Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B

Background: HBV infection is a serious global heath problem. It is crucial to monitor this disease more closely with a non-invasive marker in clinical trials. We aimed to evaluate the predictive value of serum hyaluronate for the presence of extensive liver fibrosis and inflammation. Methods: 28 healthy volunteers and 65 patients with HBeAg negative chronic hepatitis B were enrolled. Liver biopsies scored according to Ishak system. Association of serum hyaloronate with liver fibrosis and inflammation were assessed, and cut off points for serum hyaluronate levels were identified by receiver operating characteristics (ROC) curves and their values for prediction of fibrosis and inflammation were assessed. Results: In patients with CHB serum hyaluronate had the most significant correlation and predictive values for the liver fibrosis and inflammation comparing to the other variables. At the cut off point of 126.4 ngm/ml it could discriminate extensive fibrosis from milder ones with sensitivity of 90.9% and specificity of 98.1%. With the same value it could discriminate extensive inflammation from their milder counterparts with sensitivity of 63.6% and specificity of 92.6%. Conclusion: Serum hyaluronate was the best predictor of extensive liver fibrosis and inflammation and it could discriminate subgroups of patients with chronic hepatitis B. It could be used as a non-invasive test to monitor these patients more closely with developing anti viral agents in clinical trials

High-entropy high-hardness metal carbides discovered by entropy descriptors

High-entropy materials have attracted considerable interest due to the combination of useful properties and promising applications. Predicting their formation remains the major hindrance to the discovery of new systems. Here we propose a descriptor - entropy forming ability - for addressing synthesizability from first principles. The formalism, based on the energy distribution spectrum of randomized calculations, captures the accessibility of equally-sampled states near the ground state and quantifies configurational disorder capable of stabilizing high-entropy homogeneous phases. The methodology is applied to disordered refractory 5-metal carbides - promising candidates for high-hardness applications. The descriptor correctly predicts the ease with which compositions can be experimentally synthesized as rock-salt high-entropy homogeneous phases, validating the ansatz, and in some cases, going beyond intuition. Several of these materials exhibit hardness up to 50% higher than rule of mixtures estimations. The entropy descriptor method has the potential to accelerate the search for high-entropy systems by rationally combining first principles with experimental synthesis and characterization.Comment: 12 pages, 2 figure

TRUST IN CROSS-CULTURAL B2B FINANCIAL SERVICE RELATIONSHIPS: THE ROLE OF SHARED VALUES

This is the accepted version of the following article: Houjeir, R. & Brennan, R. J, 'Trust in cross-cultural b2b financial service relationships: The role of shared values', Journal of Financial Services Marketing, June 2016, Vol 21(2): 90-102 The final publication is available at Springer via http://dx.doi.org/10.1057/fsm.2016.4Trust in business-to-business supplier–customer relationships in financial services is an area of considerable research interest. The bulk of prior empirical research in this field has concentrated on trust in business relationships within a Western cultural context. However, shared values are acknowledged to be an important antecedent to trust. The premise of this study is that in circumstances where there are substantial cultural differences between parties to a supplier–customer relationship, these differences will be reflected in shared values, which will in turn be reflected in differences in the nature of trust. A qualitative study was conducted among business bankers and their corporate clients in the context of the United Arab Emirates. In all 170 respondents were interviewed; of these, 160 were paired respondents, that is, where a client and banker from the same business relationship were interviewed (yielding 80 interview dyads). Substantial differences with respect to trust were found between relationships that involved only Emiratis, those that involved Emiratis and non-Emiratis, and those that involved only non-Emiratis. For Emiratis mutual trust is substantially based on family and clan ties and exhibits strongly affective characteristics. For non-Emiratis trust is largely based on business considerations, and exhibits strongly cognitive characteristics.Peer reviewedFinal Accepted Versio

Origin of the Joumand fluorite and barite(Pb-Zn) veins of northwest Gonabad, Iran. Evidence from trace-element and stable (S) isotope data

