The quality of advice provided by pharmacists to patients taking direct oral anticoagulants: A mystery shopper study

Pharmacists report being less confident in their knowledge of direct acting oral anticoagulants (DOACs) than of vitamin K antagonists, which may influence their ability to detect and manage complications arising from DOAC use. In a mystery shopper study, patient agents were sent into community pharmacies with symptom or product-related requests related to common complications that might arise during treatment with oral anticoagulants, with each visit being assessed for the preferred outcome. Only 10/41 (24.4%) visits resulted in the preferred outcome. A complete history-taking process, obtaining a medical history, patient characteristics and pharmacist involvement were strong predictors of the preferred outcome being achieved. The preferred outcome was not consistently achieved without pharmacist involvement. The potential for strategies that support comprehensive pharmacist involvement in over-the-counter requests should be considered to ensure the provision of optimal care to patients taking high-risk medications such as DOACs

Electrochemical machining of stainless steel microelements with ultrashort voltage pulses

An electrochemical pulse technique enables the fabrication of three-dimensional microelements from stainless steel. The method is based on the application of ultrashort (nanosecond) voltage pulses, whereupon electrochemical reactions are locally confined with submicrometer precision. Employing properly shaped tool electrodes enables the machining of freestanding cantilevers or microstructures directly to a metal sheet. Due to gentle removal of the material, the grain structure of the material is revealed without any chemical or mechanical modifications. This is demonstrated by measuring the vibration frequency of a cantilever, and agrees well with the value derived from the bulk material properties

Supersymmetric black holes in 2D dilaton supergravity: baldness and extremality

We present a systematic discussion of supersymmetric solutions of 2D dilaton supergravity. In particular those solutions which retain at least half of the supersymmetries are ground states with respect to the bosonic Casimir function (essentially the ADM mass). Nevertheless, by tuning the prepotential appropriately, black hole solutions may emerge with an arbitrary number of Killing horizons. The absence of dilatino and gravitino hair is proven. Moreover, the impossibility of supersymmetric dS ground states and of nonextremal black holes is confirmed, even in the presence of a dilaton. In these derivations the knowledge of the general analytic solution of 2D dilaton supergravity plays an important role. The latter result is addressed in the more general context of gPSMs which have no supergravity interpretation. Finally it is demonstrated that the inclusion of non-minimally coupled matter, a step which is already nontrivial by itself, does not change these features in an essential way.Comment: 30 pages, LaTeX, v2: mayor revision (rearranged title, shortened abstract, revised introduction, inserted section from appendix to main text, added subsection with new material on non-SUGRA gPSMs, added clarifying remarks at some places, updated references); v3: corrected minor misprints, added note with a new referenc

Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates

Computational drug design based on artificial intelligence is an emerging research area. At the time of writing this paper, the world suffers from an outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus replication is via protease inhibition. We propose an evolutionary multi-objective algorithm (EMOA) to design potential protease inhibitors for SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA maximizes the binding of candidate ligands to the protein using the docking tool QuickVina 2, while at the same time taking into account further objectives like drug-likeliness or the fulfillment of filter constraints. The experimental part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202

Diffusion on a solid surface: Anomalous is normal

We present a numerical study of classical particles diffusing on a solid surface. The particles' motion is modeled by an underdamped Langevin equation with ordinary thermal noise. The particle-surface interaction is described by a periodic or a random two dimensional potential. The model leads to a rich variety of different transport regimes, some of which correspond to anomalous diffusion such as has recently been observed in experiments and Monte Carlo simulations. We show that this anomalous behavior is controlled by the friction coefficient, and stress that it emerges naturally in a system described by ordinary canonical Maxwell-Boltzmann statistics

Two-Dimensional N=(2,2) Dilaton Supergravity from Graded Poisson-Sigma Models II: Analytic Solution and BPS States

The integrability of N=(2,2) dilaton supergravity in two dimensions is studied by the use of the graded Poisson Sigma model approach. Though important differences compared to the purely bosonic models are found, the general analytic solutions are obtained. The latter include minimally gauged models as well as an ungauged version. BPS solutions are an especially interesting subclass.Comment: 23 p LaTe

