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We employ a first-principles-based, force-level approach to construct the anharmonic tube confinement field for entangled fluids of rigid needles, and also for chains described at the primitive-path (PP) level in two limiting situations where chain stretch is assumed to either be completely equilibrated or unrelaxed. The influence of shear and extensional deformation and polymer orientation is determined in a nonlinear elastic limit where dissipative relaxation processes are intentionally neglected. For needles and PP-level chains, a self-consistent analysis of transverse polymer harmonic dynamical fluctuations predicts that deformation-induced orientation leads to tube weakening or widening. In contrast, for deformed polymers in which chain stretch does not relax, we find tube strengthening or compression. For all three systems, a finite maximum transverse entanglement force localizing the polymers in effective tubes is predicted. The conditions when this entanglement force can be overcome by an externally applied force associated with macroscopic deformation can be crisply defined in the nonlinear elastic limit, and the possibility of a "microscopic absolute yielding" event destroying the tube confinement can be analyzed. For needles and contour-relaxed PP chains, this force imbalance occurs at a stress of order the equilibrium shear modulus and a strain of order unity, corresponding to a mechanically fragile entanglement tube field. However, for unrelaxed stretched chains, tube compression stabilizes transverse polymer confinement, and there appears to be no force imbalance. These results collectively suggest that the crossover from elastic to irreversible viscous response requires chain retraction to initiate disentanglement. We qualitatively discuss comparisons with existing phenomenological models for nonlinear startup shear, step strain, and creep rheology experiments. [ABSTRACT FROM AUTHOR]

Given a pair of graphs with the same number of vertices, the inexact graph matching problem consists in finding a correspondence between the vertices of these graphs that minimizes the total number of induced edge disagreements. We study this problem from a statistical framework in which one of the graphs is an errorfully observed copy of the other. We introduce a corrupting channel model, and show that in this model framework, the solution to the graph matching problem is a maximum likelihood estimator (MLE). Necessary and sufficient conditions for consistency of this MLE are presented, as well as a relaxed notion of consistency in which a negligible fraction of the vertices need not be matched correctly. The results are used to study matchability in several families of random graphs, including edge independent models, random regular graphs, and small-world networks. We also use these results to introduce measures of matching feasibility, and experimentally validate the results on simulated and real-world networks. Supplemental files for this article are available online. [ABSTRACT FROM AUTHOR]

Epithelia have distinct cellular architectures which are established in development, reestablished after wounding, and maintained during tissue homeostasis despite cell turnover and mechanical perturbations. In turn, cell shape also controls tissue function as a regulator of cell differentiation, proliferation, and motility. Here, we investigate cell shape changes in a model epithelial monolayer. After the onset of confluence, cells continue to proliferate and change shape over time, eventually leading to a final architecture characterized by arrested motion and more regular cell shapes. Such monolayer remodeling is robust, with qualitatively similar evolution in cell shape and dynamics observed across disparate perturbations. Here, we quantify differences in monolayer remodeling guided by the active vertex model to identify underlying order parameters controlling epithelial architecture. When monolayers are formed atop an extracellular matrix with varied stiffness, we find the cell density at which motion arrests varies significantly, but the cell shape remains constant, consistent with the onset of tissue rigidity. In contrast, pharmacological perturbations can significantly alter the cell shape at which tissue dynamics are arrested, consistent with varied amounts of active stress within the tissue. Across all experimental conditions, the final cell shape is well correlated to the cell proliferation rate, and cell cycle inhibition immediately arrests cell motility. Finally, we demonstrate cell cycle variation in junctional tension as a source of active stress within the monolayer. Thus, the architecture and mechanics of epithelial tissue can arise from an interplay between cell mechanics and stresses arising from cell cycle dynamics. [ABSTRACT FROM AUTHOR]

The phenomenological reptation-tube model is based on a single chain perspective and was originally proposed to explain the remarkable viscoelastic properties of dense entangled polymer liquids. However, simulations over the last two decades have revealed a fundamental tension in the model: it assumes that bonded, single-chain backbone stresses are the sole polymer contribution to the slowly relaxing component of stress storage and elasticity, but mounting evidence suggests that at the local level of forces it is interchain contributions that dominate, as in simple liquids. Here we show that based on a chain model constructed at the level of self-consistently determined primitive paths, an explicit force-level treatment of the correlated intermolecular contributions to stress that arise from chain uncrossability can essentially quantitatively predict the entanglement plateau modulus associated with the soft rubbery response of polymer liquids. Analogies to transient localization and elasticity in glass-forming liquids are identified. Predictions for the effect of macroscopic deformation and anisotropic orientational order on the tube diameter are also made. Based on the interchain stress perspective the theory reproduces some aspects of the rheological response to shear and extensional deformations associated with the single chain tube model. [ABSTRACT FROM AUTHOR]

We consider the problem of graph matchability in non-identically distributed networks. In a general class of edge-independent networks, we demonstrate that graph matchability can be lost with high probability when matching the networks directly. We further demonstrate that under mild model assumptions, matchability is almost perfectly recovered by centering the networks using universal singular value thresholding before matching. These theoretical results are then demonstrated in both real and synthetic simulation settings. We also recover analogous core-matchability results in a very general core-junk network model, wherein some vertices do not correspond between the graph pair. [ABSTRACT FROM AUTHOR]

The problem of finding the vertex correspondence between two noisy graphs with different number of vertices where the smaller graph is still large has many applications in social networks, neuroscience, and computer vision. We propose a solution to this problem via a graph matching matched filter: centering and padding the smaller adjacency matrix and applying graph matching methods to align it to the larger network. The centering and padding schemes can be incorporated into any algorithm that matches using adjacency matrices. Under a statistical model for correlated pairs of graphs, which yields a noisy copy of the small graph within the larger graph, the resulting optimization problem can be guaranteed to recover the true vertex correspondence between the networks. However, there are currently no efficient algorithms for solving this problem. To illustrate the possibilities and challenges of such problems, we use an algorithm that can exploit a partially known correspondence and show via varied simulations and applications to Drosophila and human connectomes that this approach can achieve good performance. [ABSTRACT FROM AUTHOR]

