Accurate prediction of the properties of materials using the CAM-B3LYP density functional.

Density functionals with asymptotic corrections to the long-range potential provide entry-level methods for calculations on molecules that can sustain charge transfer, but similar applications in materials science are rare. We describe an implementation of the CAM-B3LYP range-separated functional within the Vienna Ab-initio Simulation Package (VASP) framework, together with its analytical functional derivatives. Results obtained for eight representative materials: aluminum, diamond, graphene, silicon, NaCl, MgO, 2D h-BN, and 3D h-BN, indicate that CAM-B3LYP predictions embody mean-absolute deviations (MAD) compared to HSE06 that are reduced by a factor of six for lattice parameters, four for quasiparticle band gaps, three for the lowest optical excitation energies, and six for exciton binding energies. Further, CAM-B3LYP appears competitive compared to ab initio G0 W0 and Bethe-Salpeter equation approaches. The CAM-B3LYP implementation in VASP was verified by comparison of optimized geometries and reaction energies for isolated molecules taken from the ACCDB database, evaluated in large periodic unit cells, to analogous results obtained using Gaussian basis sets. Using standard GW pseudopotentials and energy cutoffs for the plane-wave calculations and the aug-cc-pV5Z basis set for the atomic-basis ones, the MAD in energy for 1738 chemical reactions was 0.34 kcal mol-1 , while for 480 unique bond lengths this was 0.0036 Å; these values reduced to 0.28 kcal mol-1 (largest error 0.94 kcal mol-1 ) and 0.0009 Å by increasing the plane-wave cutoff energy to 850 eV.

Feature Engineering for Materials Chemistry-Does Size Matter?

The effects of structural featurizers in the prediction of band gaps have been investigated through machine learning by application to a silver nanoparticle data set and 2254 potential light-harvesting materials with known band gaps. Elemental properties were extended with structural features via Voronoi polyhedra, allowing for neighbor effects and thus presumably giving a better representation of the extended system. However, we did not find any noticeably significant difference in the predictive performance of our model. The biggest improvement in our model was due to inclusion of band gaps calculated using density functional theory. This resulted in a model that could predict the band gaps of the 2254 light-harvesting materials in the data set with an accuracy reflected in a root-mean-square error of 0.232 eV and mean absolute error of 0.142 eV. Furthermore, the good performance of our model was transferable to the prediction of a set of 72 experimental band gaps that were independent of the training set, giving a root-mean-square error of 0.91 eV and mean absolute error of 0.76 eV.

Application of the Systematic Molecular Fragmentation by Annihilation Method to ab Initio NMR Chemical Shift Calculations.

NMR is a powerful tool for obtaining information on the structural characterization and dynamics of proteins, and nucleic acids, and their complexes. The complexity of the spectra is such that elucidation through computational simulation is a much desired thing. However, the size of most structures of interest is such that they remain out of reach of accurate quantum chemical techniques. Fragmentation methods have been shown to be a viable means of reducing the cost of ab initio calculations to enable the prediction of molecular properties of large systems to chemical accuracy. We look at the systematic molecular fragmentation by annihilation method for a model peptide system and show that this procedure reproduces the shielding constants of a full calculation at only a fraction of the cost. Discussion of the considerations needed in applying this method is discussed and comparison made with the results of the similar fragment molecular orbital and ONIOM methods.

Microsolvation within the Systematic Molecular Fragmentation by Annihilation Approach.

We have applied the systematic molecular fragmentation by annihilation (SMFA) fragmentation technique to glycine and DNA base pairs in water clusters, systems for which explicit solvation is believed to be important. The SMFA method was found to be capable of describing the structures, especially in handling the complexity of hydrogen bonding, with energies produced being comparable with those from full molecule results. Thus, the ability to break down large calculations into a manageable time without loss of accuracy shows promise for application to real biological systems for which these effects are relevant.

Distinct patterns of response to transfusion therapy for different chronic complications of sickle cell disease: A useful insight.

Two main sub-phenotypes have been described in sickle cell disease: one with higher baseline haemoglobin and a higher rate of painful crises and one with lower baseline haemoglobin, increased markers of haemolysis and a higher incidence of pulmonary hypertension, priapism and leg ulcers. We compared the patterns of response to regular automated red cell exchange transfusion over a five-year period of 21 patients with recurrent painful crises from the first group and 3 patients with pulmonary hypertension and 5 with recurrent severe stuttering priapism form the second and found them to be distinctly different. Response for pain is slow and increases gradually over years. The most pronounced clinical benefit and the one that appears first is a reduction in the severity rather than the frequency of painful crises. In contrast to the slow and gradual response we see for pain, response of patients with pulmonary hypertension and priapism is immediate with significant clinical improvement even after the first transfusion. The response appears to be directly correlated to the HbS level as the symptoms of both conditions invariably recur rapidly when transfusions are delayed or discontinued but resolve again once they are re-instituted.

