Activity of species-specific antibiotics against Crohnʼs disease–associated adherent-invasive Escherichia coli

Background: Crohn's disease (CD) is associated with bacterial dysbiosis that frequently includes colonization by adherent-invasive Escherichia coli (AIEC). AIEC are adept at forming biofilms and are able to invade host cells and stimulate the production of proinflammatory cytokines. The use of traditional antibiotics for the treatment of CD shows limited efficacy. In this study, we investigate the use of species-specific antibiotics termed colicins for treatment of CD-associated AIEC. Methods: Colicin activity was tested against a range of AIEC isolates growing in the planktonic and biofilm mode of growth. Colicins were also tested against AIEC bacteria associated with T84 intestinal epithelial cells and surviving inside RAW264.7 macrophages using adhesion assays and gentamicin protection assay, respectively. Uptake of colicins into eukaryotic cells was visualized using confocal microscopy. The effect of colicin treatment on the production of proinflammatory cytokine tumor necrosis factor alpha by macrophages was assessed by an enzyme-linked immunosorbent assay. Results: Colicins show potent activity against AIEC bacteria growing as biofilms when delivered either as a purified protein or through a colicin-producing bacterial strain. In addition, colicins E1 and E9 are able to kill cell-associated and intracellular AIEC, but do not show toxicity toward macrophage cells or stimulate the production of proinflammatory cytokines. Colicin killing of intracellular bacteria occurs after entry of colicin protein into AIEC-infected macrophage compartments by actin-mediated endocytosis. Conclusions: Our results demonstrate the potential of colicins as highly selective probiotic therapeutics for the eradication of E. coli from the gastrointestinal tract of patients with CD

Audit Quality Indicators: Perceptions of Junior-level Auditors

Purpose In an effort to develop an audit quality (AQ) framework specific to the US audit market, the Public Company Accounting Oversight Board (PCAOB) recently issued a concept release proposing 28 audit quality indicators (AQIs) along three dimensions: audit professionals, audit process and audit results. Using AQIs initially proposed by the PCAOB, as well as AQIs suggested by prior literature, the authors solicit perceptions from junior-level (senior and staff) auditors to investigate the current state of practice along many of the AQIs relating to audit professionals and audit process. Design/methodology/approach In the study, 78 junior-level auditors responded to the survey. Findings An analysis of the responses suggests auditors engage in activities and audit firms promote conditions that at times improve, and at other times, reduce audit quality. The authors find that individual auditors’ perceptions differ across experience level, gender and audit firm size for certain AQIs. Practical implications The study is useful to the PCAOB because it provides insights to help assess the value of potential AQIs in differentiating AQ. The study is also useful to other regulators because it describes audit staff and seniors’ perceptions of apparent firm and auditor compliance with accounting and auditing standards. Practitioners should find this information useful in helping to identify possible root causes of audit deficiencies, a challenge put forth to firms by the PCAOB. Originality/value This study provides academia with evidence on AQ from practicing auditors, which informs existing and future research along. The study complements existing work by showing how individual auditor characteristics (experience and gender) at the junior levels may impact AQ in practic

Numerical Homogenization of Heterogeneous Fractional Laplacians

In this paper, we develop a numerical multiscale method to solve the fractional Laplacian with a heterogeneous diffusion coefficient. When the coefficient is heterogeneous, this adds to the computational costs. Moreover, the fractional Laplacian is a nonlocal operator in its standard form, however the Caffarelli-Silvestre extension allows for a localization of the equations. This adds a complexity of an extra spacial dimension and a singular/degenerate coefficient depending on the fractional order. Using a sub-grid correction method, we correct the basis functions in a natural weighted Sobolev space and show that these corrections are able to be truncated to design a computationally efficient scheme with optimal convergence rates. A key ingredient of this method is the use of quasi-interpolation operators to construct the fine scale spaces. Since the solution of the extended problem on the critical boundary is of main interest, we construct a projective quasi-interpolation that has both $d$ and $d+1$ dimensional averages over subsets in the spirit of the Scott-Zhang operator. We show that this operator satisfies local stability and local approximation properties in weighted Sobolev spaces. We further show that we can obtain a greater rate of convergence for sufficient smooth forces, and utilizing a global $L^2$ projection on the critical boundary. We present some numerical examples, utilizing our projective quasi-interpolation in dimension $2+1$ for analytic and heterogeneous cases to demonstrate the rates and effectiveness of the method

