Orbital radar sounding systems could significantly improve our understanding of dynamic processes at ice sheet margins by enhancing the spatial and temporal coverage of subglacial observations. ...However, surface crevasses in these fast-flowing regions may contribute significant radar clutter that can impede detection of the ice sheet bed. It is currently unclear if particular radar center frequency choices might enhance or mitigate this clutter. To investigate this question, we analyze crevasse clutter returns in airborne radar sounding data collected at 195 MHz, 300 MHz, and 750 MHz. Additionally, we rescale the derived empirical angular scattering functions to simulate crevasse clutter in orbital geometries. In this data set, we find that, unlike rough surface clutter, crevasse clutter is reduced at higher frequencies. However, the small angles of incidence at orbital altitudes lead to sufficient clutter at all frequencies to dominate over the theoretical bed echo power. Our results suggest that surface crevassing may not necessarily limit the viability of UHF frequencies for orbital sounding. However, synthetic aperture focusing and narrow cross-track antenna beam patterns will be crucial regardless of system center frequency.
The HADES Europa mission concept aims to provide a framework for an astrobiological in-depth investigation of the Jupiter moon Europa, relying on existing technologies and feasibility. This mission ...study proposes a system consisting of an orbiter, lander and cryobot as a platform for detailed exploration of Europa. While the orbiter will investigate the presence of a liquid ocean and characterize Europa's internal structure, the lander will survey local dynamics of the ice layer and the surface environment. The lander releases a cryobot, that melts into the ice, will sample the pristine subsurface and is expected to provide data on organic and gaseous content and putative bio-signatures. In summary, we present the scientific objectives for an astrobiological investigation of Europa, resulting in a mission concept with a detailed evaluation of scientific instrumentation, mission sequences, basic design of the spacecraft, technology needs and cost estimations.
The Near-Infrared Spectrograph (NIRSpec) is one of the four focal plane instruments on the James Webb Space Telescope which was launched on Dec. 25, 2021. We present an overview of the as-run NIRSpec ...commissioning campaign, with particular emphasis on the sequence of activities that led to the verification of all hardware components of NIRSpec. We also discuss the mechanical, thermal, and operational performance of NIRSpec, as well as the readiness of all NIRSpec observing modes for use in the upcoming JWST science program.
Bronchiectasis guidelines recommend long-term macrolide treatment for patients with three or more exacerbations per year without Pseudomonas aeruginosa infection. Randomised controlled trials suggest ...that long-term macrolide treatment can prevent exacerbations in adult patients with bronchiectasis, but these individual studies have been too small to do meaningful subgroup analyses. We did a systematic review and individual patient data (IPD) meta-analysis to explore macrolide benefit in subpopulations, including those in which macrolide therapy is not currently recommended.
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science from Jan 1, 2000, to Sept 30, 2018, to identify double blind, randomised, placebo-controlled trials of macrolide antibiotics in adult patients with bronchiectasis. We applied no language restrictions. Randomised controlled trials were eligible if treatment was defined a priori as long term and had a primary or secondary outcome of bronchiectasis exacerbations. Studies in patients with cystic fibrosis bronchiectasis were excluded. The primary outcome of the meta-analysis was frequency of exacerbations requiring treatment with antibiotics. Secondary endpoints were time to first exacerbation, change in quality of life according to the St George's Respiratory Questionnaire (SGRQ), and change in FEV
. IPD meta-analysis was done using fixed effects models adjusting for age, sex, FEV
, and trial. We did prespecified subgroup analyses for each of the primary and secondary endpoints using one-step meta-analysis only. Subgroups were defined by age, sex, previous exacerbation frequency, smoking status, inhaled corticosteroid use at baseline, body-mass index at baseline, cause, C-reactive protein at baseline, baseline FEV
percentage of predicted, SGRQ total score, and Pseudomonas aeruginosa in sputum culture at baseline. The meta-analysis is registered with the PROSPERO international register of systematic reviews, number CRD42018102908.
