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BackgroundObservational research suggests that hypotension is a potential hazard factor of delirium. Nevertheless, previous observational articles are limited in their ability to establish causality between hypotension and delirium. The present study was sought to explore the genetic causal relationship between these two conditions using two-sample Mendelian randomization (MR).MethodsGenome-wide association study (GWAS) summarized data for hypotension and delirium were obtained from the FinnGen Consortium. The researchers utilized several statistical methods, such as inverse-variance weighted (IVW), weighted median, MR Egger, weighted mode, and simple mode in conducting the MR statistical analysis. In order to identify heterogeneity among the MR outcomes, we employed the Cochrane’s Q test. Furthermore, we used the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test to examine horizontal pleiotropy.ResultsThe findings revealed that hypotension was identified as an independent hazard variable for delirium (p = 0.010, odds ratio [OR] [95% confidence interval (CI)] = 1.302 [1.066–1.592]) using the IVW method. The presence of horizontal pleiotropy was found to have minimal impact on establishing causal relationship (p = 0.999), and there was no evidence to suggest heterogeneity between genetic variations (p = 0.379). Additionally, the leave-one-out method demonstrated the stability and robustness of this association.ConclusionWe performed two-sample MR analyses and found evidence of a genetic causal relationship between hypotension and delirium. Our findings suggest that individuals with a genetic predisposition for hypotension may have a higher risk of developing delirium. This suggests that interventions aimed at improving perioperative hypotension could aid in limiting the incidence of delirium.

Abstract Cuprizone is an amide compound that has been wildly used in various animal studies, such as in the investigation of remyelination in mouse model. It is important to control the amount of cuprizone dosed in animals to be consistent as different amounts may lead to different clinical observations. Cuprizone is usually administrated as a minor component (i.e., 0.3%) of a mixture with powdered or pelleted rodent chow. Its low content, combined with the complex nature of chow, represents a significant challenge for the quantification of cuprizone in the mixture. To the best of our knowledge, no method has been reported in the literature so far. In this study, a simple, selective, and sensitive hydrophilic interaction liquid chromatographic method was developed for the quantification of cuprizone in cuprizone pre-clinical formulations. The analytical method comprises a fast ultrasound assisted extraction with acetonitrile/water as a solvent followed by gradient separation using a Waters Xbridge HILIC column with 0.1% TFA in water and acetonitrile as mobile phases and UV detection at 220 nm. The specificity, linearity, accuracy, repeatability, and limit of quantitation (LOQ) of the method were established. The method was determined to be linear in the range of 10–200 μg/mL. Accuracy was assessed by spiking a chow placebo with various amounts of a cuprizone reference standard to achieve target concentration levels and the recoveries were within the acceptance criterion of 90–110% of the target concentrations. Repeatability was demonstrated at the nominal concentration of 100 µg/mL and LOQ level of 2.5 μg/mL. This method has been demonstrated to be suitable for its intended use and has been successfully applied to the quantification of low levels of cuprizone in chow formulations. It was found that the cuprizone content in chow could varied significantly between batches and the potential causes of the variability were investigated.

