Active-learning for global optimization of Ni-Ceria nanoparticles: The case of Ce4-xNixO8- x (x = 1, 2, 3).

Ni-CeO2 nanoparticles (NPs) are promising nanocatalysts for water splitting and water gas shift reactions due to the ability of ceria to temporarily donate oxygen to the catalytic reaction and accept oxygen after the reaction is completed. Therefore, elucidating how different properties of the Ni-Ceria NPs relate to the activity and selectivity of the catalytic reaction, is of crucial importance for the development of novel catalysts. In this work the active learning (AL) method based on machine learning regression and its uncertainty is used for the global optimization of Ce(4-x)NixO(8-x) (x = 1, 2, 3) nanoparticles, employing density functional theory calculations. Additionally, further investigation of the NPs by mass-scaled parallel-tempering Born-Oppenheimer molecular dynamics resulted in the same putative global minimum structures found by AL, demonstrating the robustness of our AL search to learn from small datasets and assist in the global optimization of complex electronic structure systems.

Pd8 Cluster: Too Small to Melt? A BOMD Study.

The question of whether a solid-liquid phase transition occurs in small clusters poses a fundamental challenge. In this study, we attempt to elucidate this phenomenon through a thorough examination of the thermal behavior and structural stability of Pd8 clusters employing ab initio simulations. Initially, a systematic global search is carried out to identify the various isomers of the Pd8 cluster. This is accomplished by employing an ab initio basin-hopping algorithm and using the PBE/SDD scheme integrated in the Gaussian code. The resulting isomers are further refined through reoptimization using the deMon2k package. To ensure the structural firmness of the lowest-energy isomer, we calculated normal modes. The structural stability as a function of temperature is analyzed through the Born-Oppenheimer molecular dynamics (BOMD) approach. Multiple BOMD trajectories at distinct simulated temperatures are examined with data clustering analysis to determine cluster isomers. This analysis establishes a connection between the potential energy landscape and the simulated temperature. To address the question of cluster melting, canonical parallel-tempering BOMD runs are performed and analyzed with the multiple-histogram method. A broad maximum in the heat capacity curve indicates a melting transition between 500 and 600 K. To further examine this transition, the mean-squared displacement and the pair-distance distribution function are calculated. The results of these calculations confirm the existence of a solid-liquid phase transition, as indicated by the heat capacity curve.

The Efficacy and Safety of a Low-Dose Tranexamic Acid Bolus-Only Protocol Compared with the Moderate-Dose Protocol in Valvular Heart Surgery.

In 873 propensity score-matched pairs of patients undergoing valvular heart surgery, we compared a "moderate dose" of tranexamic acid (TXA) protocol (group 1; median TXA dose: 24 mg/kg body weight) with a 1.5-g "bolus-only" protocol (group 2; median TXA dose: 19 mg/kg body weight). The number of transfused patients was higher in group 2 than in group 1 (74.5 vs 66.0%, p < 0.001), as was the number of transfused red blood cell concentrates (p = 0.001). The risks of re-exploration and convulsive seizures were similar between groups (p > 0.50). Data indicate an impaired efficacy following the "bolus-only" protocol, without a significant safety improvement.

European Pediatric Cardiac Anesthesia Fellowship Program: A First Proof of Concept.

The Pediatric Cardiac Anesthesia (PCA) fellowship is a demanding training program in Europe and the United States. Successful completion of the program requires years of training in anesthesiology, a thorough understanding of cardiovascular anatomy and physiology, and extensive experience in the perioperative management of neonates and children with heart disease. In the context of the first candidate to successfully complete the PCA program in Europe, this article presents excerpts from the design and structure of the European PCA program. The PCA program is evaluated critically by both external and internal reviewers, and points are highlighted that could be included in the next version of the program.

GAMaterial-A genetic-algorithm software for material design and discovery.

