ABSTRACT
Stellar magnetic activity produces time-varying distortions in the photospheric line profiles of solar-type stars. These lead to systematic errors in high-precision radial-velocity ...measurements, which limit efforts to discover and measure the masses of low-mass exoplanets with orbital periods of more than a few tens of days. We present a new data-driven method for separating Doppler shifts of dynamical origin from apparent velocity variations arising from variability-induced changes in the stellar spectrum. We show that the autocorrelation function (ACF) of the cross-correlation function used to measure radial velocities is effectively invariant to translation. By projecting the radial velocities on to a subspace labelled by the observation identifiers and spanned by the amplitude coefficients of the ACF’s principal components, we can isolate and subtract velocity perturbations caused by stellar magnetic activity. We test the method on a 5-yr time sequence of 853 daily 15-min observations of the solar spectrum from the HARPS-N instrument and solar-telescope feed on the 3.58-m Telescopio Nazionale Galileo. After removal of the activity signals, the heliocentric solar velocity residuals are found to be Gaussian and nearly uncorrelated. We inject synthetic low-mass planet signals with amplitude K = 40 cm s−1 into the solar observations at a wide range of orbital periods. Projection into the orthogonal complement of the ACF subspace isolates these signals effectively from solar activity signals. Their semi-amplitudes are recovered with a precision of ∼ 6.6 cm s−1, opening the door to Doppler detection and characterization of terrestrial-mass planets around well-observed, bright main-sequence stars across a wide range of orbital periods.
Super-Earths belong to a class of planet not found in the Solar system, but which appear common in the Galaxy. Given that some super-Earths are rocky, while others retain substantial atmospheres, ...their study can provide clues as to the formation of both rocky and gaseous planets, and – in particular – they can help to constrain the role of photoevaporation in sculpting the exoplanet population. GJ 9827 is a system already known to host three super-Earths with orbital periods of 1.2, 3.6, and 6.2 d. Here, we use new HARPS-N radial velocity measurements, together with previously published radial velocities, to better constrain the properties of the GJ 9827 planets. Our analysis cannot place a strong constraint on the mass of GJ 9827 c, but does indicate that GJ 9827 b is rocky with a composition that is probably similar to that of the Earth, while GJ 9827 d almost certainly retains a volatile envelope. Therefore, GJ 9827 hosts planets on either side of the radius gap that appears to divide super-Earths into pre-dominantly rocky ones that have radii below ∼1.5Rꚛ, and ones that still retain a substantial atmosphere and/or volatile components, and have radii above ∼2Rꚛ. That the less heavily irradiated of the three planets still retains an atmosphere, may indicate that photoevaporation has played a key role in the evolution of the planets in this system.
We experimentally demonstrate emission of two quantum-mechanically correlated light pulses with a time delay that is coherently controlled via temporal storage of photonic states in an ensemble of ...rubidium atoms. The experiment is based on Raman scattering, which produces correlated pairs of spin-flipped atoms and photons, followed by coherent conversion of the atomic states into a different photon beam after a controllable delay. This resonant nonlinear optical process is a promising technique for potential applications in quantum communication.
Context.
The solar telescope connected to HARPS-N has been observing the Sun since the summer of 2015. Such a high-cadence, long-baseline data set is crucial for understanding spurious ...radial-velocity signals induced by our Sun and by the instrument. On the instrumental side, this data set allowed us to detect sub- m s
−1
systematics that needed to be corrected for.
Aims.
The goals of this manuscript are to (i) present a new data reduction software for HARPS-N, (ii) demonstrate the improvement brought by this new software during the first three years of the HARPS-N solar data set, and (iii) release all the obtained solar products, from extracted spectra to precise radial velocities.
Methods.
To correct for the instrumental systematics observed in the data reduced with the current version of the HARPS-N data reduction software (DRS version 3.7), we adapted the newly available ESPRESSO DRS (version 2.2.3) to HARPS-N and developed new optimised recipes for the spectrograph. We then compared the first three years of HARPS-N solar data reduced with the current and new DRS.
Results.
The most significant improvement brought by the new DRS is a strong decrease in the day-to-day radial-velocity scatter, from 1.27 to 1.07 m s
−1
; this is thanks to a more robust method to derive wavelength solutions, but also to the use of calibrations closer in time. The newly derived solar radial-velocities are also better correlated with the chromospheric activity level of the Sun in the long term, with a Pearson correlation coefficient of 0.93 compared to 0.77 before, which is expected from our understanding of stellar signals. Finally, we also discuss how HARPS-N spectral ghosts contaminate the measurement of the calcium activity index, and we present an efficient technique to derive an index free of instrumental systematics.
