On the Material Constitutive Behavior of the Aortic Root in Patients with Transcatheter Aortic Valve Implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure used to treat patients with severe aortic valve stenosis. However, there is limited knowledge on the material properties of the aortic root in TAVI patients, and this can impact the credibility of computer simulations. This study aimed to develop a non-invasive inverse approach for estimating reliable material constituents for the aortic root and calcified valve leaflets in patients undergoing TAVI. METHODS: The identification of material parameters is based on the simultaneous minimization of two cost functions, which define the difference between model predictions and cardiac-gated CT measurements of the aortic wall and valve orifice area. Validation of the inverse analysis output was performed comparing the numerical predictions with actual CT shapes and post-TAVI measures of implanted device diameter. RESULTS: A good agreement of the peak systolic shape of the aortic wall was found between simulations and imaging, with similarity index in the range in the range of 83.7% to 91.5% for n.20 patients. Not any statistical difference was observed between predictions and CT measures of orifice area for the stenotic aortic valve. After TAVI simulations, the measurements of SAPIEN 3 Ultra (S3) device diameter were in agreement with those from post-TAVI angio-CT imaging. A sensitivity analysis demonstrated a modest impact on the S3 diameters when altering the elastic material property of the aortic wall in the range of inverse analysis solution. CONCLUSIONS: Overall, this study demonstrates the feasibility and potential benefits of using non-invasive imaging techniques and computational modeling to estimate material properties in patients undergoing TAVI.

MicroRNA-30d and -483-3p for bi-ventricular remodelling and miR-126-3p for pulmonary hypertension in advanced heart failure.

AIMS: MicroRNAs play a role in pathogenic mechanisms leading to heart failure. We measured a panel of 754 miRNAs in the myocardial tissue and in the serum of patients with heart failure with reduced ejection fraction due to dilatative idiopathic cardiomyopathy (DCM, N = 10) or ischaemic cardiomyopathy (N = 3), referred to left ventricular assist device implant. We aim to identify circulating miRNAs with high tissue co-expression, significantly associated to echocardiographic and haemodynamic measures. METHODS AND RESULTS: We have measured a panel of 754 miRNAs in the myocardial tissue [left ventricular (LV) apex] and in the serum obtained at the same time in a well selected study population of end-stage heart failure with reduced ejection fraction due to either DCM or ischaemic cardiomyopathy, referred to continuous flow left ventricular assist device implant. We observed moderate agreement for miR-30d, miR-126-3p, and miR-483-3p. MiR-30d was correlated to LV systolic as well as diastolic volumes (r = 0.78, P = 0.001 and r = 0.80, P = 0.005, respectively), while miR-126-3p was associated to mPAP and PCWP (r = -0.79, P = 0.007 and r = -0.80, P = 0.005, respectively). Finally, serum miR-483-3p had an association with right ventricular end diastolic diameter (r = -0.73, P = 0.02) and central venous pressure (CVP) (r - 0.68 p 0.03). CONCLUSIONS: In patients with DCM, few miRNAs are co-expressed in serum and tissue: They are related to LV remodelling (miR-30d), post-capillary pulmonary artery pressure (miR-126-3p), and right ventricular remodelling/filling pressures (miR-483-3p). Further studies are needed to confirm their role in diagnosis, prognosis or as therapeutic targets in heart failure with reduced ejection fraction.

Parametric analysis of transcatheter aortic valve replacement in transcatheter aortic valve replacement: evaluation of coronary flow obstruction.

Transcatheter aortic valve replacement (TAVR) is increasingly being considered for use in younger patients having longer life expectancy than those who were initially treated. The TAVR-in-TAVR procedure represents an appealing strategy to treat failed transcatheter heart valves (THV) likely occurring in young patients. However, the permanent displacement of first THV can potentially compromise the coronary access and ultimately inhibit the blood flow circulation. The objective of this study was to use finite-element analysis (FEA) to quantify coronary flow in a patient who underwent TAVR-in-TAVR. A parametric investigation was carried out to determine the impact of both the implantation depth and device size on coronary flow for several deployment configurations. The FEAs consisted of first delivering the SAPIEN 3 Ultra THV and then positioning the Evolut PRO device. Findings indicates that high implantation depth and device undersize of the second THV could significantly reduce coronary flow to 20% of its estimated level before TAVR. Additionally, a positive correlation was observed between coronary flow and the valve-to-coronary distance (R = 0.86 and p = 0.032 for the left coronary artery, and R = 0.93 and p = 0.014 for the right coronary artery). This study demonstrated that computational modeling can provide valuable insights to improve the pre-procedural planning of TAVR-in-TAVR.

