Critical Pairs Research Articles

Abbott ARCHITECT STAT Contemporary Troponin I Outlier Detection and Prevention of Erroneous Outlier Result Reporting Using an Immediate Repeat Testing Protocol: A 1-Year Summary

Abstract Objectives The laboratory sought to monitor and eliminate reported patient cardiac troponin outlier results using the Abbott ARCHITECT STAT Contemporary Troponin-I test. Methods The laboratory implemented an immediate repeat test for all patient samples yielding an Abbott ARCHITECT STAT contemporary Troponin I concentration greater than the combined male and female 99th percentile of 28 ng/L. The lower troponin concentration of the paired testing was reported. Samples with reference range troponin concentration were reported without repeat testing. Blood collected in Becton Dickinson Vacutainer PST Gel and Lithium Heparin tubes was centrifuged using a HemoCue StatSpin Express 4 centrifuge 4,000 g × 5 minutes and immediately tested on the primary tube. Troponin outliers were defined as paired samples showing a percentage change based on the low value of the pair exceeding the significant change threshold of 4.7x%CVanalytical for brackets of troponin concentrations (P0.0005), representing a significant change value for serial tests of 1.41xZxCVa%, where Z is 3.3. Critical troponin outliers were sample pairs with one result exceeding and one result within the 99th percentile reference range. Turnaround time was defined as time of receipt to time of verification. Results The outlier rate, based on 4,575 troponin tests performed on 3,797 patient samples, was 0.48% (N = 22) of troponin determinations, 0.58% of test samples, and critical outliers 0.13% (N = 6) of troponin determinations, 0.16% of test samples. The significant change threshold at 28 ng/L was 37%. The worst outlier pair was 5,978 ng/L, true value 3,184 ng/L; critical outlier pair 146 ng/L, true value of 14 ng/L. Twenty-one percent of test samples were tested in duplicate; 777 samples had troponin concentration >28 ng/L. Median and mean turnaround time were 32 minutes; 90% of orders completed in 54 minutes. Conclusion The laboratory detected and prevented reporting erroneously high outlier troponin results in 0.58% and critical outlier troponin results in 0.16% of test samples using an immediate repeat testing protocol.

On the essence and initiality of conflicts in [formula omitted]-adhesive transformation systems

Understanding conflicts between transformation steps and rules is an important topic in algebraic graph transformation. A conflict occurs when two transformation steps are not parallel independent, that is, when after applying one of them the other can no longer occur. A static analysis technique called Critical Pair Analysis allows the detection of all potential conflicts between pairs of rules, by enumerating Critical Pairs. Since these are often too numerous for even simple rules, finding appropriate subsets of critical pairs is the topic of ongoing research. We contribute to this thread by proposing a new characterization for root causes of conflicts, called “conflict essences”, exploiting a recently proposed characterization of parallel independence. Furthermore we show that conflict essences are at least as precise as the “conflict reasons” previously proposed, and uniquely determine the so-called “initial conflicts”, an appropriate subset of critical pairs, under relatively mild assumptions on the underlying category. Finally, we show that several M-adhesive categories of interest have the necessary properties for our results to hold, including typed, attributed and symbolic graphs. While our results are formulated for conflicts, they are directly applicable to dependencies in M-adhesive transformation systems.

A Godbillon-Vey type invariant for a 3-dimensional manifold with a plane field

We consider a 3-dimensional smooth manifold M equipped with an arbitrary, a priori non-integrable, distribution (plane field) D and a vector field T transverse to D. Using a 1-form ω such that D=ker⁡ω and ω(T)=1 we construct a 3-form analogous to that defining the Godbillon-Vey class of a foliation, and show how does this form depend on ω and T. For a compatible Riemannian metric on M, we express this 3-form in terms of the curvature and torsion of normal curves and the non-symmetric second fundamental form of D. We deduce Euler-Lagrange equations of associated functionals: for variable (D,T) on M, and for variable Riemannian metric on (M,D). We show that for a geodesic field T (e.g., for a contact structure) such (D,T) is critical, characterize critical pairs when D is integrable (with examples among twisted products) and prove that these critical pairs are not extrema.