Role of the vector genome and underlying factor IX mutation in immune responses to AAV gene therapy for hemophilia B

BACKGROUND: Self-complementary adeno-associated virus (scAAV) vectors have become a desirable vector for therapeutic gene transfer due to their ability to produce greater levels of transgene than single-stranded AAV (ssAAV). However, recent reports have suggested that scAAV vectors are more immunogenic than ssAAV. In this study, we investigated the effects of a self-complementary genome during gene therapy with a therapeutic protein, human factor IX (hF.IX). METHODS: Hemophilia B mice were injected intramuscularly with ss or scAAV1 vectors expressing hF.IX. The outcome of gene transfer was assessed, including transgene expression as well as antibody and CD8(+) T cell responses to hF.IX. RESULTS: Self-complementary AAV1 vectors induced similar antibody responses (which eliminated systemic hF.IX expression) but stronger CD8(+) T cell responses to hF.IX relative to ssAAV1 in mice with F9 gene deletion. As a result, hF.IX-expressing muscle fibers were effectively eliminated in scAAV-treated mice. In contrast, mice with F9 nonsense mutation (late stop codon) lacked antibody or T cell responses, thus showing long-term expression regardless of the vector genome. CONCLUSIONS: The nature of the AAV genome can impact the CD8(+) T cell response to the therapeutic transgene product. In mice with endogenous hF.IX expression, however, this enhanced immunogenicity did not break tolerance to hF.IX, suggesting that the underlying mutation is a more important risk factor for transgene-specific immunity than the molecular form of the AAV genome

Exploration Strategies for Discovery of Interactivity in Visualizations

We investigate how people discover the functionality of an interactive visualization that was designed for the general public. While interactive visualizations are increasingly available for public use, we still know little about how the general public discovers what they can do with these visualizations and what interactions are available. Developing a better understanding of this discovery process can help inform the design of visualizations for the general public, which in turn can help make data more accessible. To unpack this problem, we conducted a lab study in which participants were free to use their own methods to discover the functionality of a connected set of interactive visualizations of public energy data. We collected eye movement data and interaction logs as well as video and audio recordings. By analyzing this combined data, we extract exploration strategies that the participants employed to discover the functionality in these interactive visualizations. These exploration strategies illuminate possible design directions for improving the discoverability of a visualization's functionality

Genomic analysis of dominance effects on milk production and conformation traits in Fleckvieh cattle

Background Estimates of dominance variance in dairy cattle based on pedigree data vary considerably across traits and amount to up to 50% of the total genetic variance for conformation traits and up to 43% for milk production traits. Using bovine SNP (single nucleotide polymorphism) genotypes, dominance variance can be estimated both at the marker level and at the animal level using genomic dominance effect relationship matrices. Yield deviations of high-density genotyped Fleckvieh cows were used to assess cross-validation accuracy of genomic predictions with additive and dominance models. The potential use of dominance variance in planned matings was also investigated. Results Variance components of nine milk production and conformation traits were estimated with additive and dominance models using yield deviations of 1996 Fleckvieh cows and ranged from 3.3% to 50.5% of the total genetic variance. REML and Gibbs sampling estimates showed good concordance. Although standard errors of estimates of dominance variance were rather large, estimates of dominance variance for milk, fat and protein yields, somatic cell score and milkability were significantly different from 0. Cross-validation accuracy of predicted breeding values was higher with genomic models than with the pedigree model. Inclusion of dominance effects did not increase the accuracy of the predicted breeding and total genetic values. Additive and dominance SNP effects for milk yield and protein yield were estimated with a BLUP (best linear unbiased prediction) model and used to calculate expectations of breeding values and total genetic values for putative offspring. Selection on total genetic value instead of breeding value would result in a larger expected total genetic superiority in progeny, i.e. 14.8% for milk yield and 27.8% for protein yield and reduce the expected additive genetic gain only by 4.5% for milk yield and 2.6% for protein yield. Conclusions Estimated dominance variance was substantial for most of the analyzed traits. Due to small dominance effect relationships between cows, predictions of individual dominance deviations were very inaccurate and including dominance in the model did not improve prediction accuracy in the cross-validation study. Exploitation of dominance variance in assortative matings was promising and did not appear to severely compromise additive genetic gain