Self-Consistent Convolutional Density Functional Approximations: Application to Adsorption at Metal Surfaces.

The exchange-correlation (XC) functional in density functional theory is used to approximate multi-electron interactions. A plethora of different functionals are available, but nearly all are based on the hierarchy of inputs commonly referred to as "Jacob's ladder." This paper introduces an approach to construct XC functionals with inputs from convolutions of arbitrary kernels with the electron density, providing a route to move beyond Jacob's ladder. We derive the variational derivative of these functionals, showing consistency with the generalized gradient approximation (GGA), and provide equations for variational derivatives based on multipole features from convolutional kernels. A proof-of-concept functional, PBEq, which generalizes the PBE α ${\alpha }$ framework with α ${\alpha }$ being a spatially-resolved function of the monopole of the electron density, is presented and implemented. It allows a single functional to use different GGAs at different spatial points in a system, while obeying PBE constraints. Analysis of the results underlines the importance of error cancellation and the XC potential in data-driven functional design. After testing on small molecules, bulk metals, and surface catalysts, the results indicate that this approach is a promising route to simultaneously optimize multiple properties of interest.

Kohn-Sham accuracy from orbital-free density functional theory via Δ-machine learning.

We present a Δ-machine learning model for obtaining Kohn-Sham accuracy from orbital-free density functional theory (DFT) calculations. In particular, we employ a machine-learned force field (MLFF) scheme based on the kernel method to capture the difference between Kohn-Sham and orbital-free DFT energies/forces. We implement this model in the context of on-the-fly molecular dynamics simulations and study its accuracy, performance, and sensitivity to parameters for representative systems. We find that the formalism not only improves the accuracy of Thomas-Fermi-von Weizsäcker orbital-free energies and forces by more than two orders of magnitude but is also more accurate than MLFFs based solely on Kohn-Sham DFT while being more efficient and less sensitive to model parameters. We apply the framework to study the structure of molten Al0.88Si0.12, the results suggesting no aggregation of Si atoms, in agreement with a previous Kohn-Sham study performed at an order of magnitude smaller length and time scales.

Automated Generation of Microkinetics for Heterogeneously Catalyzed Reactions Considering Correlated Uncertainties.

The study presents an ab-initio based framework for the automated construction of microkinetic mechanisms considering correlated uncertainties in all energetic parameters and estimation routines. 2000 unique microkinetic models were generated within the uncertainty space of the BEEF-vdW functional for the oxidation reactions of representative exhaust gas emissions from stoichiometric combustion engines over Pt(111) and compared to experiments through multiscale modeling. The ensemble of simulations stresses the importance of considering uncertainties. Within this set of first-principles-based models, it is possible to identify a microkinetic mechanism that agrees with experimental data. This mechanism can be traced back to a single exchange-correlation functional, and it suggests that Pt(111) could be the active site for the oxidation of light hydrocarbons. The study provides a universal framework for the automated construction of reaction mechanisms with correlated uncertainty quantification, enabling a DFT-constrained microkinetic model optimization for other heterogeneously catalyzed systems.

Gaussian approximation of dispersion potentials for efficient featurization and machine-learning predictions of metal-organic frameworks.

Energy-related descriptors in machine learning are a promising strategy to predict adsorption properties of metal-organic frameworks (MOFs) in the low-pressure regime. Interactions between hosts and guests in these systems are typically expressed as a sum of dispersion and electrostatic potentials. The energy landscape of dispersion potentials plays a crucial role in defining Henry's constants for simple probe molecules in MOFs. To incorporate more information about this energy landscape, we introduce the Gaussian-approximated Lennard-Jones (GALJ) potential, which fits pairwise Lennard-Jones potentials with multiple Gaussians by varying their heights and widths. The GALJ approach is capable of replicating information that can be obtained from the original LJ potentials and enables efficient development of Gaussian integral (GI) descriptors that account for spatial correlations in the dispersion energy environment. GI descriptors would be computationally inconvenient to compute using the usual direct evaluation of the dispersion potential energy surface. We show that these new GI descriptors lead to improvement in ML predictions of Henry's constants for a diverse set of adsorbates in MOFs compared to previous approaches to this task.