Of 234 identified studies, we included three randomised controlled trials, and IPD was obtained for 341 participants. Macrolide antibiotics reduced the frequency of exacerbations (adjusted incidence rate ratio IRR 0·49, 95% CI 0·36 to 0·66; p<0·0001). We also found that macrolide treatment improved the time to first exacerbation (adjusted hazard ratio 0·46, 0·34 to 0·61; p<0·0001) and was associated with improved quality of life measured by the SGRQ (mean improvement 2·93 points, 0·03 to 5·83; p=0·048). Macrolides were not associated with a significant improvement in FEV
(67 mL at 1 year, -22 to 112; p=0·14). Effect estimates in prespecified subgroup analyses revealed a reduced frequency of exacerbations in all prespecified subgroups, including a high level of benefit in patients with P aeruginosa infection (IRR 0·36, 0·18-0·72; p=0·0044) and in patients with one to two exacerbations per year (0·37, 0·16-0·88; p=0·025). Studies were rated as low risk of bias across all domains.
Long-term macrolide treatment significantly reduces the frequency of exacerbations in patients with bronchiectasis, with similar benefits observed in all subgroups based on patient characteristics. This finding suggests that macrolides might be considered in patients in whom macrolides are not indicated according to the current guidelines, particularly if alternative approaches to reduce exacerbations have been unsuccessful. However, downsides of long-term macrolide treatment must also be taken into account.
European Respiratory Society.
Imetelstat shows activity in patients with myeloproliferative neoplasms, including primary myelofibrosis (PMF) and essential thrombocythemia. Here, we describe a case of prolonged disease ...stabilization by imetelstat treatment of a high-risk PMF patient enrolled into the clinical study MYF2001. We confirmed continuous shortening of telomere length (TL) by imetelstat treatment but observed emergence and expansion of a KRAST58I mutated clone during the patient’s clinical course. In order to investigate the molecular mechanisms involved in the imetelstat treatment response, we generated induced pluripotent stem cells (iPSC) from this patient. TL of iPSC-derived hematopoietic stem and progenitor cells, which was increased after reprogramming, was reduced upon imetelstat treatment for 14 days. However, while imetelstat reduced clonogenic growth of the patient’s primary CD34+ cells, clonogenic growth of iPSC-derived CD34+ cells was not affected, suggesting that TL was not critically short in these cells. Also, the propensity of iPSC differentiation toward megakaryocytes and granulocytes was not altered. Using human TF-1
MPL
and murine 32D
MPL
cell lines stably expressing JAK2V617F or CALRdel52, imetelstat-induced reduction of viability was significantly more pronounced in CALRdel52 than in JAK2V617F cells. This was associated with an immediate downregulation of JAK2 phosphorylation and downstream signaling as well as a reduction of
hTERT
and
STAT3
mRNA expression. Hence, our data demonstrate that imetelstat reduces TL and targets JAK/STAT signaling, particularly in CALR-mutated cells. Although the exact patient subpopulation who will benefit most from imetelstat needs to be defined, our data propose that CALR-mutated clones are highly vulnerable.
Abstract
Summary
The ongoing pandemic caused by SARS-CoV-2 emphasizes the importance of genomic surveillance to understand the evolution of the virus, to monitor the viral population, and plan ...epidemiological responses. Detailed analysis, easy visualization and intuitive filtering of the latest viral sequences are powerful for this purpose. We present CovRadar, a tool for genomic surveillance of the SARS-CoV-2 Spike protein. CovRadar consists of an analytical pipeline and a web application that enable the analysis and visualization of hundreds of thousand sequences. First, CovRadar extracts the regions of interest using local alignment, then builds a multiple sequence alignment, infers variants and consensus and finally presents the results in an interactive app, making accessing and reporting simple, flexible and fast.
Availability and implementation
CovRadar is freely accessible at https://covradar.net, its open-source code is available at https://gitlab.com/dacs-hpi/covradar.
Supplementary information
Supplementary data are available at Bioinformatics online.
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