Possible nodeless s±-wave superconductivity in twisted bilayer graphene**Project supported by the National Key R&D Program of China (Grant No. 2017YFA0303103), the National Natural Science Foundation of China (Grant Nos. 11774401 and 11522435), the State Key Development Program for Basic Research of China (Grant No. 2015CB921303), the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (Grant No. XDB07020200),

The recent discovery of superconductivity in the twisted bilayer graphene has stimulated numerous theoretical proposals concerning its exact gap symmetry. Among them, the d+ id or p+ ip-wave was believed to be the most plausible solution. Here, considering that the superconductivity emerges near a correlated insulating state and may be induced by antiferromagnetic spin fluctuations, we apply the strong-coupling Eliashberg theory with both inter- and intraband quantum critical pairing interactions and discuss the possible gap symmetry in an effective low-energy four-orbital model. Our calculations reveal a nodeless s±-wave as the most probable candidate for the superconducting gap symmetry in the experimentally relevant parameter range. This solution is distinctly different from previous theoretical proposals. It highlights the multi-gap nature of the superconductivity and puts the twisted bilayer graphene in the same class as the iron-pnictide, electron-doped cuprate, and some heavy fermion superconductors.

Simultaneous determination of neutral sugars, alditols and anhydrosugars using anion-exchange chromatography with pulsed amperometric detection: Application for marine and atmospheric samples

An improved high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) method is described for the simultaneous determination of neutral sugars (hexoses, pentoses and deoxysugars), alditols and anhydrosugars commonly found in atmospheric and marine samples. The method uses a CarboPac MA1 column, at a flow rate of 0.3 mL min−1, and a NaOH gradient (250–700 mM). The proposed method applies a temperature gradient (from 25 to 28 °C) to the column for the first 30 min of the analysis, followed by a constant temperature at 28 °C until the end of the analysis. These analytical conditions allowed the separation of 15 out of 17 carbohydrates in 75 min with resolution factors better than 0.5 for the critical pairs levoglucosan/arabitol, galactosan/arabinose, arabinose/mannose and glucose/xylose.The application of this method to field samples revealed that anhydrosugars represented 53% of total neutral carbohydrates (TCHO) in total suspended atmospheric particles (TSP), whereas they were detected for the first time in marine particulate organic matter (POM) and high-molecular-weight dissolved organic matter (HMWDOM) samples accounting 2% and 3% of TCHO, respectively. Levoglucosan and/or galactosan were the major anhydrosugars in all samples however, their concentrations are undoubtedly underestimated because hydrolysis was applied to the marine samples prior to the HPAEC-PAD analysis. Despite this underestimation, their presence in the marine samples clearly indicates possible terrestrial input most likely via atmospheric deposition as these compounds are considered terrestrial burring biomass tracers. Finally, deoxysugars were also detected for the first time in the TSP sample representing 1% of TCHO, while alditols accounted for 0.4% and 0.3% of TCHO in POM and HMWDOM, respectively.

Amphiphilic triptycene-based stationary phase for high-resolution gas chromatographic separations

