump frequency relative to the input photons, the upconversion results in only ≈100 background photons per hour. To measure such a low rate, we introduced a dark count reduction algorithm for an optical transition edge sensor.

Generalized pupil function of a compound X-ray refractive lens.

Quality of a refractive compound X-ray lens can be limited by imperfections in surfaces of unit lenses and stacking precision. In general case both the lens transmission and optical aberrations define properties of a beam in the lens exit plane; together they can be expressed in terms of the generalized pupil function. In this work we measure this function for a diamond single crystal compound refractive lens. Consequently, we apply the pupil function to evaluate the performance of the examined compound refractive X-ray lens. A number of practically important conclusions can be drawn from such analysis.

Results of a prospective randomized study assessing the efficacy of fluorescent cystoscopy-assisted transurethral resection and single instillation of doxorubicin in patients with non-muscle-invasive bladder cancer.

OBJECTIVES: To assess the efficacy of two treatment options for non-muscle-invasive bladder cancer (NMIBC): (1) transurethral resection (TUR) guided by fluorescence cystoscopy (FC) with the use of 5-aminolevulinic acid (5-ALA) and (2) single early instillation of doxorubicin in a single-center open-label prospective randomized study with a 2 × 2 factorial design. PATIENTS AND METHODS: Patients with clinical suspicion of primary or recurrent NMIBC were randomized into four study arms: FC-assisted TUR with 5-ALA and single instillation of doxorubicin, FC-assisted TUR without instillation, TUR in white light (WL) with single instillation of doxorubicin, and WL-TUR only. The study was designed to assess recurrence-free survival in arms with and without any of two interventions. RESULTS: Of 525 patients included, 377 (72 %) were eligible for primary outcome assessment. The median follow-up was 54.8 months. FC statistically significantly decreased the risk of disease recurrence and progression with hazard ratio (HR) 0.56 (95 % CI 0.39-0.80, p = 0.001) and 0.33 (95 % CI 0.12-0.91, p = 0.031), respectively. The HRs for recurrence and progression for single instillation of doxorubicin were 0.76 (95 % CI 0.54-1.07, p = 0.11) and 0.65 (95 % CI 0.28-1.52, p = 0.32), respectively. The overall and cancer-specific survival rates did not differ significantly based on the therapeutic interventions. CONCLUSIONS: In patients with NMIBC, FC-assisted TUR with 5-ALA results in a substantial recurrence and progression risk reduction as compared to WL-TUR. The single early postoperative instillation of doxorubicin did not have a statistically significant impact on recurrence and progression risks.

Statistically background-free, phase-preserving parametric up-conversion with faint light.

We demonstrate up-conversion with no statistically significant background photons and a dynamic range of 15 decades. Near-infrared 920 nm photons were converted into the visible at 577 nm using periodically poled lithium niobate waveguides pumped by a 1550 nm laser. In addition to achieving statistically noiseless frequency up-conversion, we report a high degree of phase preservation (with fringe visibilities ≥ 0.97) at the single-photon level using an up-converting Mach-Zehnder interferometer. This background-free process opens a path to single-photon detection with no intrinsic dark count. Combined with a demonstrated photon-number preserving property of an up-converter, this work demonstrates the feasibility of noiseless frequency up-conversion of entangled photon pairs.

Neural Correlates of Social Decision-Making.

Objective: Recent studies have utilized innovative techniques to investigate the neural mechanisms underlying social and individual decision-making, aiming to understand how individuals respond to the world. Method : In this review, we summarized current scientific evidence concerning the neural underpinnings of social decision-making and their impact on social behavior. Results: Critical brain regions involved in social cognition and decision-making are integral to the process of social decision-making. Notably, the medial prefrontal cortex (mPFC) and temporoparietal junction (TPJ) contribute to the comprehension of others' mental states. Similarly, the posterior superior temporal sulcus (pSTS) shows heightened activity when individuals observe faces and movements. On the lateral surface of the brain, the inferior frontal gyrus (IFG) and inferior parietal sulcus (IPS) play a role in social cognition. Furthermore, the medial surface of the brain, including the amygdala, anterior cingulate cortex (ACC), and anterior insula (AI), also participates in social cognition processes. Regarding decision-making, functional magnetic resonance imaging (fMRI) studies have illuminated the involvement of a network of brain regions, encompassing the ventromedial prefrontal cortex (vmPFC), ventral striatum (VS), and nucleus accumbens (NAcc). Conclusion: Dysfunction in specific subregions of the prefrontal cortex (PFC) has been linked to various psychiatric conditions. These subregions play pivotal roles in cognitive, emotional, and social processing, and their impairment can contribute to the development and manifestation of psychiatric symptoms. A comprehensive understanding of the unique contributions of these PFC subregions to psychiatric disorders has the potential to inform the development of targeted interventions and treatments for affected individuals.