Genetic algorithms (GAs) are stochastic global search methods inspired by biological evolution. They have been used extensively in chemistry and materials science coupled with theoretical methods, ranging from force-fields to high-throughput first-principles methods. The methodology allows an accurate and automated structural determination for molecules, atomic clusters, nanoparticles, and solid surfaces, fundamental to understanding chemical processes in catalysis and environmental sciences, for instance. In this work, we propose a new genetic algorithm software, GAMaterial, implemented in Python3.x, that performs global searches to elucidate the structures of atomic clusters, doped clusters or materials and atomic clusters on surfaces. For all these applications, it is possible to accelerate the GA search by using machine learning (ML), the ML@GA method, to build subsequent populations. Results for ML@GA applied for the dopant distributions in atomic clusters are presented. The GAMaterial software was applied for the automatic structural search for the Ti6 O12 cluster, doping Al in Si11 (4Al@Si11 ) and Na10 supported on graphene (Na10 @graphene), where DFTB calculations were used to sample the complex search surfaces with reasonably low computational cost. Finally, the global search by GA of the Mo8 C4 cluster was considered, where DFT calculations were made with the deMon2k code, which is interfaced with GAMaterial.

Perioperative Considerations in Management of the Severely Bleeding Coagulopathic Patient.

Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.

Efficient implementation of time-dependent auxiliary density functional theory.

The random phase approximation of time-dependent auxiliary density functional theory (TDADFT) is rederived from auxiliary density perturbation theory. Our exhaustive validation of TDADFT reveals an upshift of the excitation energies by ∼0.1 eV with respect to standard time-dependent density functional theory. For the computationally efficient implementation of TDADFT, floating point operation optimized three-center electron repulsion integral recurrence relations and their double asymptotic expansions are implemented into the Davidson solver. The computational efficiency of TDADFT is benchmarked with four sets of molecules comprising alkanes, fullerenes, DNA fragments, and zeolites. The results show that TDADFT has a computational scaling between 1.3 and 1.9 with respect to the number of basis functions, which is lower than the scaling of standard time-dependent density functional theory. Due to its computational simplifications, TDADFT is particularly well suited for Born-Oppenheimer molecular dynamics simulations. As illustrative examples, we present the temperature effects on the gas-phase absorption spectra of benzene, naphthalene, and anthracene.

How important is the amount of exact exchange for spin-state energy ordering in DFT? Case study of molybdenum carbide cluster, Mo4C2.

Since the form of the exact functional in density functional theory is unknown, we must rely on density functional approximations (DFAs). In the past, very promising results have been reported by combining semi-local DFAs with exact, i.e. Hartree-Fock, exchange. However, the spin-state energy ordering and the predictions of global minima structures are particularly sensitive to the choice of the hybrid functional and to the amount of exact exchange. This has been already qualitatively described for single conformations, reactions, and a limited number of conformations. Here, we have analyzed the mixing of exact exchange in exchange functionals for a set of several hundred isomers of the transition metal carbide, Mo4C2. The analysis of the calculated energies and charges using PBE0-type functional with varying amounts of exact exchange yields the following insights: (1) The sensitivity of spin-energy splitting is strongly correlated with the amount of exact exchange mixing. (2) Spin contamination is exacerbated when correlation is omitted from the exchange-correlation functional. (3) There is not one ideal value for the exact exchange mixing which can be used to parametrize or choose among the functionals. Calculated energies and electronic structures are influenced by exact exchange at a different magnitude within a given distribution; therefore, to extend the application range of hybrid functionals to the full periodic table the spin-energy splitting energies should be investigated.

Moderate Dose of Tranexamic Acid and Complications after Valvular Heart Surgery.