This work reports a new type of triptycene-based amphiphilic stationary phase (TP-2IL) for gas chromatography (GC). It is an integration of the 3D π-rich triptycene framework with ionic liquids. Its capillary column showed the efficiency of 3880 plates/m determined by n-dodecane at 120 °C (k = 2.79) and exhibited good performance for analytes from apolar to polar nature. Particularly, it has outstanding capability for resolving critical pairs of anilines and phenols with good peak shapes and shows distinct advantages over its composing counterparts (TP-2BO and O-IL) and widely-used commercial columns, namely 35% phenyl methyl polysiloxane (DB-35) and polyethylene glycol (INNOWAX). Moreover, the TP-2IL column exhibited good repeatability and reproducibility with the values of relative standard deviation in the range of 0.02%–0.07% for run-to-run, 0.10%–0.35% for day-to-day and 2.9%–5.1% for column-to-column, respectively, and good thermal stability up to 300 °C. Furthermore, its applications for determining isomer impurities in real samples demonstrate its feasibility for practical GC analysis. This work presents a facile strategy for constructing triptycene-based stationary phases with amphiphilic selectivity and provides alternatives of highly selective stationary phases for chromatographic analysis.

The Graph of Critical Pairs of a Crown

There is a natural way to associate with a poset P a hypergraph , called the hypergraph of critical pairs, so that the dimension of P is exactly equal to the chromatic number of . The edges of have variable sizes, but it is of interest to consider the graph G formed by the edges of that have size 2. The chromatic number of G is less than or equal to the dimension of P and the difference between the two values can be arbitrarily large. Nevertheless, there are important instances where the two parameters are the same, and we study one of these in this paper. Our focus is on a family $\{{S_{n}^{k}}:n\ge 3, k\ge 0\}$ of height two posets called crowns. We show that the chromatic number of the graph ${G_{n}^{k}}$ of critical pairs of the crown ${S_{n}^{k}}$ is the same as the dimension of ${S_{n}^{k}}$, which is known to be ⌈2(n + k)/(k + 2)⌉. In fact, this theorem follows as an immediate corollary to the stronger result: The independence number of ${G_{n}^{k}}$ is (k + 1)(k + 2)/2. We obtain this theorem as part of a comprehensive analysis of independent sets in ${G_{n}^{k}}$ including the determination of the second largest size among the maximal independent sets, both the reversible and non-reversible types.

110th Anniversary: High Performance Carbon Molecular Sieve Membrane Resistance to Aggressive Feed Stream Contaminants

Carbon molecular sieve (CMS) membranes show high performance for various critical gas pair separations with excellent scalable manufacturability. For practical applications it is important to evaluate such membranes for resistance to contaminants possibly present in feed streams related to an onboard inert gas generation system (OBIGGS) for aerospace applications. Here we report the performance of CMS membranes prepared by optimized dual temperature secondary oxygen doping (DTSOD) in the presence of aggressive contaminants, potentially in the bleed air of aircraft. Such feed can be used to eliminate the need for a separate compressor in membrane systems to create nitrogen enriched stream for fuel tank inerting, and we considered this case using simulated engine bypass air. Our CMS membranes were exposed to different humidity levels, combinations of gaseous contaminants (denoted as Class ‘A’), and ozone to study the membrane performance for O2/N2 separation with time at high temperatures. The CMS shows a r...

Comparison of Conflict Detection Capabilities for Well Clear and Critical Pair Identification

As air traffic management becomes increasingly automated, technologies for detecting and resolving conflicts are critical to maintain the safety of an airspace. There exists a need to understand how multiple conflict detection models may work together to provide deeper insights into the safety of an airspace with many aircraft interactions. Conflict detection capabilities can be improved by using two recently introduced models, Well Clear (WC) and Critical Pair Identification (CPI), which address separation assurance and detection of near mid-air collisions due to unexpected maneuvers, respectively. A procedure called Pairwise Sweep of a Pairwise Conflict (PSPC) is provided, which allows for the visualization of the response of WC and CPI for conflicts with a variety of initial aircraft states in the horizontal airspace. PSPC is then used to analyze a two-aircraft scenario using both WC and CPI to create a merged response. Their joint capability can benefit unmanned aerial systems as a conflict detection technology and air traffic controllers as a decision support tool.

Characterizing graphs of critical pairs of layered generalized crowns

The generalized crown Snk is a well-known family of bipartite graphs whose order dimension is given in terms of the parameters n and k. In recent work, Garcia and Silva defined the notion of layering generalized crowns, producing multipartite posets called ℓ-layered generalized crowns, whose order dimension is easily determined using ℓ, n, and k. This paper extends the authors’ prior work on characterizing the associated graphs of critical pairs of generalized crowns, by providing a new and concrete description of an infinite family of graphs arising from critical pairs of the ℓ-layered generalized crowns. Our main result gives a characterization of the adjacency matrices of these graphs. Through their associated posets with computable order dimension, these graphs have a strict upper bound on their chromatic number.

A Four-Dimensional (4D) Stability Indicating Analytical Method Optimization and Potency Assay Prediction Using MS and UV Peak Tracking

A total of 60 peaks generated by forced degradation of three active pharmaceutical ingredients (APIs) were used for the column selection in the development of a stability indicating HPLC-UV analytical method using LC-UV and LC-MS peak tracking. Two mobile phase additives and two organic modifiers were evaluated while screening a list of carefully chosen chromatography columns. The column screening was utilized and the best column selected based on total number of resolved peaks, resolutions, peak widths, and peak shapes. 0.1% TFA in ACN/water was used for the initial screening and optimization of the gradient profile. Three different concentrations of TFA in ACN/water were also evaluated. The optimum TFA concentration, 0.10% (8.77 mM), was considered as optimum for further gradient optimization based on the resolution of critical pairs. After the selection of column, mobile phase and mobile phase modifier (TFA) selection, optimization of the gradient was achieved by a combination of automated chemometric peak tracking and software-based decisions in AutoChrom MS. The correct peak retention equations (i.e., retention time vs. mobile phase ratio) were generated by using first one-step gradients with a wide range of % B followed by optimization in multi-steps gradients. It was found that extrapolation, using quadratic retention models, can lead to large errors in retention time (tR) predictions, especially for poorly-retained components. We present the challenges in resolving the critical resolution pairs, including those with the same m/z, the overestimation and the prediction errors of the software, and why the peaks model (i.e., accuracy of predicted versus experimental) fail at the extremes of the gradient. By using this approach we were able to generate a suitable stability indicating chromatographic method for an extremely challenging sample comprising of three active pharmaceutical ingredients (APIs) and related degradation products with a wide range of hydrophobicity. The APIs were in-house compounds, their identity are blinded in this paper and are not relevant for purpose of the study. There were good matches between the predicted and experimental retention times of the tracked peaks. The peak model was used for the generation of an assay/potency method using the computational tool only.

Conditions for confluence of innermost terminating term rewriting systems

This paper presents a counterexample for the open conjecture whether innermost joinability of all critical pairs ensures confluence of innermost terminating term rewriting systems. We then show that innermost joinability of all normalized instances of the critical pairs is a necessary and sufficient condition. Using this condition, we give a decidable sufficient condition for confluence of innermost terminating systems. Finally, we enrich the condition by introducing the notion of left-stable rules. As a corollary, confluence of innermost terminating left-weakly-shallow TRSs is shown to be decidable.

Real Curve Analysis and Stability of Time-delay Systems

Abstract In this work, we investigate the asymptotic stability of LTI differential commensurate time-delay systems whose dynamics are defined in the frequency domain by quasi-polynomials of the form f(S, T) = Σmj=0 pj(s) e-jTS. We propose a new approach for studying the stability with respect to the delay: we determine the asymptotic behavior of the roots of the quasi-polynomial near to the critical pairs of f(s, T) by analysing the intersection of an associated algebraic space curve with sufficiently refined 3D real boxes. Compared to the existing methods, our method does not require any Puiseux series computation.

Advancing USP compendial methods for fixed dose combinations: A case study of metoprolol tartrate and hydrochlorothiazide tablets

The current United States Pharmacopeia–National Formulary (USP–NF) includes more than 250 monographs of fixed dose combinations (FDCs), and some of them need to be updated due to incompleteness of impurity profiles and obsolescence of analytical methodologies. A case study of metoprolol tartrate and hydrochlorothiazide tablets is presented to summarize challenges encountered during the USP monograph modernization initiative of FDCs and to highlight an “adoption and adaptation” approach employed for method development. To this end, a single stability-indicating HPLC method was developed to separate the two drug substances and eight related compounds with resolution 2.0 or higher between all critical pairs. Chromatographic separations were achieved on a Symmetry column (C18, 100 mm × 4.6 mm, 3.5 µm) using sodium phosphate buffer (pH 3.0; 34 mM) and acetonitrile as mobile phase in a gradient elution mode. The stability-indicating capability of this method has been demonstrated by analyzing stressed samples of the two drug substances. The developed HPLC method was validated for simultaneous determination of metoprolol tartrate and hydrochlorothiazide and relevant impurities in the tablets. Moreover, the developed method was successfully applied to the analysis of commercial tablet dosage forms and proved to be suitable for routine quality control use. The case study could be used to streamline USP's monograph modernization process of FDCs and strengthen compendial procedures.

Design and Static Load Analysis Comparing Steel, Grey Cast Iron and Titanium Alloy as Materials for Breech Hinged Lugs in Recoil Weapons

This design innovation work is related to design validation of short recoil weapons mechanism’s critical components in context of upper receivers. It explains a new mechanism for locking and unlocking of bolt with the breech and subsequent advantageous design changes in the bolt’s construction. This design intends to build a new platform for a short recoil weapon chambered in 5.56×45 NATO ammunition which promises competency with its existing counter parts of the same domain, but exhibiting exceptionally improved reliability due to elimination of interdependence of reciprocating cycles of barrel and bolt assemblies. This work involves the design of the whole functioning system using Solidworks 2015 version and a static structural analysis to compare and choose the most suitable material among commonly used ones: steel AISI 4340, grey cast iron and titanium alloy Ti-6Al-4V, for locking lugs, being critical pair of components, using ANSYS 14.5. Results showed that titanium alloy was the most suitable material for the strength purpose. It is to be noted that this system may not only be utilized for assault rifles, but also for sub-machine guns, machine gun variants and even in handguns.

Hydrogen sulfide and hepatic lipid metabolism - a critical pairing for liver health.

Hydrogen sulfide (H2 S) is the most recently recognized gasotransmitter, influencing a wide range of physiological processes. As a critical regulator of metabolism, H2 S has been suggested to be involved in the pathology of many diseases, particularly obesity, diabetes and cardiovascular disorders. Its involvement in liver health has been brought to light more recently, particularly through knockout animal models, which show severe hepatic lipid accumulation upon ablation of H2 S metabolic pathways. A complex relationship between H2 S and lipid metabolism in the liver is emerging, which has significant implications for liver disease establishment and/or progression, regardless of the disease-causing agent. In this review, we discuss the critical importance of H2 S in hepatic lipid metabolism. We then describe the animal models so far related with H2 S and lipid-associated liver disease, as well as H2 S-based treatments available. Finally, we highlight important considerations for future studies and identify areas in which much still remains to be determined. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.

Integrated Analysis of MicroRNA (miRNA) and mRNA Profiles Reveals Reduced Correlation between MicroRNA and Target Gene in Cancer.