A 5-year cost analysis of automated red cell exchange transfusion for the management of recurrent painful crises in adult patients with sickle cell disease.

The painful vaso-occlusive crisis is the most common acute manifestation of sickle cell disease resulting in poor quality of life and high utilisation of hospital facilities. The main disease modifying strategy is treatment with hydroxycarbamide. For patients intolerant or who fail hydroxycarbamide, chronic transfusions are an alternative. Automated red cell exchange transfusion (ARCET) are more effective in lowering rapidly the HbS level while avoiding iron overload. As they require specialised equipment and specially trained staff while utilising higher volumes of blood, there have been concerns regarding the costs involved. We retrospectively analysed data on 23 patients who have been on a regular programme for 1-5 years and found that their utilisation of hospital services reduced by 20%, 48%, 58%, 71%, and 79% after 1, 2, 3, 4 and 5 years respectively. The overall mean annual cost of care per patient was £9702 and £2378 higher than baseline after the 1st and 2nd years of ARCET respectively and then reduced by £5486, £8317, and £14,664 after the 3rd, 4th and 5th year of ARCET respectively indicating that ARCET leads to cost savings to health services in the medium to long term due to reduction in hospital attendance of these patients.

Ab Initio NMR Chemical Shift Calculations Using Fragment Molecular Orbitals and Locally Dense Basis Sets.

We revisit the NMR shielding constants of a model 10-residue peptide system by investigating the use of Jensen's NMR specialized basis sets and locally dense basis sets within the fragmentation molecular orbital scheme. It is found that this procedure can reproduce the shielding constants of a full calculation at only a fraction of the cost. Strategies for choosing fragments and complications that need to be considered within the method are discussed extensively.

Safety, tolerability, and outcomes of regular automated red cell exchange transfusion in the management of sickle cell disease.

We report here our experience with regular automated red cell exchange transfusion for the management of chronic complications of sickle cell disease in 50 patients in our institution from June 2011 to December 2014. The mean sickle hemoglobin level was 44% and 8.5% pre- and post-transfusion, respectively. Platelets were reduced by a mean 70% during the procedure with a count of less than 50 × 109 /l in 6% of cases. The alloimmunization rate was 0.065/100 units of red cells with no hemolytic reactions. Patients with no iron overload at baseline showed no evidence of iron accumulation with a mean liver iron concentration of 1.6 mg/g dry tissue and 1.9 mg/g dry tissue at baseline and 36 months, respectively. All six patients with pre-existing iron overload and on chelation therapy, showed a gradual reduction of their liver iron concentration and two patients could discontinue chelation during the follow-up period. Seventy percentage of patients who were on the programme for recurrent painful crises showed a sustained reduction in the number of emergency hospital attendances; the mean number of days in hospital for emergency treatment was 103 in the year prior to commencing ARCET and reduced to 62 (40%) after the first 12 months, 51 (50%) after 24 months, and 35 days (66%) after 36 months. J. Clin. Apheresis 31:545-550, 2016. © 2015 Wiley Periodicals, Inc.

Comparison of serial serum ferritin measurements and liver iron concentration assessed by MRI in adult transfused patients with sickle cell disease.

AIMS: Transfused patients with sickle cell disease (SCD) are at risk of iron overload and identifying such patients is important to prevent associated complications. Our aim was to assess the efficacy of serial serum ferritin (SF) measurements in identifying patients with hepatic iron overload as assessed by liver MRI and its usefulness in guiding decision making regarding chelation therapy. PATIENTS/METHODS: We retrospectively compared the results of 49 liver MRI scans (LS) with the median serum ferritin (MSF) values for 28 patients in our institution. RESULTS: We found a nonlinear increment of MSF with increasing liver iron concentration (LIC). 18.4% and 47.4% of abnormal LSs corresponded to MSF <1000 mcg/L and <2000 mcg/L, respectively. 30.4% of patients with LIC of 7 mg/g dry weight or higher had a MSF <2000 mcg/L. In 38.5% of patients receiving chelation, MSF offered little information regarding the efficacy of treatment and was sometimes misleading. CONCLUSION: Serial serum ferritin measurements in adult transfused patients with sickle cell disease have a low sensitivity for identifying patients with iron overload and are of limited value in guiding decision making regarding initiation or monitoring of chelation therapy. The iron status of such high risk patients should be assessed by more definitive ways such as MRI.

Evaluation of Machine Learning Interatomic Potentials for Gold Nanoparticles-Transferability towards Bulk.