A microscopic theory for the effect of applied stress on the transverse topological confinement potential and slow dynamics of heavily entangled rigid rods is presented. The confining entanglement force localizing a polymer in a tube is predicted to have a finite strength. As a consequence, three regimes of terminal relaxation behavior are predicted with increasing stress: accelerated reptation due to tube widening (dilation), relaxation via deformation-assisted activated transverse barrier hopping, and complete destruction of the lateral tube constraints corresponding to microscopic yielding or a disentanglement transition. [ABSTRACT FROM AUTHOR]

We generalize the nonlinear Langevin equation theory of activated single particle dynamics to describe the correlated motion of two tagged spherical particles in a glass- or gel-forming fluid as a function of their initial separation. The theory is built on the concept of a two-dimensional dynamic free energy surface which quantifies the forces on two particles moving in a cooperative manner. For the hard sphere fluid, above a threshold volume fraction we generically find two relaxation channels corresponding largely, but not exclusively, to a center-of-mass-like displacement and a radial separation of the two tagged particles. The entropic barriers and mean first passage times are computed and found to systematically vary with volume fraction and initial particle separation; both oscillate as a function of the latter in a manner related to the equilibrium pair correlation function. A dynamic correlation length is estimated as the length scale beyond which the two-particle activated dynamics becomes uncorrelated in space and time, and is found to modestly grow with increasing mean relaxation time. The theory is also applied to a simplified model of cage escape, the elementary step of structural relaxation. Predictions for characteristic relaxation times, translation-relaxation decoupling, and stretched-exponential decay of time correlation functions are obtained. A novel mechanism for understanding why strong decoupling emerges in the activated regime, but stretched nonexponential time correlation functions do not change shape as the mean relaxation time grows, is presented and favorably compared with experiment. The theory may serve as a starting point for constructing a predictive model of multiple correlated caging and hopping (forward and backward) events of a pair of tagged particles. [ABSTRACT FROM AUTHOR]

Background: Clostridium difficile (CD) infection (CDI) causes marked morbidity and mortality, accounting for large healthcare expenditures annually. Current CDI treatment guidelines focus on clinical markers of patient severity to determine the preferred antibiotic regimen of metronidazole versus vancomycin. The antimicrobial resistance patterns for patients with CD are currently unknown.Aim: The aim of this study was to define the antimicrobial resistance patterns for CD.Methods: This study included all patients with stools sent for CD testing to a private laboratory (DRG Laboratory, Alpharetta, Georgia) in a 6-month period from across the USA. Patient data was de-identified, with only age, gender, and zip-code available per laboratory protocol. All samples underwent PCR testing followed by hybridization for CD toxin regions A and B. Only patients with CD-positive PCR were analyzed. Antimicrobial resistance testing using stool genomic DNA evaluated presence of imidazole- and vancomycin-resistant genes using multiplex PCR gene detection.Results: Of 2743, 288 (10.5%) stool samples were positive for CD. Six were excluded per protocol. Of 282, 193 (69.4%) were women, and average age was 49.4 ± 18.7 years. Of 282, 62 were PCR positive for toxins A and B, 160 for toxin A positive alone, and 60 for toxin B positive alone. Antimicrobial resistance testing revealed 134/282 (47.5%) patients resistant to imidazole, 17 (6.1%) resistant to vancomycin, and 9 (3.2%) resistant to imidazole and vancomycin.Conclusions: CD-positive patients with presence of imidazole-resistant genes from stool DNA extract was a common phenomenon, while vancomycin resistance was uncommon. Similar to treatment of other infections, antimicrobial resistance testing should play a role in CDI clinical decision-making algorithms to enable more expedited and cost-effective delivery of patient care. [ABSTRACT FROM AUTHOR]

Background and Aims: Surveillance colonoscopy frequently occurs prior to recommended intervals. Studies delineating the reasons why premature surveillance occurs are limited. We sought to define the frequency in which premature surveillance colonoscopy occurs in the setting of an inadequate bowel preparation or with a provided patient clinical indication versus when premature surveillance colonoscopy occurs without any provided discernible rationale in the setting of adequate bowel preparation.Methods: A retrospective cross-sectional cohort study of 700 patients undergoing colonoscopy for an indication of "surveillance of polyps" from 2008 to 2014 at two tertiary-care referral centers was carried out. Patients were deemed either "adherent" or "premature" based on US Multi-Society Task Force guideline intervals for surveillance colonoscopy. A documented decision-making rationale for premature surveillance was determined through review of the electronic medical record with assessment of clinical notes and endoscopy order and report.Results: Premature surveillance occurred in 43.0 % (n = 301) of all surveillance colonoscopies performed. Among the premature cases, rationale was attributed to inadequate bowel preparation in 17.3 % (n = 52) and due to a new clinical indication in 21.6 % (n = 65). Most commonly, in 61.1 % (n = 184) of premature cases, no rationale was documented for the early colonoscopy.Conclusions: Documented decision-making rationale for premature surveillance colonoscopy is usually absent in premature cases with inadequate bowel preparation and new clinical indications explaining only a minority of the occurrences. [ABSTRACT FROM AUTHOR]