BackgroundOver the last two decades, the prevalence of colistin resistance among the members of Enterobacteriaceae has been increasing, particularly among Klebsiella pneumoniae isolates; this limits the potential use of colistin and leads to worsened clinical outcomes.MethodsWe investigated the prevalence and genetic characteristics of colistin-resistant K. pneumoniae (COLR-KP) in clinical isolates using genomic sequencing.ResultsIn total, 53 K. pneumoniae isolates (4.5%, 53/1,171) were confirmed as COLR-KP, of which eight isolates carried mobile colistin-resistant (mcr) gene. Although the overall prevalence rate (0.7%, 8/1,171) of mcr-like genes in clinical K. pneumoniae remained relatively low, the presence of mcr (15.1%, 8/53) among the COLR-KP isolates indicated that the mobile resistance gene was already widespread among K. pneumoniae isolates in hospital setting. We randomly selected 13 COLR-KP isolates (four mcr-bearing and nine non-mcr-bearing isolates) for whole-genome sequencing, including two pandrug-resistant and four sequence type 11 (ST11) isolates. Phylogenetic analysis revealed that all COLR-KP isolates were genetically diverse. Among the four mcr-bearing isolates, three (KP4, KP18, and KP30) were positive for mcr-1 and one (KP23) for mcr-8; none of the other mcr genes were detected. The mcr-1 in the KP4 and KP30 isolates were located in an IncX4 plasmid (approximately 33 kb) and could be successfully transferred to Escherichia coli J53AZR. In contrast, for the mcr-8-bearing plasmid in KP23 (IncFII), colistin resistance could not be transferred by conjugation. The mcr-1-producing isolate KP18 coexists a novel plasmid-carried tigecycline resistance gene tmexCD1-toprJ1. The most common chromosomal mutation associated with colistin resistance was a T246A amino acid substitution in PmrB, which was identified in most COLR-KP isolates (11/13, 84.6%). All ST11 isolates additionally had an R256G amino acid substitution. Critical virulence factors associated with hypervirulent K. pneumoniae were detected in four COLR-KP isolates; these virulence factors included aerobactin, salmochelin, and yersiniabactin.ConclusionWe found that mcr-bearing COLR-KP emerged in our hospital and was growing at an increasing rate. Simultaneous emergence of hypervirulence and colistin–tigecycline–carbapenem resistance in the epidemic clone ST11 K. pneumoniae was also observed; this highlights the significance of active and continuous surveillance.

Abstract This paper is concerned with the Black–Scholes–Barenblatt equation ∂tu+r(x∂xu−u)+G(x2∂xxu)=0 $\partial _{t}u+r(x\partial _{x}u-u)+G(x^{2}\partial _{xx}u)=0$, where G(α)=12(σ‾2−σ_2)|α|+12(σ‾2+σ_2)α $G(\alpha )=\frac{1}{2}(\overline{\sigma}^{2}-\underline{\sigma}^{2})|\alpha |+\frac{1}{2}(\overline{\sigma}^{2}+\underline{\sigma}^{2})\alpha $, α∈R $\alpha \in \mathbb{R}$. This equation is usually used for derivative pricing in the financial market with volatility uncertainty. We discuss a strict comparison theorem for Black–Scholes–Barenblatt equations, and study strict sub-additivity of their solutions with respect to terminal conditions.

Candida auris emerged as a pathogenic species of fungus that causes severe and invasive outbreaks worldwide. The fungus exhibits high intrinsic resistance rates to various first-line antifungals, and the underlying molecular mechanism responsible for its multidrug resistance is still unclear. In this study, a transcriptomic analysis was performed between two C. auris isolates that exhibited different anti-drug patterns by RNA-sequencing, namely, CX1 (anti-drug sensitive) and CX2 (resistant). Transcriptomic analysis results revealed 541 upregulated and 453 downregulated genes in the resistant C. auris strain compared with the susceptible strain. In addition, our findings highlight the presence of potential differentially expressed genes (DEGs), which may play a role in drug resistance, including genes involved in ergosterol and efflux pump biosynthesis such as SNQ2, CDR4, ARB1, MDR1, MRR1, and ERG genes. We also found that Hsp related genes were upregulated for expression in the anti-drug-resistant strain. Biofilm formation and growth conditions were also compared between the two isolates. Our study provides novel clues for future studies in terms of understanding multidrug resistance mechanisms of C. auris strains.

Uncertainty propagation of large-scale discrete supply chains can be prohibitive when numerous events occur during the simulated period and when discrete-event simulations (DES) are costly. We present a time-bucket method to approximate and accelerate the DES of supply chains. Its stochastic version, which we call the L(logistic)-leap method, can be viewed as an extension of the leap methods (e.g., τ-leap [36]and D-leap [6] developed in the chemical engineering community for the acceleration of stochastic DES of chemical reactions). The L-leap method instantaneously updates the system state vector at discrete time points, and the production rates and policies of a supply chain are assumed to be stationary during each time bucket. We propose using the multilevel Monte Carlo (MLMC) method to efficiently propagate the uncertainties in a supply chain network, where the levels are naturally defined by the sizes of the time buckets of the simulations. We demonstrate the efficiency and accuracy of our methods using four numerical examples derived from a real-world manufacturing material flow application. In these examples, our multilevel L-leap approach can be faster than the standard Monte Carlo (MC) method by one or two orders of magnitude without compromising accuracy.

