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\"Go back in time with Nobel Prize laureate Michel Mayor to understand the secrets of the Universe and meet the great names in physics: Newton, Einstein and many more. This graphic-novel guide to the Universe explains complex ideas in a way anyone can understand. It's a book full of adventure-- as well as some of the most important concepts humankind has ever studied. On the program: gravitational waves, the theory of relativity, black holes-- and more!\"--back cover.

Efficient interconversion of both classical and quantum information between microwave and optical frequency is an important engineering challenge. The optomechanical approach with gigahertz-frequency mechanical devices has the potential to be extremely efficient due to the large optomechanical response of common materials, and the ability to localize mechanical energy into a micron-scale volume. However, existing demonstrations suffer from some combination of low optical quality factor, low electrical-to-mechanical transduction efficiency, and low optomechanical interaction rate. Here we demonstrate an on-chip piezo-optomechanical transducer that systematically addresses all these challenges to achieve nearly three orders of magnitude improvement in conversion efficiency over previous work. Our modulator demonstrates acousto-optic modulation with V π = 0.02 V. We show bidirectional conversion efficiency of 1 0 − 5 with 3.3 μW  red-detuned optical pump, and 5.5 % with 323 μW blue-detuned pump. Further study of quantum transduction at millikelvin temperatures is required to understand how the efficiency and added noise are affected by reduced mechanical dissipation, thermal conductivity, and thermal capacity. Current optomechanical implementations of microwave and optical frequency interconversion are lacking in efficiency and interaction strength. The authors design and demonstrate an on-chip piezo-optomechanical solution which overcomes several technical barriers to reach several orders of magnitude improvement in efficiency.

Photons with optical frequencies of a few hundred terahertz are perhaps the only way to distribute quantum information over long distances. Superconducting qubits, which are one of the most promising approaches for realizing large-scale quantum machines, operate on microwave photons at frequencies that are ~40,000 times lower. To network these quantum machines across appreciable distances, we must bridge this frequency gap. Here we implement and demonstrate a transducer that can generate correlated optical and microwave photons. We use it to show that by detecting an optical photon we generate an added microwave photon with an efficiency of ~35%. Our device uses a gigahertz nanomechanical resonance as an intermediary, which efficiently couples to optical and microwave channels through strong optomechanical and piezoelectric interactions. We show continuous operation of the transducer with 5% frequency conversion efficiency, input-referred added noise of ~100, and pulsed microwave photon generation at a heralding rate of 15 Hz. Optical absorption in the device generates thermal noise of less than two microwave photons. Improvements of the system efficiencies and device performance are necessary to realize a high rate of entanglement generation between distant microwave-frequency quantum nodes, but these enhancements are within reach.Many quantum devices operate in the microwave regime, but long-distance communication relies on optical photons. A nanomechanical resonator can be used to create entangled optical and microwave photons linking the two frequency regimes.

Integrated optomechanical systems are a leading platform for manipulating, sensing, and distributing quantum information, but are limited by residual optical heating. Here, we demonstrate a two-dimensional optomechanical crystal (OMC) geometry with increased thermal anchoring and a mechanical mode at 7.4 GHz, well aligned with the operation range of cryogenic microwave hardware and piezoelectric transducers. The eight times better thermalization than current one-dimensional OMCs, large optomechanical coupling rates, g 0 /2 π   ≈  880 kHz, and high optical quality factors, Q opt  = 2.4 × 10 5 , allow ground-state cooling ( n m  = 0.32) of the acoustic mode from 3 K and entering the optomechanical strong-coupling regime. In pulsed sideband asymmetry measurements, we show ground-state operation ( n m  < 0.45) at temperatures below 10 mK, with repetition rates up to 3 MHz, generating photon-phonon pairs at  ≈ 147 kHz. Our results extend optomechanical system capabilities and establish a robust foundation for future microwave-to-optical transducers with entanglement rates exceeding state-of-the-art superconducting qubit decoherence rates. Here the authors overcome the temperature increase in integrated optomechanical systems, harnessing two-dimensional optomechanical crystal geometry. These results set the ground for microwave-to-optical transducers with entanglement rates overcoming the decoherence rates of state-of-the-art superconducting qubits.

