A new realization of the International Celestial Reference Frame (ICRF) is presented based on the work achieved by a working group of the International Astronomical Union (IAU) mandated for this ...purpose. This new realization follows the initial realization of the ICRF completed in 1997 and its successor, ICRF2, adopted as a replacement in 2009. The new frame, referred to as ICRF3, is based on nearly 40 years of data acquired by very long baseline interferometry at the standard geodetic and astrometric radio frequencies (8.4 and 2.3 GHz), supplemented with data collected at higher radio frequencies (24 GHz and dual-frequency 32 and 8.4 GHz) over the past 15 years. State-of-the-art astronomical and geophysical modeling has been used to analyze these data and derive source positions. The modeling integrates, for the first time, the effect of the galactocentric acceleration of the solar system (directly estimated from the data) which, if not considered, induces significant deformation of the frame due to the data span. The new frame includes positions at 8.4 GHz for 4536 extragalactic sources. Of these, 303 sources, uniformly distributed on the sky, are identified as “defining sources” and as such serve to define the axes of the frame. Positions at 8.4 GHz are supplemented with positions at 24 GHz for 824 sources and at 32 GHz for 678 sources. In all, ICRF3 comprises 4588 sources, with three-frequency positions available for 600 of these. Source positions have been determined independently at each of the frequencies in order to preserve the underlying astrophysical content behind such positions. They are reported for epoch 2015.0 and must be propagated for observations at other epochs for the most accurate needs, accounting for the acceleration toward the Galactic center, which results in a dipolar proper motion field of amplitude 0.0058 milliarcsecond yr
−1
(mas yr
−1
). The frame is aligned onto the International Celestial Reference System to within the accuracy of ICRF2 and shows a median positional uncertainty of about 0.1 mas in right ascension and 0.2 mas in declination, with a noise floor of 0.03 mas in the individual source coordinates. A subset of 500 sources is found to have extremely accurate positions, in the range of 0.03–0.06 mas, at the traditional 8.4 GHz frequency. Comparing ICRF3 with the recently released
Gaia
Celestial Reference Frame 2 in the optical domain, there is no evidence for deformations larger than 0.03 mas between the two frames, in agreement with the ICRF3 noise level. Significant positional offsets between the three ICRF3 frequencies are detected for about 5% of the sources. Moreover, a notable fraction (22%) of the sources shows optical and radio positions that are significantly offset. There are indications that these positional offsets may be the manifestation of extended source structures. This third realization of the ICRF was adopted by the IAU at its 30th General Assembly in August 2018 and replaced the previous realization, ICRF2, on January 1, 2019.
A systematic review from 1 January to 30 June 2020 revealed 42 patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection. Single cases and small series were reported from 13 ...countries, the majority from Europe (79.4%) and especially from Italy (30.9%). SARS-CoV-2 infection was demonstrated by nasopharyngeal swab (85.7%) and serology (14.3%). Median time between COVID-19 and GBS onset in 36 patients was 11.5 days (IQR: 7.7-16). The most common clinical features were: limb weakness (76.2%), hypoareflexia (80.9 %), sensory disturbances (66.7 %) and facial palsy (38.1%). Dysautonomia occurred in 19%, respiratory failure in 33.3% and 40.5% of patients were admitted in intensive care unit. Most patients (71.4%) had the classical clinical presentation but virtually all GBS variants and subtypes were reported. Cerebrospinal fluid (CSF) albumin-cytological dissociation was found in 28/36 (77.8%) and PCR for SARS-CoV-2 was negative in 25/25 patients. Electrodiagnosis was demyelinating in 80.5% and levels 1 and 2 of Brighton criteria of diagnostic certainty, when applicable, were fulfilled in 94.5% patients. Antiganglioside antibodies were positive in only 1/22 patients. Treatments were intravenous immunoglobulin and/or plasma exchange (92.8%) with, at short-time follow-up, definite improvement or recovery in 62.1% of patients. One patient died. In conclusion, the most frequent phenotype of GBS in SARS-CoV-2 infection is the classical sensorimotor demyelinating GBS responding to the usual treatments. The time interval between infectious and neuropathic symptoms, absence of CSF pleocytosis and negative PCR support a postinfectious mechanism. The abundance of reports suggests a pathogenic link between SARS-CoV-2 infection and GBS but a case-control study is greatly needed.