Background: Obtaining quality endoscopic biopsy specimens is vital in making successful histological diagnoses. The influence of forceps cup shape and size on quality of biopsy specimens is unclear.Aim: To identify whether oval cup or two different serrated jaw biopsy forceps could obtain specimens of superior size. Secondary endpoints were tissue adequacy, depth of tissue acquisition, and crush artifact.Methods: A single-center, prospective, pathologist-masked, randomized controlled trial was performed. In total 136 patients with a clinical indication for esophagogastroduodenoscopy with biopsy were randomized to receive serial biopsies with a large-capacity serrated forceps with jaw diameter 2.2 mm (SER1) and either a large-capacity oval forceps with jaw diameter 2.4 mm (OVL) or large-capacity serrated biopsy forceps with jaw diameter 2.4 mm (SER2) in two parallel groups.Results: SER2 provided significantly larger specimens than did the other forceps (SER2 3.26 ± 1.09 vs. SER1 2.92 ± 0.88 vs. OVL 2.92 ± 0.76; p = 0.026), with an average size difference of 0.34 mm greater with SER2 compared to SER1 and OVL. OVL provided significantly deeper biopsies compared to SER1 and SER2 (p = 0.02), with 31 % of OVL biopsies reaching the submucosa. SER2 had significantly less crush artifact than SER1 and OVL (p < 0.0001).Conclusion: Serrated forceps provided larger samples compared to oval jaw forceps of the same size, with SER2 providing the largest specimen size. Oval cup forceps had deeper penetration of epithelium, while the larger jaw diameter serrated jaw forceps had less crush artifact. All three forceps provided specimens adequate for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Nanometrically thin glassy films depart strikingly from the behavior of their bulk counterparts. We investigate whether the dynamical differences between a bulk and thin film polymeric glass former can be understood by differences in local microscopic structure. Machine learning methods have shown that local structure can serve as the foundation for successful, predictive models of particle rearrangement dynamics in bulk systems. By contrast, in thin glassy films, we find that particles at the center of the film and those near the surface are structurally indistinguishable despite exhibiting very different dynamics. Next, we show that structure-independent processes, already present in bulk systems and demonstrably different from simple facilitated dynamics, are crucial for understanding glassy dynamics in thin films. Our analysis suggests a picture of glassy dynamics in which two dynamical processes coexist, with relative strengths that depend on the distance from an interface. One of these processes depends on local structure and is unchanged throughout most of the film, while the other is purely Arrhenius, does not depend on local structure, and is strongly enhanced near the free surface of a film. [ABSTRACT FROM AUTHOR]

Objectives: Precolonoscopy dietary regimens often are restricted to clear liquids; however, the superiority of a clear liquid diet (CLD) for bowel preparation quality is ambiguous. We performed a meta-analysis of randomized trials comparing bowel preparation outcomes between a low-residue diet (LRD) or regular diet (RD) compared with a CLD.Methods: MEDLINE, clinicaltrials.gov, Cochrane Central Register, Scopus, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Web of Science databases were used to conduct a search for randomized controlled trials from 1976 to March 2015. Of 122 relevant references, 12 studies met our inclusion criteria, 7 studies of which were classified as being of high quality. Pooled estimates of bowel preparation quality were defined as adequate versus inadequate. Secondary outcomes included tolerability, willingness to repeat bowel preparation, adverse events, and adenoma detection rate. Pooled estimates of relative risk (RR) were used for dichotomous variables and standardized mean difference for continuous variables.Results: In the high-quality studies, there were no differences in bowel preparation quality among the LRD/RD and CLD groups (RR 0.98; 95% confidence interval [CI] 0.93-1.04). Analysis of secondary outcomes included all of the studies. Tolerability (RR 1.04, 95% CI 1.01-1.08) and willingness to repeat favored the liberalized diet arm (RR 1.08, 95% CI 1.01-1.16). There was no significant difference in the adenoma detection rate, whereas hunger was more common in the CLD group.Conclusions: An LRD/RD provided no difference in bowel preparation quality as compared with a CLD. As such, it may be reasonable for patients without risk factors for poor preparation to undergo an LRD until lunch the day before their colonoscopy given that bowel preparation tolerability and willingness to repeat were greater among groups with a liberalized diet. [ABSTRACT FROM AUTHOR]

Statistical inference on graphs is a burgeoning field in the applied and theoretical statistics communities, as well as throughout the wider world of science, engineering, business, etc. In many applications, we are faced with the reality of errorfully observed graphs. That is, the existence of an edge between two vertices is based on some imperfect assessment. In this article, we consider a graphG= (V,E). We wish to perform an inference task—the inference task considered here is “vertex classification,” that is, given a vertexvwith unknown labelY(v), we want to infer the label forvbased on the graphGand the given labels for some set of vertices inGnot containingv. However, we do not observeG; rather, for each potential edgewe observe an “edge feature” that we use to classifyuvas edge/not-edge. Thus, weerrorfullyobserveGwhen we observe the graphas the edges inarise from the classifications of the “edge features,” and are expected to be errorful. Moreover, we face a quantity/quality trade-off regarding the edge features we observe—more informative edge features are more expensive, and hence the number of potential edges that can be assessed decreases with the quality of the edge features. We studied this problem by formulating a quantity/quality trade-off for a simple class of random graphs model, namely, the stochastic blockmodel. We then consider a simple but optimal vertex classifier for classifyingvand we derive the optimal quantity/quality operating point for subsequent graph inference in the face of this trade-off. The optimal operating points for the quantity/quality trade-off are surprising and illustrate the issue that methods for intermediate tasks should be chosen to maximize performance for the ultimate inference task. Finally, we investigate the quantity/quality tradeoff for errorful observations of theC. elegansconnectome graph. [ABSTRACT FROM PUBLISHER]

Recently there has been a surge in interest in using video-microscopy techniques to infer the local mechanical properties of disordered solids. One common approach is to minimize the difference between particle vibrational displacements in a local coarse-graining volume and the displacements that would result from a best-fit affine deformation. Effective moduli are then inferred under the assumption that the components of this best-fit affine deformation tensor have a Boltzmann distribution. In this paper, we combine theoretical arguments with experimental and simulation data to demonstrate that the above does not reveal information about the true elastic moduli of jammed packings and colloidal glasses. [ABSTRACT FROM AUTHOR]

We present a parallelized bijective graph matching algorithm that leverages seeds and is designed to match very large graphs. Our algorithm combines spectral graph embedding with existing state-of-the-art seeded graph matching procedures. We justify our approach by proving that modestly correlated, large stochastic block model random graphs are correctly matched utilizing very few seeds through our divide-and-conquer procedure. We also demonstrate the effectiveness of our approach in matching very large graphs in simulated and real data examples, showing up to a factor of 8 improvement in runtime with minimal sacrifice in accuracy. [ABSTRACT FROM AUTHOR]

