Aims
The diastolic pressure gradient (DPG) has been proposed as a marker pulmonary vascular disease in the setting of left heart failure (HF). However, its diagnostic utility is compromised by the ...high prevalence of physiologically incompatible negative values (DPG
NEG
) and the contradictory evidence on its prognostic value. Pressure pulsatility impacts on DPG measurements, thus conceivably, pulmonary artery wedge pressure (PAWP) measurements insusceptible to the oscillatory effect of the V-wave might yield a more reliable DPG assessment. We set out to investigate how the instantaneous PAWP at the trough of the
Y
-descent (PAWP
Y
) influences the prevalence of DPG
NEG
and the prognostic value of the resultant DPG
Y
.
Methods
Hundred and fifty-three consecutive HF patients referred for right heart catheterisation were enrolled prospectively. DPG, as currently recommended, was calculated. Subsequently, PAWP
Y
was measured and the corresponding DPG
Y
was calculated.
Results
DPG
Y
yielded higher values (median, IQR: 3.2, 0.6–5.7 mmHg) than DPG (median, IQR: 0.9, − 1.7–3.8 mmHg);
p
< 0.001. Conventional DPG was negative in 45% of the patients whereas DPG
Y
in only 15%. During follow-up (22 ± 14 months) 58 patients have undergone heart-transplantation or died. The predictive ability of DPG
Y
≥ 6 mmHg for the above defined end-point events was significant HR 2.1;
p
= 0.007 and independent of resting mean pulmonary artery pressure (PAP
M
). In contrast, conventional DPG did not comprise significant prognostic value following adjustment for PAP
M
.
Conclusion
Instantaneous pressures at the trough of
Y
-descent yield significantly fewer DPG
NEG
than conventional DPG and entail superior prognostic value in HF patients with and without PH.
Graphic abstract
Real-time three-dimensional transesophageal echocardiography has increased our understanding of the distinct pathomechanisms underlying functional, ischaemic or degenerative mitral regurgitation. ...However, potential differences in dynamic morphology between the subtypes of degenerative mitral prolapse have scarcely been investigated.
In order to compare the dynamic behavior of the different phenotypes of degenerative mitral valve prolapse, real-time three-dimensional transesophageal echocardiography recordings of 77 subjects, 27 with Barlow disease (BD), 32 with Fibroelastic deficiency (FED) and 18 normal controls (NC) were analysed.
Geometric annular and valvular parameters of the myxomatous patients were significantly larger compared to controls (BD vs. FED vs. NC 3D annular area: 15 ± 2.8 vs. 13.3 ± 2.4 vs. 10.6 ± 2.3cm(2), all p < 0.01). Beside similar ellipticity, BD annuli were significantly flatter compared to FED. Myxomatous annuli appeared less dynamic than normals, with decreased overall 3D area change, however only the BD group differed from NC significantly (BD vs. FED vs. NC normalized 3D area change 4.40 vs. 6.81 vs. 9.69 %; BD vs. NC p = 0.000; FED vs. NC p = not significant, BD vs. FED p = 0.025).
BD and FED differ not only in terms of valve morphology, but also annular dynamics. Both pathologies are characterized by annular dilatation. However, in BD the annulus is remarkably flattened and hypodynamic, whereas in FED its saddle-shape and contractile function is relatively preserved. These features might influence the choice of repair technique and the selection of annuloplasty ring.
Obesity and diabetes are a progressively more and more deleterious hallmark of modern, well fed societies. In order to study the potential impact of strategies designed to obviate the pathological ...consequences of detrimental lifestyles, a model for the development of Type 2 diabetes geared towards large population simulations would be useful. The present work introduces such a model, representing in simplified fashion the interplay between average glycemia, average insulinemia and functional beta-cell mass, and incorporating the effects of excess food intake or, conversely, of physical activity levels. Qualitative properties of the model are formally established and simulations are shown as examples of its use.