ObjectivesTo assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months.DesignAn open-label, multicentre, non-randomised clinical trial.SettingEight secondary and tertiary care hospitals (public and private) in Puerto Rico.Participants300 Caribbean Hispanic patients on clopidogrel, both genders, underwent percutaneous coronary intervention (PCI) for acute coronary syndromes, stable ischaemic heart disease and documented extracardiac vascular diseases.InterventionsPatients were separated into standard-of-care (SoC) and genotype-guided (pharmacogenetic (PGx)-CDS) groups (150 each) and stratified by risk scores. Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Individual platelet function, genotypes, clinical and demographic data were included. Ticagrelor was recommended for patients with a high-risk score ≥2 in the PGx-CDS group only, the rest were kept or de-escalated to clopidogrel. The intervention took place within 3–5 days after PCI. Adherence medication score was also measured.Primary and secondary outcomesThe occurrence rate of MACCEs (primary) and bleeding episodes (secondary). Statistical associations between patient time free of events and predictor variables (ie, treatment groups, risk scores) were tested using Kaplan-Meier survival analyses and Cox proportional-hazards regression models.ResultsThe genotype-guided group had a clinically lower but not significantly different risk of MACCEs compared with the SoC group (8.7% vs 10.7%, p=0.56; HR=0.56). Among high-risk score patients, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in reducing MACCE incidence 6 months postcoronary stenting (adjusted HR=0.104; p< 0.0001).ConclusionsThe potential benefit of implementing our PGx-CDS algorithm to significantly reduce the incidence rate of MACCEs in post-PCI Caribbean Hispanic patients on clopidogrel was observed exclusively among high-risk patients, with apparently no evident effect in other patient groups.Trial registration numberNCT03419325.

Hot Jupiter WASP-18b: a too-close encounter 'Hot Jupiter' extrasolar planets are thought to have formed at some distance from their host stars and to have migrated inwards at a later date. These planets provide new perspectives on the evolution of planetary systems, and the discovery of WASP-18b, the closest-orbiting and most extreme hot Jupiter yet, provides a glimpse of what may be a planet nearing the end of its life. With a close orbit, high mass (ten times that of Jupiter), and brief (0.94-day) orbital period, WASP-18b has the strongest tidal interaction of any known star–planet system. We appear to be seeing WASP-18b in a rare and short-lived state as it spirals towards its host star, destined to be destroyed within the host star's lifetime. Alternatively, the tidal dissipation this system — and perhaps other hot Jupiters — must be much weaker than that in our Solar System. 'Hot Jupiters' abound in lists of known extrasolar planets. Those closest to their parent stars have strong tidal interactions, leading to the suggestion that systems such as OGLE-TR-56 could be used as tests of tidal dissipation theory. Here, the discovery of planet WASP-18b is reported, with an orbital period of 0.94 days and a tidal interaction an order of magnitude stronger than that of OGLE-TR-56b. Either WASP-18 is in a rare, short-lived state, or the tidal dissipation in this system must be weaker than in the Solar System. The ‘hot Jupiters’ that abound in lists of known extrasolar planets are thought to have formed far from their host stars, but migrate inwards through interactions with the proto-planetary disk from which they were born 1 , 2 , or by an alternative mechanism such as planet–planet scattering 3 . The hot Jupiters closest to their parent stars, at orbital distances of only ∼0.02 astronomical units, have strong tidal interactions 4 , 5 , and systems such as OGLE-TR-56 have been suggested as tests of tidal dissipation theory 6 , 7 . Here we report the discovery of planet WASP-18b with an orbital period of 0.94 days and a mass of ten Jupiter masses (10  M Jup ), resulting in a tidal interaction an order of magnitude stronger than that of planet OGLE-TR-56b. Under the assumption that the tidal-dissipation parameter Q of the host star is of the order of 10 6 , as measured for Solar System bodies and binary stars and as often applied to extrasolar planets, WASP-18b will be spiralling inwards on a timescale less than a thousandth that of the lifetime of its host star. Therefore either WASP-18 is in a rare, exceptionally short-lived state, or the tidal dissipation in this system (and possibly other hot-Jupiter systems) must be much weaker than in the Solar System.