We use a regular arrangement of kirigami elements to demonstrate an inverse design paradigm for folding a flat surface into complex target configurations. We first present a scheme using arrays of disclination defect pairs on the dual to the honeycomb lattice; by arranging these defect pairs properly with respect to each other and choosing an appropriate fold pattern a target stepped surface can be designed. We then present a more general method that specifies a fixed lattice of kirigami cuts to be performed on a flat sheet. This single pluripotent lattice of cuts permits a wide variety of target surfaces to be programmed into the sheet by varying the folding directions. [ABSTRACT FROM AUTHOR]

Background Inflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining. Methods TLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods. Results A strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also overexpressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47% of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining. Conclusions Increased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage. [ABSTRACT FROM AUTHOR]

In this work, we show that using the eigen-decomposition of the adjacency matrix, we can consistently estimate latent positions for random dot product graphs provided the latent positions are i.i.d. from some distribution. If class labels are observed for a number of vertices tending to infinity, then we show that the remaining vertices can be classified with error converging to Bayes optimal using the $(k)$-nearest-neighbors classification rule. We evaluate the proposed methods on simulated data and a graph derived from Wikipedia. [ABSTRACT FROM AUTHOR]

We build upon our recently developedmicroscopic theory for the tube confinement potential of rigid macromoleculesto treat the relaxation of stress and orientation of fluids of topologicallyentangled needles during a continuous startup shear deformation. Twocoupled and highly nonlinear evolution equations for stress and rodorientation are proposed. The novel feature is our ability to self-consistentlyrelate the current stress- and orientation-dependent state of thefluid with an effective instantaneous relaxation time that combines(perturbed) reptation and transverse activated barrier hopping. Theeffective relaxation time follows from a microscopic, time-dependentprediction of the tube confinement potential during the deformation.Results for the strain and Weissenberg number dependence of the confinementpotential are presented for two degrees of entanglement. As a naturalconsequence of the predicted stress dependence of the confinementpotential, our self-consistent single-rod theory emergently manifestsfeatures normally associated with many-polymer convective constraintrelease, such as a monotonic flow curve and an effective relaxationtime that (nearly) scales with the inverse of the deformation rate.Comparisons with the original Doi–Edwards theory reveal qualitativedifferences as a consequence of stress- and orientation-induced softeningof the tube constraints. Severe tube dilation often occurs, and thecomplete destruction of transverse localization is possible dependingon system-specific conditions. [ABSTRACT FROM AUTHOR]

Colonic bacteria have been implicated in the development of colon cancer. We have previously demonstrated that toll-like receptor 4 (TLR4), the receptor for bacterial lipopolysaccharide (LPS), is over-expressed in humans with colitis-associated cancer. Genetic epidemiologic data support a role for TLR4 in sporadic colorectal cancer (CRC) as well, with over-expression favoring more aggressive disease. The goal of our study was to determine whether TLR4 played a role as a tumor promoter in sporadic colon cancer. Using immunofluorescence directed to TLR4, we found that a third of sporadic human colorectal cancers over-express this marker. To mechanistically investigate this observation, we used a mouse model that over-expresses TLR4 in the intestinal epithelium (villin-TLR4 mice). We found that these transgenic mice had increased epithelial proliferation as measured by BrdU labeling, longer colonic crypts and an expansion of Lgr5+ crypt cells at baseline. In addition, villin-TLR4 mice developed spontaneous duodenal dysplasia with age, a feature that is not seen in any wild-type (WT) mice. To model human sporadic CRC, we administered the genotoxic agent azoxymethane (AOM) to villin-TLR4 and WT mice. We found that villin-TLR4 mice showed an increased number of colonic tumors compared to WT mice as well as increased β-catenin activation in non-dysplastic areas. Biochemical studies in colonic epithelial cell lines revealed that TLR4 activates β-catenin in a PI3K-dependent manner, increasing phosphorylation of β-cateninSer552, a phenomenon associated with activation of the canonical Wnt pathway. Our results suggest that TLR4 can trigger a neoplastic program through activation of the Wnt/β-catenin pathway. Our studies highlight a previously unexplored link between innate immune signaling and activation of oncogenic pathways, which may be targeted to prevent or treat CRC. [ABSTRACT FROM AUTHOR]

For random graphs distributed according to a stochastic block model, we consider the inferential task of partitioning vertices into blocks using spectral techniques. Spectral partitioning using the normalized Laplacian and the adjacency matrix have both been shown to be consistent as the number of vertices tend to infinity. Importantly, both procedures require that the number of blocks and the rank of the communication probability matrix be known, even as the rest of the parameters may be unknown. In this paper, we prove that the (suitably modified) adjacency-spectral partitioning procedure, requiring only an upper bound on the rank of the communication probability matrix, is consistent. Indeed, this result demonstrates a robustness to model mis-specification; an overestimate of the rank may impose a moderate performance penalty, but the procedure is still consistent. Furthermore, we extend this procedure to the setting where adjacencies may have multiple modalities and we allow for either directed or undirected graphs. [ABSTRACT FROM AUTHOR]

We qualitatively extend a microscopic dynamical theory for the transverse confinement of infinitely thin rigid rods to study topologically entangled melts of flexible polymer chains. Our main result treats coils as ideal random walks of self-consistently determined primitive-path (PP) steps and exactly includes chain uncrossability at the binary collision level. A strongly anharmonic confinement potential ("tube") for a primitive path is derived and favorably compared with simulation results. The relationship of the PP-level theory to two simpler models, the melt as a disconnected fluid of primitive-path steps and a "supercoarse graining" that replaces the entire chain by a needle corresponding to its end-to-end vector, is examined. Remarkable connections between the different levels of coarse graining are established. [ABSTRACT FROM AUTHOR]

