Accuracy of inference on the physics of binary evolution from gravitational-wave observations

The properties of the population of merging binary black holes encode some of the uncertain physics of the evolution of massive stars in binaries. The binary black hole merger rate and chirp mass distribution are being measured by ground-based gravitational-wave detectors. We consider isolated binary evolution and explore how accurately the physical model can be constrained with such observations by applying the Fisher information matrix to the merging black hole population simulated with the rapid binary population synthesis code COMPAS. We investigate variations in four COMPAS parameters: common envelope efficiency, kick velocity dispersion, and mass loss rates during the luminous blue variable and Wolf--Rayet stellar evolutionary phases. We find that 1000 observations would constrain these model parameters to a fractional accuracy of a few percent. Given the empirically determined binary black hole merger rate, we can expect gravitational-wave observations alone to place strong constraints on the physics of stellar and binary evolution within a few years.Comment: 12 pages, 9 figures; version accepted by Monthly Notices of the Royal Astronomical Societ

Transarterial RAdioembolization versus ChemoEmbolization for the treatment of hepatocellular carcinoma (TRACE) : study protocol for a randomized controlled trial

Background: Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (Y-90-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a beta-emitting isotope, delivering selective internal radiation to the tumor. Y-90-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and Y-90-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma. Methods/design: In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either Y-90-RE or TACE with drug eluting beads. Patients assigned to Y-90-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease. Patients assigned to TACE will receive a maximum of three consecutive transarterial treatment sessions. Patients will undergo structural follow-up for a timeframe of two years post treatment. Post procedural magnetic resonance imaging (MRI) will be performed at one and three months post trial entry and at three-monthly intervals thereafter for two years to assess tumor response. Primary outcome will be time to progression. Secondary outcomes will be overall survival, tumor response according to the modified RECIST criteria, toxicities/adverse events, treatment related effect on total liver function, quality of life, treatment-related costs and cost-effectiveness

Tricyclic antidepressant overdose necessitating ICU admission

Tricyclic antidepressant (TCA) overdose necessitating intensive care unit (ICU) admission remains a significant problem in the Western Cape. In this retrospective study, we reviewed the course of life-threatening TCA overdose in our centre to identify potential prognostic indicators. TCA levels >1000 ng/ml were associated with QT and QRS prolongation and convulsions. However, no single parameter predicted non-survival. The overall mortality of TCA overdose was very low. Our findings should encourage clinicians to offer medical care including ICU admission, if necessary, to patients with TCA overdose

Experimental Bearing Capacity Determination of Bonded Rock Bolts

Import 26/02/2015Diplomová práce se zabývá únosností tmelených horninových svorníků a jejím experimentální stanovením. Tato práce analyzuje a poukazuje na možné způsoby porušení, které vznikají zatížením v těsné blízkosti svorníkové tyče a to především v prstenci tmele na kontaktech svorník – tmel a tmel – hornina. V teoretické části byl navržen způsob měření a stanovení pevnostních a deformačních charakteristik tahem zatížených tmelených svorníků napodobujících zatížení v kořenové délce svorníkové výztuže. V praktické části byly pak navržené postupy uskutečněny sérií laboratorních zkoušek. Výstupem z provedených zkoušek je pracovně-deformační charakteristika tmelené svorníkové výztuže zvoleného testovaného materiálu.The thesis focuses on the bearing capacity of bonded rock bolts and experimental determination of this capacity. Possible ways of failure, which is caused by the load near the rock bolt, especially in the circular ring of the grout and between the rock bolt - the grout and between the grout - the rock, are analysed. The theoretical part includes design of measuring and assessment of strength and deformation characteristics on drawn rock bolts as it simulates the load in the root length of bolt reinforcement. This theory was applied in the laboratory tests and presents the practical part of the thesis. In conclusion, the load - deformation characteristics of bonded rock bolt reinforcement made from chosen material are stated.224 - Katedra geotechniky a podzemního stavitelstvívýborn

The effects of liraglutide and dapagliflozin on cardiac function and structure in a multi-hit mouse model of Heart Failure with Preserved Ejection Fraction

