In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density ...lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers.
We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240.
A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran.
In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127 .).
Approximately 10% of active galactic nuclei exhibit relativistic jets, which are powered by the accretion of matter onto supermassive black holes. Although the measured width profiles of such jets on ...large scales agree with theories of magnetic collimation, the predicted structure on accretion disk scales at the jet launch point has not been detected. We report radio interferometry observations, at a wavelength of 1.3 millimeters, of the elliptical galaxy M87 that spatially resolve the base of the jet in this source. The derived size of 5.5 ± 0.4 Schwarzschild radii is significantly smaller than the innermost edge of a retrograde accretion disk, suggesting that the M87 jet is powered by an accretion disk in a prograde orbit around a spinning black hole.
The redistribution of angular momentum is a long standing problem in our understanding of protoplanetary disc (PPD) evolution. The magnetorotational instability (MRI) is considered a likely ...mechanism. We present the results of a study involving multifluid global simulations including Ohmic dissipation, ambipolar diffusion and the Hall effect in a dynamic, self-consistent way. We focus on the turbulence resulting from the non-linear development of the MRI in radially stratified PPDs and compare with ideal magnetohydrodynamics simulations. In the multifluid simulations, the disc is initially set up to transition from a weak Hall-dominated regime, where the Hall effect is the dominant non-ideal effect but approximately the same as or weaker than the inductive term, to a strong Hall-dominated regime, where the Hall effect dominates the inductive term. As the simulations progress, a substantial portion of the disc develops into a weak Hall-dominated disc. We find a transition from turbulent to laminar flow in the inner regions of the disc, but without any corresponding overall density feature. We introduce a dimensionless parameter, αRM, to characterize accretion with αRM ≳ 0.1 corresponding to turbulent transport. We calculate the eddy turnover time, t
eddy, and compared this with an effective recombination time-scale, t
rcb, to determine whether the presence of turbulence necessitates non-equilibrium ionization calculations. We find that t
rcb is typically around three orders of magnitude smaller than t
eddy. Also, the ionization fraction does not vary appreciably. These two results suggest that these multifluid simulations should be comparable to single-fluid non-ideal simulations.
Abstract
We investigate the ionizing effect of low-energy cosmic rays (CRs) from a young star on its protoplanetary disc (PPD). We consider specifically the effect of ∼3 GeV protons injected at the ...inner edge of the PPD. An increase in the ionization fraction as a result of these CRs could allow the magnetorotational instability to operate in otherwise magnetically dead regions of the disc. For the typical values assumed we find an ionization rate of ζCR ∼ 10−17 s−1 at 1 au. The transport equation is solved by treating the propagation of the CRs as diffusive. We find for increasing diffusion coefficients the CRs penetrate further in the PPD, while varying the mass density profile of the disc is found to have little effect. We investigate the effect of an energy spectrum of CRs. The influence of a disc wind is examined by including an advective term. For advective wind speeds between 1 and 100 km s−1 diffusion dominates at all radii considered here (out to 10 au) for reasonable diffusion coefficients. Overall, we find that low-energy CRs can significantly ionize the mid-plane of PPDs out to ∼1 au. By increasing the luminosity or energy of the CRs, within plausible limits, their radial influence could increase to ∼2 au at the mid-plane but it remains challenging to significantly ionize the mid-plane further out.
Abstract
We assess the ionising effect of low energy protostellar cosmic rays in protoplanetary disks around a young solar mass star for a wide range of disk parameters. We assume a source of low ...energy cosmic rays located close to the young star which travel diffusively through the protoplanetary disk. We use observationally inferred values from nearby star-forming regions for the total disk mass and the radial density profile. We investigate the influence of varying the disk mass within the observed scatter for a solar mass star. We find that for a large range of disk masses and density profiles that protoplanetary disks are “optically thin” to low energy (∼3 GeV) cosmic rays. At R ∼ 10 au, for all of the disks that we consider (Mdisk = 6.0 × 10−4 − 2.4 × 10−2M⊙), the ionisation rate due to low energy stellar cosmic rays is larger than that expected from unmodulated galactic cosmic rays. This is in contrast to our previous results which assumed a much denser disk which may be appropriate for a more embedded source. At R ∼ 70 au, the ionisation rate due to stellar cosmic rays dominates in ∼50% of the disks. These are the less massive disks with less steep density profiles. At this radius there is at least an order of magnitude difference in the ionisation rate between the least and most massive disk that we consider. Our results indicate, for a wide range of disk masses, that low energy stellar cosmic rays provide an important source of ionisation at the disk midplane at large radii (∼70 au).
Abstract
Background
Rapid identification of COVID-19 cases, which is crucial to outbreak containment efforts, is challenging due to the lack of pathognomonic symptoms and in settings with limited ...capacity for specialized nucleic acid–based reverse transcription polymerase chain reaction (PCR) testing.
