Comparison of whole-blood sirolimus concentrations measured by EMIT-based Siemens Viva-ProE® System and LC-MS/MS in Chinese transplant patients.

Sirolimus (SRL) is commonly used in transplant patients to prevent organ transplant rejection. The current guidelines recommend to perform SRL therapeutic drug monitoring regularly to improve treatment outcomes and avoid adverse effects. Consequently, a precise and accurate method for determining SRL is crucial in clinical practice. Currently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassays have been widely adopted for determining SRL concentrations. However, previous studies have shown that immunoassays exhibit a positive bias compared to LC-MS/MS. As the new updated version of the EMIT-based Viva-E® System (SVPS), this study aims to compare SRL blood concentrations measured by the SVPS and LC-MS/MS. The residual whole-blood samples obtained from transplant patients were simultaneously analyzed using the SVPS and LC-MS/MS, respectively. The correlation between the two assays was analyzed using the linear regression analysis and Deming linear regression. The Pearson correlation coefficient and Intraclass correlation coefficient (ICC) analysis were executed. The Paired Wilcoxon test and Bland-Altman analysis were performed to assess the concordance between the two methods. The SVPS considerably increased SRL concentration value by 46.62 % as compared to the LC-MS/MS method. When SRL concentrations measured by the SVPS were above 4.0 ng/mL, there was no significant difference between the corrected SVPS concentrations after using the Deming linear regression equation, indicating their interchangeability. Given the significant disparities observed between EMIT and LC-MS/MS, it is crucial to indicate the methodology and instruments in both TDM reports and future clinical guidelines. Our study also provides the conversion formulas between the SVPS and LC-MS/MS, which can be applied as a reference for different clinical centers.

Two superconducting states with broken time-reversal symmetry in FeSe1-xSx.

Iron-chalcogenide superconductors FeSe1-xSx possess unique electronic properties such as nonmagnetic nematic order and its quantum critical point. The nature of superconductivity with such nematicity is important for understanding the mechanism of unconventional superconductivity. A recent theory suggested the possible emergence of a fundamentally new class of superconductivity with the so-called Bogoliubov Fermi surfaces (BFSs) in this system. However, such an ultranodal pair state requires broken time-reversal symmetry (TRS) in the superconducting state, which has not been observed experimentally. Here, we report muon spin relaxation (µSR) measurements in FeSe1-xSx superconductors for 0 ≤ x ≤ 0.22 covering both orthorhombic (nematic) and tetragonal phases. We find that the zero-field muon relaxation rate is enhanced below the superconducting transition temperature Tc for all compositions, indicating that the superconducting state breaks TRS both in the nematic and tetragonal phases. Moreover, the transverse-field µSR measurements reveal that the superfluid density shows an unexpected and substantial reduction in the tetragonal phase (x > 0.17). This implies that a significant fraction of electrons remain unpaired in the zero-temperature limit, which cannot be explained by the known unconventional superconducting states with point or line nodes. The TRS breaking and the suppressed superfluid density in the tetragonal phase, together with the reported enhanced zero-energy excitations, are consistent with the ultranodal pair state with BFSs. The present results reveal two different superconducting states with broken TRS separated by the nematic critical point in FeSe1-xSx, which calls for the theory of microscopic origins that account for the relation between nematicity and superconductivity.

Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation.

PURPOSE: This study aimed to investigate the interactions between posaconazole (POS) and intravenously/orally administered cyclosporine A (CsA) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: We included 118 allogeneic HSCT patients who received CsA and POS simultaneously between January 2017 and June 2020 in this study. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) before and after POS initiation was compared. RESULTS: After the initiation of POS, the level of CsA increased 1 to 2 times in 66% (78/118) of patients compared to those without POS. However, the CsA C/D ratio increased by more than threefold in 6% (7/118) of patients after POS initiation, with an increase of more than fourfold in two patients. The median C/D ratio of CsA increased from 0.89 to 1.23 (P < 0.001) and 0.78 to 1.22 (P < 0.001) after POS initiation when CsA was administered intravenously and orally, respectively. In patients who received POS at the time of transition from intravenous to oral CsA, the value increased from 1.01 to 1.38 (P = 0.001). The route of administration had no significant effect on the change in the CsA C/D ratio (P = 0.615). Additionally, we observed the time required for the C/D ratio to reach a plateau after POS initiation was similar on days 13, 8, and 15 under various scenarios. CONCLUSION: POS treatment increased blood CsA levels. A large variability was found in the fold-change in the CsA C/D ratio. Therefore, CsA doses should be adjusted by closely monitoring the blood levels of CsA after POS initiation.

Rapid, simple, and economical LC-MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring.

WHAT IS KNOWN AND OBJECTIVE: Carbapenem-resistant Gram-negative bacterial pathogens continue to threaten public health. Avibactam (AVI), a novel non-ß-lactam ß-lactamase inhibitor, has been approved for use with ceftazidime (CAZ) mainly against carbapenem-resistant Enterobacteriaceae. Therapeutic drug monitoring (TDM) is urgently needed to optimize dosage regimens to maximize efficacy, minimize toxicity, and delay the emergence of resistance. This study aims to develop and validate a rapid, simple, and economical LC-MS/MS method for simultaneous determination of CAZ/AVI in human plasma. METHODS: Samples were processed by simple protein precipitation, and gradient elution strategy was applied to separate CAZ and AVI on a reverse-phase C18 column; with subsequent detection by the mass spectrometer in a positive and negative ion switching mode. Plasma samples from patients were analysed. RESULTS AND DISCUSSION: A 4-min run of LC-MS/MS was developed. The precision, trueness, matrix effect, extraction recovery, carry-over, dilution integrity, and stability were all acceptable for a bioanalytical method. The method was successfully applied to the determination of CAZ and AVI in patients, and a considerable PK variability of CAZ/AVI was observed among patients. WHAT IS NEW AND CONCLUSION: A robust, rapid, simple, and economical LC-MS/MS method for the simultaneous determination of CAZ and AVI was developed. The considerable PK variability of CAZ/AVI among patients demonstrates the clinical significance of TDM.

