Association between tumour somatic mutations and venous thromboembolism in the 100,000 Genomes Project cancer cohort:A study protocol

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with cancer, and there is evidence that specific aberrations in tumour biology contribute to the pathophysiology of this condition. We plan to examine the association between tumour somatic mutations and VTE in an existing cohort of patients with cancer, who were enrolled to the flagship Genomics England 100,000 Genomes Project. Here, we outline an a-priori analysis plan to address this objective, including details on study cohort selection, exposure and outcome definitions, annotation of genetic variants and planned statistical analyses. We will assess the effect of 1) deleterious somatic DNA variants in each gene; 2) tumour mutational burden and 3) tumour mutational signatures on the rate of VTE (outcome) in a pan-cancer cohort. Sensitivity analyses will be performed to examine the robustness of any associations, including adjustment for potentially correlated co-variates including tumour type, stage and systemic anti-cancer therapy. We hope that results from this study may help to identify key genes which are implicated in the development of cancer associated thrombosis, which may shed light on related mechanistic pathways and/or provide data which can be integrated into genetic risk prediction models for these patients

Representations of the exceptional and other Lie algebras with integral eigenvalues of the Casimir operator

The uniformity, for the family of exceptional Lie algebras g, of the decompositions of the powers of their adjoint representations is well-known now for powers up to the fourth. The paper describes an extension of this uniformity for the totally antisymmetrised n-th powers up to n=9, identifying (see Tables 3 and 6) families of representations with integer eigenvalues 5,...,9 for the quadratic Casimir operator, in each case providing a formula (see eq. (11) to (15)) for the dimensions of the representations in the family as a function of D=dim g. This generalises previous results for powers j and Casimir eigenvalues j, j<=4. Many intriguing, perhaps puzzling, features of the dimension formulas are discussed and the possibility that they may be valid for a wider class of not necessarily simple Lie algebras is considered.Comment: 16 pages, LaTeX, 1 figure, 9 tables; v2: presentation improved, typos correcte

Tongue-surface movement patterns during speech and swallowing

The tongue has been frequently characterized as being composed of several functionally independent articulators. The question of functional regionality within the tongue was examined by quantifying the strength of coupling among four different tongue locations across a large number of consonantal contexts and participants. Tongue behavior during swallowing was also described. Vertical displacements of pellets affixed to the tongue were extracted from the x-ray microbeam database. Forty-six participants recited 20 vowel-consonant-vowel (VCV) combinations and swallowed 10 ccs of water. Tongue-surface movement patterns were quantitatively described by computing the covariance between the vertical time-histories of all possible pellet pairs. Phonemic differentiation in vertical tongue motions was observed as coupling varied predictably across pellet pairs with place of articulation. Moreover, tongue displacements for speech and swallowing clustered into distinct groups based on their coupling profiles. Functional independence of anterior tongue regions was evidenced by a wide range of movement coupling relations between anterior tongue pellets. The strengths and weaknesses of the covariance-based analysis for characterizing tongue movement are considered