Methods
This retrospective case-control study involves subjects (7–98 years) presenting at the designated national outbreak screening center and tertiary care hospital in Singapore for SARS-CoV-2 testing from 26 January to 16 February 2020. COVID-19 status was confirmed by PCR testing of sputum, nasopharyngeal swabs, or throat swabs. Demographic, clinical, laboratory, and exposure-risk variables ascertainable at presentation were analyzed to develop an algorithm for estimating the risk of COVID-19. Model development used Akaike’s information criterion in a stepwise fashion to build logistic regression models, which were then translated into prediction scores. Performance was measured using receiver operating characteristic curves, adjusting for overconfidence using leave-one-out cross-validation.
Results
The study population included 788 subjects, of whom 54 (6.9%) were SARS-CoV-2 positive and 734 (93.1%) were SARS-CoV-2 negative. The median age was 34 years, and 407 (51.7%) were female. Using leave-one-out cross-validation, all the models incorporating clinical tests (models 1, 2, and 3) performed well with areas under the receiver operating characteristic curve (AUCs) of 0.91, 0.88, and 0.88, respectively. In comparison, model 4 had an AUC of 0.65.
Conclusions
Rapidly ascertainable clinical and laboratory data could identify individuals at high risk of COVID-19 and enable prioritization of PCR testing and containment efforts. Basic laboratory test results were crucial to prediction models.
A risk score incorporating easily ascertainable demographic, clinical evaluation, and clinical testing covariates to identify patients at high risk of COVID-19 can help prioritize subjects for testing and public health measures to prevent onward transmission, especially in resource-limited settings.
Testing for SARS-CoV-2: Can We Stop at 2? Lee, Tau Hong; Junhao Lin, Ray; Lin, Raymond T P ...
Clinical infectious diseases,
11/2020, Volume:
71, Issue:
16
Journal Article
Peer reviewed
Open access
Abstract
The COVID-19 epidemic requires accurate identification and isolation of confirmed cases for effective control. This report describes the effectiveness of our testing strategy and highlights ...the importance of repeat testing in suspected cases in our cohort.
MIRI (the Mid-Infrared Instrument for the James Webb Space Telescope JWST) operates from 5 to 28.5 μm and combines over this range: (1) unprecedented sensitivity levels; (2) subarcsecond angular ...resolution; (3) freedom from atmospheric interference; (4) the inherent stability of observing in space; and (5) a suite of versatile capabilities including imaging, low- and medium-resolution spectroscopy (with an integral field unit), and coronagraphy. We illustrate the potential uses of this unique combination of capabilities with various science examples: (1) imaging exoplanets; (2) transit and eclipse spectroscopy of exoplanets; (3) probing the first stages of star and planet formation, including identifying bioactive molecules; (4) determining star formation rates and mass growth as galaxies are assembled; and (5) characterizing the youngest massive galaxies.
The space-weather conditions that result from stellar winds significantly impact the habitability of exoplanets. The conditions can be calculated from first principles if the necessary boundary ...conditions are specified, namely the plasma density in the outer corona and the radial distance at which the plasma forces the closed magnetic field into an open geometry. Low frequency radio observations (
ν
≲ 200 MHz) of plasma and cyclotron emission from stars probe these magneto-ionic conditions. Here we report the detection of low-frequency (120–167 MHz) radio emission associated with the dMe6 star WX UMa. If the emission originates in WX UMa’s corona, we show that the closed field region extends to at least ≈10 stellar radii, which is about a factor of a few larger than the solar value, and possibly to ≳20 stellar radii. Our results suggest that the magnetic-field structure of M dwarfs is in between Sun-like and planet-like configurations, where compact over-dense coronal loops with X-ray emitting plasma co-exist with a large-scale magnetosphere with a lower plasma density and closed magnetic geometry.
Abstract We investigate the properties of strong (H β + O iii ) emitters before and after the end of the “Epoch of Reionization” from z = 8 to z = 5.5. We make use of ultradeep JWST / NIRCam imaging ...in the parallel field (P2) of the MIRI Deep Imaging Survey (MIDIS) in the Hubble eXtreme Deep Field (H-XDF), in order to select prominent (H β + O iii ) emitters (with rest-frame equivalent width (EW 0 ) ≳ 100 Å) at z = 5.5–7, based on their flux density enhancement in the F356W band with respect to the spectral energy distribution continuum. We complement our selection with other (H β + O iii ) emitters from the literature at similar and higher ( z = 7−8) redshifts. We find (nonindependent) anticorrelations between EW 0 (H β + O iii ) and both galaxy stellar mass and age, in agreement with previous studies, and a positive correlation with specific star formation rate (sSFR). On the SFR– M ⋆ plane, the (H β + O iii ) emitters populate both the star formation main sequence and the starburst region, which become indistinguishable at low stellar masses ( log 10 ( M ⋆ ) < 7.5 ). We find tentative evidence for a nonmonotonic relation between EW 0 (H β + O iii ) and SFR, such that both parameters correlate with each other at SFR ≳ 1 M ⊙ yr −1 , while the correlation flattens out at lower SFRs. This suggests that low metallicities producing high EW 0 (H β + O iii ) could be important at low SFR values. Interestingly, the properties of the strong emitters and other galaxies (33% and 67% of our z = 5.5–7 sample, respectively) are similar, including, in many cases, high sSFR. Therefore, it is crucial to consider both emitters and nonemitters to obtain a complete picture of the cosmic star formation activity around the Epoch of Reionization.
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