Diagnosing Aging: I. Problem of Reliability of Linear Regression Models of Biological Age

Abstract-The problem of the reliability of linear regression models of biological age assessment was studied using an experimental population of patients of a geroprophylactic center. The main factors of the model quality (interpopulation difference, method of approximation of biological age, and methods of approximation of statistical significance of parameters of biological age models) were tested. New equations were derived for calculating biological age. All parameters of these equations meet the requirements of significance. It was shown that if the nonlinear character of age dynamics of biological markers of aging and the statistical significance of model parameter estimates are taken into account, the model of biological age is substantially simplified and its reliability increases

ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ТРОМБОЦИТАРНОГО ФАКТОРА РОСТА PDGF-BB И ST2 ПРИ ОТТОРЖЕНИИ ТРАНСПЛАНТИРОВАННОГО СЕРДЦА

Aim: to determine the association between plasma concentrations of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) with histochemical and immunohistochemical signs of heart rejection.Materials and methods. The study included 98 heart recipients aged from 12 to 69 (mean age 43 ± 14) years, of which 78 men. In 68 patients dilated cardiomyopathy was diagnosed, 30 recipients were diagnosed with coronary heart disease. The concentrations of placental growth factor (PlGF-1), platelet-derived growth factor (PDGF-BB), soluble CD40 ligand (sCD40L) were measured using xMAP technology. The concentrations of ST2 cardiac biomarker were measured by ELISA.Results. No correlation was found between the levels of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) and gender, age and diagnosis. The rejection was diagnosed via biopsy in 49 biopsies taken from 37 recipients. 1A rejection was found in 25 patients (34 biopsies), 1B rejection was identifi ed in 2 patients (3 biopsies), 3A rejection was diagnosed in 4 patients. Immunohistochemical signs of humoral rejection were identifi ed in 3 patients. The combination of acute cellular and humoral rejection was found in 4 patients (5 biopsies). The PDGFBB level was measured at the same day as the biopsy was taken, and it was shown to be signifi cantly higher in patients with rejection (p = 0.02). Rejection frequency was signifi cantly higher in patients with high PDGF-BB level (≥2473.7 pg/ml, RR = 1.64 ± 0.23; 95% CI [1.03–2.61]). Rejection frequency increased to 2.11 ± 0.34 [95% CI [1.08–4.11]] in recipients with ST2 and PDGF-BB concentration higher than the median value. The highest predictive value for heart rejection can be reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2 (RR = 2.51 ± 0.38; 95% CI [1.18–5.3]).Conclusion. PDGF-BB has moderate predictive value for heart rejection. The highest predictive value for heart rejection was reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2.Цель: определить связь концентрации биомаркеров sCD40L, PDGF-BB, PlGF-1, ST2 в плазме крови реципиентов сердца с наличием и выраженностью гистохимических и иммуногистохимических признаков отторжения сердечного трансплантата.Материалы и методы. В исследование включены 98 пациентов с трансплантированным сердцем в возрасте от 12 до 69 (43 ± 14) лет, из них 78 мужчин. У 68 реципиентов до трансплантации сердца была диагностирована дилатационная кардиомиопатия, у 30 – ишемическая болезнь сердца. Концентрацию плацентарного фактора роста (PlGF-1), фактора роста тромбоцитов (PDGF-BB), растворимой формы лиганда CD40 (sCD40L) измеряли с использованием мультиплексной технологии; концентрацию стимулирующего фактора роста ST2 – с помощью иммуноферментного анализа.Результаты. Концентрация каждого биомаркера не зависела от пола, возраста и диагноза до трансплантации. У 37 пациентов (по результатам 49 биопсий) были диагностированы признаки отторжения. Гистохимические признаки острого клеточного отторжения – у 30 реципиентов (в 41 биоптате): 1А – у 25 пациентов (в 34 биоптатах), 1В – у двух пациентов (в трех биоптатах), 3А – у четырех пациентов. Иммуногистохимические признаки антителоопосредованного отторжения выявлены у трех пациентов. Сочетание острого клеточного и гуморального отторжения обнаружено у четырех пациентов (в пяти биоптатах). Концентрация PDGF-BB, измеренная в день эндомиокардиальной биопсии, была достоверно выше у пациентов с отторжением (p = 0,02). У реципиентов сердца с уровнем PDGF-BB выше медианы (2473,7 пг/мл) риск отторжения был в 1,64 раза выше, чем у пациентов с уровнем ниже медианы. У реципиентов с концентрацией и ST2, и PDGF-BB, превышающей значения медианы, относительный риск отторжения возрастал до 2,11 ± 0,34 [95% ДИ 1,08–4,11]. Наибольшей диагностической значимостью в отношении отторжения трансплантата обладала панель из трех биомаркеров (sCD40L, PlGF-1, ST2): RR = 2,51 ± 0,38 [95% ДИ 1,18–5,3].Заключение. PDGF-BB обладает умеренной прогностической значимостью в отношении отторжения трансплантированного сердца. Наибольшей диагностической значимостью обладает панель из трех биомаркеров: sCD40L, PlGF-1, ST2

