Multiscale modelling of vascular tumour growth in 3D: the roles of domain size & boundary condition

We investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. In particular, we determine how the domain size, aspect ratio and initial vascular network influence the tumour's growth dynamics and its long-time composition. We establish whether it is possible to extrapolate simulation results obtained for small domains to larger ones, by constructing a large simulation domain from a number of identical subdomains, each subsystem initially comprising two parallel parent vessels, with associated cells and diffusible substances. We find that the subsystem is not representative of the full domain and conclude that, for this initial vessel geometry, interactions between adjacent subsystems contribute to the overall growth dynamics. We then show that extrapolation of results from a small subdomain to a larger domain can only be made if the subdomain is sufficiently large and is initialised with a sufficiently complex vascular network. Motivated by these results, we perform simulations to investigate the tumour's response to therapy and show that the probability of tumour elimination in a larger domain can be extrapolated from simulation results on a smaller domain. Finally, we demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour

INTERACTION OF BIORESORBABLE COMPOSITE IMPLANTS MADE BY SOLUTION BLOW SPINNING WITH TISSUES

This work represents the results of the study of the surrounding tissues reaction to the implantation of bioresorbable implants formed by the solution blow spinning from polylactic acid and ultrafine calcium phosphate powders, depending on the time and place of implantation. Using scanning electron microscopy it is shown that implants formed from randomly interwoven fibers have interconnected open porosity. It was established that the addition of calcium phosphate ultrafine powders does not cause changes in the formed implants structure. Histological investigation of tissue specimens from the implantation site revealed a high ability of created implants to successful integration with surrounding tissue after 15 days from the moment of implantation. Complete or partial implant resorption with substitution by own tissues was registered at 90 days after implantation. It was established that implantation of composite bioresorbable implants on the ilium bone stimulates the osteogenic process better than the implantation on skull bone within the same period. It was defined that scarification of the outer cortical plate in implant contact points with bone tissue increases the implants ability to stimulate osteogenic process. It was shown that the composite implants filled with calcium phosphate dibasic dehydrate in ultrafine powder form have the largest ability to stimulate osteogenesis

Epizootic Activity of Natural and Anthropourgic Tularemia Foci in the Territory of the Jewish Autonomous Region and the Khabarovsk City Outskirts during the Amur River Flood

Widespread epizootiological investigations were performed to estimate the influence of the Amur River flood on the epizootic activity of tularemia in small rodent populations within natural and anthropourgic foci. Determined were the numbers of the rodent-carriers and epizootic activity of tularemia infection in the forest type, lowland, flood-swamped as well as anthropourgic foci. The capture and enumeration of the rodents was conducted using Gero rat traps. Tested were water and silt samples, rodent nests, pellets and excrements of carnivorous mammals. Blood sera of healthy persons living within the focal territory were examined to reveal the immune-competent cohort. Collected materials were analyzed using bacteriological, genetic diagnostic and serological methods. Extremely high numbers of the carriers were registered in the lowland meadow-field and anthropourgic foci adjacent to the flooded areas. The signs of tularemia epizootic process were observed in the meadow-field and flood-swamped foci. Failed to reveal during the period of high water were the epizooties in the forest foci

Influence of silicone mammoplasty on the immunoendocrine status of female recipients

The article concerns a study of early influence of silicone breast implants on the development of autoimmune reactions and dynamics of prolactin and thyroid hormone levels in women after mammoplasty. At the present time, this issue remains relevant for several reasons: more than 20 million pairs of implants have been installed in the world and the number of their implantations is constantly growing. Despite relative safety of the silicone implants, some of them are periodically banned by regulatory bodies in various countries. At the same time, there is a growing number of controversial publications in the scientific literature, about potential adverse consequences of their use. Some authors suggest an association between the silicone implants and risk of developing autoimmune conditions, connective tissue disorders, and occasional malignancies. On the other hand, the journals are full of publications about the overall safe tolerance of such medical devices by the patients. These considerations served as a pre-requisite to our research. As part of this project, we have assayed serum levels of autoantibodies to ten antigens, as well as contents of prolactin and thyroid hormones by means of ELISA technique in 27 patients before, 3 and 6 months after aesthetic and reconstructive mammoplastics performed within a period of September 2018 to November 2019. As a result, it was found that 5 out of 27 patients exhibited changes in the autoimmunity spectrum and intensity after mammoplasty. In particular, the concentrations of autoantibodies to modified citrullinated vimentin and IgM autoantibodies to cardiolipin exceeded the normal level at 3 and 6 months. In addition, the initially high prolactin concentration in mammoplasty recipients dropped to normal ranges by 3 months after breast surgery, even after several-fold increased initial levels. As for thyroid hormones, there were no statistically significant changes in their dynamics. The increase of autoantibodies to various target antigens after mammoplasty was statistically significant and positively correlated with each other. This can be explained, for example, by dependence on the adjuvant effect of silicone, which is not associated with antigen specificity. However, it may generally stimulate the immune responses