A Review of the Open Educational Resources (OER) Movement: Achievements, Challenges, and New Opportunities

Examines the state of the foundation's efforts to improve educational opportunities worldwide through universal access to and use of high-quality academic content

Polarimetric variations of binary stars. II. Numerical simulations for circular and eccentric binaries in Mie scattering envelopes

We present numerical simulations of the periodic polarimetric variations produced by a binary star placed at the center of an empty spherical cavity inside a circumbinary ellipsoidal and optically thin envelope made of dust grains. Mie single-scattering is considered along with pre- and post-scattering extinction factors which produce a time-varying optical depth and affect the morphology of the periodic variations. We are interested in the effects that various parameters will have on the average polarization, the amplitude of the polarimetric variations, and the morphology of the variability. We show that the absolute amplitudes of the variations are smaller for Mie scattering than for Thomson scattering. Among the four grain types that we have studied, the highest polarizations are produced by grains with sizes in the range 0.1-0.2 micron. In general, the variations are seen twice per orbit. In some cases, because spherical dust grains have an asymmetric scattering function, the polarimetric curves produced also show variations seen once per orbit. Circumstellar disks produce polarimetric variations of greater amplitude than circumbinary envelopes. Another goal of these simulations is to see if the 1978 BME (Brown, McLean, & Emslie, ApJ, 68, 415) formalism, which uses a Fourier analysis of the polarimetric variations to find the orbital inclination for Thomson-scattering envelopes, can still be used for Mie scattering. We find that this is the case, if the amplitude of the variations is sufficient and the true inclinations is i_true > 45 deg. For eccentric orbits, the first-order coefficients of the Fourier fit, instead of second-order ones, can be used to find almost all inclinations.Comment: 23 pages, 5 figures, to be published in Astronomical Journa

Estimating the weak-lensing rotation signal in radio cosmic shear surveys

Weak lensing has become an increasingly important tool in cosmology and the use of galaxy shapes to measure cosmic shear has become routine. The weak-lensing distortion tensor contains two other effects in addition to the two components of shear: the convergence and rotation. The rotation mode is not measurable using the standard cosmic shear estimators based on galaxy shapes, as there is no information on the original shapes of the images before they were lensed. Due to this, no estimator has been proposed for the rotation mode in cosmological weak-lensing surveys, and the rotation mode has never been constrained. Here, we derive an estimator for this quantity, which is based on the use of radio polarisation measurements of the intrinsic position angles of galaxies. The rotation mode can be sourced by physics beyond $\Lambda$CDM, and also offers the chance to perform consistency checks of $\Lambda$CDM and of weak-lensing surveys themselves. We present simulations of this estimator and show that, for the pedagogical example of cosmic string spectra, this estimator could detect a signal that is consistent with the constraints from Planck. We examine the connection between the rotation mode and the shear $B$-modes and thus how this estimator could help control systematics in future radio weak-lensing surveys

Perceptions of High Quality Professional Development: Do Teachers and Administrators Agree?

This study used a survey research design to gather educator perceptions about a particular professional development (PD) event they deemed effective. Responses were used to measure HQPD characteristics by PD event, across roles, grade levels and the combination of roles and grade levels. Authors of Garet et. al. (2001, Winter), granted permission to use the Teacher Activity Survey (TAS), so it was modified for this study (Appendix B), mapped to the HQPD characteristics (Appendix D) and was used to collect participant responses. Work by Garet et. al. (2001, Winter) and Sappington et. al. (2012) were used to create the Structures, Processes and Features (SPF) model (Appendix A). SPF is a three-dimensional model used to display levels of duration, collaboration, and core features to identify a resultant frame classification for the PD event. Emergent themes were identified through statistical analyses that included descriptive statistics, factor analysis, ANOVA, MANOVA, correlation studies and X2 (Chi-squared) tests. Findings were reviewed to determine accuracy of the modified TAS and SPF instruments. Additionally, the impact of leadership was evaluated as one component of the core features characteristic. Finally, recommendations for improvement and further research were offered

Are oral agents effective for the treatment of verruca vulgaris?

Of the available oral therapies for common warts, none has sufficient evidence to recommend it as an effective therapy (strength of recommendation [SOR]: B). To date, no oral agent has been shown to be effective in a randomized, placebo-controlled, double-blinded trial. Very limited evidence is emerging that zinc may be effective (SOR: C)