BACKGROUND: In valvular open-heart surgery, data regarding the effect of a moderate dose of tranexamic acid (TXA) on clinical outcomes are limited. METHODS: Out of a cohort of 13,293 patients, we performed a propensity-score-matched analysis in 6,106 patients and assessed the risk of convulsive seizures (CS, primary endpoint), stroke, renal replacement therapy, and mortality (secondary endpoints). In the entire study cohort of 13,293 patients, we also assessed the multivariable-adjusted association of CS with postoperative outcomes. RESULTS: The risk of CS was significantly higher in the TXA group (2.4%; n = 72) than in the non-TXA group (1.0%; n = 32), with a relative risk ratio (RR) of 2.28 (95% confidence interval [CI]: 1.50-3.47; p < 0.001). The risk of CS was also higher in patients receiving TXA doses ≥25 mg/kg body weight (3.7%; n = 40) than in patients receiving <25 mg/kg body weight (1.6%; n = 32; p < 0.001). Perioperative secondary clinical endpoints and 1-year mortality did not differ significantly between study groups (p-value > 0.05). Compared with non-CS patients (n = 13,000), patients with nonhemorrhagic, nonembolic CS (n = 253) revealed higher multivariable-adjusted in-hospital risks of stroke (RR: 3.82 [95% CI: 2.44-5.60; p < 0.001]) and mortality (RR: 2.07 [95% CI: 1.23-3.48; p = 0.006]), and a higher 1-year mortality risk (RR: 1.85 [95% CI: 1.42-2.41; p < 0.001]). CONCLUSION: A moderate TXA dose was associated with a significantly higher risk of seizure, but not with other clinical complications such as stroke, renal replacement therapy, and mortality. However, in the small group of patients experiencing a seizure, the risks of stroke and short- and mid-term mortality were substantially higher than in patients not experiencing a seizure, indicating that the use of a low-dose TXA protocol (<25 mg/kg body weight) should be considered.

Use of the CytoSorb® filter for elimination of residual therapeutic argatroban concentrations during heparinized cardiopulmonary bypass for heart transplantation.

INTRODUCTION: No antidote or established extracorporeal elimination strategy is available for argatroban. Hemadsorption facilitates elimination of smaller drugs. CASE REPORT: A 34-year-old patient underwent urgent heart transplantation. Because of a history of heparin-induced thrombocytopenia, preoperative anticoagulation was performed with argatroban. Despite ceasing of the continuous infusion of argatroban 2 h before surgery, concentration only declined from 0.60 µg/ml to 0.58 µg/ml before surgery, and the activated clotting time (ACT) value shortly was 223 s. Microvascular bleeding had been observed when starting surgery. A CytoSorb® absorption column was integrated into the system of the heparin-anticoagulated cardiopulmonary bypass (CPB) circuit and a flow of 400 mL/min provided during the 2 h of extracorporeal circulation. The argatroban concentration after weaning from CPB was 0.04 µg/ml and satisfying hemostasis had been achieved after protamine administration. CONCLUSION: Data indicate that the CytoSorb® absorption column might be an effective tool for quick extracorporeal removal of therapeutic concentrations of argatroban.

Automatic structural elucidation of vacancies in materials by active learning.

Finding the optimum structures of non-stoichiometric or berthollide materials, such as (1D, 2D, 3D) materials or nanoparticles (0D), is challenging due to the huge chemical/structural search space. Computational methods coupled with global optimization algorithms have been used successfully for this purpose. In this work, we have developed an artificial intelligence method based on active learning (AL) or Bayesian optimization for the automatic structural elucidation of vacancies in solids and nanoparticles. AL uses machine learning regression algorithms and their uncertainties to take decisions (from a policy) on the next unexplored structures to be computed, increasing the probability of finding the global minimum with few calculations. The methodology allows an accurate and automated structural elucidation for vacancies, which are common in non-stoichiometric (berthollide) materials, helping to understand chemical processes in catalysis and environmental sciences, for instance. The AL vacancies method was implemented in the quantum machine learning software/agent for material design and discovery (QMLMaterial). Also, two additional acquisition functions for decision making were implemented, besides the expected improvement (EI): the lower confidence bound (LCB) and the probability of improvement (PI). The new software was applied for the automatic structural search for graphite (C36) with 3 (C36-3) and 4 (C36-4) carbon vacancies and C60 (C60-4) fullerene with 4 carbon vacancies. DFTB calculations were used to build the complex search surfaces with reasonably low computational cost. Furthermore, with the AL method for vacancies, it was possible to elucidate the optimum oxygen vacancy distribution in CaTiO3 perovskite by DFT, where a semiconductor behavior results from oxygen vacancies. Throughout the work, a Gaussian process with its uncertainty was employed in the AL framework using different acquisition functions (EI, LCB and PI), and taking into account different descriptors: Ewald sum matrix and sine matrix. Finally, the performance of the proposed AL method was compared to random search and genetic algorithm.