Hadron Energy Reconstruction for the ATLAS Calorimetry in the Framework of the Non-parametrical Method

This paper discusses hadron energy reconstruction for the ATLAS barrel prototype combined calorimeter (consisting of a lead-liquid argon electromagnetic part and an iron-scintillator hadronic part) in the framework of the non-parametrical method. The non-parametrical method utilizes only the known $e/h$ ratios and the electron calibration constants and does not require the determination of any parameters by a minimization technique. Thus, this technique lends itself to an easy use in a first level trigger. The reconstructed mean values of the hadron energies are within $\pm 1$ of the true values and the fractional energy resolution is $[(58\pm3)/\sqrt{E}+(2.5\pm0.3)$. The value of the $e/h$ ratio obtained for the electromagnetic compartment of the combined calorimeter is $1.74\pm0.04$ and agrees with the prediction that $e/h > 1.7$ for this electromagnetic calorimeter. Results of a study of the longitudinal hadronic shower development are also presented. The data have been taken in the H8 beam line of the CERN SPS using pions of energies from 10 to 300 GeV.Comment: 33 pages, 13 figures, Will be published in NIM

RANGING OF ANTIPHOSPOLIPID ANTIBODIES IN THE PATIENTS WITH THROMBOPHILIA AND RECURRENT MISCARRIAGE

Laboratory diagnosis of antiphospholipid syndrome (APS) is based on detection of antiphospholipid antibodies (aPLs). E.g., aPLs are directed against conformational epitopes of the so-called “co-factor” proteins: β2-gycoprotein 1 (β2-GP1), annexin V (An V) and prothrombin (Pt) that are formed during interaction with phospholipids – cardiolipin (CL), phosphatic acid (Pha), phosphatidylcholine (Pch), phosphatidylethanolamine (Pe), phosphatidylglycerol (Pg), phosphatidylinositol (Pi), phosphatidylserine (Ps). A routine methodology of detection based on ELISA testing is challenged by new tests when the antigen is absorbed on another kind of support like microbeads or membranes that can influence density of conformational epitopes for aPL’s binding. The aim of our study was to compare the results of aPLs detection by ELISA and multi-line immunodot assay (MLD). We collected blood serum samples from 45 patients with noncardioembolic ischemic strokes, 19 patients with recurrent deep vein thrombosis of lower limbs, 44 females with recurrent miscarriages, and 50 clinically healthy donors. To compare the results of aPL detection by ELISA and MLD kits, the test systems from different manufacturers were evaluated. We used an ELISA kits for detection of antibodies to CL IgG, aCL IgM, β2-GP1 produced by Euroimmun AG (Mr1) and Orgentec Diagnostica GmbH (Mr2) and MLD – for detection of antibodies to CL, β2-GP1, Pch, Pe, Pg, Pi, Ps, AnV and Pt (Medipan GmbH, Mr3). When a cut-off titer was used as the main index, 30.5% of patients were aPLs-positive with ELISA method by Mr1 and 38%, wiht Mr2. By MLD aPls were detected in 30% of patients. In the same cohort, medium and high aPLs titers (> 40 U/mL) were determined in 12% of patients using ELISA kits. Positive and highly positive aPLs titers were determined in 16% when using a new method by Mr3. Medium and high titer were detected only for antibodies to β2-GP1, CL, An V, Pha and Phs. The use of ELISA approach for detection of aPLs in patients with thrombosis and obstetric pathology is associated with relatively high number of low-positive ELISA results. Due to higher sensitivity for medium and high aPLs titers, MLD testing may be used as a confirming method for APS diagnosis