We analyse the efficacy of machine learning (ML) interatomic potentials (IP) in modelling gold (Au) nanoparticles. We have explored the transferability of these ML models to larger systems and established simulation times and size thresholds necessary for accurate interatomic potentials. To achieve this, we compared the energies and geometries of large Au nanoclusters using VASP and LAMMPS and gained better understanding of the number of VASP simulation timesteps required to generate ML-IPs that can reproduce the structural properties. We also investigated the minimum atomic size of the training set necessary to construct ML-IPs that accurately replicate the structural properties of large Au nanoclusters, using the LAMMPS-specific heat of the Au147 icosahedral as reference. Our findings suggest that minor adjustments to a potential developed for one system can render it suitable for other systems. These results provide further insight into the development of accurate interatomic potentials for modelling Au nanoparticles through machine learning techniques.

Evaluation of Machine Learning Interatomic Potentials for the Properties of Gold Nanoparticles.

We have investigated Machine Learning Interatomic Potentials in application to the properties of gold nanoparticles through the DeePMD package, using data generated with the ab-initio VASP program. Benchmarking was carried out on Au20 nanoclusters against ab-initio molecular dynamics simulations and show we can achieve similar accuracy with the machine learned potential at far reduced cost using LAMMPS. We have been able to reproduce structures and heat capacities of several isomeric forms. Comparison of our workflow with similar ML-IP studies is discussed and has identified areas for future improvement.

Density functionals with asymptotic-potential corrections are required for the simulation of spectroscopic properties of materials.

Five effects of correction of the asymptotic potential error in density functionals are identified that significantly improve calculated properties of molecular excited states involving charge-transfer character. Newly developed materials-science computational methods are used to demonstrate how these effects manifest in materials spectroscopy. Connection is made considering chlorophyll-a as a paradigm for molecular spectroscopy, 22 iconic materials as paradigms for 3D materials spectroscopy, and the VN - defect in hexagonal boron nitride as an example of the spectroscopy of defects in 2D materials pertaining to nanophotonics. Defects can equally be thought of as being "molecular" and "materials" in nature and hence bridge the relms of molecular and materials spectroscopies. It is concluded that the density functional HSE06, currently considered as the standard for accurate calculations of materials spectroscopy, should be replaced, in most instances, by the computationally similar but asymptotically corrected CAM-B3LYP functional, with some specific functionals for materials-use only providing further improvements.

Automated Red Cell Exchange in the Management of Sickle Cell Disease.

Red cell transfusion represents one of the cornerstones of the chronic management of sickle cell disease, as well as its acute complications. Automated red cell exchange can rapidly lower the number of circulating sickle erythrocytes, without causing iron overload. Here, we describe our experience, having offered this intervention since 2011. A transient reduction in the platelet count by 61% was observed after the procedure. This was not associated with any haemorrhagic complications. Despite exposure to large volumes of blood, the alloimmunisation rate was only 0.027/100 units of red cells. The absence of any iron loading was confirmed by serial Ferriscans, performed over a number of years. However, patients with advanced chronic kidney disease showed evidence of iron loading due to reduced innate haemopoiesis and were subsequently switched to simple transfusions. A total of 59% of patients were on regular automated red cell exchange with a history of recurrent painful crises. A total of 77% responded clinically, as evidenced by at least a 25% reduction in their emergency hospital attendance for pain management. The clinical response was gradual and increased the longer patients stayed on the program. The earliest sign of clinical response was a reduction in the length of stay when these patients were hospitalised, indicating that a reduction in the severity of crises precedes the reduction in their frequency. Automated red cell exchange also appeared to be beneficial for patients with recurrent leg ulcers and severe, drug resistant stuttering priapism, while patients with pulmonary hypertension showed a dramatic improvement in their symptoms as well as echocardiographic parameters.

Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London.

BACKGROUND AND OBJECTIVES: We investigated outcomes in a UK neonatal cohort as a benchmark for care of children with sickle cell disease (SCD). DESIGN AND METHODS: Two-hundred and fifty-two children (180 with hemoglobin [Hb] SS, 64 with HbSC, and 8 with HbS/beta thalassemia), identified during 1983-2005 by universal birth screening in East London, were followed in a hospital and community-based program which included penicillin V prophylaxis from 3 months of age, 23-valent pneumococcal polysaccharide vaccine from 1993, conjugate pneumococcal vaccine from 2002 and transcranial Doppler screening from 1991. RESULTS: At the end of 2005, there were 2158 patient years of observation. The median age of the patients was 7.8 (interquartile range 3.3-13.0) years, and 2.8% of those enrolled had been lost to follow-up. The estimated survival of children with HbSS at 16 years was 99.0% (95% confidence interval, CI, 93.2 to 99.9%) and pneumococcal sepsis rate was 0.3 (95% CI 0.1-0.8) episodes per 100 patient-years. The risk of overt stroke was 4.3% (95%CI 1.5 to 11.4%) and could be further reduced by transcranial Doppler screening from infancy and transfusing all children with high-risk scans. No deaths, strokes or episodes of pneumococcal sepsis were observed in children with HbSC or HbS/beta thalassemia. The mortality rates from HbSS were significantly lower than those in other reported cohorts. INTERPRETATION AND CONCLUSIONS: Mortality in childhood SCD can virtually be eliminated in a well-resourced health service setting linking community-based care with a specialized, hospital-based center. SCD continues to cause substantial morbidity from acute complications and chronic organ damage. We recommend setting up of clinical networks to optimize the management of SCD.