New Fluoride-arsenide Diluted Magnetic Semiconductor (Ba,K)F(Zn,Mn)As with Independent Spin and Charge Doping.

We report the discovery of a new fluoride-arsenide bulk diluted magnetic semiconductor (Ba,K)F(Zn,Mn)As with the tetragonal ZrCuSiAs-type structure which is identical to that of the "1111" iron-based superconductors. The joint hole doping via (Ba,K) substitution &spin doping via (Zn,Mn) substitution results in ferromagnetic order with Curie temperature up to 30 K and demonstrates that the ferromagnetic interactions between the localized spins are mediated by the carriers. Muon spin relaxation measurements confirm the intrinsic nature of the long range magnetic order in the entire volume in the ferromagnetic phase. This is the first time that a diluted magnetic semiconductor with decoupled spin and charge doping is achieved in a fluoride compound. Comparing to the isostructure oxide counterpart of LaOZnSb, the fluoride DMS (Ba,K)F(Zn,Mn)As shows much improved semiconductive behavior that would be benefit for further application developments.

Cubic Re6+ (5d1) Double Perovskites, Ba2MgReO6, Ba2ZnReO6, and Ba2Y2/3ReO6: Magnetism, Heat Capacity, µSR, and Neutron Scattering Studies and Comparison with Theory.

Double perovskites (DP) of the general formula Ba2MReO6, where M = Mg, Zn, and Y2/3, all based on Re6+ (5d1, t2g1), were synthesized and studied using magnetization, heat capacity, muon spin relaxation, and neutron-scattering techniques. All are cubic, Fm3̅m, at ambient temperature to within the resolution of the X-ray and neutron diffraction data, although the muon data suggest the possibility of a local distortion for M = Mg. The M = Mg DP is a ferromagnet, Tc = 18 K, with a saturation moment ∼0.3 bohr magnetons at 3 K. There are two anomalies in the heat capacity: a sharp feature at 18 K and a broad maximum centered near 33 K. The total entropy loss below 45 K is 9.68 e.u., which approaches R ln 4 (11.52 e.u.) supporting a j = 3/2 ground state. The unit cell constants of Ba2MgReO6 and the isostructural, isoelectronic analogue, Ba2LiOsO6, differ by only 0.1%, yet the latter is an anti-ferromagnet. The M = Zn DP also appears to be a ferromagnet, Tc = 11 K, µsat(Re) = 0.1 µB. In this case the heat capacity shows a somewhat broad peak near 10 K and a broader maximum at ∼33 K, behavior that can be traced to a smaller particle size, ∼30 nm, for this sample. For both M = Mg and Zn, the low-temperature magnetic heat capacity follows a T3/2 behavior, consistent with a ferromagnetic spin wave. An attempt to attribute the broad 33 K heat capacity anomalies to a splitting of the j = 3/2 state by a crystal distortion is not supported by inelastic neutron scattering, which shows no transition at the expected energy of ∼7 meV nor any transition up to 100 meV. However, the results for the two ferromagnets are compared to the theory of Chen, Pereira, and Balents, and the computed heat capacity predicts the two maxima observed experimentally. The M = Y2/3 DP, with a significantly larger cell constant (3%) than the ferromagnets, shows predominantly anti-ferromagnetic correlations, and the ground state is complex with a spin frozen component Tg = 16 K from both direct current and alternating current susceptibility and µSR data but with a persistent dynamic component. The low-temperature heat capacity shows a T1 power law. The unit cell constant of B = Y2/3 is less than 1% larger than that of the ferromagnetic Os7+ (5d1) DP, Ba2NaOsO6.

Volume-wise destruction of the antiferromagnetic Mott insulating state through quantum tuning.

RENiO3 (RE=rare-earth element) and V2O3 are archetypal Mott insulator systems. When tuned by chemical substitution (RENiO3) or pressure (V2O3), they exhibit a quantum phase transition (QPT) between an antiferromagnetic Mott insulating state and a paramagnetic metallic state. Because novel physics often appears near a Mott QPT, the details of this transition, such as whether it is first or second order, are important. Here, we demonstrate through muon spin relaxation/rotation (µSR) experiments that the QPT in RENiO3 and V2O3 is first order: the magnetically ordered volume fraction decreases to zero at the QPT, resulting in a broad region of intrinsic phase separation, while the ordered magnetic moment retains its full value until it is suddenly destroyed at the QPT. These findings bring to light a surprising universality of the pressure-driven Mott transition, revealing the importance of phase separation and calling for further investigation into the nature of quantum fluctuations underlying the transition.

Comparative physiology in China 1984-2007.

We briefly summarize the history of the rise of comparative physiology in China, the research work focused on by domestic and international counterparts in the field of comparative physiology of China, and international academic exchange and collaboration during this period. We also introduce some of the interesting model systems used in past and current research. This paper is based on documents in historical materials such as the proceedings of the 1st (August 1988) to 6th (October, 2007) Comparative Physiology Academic Session of the Chinese Association for Physiological Sciences, collected physiological works in commemoration academic papers of the 70th (1926-1999) and 80th anniversary of the Chinese Association for Physiological Sciences (1926-2006), CBP and the Physiology History of China, and the authors' own research experience.