Epidemiology of pleural empyema in English hospitals and the impact of influenza.

Pleural empyema represents a significant healthcare burden due to extended hospital admissions and potential requirement for surgical intervention. This study aimed to assess changes in incidence and management of pleural empyema in England over the past 10 years and the potential impact of influenza on rates.Hospital Episode Statistics data were used to identify patients admitted to English hospitals with pleural empyema between 2008 and 2018. Linear regression was used to analyse the relationship between empyema rates and influenza incidence recorded by Public Health England. The relationship between influenza and empyema was further explored using serological data from a prospective cohort study of patients presenting with pleural empyema.Between April 2008 and March 2018 there were 55 530 patients admitted with pleural empyema. There was male predominance (67% versus 33%), which increased with age. Cases have increased significantly from 4447 in 2008 to 7268 in 2017. Peaks of incidence correlated moderately with rates of laboratory-confirmed influenza in children and young adults (r=0.30). For nine of the 10 years studied, the highest annual point incidence of influenza coincided with the highest admission rate for empyema (with a 2-week lag). In a cohort study of patients presenting to a single UK hospital with pleural empyema/infection, 24% (17 out of 72) had serological evidence of recent influenza infection, compared to 7% in seasonally matched controls with simple parapneumonic or cardiogenic effusions (p<0.001).Rates of empyema admissions in England have increased steadily with a seasonal variation that is temporally related to influenza incidence. Patient-level serological data from a prospective study support the hypothesis that influenza may play a pathogenic role in empyema development.

Heterogeneity in susceptibility dictates the order of epidemic models.

The fundamental models of epidemiology describe the progression of an infectious disease through a population using compartmentalized differential equations, but typically do not incorporate population-level heterogeneity in infection susceptibility. Here we combine a generalized analytical framework of contagion with computational models of epidemic dynamics to show that variation strongly influences the rate of infection, while the infection process simultaneously sculpts the susceptibility distribution. These joint dynamics influence the force of infection and are, in turn, influenced by the shape of the initial variability. We find that certain susceptibility distributions (the exponential and the gamma) are unchanged through the course of the outbreak, and lead naturally to power-law behavior in the force of infection; other distributions are often sculpted towards these "eigen-distributions" through the process of contagion. The power-law behavior fundamentally alters predictions of the long-term infection rate, and suggests that first-order epidemic models that are parameterized in the exponential-like phase may systematically and significantly over-estimate the final severity of the outbreak. In summary, our study suggests the need to examine the shape of susceptibility in natural populations as part of efforts to improve prediction models and to prioritize interventions that leverage heterogeneity to mitigate against spread.

Pleural Fluid suPAR Levels Predict the Need for Invasive Management in Parapneumonic Effusions.

