Materials informatics for the screening of multi-principal elements and high-entropy alloys.

The field of multi-principal element or (single-phase) high-entropy (HE) alloys has recently seen exponential growth as these systems represent a paradigm shift in alloy development, in some cases exhibiting unexpected structures and superior mechanical properties. However, the identification of promising HE alloys presents a daunting challenge given the associated vastness of the chemistry/composition space. We describe here a supervised learning strategy for the efficient screening of HE alloys that combines two complementary tools, namely: (1) a multiple regression analysis and its generalization, a canonical-correlation analysis (CCA) and (2) a genetic algorithm (GA) with a CCA-inspired fitness function. These tools permit the identification of promising multi-principal element alloys. We implement this procedure using a database for which mechanical property information exists and highlight new alloys having high hardnesses. Our methodology is validated by comparing predicted hardnesses with alloys fabricated by arc-melting, identifying alloys having very high measured hardnesses.

Extending ζ-factor microanalysis to boron-rich ceramics: Quantification of bulk stoichiometry and grain boundary composition.

Accurate quantification of light elements which produce only soft X-ray lines via X-ray energy dispersive spectrometry (XEDS) has been traditionally difficult due to poor X-ray emission and detector efficiencies at low energies and significant X-ray absorption effects. The ζ-factor microanalysis method enables one to correct for these shortcomings; however, ζ-factor microanalysis has not yet been thoroughly applied to inorganic materials which are entirely or mostly composed of light elements such as boron carbide, boron nitride, or boron suboxide. This work successfully extended ζ-factor microanalysis to boron-rich ceramics and accurately determined stoichiometries of multiple boron carbides and measured grain boundary compositions of a boron carbide mixed with additives consisting of rare-earth ions. Various strategies were employed to experimentally determine a full range of ζ-factors and measurements were validated using materials of known composition including silicon hexaboride and silicon carbide. Overall, this work has shown that XEDS is a viable technique for light element quantification in (scanning) transmission electron microscopy, in terms of both the accuracy and precision, which is comparable or superior to the complementary electron energy loss spectrometry.

Recurring BALB/c mouse lung inflammatory responses to episodic allergen exposure.

This study detailed the sequence of recurring inflammatory events associated with episodic allergen exposures of mice resulting in airway hyperreactivity, sustained inflammation, goblet-cell hyperplasia, and fibrogenesis that characterize a lung with chronic asthma. Ovalbumin (OVA)-sensitized female BALB/c mice were exposed to saline-control or OVA aerosols for 1 h per day for episodes of 3 d/wk for up to 8 wk. Lung inflammation was assessed by inflammatory cell recoveries using bronchoalveolar lavages (BAL) and tissue collagenase dispersions. Cell accumulations were observed within airway submucosal and associated perivascular spaces using immunohistochemical and tinctorial staining methods. Airway responsiveness to methacholine aerosols were elevated after 2 wk and further enhanced to a sustained level after wk 4 and 8. Although by wk 8 diminished OVA-induced accumulations of eosinophils, neutrophils, and monocyte-macrophages were observed, suggesting diminished responsiveness, the BAL recovery of lymphocytes remained elevated. Airway but not perivascular lesions persisted with a proliferating cell population, epithelial goblet-cell hyperplasia, and evidence of enhanced collagen deposition. Examination of lung inflammatory cell content before the onset of the first, second, and fourth OVA exposure episodes demonstrated enhancements in residual BAL lymphocyte and BAL and tissue eosinophil recoveries with each exposure episode. Although tissue monocyte-macrophage numbers returned to baseline prior to each exposure episode, the greatest level of accumulation was observed after wk 4. These results provide the basis for establishing the inflammatory and exposure criteria by which episodic environmental exposures to allergen might result in the development of a remodeled lung in asthma.

Cardiopulmonary bypass temperature and brain function.

A debate has emerged in recently published studies about the optimum cardiopulmonary bypass temperature for good neurological outcome - warm vs. cold, i.e. normothermic vs. hypothermic. Although many comparative studies have been performed, the results of these studies are inconclusive and are difficult to interpret. Brain function has been studied in terms of neurological and neuropsychological outcome, protein S100beta levels as a marker of brain damage, and cerebral oxygenation using jugular bulb oximetry and near-infrared spectroscopy. The studies produce no conclusive proof of the superiority of warm or cold cardiopulmonary bypass. However, it appears that any degree of bypass hypothermia (< 35 degrees C) may protect the brain. On the other hand, even a slight increase in bypass temperature to > 37 degrees C may cause marked brain injury.