Sambucus nigra L. (fam. Viburnaceae) in Sicily: Distribution, Ecology, Traditional Use and Therapeutic Properties.

Sambucus nigra, the elderberry, has long been used for its medicinal properties in treating numerous diseases. Based on this traditional knowledge, its different pharmacological activities have been the focus of active research. All parts of the tree have long been used in traditional medicine, that is, the bark, the leaves, the flowers and the fruit. This study, carried out in Sicily (Italy), concerns the traditional uses of elder against human diseases. In order to trace the history of man's interaction with elder on the island, multidisciplinary research was carried out, aiming at (1) presenting a comprehensive overview of elderberry's applications and activities and (2) bridging traditional knowledge (uses and beliefs) with modern science, i.e., the most recent scientific findings in the biomedical and pharmacological fields. A rigorous literature review of scientific (and other local) reports on the elderberry tree and its application in food, health and household applications was undertaken. This article also provides a synthetic and updated picture of the ecology and distribution of S. nigra in Sicily. The elderberry is quite widespread in Sicily, yet its distribution is discontinuous. It prefers hedges, riparian woodlands, forest margins and clearings and is rather common along the watercourses flowing in the canyons of the Hyblaean Plateau, in the Madonie Mts. and in Enna province. Indeed, many old plants are often found near sacred places and rural houses, suggesting that in the past, it was extensively planted on purpose for its multiple uses. The complementary data obtained from multidisciplinary research confirm the usefulness of this approach in building a comprehensive and correct picture of the distribution of the most common woody species, for which the available knowledge is often fragmentary and imprecise.

A custom-built planar biaxial system for soft tissue material testing.

Accurate material characterization of soft tissues is crucial for understanding the physiopathology of cardiovascular diseases. However, commercial biaxial testing systems are expensive, prompting the need for affordable custom solutions. This study aimed to develop a low-cost custom biaxial system capable of accurately characterizing the mechanical behavior of soft tissues. The biaxial system was constructed using 3D printing technology and non-captive linear actuators for precise displacement control. A real-time marker tracking system was implemented to estimate dis-placements without the need for costly hardware. The system's performance was evaluated through tests on a calibration spring and frozen porcine aorta samples. The linear actuators demonstrated excellent response to user position input after motor tuning, showing no discrepancies between commands and actual positions. The experimental testing of the calibration spring showed good agreement with the analytical solution, validating the system's ability to accurately test materials. Testing on porcine aorta samples revealed stress-strain responses consistent with existing literature, accounting for potential variations due to tissue preservation and regional material property heterogeneity. Overall, this custom biaxial system demonstrates promising performance in accurately assessing the mechanical behavior of soft tissues, providing researchers with a valuable tool for cardiovascular disease research and tissue engineering applications.

Regional biomechanical characterization of human ascending aortic aneurysms: Microstructure and biaxial mechanical response.

The ascending thoracic aortic aneurysm (ATAA) is a permanent dilatation of the vessel with a high risk of adverse events, and shows heterogeneous properties. To investigate regional differences in the biomechanical properties of ATAAs, tissue samples were collected from 10 patients with tricuspid aortic valve phenotype and specimens from minor, anterior, major, and posterior regions were subjected to multi-ratio planar biaxial extension tests and second-harmonic generation (SHG) imaging. Using the data, parameters of a microstructure-motivated constitutive model were obtained considering fiber dispersion. SHG imaging showed disruptions in the organization of the layers. Structural and material parameters did not differ significantly between regions. The non-symmetric fiber dispersion model proposed by Holzapfel et al. [25] was used to fit the data. The mean angle of collagen fibers was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. The experimental data collected in this study contribute to the biomechanical data available in the literature on human ATAAs. Region-specific parameters for the constitutive models are fundamental to improve the current risk stratification strategies, which are mainly based on aortic size. Such investigations can facilitate the development of more advanced finite element models capable of capturing the regional heterogeneity of pathological tissues. STATEMENT OF SIGNIFICANCE: Tissue samples of human ascending thoracic aortic aneurysms (ATAA) were collected. Samples from four regions underwent multi-ratio planar biaxial extension tests and second-harmonic generation imaging. Region-specific parameters of a microstructure-motivated model considering fiber dispersion were obtained. Structural and material parameters did not differ significantly between regions, however, the mean fiber angle was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. This study provides a unique set of mechanical and structural data, supporting the microstructural influence on the tissue response. It may facilitate the development of better finite element models capable of capturing the regional tissue heterogeneity.

