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.
Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with ...peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy.
Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in ...preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation.
The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers.
GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ-induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs.
Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population.
NCT02723786.
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.
Stellar surface magnetoconvection (granulation) creates asymmetries in the observed stellar absorption lines that can subsequently manifest themselves as spurious radial velocities (RVs) shifts. In ...turn, this can then mask the Doppler reflex motion induced by orbiting planets on their host stars and represents a particular challenge for determining the masses of low-mass, long-period planets. Herein, we study this impact by creating Sun-as-a-star observations that encapsulate the granulation variability expected from 3D magnetohydrodynamic simulations. These Sun-as-a-star model observations are in good agreement with empirical observations of the Sun but may underestimate the total variability relative to the quiet Sun due to the increased magnetic field strength in our models. We find numerous line profile characteristics that linearly correlate with the disk-integrated convection-induced velocities. Removing the various correlations with the line bisector, equivalent width, and the Vasy indicator may reduce ∼50%-60% of the granulation noise in the measured velocities. We also find that simultaneous photometry may be a key diagnostic, as our proxy for photometric brightness also allowed us to remove ∼50% of the granulation-induced RV noise. These correlations and granulation-noise mitigations break down in the presence of low instrumental resolution and/or increased stellar rotation, as both act to smooth the observed line profile asymmetries.
Urban subsidence poses significant challenges for rapidly developing cities. Published InSAR data reveal Kathmandu as a prime example, demonstrating an alarming rate of subsidence during rapid urban ...expansion. To monitor the spatiotemporal evolution of recent subsidence, we use Sentinel-1 Synthetic Aperture Radar (SAR) data and the LiCSBAS open-source processing package. Vertical surface motion maps from 2015 to present reveal many localized zones with high subsidence rates (>100 mm year
−1
), while the mountains that surround the valley have experienced slight surface uplift of ~5 mm year
−1
. The highest subsidence rate is ~200 mm year
−1
and occurs in the centre of the Kathmandu metropolitan area. The distribution of subsidence in the valley matches with areas of the Pliocene to recent sediment up to 500 m thick. The deep aquifer compaction is likely to be the main driver of subsidence in the Kathmandu Valley. Time-series data show a dominant linear subsidence signal with weak sinusoidal signal peaks associated with groundwater recharge of shallow aquifers during the monsoon season. Subsidence rates decrease in proximity to the main river channels, likely driven by the seasonal recharge into the distal floodplain. The distribution of subsidence in the Kathmandu Valley has significant implications for future flood risk and infrastructure in the city.
A laboratory incubation study was conducted with nine UK soils to determine the effect of soil physical and chemical properties, and temperature, on the efficacy the nitrification inhibitor ...dicyandiamide (DCD). Nitrogen was applied to soil as ammonium chloride at a rate of 100 μg N g−1 dry soil, and incubated at 60% water-filled-pore-space at either 5, 15 or 25 °C. The ammonium (NH4+) pool was enriched with 15N to 60 atom% excess and DCD was applied at a rate of 10 μg g−1 dry soil. The concentrations and enrichments of the NH4+ and nitrate (NO3−) pools, along with nitrous oxide (N2O) flux measurements, were determined regularly for 60 days after N application. Gross soil N transformation rates were quantified with a 15N tracing model. The persistence of DCD was strongly related (P < 0.001) to temperature with the measured half-life across all soils of 89, 37 and 18 days at 5, 15, and 25 °C, respectively. There was wide variation in the half-life of DCD among soils; which was predominantly associated with the soil oxalate extractable Fe concentration. Greater (P < 0.001) inhibition in autotrophic nitrification by DCD occurred at 5 and 15 °C compared to 25 °C. Across all soils and temperatures DCD increased the rate of mineralisation of recalcitrant organic-N and the rate of adsorption of free NH4+, however, effects varied between soils. DCD did not have a significant effect on the rate of oxidation of recalcitrant organic-N to NO3− or on any of the immobilisation processes or mineralisation of labile N to NH4+. The efficacy of DCD in inhibiting net NO3− production best correlated with soil Cu (r = −0.82), % clay (r = −0.71), total N (r = −0.66) and LOI (r = −0.61). Stepwise multiple regression showed that Cu, oxalate extractable Fe and oxalate extractable Al explained 85.0% of the variation in the percentage inhibition of net NO3− production by DCD. The inhibitor also reduced cumulative N2O emissions, with reductions negatively correlated with a range of soil properties associated with organic matter. We provide evidence that the interaction between temperature, soil clay content and soil organic matter governs the efficacy of DCD. The grassland soils had higher native total N concentrations than the arable soils, hence the inhibition of net NO3− production by DCD was lower and this resulted in an overall inhibition in N2O emissions of 58% and 81% for grassland and arable soils respectively.