The microscopic nonlinear Langevin equation (NLE) theory of correlated two-particle dynamics in dense fluids of spherical particles is extended to construct a predictive model of multiple correlated hopping and recaging events of a pair of tagged particles as a function of their initial separation. Modest coarse graining over the liquid structural disorder allows contact to be made with various definitions of irreversible particle motion within the context of a multistate Markov model. The correlated space-time hopping process that underlies structural relaxation can also be analyzed in the context of kinetically constrained models. The dependence of microscopically defined mean persistence and exchange times, their distributions, and relaxation-diffusion decoupling on hard-sphere fluid volume fraction is derived from a model in which irreversible jumps serve as the nucleating persistence event. For a subset of questions, the predictions of the two-particle theory are compared with results from the earlier single-particle NLE approach. [ABSTRACT FROM AUTHOR]

We describe in detail a new self-consistent microscopictheoryfor the transverse tube confinement potential and the slow dynamicsof topologically entangled rod polymer solutions under quiescent (equilibrium)and stressed conditions. Building on this advance, a theory is formulatedfor the nonlinear relaxation of stress and orientational order afteran instantaneous step-strain deformation. The theory accounts fora time- and deformation-dependent (dilated) tube diameter, a maximumconfinement force, and a transverse entropic barrier. These aspectsresult in competing (and coupled) time-dependent relaxation mechanismsunder stress: reptative rotational motion and activated transversebarrier hopping. We predict an acceleration of the terminal rotationalrelaxation due to tube dilation and at sufficiently high deformationsthe emergence of a competitive transverse hopping (tube breaking)relaxation process. Both of these effects are a consequence of thepredicted anharmonic form of the dynamic tube confinement potentialand the finite strength of the entanglement force experienced by atagged rod. After a large enough strain the entanglement network ispredicted to break down, and the tube is destroyed in a manner akinto a microscopic yielding event. This results in a regime of ultrafastrelaxation of stress and orientation on a time scale much shorterthan the terminal relaxation time, and additional dynamical featuresat intermediate times not present under equilibrium conditions. Asstress relaxes, the entanglement constraints and confining tube re-emerge,resulting in a return to an unperturbed reptative relaxation processat long times. The approach to this state is characterized by apparentpower-law healing kinetics of the tube diameter, maximum confinementforce, and rotational relaxation time. An important consequence ofthe dynamical evolution of the transverse confinement field is theprediction of a different damping function compared to the classictube model. [ABSTRACT FROM AUTHOR]

We present a first-principles theory for the slow dynamics of a fluid of entangling rigid crosses of zero excluded volume based on a generalization of the dynamic mean-field approach of Szamel for infinitely thin nonrotating rods. The latter theory exactly includes topological constraints at the two-body collision level and self-consistently renormalizes an effective diffusion tensor to account for many-body effects. Remarkably, it predicts scaling laws consistent with the phenomenological reptation-tube predictions of Doi and Edwards for the long-time diffusion and the localization length in the heavily entangled limit. We generalize this approach to a different macromolecular architecture, infinitely thin three-dimensional crosses, and also extend the range of densities over which a dynamic localization length can be calculated for rods. Ideal gases of nonrotating crosses have recently received attention in computer simulations and are relevant as a simple model of both a strong-glass former and entangling star-branched polymers. Comparisons of our theory with these simulations reveal reasonable agreement for the magnitude and reduced density dependence of the localization length and also the self-diffusion constant if the consequences of local density fluctuations are taken into account. [ABSTRACT FROM AUTHOR]

Dendritic arborization is required for proper neuronal connectivity. Rho GTPases have been implicated in the regulation of dendrite development. However, the signaling pathways that impinge on these molecular switches remain poorly understood. Here we show that Wnt7b, which is expressed in the mouse hippocampus, increases dendritic branching in cultured hippocampal neurons. This effect is mimicked by the expression of Dishevelled (Dvl) and is blocked by Sfrp1, a secreted Wnt antagonist. Consistent with these findings, hippocampal neurons from mice lacking Dvl1 show reduced dendritic arborization. Activation of the canonical Wnt-Gsk3ßpathway does not affect dendritic development. In contrast, Wnt7b and Dvl activate Rac and JNK in hippocampal neurons. Dominant-negative Rac, dominant-negative JNK or inhibition of JNK blocks Dvl-mediated dendritic growth. These findings demonstrate a new function for the non-canonical Wnt pathway in dendrite development and identify Dvl as a regulator of Rho GTPases and JNK during dendritic morphogenesis. [ABSTRACT FROM AUTHOR]

Investigates the effects of realism and perceived control on student satisfaction with the SuperShrink interview simulation. Attitudes of students toward the interview simulation; Efficiency of SuperShrink interview simulation in teaching psychology; Enhancement of realism in the interview simulation.

Background: Patients with Clostridioides difficile infection (CDI) often have coexisting medical problems requiring immunosuppressive therapy. However, limited data are available on the association between immunosuppressive therapy and CDI outcomes. Aim: To determine the association between immunosuppressive therapy and CDI outcomes. Methods: PubMed, Embase, and Cochrane Library were searched through February 2021. Two reviewers independently reviewed and included studies that compared adult CDI patients who received immunosuppressive therapy to those who did not. The primary outcome was complicated CDl, including death, surgery, shock, or ICU admission. Raw data or unadjusted odds ratios (ORs) were used to calculate pooled ORs with 95% confidence intervals (CIs). Results: Twenty-two studies with a total of 5759 CDI patients were selected. Immunosuppressive therapy was significantly associated with both primary outcome and death, with pooled ORs of 1.61 (95% CI 1.33–1.96) and 1.73 (95% CI 1.39–2.15) separately. The association between corticosteroids and primary outcome was also significant with OR of 1.73 (95% CI 1.41, 2.12). In subgroup analysis, the factors explaining differences in study results included study quality, patient age, and whether individual studies had adjusted for potential confounders. In a systematic review, most studies suggested a positive association between immunosuppressive therapy and complicated outcomes of CDI in patients comorbid for IBD. Conclusions: Our systematic review and meta-analysis demonstrate that immunosuppressive therapy is a risk factor for complicated outcomes of CDI. [ABSTRACT FROM AUTHOR]

Lui et al. performed a randomized trial to compare endoscopic variceal band ligation (EVL) with pharmacological treatment, using propanolol (PPL) or isosorbide mononitrate (IMN), for primary prevention of esophageal variceal bleeding. A total of 172 cirrhotic patients with Grade II–III esophageal varices were randomly assigned to receive either esophageal banding (44 patients) or pharmacological monotherapy with PPL (66 patients) or IMN (62 patients). The main endpoint evaluated was primary hemorrhage. Bleeding outcomes were calculated as 2-yr actuarial risks. Eradication of varices was defined as complete absence of varices or a regression to Grade I varices. EVL sessions were performed on a schedule of biweekly endoscopies and band ligations until eradication was achieved. Varices were eradicated after a mean of 3.1 ± 2.5 endoscopy sessions. PPL administration was started at a dose of 40 mg b.i.d. and increased incrementally every 3 days to a target dose of 160 mg/day. IMN dosage began at 20 mg b.i.d. and was increased after 3 days to a target dose of 80 mg per day.Two-year actuarial risks for primary variceal bleed were 6.2% for the EVL group, 19.4% for the PPL group, and 27.7% for the IMN group. One patient in the EVL group had a complication consisting of perforation of the upper esophagus secondary to insertion of the overtube. Of patients in the PPL group, 45% complained of adverse effects from treatment, resulting in a 30% withdrawal rate. Of IMN-receiving patients, 42% reported adverse effects, causing a 21% withdrawal rate. The most often encountered adverse effects of pharmacological monotherapy include breathlessness, headache, and fatigue. The only statistically significant difference between therapies showed less variceal bleeding with EVL when compared with IMN therapy. No statistical significance was achieved when comparing EVL with PPL or PPL with IMN. Pharmacological monotherapy produced a considerable adverse effect profile. Significantly fewer treatment withdrawals were observed with EVL compared with pharmacotherapy (p = 0.00).The authors concluded that EVL was as effective as PPL and more effective than IMN in prophylaxis of first variceal bleed in patients with esophageal varices. The authors suggested that EVL be considered as first-line therapy alongside PPL monotherapy in prevention of first variceal bleed in cirrhotic patients, given the extensive adverse effects of pharmacotherapy resulting in withdrawal from treatment. [Copyright &y& Elsevier]

Background: Adherence to colorectal cancer screening in the United States is suboptimal, particularly in medically underserved populations due to significant barriers to care. Unique accessible, low-cost, and non-invasive screening tests for this population could greatly benefit current rates. In this article, we assess patient preference and the impact of offering a blood-based test on screening rates in a cost-free health fair setting from April 2017 to April 2019.Methods: Participants who met colorectal cancer screening eligibility criteria set forth by the United States Preventive Services Task Force were recommended to attend the colon cancer screening station. Those participants who elected to attend were offered various, accepted screening methods, and if they declined, were offered alternative blood-based testing. Screening rates, test outcomes, and the rate of follow up completion of colonoscopy were measured and compared with historic screening outcomes.Results: Of 1401 participants who were recommended to attend, 640 (45.7%) participants were evaluated at the colon cancer screening station, of whom 460 were eligible for testing. Amongst these, none selected colonoscopy, 30 (6.5%) selected fecal immunochemical testing, and 430 (93.5%) selected blood-based testing. Only 2 participants returned the fecal immunochemical tests. In the blood test cohort, 88 were positive and 20 received a follow up colonoscopy.Conclusions: Based on this assessment, blood-based testing is an effective method to increase screening rates in medically underserved populations, though efforts to further improve access to follow up colonoscopy are necessary. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal (GI) luminal cancers can be detected at early stages by endoscopic procedures. Place-based factors, such as social deprivation and distance to specialist care, are under-investigated with regard to the stage of diagnosis. Methods This was a retrospective cohort study among persons ≥18 years of age in the Florida Cancer Data System, a population-based cancer incidence registry. We included persons diagnosed with esophageal cancer, gastric canceror colorectal cancer, with at least 1 measure of geographic location during the period January 1, 1981, to December 31, 2016. Multivariate multinomial logistic regression was used to identify factors associated with the stage of diagnosis, including social deprivation and proximity to GI care. Results Among 379,054 persons, the median age was 71 years, and 54% were male. Distant stage disease was significantly less likely than local stage in those of non-Hispanic/Latino ethnicity (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.89-0.94, P<0.001). Distant disease was more likely in African Americans (OR 1.30, 95%CI 1.26-1.34) and Asians (OR 1.41, 95%CI 1.27-1.56, P<0.001), with each 5-min increase in travel time to specialists, (OR 1.02, 95%CI 1.01-1.02, P<0.001), and with each 10-point increase in Social Deprivation Index (OR 1.01, 95%CI 1.01-1.02, P<0.001). Conclusions A greater distance from care and living in areas with increased deprivation are associated with an advanced stage of diagnosis and should be recipients of policy-driven efforts to improve access to care. That the strongest risk factors include minority race and ethnicity underlines the complexity of healthcare disparities. [ABSTRACT FROM AUTHOR]

How can dense biological tissue maintain sharp boundaries between coexisting cell populations? We explore this question within a simple vertex model for cells, focusing on the role of topology and tissue surface tension. We show that the ability of cells to independently regulate adhesivity and tension, together with neighbor-based interaction rules, lets them support strikingly unusual interfaces. In particular, we show that mechanical- and fluctuation-based measurements of the effective surface tension of a cellular aggregate yield different results, leading to mechanically soft interfaces that are nevertheless extremely sharp. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article by Giardiello et al. which recommended new strategies for molecular marker reporting in colorectal cancer.

Current recommendations of The US Preventive Services Task Force (USPSTF) on colorectal cancer (CRC) screening strategies are based on models that assume 100% adherence. Since adherence can have a large effect on screening outcomes, we aimed to compare the effectiveness of CRC screening strategies under reported adherence rates at the population level. We developed and validated a microsimulation model to assess the effectiveness of colonoscopy (COL), flexible sigmoidoscopy (FS), high‐sensitivity guaiac fecal occult blood‐test (HS‐gFOBT), fecal immunochemical test (FIT), multitarget stool DNA test (FIT‐DNA), computed tomography colonography (CTC), and methylated SEPT9 DNA test (SEPT9) in terms of CRC incidence and mortality, incremental life years gained (LYG), number of colonoscopies, and adverse events for men and women 50 years or older over their lifetime. We assessed outcomes under 100% adherence rates and reported adherence rates. We also performed sensitivity analyses to evaluate the impact of varying adherence levels on CRC outcomes. Assuming 100% adherence, FIT‐DNA, FIT, HS‐gFOBT, and SEPT9 averted 42‐45 CRC cases and 25‐26 CRC deaths, COL 46 cases and 26 deaths, CTC 39 cases and 23 deaths, FS 32 cases and 19 deaths per 1000 individuals. Assuming reported adherence, SEPT9 averted 37 CRC cases and 23 CRC deaths, COL 34 cases and 20 deaths, FIT‐DNA, FIT, CTC and HS‐gFOBT 16‐25 cases and 10‐16 deaths per 1000 individuals. LYG reflected the effectiveness of each strategy in reducing CRC cases and deaths. Adverse events were more common for COL (3.7 per 1000 screened) and annual SEPT9 (3.4 per 1000 screened), and proportional to the number of colonoscopies. Among the screening strategies recommended by USPSTF, colonoscopy results in the largest benefit when we account for adherence. Adherence rates higher than 65%‐70% would be required for any stool or blood‐based screening modality to match the benefits of colonoscopy. [ABSTRACT FROM AUTHOR]

We simulate entangled linear polymers in free-standing thin film geometries where the confining dimension is on the same scale as or smaller than the bulk chain dimensions. We compare both film-averaged and layer-resolved, spatially inhomogeneous measures of the polymer structure and entanglement network with theoretical models. We find that these properties are controlled by the ratio of both chain- and entanglement-strand length scales to the film thickness. While the film-averaged entanglement properties can be accurately predicted, we identify outstanding challenges in understanding the spatially resolved character of the heterogeneities in the entanglement network, particularly when the scale of both the entanglement strand and the chain end-to-end vector is comparable to or smaller than the film thickness. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about diet resistant celiac disease published in the previous issue.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. CRC incidence and mortality can be reduced through screening. However, in the United States, screening participation remains suboptimal, particularly among underserved populations such as the uninsured, recent immigrants, and racial/ethnic minority groups. Increasing screening rates among underserved populations will reduce the US burden of CRC. In this commentary focusing on underserved populations, we highlight the public health impact of CRC screening, list key challenges to screening the underserved, and review promising approaches to boost screening rates. We identify four key policy and research priorities to increase screening among underserved populations: 1) actively promote the message, “the best test is the one that gets done”; 2) develop and implement methods to identify unscreened individuals within underserved population groups for screening interventions; 3) develop and implement approaches for organized screening delivery; and 4) fund and enhance programs and policies that provide access to screening, diagnostic follow-up, and CRC treatment for underserved populations. This commentary represents the consensus of a diverse group of experts in cancer control and prevention, epidemiology, gastroenterology, and primary care from across the country who formed the Coalition to Boost Screening among the Underserved in the United States. The group was organized and held its first annual working group meeting in conjunction with the World Endoscopy Organization’s annual Colorectal Cancer Screening Committee meeting during Digestive Disease Week 2012 in San Diego, California. [ABSTRACT FROM AUTHOR]

Two-sample hypothesis testing for random graphs arises naturally in neuroscience, social networks, and machine learning. In this article, we consider a semiparametric problem of two-sample hypothesis testing for a class of latent position random graphs. We formulate a notion of consistency in this context and propose a valid test for the hypothesis that two finite-dimensional random dot product graphs on a common vertex set have the same generating latent positions or have generating latent positions that are scaled or diagonal transformations of one another. Our test statistic is a function of a spectral decomposition of the adjacency matrix for each graph and our test procedure is consistent across a broad range of alternatives. We apply our test procedure to real biological data: in a test-retest dataset of neural connectome graphs, we are able to distinguish between scans from different subjects; and in theC. elegansconnectome, we are able to distinguish between chemical and electrical networks. The latter example is a concrete demonstration that our test can have power even for small-sample sizes. We conclude by discussing the relationship between our test procedure and generalized likelihood ratio tests. Supplementary materials for this article are available online. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to assess the correlation between serum and intestinal anti-tumour necrosis factor (TNF) levels, and their relationship to endoscopic disease activity and levels of TNF. Design Cross-sectional study of 30 patients receiving treatment with infliximab or adalimumab for Crohn's disease or UC. For each patient, a sample of serum was matched to tissue biopsies. Endoscopic and histological disease activity was recorded for each tissue sample. Results There was a significant positive correlation between anti-TNF in serum and tissue (r=0.3920, p=0.002), especially in uninflamed tissue (r=0.50, p<0.001), but not with those samples that had inflammation (r=0.19, p=0.54). Anti-TNF concentration in tissue correlated with degree of endoscopic inflammation, except for tissue with severe inflammation in which anti-TNF levels were again lower (mean normalised anti-TNF in tissue: uninflamed=0.93, mild=2.17, moderate=13.71, severe=2.2 inflammation (p=0.0042)). The ratio of anti-TNF-to-TNF in tissue was highest in uninflamed areas and lowest in severely inflamed areas. Patients with active mucosal disease had a higher rate of serum to tissue drug level mismatch when compared to those in remission (73.3% vs 33.3%, respectively; p=0.03). Conclusions Our data suggest that local tissue inflammation characterised by high levels of TNF serves as a sink for anti-TNF. We further postulate that some patients with high serum anti-TNF levels have active disease because tissue levels of anti-TNF are insufficient to neutralise local TNF production. [ABSTRACT FROM AUTHOR]

A complete set of mutually unbiased bases (MUBs) in a Hilbert space of dimension d defines a set of d + 1 orthogonal measurements. Relative to such a set, we define a MUB-balanced state to be a pure state for which the list of probabilities of the d outcomes of any of these measurements is independent of the choice of measurement, up to permutations. In this paper, we explicitly construct a MUB-balanced state for each prime power dimension d for which d = 3 (mod 4). These states have already been constructed by Appleby in unpublished notes, but our presentation here is different in that both the expression for the states themselves and the proof of MUB-balancedness are given in terms of the discrete Wigner function, rather than the density matrix or state vector. The discrete Wigner functions of these states are "rotationally symmetric" in a sense roughly analogous to the rotational symmetry of the energy eigenstates of a harmonic oscillator in the continuous two-dimensional phase space. Upon converting the Wigner function to a density matrix, we find that the states are expressible as real state vectors in the standard basis. We observe numerically that when d is large (and not a power of 3), a histogram of the components of such a state vector appears to form a semicircular distribution. [ABSTRACT FROM AUTHOR]

Colon extranodal marginal zone lymphoma (EMZL) is poorly characterized in the literature. We performed a retrospective review of patients with colon EMZL at our institution and from the Surveillance Epidemiology and End Results (SEER) database. Eight patients were identified in our institution with majority (88%) presenting with stage-I disease. Initial management included active surveillance, polypectomy followed by surveillance, and surgical resection followed by chemotherapy. One patient with concurrent prostate carcinoma received radiation to the rectum. Initial therapy led to complete remission in five out of six treated patients with four of them maintaining remission at 88 months. SEER database identified 361 patients with stage-I colon EMZL. Overall survival for this cohort was 73.9% at 10 years with no significant difference in outcomes between treatment groups. Our single institution experience and the SEER data analysis emphasize indolent nature of colon EMZL and need for non-aggressive therapeutic approaches. [ABSTRACT FROM AUTHOR]

Context.--The gastrointestinal (GI) tract is the most common site of extranodal non-Hodgkin lymphoma, accounting for 20% to 40% of all extranodal lymphomas. The majority of these are systemic processes secondarily involving the GI tract. Primary GI lymphomas are less common, accounting for approximately 10% to 15% of all non-Hodgkin lymphomas. Most non-Hodgkin lymphomas involving the GI tract are of B-cell lineage, of which diffuse large B-cell lymphoma is the most common subtype, irrespective of location. Objective.--To review the lymphoproliferative neoplasms of B-cell and T-cell lineage involving the luminal GI tract according to the most prevalent subtypes at each anatomic site. Data Source.--Systematic search of the PubMed database for updated literature on GI lymphoma epidemiology, subtypes, clinical, endoscopic, and genetic findings. Histologic images are derived from our collection of clinical cases. Conclusions.--The GI tract is the most common site of extranodal lymphoproliferative neoplasms. Recognition of the most frequently encountered GI lymphomas is imperative for patient management and treatment. [ABSTRACT FROM AUTHOR]

Background: Underserved ethnic minority populations experience significant disparities in HIV, hepatitis C virus (HCV), colorectal cancer (CRC), and cervical cancer incidence and mortality. Much of the excess burden of these diseases among underserved communities is due to lack of preventive care, including screening. Barriers to disease screening include low awareness, lack of access to care and health insurance, and cultural beliefs regarding disease prevention. Our current trial aims to examine community health worker (CHW)-delivered, home-based multi-modality screening for HIV, HCV, CRC, and cervical cancer simultaneously.Design: We are conducting a randomized pragmatic trial among 900 Haitian, Hispanic, and African-American participants from diverse underserved communities in South Florida. People between the ages of 50 and 65 who have not had appropriate HIV, HCV, CRC, and cervical cancer screening per United States Preventive Services Task Force (USPSTF) recommendations are eligible for the study. Participants are recruited by CHWs and complete a structured interview to assess multilevel determinants of disease risk. Participants are then randomized to receive HIV, HCV, CRC, and cervical cancer screening via navigation to care by a CHW (Group 1) or via CHW-delivered home-based screening (Group 2). The primary outcome is completion of screening for each of these diseases within 6 months post-enrollment.Discussion: Our trial is among the first to examine the effectiveness of a CHW-delivered, multimodality, home-based disease-screening approach. If found to be effective, this approach may represent a cost-effective strategy for disease screening within underserved and underscreened minority groups.Trial Registration: Clinical Trials.gov # NCT02970136, registered November 21, 2016. [ABSTRACT FROM AUTHOR]

In brain imaging and connectomics, the study of brain networks, estimating the mean of a population of graphs based on a sample is a core problem. Often, this problem is especially difficult because the sample or cohort size is relatively small, sometimes even a single subject, while the number of nodes can be very large with noisy estimates of connectivity. While the element-wise sample mean of the adjacency matrices is a common approach, this method does not exploit the underlying structural properties of the graphs. We propose using a low-rank method that incorporates dimension selection and diagonal augmentation to smooth the estimates and improve performance over the naïve methodology for small sample sizes. Theoretical results for the stochastic block model show that this method offers major improvements when there are many vertices. Similarly, we demonstrate that the low-rank methods outperform the standard sample mean for a variety of independent edge distributions as well as human connectome data derived from the magnetic resonance imaging, especially when the sample sizes are small. Moreover, the low-rank methods yield “eigen-connectomes,” which correlate with the lobe-structure of the human brain and superstructures of the mouse brain. These results indicate that the low-rank methods are the important parts of the toolbox for researchers studying populations of graphs in general and statistical connectomics in particular. [ABSTRACT FROM AUTHOR]