Yiannis Ventikos

Modifiable Lifestyle Factors in Dementia: A Systematic Review of Longitudinal Observational Cohort Studies

BACKGROUND Numerous population-based longitudinal studies suggest an association between modifiable lifestyle factors and late-life dementia. A comprehensive description of these factors and their quantification criteria is an important preliminary step toward the elucidation of causes and mechanisms underlying the onset and progression of dementia. OBJECTIVE To present a systematic review of modifiable lifestyle factors associated with dementia risk in longitudinal observational cohort-studies. METHODS A systematic review of original articles, published in English until December 2013, listed in four electronic databases (including PubMed, MEDLINE, PsycINFO) was conducted. RESULTS 75 papers from 33 epidemiologic studies met the inclusion criteria. Included papers focused on dietary habits (n = 26), leisure activities (social, physical, mental) (n = 23), beverages (juice, tea, coffee, alcohol) (n = 15), smoking (n = 13), social network (n = 6), and combined lifestyle factors (n = 2). CONCLUSIONS Broad consensus emerged on the protective role against dementia of leisure activities. Conflicting results were found for the association between dementia and putative risk factors (smoking) and protective factors (mild-to-moderate alcohol consumption, dietary antioxidants, Mediterranean diet, and living with others). However, studies varied largely in the quantification of lifestyle factors in terms of intensity, frequency and duration of exposure, and in the choice of confounders in statistical analyses. The need for standardized quantification criteria emerges, together with the current limitation in reliably tracking the past history of each patient, from childhood and young adulthood to midlife.

Morphomechanical Innovation Drives Explosive Seed Dispersal

Summary How mechanical and biological processes are coordinated across cells, tissues, and organs to produce complex traits is a key question in biology. Cardamine hirsuta, a relative of Arabidopsis thaliana, uses an explosive mechanism to disperse its seeds. We show that this trait evolved through morphomechanical innovations at different spatial scales. At the organ scale, tension within the fruit wall generates the elastic energy required for explosion. This tension is produced by differential contraction of fruit wall tissues through an active mechanism involving turgor pressure, cell geometry, and wall properties of the epidermis. Explosive release of this tension is controlled at the cellular scale by asymmetric lignin deposition within endocarp b cells—a striking pattern that is strictly associated with explosive pod shatter across the Brassicaceae plant family. By bridging these different scales, we present an integrated mechanism for explosive seed dispersal that links evolutionary novelty with complex trait innovation. Video Abstract

A patient-specific study of type-B aortic dissection: evaluation of true-false lumen blood exchange

BackgroundAortic dissection is a severe pathological condition in which blood penetrates between layers of the aortic wall and creates a duplicate channel – the false lumen. This considerable change on the aortic morphology alters hemodynamic features dramatically and, in the case of rupture, induces markedly high rates of morbidity and mortality.MethodsIn this study, we establish a patient-specific computational model and simulate the pulsatile blood flow within the dissected aorta. The k-ω SST turbulence model is employed to represent the flow and finite volume method is applied for numerical solutions. Our emphasis is on flow exchange between true and false lumen during the cardiac cycle and on quantifying the flow across specific passages. Loading distributions including pressure and wall shear stress have also been investigated and results of direct simulations are compared with solutions employing appropriate turbulence models.ResultsOur results indicate that (i) high velocities occur at the periphery of the entries; (ii) for the case studied, approximately 40% of the blood flow passes the false lumen during a heartbeat cycle; (iii) higher pressures are found at the outer wall of the dissection, which may induce further dilation of the pseudo-lumen; (iv) highest wall shear stresses occur around the entries, perhaps indicating the vulnerability of this region to further splitting; and (v) laminar simulations with adequately fine mesh resolutions, especially refined near the walls, can capture similar flow patterns to the (coarser mesh) turbulent results, although the absolute magnitudes computed are in general smaller.ConclusionsThe patient-specific model of aortic dissection provides detailed flow information of blood transport within the true and false lumen and quantifies the loading distributions over the aorta and dissection walls. This contributes to evaluating potential thrombotic behavior in the false lumen and is pivotal in guiding endovascular intervention. Moreover, as a computational study, mesh requirements to successfully evaluate the hemodynamic parameters have been proposed.

Transitional flow in aneurysms and the computation of haemodynamic parameters

Haemodynamic forces appear to play an influential role in the evolution of aneurysms. This has led to numerous studies, usually based on computational fluid dynamics. Their focus is predominantly on the wall shear stress (WSS) and associated derived parameters, attempting to find correlations between particular patterns of haemodynamic indices and regions subjected to disease formation and progression. The indices are generally determined by integration of flow properties over a single cardiac cycle. In this study, we illustrate that in some cases the transitional flow in aneurysms can lead to significantly different WSS distributions in consecutive cardiac cycles. Accurate determination of time-averaged haemodynamic indices may thus require simulation of a large number of cycles, which contrasts with the common approach to determine parameters using data from a single cycle. To demonstrate the role of transitional flow, two exemplary cases are considered: flow in an abdominal aortic aneurysm and in an intracranial aneurysm. The key differences that are observed between these cases are explained in terms of the integral timescale of the transitional flows in comparison with the cardiac cycle duration: for relatively small geometries, transients will decay before the next cardiac cycle. In larger geometries, transients are still present when the systolic phase produces new instabilities. These residual fluctuations serve as random initial conditions and thus seed different flow patterns in each cycle. To judge whether statistics are converged, the derived indices from at least two successive cardiac cycles should be compared.

Modelling evolution of saccular cerebral aneurysms

A computational model for the evolution of a saccular cerebral aneurysm of the internal carotid artery is developed. The artery is modelled as a two-layered non-linear elastic cylindrical membrane using a physiologically realistic constitutive model. It is subject to a constant systolic pressure and a physiological axial prestretch. The development of the aneurysm is assumed to be a consequence of the growth and remodelling of its material constituents. The elastinous constituents are prescribed to degrade in a localized circular patch. Microstructural recruitment and fibre concentration variables for the collagen fibres enable the growth and remodelling of collagen fabric to be simulated. The model predicts realistic saccular aneurysm geometries that stabilize in size. It provides the foundations for the development of more sophisticated models of cerebral aneurysm evolution.

Personalizing flow‐diverter intervention for cerebral aneurysms: from computational hemodynamics to biochemical modeling

This paper presents the computational modeling of a variety of flow-diverting stents, deployed in a number of patient-specific aneurysm geometries. We consider virtual device deployment and hemodynamics as well as thrombus formation, with the scope to assess pre-operatively the efficacy of specific devices in treating particular aneurysms. An algorithm based on a linear and torsional spring analogy is developed for the fast virtual deployment of stents and similar minimally invasive devices in patient-specific vessel geometries. The virtual deployment algorithm is used to accurately deploy a total of four stent designs in three aneurysm geometries. A variety of different flow-diverting stent designs, representing the commercially available and the entirely novel, are presented, varying in both mesh design and porosity. Transient computational hemodynamics simulations are performed on multiple patient-specific geometries to predict the reduction in aneurysm inflow after the deployment of each device. Further, a thrombosis initiation and growth model is implemented, coupled with the hemodynamic computations. Hemodynamic simulations show large variations in flow reduction between devices and across different aneurysm geometries. The industry standard of flow-diverters with 70% porosity, assumed to offer the best compromise in flexibility and flow reduction, is challenged in at least one aneurysm geometry.

Which Spring is the Best? Comparison of Methods for Virtual Stenting

This paper presents a methodology for modeling the deployment of implantable devices used in minimally invasive vascular interventions. Motivated by the clinical need to perform preinterventional rehearsals of a stent deployment, we have developed methods enabling virtual device placement inside arteries, under the constraint of real-time application. This requirement of rapid execution narrowed down the search for a suitable method to the concept of a dynamic mesh. Inspired by the idea of a mesh of springs, we have found a novel way to apply it to stent modeling. The experiments conducted in this paper investigate properties of the stent models based on three different spring types: lineal, semitorsional, and torsional springs. Furthermore, this paper compares the results of various deployment scenarios for two different classes of devices: a stent graft and a flow diverter. The presented results can be of a high-potential clinical value, enabling the predictive evaluation of the outcome of a stent deployment treatment.

Computational modelling of the interaction of shock waves with multiple gas-filled bubbles in a liquid

This study presents a computational investigation of the interactions of a single shock wave with multiple gas-filled bubbles in a liquid medium. This work illustrates how multiple bubbles may be used in shock-bubble interactions to intensify the process on a local level. A high resolution front-tracking approach is used, which enables explicit tracking of the gas-liquid interface. The collapse of two identical bubbles, one placed behind the other is investigated in detail, demonstrating that peak pressures in a two bubble arrangement can exceed those seen in single bubble collapse. Additionally, a parametric investigation into the effect of bubble separation is presented. It is found that the separation distance has a significant effect on both the shape and velocity of the main transverse jet of the second bubble. Extending this analysis to effects of relative bubble size, we show that if the first bubble is sufficiently small relative to the second, it may become entirely entrained in the second bubble...

Cerebral oxygenation and optimal vascular brain organization

The cerebral vascular network has evolved in such a way so as to minimize transport time and energy expenditure. This is accomplished by a subtle combination of the optimal arrangement of arteries, arterioles and capillaries and the transport mechanisms of convection and diffusion. Elucidating the interaction between cerebral vascular architectonics and the latter physical mechanisms can catalyse progress in treating cerebral pathologies such as stroke, brain tumours, dementia and targeted drug delivery. Here, we show that brain microvascular organization is predicated on commensurate intracapillary oxygen convection and parenchymal diffusion times. Cross-species grey matter results for the rat, cat, rabbit and human reveal very good correlation between the cerebral capillary and tissue mean axial oxygen convective and diffusion time intervals. These findings agree with the constructal principle.

Computational modelling of clot development in patient-specific cerebral aneurysm cases.

Essentials Clotting in cerebral aneurysms is a process that can either stabilize the aneurysm or lead to rupture. A patient‐specific computational model capable of predicting cerebral aneurysm thrombosis is presented. The different clotting outcomes highlight the importance of personalization of treatment. Once validated, the model can be used to tailor treatment and to clarify clotting processes in aneurysms.