Conclusions.
This paper presents a new data reduction software for HARPS-N and demonstrates its improvements, mainly in terms of radial-velocity precision, when applied to the first three years of the HARPS-N solar data set. Those newly reduced solar data, representing an unprecedented time series of 34 550 high-resolution spectra and precise radial velocities, are released alongside this paper. Those data are crucial to understand stellar activity signals in solar-type stars further and develop the mitigating techniques that will allow us to detect other Earths.
Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct ...patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.
Background
Accurate rapid diagnostic tests for SARS‐CoV‐2 infection would be a useful tool to help manage the COVID‐19 pandemic. Testing strategies that use rapid antigen tests to detect current ...infection have the potential to increase access to testing, speed detection of infection, and inform clinical and public health management decisions to reduce transmission. This is the second update of this review, which was first published in 2020.
Objectives
To assess the diagnostic accuracy of rapid, point‐of‐care antigen tests for diagnosis of SARS‐CoV‐2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Sources of heterogeneity investigated included setting and indication for testing, assay format, sample site, viral load, age, timing of test, and study design.
Search methods
We searched the COVID‐19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) on 08 March 2021. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions.
Selection criteria
We included studies of people with either suspected SARS‐CoV‐2 infection, known SARS‐CoV‐2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen tests. We included evaluations of single applications of a test (one test result reported per person) and evaluations of serial testing (repeated antigen testing over time). Reference standards for presence or absence of infection were any laboratory‐based molecular test (primarily reverse transcription polymerase chain reaction (RT‐PCR)) or pre‐pandemic respiratory sample.
Data collection and analysis
We used standard screening procedures with three people. Two people independently carried out quality assessment (using the QUADAS‐2 tool) and extracted study results. Other study characteristics were extracted by one review author and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test, and pooled data using the bivariate model. We investigated heterogeneity by including indicator variables in the random‐effects logistic regression models. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status.
Main results
We included 155 study cohorts (described in 166 study reports, with 24 as preprints). The main results relate to 152 evaluations of single test applications including 100,462 unique samples (16,822 with confirmed SARS‐CoV‐2). Studies were mainly conducted in Europe (101/152, 66%), and evaluated 49 different commercial antigen assays. Only 23 studies compared two or more brands of test.
Risk of bias was high because of participant selection (40, 26%); interpretation of the index test (6, 4%); weaknesses in the reference standard for absence of infection (119, 78%); and participant flow and timing 41 (27%). Characteristics of participants (45, 30%) and index test delivery (47, 31%) differed from the way in which and in whom the test was intended to be used. Nearly all studies (91%) used a single RT‐PCR result to define presence or absence of infection.
The 152 studies of single test applications reported 228 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies, with consistently high specificities. Average sensitivity was higher in symptomatic (73.0%, 95% CI 69.3% to 76.4%; 109 evaluations; 50,574 samples, 11,662 cases) compared to asymptomatic participants (54.7%, 95% CI 47.7% to 61.6%; 50 evaluations; 40,956 samples, 2641 cases). Average sensitivity was higher in the first week after symptom onset (80.9%, 95% CI 76.9% to 84.4%; 30 evaluations, 2408 cases) than in the second week of symptoms (53.8%, 95% CI 48.0% to 59.6%; 40 evaluations, 1119 cases). For those who were asymptomatic at the time of testing, sensitivity was higher when an epidemiological exposure to SARS‐CoV‐2 was suspected (64.3%, 95% CI 54.6% to 73.0%; 16 evaluations; 7677 samples, 703 cases) compared to where COVID‐19 testing was reported to be widely available to anyone on presentation for testing (49.6%, 95% CI 42.1% to 57.1%; 26 evaluations; 31,904 samples, 1758 cases). Average specificity was similarly high for symptomatic (99.1%) or asymptomatic (99.7%) participants.
We observed a steady decline in summary sensitivities as measures of sample viral load decreased.
