Quantum-limited optical time transfer for future geosynchronous links

The combination of optical time transfer and optical clocks opens up the possibility of large-scale free-space networks that connect both ground-based optical clocks and future space-based optical clocks. Such networks promise better tests of general relativity, dark matter searches, and gravitational wave detection. The ability to connect optical clocks to a distant satellite could enable space-based very long baseline interferometry (VLBI), advanced satellite navigation, clock-based geodesy, and thousand-fold improvements in intercontinental time dissemination. Thus far, only optical clocks have pushed towards quantum-limited performance. In contrast, optical time transfer has not operated at the analogous quantum limit set by the number of received photons. Here, we demonstrate time transfer with near quantum-limited acquisition and timing at 10,000 times lower received power than previous approaches. Over 300 km between mountaintops in Hawaii with launched powers as low as 40 $\mu$W, distant timescales are synchronized to 320 attoseconds. This nearly quantum-limited operation is critical for long-distance free-space links where photons are few and amplification costly -- at 4.0 mW transmit power, this approach can support 102 dB link loss, more than sufficient for future time transfer to geosynchronous orbits

Synchronization of Distant Optical Clocks at the Femtosecond Level

The use of optical clocks/oscillators in future ultra-precise navigation, gravitational sensing, coherent arrays, and relativity experiments will require time comparison and synchronization over terrestrial or satellite free-space links. Here we demonstrate full unambiguous synchronization of two optical timescales across a free-space link. The time deviation between synchronized timescales is below 1 fs over durations from 0.1 s to 6500 s, despite atmospheric turbulence and kilometer-scale path length variations. Over several days, the time wander is 40 fs peak-to-peak. Our approach relies on the two-way reciprocity of a single-spatial-mode optical link, valid to below 225 attoseconds across a turbulent 4-km path. This femtosecond level of time-frequency transfer should enable optical networks using state-of-the-art optical clocks/oscillators.Comment: 19 pages, 9 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The Time Programmable Frequency Comb: Generation and Application to Quantum-Limited Dual-Comb Ranging

The classic self-referenced frequency comb acts as an unrivaled ruler for precision optical metrology in both time and frequency. Two decades after its invention, the frequency comb is now used in numerous active sensing applications. Many of these applications, however, are limited by the tradeoffs inherent in the rigidity of the comb output and operate far from quantum-limited sensitivity. Here we demonstrate an agile programmable frequency comb where the pulse time and phase are digitally controlled with +/- 2 attosecond accuracy. This agility enables quantum-limited sensitivity in sensing applications since the programmable comb can be configured to coherently track weak returning pulse trains at the shot-noise limit. To highlight its capabilities, we use this programmable comb in a ranging system, reducing the detection threshold by ~5,000-fold to enable nearly quantum-limited ranging at mean pulse photon number of 1/77 while retaining the full accuracy and precision of a rigid frequency comb. Beyond ranging and imaging, applications in time/frequency metrology, comb-based spectroscopy, pump-probe experiments, and compressive sensing should benefit from coherent control of the comb-pulse time and phase

Application of quantum-limited optical time transfer to space-based optical clock comparisons and coherent networks

With the demonstration of quantum-limited optical time transfer capable of tolerating the losses associated with long ground-to-space links, two future applications of free-space time transfer have emerged: intercontinental clock comparisons for time dissemination and coherence transfer for future distributed sensing in the mm-wave region. In this paper, we estimated the projected performance of these two applications using quantum-limited optical time transfer and assuming existing low-size, low-weight, and low-power hardware. In both cases, we limit the discussion to the simplest case of a single geosynchronous satellite linked to either one or two ground stations. One important consideration for such future space-based operations is the choice of reference oscillator onboard the satellite. We find that with a modestly performing optical reference oscillator and low-power fiber-based frequency combs, quantum-limited time transfer could support intercontinental clock comparisons through a common-view node in geostationary orbit with a modified Allan deviation at the 10−16 level at 10-s averaging time, limited primarily by residual turbulence piston noise. In the second application of coherence transfer from ground-to-geosynchronous orbit, we find the system should support high short-term coherence with ∼10 millirad phase noise on a 300 GHz carrier at essentially unlimited integration times

