Undulation instabilities in the meniscus of smectic membranes

Using optical microscopy, phase shifting interferometry and atomic force microscopy, we demonstrate the existence of undulated structures in the meniscus of ferroelectric smectic-C* films. The meniscus is characterized by a periodic undulation of the smectic-air interface, which manifests itself in a striped pattern. The instability disappears in the untilted smectic-A phase. The modulation amplitude and wavelength both depend on meniscus thickness. We study the temperature evolution of the structure and propose a simple model that accounts for the observed undulations.Comment: Submitted to PR

Clinical practice guidelines: towards better quality guidelines and increased international collaboration

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Measurable Residual Disease in High-Risk Acute Myeloid Leukemia

Mounting evidence suggests measurable residual disease (MRD) assessments are prognostic in acute myeloid leukemia (AML). High-risk AML encompasses a subset of AML with poor response to therapy and prognosis, with features such as therapy-related AML, an antecedent hematologic disorder, extramedullary disease (in adults), and selected mutations and cytogenetic abnormalities. Historically, few patients with high-risk AML achieved deep and durable remission with conventional chemotherapy; however, newer agents might be more effective in achieving MRD-negative remission. CPX-351 (dual-drug liposomal encapsulation of daunorubicin/cytarabine at a synergistic ratio) demonstrated MRD-negativity rates of 36\u201364% across retrospective studies in adults with newly diagnosed high-risk AML and 84% in pediatric patients with first-relapse AML. Venetoclax (BCL2 inhibitor) demonstrated MRD-negativity rates of 33\u201353% in combination with hypomethylating agents for high-risk subgroups in studies of older adults with newly diagnosed AML who were ineligible for intensive therapy and 65% in combination with chemotherapy in pediatric patients with relapsed/refractory AML. However, there is no consensus on optimal MRD methodology in AML, and the use of different techniques, sample sources, sensitivity thresholds, and the timing of assessments limit comparisons across studies. Robust MRD analyses are needed in future clinical studies, and MRD monitoring should become a routine aspect of AML management

A constructive study of the module structure of rings of partial differential operators

The purpose of this paper is to develop constructive versions of Stafford's theorems on the module structure of Weyl algebras A n (k) (i.e., the rings of partial differential operators with polynomial coefficients) over a base field k of characteristic zero. More generally, based on results of Stafford and Coutinho-Holland, we develop constructive versions of Stafford's theorems for very simple domains D. The algorithmization is based on the fact that certain inhomogeneous quadratic equations admit solutions in a very simple domain. We show how to explicitly compute a unimodular element of a finitely generated left D-module of rank at least two. This result is used to constructively decompose any finitely generated left D-module into a direct sum of a free left D-module and a left D-module of rank at most one. If the latter is torsion-free, then we explicitly show that it is isomorphic to a left ideal of D which can be generated by two elements. Then, we give an algorithm which reduces the number of generators of a finitely presented left D-module with module of relations of rank at least two. In particular, any finitely generated torsion left D-module can be generated by two elements and is the homomorphic image of a projective ideal whose construction is explicitly given. Moreover, a non-torsion but non-free left D-module of rank r can be generated by r+1 elements but no fewer. These results are implemented in the Stafford package for D=A n (k) and their system-theoretical interpretations are given within a D-module approach. Finally, we prove that the above results also hold for the ring of ordinary differential operators with either formal power series or locally convergent power series coefficients and, using a result of Caro-Levcovitz, also for the ring of partial differential operators with coefficients in the field of fractions of the ring of formal power series or of the ring of locally convergent power series. © 2014 Springer Science+Business Media

Holonomic functions of several complex variables and singularities of anisotropic Ising n-fold integrals

Lattice statistical mechanics, often provides a natural (holonomic) framework to perform singularity analysis with several complex variables that would, in a general mathematical framework, be too complex, or could not be defined. Considering several Picard-Fuchs systems of two-variables "above" Calabi-Yau ODEs, associated with double hypergeometric series, we show that holonomic functions are actually a good framework for actually finding the singular manifolds. We, then, analyse the singular algebraic varieties of the n-fold integrals $\chi^{(n)}$, corresponding to the decomposition of the magnetic susceptibility of the anisotropic square Ising model. We revisit a set of Nickelian singularities that turns out to be a two-parameter family of elliptic curves. We then find a first set of non-Nickelian singularities for $\chi^{(3)}$ and $\chi^{(4)}$, that also turns out to be rational or ellipic curves. We underline the fact that these singular curves depend on the anisotropy of the Ising model. We address, from a birational viewpoint, the emergence of families of elliptic curves, and of Calabi-Yau manifolds on such problems. We discuss the accumulation of these singular curves for the non-holonomic anisotropic full susceptibility.Comment: 36 page