Sensitivity varied between brands. When tests were used according to manufacturer instructions, average sensitivities by brand ranged from 34.3% to 91.3% in symptomatic participants (20 assays with eligible data) and from 28.6% to 77.8% for asymptomatic participants (12 assays). For symptomatic participants, summary sensitivities for seven assays were 80% or more (meeting acceptable criteria set by the World Health Organization (WHO)). The WHO acceptable performance criterion of 97% specificity was met by 17 of 20 assays when tests were used according to manufacturer instructions, 12 of which demonstrated specificities above 99%. For asymptomatic participants the sensitivities of only two assays approached but did not meet WHO acceptable performance standards in one study each; specificities for asymptomatic participants were in a similar range to those observed for symptomatic people.
At 5% prevalence using summary data in symptomatic people during the first week after symptom onset, the positive predictive value (PPV) of 89% means that 1 in 10 positive results will be a false positive, and around 1 in 5 cases will be missed. At 0.5% prevalence using summary data for asymptomatic people, where testing was widely available and where epidemiological exposure to COVID‐19 was suspected, resulting PPVs would be 38% to 52%, meaning that between 2 in 5 and 1 in 2 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed.
Authors' conclusions
Antigen tests vary in sensitivity. In people with signs and symptoms of COVID‐19, sensitivities are highest in the first week of illness when viral loads are higher. Assays that meet appropriate performance standards, such as those set by WHO, could replace laboratory‐based RT‐PCR when immediate decisions about patient care must be made, or where RT‐PCR cannot be delivered in a timely manner. However, they are more suitable for use as triage to RT‐PCR testing. The variable sensitivity of antigen tests means that people who test negative may still be infected. Many commercially available rapid antigen tests have not been evaluated in independent validation studies.
Evidence for testing in asymptomatic cohorts has increased, however sensitivity is lower and there is a paucity of evidence for testing in different settings. Questions remain about the use of antigen test‐based repeat testing strategies. Further research is needed to evaluate the effectiveness of screening programmes at reducing transmission of infection, whether mass screening or targeted approaches including schools, healthcare setting and traveller screening.
In a 2-year, placebo-controlled trial (the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis AFFIRM study), involving 942 patients with relapsing multiple sclerosis (MS), ...natalizumab significantly reduced the relapse rate by 68% and progression of sustained disability by 42% vs placebo. We report the effect of natalizumab on MRI measures from the AFFIRM study.
The number and volume of gadolinium (Gd)-enhancing, new or enlarging T2-hyperintense, and new T1-hypointense lesions and brain parenchymal fraction were measured from annual scans obtained at baseline, 1 year, and 2 years.
Compared with placebo, natalizumab produced a 92% decrease in Gd-enhancing lesions (means 2.4 vs 0.2; p < 0.001), an 83% decrease in new or enlarging T2-hyperintense lesions (means 11.0 vs 1.9; p < 0.001), and a 76% decrease in new T1-hypointense lesions (means 4.6 vs 1.1; p < 0.001) over 2 years. Median T2-hyperintense lesion volume increased by 8.8% in the placebo group and decreased by 9.4% in the natalizumab group (p < 0.001); median T1-hypointense lesion volume decreased by 1.5% in the placebo group and decreased by 23.5% in the natalizumab group (p < 0.001). Brain atrophy was greater in year 1 and less in year 2 in natalizumab-treated patients.
Natalizumab has a sustained effect in preventing the formation of new lesions in patients with relapsing multiple sclerosis.
This placebo-controlled, randomized trial of patients with relapsing multiple sclerosis demonstrated benefits of natalizumab (an α
4
integrin antagonist) in all the primary and secondary outcome ...measures. After two years, the probability of sustained progression of disability was 17 percent with natalizumab and 29 percent with placebo. Fatigue and allergic reaction were more common among patients receiving natalizumab.
This trial of patients with relapsing multiple sclerosis demonstrated benefits of natalizumab in all the primary and secondary outcome measures. In this trial, natalizumab in combination with interferon was more effective than interferon alone. Progressive multifocal leukoencephalopathy developed in two patients. In this systematic evaluation for PML in patients who received natalizumab in clinical trials, no additional cases were identified.
Relapsing multiple sclerosis is characterized by the intermittent development of inflammatory lesions in the brain and spinal cord, resulting in plaques of demyelination and axonal loss. Lymphocyte migration across the blood–brain barrier is thought to be an important early step in the formation of lesions.
1
The interaction of α
4
β
1
integrin, a protein on the surface of lymphocytes, with vascular-cell adhesion molecule 1 (VCAM-1), which is expressed on the surface of vascular endothelial cells in brain and spinal cord blood vessels, mediates the adhesion and migration of lymphocytes in areas of inflammation.
2
–
6
Furthermore, the interaction of α . . .
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