The Biqian-10 block, located in Henan Oilfield of Sinopic, contains many thin and interbedded reservoirs, which have been operated by cyclic steam stimulation for 20 years or more. Therefore, it is a challenge to implement the conventional steam flooding. In order to improve the recovery of steam flooding, urea was used to assist steam flooding. Urea can decompose into CO2 and NH3, which are beneficial to enhance oil recovery (EOR). For the sake of exactly quantifying the mechanism of urea assisted steam flooding (UASF), the UASF model was built according to the experimental results. The simulation results show that CO2 is the key point for EOR, and its pressurization function is more effective than the decrease in oil viscosity by dissolving CO2. The emulsification of crude oil for NH3 is weak in interfacial tension tests; thus the effect of emulsification can be ignored in the simulation. The UASF can improve the recovery by about 17.4%, which is 6.8% higher than steam flooding.

CO2 injection is an effective technique for improved oil recovery in light oil reservoirs, especially for water flooding abandoned reservoirs. In this study, the lower part of Es1 reservoirs in Pucheng oilfield was introduced as the target reservoir. By studying the minimum miscible pressure in CO2 flooding, the reservoir could achieve miscible flooding. Long core displacement experiments proved that water alternating CO2 flooding could significantly improve the recovery. For the reservoir characteristics, anti-corrosion technology in the process of injection was researched, and the H-20 inhibitor was screened. A channeling blocking agent in combination with the delayed expansion of gel particles and cross-linked copolymer was used to control the gas fluidity. The Pu 1-1 well groups were optimized to conduct a field trial. The cumulative injected liquid CO2 was 19219.95 ton, 0.248 PV and the cumulative increasing oil was 4520.9 t. The predicted recovery will increase by 8.3%. The successful implementation of the project can provide technical attempt for completion of energy to succeed and energy-saving emission reduction targets.

A study was carried out to provide a detailed comparison of the binding modes of the two complexes formed between an oligodeoxynucleotide containing a two-base bulge and SCA-[alpha]2 and provide new insights into the importance of shape and space, as opposed to simple nucleotide sequence. Results reveal that SCA-[alpha]2 has a better hand-in-glove fit at the bulge site, making it an ideal platform for the placement of moieties that could react covalently with the DNA and for generating congeners specific for bulges in RNA.

The study was conducted to establish the biological significance of DNA bulge binding of the analogues by assessing their ability to block bulge-specific strand cleavage by NCS-chrom the most potent and highly specific strand cleaver at DNA bulges. The analogues were found to interfere with bulge-specific cleavage by NCS-chrom and the ability of bulged DNA to serve as a template for DNA polymerase 1 in accordance with their binding affinities for DNA containing a two-base bulge.

Microcrystal electron diffraction (MicroED) has established its complementary role alongside X-ray diffraction in crystal structure elucidation. Unfortunately, kinematical refinement of MicroED data lacks the differentiation power to assign the absolute structure solely based on the measured intensities. Here we report a method for absolute configuration determination via MicroED by employing salt formation with chiral counterions. [ABSTRACT FROM AUTHOR]

We consider a general formulation of the random horizon principal-agent problem with a continuous payment and a lump-sum payment at termination. In the European version of the problem, the random horizon is chosen solely by the principal with no other possible action from the agent than exerting effort on the dynamics of the output process. We also consider the American version of the contract, where the agent can also quit by optimally choosing the termination time of the contract. Our main result reduces such nonzero-sum stochastic differential games to appropriate stochastic control problems which may be solved by standard methods of stochastic control theory. This reduction is obtained by following the Sannikov [Rev. Econom. Stud., 75 (2008), pp. 957-984] approach, further developed in [J. Cvitani\'c, D. Possama\"{\i}, and N. Touzi, Finance Stoch., 22 (2018), pp. 1-37]. We first introduce an appropriate class of contracts for which the agent's optimal effort is immediately characterized by the standard verification argument in stochastic control theory. We then show that this class of contracts is dense in an appropriate sense, so that the optimization over this restricted family of contracts represents no loss of generality. The result is obtained by using the recent well-posedness result of random horizon second-order backward SDEs in [Y. Lin, Z. Ren, N. Touzi, and J. Yang, Electron. J. Probab., 25 (2020), 99]. [ABSTRACT FROM AUTHOR]

Polycrystalline GaAs films are synthesized using economical, simple and environment-friendly electrodeposition technique. Enhanced technological parameters produce high quality films. Electrodeposition of polycrystalline GaAs films are performed on SnO2-coated glass and Ti substrates. Energy spectrum analyses are used to measure deposition on film materials.