Guillain-Barré syndrome Willison, Hugh J, Prof; Jacobs, Bart C, Prof; van Doorn, Pieter A, Prof
The Lancet,
08/2016, Letnik:
388, Številka:
10045
Journal Article
Recenzirano
Odprti dostop
Summary Guillain-Barré syndrome is the most common and most severe acute paralytic neuropathy, with about 100 000 people developing the disorder every year worldwide. Under the umbrella term of ...Guillain-Barré syndrome are several recognisable variants with distinct clinical and pathological features. The severe, generalised manifestation of Guillain-Barré syndrome with respiratory failure affects 20–30% of cases. Treatment with intravenous immunoglobulin or plasma exchange is the optimal management approach, alongside supportive care. Understanding of the infectious triggers and immunological and pathological mechanisms has advanced substantially in the past 10 years, and is guiding clinical trials investigating new treatments. Investigators of large, worldwide, collaborative studies of the spectrum of Guillain-Barré syndrome are accruing data for clinical and biological databases to inform the development of outcome predictors and disease biomarkers. Such studies are transforming the clinical and scientific landscape of acute autoimmune neuropathies.
Abstract
We train and apply convolutional neural networks, a machine learning technique developed to learn from and classify image data, to Canada–France–Hawaii Telescope Legacy Survey (CFHTLS) ...imaging for the identification of potential strong lensing systems. An ensemble of four convolutional neural networks was trained on images of simulated galaxy–galaxy lenses. The training sets consisted of a total of 62 406 simulated lenses and 64 673 non-lens negative examples generated with two different methodologies. An ensemble of trained networks was applied to all of the 171 deg2 of the CFHTLS wide field image data, identifying 18 861 candidates including 63 known and 139 other potential lens candidates. A second search of 1.4 million early-type galaxies selected from the survey catalogue as potential deflectors, identified 2465 candidates including 117 previously known lens candidates, 29 confirmed lenses/high-quality lens candidates, 266 novel probable or potential lenses and 2097 candidates we classify as false positives. For the catalogue-based search we estimate a completeness of 21–28 per cent with respect to detectable lenses and a purity of 15 per cent, with a false-positive rate of 1 in 671 images tested. We predict a human astronomer reviewing candidates produced by the system would identify 20 probable lenses and 100 possible lenses per hour in a sample selected by the robot. Convolutional neural networks are therefore a promising tool for use in the search for lenses in current and forthcoming surveys such as the Dark Energy Survey and the Large Synoptic Survey Telescope.
CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we ...describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells. Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells. Importantly, daratumumab-induced Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not affected by the presence of bone marrow stromal cells, indicating that daratumumab can effectively kill MM tumor cells in a tumor-preserving bone marrow microenvironment. In vivo, daratumumab was highly active and interrupted xenograft tumor growth at low dosing. Collectively, our results show the versatility of daratumumab to effectively kill CD38-expressing tumor cells, including patient MM cells, via diverse cytotoxic mechanisms. These findings support clinical development of daratumumab for the treatment of CD38-positive MM tumors.
The primary cilium is a mechanosensor in a variety of mammalian cell types, initiating and directing intracellular signalling cascades in response to external stimuli. When primary cilia formation is ...disrupted, cells have diminished mechanosensitivity and an abrogated response to mechanical stimulation. Due to this important role, we hypothesised that increasing primary cilia length would enhance the downstream response and therefore, mechanosensitivity. To test this hypothesis, we increased osteocyte primary cilia length with fenoldopam and lithium and found that cells with longer primary cilia were more mechanosensitive. Furthermore, fenoldopam treatment potentiated adenylyl cyclase activity and was able to recover primary cilia form and sensitivity in cells with impaired cilia. This work demonstrates that modulating the structure of the primary cilium directly impacts cellular mechanosensitivity. Our results implicate cilium length as a potential therapeutic target for combating numerous conditions characterised by impaired cilia function.