The Joumand fluorite deposit is located 15 Km northwest of Gonabad, Eastern Iran. The fluorite mineralization mainly occurs within metasedimentary rocks (Shemshak formation). The intrusive rocks consist of dykes with porphyritic texture and granitic composition crosscutting the Shemshak formation. These dykes outcrop near the deposit. Fluorite veins are controled by fractures and faults. The most common primary (hypogene) minerals are fluorite, barite, galena, and quartz, with minor amounts of other sulfide minerals (chalcopyrite and pyrite). The samples show a pattern characterized by an increase from the LREE to the HREE. Fluorites exhibit high Y contents, strong positive Y anomalies, slightly positive Ce and negative Eu anomalies. 34δS measurements (-2.7 to +0.25‰) are an evidence for a primary source of sulphur derived from magmas. Microthermometric measurement, as well as geological and mineralogical evidence (for example Mn oxide crusts) indicate epithermal environment for flourite

Modelling and synthesis of high-entropy refractory carbides

Bulk samples of equiatomic, hexanery (5-metal), high-entropy refractory carbides were fabricated using a combination of high-energy ball milling (HEBM), spark plasma sintering (SPS), and hot pressing (HP) annealing. To select candidate composition that are likely to form single phase high-entropy materials at lower processing temperatures (\u3c2500°C), a novel, first-principles materials design method was developed. The theory follows that for low temperature single phase formation, the different configurations should have similar energies to increase the number of thermodynamically accessible states. A partial occupation method was implemented within AFLOW to automate the generation and calculation of the different configurations. The energy distributions were then used to construct a descriptor of Entropy Forming Ability (EFA) to predict the formation of high-entropy materials. CALPHAD results were found to agree with the configuration energy range descriptor for each composition, and these carbides exhibited broad, single-phase solubility across each system, making processing possible at reasonable temperatures. Many of the complex carbide compositions, including (Hf0.2Nb0.2Ta0.2Ti0.2Zr0.2)C, (Hf0.2Nb0.2Ta0.2Ti0.2V0.2)C, (Hf0.2Nb0.2Ta0.2Ti0.2W0.2)C, and (Nb0.2Ta0.2Ti0.2V0.2W0.2)C demonstrated virtually single-phase, solid-solution compounds with the NaCl crystal structure as determined by x-ray diffraction (XRD) and energy dispersive x-ray spectroscopy (EDS), while some compositions, including (Hf0.2Mo 0.2Ta0.2W0.2Zr0.2)C and (Hf0.2Mo0.2V0.2W0.2Zr0.2)C, exhibited multiple phases. Results were found to be in good agreement with the ab initio based formulation of entropic stability, where the compositions with the highest EFA values were found to form a single rocksalt structure and compositions with the lower EFA values were found to exhibit multiple phases. Further, among the systems that were found to form single phase materials at 2500°C, artificial segregation was introduced via lower processing temperatures. In these artificially segregated samples, the extent of mixing was analyzed via peak broadening in XRD according to the formulation of Williamson and Hall [1] and compositional mapping in EDS. Results of artificially segregated samples provide continued support for the viability of the EFA formulation, where broadening was found to be more pronounced (i.e. more chemical segregation) in samples that were determined to have a lower EFA value. This work demonstrates the extension of entropic-stabilization into refractory interstitial carbides, paving the way for development of an entirely new class of UHTCs. This work is supported by the U.S. Office of Naval Research MURI program (Grant No. N00014-15- 1-2863). [1] G.. Williamson, W.. Hall, X-ray line broadening from filed aluminium and wolfram, Acta Metall. 1 (1953) 22–31. doi:10.1016/0001-6160(53)90006-6

Liver stage P. falciparum antigens highly targeted by CD4+ T cells in malaria-exposed Ugandan children