Abstract Background Cerebral infarction (CI) is an unusual complication in patients with bleeding disorders. To our knowledge, this is the first case of postoperative internal border-zone infarction (I-BZI) from Hemophilia A. Case presentation We present a case of Hemophilia A developing I-BZI, after surgical treatment of giant hemophilic pseudotumor. A 36-year-old man was introduced from other hospital by Hemophilia with giant hemophilic pseudotumor in his left thigh. Patient and his relatives did not have a history of thrombophilia. After excluding the relevant surgical contraindications, we performed the operation of pseudotumor resection. Prior to surgery, blood tests revealed hemoglobin of 137 g/L. FVIII activity was 1.5%. Activated partial thromboplastin time (APTT) was 71.50 s and D-dimer was 3.33 mg/L FEU. Immediately before surgery, the patient received an intravenous infusion of FVIII products (Xyntha®) at a dose of 3500 IU for his body weight of 80 kg. Post-operative day two (POD2), patient developed vomiting, decreased response, and dysarthria. Hemoglobin was 54 g/L with blood pressure of 110/70 mmHg. Magnetic resonance imaging of the brain showed there were multiple acute cerebral infarctions in bilateral lateral ventricles (internal border zone) and multiple ischemic foci in the white matter areas and basal ganglia of the bilateral cerebral hemispheres. This case suggested that acute severe anemia can be one of the causes of I-BZI. Conclusions For the treatment of I-BZI caused by acute anemia from Hemophilia A, volume expansion, red blood cell supplement and continuous improvement of coagulation with suitable dose of factor VIII (FVIII) should be considered to improve prognosis.

Loosely speaking, causal transport plans are a relaxation of adapted processes in the same sense as Kantorovich transport plans extend Monge-type transport maps. The corresponding causal version of the transport problem has recently been introduced by Lassalle. Working in a discrete time setup, we establish a dynamic programming principle that links the causal transport problem to the transport problem for general costs recently considered by Gozlan et al. Based on this recursive principle, we give conditions under which the celebrated Knothe-Rosenblatt rearrangement can be viewed as a causal analogue to the Brenier map. Moreover, these considerations provide transport-information inequalities for the nested distance between stochastic processes pioneered by Pflug and Pichler and so serve to gauge the discrepancy between stochastic programs driven by different noise distributions. [ABSTRACT FROM AUTHOR]

Abstract Background We investigated the image quality of 11C, 68Ga, 18F and 89Zr, which have different positron fractions, physical half-lifes and positron ranges. Three small animal positron emission tomography/computed tomography (PET/CT) systems were used in the evaluation, including the Siemens Inveon, RAYCAN X5 and Molecubes β-cube. The evaluation was performed on a single scanner level using the national electrical manufacturers association (NEMA) image quality phantom and analysis protocol. Acquisitions were performed with the standard NEMA protocol for 18F and using a radionuclide-specific acquisition time for 11C, 68Ga and 89Zr. Images were assessed using percent recovery coefficient (%RC), percentage standard deviation (%STD), image uniformity (%SD), spill-over ratio (SOR) and evaluation of image quantification. Results 68Ga had the lowest %RC ( 85%) and lowest %STD for the 5 mm rod across all systems. For 11C and 89Zr, the maximum %RC was close (> 76%) to the %RC with 18F. A larger SOR were measured in water with 11C and 68Ga compared to 18F on all systems. SOR in air reflected image reconstruction and data correction performance. Large variation in image quantification was observed, with maximal errors of 22.73% (89Zr, Inveon), 17.54% (89Zr, RAYCAN) and − 14.87% (68Ga, Molecubes). Conclusions The systems performed most optimal in terms of NEMA image quality parameters when using 18F, where 11C and 89Zr performed slightly worse than 18F. The performance was least optimal when using 68Ga, due to large positron range. The large quantification differences prompt optimization not only by terms of image quality but also quantification. Further investigation should be performed to find an appropriate calibration and harmonization protocol and the evaluation should be conducted on a multi-scanner and multi-center level.

