Three scales asymptotic homogenization and its application to layered hierarchical hard tissues

In the present work a novel multiple scales asymptotic homogenization approach is proposed to study the effective properties of hierarchical composites with periodic structure at different length scales. The method is exemplified by solving a linear elastic problem for a composite material with layered hierarchical structure. We recover classical results of two-scale and reiterated homogenization as particular cases of our formulation. The analytical effective coefficients for two phase layered composites with two structural levels of hierarchy are also derived. The method is finally applied to investigate the effective mechanical properties of a single osteon, revealing its practical applicability in the context of biomechanical and engineering applications

The influence of anisotropic growth and geometry on the stress of solid tumors

Solid stresses can affect tumor patho-physiology in at least two ways: directly, by compressing cancer and stromal cells, and indirectly, by deforming blood and lymphatic vessels. In this work, we model the tumor mass as a growing hyperelastic material. We enforce a multiplicative decomposition of the deformation gradient to study the role of anisotropic tumor growth on the evolution and spatial distribution of stresses. Specifically, we exploit radial symmetry and analyze the response of circumferential and radial stresses to (a) degree of anisotropy, (b) geometry of the tumor mass (cylindrical versus spherical shape), and (c) different tumor types (in terms of mechanical properties). According to our results, both radial and circumferential stresses are compressive in the tumor inner regions, whereas circumferential stresses are tensile at the periphery. Furthermore, we show that the growth rate is inversely correlated with the stresses’ magnitudes. These qualitative trends are consistent with experimental results. Our findings therefore elucidate the role of anisotropic growth on the tumor stress state. The potential of stress-alleviation strategies working together with anticancer therapies can result in better treatments

The role of malignant tissue on the thermal distribution of cancerous breast

The present work focuses on the integration of analytical and numerical strategies to investigate the thermal distribution of cancerous breasts. Coupled stationary bioheat transfer equations are considered for the glandular and heterogeneous tumor regions, which are characterized by different thermophysical properties. The cross-section of the cancerous breast is identified by a homogeneous glandular tissue that surrounds the heterogeneous tumor tissue, which is assumed to be a two-phase periodic composite with non-overlapping circular inclusions and a square lattice distribution, wherein the constituents exhibit isotropic thermal conductivity behavior. Asymptotic periodic homogenization method is used to find the effective properties in the heterogeneous region. The tissue effective thermal conductivities are computed analytically and then used in the homogenized model, which is solved numerically. Results are compared with appropriate experimental data reported in the literature. In particular, the tissue scale temperature profile agrees with experimental observations. Moreover, as a novelty result we find that the tumor volume fraction in the heterogeneous zone influences the breast surface temperature

Effective coefficients of isotropic complex dielectric composites in a hexagonal array

Based on the asymptotic homogenization method, the local problems related to two-phase periodic fibrous dielectric composites with isotropic and complex constituents are solved. A hexagonal periodicity distribution of the fibers is considered. Explicit formulas for the real and imaginary parts of the effective dielectric properties are derived. Such formulas can be computed for any desired precision related to a truncation order of an infinite system of algebraic linear equations. Two simple analytical expressions are specified for the first two truncation orders. Comparisons with results via other approachess how a good concordance. Hexagonal periodic lattices of acoustic scatterers are useful structures for acoustic applications

Mathematical modeling of the interplay between stress and anisotropic growth of avascular tumors

In this work, we propose a new mathematical framework for the study of the mutual interplay between anisotropic growth and stresses of an avascular tumor surrounded by an external medium. The mechanical response of the tumor is dictated by anisotropic growth, and reduces to that of an elastic, isotropic, and incompressible material when the latter is not taking place. Both proliferation and death of tumor cells are in turn assumed to depend on the stresses. We perform a parametric analysis in terms of key parameters representing growth anisotropy and the influence of stresses on tumor growth in order to determine how these effects affect tumor progression. We observe that tumor progression is enhanced when anisotropic growth is considered, and that mechanical stresses play a major role in limiting tumor growth

Cardiovascular morbidity and associated risk factors in Spanish patients with chronic inflammatory rheumatic diseases attendingrheumatology clinics: Baseline data of the CARMA Project

Objective: To establish the cardiovascular (CV) morbidity and associated risk factors for CV disease (CVD) in Spanish patients with chronic inflammatory rheumatic diseases (CIRD) and unexposed individuals attending rheumatology clinics. Methods: Analysis of data from the baseline visit of a 10-year prospective study [CARdiovascular in rheuMAtology (CARMA) project] that includes a cohort of patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and another cohort of matched individuals without CIRD attending outpatient rheumatology clinics from 67 hospitals in Spain. Prevalence of CV morbidity, CV risk factors, and systematic coronary risk evaluation (SCORE) assessment were analyzed. Results: A total of 2234 patients (775 RA, 738 AS, and 721 PsA) and 677 unexposed subjects were included. Patients had low disease activity at the time of recruitment. PsA patients had more commonly classic CV risk factors and metabolic syndrome features than did the remaining individuals. The prevalence of CVD was higher in RA (10.5%) than in AS (7.6%), PsA (7.2%), and unexposed individuals (6.4%). A multivariate analysis adjusted for the presence of classic CV risk factors and disease duration revealed a positive trend for CVD in RA (OR = 1.58; 95% CI: 0.90-2.76; p = 0.10) and AS (OR = 1.77; 95% CI: 0.96-3.27; p = 0.07). Disease duration in all CIRD groups and functional capacity (HAQ) in RA were associated with an increased risk of CVD (OR = 2.15; 95% CI: 1.29-3.56; p = 0.003). Most patients had a moderate CV risk according to the SCORE charts. Conclusions: Despite recent advances in the management of CIRD, incidence of CVD remains increased in Spanish subjects with CIRD attending outpatient rheumatology clinics

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN