Tverberg's Theorem at 50: Extensions and Counterexamples

We describe how a powerful new “constraint method” yields many different extensions of the topological version of Tverberg’s 1966 Theorem in the prime power case— and how the same method also was instrumental in the recent spectacular construction of counterexamples for the general case

On a new conformal functional for simplicial surfaces

We introduce a smooth quadratic conformal functional and its weighted version $$W_2=\sum_e \beta^2(e)\quad W_{2,w}=\sum_e (n_i+n_j)\beta^2(e),$$ where $\beta(e)$ is the extrinsic intersection angle of the circumcircles of the triangles of the mesh sharing the edge $e=(ij)$ and $n_i$ is the valence of vertex $i$. Besides minimizing the squared local conformal discrete Willmore energy $W$ this functional also minimizes local differences of the angles $\beta$. We investigate the minimizers of this functionals for simplicial spheres and simplicial surfaces of nontrivial topology. Several remarkable facts are observed. In particular for most of randomly generated simplicial polyhedra the minimizers of $W_2$ and $W_{2,w}$ are inscribed polyhedra. We demonstrate also some applications in geometry processing, for example, a conformal deformation of surfaces to the round sphere. A partial theoretical explanation through quadratic optimization theory of some observed phenomena is presented.Comment: 14 pages, 8 figures, to appear in the proceedings of "Curves and Surfaces, 8th International Conference", June 201

Realizability of Polytopes as a Low Rank Matrix Completion Problem

This article gives necessary and sufficient conditions for a relation to be the containment relation between the facets and vertices of a polytope. Also given here, are a set of matrices parameterizing the linear moduli space and another set parameterizing the projective moduli space of a combinatorial polytope

GPs' willingness to prescribe aspirin for cancer preventive therapy in Lynch syndrome: a factorial randomised trial investigating factors influencing decisions.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) 2020 guidelines recommends aspirin for colorectal cancer prevention for people with Lynch syndrome. Strategies to change practice should be informed by understanding the factors influencing prescribing. AIM: To investigate the optimal type and level of information to communicate with GPs to increase willingness to prescribe aspirin. DESIGN AND SETTING: GPs in England and Wales (n = 672) were recruited to participate in an online survey with a 23 factorial design. GPs were randomised to one of eight vignettes describing a hypothetical patient with Lynch syndrome recommended to take aspirin by a clinical geneticist. METHOD: Across the vignettes, the presence or absence of three types of information was manipulated: 1) existence of NICE guidance; 2) results from the CAPP2 trial; 3) information comparing risks/benefits of aspirin. The main effects and all interactions on the primary (willingness to prescribe) and secondary outcomes (comfort discussing aspirin) were estimated. RESULTS: There were no statistically significant main effects or interactions of the three information components on willingness to prescribe aspirin or comfort discussing harms and benefits. In total, 80.4% (540/672) of GPs were willing to prescribe, with 19.7% (132/672) unwilling. GPs with prior awareness of aspirin for preventive therapy were more comfortable discussing the medication than those unaware (P = 0.031). CONCLUSION: It is unlikely that providing information on clinical guidance, trial results, and information comparing benefits and harms will increase aspirin prescribing for Lynch syndrome in primary care. Alternative multilevel strategies to support informed prescribing may be warranted

How much contextuality?

The amount of contextuality is quantified in terms of the probability of the necessary violations of noncontextual assignments to counterfactual elements of physical reality.Comment: 5 pages, 3 figure

Parameter Estimation and Quantitative Parametric Linkage Analysis with GENEHUNTER-QMOD

Objective: We present a parametric method for linkage analysis of quantitative phenotypes. The method provides a test for linkage as well as an estimate of different phenotype parameters. We have implemented our new method in the program GENEHUNTER-QMOD and evaluated its properties by performing simulations. Methods: The phenotype is modeled as a normally distributed variable, with a separate distribution for each genotype. Parameter estimates are obtained by maximizing the LOD score over the normal distribution parameters with a gradient-based optimization called PGRAD method. Results: The PGRAD method has lower power to detect linkage than the variance components analysis (VCA) in case of a normal distribution and small pedigrees. However, it outperforms the VCA and Haseman-Elston regression for extended pedigrees, nonrandomly ascertained data and non-normally distributed phenotypes. Here, the higher power even goes along with conservativeness, while the VCA has an inflated type I error. Parameter estimation tends to underestimate residual variances but performs better for expectation values of the phenotype distributions. Conclusion: With GENEHUNTER-QMOD, a powerful new tool is provided to explicitly model quantitative phenotypes in the context of linkage analysis. It is freely available at http://www.helmholtz-muenchen.de/genepi/downloads. Copyright (C) 2012 S. Karger AG, Base

Virtual screening for inhibitors of the human TSLP:TSLPR interaction

The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation

Computing the vertices of tropical polyhedra using directed hypergraphs

We establish a characterization of the vertices of a tropical polyhedron defined as the intersection of finitely many half-spaces. We show that a point is a vertex if, and only if, a directed hypergraph, constructed from the subdifferentials of the active constraints at this point, admits a unique strongly connected component that is maximal with respect to the reachability relation (all the other strongly connected components have access to it). This property can be checked in almost linear-time. This allows us to develop a tropical analogue of the classical double description method, which computes a minimal internal representation (in terms of vertices) of a polyhedron defined externally (by half-spaces or hyperplanes). We provide theoretical worst case complexity bounds and report extensive experimental tests performed using the library TPLib, showing that this method outperforms the other existing approaches.Comment: 29 pages (A4), 10 figures, 1 table; v2: Improved algorithm in section 5 (using directed hypergraphs), detailed appendix; v3: major revision of the article (adding tropical hyperplanes, alternative method by arrangements, etc); v4: minor revisio

What’s in a Name? Parents’ and Healthcare Professionals’ Preferred Terminology for Pathogenic Variants in Childhood Cancer Predisposition Genes

Current literature/guidelines regarding the most appropriate term to communicate a cancer-related disease-causing germline variant in childhood cancer lack consensus. Guidelines also rarely address preferences of patients/families. We aimed to assess preferences of parents of children with cancer, genetics professionals, and pediatric oncologists towards terminology to describe a disease-causing germline variant in childhood cancer. Using semi-structured interviews we asked participants their most/least preferred terms from; ‘faulty gene,’ ‘altered gene,’ ‘gene change,’ and ‘genetic variant,’ analyzing responses with directed content analysis. Twenty-five parents, 6 genetics professionals, and 29 oncologists participated. An equal number of parents most preferred ‘gene change,’ ‘altered gene,’ or ‘genetic variant’ (n = 8/25). Parents least preferred ‘faulty gene’ (n = 18/25). Half the genetics professionals most preferred ‘faulty gene’ (n = 3/6); however this was least preferred by the remaining genetics professionals (n = 3/6). Many oncologists most preferred ‘genetic variant’ (n = 11/29) and least preferred ‘faulty gene’ (n = 19/29). Participants across all groups perceived ‘faulty gene’ as having negative connotations, potentially placing blame/guilt on parents/children. Health professionals described challenges selecting a term that was scientifically accurate, easily understood and not distressing to families. Lack of consensus highlights the need to be guided by families’ preferred terminology, while providing accurate explanations regarding implications of genetic findings