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

Proppant transport in hydraulic fracturing : crack tip screen-out in KGD and P3D models

The aim of this study is to develop a model for proppant transport in hydraulic fractures capable of capturing both gravitational settling and tip screen-out effects, while prohibiting the particles from reaching the crack tips by imposing a width restriction based on the particle size. First, the equations that govern the propagation of hydraulic fractures and the proppant transport inside them are formulated. They are based on the solution for the steady flow of a viscous fluid, mixed with spherical particles, in a channel, which is obtained assuming an empirical constitutive model. This proppant transport model is applied to two fracture geometries – Khristianovich-Zheltov-Geertsma-De Klerk (KGD) and pseudo-3D (P3D). Numerical simulations show that the proposed method makes it possible to capture proppant plug formation and growth, as well as the gravitational settling for both geometries. A dimensionless parameter, whose magnitude reflects the intensity of the settling, is introduced for the P3D fracture. [The previous file was updated 2014-08-13 to reflect changes to publication].Science, Faculty ofMathematics, Department ofUnreviewedFacult

An enhanced pseudo-3D model for hydraulic fracturing accounting for viscous height growth, non-local elasticity, and lateral toughness

The goal of this paper is to develop an enhanced pseudo-3D (P3D) model for hydraulic fracturing (HF), whose predictions are more accurate compared to that of the original P3D model, but which requires significantly less computational resources than a fully planar HF simulator. We show that the lack of viscous resistance in the height growth and the local approximation in the computation of elastic interactions, which precludes the incorporation of lateral toughness, are the primary weaknesses of the original P3D model that considers symmetric stress barriers and no leak-off. To account for the viscous resistance, an apparent fracture toughness is introduced. The apparent toughness is calibrated using a one-dimensional HF model resulting in an approximate expression that captures all regimes of propagation. To incorporate non-local elastic interactions, the fracture opening in every vertical cross-section is approximated by a plane-strain solution, and then the 2D elasticity interaction integral is evaluated. To increase the computational efficiency, this 2D integral is further approximated by two one-dimensional integrals. The use of non-local elasticity allows us to include the asymptotic solution in the tip element, and, in particular, to include the effect of lateral fracture toughness. To further increase the accuracy of the P3D model, the flat fracture tip is replaced by its curved counterpart. This also permits us to capture radial behaviour at early times before the fracture has reached the stress barriers. To evaluate the accuracy of the model we have developed, the results are compared to the predictions calculated using a recently developed fully planar HF simulator, which is able to capture viscous, toughness, and intermediate propagation regimes. It is shown that the enhanced P3D model is able to approximate the propagation of hydraulic fractures accurately for various regimes of propagation, as well as for different fracture aspect ratios.Science, Faculty ofMathematics, Department ofUnreviewedFacult

Slurry flow, gravitational settling, and a proppant transport model for hydraulic fractures

The goal of this study is to analyze the steady flow of a Newtonian fluid mixed with spherical particles in a channel based on a continuum model, where the constitutive behaviour of the slurry is approximated by an empirical formula. In order to account for the gravitational settling of particles, two-dimensional flow needs to be considered as the pressure gradient and gravity may not always be collinear. It is shown that the problem under consideration features a boundary layer, whose size is on the order of the particle radius. The expressions for both the outer (i.e. outside the boundary layer) and inner (i.e. within the boundary layer) solutions are obtained in terms of the particle concentration, particle velocity, and fluid velocity. Unfortunately, these solutions require numerical solution of an integral equation, depend on the ratio between the pressure gradient and the gravity force, and the orientation of the pressure gradient relative to the gravity. Consequently, the development of a proppant transport model for hydraulic fracturing based on these results is not practical. For this reason, an approximate solution is introduced, where the effect of gravity is accounted for in an approximate fashion, reducing the complexity of the slurry flow solution. To validate the use of this approximation, the error is estimated for different regimes of flow. The approximate solution is then used to calculate the expressions for the slurry flux and the proppant flux, which are the basis for a model that can be used to account for proppant transport with gravitational settling in a fully coupled hydraulic fracturing simulator.Science, Faculty ofMathematics, Department ofUnreviewedFacult