An LC-MS-NMR platform is demonstrated, which combines two innovations in microscale analysis, nanoSplitter LC-MS and microdroplet NMR, for the identification of unknown compounds found at low concentrations in complex sample matrixes as frequently encountered in metabolomics or natural products discovery. The nanoSplitter provides the high sensitivity of nanoelectrospray MS while allowing 98% of the HPLC effluent from a large-bore LC column to be collected and concentrated for NMR. Microdroplet NMR is a droplet microfluidic NMR loading method providing several-fold higher sample efficiency than conventional flow injection methods. Performing NMR offline from LC-UV-MS accommodates the disparity between MS and NMR in their sample mass and time requirements, as well as allowing NMR spectra to be requested retrospectively, after review of the LC-MS data. Interpretable 1D NMR spectra were obtained from analytes at the 200-ng level, in 1 h/well automated NMR data acquisitions. The system also showed excellent intra- and interdetector reproducibility with retention time RSD values less than 2% and sample recovery on the order of 93%. When applied to a cyanobacterial extract showing antibacterial activity, the platform recognized several previously known metabolites, down to the 1% level, in a single 30-μg injection, and prioritized one unknown for further study. [ABSTRACT FROM AUTHOR]

An ion-pair reversed-phase nano-high-performance liquid chromatography (IP-RP-nano-HPLC) method using a monolithic poly(styrene—divinylbenzene) (PS—DVB) column coupled to nanoelectrospray ionization mass spectrometry (nano-ESI-MS) was evaluated to separate and identify isomeric oligonucleotide adducts derived from the covalent binding of (±)-anti-7r,8t-dihydroxy-9t, 10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(±)-anti-BPDE] to double-stranded (ds) 5′-PO4--ACCCGCGTCCGCGC-3′/5′- GCGCGGGCGCGGGT-3′ oligonucleotide. The influence of three different nanospray emitters on electrospray signal was evaluated in terms of analyte ion sensitivity. The best nanoelectrospray performance for the oligonucleotides was observed with the distal metal-coated emitter. The performance of three different stationary phases was also investigated. The chromatographic separation performance of the polymeric monolithic PS—DVB stationary phase significantly surpassed that of columns packed with the microparticulate sorbents C18 or PS—DVB. Different mobile phase organic solvents and ion-pairing reagents were also evaluated. An optimized mobile phase consisting of methanol and 25 mM triethylammonium bicarbonate resulted in the best chromatographic resolution and increased MS sensitivity of the oligonucleotides. By using a monolithic PS—DYB stationary phase fabricated in a nanocolumn, four positional isomeric (±).BPDE—oligo-nucleotide adducts were separated and identified. In addition to four of the possible five positional isomers, three positional isomers were also resolved to several diastereoisomers, although their stereostructures could not be identified in the absence of reference standards. [ABSTRACT FROM AUTHOR]

In this study, six Chinese strains of Mycoplasma mycoides subsp, mycoides small colony type (MmmSC) isolated between 1953-1960 were analysed and their molecular characteristics compared to those of the African PG1 and Afade strains, the European C305 and 138/5 strains and the closely related caprine M. mycoides subsp, mycoides large colony type Y-goat strain. PCR amplification of long DNA fragments showed that the six Chinese strains, the PG1 strain and the Y-goat strain, just like Afade, did not have the 8.84 kb deletion characteristic of the European strains C305 and 138/5. In comparison, the lppB gene sequence of the six MmmSC Chinese strains was found to be 99% homologous to that of PGl and Afade, but <93% homologous to the Y-goat sequence. The anti-rLppB antiserum reacted with PGI, Y-goat and the six Chinese strains at 67 kDa sites in Western blot, indicating that the lppB gene and its encoding protein exist in the Chinese strains. Multilocus sequence analysis (MLSA) of MmmSC strains from various regions confirmed that the Chinese strains were identical to the African and Australian cluster. This finding was further supported by the outcome of selective primer amplification. Based on these results, it is suggested that CBPP in China may have originated from Australia. [ABSTRACT FROM AUTHOR]