Rationale: Parapneumonic effusions have a wide clinical spectrum. The majority settle with conservative management but some progress to complex collections requiring intervention. For decades, physicians have relied on pleural fluid pH to determine the need for chest tube drainage despite a lack of prospective validation and no ability to predict the requirement for fibrinolytics or thoracic surgery.Objectives: To study the ability of suPAR (soluble urokinase plasminogen activator receptor), a potential biomarker of pleural fluid loculation, to predict the need for invasive management compared with conventional fluid biomarkers (pH, glucose, and lactate dehydrogenase) in parapneumonic effusions.Methods: Patients presenting with pleural effusions were prospectively recruited to an observational study with biological samples stored at presentation. Pleural fluid and serum suPAR levels were measured using the suPARnostic double-monoclonal antibody sandwich ELISA on 93 patients with parapneumonic effusions and 47 control subjects (benign and malignant effusions).Measurements and Main Results: Pleural suPAR levels were significantly higher in effusions that were loculated versus nonloculated parapneumonic effusions (median, 132 ng/ml vs. 22 ng/ml; P < 0.001). Pleural suPAR could more accurately predict the subsequent insertion of a chest tube with an area under the curve (AUC) of 0.93 (95% confidence interval, 0.89-0.98) compared with pleural pH (AUC 0.82; 95% confidence interval, 0.73-0.90). suPAR was superior to the combination of conventional pleural biomarkers (pH, glucose, and lactate dehydrogenase) when predicting the referral for intrapleural fibrinolysis or thoracic surgery (AUC 0.92 vs. 0.76).Conclusions: Raised pleural suPAR was predictive of patients receiving more invasive management of parapneumonic effusions and added value to conventional biomarkers. These results need validation in a prospective multicenter trial.

Investigation of a unilateral pleural effusion: What CT scan coverage is optimal?

The use of thoracic CT for patients presenting with a unilateral pleural effusion is well established. However, there is no consensus with regard to the inclusion of the entire abdomen and pelvis in the initial imaging protocol. In this prospective UK-based study, 249 patients presenting with a unilateral effusion had a CT thorax/abdomen/pelvis performed. The prevalence of malignancy on thoracic CT was 56% (140/249). Clinically significant findings below the diaphragm were identified in 59 patients (24%). Integrating this approach into standard practice allows more rapid identification of the primary malignancy, upstaging lesions or alternative sites for biopsy.

Classification of biomass reactions and predictions of reaction energies through machine learning.

Elementary steps and intermediate species of linearly structured biomass compounds are studied. Specifically, possible intermediates and elementary reactions of 15 key biomass compounds and 33 small molecules are obtained from a recursive bond-breaking algorithm. These are used as inputs to the unsupervised Mol2Vec algorithm to generate vector representations of all intermediates and elementary reactions. The vector descriptors are used to identify sub-classes of elementary steps, and linear discriminant analysis is used to accurately identify the reaction type and reduce the dimension of the vectors. The resulting descriptors are applied to predict gas-phase reaction energies using linear regression with accuracies that exceed the commonly employed group additivity approach. They are also applied to quantitatively assess model compound similarity, and the results are consistent with chemical intuition. This workflow for creating vector representations of complex molecular systems requires no input from electronic structure calculations, and it is expected to be applicable to other similar systems where vector representations are needed.

The Role of Adventitious Carbon in Photo-catalytic Nitrogen Fixation by Titania.

Photo-catalytic fixation of nitrogen by titania catalysts at ambient conditions has been reported for decades, yet the active site capable of adsorbing an inert N2 molecule at ambient pressure and the mechanism of dissociating the strong dinitrogen triple bond at room temperature remain unknown. In this work in situ near-ambient-pressure X-ray photo-electron spectroscopy and density functional theory calculations are used to probe the active state of the rutile (110) surface. The experimental results indicate that photon-driven interaction of N2 and TiO2 is observed only if adventitious surface carbon is present, and computational results show a remarkably strong interaction between N2 and carbon substitution (C*) sites that act as surface-bound carbon radicals. A carbon-assisted nitrogen reduction mechanism is proposed and shown to be thermodynamically feasible. The findings provide a molecular-scale explanation for the long-standing mystery of photo-catalytic nitrogen fixation on titania. The results suggest that controlling and characterizing carbon-based active sites may provide a route to engineering more efficient photo(electro)-catalysts and improving experimental reproducibility.

Investigating unilateral pleural effusions: the role of cytology.

