3D Radiative Transfer in η\eta Carinae: Application of the SimpleX Algorithm to 3D SPH Simulations of Binary Colliding Winds

Eta Carinae is an ideal astrophysical laboratory for studying massive binary interactions and evolution, and stellar wind-wind collisions. Recent three-dimensional (3D) simulations set the stage for understanding the highly complex 3D flows in $\eta$ Car. Observations of different broad high- and low-ionization forbidden emission lines provide an excellent tool to constrain the orientation of the system, the primary's mass-loss rate, and the ionizing flux of the hot secondary. In this work we present the first steps towards generating synthetic observations to compare with available and future HST/STIS data. We present initial results from full 3D radiative transfer simulations of the interacting winds in $\eta$ Car. We use the SimpleX algorithm to post-process the output from 3D SPH simulations and obtain the ionization fractions of hydrogen and helium assuming three different mass-loss rates for the primary star. The resultant ionization maps of both species constrain the regions where the observed forbidden emission lines can form. Including collisional ionization is necessary to achieve a better description of the ionization states, especially in the areas shielded from the secondary's radiation. We find that reducing the primary's mass-loss rate increases the volume of ionized gas, creating larger areas where the forbidden emission lines can form. We conclude that post processing 3D SPH data with SimpleX is a viable tool to create ionization maps for $\eta$ Car.Comment: 18 pages, 11 figures, accepted for publication in MNRA

Estimating incidence of venous thromboembolism in COVID-19:Methodological considerations

Background Coagulation abnormalities and coagulopathy are recognized as consequences of severe acute respiratory syndrome coronavirus 2 infection and the resulting coronavirus disease 2019 (COVID-19). Specifically, venous thromboembolism (VTE) has been reported as a frequent complication. By May 27, 2021, at least 93 original studies and 25 meta-analyses investigating VTE incidence in patients with COVID-19 had been published, showing large heterogeneity in reported VTE incidence ranging from 0% to 85%. This large variation complicates interpretation of individual study results as well as comparisons across studies, for example, to investigate changes in incidence over time, compare subgroups, and perform meta-analyses. Objectives This study sets out to provide an overview of sources of heterogeneity in VTE incidence studies in patients with COVID-19, illustrated using examples. Methods The original studies of three meta-analyses were screened and a list of sources of heterogeneity that may explain observed heterogeneity across studies was composed. Results The sources of heterogeneity in VTE incidence were classified as clinical sources and methodologic sources. Clinical sources of heterogeneity include differences between studies regarding patient characteristics that affect baseline VTE risk and protocols used for VTE testing. Methodologic sources of heterogeneity include differences in VTE inclusion types, data quality, and the methods used for data analysis. Conclusions To appreciate reported estimates of VTE incidence in patients with COVID-19 in relation to its etiology, prevention, and treatment, researchers should unambiguously report about possible clinical and methodological sources of heterogeneity in those estimates. This article provides suggestions for that.Thrombosis and Hemostasi

Maternal and neonatal bleeding complications in relation to peripartum management in hemophilia carriers:A systematic review

Currently, there is no consensus on the optimal management to prevent postpartum hemorrhage (PPH) in hemophilia carriers. We aimed to evaluate peripartum management strategies in relation to maternal and neonatal bleeding outcomes by performing an extensive database search up to August 2020. Seventeen case-reports/series and 11 cohort studies were identified of overall 'poor' quality describing 502 deliveries. The PPH incidence in the individual patient data was 63%; 44% for those women receiving prophylaxis to correct coagulation and 77% for those without (OR 0.23, CI 0.09-0.58) and in cohort data 20.3% (26.8% (11/41) vs. 19.4% (55/284) (OR: 1.53, 95% CI: 0.72-3.24), respectively. Peripartum management strategies mostly consisted of clotting factor concentrates, rarely of desmopressin or plasma. Tranexamic acid appears promising in preventing secondary PPH, but was not used consistently. Neonatal bleeding was described in 6 affected male neonates, mostly after instrumental delivery or emergency CS, but insufficient information was provided to reliably investigate neonatal outcome in relation to management. The high PPH risk seems apparent, at most mildly attenuated by prophylactic treatment. Prospective cohort studies are needed to determine the optimal perinatal management in hemophilia.Thrombosis and Hemostasi

Levels of Fibrinogen Variants Are Altered in Severe COVID-19

Background  Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk. Aim  To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. Methods  In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (α E ), and γ' fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Results  Healthy controls and ward patients with COVID-19 ( n  = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did ( n  = 19) or did not develop thrombosis ( n  = 18) and ICU patients with pneumococcal infection ( n  = 6) had higher absolute levels of functional, total, intact, and α E fibrinogen than healthy controls ( n  = 7). The relative α E fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ' fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Conclusion  Our results show that severe COVID-19 is associated with increased levels of α E fibrinogen and decreased relative levels of γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.</p

Levels of Fibrinogen Variants Are Altered in Severe COVID-19

Background  Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk. Aim  To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. Methods  In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (α E ), and γ' fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Results  Healthy controls and ward patients with COVID-19 ( n  = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did ( n  = 19) or did not develop thrombosis ( n  = 18) and ICU patients with pneumococcal infection ( n  = 6) had higher absolute levels of functional, total, intact, and α E fibrinogen than healthy controls ( n  = 7). The relative α E fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ' fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Conclusion  Our results show that severe COVID-19 is associated with increased levels of α E fibrinogen and decreased relative levels of γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.</p

Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders

Background: In recent years, more awareness is raised about sex-specific dilemmas in inherited bleeding disorders. However, no large studies have been performed to assess differences in diagnosis, bleeding phenotype and management of men and women with bleeding disorders. Therefore, we investigated sex differences in a large cohort of well-defined patients with autosomal inherited bleeding disorders (von Willebrand disease (VWD), rare bleeding disorders (RBDs) and congenital platelet defects (CPDs)).Methods: We included patients from three nationwide cross-sectional studies on VWD, RBDs and CPDs in the Netherlands, respectively the WiN, RBiN and TiN study. In all studies a bleeding score (BS) was obtained, and patients filled in an extensive questionnaire on the management and burden of their disorder.Findings: We included 1092 patients (834 VWD; 196 RBD; 62 CPD), of whom 665 (60.9%) were women. Women were more often referred because of a bleeding diathesis than men (47.9% vs 36.6%, p = 0.002). Age of first bleeding was similar between men and women, respectively 8.9 +/- 13.6 (mean +/- sd) years and 10.6 +/- 11.3 years (p = 0.075). However, the diagnostic delay, which was defined as time from first bleeding to diagnosis, was longer in women (11.6 +/- 16.4 years) than men (7.7 +/- 16.6 years, p = 0.002). Similar results were found when patients referred for bleeding were analyzed separately. Of women aging 12 years or older, 469 (77.1%) had received treatment because of sex-specific bleeding.Interpretation: Women with autosomal inherited bleeding disorders are more often referred for bleeding, have a longer diagnostic delay, and often require treatment because of sex-specific bleeding. (C) 2021 The Authors. Published by Elsevier Ltd.Clinical epidemiolog

Peri-operative desmopressin combined with pharmacokinetic-guided factor VIII concentrate in non-severe haemophilia A patients

Introduction: Non-severe haemophilia A patient can be treated with desmopressin or factor VIII (FVIII) concentrate. Combining both may reduce factor consumption, but its feasibility and safety has never been investigated. Aim: We assessed the feasibility and safety of combination treatment in nonsevere haemophilia A patients. Methods: Non-severe, desmopressin responsive, haemophilia A patients were included in one of two studies investigating peri-operative combination treatment. In the single-arm DAVID study intravenous desmopressin (0.3 μg/kg) once-a-day was, after sampling, immediately followed by PK-guided FVIII concentrate, for maximally three consecutive days. The Little DAVID study was a randomized trial in patients undergoing a minor medical procedure, whom received either PK-guided combination treatment (intervention arm) or PK-guided FVIII concentrate only (standard arm) up to 2 days. Dose predictions were considered accurate if the absolute difference between predicted and measured FVIII:C was ≤0.2 IU/mL. Results: In total 32 patients (33 procedures) were included. In the DAVID study (n = 21), of the FVIII:C trough levels 73.7% (14/19) were predicted accurately on day 1 (D1), 76.5% (13/17) on D2. On D0, 61.9% (13/21) of peak FVIII:C levels predictions were accurate. In the Little DAVID study (n = 12), on D0 83.3% (5/6) FVIII:C peak levels for both study arms were predicted accurately. Combination treatment reduced preoperative FVIII concentrate use by 47% versus FVIII monotherapy. Desmopressin side effects were mild and transient. Two bleeds occurred, both despite FVIII:C &gt; 1.00 IU/mL. Conclusion: Peri-operative combination treatment with desmopressin and PK-guided FVIII concentrate dosing in nonsevere haemophilia A is feasible, safe and reduces FVIII consumption.</p

The escape of ionising radiation from high-redshift dwarf galaxies

The UV escape fraction from high-redshift galaxies plays a key role in models of cosmic reionisation. Because it is currently not possible to deduce the escape fractions during the epoch of reionisation from observations, we have to rely on numerical simulations. Our aim is to better constrain the escape fraction from high-redshift dwarf galaxies, as these are the most likely sources responsible for reionising the Universe. We employ a N-body/SPH method that includes realistic prescriptions for the physical processes that are important for the evolution of dwarf galaxies. These models are post-processed with radiative transfer to determine the escape fraction of ionising radiation. We perform a parameter study to assess the influence of the spin parameter, gas fraction and formation redshift of the galaxy and study the importance of numerical parameters as resolution, source distribution and local gas clearing. We find that the UV escape fraction from high-redshift dwarf galaxies that have formed a rotationally supported disc lie between 1e-5 and 0.1. The mass and angular momentum of the galaxy are the most important parameters that determine the escape fraction. We compare our results to previous work and discuss the uncertainties of our models. The low escape fraction we find for high-redshift dwarf galaxies is balanced by their high stellar content, resulting in an efficiency parameter for stars that is only marginally lower than the values found by semi-analytic models of reionisation. We therefore conclude that dwarf galaxies play an important role in cosmic reionisation also after the initial starburst phase, when the gas has settled into a disc.Comment: 19 pages, 14 figures. Accepted for publication in A&

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: a research protocol for the development and implementation of the SERENITY shared decision support tool Thrombosis Research

Background: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. Methods: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe.Results: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. Conclusions: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers