Percolation, Morphogenesis, and Burgers Dynamics in Blood Vessels Formation

Experiments of in vitro formation of blood vessels show that cells randomly spread on a gel matrix autonomously organize to form a connected vascular network. We propose a simple model which reproduces many features of the biological system. We show that both the model and the real system exhibit a fractal behavior at small scales, due to the process of migration and dynamical aggregation, followed at large scale by a random percolation behavior due to the coalescence of aggregates. The results are in good agreement with the analysis performed on the experimental data.Comment: 4 pages, 11 eps figure

Semi-Analytic Stellar Structure in Scalar-Tensor Gravity

Precision tests of gravity can be used to constrain the properties of hypothetical very light scalar fields, but these tests depend crucially on how macroscopic astrophysical objects couple to the new scalar field. We develop quasi-analytic methods for solving the equations of stellar structure using scalar-tensor gravity, with the goal of seeing how stellar properties depend on assumptions made about the scalar coupling at a microscopic level. We illustrate these methods by applying them to Brans-Dicke scalars, and their generalization in which the scalar-matter coupling is a weak function of the scalar field. The four observable parameters that characterize the fields external to a spherically symmetric star (the stellar radius, R, mass, M, scalar `charge', Q, and the scalar's asymptotic value, phi_infty) are subject to two relations because of the matching to the interior solution, generalizing the usual mass-radius, M(R), relation of General Relativity. We identify how these relations depend on the microscopic scalar couplings, agreeing with earlier workers when comparisons are possible. Explicit analytical solutions are obtained for the instructive toy model of constant-density stars, whose properties we compare to more realistic equations of state for neutron star models.Comment: 39 pages, 9 figure

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

<b>Background</b> Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. <p></p> <b>Methods</b> 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. <p></p> <b>Results</b> People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. <p></p> <b>Conclusion</b> People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

Initial/boundary-value problems of tumor growth within a host tissue

This paper concerns multiphase models of tumor growth in interaction with a surrounding tissue, taking into account also the interplay with diffusible nutrients feeding the cells. Models specialize in nonlinear systems of possibly degenerate parabolic equations, which include phenomenological terms related to specific cell functions. The paper discusses general modeling guidelines for such terms, as well as for initial and boundary conditions, aiming at both biological consistency and mathematical robustness of the resulting problems. Particularly, it addresses some qualitative properties such as a priori nonnegativity, boundedness, and uniqueness of the solutions. Existence of the solutions is studied in the one-dimensional time-independent case.Comment: 30 pages, 5 figure

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Colloquium: Mechanical formalisms for tissue dynamics

The understanding of morphogenesis in living organisms has been renewed by tremendous progressin experimental techniques that provide access to cell-scale, quantitative information both on theshapes of cells within tissues and on the genes being expressed. This information suggests that ourunderstanding of the respective contributions of gene expression and mechanics, and of their crucialentanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assistthe design and interpretation of experiments, point out the main ingredients and assumptions, andultimately lead to predictions. The newly accessible local information thus calls for a reflectionon how to select suitable classes of mechanical models. We review both mechanical ingredientssuggested by the current knowledge of tissue behaviour, and modelling methods that can helpgenerate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and tissue scale ("inter-cell") contributions. We recall the mathematical framework developpedfor continuum materials and explain how to transform a constitutive equation into a set of partialdifferential equations amenable to numerical resolution. We show that when plastic behaviour isrelevant, the dissipation function formalism appears appropriate to generate constitutive equations;its variational nature facilitates numerical implementation, and we discuss adaptations needed in thecase of large deformations. The present article gathers theoretical methods that can readily enhancethe significance of the data to be extracted from recent or future high throughput biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few corrections to the published version, all in Appendix D.2 devoted to large deformation

Strategies to augment non-immune system based defence mechanisms against gastrointestinal diseases in pigs

AbstractOur study addresses the first two weeks of the weaning period of piglets during which stressful physiological and environmental conditions experienced by the animals can promote the proliferation of pathogens in the digestive tract. The aim of the study was to identify new feeding strategies that result in boosting the gastrointestinal tract (GIT) microbiota of piglets and improve growth performance, reducing the negative impact of weaning. In order to identify a new synbiotic combination, 12 new putative probiotic strains of Bifidobacterium spp. and three non-digestible oligosaccharides [NDO] were screened in newly weaned piglets. The ability to increase the level of autochthonous bifidobacteria and improve growth performance were assessed. Bifidobacteria strains with a similar ability to develop in the hindgut showed a different effect on piglet performance depending on the dose in which they were provided. Our data support the idea that the presence of fructo-oligosaccharides would stimulate the occurrence of bifidobacteria in the caecum. It was shown that dietary intake of nitrate can generate salivary nitrite, which in turn is acidified in the stomach and could have antimicrobial activity against swallowed pathogens. The efficacy of the resulting synbiotic formula was improved by adding nitrate as antimicrobial. To enhance probiotic survival during gastric transit, a novel technology of microencapsulation was developed and applied to bacteria. The final synbiotic, containing the strain RA 18 of Bifidobacterium animalis subsp. lactis [1011cfu/day], the prebiotic Actilight® [4% of the diet], and nitrate [150mg KNO3/kg feed/day] was tested in organic weaned piglets reared under field conditions. Results show that the strain Ra 18 had a probiotic effect in organic weaned piglets, as it colonized and remained detectable in faecal samples until two weeks after addition. The use of our synbiotic formula improved weight gain, feed efficiency and health status of the weaned piglets

A Mathematical Model of Liver Cell Aggregation In Vitro

The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work

The Exhibition as an Experiment: An Analogy and its Implications

The analogy of the exhibition as an experiment suggests innovative curatorial approaches that challenge institutional practices. This analogy has however a historical precedence in modernism when itbecame paradigmatic of the exhibitions at the Museum of ModernArt in New York in the 1940s, defining the curatorial approach of its founding director Alfred J Barr. This article considers this early useof the analogy of the exhibition as an experiment and further reflects on its redefinition at the turn of the 20th century by examining how both the notions of the exhibition and of the experiment havechanged over time. In particular, the article examines the different meanings and practices inferred by the concepts of the exhibition and the experiment in the first decades of the 20th century and in the present. It outlines how correspondences between cultural and scientific paradigms can be deployed to tease unacknowledged synergies between two modes of knowledge production (i.e. the art exhibition and the experiment) and address questions of presentness, authority and legitimacy that they imply