Abstract Introduction Fibrin structure and cellular composition of thrombi profoundly affect the clinical outcomes in ischemic coronary and peripheral artery disease. Our study addressed the ...interrelations of structural features of thrombi and routinely measured laboratory parameters. Materials and methods Thrombi removed by thromboaspiration following acute myocardial infarction (n = 101) or thrombendarterectomy of peripheral arteries (n = 50) were processed by scanning electron microscopy and immunostaining for fibrin and platelet antigen GPIIb/IIIa to determine fibrin fibre diameter and relative occupancy by fibrin and cells. Correlations between the structural characteristics and selected clinical parameters (age, sex, vascular localization, blood cell counts, ECG findings, antiplatelet medication, accompanying diseases, smoking) were assessed. Results We observed significant differences in mean fibre diameter (122 vs. 135 nm), fibrin content (70.5% vs. 83.9%), fluorescent fibrin/platelet coverage ratio (0.18 vs. 1.06) between coronary and peripheral thrombi. Coronary thrombi from smokers contained more fibrin than non-smokers (78.1% vs. 62.2% mean occupancy). In the initial 24 h, fibrin content of coronary thrombi decreased with time, whereas in peripheral thrombi platelet content increased in the first 7 days. In coronaries, higher platelet content and smaller vessel diameter were associated with thinner fibrin fibres, whereas hematocrit higher than 0.35 correlated with larger intrathrombotic platelet occupancy. Smoking and dyslipidaemia strengthened the dependence of clot platelet content on systemic platelet count (the adjusted determination coefficient increased from 0.33 to 0.43 and 0.65, respectively). Conclusion Easily accessible clinical parameters could be identified as significant determinants of ultrastructure and composition of coronary and peripheral thrombi.
We carry out qualitative analysis of a fourth‐order tumor growth control model using ordinary differential equations. We show that the system has one positive equilibrium point, and its stability is ...independent of the feedback gain. Using a Lyapunov function method, we prove that there exist realistic parameter values for which the systems admit limit cycle oscillations due to a supercritical Hopf bifurcation. The time evolution of the state variables is also represented.
Key points
A hallmark of mitral stenosis (MS) is the markedly altered left ventricular (LV) loading.
As most of the methods used to determine LV performance in MS patients are influenced by loading ...conditions, previous studies have shown conflicting results.
The present study calculated LV elastance, which is a robust method to quantify LV function. We demonstrate that LV loading in MS patients is elevated but normalizes after valve repair and might be a result of reflex pathways.
Additionally, we show that the LV in MS is less compliant than normal due to a combination of right ventricular loading and the valvular disease itself. Immediately after valve dilatation the increase in blood inflow into the LV results in even greater LV stiffness.
Our findings enrich our understanding of heart function in MS patients and provide a simple reproducible way of assessing LV performance in MS.
Left ventricular (LV) function in rheumatic mitral stenosis (MS) remains an issue of controversy, due to load dependency of previously employed assessment methods. We investigated LV performance in MS employing relatively load‐independent indices robust to the altered loading state. We studied 106 subjects (32 ± 8 years, 72% female) with severe MS (0.8 ± 0.2 cm2) and 40 age‐matched controls. MS subjects underwent simultaneous bi‐ventricular catheterization and transthoracic echocardiography (TTE) before and immediately after percutaneous transvenous mitral commisurotomy (PTMC). Sphygmomanometric brachial artery pressures and TTE recordings were simultaneously acquired in controls. Single‐beat LV elastance (Ees) was employed for LV contractility measurements. Effective arterial elastance (Ea) and LV diastolic stiffness were measured. MS patients demonstrated significantly elevated afterload (Ea: 3.0 ± 1.3 vs. 1.5 ± 0.3 mmHg ml−1; P < 0.001) and LV contractility (Ees: 4.1 ± 1.6 vs. 2.4 ± 0.5 mmHg ml−1; P < 0.001) as compared to controls, with higher Ea in subjects with smaller mitral valve area (≤ 0.8 cm2) and pronounced subvalvular fusion. Stroke volume (49 ± 16 to 57 ± 17 ml; P < 0.001) and indexed LV end‐diastolic volume (LVEDVindex: 57 ± 16 to 64 ± 16 ml m−2; P < 0.001) increased following PTMC while Ees and Ea returned to more normal levels. Elevated LV stiffness was demonstrated at baseline and increased further following PTMC. Our findings provide evidence of elevated LV contractility, increased arterial load and increased diastolic stiffness in severe MS. Following PTMC, both LV contractility and afterload tend to normalize.
This doctoral dissertation deals with deterministic models of chemical reactions from three points of view, namely transient behavior, stationary behavior and the existence of periodic solutions. The ...first chapter summarizes the basic concepts of formal reaction kinetics. The second chapter is about the transient behavior of chemical reactions. We determined classes of mass action type kinetic differential equations that have a quadratic first integral. The main tool to find such first integrals is the comparison of the coefficients of polynomials, taking into account that kinetic differential equations are polynomial differential equations with no negative cross-effect. We investigated the conditions for mass conservation and found that it excludes the existence of certain types of quadratic first integrals. We also constructed chemical reactions for these classes of differential equations. The third chapter deals with the stationary behavior of chemical reactions as models of ion channels of nerve cells. Mass action type deterministic kinetic models of ion channels are usually constructed in such a way that the principle of detailed balancing or microscopic reversibility holds. This has a dual purpose: first, to ensure that these models are in accordance with the laws of thermodynamics, and second, to measure less, since the conditions to ensure detailed balancing reduce the number of reaction rate coefficients to be measured. We investigated several ion channel models that are detailed balanced according to the literature, however, on the one hand these models violate mass conservation, and on the other hand, in their case only the necessary conditions (the so-called circuit conditions) are taken into account. We showed that ion channel models have such a special structure that leads to correct conclusions in spite of inaccurate assumptions. First, we transformed the models to meet mass conservation and then we showed that the necessary and sufficient conditions to ensure detailed balancing (the so-called circuit conditions and spanning forest conditions) lead to the same equations for the reaction rate coefficients both for the original models and the transformed ones. The fourth chapter is devoted to the investigation of the existence of periodic solutions. We searched for limit cycles in the kinetic models of two-species chemical reactions that contain a third-order reaction step, that is, the corresponding kinetic equations are such planar polynomial differential equations that contain a cubic term. We investigated three models. The first model consists of five reaction steps and originally contains five parameters that can be reduced to three. Using symbolic methods, we formulated necessary and sufficient conditions for the parameters to achieve that around the stationary point in the first quadrant a stable limit cycle appears as a result of a supercritical Hopf bifurcation. In the global investigation of the phase portrait we used two important techniques, these are the Poincaré compactification and the blow-up of singularities, while in the local investigation we used a Lyapunov method. The second and third model contain seven parameters and performing local investigation of the phase portrait we provided necessary and sufficient conditions for the existence of two nested limit cycles around the stationary point in the first quadrant. Symbolic calculations were carried out using the Wolfram language and it was used for the numerical verifications as well.
Classes of kinetic differential equations are delineated which do have a quadratic first integral, and classes which can not have one. Example reactions corresponding to the obtained kinetic ...differential equations are shown, and a few figures showing the trajectories of the corresponding systems are also included. Connections to other areas are mentioned and unsolved problems collected. The new results are theoretical, although computational tools are heavily used. Applications from biology and combustion theory will come later.
In our research program we analysed the employee competences expected by the employer. We assumed that it is not qualifications but these competences that determine, on the one hand, the criteria of ...selecting future employees, and define, on the other hand, the areas that should be developed by the training providers. We examined the competences to be acquired by the employees in terms of four competence categories: basic competences, key competences, generic competences and special competences. Since the majority of employers work in the service sector, they emphasize the key competences instead of the professional ones, with the employees working much more intensively with their personality than with their acquired professional knowledge. From our analyses the picture emerged that the contacts between training providers and companies do not work too well: only one fifth of them possess tried and tested information on trainers or young professional who have been trained by them, and 89% of the enterprises have never told training providers what kind of professional knowledge or skill elements they expect from the training courses. 80 % of Hungarian entrepreneurs and 66% of Romanian entrepreneurs are not planning to contact training providers in the near future. The training providers do not take up the initiative either, they are waiting for ‘somebody’ to approach them. The dialogue is missing between trainers and entrepreneurs.
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