DFT exchange: sharing perspectives on the workhorse of quantum chemistry and materials science.

In this paper, the history, present status, and future of density-functional theory (DFT) is informally reviewed and discussed by 70 workers in the field, including molecular scientists, materials scientists, method developers and practitioners. The format of the paper is that of a roundtable discussion, in which the participants express and exchange views on DFT in the form of 302 individual contributions, formulated as responses to a preset list of 26 questions. Supported by a bibliography of 777 entries, the paper represents a broad snapshot of DFT, anno 2022.

Treatment Algorithm for Patients With von Willebrand Syndrome Type 2A and Congenital Heart Disease-A Treatment Algorithm May Reduce Perioperative Blood Loss in Children With Congenital Heart Disease.

OBJECTIVES: In children with congenital heart disease (CHD), excessive perioperative bleeding is associated with increased morbidity and mortality, thus making adequate perioperative hemostasis crucial. We investigate the prevalence of acquired von Willebrand syndrome type 2A (aVWS) in CHD and develop a treatment algorithm for patients with aVWS and CHD (TAPAC) to reduce perioperative blood loss. DESIGN: Retrospective cohort study. SETTING: Single-center study. PATIENTS: A total of 627 patients with CHD, undergoing corrective cardiac surgery between January 2008 and May 2017. INTERVENTIONS: The evaluation of perioperative bleeding risk was based on the laboratory parameters von Willebrand factor (VWF) antigen, ristocetin cofactor activity, platelet function analyzer (PFA) closure time adenosine diphosphate, and PFA epinephrine. According to the bleeding risk, treatment was performed with desmopressin or VWF. MEASUREMENTS AND MAIN RESULTS: aVWS was confirmed in 63.3 %, with a prevalence of 45.5% in the moderate and 66.3 % in the high-risk group. In addition, prevalence increased with ascending peak velocity above the stenosis (v max ) from 40.0% at less than or equal to 3 m/s to 83.3% at greater than 5 m/s. TAPAC reduced mean blood loss by 36.3% in comparison with a historical control cohort ( p < 0.001), without increasing the number of thrombotic or thromboembolic events during the hospital stay. With ascending v max , there was an increase in perioperative blood loss in the historical cohort ( p < 0.001), which was not evident in the TAPAC cohort ( p = 0.230). CONCLUSIONS: The prevalence of aVWS in CHD seems to be higher than assumed and leads to significantly higher perioperative blood loss, especially at high v max . Identifying these patients through appropriate laboratory analytics and adequate treatment could reduce blood loss effectively.

Tranexamic Acid and the Risk of Delirium after Off-Pump Surgery.

We investigated whether in patients undergoing off-pump coronary artery bypass grafting surgery a single bolus of 1 g tranexamic acid (TXA) impacts the risk of postoperative delirium using the propensity score matching approach. In 2,757 pairs, the risk of delirium was 4.2% (TXA group) and 5.0% (non-TXA group), with a relative risk in the TXA versus the non-TXA group of 0.83 (95% confidence interval: 0.65-1.07; p = 0.16). There was no significant interaction between TXA administration and renal function on the risk of delirium (p = 0.12). Data indicate that a single bolus of 1 g TXA does not increase the risk of delirium in patients undergoing off-pump surgery.

Preoperative Risk Factors and Early Outcomes of Delirium in Valvular Open-Heart Surgery.