T cell responses against liver stage Plasmodium help protect against reinfection, but the antigens and epitopes targeted by these T cells are largely unknown. This knowledge gap has impeded mechanistic studies to identify the effector functions most critical for protection. We performed a bioinformatic analysis of gene expression datasets to identify plasmodial genes that are highly and selectively expressed during liver stage infection and predict epitopes within them likely to bind MHC-II molecules prevalent in Uganda. We then tested their recognition by malaria-exposed Ugandan children. In over two-thirds of the children, we detected a peripheral blood CD4+ T cell response to one or more antigens. The most highly targeted antigen, LISP1, contained several epitopes, including one that was promiscuously presented and recognized by most participants. These novel liver stage P. falciparum epitopes should be explored as potential vaccine targets and will facilitate the development of tools to interrogate antimalarial immunity at the single-cell level and inform future vaccine development efforts

Methadone dosing strategies in preterm neonates can be simplified

Aims: A dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms. Despite its abundant use, hardly any data on the pharmacokinetics (PK) of methadone is available in preterm neonates. Therefore we investigated developmental PK of methadone and evaluated current dosing strategies and possible simplification in this vulnerable population. Methods: A single-centre open-label prospective study was performed to collect PK data after a single oral dose of methadone in preterm neonates. A population PK model was built to characterize developmental PK of (R)- and (S)-methadone. Model-based simulations were performed to identify a simplified dosing strategy to reach and maintain target methadone exposure. Results: A total of 121 methadone concentrations were collected from 31 preterm neonates. A one-compartment model with first order absorption and elimination kinetics best described PK data for (R)- and (S)-methadone. Clearance increases with advancing gestational age and differs between R- and S-enantiomer, being slightly higher for the former (0.244 vs 0.167 L/h). Preterm neonates reached target exposure after 48 hours with currently used dosing schedules. Output from simulations revealed that target exposures can be achieved with a simplified dosing strategy during the first 4 days of treatment. Conclusion: Methadone clearance in preterm neonates increases with advancing gestational age and its disposition is influenced by its chirality. Simulations that account for developmental PK changes indicate a shorter methadone dosing strategy can maintain target exposure to control withdrawal symptoms. © 2019 The British Pharmacological Societ

Continues renal replacement therapy (CRRT) with disposable hemoperfusion cartridge: A promising option for severe COVID-19

Cytokine release syndrome is prevalent in severe cases of COVID-19. In this syndrome, an uncontrolled response of immune system occurs. Extracorporeal blood purification has been proven to effectively remove the released inflammatory cytokines. Here, we reported a successful case to represent our experience of extracorporeal blood purification in a patient with severe COVID-19. © 2020 The Author

Oral ibuprofen is more effective than intravenous ibuprofen for closure of a patent ductus arteriosus: can pharmacokinetic modeling help us to understand why?

Introduction: Oral ibuprofen is more effective than intravenous (IV) ibuprofen for closure of a patent ductus arteriosus (PDA). This study explored whether higher concentrations of the biologically active S-enantiomer or increased R- to S-conversion following oral dosing could explain this finding. Methods: Two datasets containing 370 S- and R-ibuprofen concentrations from 95 neonates with PDA treated with oral (n = 27, 28%) or IV ibuprofen were analyzed using nonlinear mixed effects modeling. Concentration-time profiles in typical neonates were explored and compared in different dosing or R- to S-conversion scenarios. Results: Postnatal age (PNA), gestational age (GA), and being small for GA impacted S- and R-ibuprofen clearance. Upon oral dosing, S-ibuprofen concentrations were lower compared to IV ibuprofen for a large part of the dosing interval. We could show that R- to Sconversion will not exceed 45%. Exploration of a 30% presystemic R- to S-conversion resulted in a 25-32% increase in S-ibuprofen exposure following oral administration with AUC(72h) values varying between 700-2,213 mg*h/L (oral) and 531-1,762 (IV) for the standard or 1,704-2,893 (oral) and 1,295-2,271 mg*h/L (IV) for PNA-based dosing. Discussion: The absence of higher S-ibuprofen concentrations does not support a beneficial concentration-time profile after oral dosing. While a fraction of up to 45% presystemic R- to S-conversion could not be ruled out, the impact of such a low conversion might be only relevant for the standard but not high dosing regimens, considering reported exposure-response targets. Perhaps, the lack of high peak concentrations observed following IV dosing may play a role in the observed effects upon oral dosing. 1.% 2022 The Author(s).Pharmacolog