Clinical efficacy of plasmid encoding p62/SQSTM1 (Elenagen) in combination with gemcitabine in patients with platinum-resistant ovarian cancer: a randomized controlled trial.

Background: The purpose of this trial is to evaluate the safety and efficacy of ELENAGEN, a novel anticancer therapeutic DNA plasmid encoding p62/SQSTM1 protein, as an adjuvant to chemotherapy with gemcitabine (GEM) in patients with advanced platinum-resistant ovarian cancer. Methods: This open-label prospective randomized study with two arms. GEM (1000 mg/m2) on days 1 and 8 every 3 weeks was administered in both arms: in the Chemo arm (n = 20), GEM was the only treatment, and in the ELENAGEN arm (n = 20), GEM was supplemented with ELENAGEN (2.5 mg i.m. weekly). The primary endpoint was progression-free survival (PFS), and the secondary endpoint was safety. Antitumor activity was assessed by RECIST 1.1, and criteria safety was assessed according to NCI CTCAE version 5.0. Results: According to the cutoff data, the median follow-up was 13.8 months. There were no serious adverse events related to ELENAGEN treatment. The median PFS was 2.8 and 7.2 months in the Chemo and ELENAGEN arms, respectively (p Log-Rank = 0.03). Notably, at the time of cutoff, 9 patients (45%) in the ELENAGEN arm did not progress, with the longest PFS recorded thus far being 24 months. Subgroup analysis of patients in both arms demonstrated high efficacy of ELENAGEN in patients with worse prognostic factors: high pretreatment levels of CA125 and progression after platinum-free interval <3 months. Conclusions: The addition of ELENAGEN to gemcitabine is effective in patients with platinum-resistant ovarian cancer, including those with a worse prognosis. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT05979298, identifier NCT05979298, 2023-08-07.

Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time: Planned Subgroup Analysis of the Phase 3 ARAMIS Trial.

BACKGROUND: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo. OBJECTIVE: To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo. DESIGN, SETTING, AND PARTICIPANTS: A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted. INTERVENTION: Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study. RESULTS AND LIMITATIONS: Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26-0.55]; PSADT ≤6 mo, 0.41 [0.33-0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations. CONCLUSIONS: In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability. PATIENT SUMMARY: In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, "PSA doubling time" [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients' quality of life without disruptions.

Dynamics of nonclassical light from a single solid-state quantum emitter.

We measure the dynamics of a nonclassical optical field using two-time second-order correlations in conjunction with pulsed excitation. The technique quantifies single-photon purity and coherence during the excitation-decay cycle of an emitter, illustrated here using a quantum dot. We observe that for certain pump wavelengths, photons detected early in the cycle have reduced single-photon purity and coherence compared to those detected later. A model indicates that the single-photon purity dynamics are due to exciton recapture after initial emission and within the same pulse cycle.

Coalescence of single photons emitted by disparate single-photon sources: the example of InAs quantum dots and parametric down-conversion sources.

Single photons produced by fundamentally dissimilar physical processes will in general not be indistinguishable. We show how photons produced from a quantum dot and by parametric down-conversion in a nonlinear crystal can be manipulated to be indistinguishable. The measured two-photon coalescence probability is 16%, and is limited by quantum-dot decoherence. Temporal filtering to the quantum-dot coherence time and accounting for detector time response increases this to 61% while retaining 25% of the events. This technique can connect different elements in a scalable quantum network.

Analytical method for parameterizing the random profile components of nanosurfaces imaged by atomic force microscopy.

The functional properties of many technological surfaces in biotechnology, electronics, and mechanical engineering depend to a large degree on the individual features of their nanoscale surface texture, which in turn is a function of the surface manufacturing process. Among these features, the surface irregularities and self-similarity structures at different spatial scales, especially in the range of 1 to 100 nm, are of high importance because they greatly affect the surface interaction forces acting at a nanoscale distance. An analytical method for parameterizing the surface irregularities and their correlations in nanosurfaces imaged by atomic force microscopy (AFM) is proposed. In this method, flicker noise spectroscopy--a statistical physics approach--is used to develop six nanometrological parameters characterizing the high-frequency contributions of jump- and spike-like irregularities into the surface texture. These contributions reflect the stochastic processes of anomalous diffusion and inertial effects, respectively, in the process of surface manufacturing. The AFM images of the texture of corrosion-resistant magnetite coatings formed on low-carbon steel in hot nitrate solutions with coating growth promoters at different temperatures are analyzed. It is shown that the parameters characterizing surface spikiness are able to quantify the effect of process temperature on the corrosion resistance of the coatings. It is suggested that these parameters can be used for predicting and characterizing the corrosion-resistant properties of magnetite coatings.