BACKGROUND: Compared with coronary artery bypass grafting surgery, data regarding postoperative delirium are scant in valvular open-heart surgery. Therefore, the goal of this retrospective study was to investigate the incidence, preoperative risk factors, and early outcomes of delirium in a large group of patients undergoing valvular open-heart surgery. METHODS: In 13,229 patients with isolated valvular or combined valvular and bypass surgery, the incidence of postoperative delirium was assessed until discharge. Independent risk factors of delirium were evaluated by multivariable logistic regression analysis. Moreover, we assessed the multivariable-adjusted risk of prolonged intensive care unit (ICU) stay (>48 hours) and in-hospital mortality in patients with delirium. RESULTS: Overall, the incidence of postoperative delirium was 8.4%. The incidence in patients experiencing a postoperative stroke or seizure was 23.1 and 29.7%, respectively. Twelve preoperative risk factors, mostly nonmodifiable, were independently associated with the risk of delirium, including advanced age, renal impairment, stroke, the need for emergency surgery, and severe preoperative anemia (hemoglobin < 9 g/dL). Postoperative delirium was associated with an adjusted odds ratio (OR) of prolonged ICU stay of 9.48 (95% confidence interval [CI]: 7.96-11.30). Adjusted in-hospital mortality was, however, significantly lower in patients with delirium versus patients without delirium (OR, 0.56; 95% CI: 0.38-0.83). CONCLUSION: In valvular open-heart surgery, postoperative delirium is a frequent neurological complication that is associated with other postoperative neurological complications and several, mostly nonmodifiable, preoperative risk factors. Although postoperative delirium was associated with a significantly increased risk of prolonged ICU stay, this did not translate into an increased short-term mortality.

How would we treat our own heparin-induced thrombocytopenia during cardiac surgery?

The aim of this article is to provide a comprehensive review of the current state of knowledge on heparin-induced thrombocytopenia (HIT) in cardiac surgery. The management of HIT patients undergoing cardiac surgery with cardiopulmonary bypass is complex and requires an interdisciplinary and patient-tailored approach because available evidence is limited and current anticoagulation strategies have potential risks. An index case is used to discuss both the established and new perioperative therapeutic options in HIT patients undergoing urgent cardiac surgery with cardiopulmonary bypass.

Associations of preoperative stroke and tranexamic acid administration with convulsive seizures in valvular open-heart surgery.

In cardiac surgery, use of the antifibrinolytic agent tranexamic acid (TXA) and acute perioperative stroke are both associated with convulsive seizures. We hypothesized that an older (preoperative) stroke increases the risk of TXA-associated seizures as well. To test this hypothesis, we retrospectively analyzed data from 16,110 patients who had undergone open-heart valvular surgery at our institution between 2009 and 2020. The dosing of TXA was moderate. Use of TXA and a history of stroke were both independently associated with convulsive seizure with an adjusted odds ratio (OR) of 2.40 (95%CI: 1.71-3.37) and 1.79 (95%CI: 1.27-2.54), respectively. Compared to patients without TXA administration, the adjusted OR of experiencing a seizure in TXA patients without a history of stroke was 2.44 (95%CI: 1.71-3.46) and in patients receiving TXA with a history of stroke 4.30 (95%CI: 2.65-6.99). However, there was no significant interaction between TXA use and preoperative stroke on convulsive seizures (P = 0.77). Compared to patients without seizure, for patients with seizure, the inverse probability-weighted ORs of in-hospital mortality and 30-day mortality were 3.58 (95%CI: 2.20-5.83) and 4.04 (95%CI: 2.34-6.98), respectively. We conclude that, in patients undergoing open-heart surgery, a history of stroke is independently associated with convulsive seizures but is not a contraindication for TXA use.

Variational fitting of the Fock exchange potential with modified Cholesky decomposition.