Quality and methods of developing practice guidelines

BACKGROUND: It is not known whether there are differences in the quality and recommendations between evidence-based (EB) and consensus-based (CB) guidelines. We used breast cancer guidelines as a case study to assess for these differences. METHODS: Five different instruments to evaluate the quality of guidelines were identified by a literature search. We also searched MEDLINE and the Internet to locate 8 breast cancer guidelines. These guidelines were classified in three categories: evidence based, consensus based and consensus based with no explicit consideration of evidence (CB-EB). Each guideline was evaluated by three of the authors using each of the instruments. For each guideline we assessed the agreement among 14 decision points which were selected from the NCCN (National Cancer Comprehensive Network) guidelines algorithm. For each decision point we recorded the level of the quality of the information used to support it. A regression analysis was performed to assess if the percentage of high quality evidence used in the guidelines development was related to the overall quality of the guidelines. RESULTS: Three guidelines were classified as EB, three as CB-EB and two as CB. The EB guidelines scored better than CB, with the CB-EB scoring in the middle among all instruments for guidelines quality assessment. No major disagreement in recommendations was detected among the guidelines regardless of the method used for development, but the EB guidelines had a better agreement with the benchmark guideline for any decision point. When the source of evidence used to support decision were of high quality, we found a higher level of full agreement among the guidelines' recommendations. Up to 94% of variation in the quality score among guidelines could be explained by the quality of evidence used for guidelines development. CONCLUSION: EB guidelines have a better quality than CB guidelines and CB-EB guidelines. Explicit use of high quality evidence can lead to a better agreement among recommendations. However, no major disagreement among guidelines was noted regardless of the method for their development

Basic Module Theory over Non-Commutative Rings with Computational Aspects of Operator Algebras

The present text surveys some relevant situations and results where basic Module Theory interacts with computational aspects of operator algebras. We tried to keep a balance between constructive and algebraic aspects.Comment: To appear in the Proceedings of the AADIOS 2012 conference, to be published in Lecture Notes in Computer Scienc

Dislocation loops in overheated free-standing smectic films

Static and dynamic phenomena in overheated free-standing smectic-A films are studied using a generalization of de Gennes' theory for a confined presmectic liquid. A static application is to determine the profile of the film meniscus and the meniscus contact angle, the results being compared with those of a recent study employing de Gennes' original theory. The dynamical generalization of the theory is based on on a time-dependent Ginzburg-Landau approach. This is used to compare two modes for layer-thinning transitions in overheated films, namely "uniform thinning" vs. nucleation of dislocation loops. Properties such as the line tension and velocity of a moving dislocation line are evaluated self-consistently by the theory.Comment: 16 pages, 8 figure

Modeling Dipolar and Quadrupolar Defect Structures generated by Chiral Islands in Freely-Suspended Liquid Crystal Films

We report a detailed theoretical analysis of novel quadrupolar interactions observed between islands, which are disk-like inclusions of extra layers, floating in thin, freely suspended smectic C liquid crystal films. Strong tangential anchoring at the island boundaries result in a strength +1 chiral defect in each island and a companion -1 defect in the film, these forming a topological dipole. While islands of the same handedness form linear chains with the topological dipoles pointing in the same direction, as reported in the literature, islands with different handedness form compact quadrupolar structures with the associated dipoles pointing in opposite directions. The interaction between such heterochiral island--defect pairs is complex, with the defects moving to minimize the director field distortion as the distance between the islands changes. The details of the inter-island potential and the trajectories of the -1 defects depend strongly on the elastic anisotropy of the liquid crystal, which can be modified in the experiments by varying the material chirality of the liquid crystal. A Landau model that describes the energetics of freely mobile defects is solved numerically to find equilibrium configurations for a wide range of parameters.Comment: 8 pages, 9 figure

Development and Validation of a Tool to Assess the Quality of Clinical Practice Guideline Recommendations

Clinical practice guidelines (CPGs) may lack rigor and suitability to the setting in which they are to be applied. Methods to yield clinical practice guideline recommendations that are credible and implementable remain to be determined. To describe the development of AGREE-REX (Appraisal of Guidelines Research and Evaluation-Recommendations Excellence), a tool designed to evaluate the quality of clinical practice guideline recommendations. A cross-sectional study of 322 international stakeholders representing CPG developers, users, and researchers was conducted between December 2015 and March 2019. Advertisements to participate were distributed through professional organizations as well as through the AGREE Enterprise social media accounts and their registered users. Between 2015 and 2017, participants appraised 1 of 161 CPGs using the Draft AGREE-REX tool and completed the AGREE-REX Usability Survey. Usability and measurement properties of the tool were assessed with 7-point scales (1 indicating strong disagreement and 7 indicating strong agreement). Internal consistency of items was assessed with the Cronbach, and the Spearman-Brown reliability adjustment was used to calculate reliability for 2 to 5 raters. A total of 322 participants (202 female participants [62.7%]; 83 aged 40-49 years [25.8%]) rated the survey items (on a 7-point scale). All 11 items were rated as easy to understand (with a mean [SD] ranging from 5.2 [1.38] for the alignment of values item to 6.3 [0.87] for the evidence item) and easy to apply (with a mean [SD] ranging from 4.8 [1.49] for the alignment of values item to 6.1 [1.07] for the evidence item). Participants provided favorable feedback on the tool's instructions, which were considered clear (mean [SD], 5.8 [1.06]), helpful (mean [SD], 5.9 [1.00]), and complete (mean [SD], 5.8 [1.11]). Participants considered the tool easy to use (mean [SD], 5.4 [1.32]) and thought that it added value to the guideline enterprise (mean [SD], 5.9 [1.13]). Internal consistency of the items was high (Cronbach = 0.94). Positive correlations were found between the overall AGREE-REX score and the implementability score (r = 0.81) and the clinical credibility score (r = 0.76). This cross-sectional study found that the AGREE-REX tool can be useful in evaluating CPG recommendations, differentiating among them, and identifying those that are clinically credible and implementable for practicing health professionals and decision makers who use recommendations to inform clinical policy.