The vast majority of undiagnosed unilateral pleural effusions have fluid sent for cytological analysis. Despite widespread use, there is uncertainty about its sensitivity to diagnose malignant pleural effusions (MPEs). Our aim was to ascertain the utility of cytology using a large prospective cohort.Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited to this UK-based study. All had pleural fluid sent for cytological analysis. Cytological sensitivity was based on the final diagnosis at 12 months, confirmed by two consultants.Over 8 years, 921 patients were recruited, of which 515 had a MPE. Overall sensitivity of fluid cytology to diagnose malignancy was 46% (95% CI 42-58%). There was variation in sensitivity depending on cancer primary, with mesothelioma (6%) and haematological malignancies (40%) being significantly lower than adenocarcinomas (79%). MPEs secondary to ovarian cancer had high pick-up rates (95%). In asbestos-exposed males with exudative effusions, the risk of MPE was 60%, but cytological sensitivity was 11%.This is the largest prospective study of pleural fluid cytology and informs discussions with patients about the likely requirement for investigations following thoracentesis. In patients presenting with a clinical suspicion of mesothelioma, cytological sensitivity is low, so more definitive investigations could be performed sooner.

A Prospective Study to Evaluate a Diagnostic Algorithm for the Use of Fluid Lymphocyte Subset Analysis in Undiagnosed Unilateral Pleural Effusions.

BACKGROUND: Haematological malignancy is an important cause of pleural effusion. Pleural effusions secondary to haematological malignancy are usually lymphocyte predominant. However, several other conditions such as carcinoma, tuberculosis, and chronic heart failure also cause lymphocytic effusions. Lymphocyte subset (LS) analysis may be a useful test to identify haematological malignancy in patients with lymphocytic effusions. However, research into their utility in pleural effusion diagnostic algorithms has not yet been published. OBJECTIVES: We aimed to determine the clinical utility of pleural fluid LS analysis and whether it can be applied to a diagnostic algorithm to identify effusions secondary to haematological malignancy. The secondary aim was to evaluate the diagnostic value of pleural fluid differential cell count. METHODS: Consecutive consenting patients presenting to our pleural service between 2008 and 2013 underwent thoracentesis and differential cell count analysis. We proposed an algorithm which selected patients with lymphocytic effusions (>50%) to have further fluid sent for LS analysis. Two independent consultants agreed on the cause of the original effusion after a 12-month follow-up period. RESULTS: A total of 60 patients had samples sent for LS analysis. LS analysis had an 80% sensitivity (8/10) and a 100% specificity for the diagnosis of haematological malignancy. The positive and negative predictive values were 100 and 96.1%, respectively. Overall 344 differential cell counts were analysed; 16% of pleural effusions with a malignant aetiology were neutrophilic or eosinophilic at presentation. A higher neutrophil and eosinophil count was associated with benign diagnoses, whereas a higher lymphocyte count was associated with malignant diagnoses. CONCLUSIONS: LS analysis may identify haematological malignancy in a specific cohort of patients with undiagnosed pleural effusions. A pleural fluid differential cell count provides useful additional information to streamline patient pathway decisions.

Linear probe 19-gauge endobronchial ultrasound diagnosis of a benign chondroid hamartoma.

We report a case of a 68-year-old gentleman, found to have a right hilar soft tissue mass whilst undergoing CT staging for prostate cancer. MRI imaging showed a heterogenous, enhancing solid mass without evidence of fat content. A linear probe endobronchial ultrasound-guided transbronchial needle aspiration was performed using a 19G needle. This confirmed the diagnosis of a benign chondroid hamartoma, avoiding the need for more invasive surgical biopsy.

The effect of 19-gauge endobronchial ultrasound-guided transbronchial needle aspiration biopsies on characterisation of malignant and benign disease. The Bristol experience.