Changes in cerebral oxygenation during cold (28 degrees C) and warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat) in patients undergoing coronary artery bypass graft surgery.

BACKGROUND: Impaired cerebral oxygenation, which is reflected by measuring jugular bulb oxygenation, is thought to play an important role in the development of neurological injury after cardiac operations with cardiopulmonary bypass (CPB). The effects of cardiopulmonary temperature and blood gas strategy on cerebral oxygenation are not fully appreciated. METHODS: Sixty patients were randomly allocated into four equal groups (cold alpha-stat, cold pH-stat, warm alpha-stat and warm pH-stat) to compare the effect of these perfusion strategies on cerebral oxygenation monitored by jugular bulb oximetry [jugular bulb oxygen saturation (SjO(2)) and arterial-jugular bulb oxygen content difference (AjDO(2))]. Jugular bulb oxygen saturation and AjDO(2) were measured before CPB, after 5, 20, 40 min on CPB, at start and end of rewarming, 5 min before the end of CPB and 10 min after CPB. Two-way analysis of variance was used to model the lowest SjO(2) and highest AjDO(2) during CPB, with CPB temperature and blood gas management as contributing factors. RESULTS: Significant changes in SjO(2) were only related to the type of blood gas management, with no significant difference between warm and cold CPB patients. In addition, during rewarming, desaturation (SjO(2)

A comparison of 8% and 12% sevoflurane for inhalation induction in adults.

Sevoflurane is a non-pungent volatile anaesthetic agent with a low blood-gas solubility coefficient. It has been studied in concentrations of up to 8% for induction of anaesthesia. Previous work has suggested that there may be a ceiling effect with increasing concentration of sevoflurane above 6%, but there are no published studies using 12% sevoflurane. This study compared 8 and 12% sevoflurane to induce anaesthesia in adults. Sevoflurane was administered using two adapted datum vaporisers with the interlock removed. Induction with 12% sevoflurane compared to 8% sevoflurane produced a significant decrease in the time to achieve central pupils, corresponding to surgical anaesthesia and the third part of Guedel's stage 3 of anaesthesia (mean time (SD) 201 s (81) and 247 s (39), respectively, p < 0.05). Twelve-percent sevoflurane produced a similar stable cardiovascular profile to 8% sevoflurane, and there was no increase in respiratory complications.

A pilot study of evaluation of cerebral function by S100beta protein and near-infrared spectroscopy during cold and warm cardiopulmonary bypass in infants and children undergoing open-heart surgery.

Cerebral injury in children undergoing cardiopulmonary bypass (CPB) remains a major source of morbidity. The effect of cardiopulmonary bypass temperature on cerebral function in terms of serum S100beta protein level and cerebral oxygenation monitored by near infrared spectroscopy (NIRO-300) in children is not known. In this study, 18 children undergoing open-heart surgery at the Hospital for Sick Children in London were equally assigned by minimisation to warm (35 +/- 1 degrees C) or cold (25 +/- 1 degrees C) CPB. Changes in S100beta protein and cerebral oxygenation were studied in both groups. S100beta protein serum level increased significantly after CPB in both groups. There was no significant difference in serum S100beta protein concentrations between the two groups. However, cerebral oxygenation in terms of tissue oxygen index (TOI) was significantly impaired during rewarming from cold CPB. Five patients were desaturated (TOI < 50%) during rewarming in the cold bypass group compared to two in the warm patients. This study supports the use of warm CPB in children undergoing open-heart surgery, although further studies recruiting more patients are warranted.

Evaluation of personal, environmental and biological exposure of paediatric anaesthetists to nitrous oxide and sevoflurane.

Paediatric anaesthetists are at higher risk of exposure to waste anaesthetic gases, which often exceed set safety limits. Recommended personal diffusive sampling techniques for monitoring exposure to waste anaesthetic gases may not give a true profile of exposure and hence biological sampling may also be necessary. We evaluated the exposure of paediatric anaesthetists to nitrous oxide and sevoflurane as assessed by personal environmental and biological samples. The influence of venue and technique, and the strength of the relationship among the various sampling techniques were analysed. The study found that exposure to nitrous oxide during paediatric anaesthetic inductions is still a major problem, although exposure to sevoflurane was usually within the accepted limits. The type of breathing system used and the presence of scavenging seem to influence this exposure, though surprisingly, the induction technique or the methods of airway control do not. No significant relationship was found between the various biological indicators measured.