Background Accumulating evidences demonstrated that microRNA-target gene pairs were closely related to tumorigenesis and development. However, the correlation between miRNA and target gene was insufficiently understood, especially its changes between tumor and normal tissues. Objectives The aim of this study was to evaluate the changes of correlation of miRNAs-target pairs between normal and tumor. Materials and Methods 5680 mRNA and 5740 miRNA expression profiles of 11 major human cancers were downloaded from the Cancer Genome Atlas (TCGA). The 11 cancer types were bladder urothelial carcinoma, breast invasive carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and thyroid carcinoma. For each cancer type, we firstly obtained differentially expressed miRNAs (DEMs) and genes (DEGs) in tumor and then acquired critical miRNA-target gene pairs by combining DEMs, DEGs and two experimentally validated miRNA-target interaction databases, miRTarBase and miRecords. We collected samples with both miRNA and mRNA expression values and performed a correlation analysis by Pearson method for miRNA-target pairs in normal and tumor, respectively. Results We totally got 4743 critical miRNA-target pairs across 11 cancer types, and 4572 of them showed weaker correlation in tumor than in normal. The average correlation coefficients of miRNA-target pairs were different greatly between normal (-0.38 ~ -0.61) and tumor (-0.04 ~ -0.26) for 11 cancer type. The pan-cancer network, which consisted of 108 edges connecting 35 miRNAs and 89 target genes, showed the interactions of pairs appeared in multicancers. Conclusions This comprehensive analysis revealed that correlation between miRNAs and target genes was greatly reduced in tumor and these critical pairs we got were involved in cellular adhesion, proliferation, and migration. Our research could provide opportunities for investigating cancer molecular regulatory mechanism and seeking therapeutic targets.

Effects of lexical ambiguity on perception: A test of the label feedback hypothesis using a visual oddball paradigm.

We used a visual oddball paradigm to investigate whether a shared verbal label makes two objects belonging to different conceptual categories less perceptually distinct. In Experiment 1, the critical images shared a label as well as some perceptual features (orange, referring to the color and the fruit), and in Experiment 2, the critical images shared a label but no perceptual features (bat, referring to the animal and the sports equipment). In both experiments comparison images were similar to each of the critical images but they did not share a label. A reduced deviant-related negativity (DRN) was observed for critical images compared with comparison images in both experiments, suggesting that the critical image pairs were perceived as less distinct than comparison pairs. These results extend previous research using the visual oddball paradigm that has shown that images from the same conceptual category are perceived as more distinct when they have different labels, and provide further support for the label-feedback hypothesis (Lupyan, 2012) in which language is assumed to modulate perception online. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Conditionally averaged flow topology about a critical point pair in the skin friction field of pipe flows using direct numerical simulations

It has recently been shown that critical points in the skin friction field of wall turbulence exist and negative streamwise skin friction events occur. Further analysis of the critical points at the wall using direct numerical simulation data of turbulent pipe flow is presented here. After identifying and characterizing features of the no-slip critical points in a turbulent pipe flow, conditional averages of the flow are presented to reveal the magnitude and extent of the fluctuations in the flow around these extreme events. It is found that the velocity and skin friction fields near critical points resemble the three-dimensional U separation proposed by Perry and Chong [J. Fluid Mech. 173, 207 (1986)JFLSA70022-112010.1017/S0022112086001143].

Variations of the Godbillon–Vey Invariant of Foliated 3-Manifolds

Let M be a smooth three-dimensional manifold equipped with a vector field T transverse to a plane field $${\mathcal {D}}$$ —the kernel of a one form $$\omega $$ such that $$\omega (T)=1$$ . Recently, in Rovenski and Walczak (A Godbillon–Vey type invariant for a 3-dimensional manifold with a plane field, 2017. arXiv:1707.04847 ), we constructed a three-form analogous to that defining the Godbillon–Vey class of a foliation, showed how does this form depend on $$\omega $$ and T, and deduced Euler–Lagrange equations of the associated functional. In this paper, we continue our study when distributions/foliations and forms are defined outside a “singularity set” (a finite union of pairwise disjoint closed submanifolds of codimension $$\ge 2$$ ) under additional assumption of convergence of certain integrals. We characterize critical pairs $$(\omega ,T)$$ and foliations for different types of variations, find sufficient conditions for critical pairs when variations are among foliations, consider applications to transversely holomorphic flows, calculate the index form and present examples of critical foliations among Reeb foliations and twisted products.