EBUS-TBNA is a recent mediastinal staging and diagnostic technique. We have previously reported superior characterisation with 21G biopsies over 22G biopsies for benign and malignant mediastinal nodes. A new 19G needle now exists but there are limited studies. We hypothesised 19G biopsies would improve both benign and malignant characterisation due to larger samples. We retrospectively analysed sequential patients referred for EBUS-TBNA with unexplained mediastinal adenopathy performed with 19G, 21G and 22G needles respectively (100 patients each). Contingency table analysis was performed.  There were no complications. Sensitivity for malignancy was highest in the 19G group (95.7% versus 94.7% and 87.5%, respectively). The 19G group had higher mean lymph node size (19.4mm versus 18.6mm and 13.5mm, respectively), the highest proportion of lymphoma (9% versus 5% and 0%, respectively), the lowest proportion of NSCLC-NOS (2% versus 12% and 5%, respectively), the highest proportion of subcharacterised benign disease (89.6% versus 69.8% and 37.9%, respectively). This large single centre retrospective UK study suggests the 19G needle appears safe with the suggestion of better sensitivity for malignancy subcharacterisation of benign disease but this requires further study in adequately powered comparative controlled studies with univariate and multivariate analysis.

A Highly Active Molybdenum Phosphide Catalyst for Methanol Synthesis from CO and CO2.

Methanol is a major fuel and chemical feedstock currently produced from syngas, a CO/CO2 /H2 mixture. Herein we identify formate binding strength as a key parameter limiting the activity and stability of known catalysts for methanol synthesis in the presence of CO2 . We present a molybdenum phosphide catalyst for CO and CO2 reduction to methanol, which through a weaker interaction with formate, can improve the activity and stability of methanol synthesis catalysts in a wide range of CO/CO2 /H2 feeds.

Intrinsic Selectivity and Structure Sensitivity of Rhodium Catalysts for C(2+) Oxygenate Production.

Synthesis gas (CO + H2) conversion is a promising route to converting coal, natural gas, or biomass into synthetic liquid fuels. Rhodium has long been studied as it is the only elemental catalyst that has demonstrated selectivity to ethanol and other C2+ oxygenates. However, the fundamentals of syngas conversion over rhodium are still debated. In this work a microkinetic model is developed for conversion of CO and H2 into methane, ethanol, and acetaldehyde on the Rh (211) and (111) surfaces, chosen to describe steps and close-packed facets on catalyst particles. The model is based on DFT calculations using the BEEF-vdW functional. The mean-field kinetic model includes lateral adsorbate-adsorbate interactions, and the BEEF-vdW error estimation ensemble is used to propagate error from the DFT calculations to the predicted rates. The model shows the Rh(211) surface to be ∼6 orders of magnitude more active than the Rh(111) surface, but highly selective toward methane, while the Rh(111) surface is intrinsically selective toward acetaldehyde. A variety of Rh/SiO2 catalysts are synthesized, tested for catalytic oxygenate production, and characterized using TEM. The experimental results indicate that the Rh(111) surface is intrinsically selective toward acetaldehyde, and a strong inverse correlation between catalytic activity and oxygenate selectivity is observed. Furthermore, iron impurities are shown to play a key role in modulating the selectivity of Rh/SiO2 catalysts toward ethanol. The experimental observations are consistent with the structure-sensitivity predicted from theory. This work provides an improved atomic-scale understanding and new insight into the mechanism, active site, and intrinsic selectivity of syngas conversion over rhodium catalysts and may also guide rational design of alloy catalysts made from more abundant elements.

Analyzing the Case for Bifunctional Catalysis.

Bifunctional coupling of two different catalytic site types has often been invoked to explain experimentally observed enhanced catalytic activities. We scrutinize such claims with generic scaling-relation-based microkinetic models that allow exploration of the theoretical limits for such a bifunctional gain for several model reactions. For sites at transition-metal surfaces, the universality of the scaling relations between adsorption energies largely prevents any improvements through bifunctionality. Only the consideration of systems that involve the combination of different materials, such as metal particles on oxide supports, offers hope for significant bifunctional gains.

Pleural irrigation trial (PIT): a randomised controlled trial of pleural irrigation with normal saline versus standard care in patients with pleural infection.