Summary Guillain-Barré syndrome (GBS) is an important cause of acute neuromuscular paralysis. Molecular mimicry and a cross-reactive immune response play a crucial part in its pathogenesis, at least ...in those cases with a preceding Campylobacter jejuni infection and with antibodies to gangliosides. The type of preceding infection and patient-related host factors seem to determine the form and severity of the disease. Intravenous immunoglobulin (IVIg) and plasma exchange are effective treatments in GBS; mainly for practical reasons, IVIg is the preferred treatment. Whether mildly affected patients or patients with Miller Fisher syndrome also benefit from IVIg is unclear. Despite medical treatment, GBS often remains a severe disease; 3–10% of patients die and 20% are still unable to walk after 6 months. In addition, many patients have pain and fatigue that can persist for months or years. Advances in prognostic modelling have resulted in the development of a new and simple prognostic outcome scale that might also help to guide new treatment options, particularly in patients with GBS who have a poor prognosis.
Measurements of 21 cm Epoch of Reionization (EoR) structure are subject to systematics originating from both the analysis and the observation conditions. Using 2013 data from the Murchison Widefield ...Array (MWA), we show the importance of mitigating both sources of contamination. A direct comparison between results from Beardsley et al. and our updated analysis demonstrates new precision techniques, lowering analysis systematics by a factor of 2.8 in power. We then further lower systematics by excising observations contaminated by ultra-faint RFI, reducing by an additional factor of 3.8 in power for the zenith pointing. With this enhanced analysis precision and newly developed RFI mitigation, we calculate a noise-dominated upper limit on the EoR structure of Δ2 ≤ 3.9 × 103 mK2 at k = 0.20 h Mpc−1 and z = 7 using 21 hr of data, improving previous MWA limits by almost an order of magnitude.
IMPORTANCE Long-term data on mortality after first-ever stroke in adults aged 18 through 50 years are scarce and usually restricted to ischemic stroke. Moreover, expected mortality not related to ...first-ever stroke is not taken in account. OBJECTIVES To investigate long-term mortality and cause of death after acute stroke in adults aged 18 through 50 years and to compare this with nationwide age- and sex-matched mortality rates. DESIGN, SETTING, AND PARTICIPANTS The Follow -Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study, a prospective cohort study of prognosis after transient ischemic attack (TIA), ischemic stroke, or hemorrhagic stroke in adults aged 18 through 50 years admitted to Radboud University Nijmegen Medical Centre, the Netherlands, between January 1, 1980, and November 1, 2010. The survival status of 959 consecutive patients with a first-ever TIA (n = 262), ischemic stroke (n = 606), or intracerebral hemorrhage (n = 91) was assessed as of November 1, 2012. Mean follow-up duration was 11.1 (SD, 8.7) years (median, 8.3 interquartile range, 4.0-17.4). Observed mortality was compared with the expected mortality, derived from mortality rates in the general population with similar age, sex, and calendar-year characteristics. MAIN OUTCOME MEASURES Cumulative 20-year mortality among 30-day survivors of stroke. RESULTS At the end of follow-up, 192 patients (20.0%) had died. Among 30-day survivors, cumulative 20-year risk of death was 24.9% (95% CI, 16.0%-33.7%) for TIA, 26.8% (95% CI, 21.9%-31.8%) for ischemic stroke, and 13.7% (95% CI, 3.6%-23.9%) for intracerebral hemorrhage. Observed mortality was increased compared with expected mortality (standardized mortality ratio SMR, 2.6 95% CI, 1.8-3.7 for TIA, 3.9 95% CI, 3.2-4.7 for ischemic stroke, and 3.9 95% CI, 1.9-7.2 for intracerebral hemorrhage, respectively). For ischemic stroke, cumulative 20-year mortality among 30-day survivors was higher in men than in women (33.7% 95% CI, 26.1%-41.3% vs 19.8% 95% CI, 13.8%-25.9%). The SMR was 4.3 (95% CI, 3.2-5.6) for women and 3.6 (95% CI, 2.8-4.6) for men. For all etiologic subtypes of ischemic stroke, observed mortality exceeded expected mortality. CONCLUSIONS AND RELEVANCE Among adults aged 18 through 50 years, 20-year mortality following acute stroke was relatively high compared with expected mortality. These findings may warrant further research evaluating secondary prevention strategies in these patients.
PDF