•DCD's longevity was strongly related to temperature and soil oxalate extractable iron concentration.•Evidence that an interaction among temperature, soil clay content and soil organic matter govern the efficacy of DCD.•The efficacy of DCD in inhibiting net nitrate production and nitrous oxide emissions was lower in grassland soils than in arable soils.
Space-borne Synthetic Aperture Radar (SAR) Interferometry (InSAR) is now a key geophysical tool for surface deformation studies. The European Commission’s Sentinel-1 Constellation began acquiring ...data systematically in late 2014. The data, which are free and open access, have global coverage at moderate resolution with a 6 or 12-day revisit, enabling researchers to investigate large-scale surface deformation systematically through time. However, full exploitation of the potential of Sentinel-1 requires specific processing approaches as well as the efficient use of modern computing and data storage facilities. Here we present Looking Into Continents from Space with Synthetic Aperture Radar (LiCSAR), an operational system built for large-scale interferometric processing of Sentinel-1 data. LiCSAR is designed to automatically produce geocoded wrapped and unwrapped interferograms and coherence estimates, for large regions, at 0.001° resolution (WGS-84 coordinate system). The products are continuously updated at a frequency depending on prioritised regions (monthly, weekly or live update strategy). The products are open and freely accessible and downloadable through an online portal. We describe the algorithms, processing, and storage solutions implemented in LiCSAR, and show several case studies that use LiCSAR products to measure tectonic and volcanic deformation. We aim to accelerate the uptake of InSAR data by researchers as well as non-expert users by mass producing interferograms and derived products.
A set of supraglacial ponds filled rapidly between April and July 2017 on
Changri Shar Glacier in the Everest region of Nepal, coalescing into a ∼180 000 m2 lake before sudden and complete drainage ...through Changri
Shar and Khumbu glaciers (15–17 July). We use PlanetScope and Pléiades
satellite orthoimagery to document the system's evolution over its very short
filling period and to assess the glacial and proglacial effects of the
outburst flood. We also use high-resolution stereo digital elevation models
(DEMs) to complete a detailed analysis of the event's glacial and geomorphic
effects. Finally, we use discharge records at a stream gauge 4 km downstream
to refine our interpretation of the chronology and magnitude of the outburst.
We infer largely subsurface drainage through both of the glaciers located on
its flow path, and efficient drainage through the lower portion of Khumbu
Glacier. The drainage and subsequent outburst of 1.36±0.19×106 m3 of impounded water had a clear geomorphic impact on glacial and
proglacial topography, including deep incision and landsliding along the
Changri Nup proglacial stream, the collapse of shallow englacial conduits
near the Khumbu terminus and extensive, enhanced bank erosion at least as far
as 11 km downstream below Khumbu Glacier. These sudden changes destroyed
major trails in three locations, demonstrating the potential hazard that
short-lived, relatively small glacial lakes pose.
Seizures can emerge from multiple or large foci in temporal lobe epilepsy, complicating focally targeted strategies such as surgical resection or the modulation of the activity of specific ...hippocampal neuronal populations through genetic or optogenetic techniques. Here, we evaluate a strategy in which optogenetic activation of medial septal GABAergic neurons, which provide extensive projections throughout the hippocampus, is used to control seizures. We utilized the chronic intrahippocampal kainate mouse model of temporal lobe epilepsy, which results in spontaneous seizures and as is often the case in human patients, presents with hippocampal sclerosis. Medial septal GABAergic neuron populations were immunohistochemically labelled and were not reduced in epileptic conditions. Genetic labelling with mRuby of medial septal GABAergic neuron synaptic puncta and imaging across the rostral to caudal extent of the hippocampus, also indicated an unchanged number of putative synapses in epilepsy. Furthermore, optogenetic stimulation of medial septal GABAergic neurons consistently modulated oscillations across multiple hippocampal locations in control and epileptic conditions. Finally, wireless optogenetic stimulation of medial septal GABAergic neurons, upon electrographic detection of spontaneous hippocampal seizures, resulted in reduced seizure durations. We propose medial septal GABAergic neurons as a novel target for optogenetic control of seizures in temporal lobe epilepsy.
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