Pleural infection is increasing in incidence. Despite optimal medical management, up to 30% of patients will die or require surgery. Case reports suggest that irrigation of the pleural space with saline may be beneficial.A randomised controlled pilot study in which saline pleural irrigation (three times per day for 3 days) plus best-practice management was compared with best-practice management alone was performed in patients with pleural infection requiring chest-tube drainage. The primary outcome was percentage change in computed tomography pleural fluid volume from day 0 to day 3. Secondary outcomes included surgical referral rate, hospital stay and adverse events.35 patients were randomised. Patients receiving saline irrigation had a significantly greater reduction in pleural collection volume on computed tomography compared to those receiving standard care (median (interquartile range) 32.3% (19.6-43.7%) reduction versus 15.3% (-5.5-28%) reduction) (p<0.04). Significantly fewer patients in the irrigation group were referred for surgery (OR 7.1, 95% CI 1.23-41.0; p=0.03). There was no difference in length of hospital stay, fall in C-reactive protein, white cell count or procalcitonin or adverse events between the treatment groups, and no serious complications were documented.Saline irrigation improves pleural fluid drainage and reduces referrals for surgery in pleural infection. A large multicentre randomised controlled trial is now warranted to evaluate its effects further.

Differentiating benign from malignant mediastinal lymph nodes visible at EBUS using grey-scale textural analysis.

BACKGROUND AND OBJECTIVE: Recent data suggest that grey-scale textural analysis on endobronchial ultrasound (EBUS) imaging can differentiate benign from malignant lymphadenopathy. The objective of studies was to evaluate grey-scale textural analysis and examine its clinical utility. METHODS: Images from 135 consecutive clinically indicated EBUS procedures were evaluated retrospectively using MATLAB software (MathWorks, Natick, MA, USA). Manual node mapping was performed to obtain a region of interest and grey-scale textural features (range of pixel values and entropy) were analysed. The initial analysis involved 94 subjects and receiver operating characteristic (ROC) curves were generated. The ROC thresholds were then applied on a second cohort (41 subjects) to validate the earlier findings. RESULTS: A total of 371 images were evaluated. There was no difference in proportions of malignant disease (56% vs 53%, P = 0.66) in the prediction (group 1) and validation (group 2) sets. There was no difference in range of pixel values in group 1 but entropy was significantly higher in the malignant group (5.95 vs 5.77, P = 0.03). Higher entropy was seen in adenocarcinoma versus lymphoma (6.00 vs 5.50, P < 0.05). An ROC curve for entropy gave an area under the curve of 0.58 with 51% sensitivity and 71% specificity for entropy greater than 5.94 for malignancy. In group 2, the entropy threshold phenotyped only 47% of benign cases and 20% of malignant cases correctly. CONCLUSIONS: These findings suggest that use of EBUS grey-scale textural analysis for differentiation of malignant from benign lymphadenopathy may not be accurate. Further studies are required.

Advances in understanding of the pathogenesis of acute respiratory distress syndrome.

The clinical syndrome of acute lung injury (ALI) occurs as a result of an initial acute systemic inflammatory response. This can be consequent to a plethora of insults, either direct to the lung or indirect. The insult results in increased epithelial permeability, leading to alveolar flooding with a protein-rich oedema fluid. The resulting loss of gas exchange leads to acute respiratory failure and typically catastrophic illness, termed acute respiratory distress syndrome (ARDS), requiring ventilatory and critical care support. There remains a significant disease burden, with some estimates showing 200,000 cases each year in the USA with a mortality approaching 50%. In addition, there is a significant burden of morbidity in survivors. There are currently no disease-modifying therapies available, and the most effective advances in caring for these patients have been in changes to ventilator strategy as a result of the ARDS network studies nearly 15 years ago. Here, we will give an overview of more recent advances in the understanding of the cellular biology of ALI and highlight areas that may prove fertile for future disease-modifying therapies.