Successful outcome of three patients with sickle-cell disease and fat embolism syndrome treated with intensive exchange transfusion.

Fat embolism syndrome (FES) is a rare complication of sickle-cell disease (SCD) associated with extremely high mortality rates. It affects predominantly non-SS patients and those with previously mild disease. Rapid institution of exchange transfusion with an aim to reduce HbS to very low levels as soon as FES is suspected can be life-saving.

Density functional theory for charge transfer: the nature of the N-bands of porphyrins and chlorophylls revealed through CAM-B3LYP, CASPT2, and SAC-CI calculations.

While density functional theory (DFT) has been proven to be extremely useful for the prediction of thermodynamic and spectroscopic properties of molecules, to date most functionals used in common implementations of DFT display a systematic failure to predict the properties of charge-transfer processes. While this is explicitly manifest in Rydberg transitions of atoms and molecules and in molecular charge-transfer spectroscopy, it also becomes critical for systems containing extended conjugation such as polyenes and other conducting polymers, porphyrins, chlorophylls, etc. A new density functional, a Coulomb-attenuated hybrid exchange-correlation functional (CAM-B3LYP), has recently been developed specifically to overcome these limitations, and it has been shown to properly predict molecular charge-transfer spectra. Here, we demonstrate that it predicts qualitatively reasonable spectra for porphyrin, some oligoporphyrins, and chlorophyll. However, alternate density functionals developed to overcome the same limitations such as current-density functional theory are shown, in their present implementation, to remain inadequate. The CAM-B3LYP results are shown to be in excellent agreement with complete-active-space plus second-order Møller-Plesset perturbation theory and symmetry-adapted cluster configuration interaction calculations: These depict the N and higher bands of porphyrins and chlorophylls as being charge-transfer bands associated with localization of molecular orbitals on individual pyrrole rings. The validity of the basic Gouterman model for the spectra of porphyrins and chlorophylls is confirmed, rejecting modern suggestions that non-Gouterman transitions lie close in energy to the Q-bands of chlorophylls. As porphyrins and chlorophylls provide useful paradigms for problems involving extended conjugation, the results obtained suggest that many significant areas of nanotechnology and biotechnology may now be realistically treated by cost-effective density-functional-based computational methods.

Prophylaxis of venous thromboembolism during early inpatient rehabilitation after acquired brain injury: how guidelines change management.

PURPOSE: To establish guidelines for prophylaxis of venous thromboembolism (VTE) in younger adults undergoing early inpatient rehabilitation following acquired brain injury (ABI). METHOD: A two-phase (phase 1: retrospective; phase 2: prospective) observational study was carried out involving patients admitted to an inpatient neurological rehabilitation unit during a 40-month period. In phase 1, VTE prophylaxis was prescribed on an ad hoc basis. In phase 2, prophylaxis was considered in accordance with guidelines agreed locally. The prescribing behaviour in each phase of the study was compared using a VTE risk stratification tool based on expert opinion and a review of the literature. RESULTS: Data were obtained on 94 patients in phase 1 and 23 patients in phase 2. During phase 1, the prophylactic prescribing behaviour of the referring hospitals and our unit after admission were similar ( p = 0.13). In phase 2, our prescribing behaviour had changed compared with that of the referring hospitals, with a significant increase in the proportion of patients on appropriate treatment ( p = 0.01) and a decrease in the numbers under-treated ( p = 0.002). We were also significantly less likely to under-treat ( p = 0.005) and more likely to over-treat ( p = 0.004) after admission during phase 2 compared with phase 1, whilst practice was variable in patients at moderate risk. CONCLUSIONS: Guidelines modify behaviour. They must stratify risk, particularly to avoid inconsistencies in the management of patients at moderate risk. There is a need to establish national guidelines for VTE prophylaxis during early inpatient rehabilitation after ABI; these guidelines should include a risk stratification tool.