Changes in serum S100beta protein and Mini-Mental State Examination after cold (28 degrees C) and warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat).

BACKGROUND: The effect of cardiopulmonary bypass temperature and blood gas management on the brain is still controversial. This study was designed to compare the changes in S100beta protein concentration and Mini-Mental State Examination in patients undergoing cold (28 degrees C) vs. warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat). METHODS: Sixty patients were randomly allocated to one of four equal groups (cold alpha-stat, cold pH-stat, warm alpha-stat, warm pH-stat). Serum S100beta concentrations were measured before CPB, directly after CPB, at 4.5 h and at 24 h after CPB. Mini-Mental State Examination was performed one day before surgery and on day five after the operation. Antegrade warm blood cardioplegia (37 degrees C) was used in all patients. RESULTS: There was no significant difference in postoperative S100beta protein levels between the four groups. Also, there was no interaction between bypass temperature and type of blood gas strategy on S100beta levels after bypass (directly after bypass, 4.5 h and 24 h after bypass). Mini-Mental State Examination score was not affected by blood gas strategy but it was significantly lower in patients undergoing cold cardiopulmonary bypass surgery: median (range), 26 (12-29) vs. 27 (23-30) in warm patients, P = 0.014. There was no significant correlation between Mini-Mental State Examination score 5 days after CPB and S100beta levels at any of the studied time-points after CPB. CONCLUSION: These results support the use of warm CPB (34 degrees C) in patients undergoing coronary artery bypass surgery regardless of the type of blood gas strategy.

Gastric residual volume in children: a study comparing efficiency of erythromycin and metoclopramide as prokinetic agents.

Metoclopramide may be used to stimulate gastric emptying when anaesthetizing children for emergency operations. Unfortunately, metoclopramide is associated with extrapyramidal side effects. Erythromycin, a motilin receptor agonist, is a prokinetic agent but its use has been little investigated in children. This randomized double-blind study compared the effects of premedication with oral metoclopramide 0.15 mg kg(-1) or erythromycin 1 mg kg(-1) on gastric emptying in 80 children undergoing tonsillectomy. Pre-operative fluids, premedication and anaesthetic technique were standardized and gastric volume was measured with an orogastric tube. Post-operative nausea and vomiting was recorded. Metoclopramide and erythromycin produced similar gastric volumes (0.29 and 0.24 ml kg(-1)) and there was no difference in post-operative vomiting. In the erythromycin group there were more patients with negative aspirates (45.9%) than in the metoclopramide group (35.1%), but the difference was not statistically significant. These results indicate that erythromycin may be as effective as metoclopramide as a prokinetic agent.

Spatially resolved spectroscopy (NIRO-300) does not agree with jugular bulb oxygen saturation in patients undergoing warm bypass surgery.

PURPOSE: Near infrared spectroscopy (NIRS) is a promising non-invasive method for continuous monitoring of cerebral oxygenation during cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to study the agreement between tissue oxygen index (TOI) measured by spatially resolved spectroscopy (NIRO-300) and jugular bulb oxygen saturation (SjO2) in patients undergoing warm coronary bypass surgery. METHODS: Seventeen patients undergoing warm coronary artery bypass surgery were studied. NIRS was continuously monitored and was averaged before CPB, five, 20, 40, 60 min on CPB, five minutes before end of CPB and ten minutes after CPB to coincide with SjO2 measurements. Bypass temperature was maintained at 34-37 degrees C. RESULTS: Bland and Altman analysis showed a bias (TOI-SjO2) of -6.7%, and wide limits of agreement (from 16% to -28%) between the two methods. In addition, mean TOI was lower than mean SjO2 during and after CPB. We observed a statistically significant correlation between arterial carbon dioxide and SjO2 measurements (r2=0.33; P=0.0003), but the former did not correlate with TOI values (r2=0.001; P=0.7). CONCLUSION: Our results demonstrate a lack of agreement between SjO2 and TOI for monitoring cerebral oxygenation during cardiac surgery. We conclude that the two methods are not interchangeable.

