Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry

Totes les malalties cerebrovasculars/ictus; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Trombosi venosa cerebralTodas las enfermedades cerebrovasculares/ictus; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Trombosis venosa cerebralAll cerebrovascular diseases/stroke; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cerebral venous thrombosisBackground Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. Aim To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. Methods Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). Results Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. Conclusions COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.The author(s) received no financial support for the research, authorship, and/or publication of this article

Global Hopf bifurcation in the ZIP regulatory system

Regulation of zinc uptake in roots of Arabidopsis thaliana has recently been modeled by a system of ordinary differential equations based on the uptake of zinc, expression of a transporter protein and the interaction between an activator and inhibitor. For certain parameter choices the steady state of this model becomes unstable upon variation in the external zinc concentration. Numerical results show periodic orbits emerging between two critical values of the external zinc concentration. Here we show the existence of a global Hopf bifurcation with a continuous family of stable periodic orbits between two Hopf bifurcation points. The stability of the orbits in a neighborhood of the bifurcation points is analyzed by deriving the normal form, while the stability of the orbits in the global continuation is shown by calculation of the Floquet multipliers. From a biological point of view, stable periodic orbits lead to potentially toxic zinc peaks in plant cells. Buffering is believed to be an efficient way to deal with strong transient variations in zinc supply. We extend the model by a buffer reaction and analyze the stability of the steady state in dependence of the properties of this reaction. We find that a large enough equilibrium constant of the buffering reaction stabilizes the steady state and prevents the development of oscillations. Hence, our results suggest that buffering has a key role in the dynamics of zinc homeostasis in plant cells.Comment: 22 pages, 5 figures, uses svjour3.cl

Young Stellar Objects and Triggered Star Formation in the Vulpecula OB Association

The Vulpecula OB association, VulOB1, is a region of active star formation located in the Galactic plane at 2.3 kpc from the Sun. Previous studies suggest that sequential star formation is propagating along this 100 pc long molecular complex. In this paper, we use Spitzer MIPSGAL and GLIMPSE data to reconstruct the star formation history of VulOB1, and search for signatures of past triggering events. We make a census of Young Stellar Objects (YSO) in VulOB1 based on IR color and magnitude criteria, and we rely on the properties and nature of these YSOs to trace recent episodes of massive star formation. We find 856 YSO candidates, and show that the evolutionary stage of the YSO population in VulOB1 is rather homogeneous - ruling out the scenario of propagating star formation. We estimate the current star formation efficiency to be ~8 %. We also report the discovery of a dozen pillar-like structures, which are confirmed to be sites of small scale triggered star formation.Comment: 30 pages, 11 figures, accepted for publication in Ap

A multi-wavelength census of stellar contents in the young cluster NGC 1624

We present a comprehensive multi-wavelength analysis of the young cluster NGC 1624 associated with the H II region Sh2-212 using optical UBVRI photometry, optical spectroscopy and GMRT radio continuum mapping along with the near-infrared (NIR) JHK archival data. Reddening E(B-V) and distance to the cluster are estimated to be 0.76 - 1.00 mag and 6.0 +/- 0.8 kpc, respectively. Present analysis yields a spectral class of O6.5V for the main ionizing source of the region. The distribution of YSOs in (J-H)/ (H-K) NIR colour-colour diagram shows that a majority of them have A_V $\le$ 4 mag. Based on the NIR excess characteristics, we identified 120 probable candidate YSOs in this region which yield a disk frequency of ~ 20%. These YSOs are found to have an age spread of ~ 5 Myr with a median age of ~ 2-3 Myr and a mass range of ~ 0.1 - 3.0 $M_\odot$. A significant number of YSOs are located close to the cluster centre and we detect an enhanced density of reddened YSOs located/projected close to the molecular clumps at the periphery of NGC 1624. This indicates that the YSOs located within the cluster core are relatively older in comparison to those located/projected near the clumps. From the radio continuum flux, spectral class of the ionizing source of the ultra-compact H II region at the periphery of Sh2-212 is estimated to be ~ B0.5V. From optical data, slope of the mass function (MF) $\Gamma$, in the mass range $1.2 \le M/M_{\odot}<27$ can be represented by a single power law with a slope -1.18 +/- 0.10, whereas the NIR data in the mass range $0.65 \le M/M_{\odot}<27$ yields $\Gamma$ = -1.31 +/- 0.15. The slope of the K-band luminosity function (KLF) for the cluster is found to be 0.30 +/- 0.06 which is in agreement with the values obtained for other young clusters.Comment: Accepted for publication in MNRA

HERSCHEL-HIFI spectroscopy of the intermediate mass protostar NGC7129 FIRS 2

HERSCHEL-HIFI observations of water from the intermediate mass protostar NGC7129 FIRS 2 provide a powerful diagnostic of the physical conditions in this star formation environment. Six spectral settings, covering four H216O and two H218O lines, were observed and all but one H218O line were detected. The four H2 16 O lines discussed here share a similar morphology: a narrower, \approx 6 km/s, component centered slightly redward of the systemic velocity of NGC7129 FIRS 2 and a much broader, \approx 25 km/s component centered blueward and likely associated with powerful outflows. The narrower components are consistent with emission from water arising in the envelope around the intermediate mass protostar, and the abundance of H2O is constrained to \approx 10-7 for the outer envelope. Additionally, the presence of a narrow self-absorption component for the lowest energy lines is likely due to self-absorption from colder water in the outer envelope. The broader component, where the H2O/CO relative abundance is found to be \approx 0.2, appears to be tracing the same energetic region that produces strong CO emission at high J.Comment: 6 pages, 4 figures, accepted by A&

Oral Anticoagulation and Risk of Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Mechanical Thrombectomy: Data From the Nordictus Registry