Population pharmacokinetics and pharmacodynamics of cysteamine in nephropathic cystinosis patients

<p>Abstract</p> <p>Background</p> <p>Nephropathic cystinosis is an autosomal recessive disorder resulting in an impaired transport of cystine trough the lysosomal membrane causing an accumulation of free cystine in lysosomes. The only specific treatment for nephropathic cystinosis is cysteamine bitartrate. This study was aimed to describe the relationship between cysteamine plasma concentrations and white blood cell cystine levels, and to simulate an optimized administration scheme to improve the management of patients with cystinosis.</p> <p>Methods</p> <p>Cysteamine and cystine concentrations were measured in 69 nephropathic cystinosis patients. A total of 250 cysteamine plasma concentrations and 243 intracellular cystine concentrations were used to perform a population pharmacokinetic and pharmacodynamic analysis. An optimized administration scheme was simulated in order to maintain cystine levels below 1 nmol half-cystine/mg of protein and to investigate the possibility of administrating the treatment less than 4 times a day (QID, recommended). The current dosing recommendations are 1.3 g/m²/day for less than 50 kg BW and 2 g/day thereafter; the maximum dose should not exceed 1.95 g/m²/day.</p> <p>Results</p> <p>Cysteamine concentrations were satisfactorily described by a one-compartment model. Parameter estimates were standardized for a mean standard bodyweight using an allometric model. WBC cystine levels were adequately described by an indirect response model where the first-order removal rate constant is stimulated by the cysteamine concentrations.</p> <p>Conclusions</p> <p>According to simulations, in order to increase the percentage of patient with cystine levels below 1 nmol half-cystine/mg of protein, the current dosages could be changed as follows: 80 mg/kg/day (QID) from 10 to 17 kg, 70 mg/kg/day (QID) from 17 to 25 kg, 60 mg/kg/day (QID) from 25 to 40 kg and 50 mg/kg/day (QID) from 40 to 70 kg (these dosages remain under the maximum recommended dose). However an 8-hourly daily treatment (TID) did not provide acceptable cystine levels and should not be proposed.</p

Histological prognostic factors in children with Henoch-Schönlein purpura nephritis

International audienceBACKGROUND: The management of IgA vasculitis with nephritis (IgAVN) remains controversial because of the difficulty to identify prognostic factors. This study reports the prognosis of children with IgAVN in relation to histological parameters.METHODS: All children with IgAVN diagnosed between 2000 and 2015 in three pediatric nephrology centers were included. The following histological parameters were analyzed: mesangial proliferation (MP), endocapillary proliferation (EP), crescents, active, or chronic tubular and interstitial lesions (TIa lesions/TIc lesions), and segmental glomerulosclerosis (GS). Clinical and biological data were collected at the time of renal biopsy. The primary endpoint was IgAVN remission defined as a proteinuria < 200 mg/l without renal failure.RESULTS: One hundred fifty-nine children were included with a median age of 7.6 years. Acute glomerular or TI lesions including MP, EP, crescents, and TIa lesions were observed, respectively, in 81%, 86%, 49%, and 21% of patients. Chronic glomerular lesions including GS and TIc lesions were observed in 6 and 7% of patients. Median initial proteinuria was 330 mg/mmol, albuminemia 32 g/l, and eGFR 110 ml/min/1.73 m2. One hundred twelve (70%) patients were in remission at the end of a median follow-up of 37.4 months. Chronic lesions were significantly associated with the absence of remission in multivariate analysis, whereas EP, crescents and TIa were not associated with a poor prognosis.CONCLUSIONS: Of children with IgAVN, 30% present a persistent renal disease at the end of a 3-year follow-up. Chronic histological lesions, but not EP or crescents, are associated with a bad prognosis and must be evaluated in IgAVN histological classification