Changes in jugular bulb oxygenation in patients undergoing warm coronary artery bypass surgery (34-37 degrees C).

BACKGROUND AND OBJECTIVE: Imbalance between cerebral oxygen supply and demand is thought to play an important role in the development of cerebral injury during cardiac surgery with cardiopulmonary bypass. METHODS: We studied jugular bulb oxygen saturation, jugular bulb oxygen tension, arterial-jugular bulb oxygen content difference and oxygen extraction ratio in 20 patients undergoing warm coronary artery bypass surgery (34-37 degrees C) with pH-stat blood gas management. RESULTS: Only two patients showed desaturation (jugular bulb oxygen saturation < 50%) at 5 min on bypass, and none from 20 min onwards. Multiple regression models were performed after using bypass temperature, mean arterial pressure, cerebral perfusion pressure, haemoglobin concentration and arterial carbon dioxide tension as independent variables, and arterial-jugular bulb oxygen content difference, jugular bulb oxygen saturation, oxygen extraction ratio and jugular bulb oxygen tension as individual dependent variables. CONCLUSIONS: We found that jugular bulb oxygen saturation, jugular bulb oxygen tension and oxygen extraction ratio are mainly dependent on arterial carbon dioxide tension, and arterial-jugular bulb oxygen content difference is dependent on arterial carbon dioxide tension and the bypass temperature. Our results suggest jugular bulb oxygenation is mainly dependent on arterial carbon dioxide tension during warm cardiopulmonary bypass.

Jugular bulb oximetry during cardiac surgery.

Imbalance between cerebral oxygen supply and demand is thought to play an important role in the development of cerebral injury during cardiac surgery. This article presents an overview of cerebral oxygenation monitored by jugular bulb oximetry during cardiac surgery with cardiopulmonary bypass. The general principles of jugular bulb oximetry including physiology, intermittent and continuous monitoring, technical considerations, limitations and potential complications are discussed. Different applications of jugular bulb oximetry during bypass surgery and the possible therapeutic approaches to impaired cerebral oxygenation are described.

Serum S100 protein as a marker of cerebral damage during cardiac surgery.

The identification of a serum marker to assist in the diagnosis of cerebral injury after cardiac surgery is potentially useful. S100 protein is an early marker of cerebral damage. It is released after cardiac surgery performed under cardiopulmonary bypass (CPB). Its level is correlated with the duration of CPB, deep circulatory arrest and aortic cross-clamping. Increased levels of S100 protein are correlated with the age of the patient and the number of microemboli, especially during aortic cannulation. Perioperative cerebral complications such as stroke, delayed awakening and confusion are associated with increased levels of S100 protein directly after bypass and from 15 to 48 h after it. In addition, increased levels of S100 protein are related to neuropsychological dysfunction after cardiac surgery. S100 protein has early and late release patterns after CPB; the early pattern may be due to sub-clinical brain injury. The late release pattern may be due to perioperative cerebral complications. Patients undergoing intracardiac operations combined with coronary artery bypass surgery are more susceptible to brain injury and have higher levels of S100 after CPB. Furthermore, adults and children undergoing deep circulatory arrest are more susceptible to brain injury, in terms of higher S100 protein release after CPB. Serum S100 protein levels are reduced after using arterial line filtration and covalent-bonded heparin to coat the inner surface of the CPB circuit.

Early release pattern of S100 protein as a marker of brain damage after warm cardiopulmonary bypass.

Warm blood cardioplegia may be more beneficial to the heart than cold cardioplegia, but the effects of warm cardiopulmonary bypass and warm blood cardioplegia on the brain are controversial. S100 protein is an early marker of brain damage and has been detected after cold cardiopulmonary bypass. We studied S100 concentrations in 20 patients undergoing coronary artery bypass surgery before and after warm cardiopulmonary bypass (34-37 degrees C) using warm blood cardioplegia (37 degrees C) for all patients. The peak level of S100 protein occurred immediately after warm cardiopulmonary bypass, then decreased progressively until the last measurement at 4.5 h after bypass. The peak level appears to be dependent upon the age of the patient, with the following regression equation: y = -3.2 + 0.08x, where y is S100 protein concentration in microg.l-1 and x is patient age in years. Further studies are needed to investigate the clinical significance of this early release pattern. Patient age should be taken into account when studying S100 protein levels after cardiopulmonary bypass.