Introduction: We aimed to evaluate if prior oral anticoagulation (OAC) and its type determines a greater risk of symptomatic hemorrhagic transformation in patients with acute ischemic stroke (AIS) subjected to mechanical thrombectomy. Materials and Methods: Consecutive patients with AIS included in the prospective reperfusion registry NORDICTUS, a network of tertiary stroke centers in Northern Spain, from January 2017 to December 2019 were included. Prior use of oral anticoagulants, baseline variables, and international normalized ratio (INR) on admission were recorded. Symptomatic intracranial hemorrhage (sICH) was the primary outcome measure. Secondary outcome was the relation between INR and sICH, and we evaluated mortality and functional outcome at 3 months by modified Rankin scale. We compared patients with and without previous OAC and also considered the type of oral anticoagulants. Results: About 1.455 AIS patients were included, of whom 274 (19%) were on OAC, 193 (70%) on vitamin K antagonists (VKA), and 81 (30%) on direct oral anticoagulants (DOACs). Anticoagulated patients were older and had more comorbidities. Eighty-one (5.6%) developed sICH, which was more frequent in the VKA group, but not in DOAC group. OAC with VKA emerged as a predictor of sICH in a multivariate regression model (OR, 1.89 [95% CI, 1.01–3.51], p = 0.04) and was not related to INR level on admission. Prior VKA use was not associated with worse outcome in the multivariate regression model nor with mortality at 3 months. Conclusions: OAC with VKA, but not with DOACs, was an independent predictor of sICH after mechanical thrombectomy. This excess risk was associated neither with INR value by the time thrombectomy was performed, nor with a worse functional outcome or mortality at 3 months

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry

© 2020 World Stroke Organization.[Background]: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. [Aim]: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. [Methods]: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). [Results]: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p ¼ 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p ¼ 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. [Conclusions]: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes

Pathways to cellular supremacy in biocomputing

Synthetic biology uses living cells as the substrate for performing human-defined computations. Many current implementations of cellular computing are based on the “genetic circuit” metaphor, an approximation of the operation of silicon-based computers. Although this conceptual mapping has been relatively successful, we argue that it fundamentally limits the types of computation that may be engineered inside the cell, and fails to exploit the rich and diverse functionality available in natural living systems. We propose the notion of “cellular supremacy” to focus attention on domains in which biocomputing might offer superior performance over traditional computers. We consider potential pathways toward cellular supremacy, and suggest application areas in which it may be found.A.G.-M. was supported by the SynBio3D project of the UK Engineering and Physical Sciences Research Council (EP/R019002/1) and the European CSA on biological standardization BIOROBOOST (EU grant number 820699). T.E.G. was supported by a Royal Society University Research Fellowship (grant UF160357) and BrisSynBio, a BBSRC/ EPSRC Synthetic Biology Research Centre (grant BB/L01386X/1). P.Z. was supported by the EPSRC Portabolomics project (grant EP/N031962/1). P.C. was supported by SynBioChem, a BBSRC/EPSRC Centre for Synthetic Biology of Fine and Specialty Chemicals (grant BB/M017702/1) and the ShikiFactory100 project of the European Union’s Horizon 2020 research and innovation programme under grant agreement 814408

CariesCare International adapted for the pandemic in children: Caries OUT multicentre single-group interventional study protocol

Background Comprehensive caries care has shown effectiveness in controlling caries progression and improving health outcomes by controlling caries risk, preventing initial-caries lesions progression, and patient satisfaction. To date, the caries-progression control effectiveness of the patient-centred risk-based CariesCare International (CCI) system, derived from ICCMS™ for the practice (2019), remains unproven. With the onset of the COVID-19 pandemic a previously planned multi-centre RCT shifted to this “Caries OUT” study, aiming to assess in a single-intervention group in children, the caries-control effectiveness of CCI adapted for the pandemic with non-aerosols generating procedures (non-AGP) and reducing in-office time. Methods In this 1-year multi-centre single-group interventional trial the adapted-CCI effectiveness will be assessed in one single group in terms of tooth-surface level caries progression control, and secondarily, individual-level caries progression control, children’s oral-health behaviour change, parents’ and dentists’ process acceptability, and costs exploration. A sample size of 258 3–5 and 6–8 years old patients was calculated after removing half from the previous RCT, allowing for a 25% dropout, including generally health children (27 per centre). The single-group intervention will be the adapted-CCI 4D-cycle caries care, with non-AGP and reduced in-office appointments’ time. A trained examiner per centre will conduct examinations at baseline, at 5–5.5 months (3 months after basic management), 8.5 and 12 months, assessing the child’s CCI caries risk and oral-health behaviour, visually staging and assessing caries-lesions severity and activity without air-drying (ICDAS-merged Epi); fillings/sealants; missing/dental-sepsis teeth, and tooth symptoms, synthetizing together with parent and external-trained dental practitioner (DP) the patient- and tooth-surface level diagnoses and personalised care plan. DP will deliver the adapted-CCI caries care. Parents’ and dentists’ process acceptability will be assessed via Treatment-Evaluation-Inventory questionnaires, and costs in terms of number of appointments and activities. Twenty-one centres in 13 countries will participate. Discussion The results of Caries OUT adapted for the pandemic will provide clinical data that could help support shifting the caries care in children towards individualised oral-health behaviour improvement and tooth-preserving care, improving health outcomes, and explore if the caries progression can be controlled during the pandemic by conducting non-AGP and reducing in-office time. Trial registration: Retrospectively-registered-ClinicalTrials.gov-NCT04666597-07/12/2020: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AGM4&selectaction=Edit&uid=U00019IE&ts=2&cx=uwje3h. Protocol-version 2: 27/01/2021