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial disease that constitutes several distinct phenotypes, including a common cardiometabolic phenotype with obesity and type 2 diabetes mellitus. Treatment options for HFpEF are limited, and development of novel therapeutics is hindered by the paucity of suitable preclinical HFpEF models that recapitulate the complexity of human HFpEF. Metabolic drugs, like Glucagon Like Peptide Receptor Agonist (GLP-1RA) and Sodium Glucose Transporter 2 inhibitors (SGLT2i), have emerged as promising drugs to restore metabolic perturbations and may have value in the treatment of the cardiometabolic HFpEF phenotype. We aimed to develop a multifactorial HFpEF mouse model that closely resembles the cardiometabolic HFpEF phenotype, and evaluated the GLP-1 RA liraglutide and a SGLT2i dapagliflozin. METHODS & RESULTS: Aged (18-22 months old) female C57BL/6J mice were fed a standardized chow (CTRL) or high fat diet (HFD) for 12 weeks. After 8 weeks HFD, Angiotensin-II (ANGII), was administered for 4 weeks via osmotic mini-pumps. HFD+ANGII resulted in a cardiometabolic HFpEF phenotype, including obesity, impaired glucose handling and metabolic dysregulation with inflammation. The multiple-hit resulted in typical clinical HFpEF features, including cardiac hypertrophy and fibrosis with preserved fractional shortening but with impaired myocardial deformation, atrial enlargement lung congestion, and elevated blood pressures. Treatment with liraglutide attenuated the cardiometabolic dysregulation and improved cardiac function, with reduced cardiac hypertrophy, less myocardial fibrosis, and attenuation of atrial weight, natriuretic peptide levels, and lung congestion. Dapagliflozin treatment improved glucose handling, but had mild effects on the HFpEF phenotype. CONCLUSIONS: We developed a mouse model that recapitulates the human HFpEF disease, providing a novel opportunity to study disease pathogenesis and development of enhanced therapeutic approaches. We furthermore show that attenuation of cardiometabolic dysregulation may represent a novel therapeutic target for treatment of HFpEF. TRANSLATIONAL PERSPECTIVE: The failure of many treatment modalities for HFpEF may -at least in part- be explained by the lack of an adequate animal model. The diverse etiology of HFpEF is still largely neglected in pre-clinical research. In this study we developed a murine model that includes advanced age, female sex, in concert with co-morbidities: elevated blood pressure, obesity and T2DM. We demonstrate that this model recapitulates the human cardiometabolic HFpEF phenotype. We showed that contemporary glucose lowering drugs, liraglutide and dapagliflozin, which are both under study for HFpEF, have positive results. Our model may be useful to evaluate novel cardiometabolic, anti-fibrotic, and anti-inflammatory treatments for HFpEF

Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

An investigation into the correlation of vitamin D status and management outcomes in patients with severe COVID-19 at a South African tertiary hospital

Background: Severe coronavirus disease 2019 (COVID-19) has a poor prognosis, and biomarkers may predict disease severity. The aim of this study was to assess the effect of baseline vitamin D (VitD) inadequacy on the outcomes of patients with severe COVID-19 admitted to the intensive care unit (ICU) of a tertiary hospital in South Africa. // Methods: Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited during wave II of the pandemic in Cape Town. Eighty-six patients were included in the study. They were categorized into three groups: VitD deficient, VitD insufficient, and VitD sufficient. The VitD deficient and VitD insufficient groups were combined to form a ‘VitD inadequate’ group. Cox regression analysis was done to assess the association between VitD status and mortality. Factors with P < 0.05 in the adjusted multivariable Cox regression analysis were considered statistically significant. // Results: The proportion of VitD inadequacy was 64% (55/86); this group had a significantly higher proportion with hypertension (66%; P = 0.012). The Kaplan–Meier curve showed no significant difference in the probability of survival among the COVID-19 patients admitted to the ICU with or without VitD inadequacy. However, patients with elevated serum creatinine were significantly more at risk of dying (adjusted hazard ratio 1.008, 95% confidence interval 1.002–1.030; P = 0.017). // Conclusions: This study found a high prevalence of VitD inadequacy (combined deficiency and insufficiency) in COVID-19 patients admitted to the ICU. This may indicate a possible risk of severe disease. Whilst there was no statistically significant relationship between VitD status and mortality in this cohort, baseline VitD may be an important prognostic biomarker in COVID-19 patients admitted to the ICU, particularly in those with comorbidities that predispose to VitD deficiency

Study Protocol PROMETHEUS:Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma

Purpose: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan–Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. Discussion: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713