The variational fitting of the Fock potential employing localized molecular orbitals requires either the inversion of the local two-center Coulomb matrices or alternatively the solution of corresponding linear equation systems with these matrices. In both cases, the method of choice is the Cholesky decomposition of the formally positive definite local two-center Coulomb matrices. However, due to finite-precision round-off errors, the local Coulomb matrices may be indefinite, and thus, the Cholesky decomposition is not applicable. To overcome this problem, we propose to make use of a modified Cholesky decomposition based on the indefinite factorization of local two-center Coulomb matrices. To this end, the working equations for the use of the modified Cholesky decomposition within the variational fitting of the Fock potential are presented. Benchmark calculations with global and range-separated hybrid functionals show that the proposed method can improve considerably the workload balance in parallel calculations.

Role of Bivalirudin for Anticoagulation in Adult Perioperative Cardiothoracic Practice.

Bivalirudin, a direct thrombin inhibitor with a fast onset of action and short half-life, is often referred to as an alternative anticoagulant to a heparin/protamine regimen. Bivalirudin demonstrated promising results as an anticoagulant in cardiac surgery with and without cardiopulmonary bypass, postcardiotomy extracorporeal membrane oxygenation, interventional cardiology and endovascular procedures, and particularly in the treatment of patients with heparin-induced thrombocytopenia undergoing high-risk cardiac surgery. Currently, bivalirudin in cardiac surgery with cardiopulmonary bypass has a limited clinical spectrum, likely because the still obvious advantages of its competitor, heparin, outweigh it in terms of medical costs, established point-of-care monitoring systems, and availability of protamine as a reversal agent. The unique pharmacology of the drug also requires adjustment of surgical and perfusion strategy. In contrast, in off-pump coronary artery surgery, established protocols from interventional cardiology can be easily translated into the operating room. In this setting bivalirudin has the potential for a more important role in the future. Through a triple mechanism of action-inhibition of plasma thrombin, clot bound thrombin, and collagen-induced platelet activation-bivalirudin may perform better than heparin by attenuating the immediate postoperative prothrombotic state and thus positively impacting the early coronary graft patency after off-pump coronary artery bypass grafting. Further studies are necessary to better evaluate this niche field and discover further applications for this unique anticoagulant.

Risk factors of early right ventricular failure in patients undergoing LVAD implantation with intermediate Intermacs profile for advanced heart failure.

BACKGROUND: The clinical profile of left ventricular assist device (LVAD) candidates is rapidly changing, with increasing proportion of patients in more stable clinical conditions. However, early postoperative right ventricular failure (eRVF) is still one of the cornerstones associated with increased mortality and the preoperative recognition of associated risk factors remains challenging. The aim of this study was to identify predictive parameters for eRVF after LVAD implantation in patients with preoperative intermediate Intermacs (InM) risk profile 3-5. METHODS: Preoperative laboratory, echocardiography, and right heart catheterization data collected from 80 patients with InM profile 3-5 before LVAD implantation were retrospectively tested with respect to their ability to predict the risk for eRVF after the implantation of a continuous-flow LVAD. RESULTS: Preoperative higher bilirubin and blood urea nitrogen (BUN) levels, higher Model for End-stage Liver Disease score, lower estimated glomerular filtration rate, and higher central venous pressure to pulmonary capillary wedge pressure ratio (CVP/PCWP) were associated to higher risk of eRVF. Regarding the echocardiographic assessment, higher end diastolic linear dimensions of the RV, higher basal end diastolic RV linear dimension to LV ratio, severe tricuspid regurgitation, lower tricuspid annular plane systolic excursion, and lower RV fractional area contraction identified patients with higher risk for eRVF. In the multivariable analysis, a CVP/CPWP > 0.55 (odds ratio [OR]: 4, 95% confidence interval [CII]: 1.4-11.8;P = .01) and BUN > 44.5 mg/dL (OR: 6.6, 95% CI: 1.51-23; P = .011) independently predicted the risk of eRVF. CONCLUSION: Preoperative BUN > 44.5 mg/dL and CVP/PCWP > 0.55 are associated to an increased risk of eRVF following LVAD implantation in intermediate InM patients.