Background To compare the main outcomes of trauma patients with and without traumatic brain injury (TBI), hemorrhagic shock, and the combination of both using data from the Spanish trauma intensive care unit (ICU) registry (RETRAUCI). Methods Patients admitted to the participating ICUs from March 2015 to May 2019 were included in the study. The main outcomes were analyzed according to the presence of TBI, hemorrhagic shock, and/or both. Comparison of groups with quantitative variables was performed using the Kruskal-Wallis test, and differences between groups with categorical variables were compared using the Chi-square test or Fisher’s exact test as appropriate. A P value <.05 was considered significant. Results Overall, 310 patients (3.98%) were presented with TBI and hemorrhagic shock. Patients with TBI and hemorrhagic shock received more red blood cell (RBC) concentrates, fresh frozen plasma (FFP), a higher ratio FFP/RBC, and had a higher incidence of trauma-induced coagulopathy (60%) (P < .001). These patients had higher mortality (P < .001). Intracranial hypertension was the leading cause of death (50.4%). Conclusions Concomitant TBI and hemorrhagic shock occur in nearly 4% of trauma ICU patients. These patients required a higher amount of RBC concentrates and FFP and had an increased mortality.

The planet in the system HD209458 is the first one for which repeated transits across the stellar disk have been observed. Together with radial velocity measurements, this has led to a determination of the planet's radius and mass, confirming it to be a gas giant. But despite numerous searches for an atmospheric signature, only the dense lower atmosphere of HD209458b has been observed, through the detection of neutral sodium absorption. Here we report the detection of atomic hydrogen absorption in the stellar Lyman alpha line during three transits of HD209458b. An absorption of 15 +/- 4% (1sigma) is observed. Comparison with models shows that this absorption should take place beyond the Roche limit and therefore can be understood in terms of escaping hydrogen atoms.

Objective To measure the efficacy of mecasermin (recombinant human insulin‐like growth factor 1, rhIGF‐1), for treating symptoms of Rett syndrome (RTT) in a pediatric population using a double‐blind crossover study design. Methods Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rhIGF‐1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28‐week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale (ADAMS) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire (RSBQ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale (PTSVAS) top three concerns, Clinical Global Impression (CGI), Parent Global Impression (PGI), and the Kerr severity scale. Cardiorespiratory‐ and electroencephalography (EEG)‐based biomarkers were also analyzed. Results There were no significant differences between randomization groups. The majority of AEs were mild to moderate, although 12 episodes of serious AEs occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography (EEG) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication. Interpretation As in the phase 1 trial, rhIGF‐1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.

Background Anemia is common and associated with increased morbidity among people with HIV (PWH). Classification of anemia using the mean corpuscular volume (MCV) can help investigate the underlying causative factors of anemia. We characterize anemia using MCV among PWH receiving antiretroviral therapy (ART), and identify the risk factors for normocytic, macrocytic, and microcytic anemias. Methods Including PWH with anemia (hemoglobin measure < 12.9 g/dL among men and < 11.9 g/dL among women) in the NA-ACCORD from 01/01/2007 to 12/31/2017, we estimated the annual distribution of normocytic (80–100 femtolitre (fL)), macrocytic (> 100 fL) or microcytic (< 80 fL) anemia based on the lowest hemoglobin within each year. Poisson regression models with robust variance and general estimating equations were used to estimate crude and adjusted prevalence ratios and 95% confidence intervals for risk factors for macrocytic (vs. normocytic) and microcytic (vs. normocytic) anemia stratified by sex. Results Among 37,984 hemoglobin measurements that identified anemia in 14,590 PWH, 27,909 (74%) were normocytic, 4257 (11%) were microcytic, and 5818 (15%) were macrocytic. Of the anemic PWH included over the study period, 1910 (13%) experienced at least one measure of microcytic anemia and 3208 (22%) at least one measure of macrocytic anemia. Normocytic anemia was most common among both males and females, followed by microcytic among females and macrocytic among males. Over time, the proportion of anemic PWH who have macrocytosis decreased while microcytosis increased. Macrocytic (vs. normocytic) anemia is associated with increasing age and comorbidities. With increasing age, microcytic anemia decreased among females but not males. A greater proportion of PWH with normocytic anemia had CD4 counts ≤ 200 cells/mm 3 and had recently initiated ART. Conclusion In anemic PWH, normocytic anemia was most common. Over time macrocytic anemia decreased, and microcytic anemia increased irrespective of sex. Normocytic anemia is often due to chronic disease and may explain the greater risk for normocytic anemia among those with lower CD4 counts or recent ART initiation. Identified risk factors for type-specific anemias including sex, age, comorbidities, and HIV factors, can help inform targeted investigation into the underlying causes.