A new species of Contarinia (Diptera: Cecidomyiidae) from flower galls on the relict tree Zelkova abelicea (Ulmaceae) endemic to Crete (Greece).

Contarinia ampelitsiae n. sp. Dorchin & Fazan is described as a newly discovered gall-midge species (Diptera: Cecidoymiidae) forming galls in flowers of Zelkova abelicea (Ulmaceae), a tree species endemic to the Mediterranean island of Crete (Greece). Larvae develop within modified filaments of male flowers, contrary to many Contarinia species that develop freely in flowers or in simple flower galls. The species has one generation per year, and its galls are sometimes found in great numbers on individual trees, thus affecting both fruit quantity and weight. This is the first report of a gall midge from Zelkova and the first record of Contarinia from Ulmaceae. Based on its host-plant association and on the barcoding section of the mtCOI gene, this species has no obvious relatives within Contarinia.

Biomechanical performance of the Bicaval Transcatheter System for the treatment of severe tricuspid regurgitation.

Introduction: Tricuspid regurgitation (TR) is a relatively common valvular disease, which can result from structural abnormalities of any anatomic part of the tricuspid valve. Severe TR is linked to congestive heart failure and hemodynamic impairment, resulting in high mortality when repaired by elective surgery. This study was undertaken to quantify the structural and hemodynamic performance of the novel Transcatheter Bicaval Valves System (TricValve) percutaneously implanted in the superior vena cava (SVC) and inferior vena cava (IVC) of two patients with severe TR and venous congestion. Methods: After developing the SVC and IVC device models, the contact pressure exerted on the vena cava wall was obtained by computational analysis. Both smoothed-particle hydrodynamics (SPH) and computational fluid dynamics were carried out to quantify caval reflux in the right atrium and the pressure field of pre- and post-TricValve scenarios, respectively. Results: Analysis of contact pressure highlighted the main anchoring area of the SVC device occurring near the SVC device belly, while the IVC device exerted pronounced forces in the device's proximal and distal parts. SPH-related flow velocities revealed the absence of caval reflux, and a decrease in time-averaged pressure was observed near the SVC and IVC after TricValve implantation. Discussion: Findings demonstrated the potential of computational tools for enhancing our understanding of the biomechanical performance of structural tricuspid valve interventions and improving the way we design next-generation transcatheter therapies to treat the tricuspid valve with heterotopic caval valve implantation.

Titanium Lattice Structures Produced via Additive Manufacturing for a Bone Scaffold: A Review.

The progress in additive manufacturing has remarkably increased the application of lattice materials in the biomedical field for the fabrication of scaffolds used as bone substitutes. Ti6Al4V alloy is widely adopted for bone implant application as it combines both biological and mechanical properties. Recent breakthroughs in biomaterials and tissue engineering have allowed the regeneration of massive bone defects, which require external intervention to be bridged. However, the repair of such critical bone defects remains a challenge. The present review collected the most significant findings in the literature of the last ten years on Ti6Al4V porous scaffolds to provide a comprehensive summary of the mechanical and morphological requirements for the osteointegration process. Particular attention was given on the effects of pore size, surface roughness and the elastic modulus on bone scaffold performances. The application of the Gibson-Ashby model allowed for a comparison of the mechanical performance of the lattice materials with that of human bone. This allows for an evaluation of the suitability of different lattice materials for biomedical applications.

Shedding light on the effects of climate and anthropogenic pressures on the disappearance of Fagus sylvatica in the Italian lowlands: evidence from archaeo-anthracology and spatial analyses.

Fagus sylvatica is one of the most representative trees of the European deciduous broadleaved forests, yet the impact of changing climatic conditions and anthropogenic pressures (anthromes) on its presence and distribution in the coastal and lowland areas of the Mediterranean Basin has long been overlooked. Here, we first analysed the local forest composition in two different time intervals (350-300 Before Current Era, BCE and 150-100 BCE) using charred wood remains from the Etruscan site of Cetamura (Tuscany, central Italy). Additionally, we reviewed all the relevant publications and the wood/charcoal data obtained from anthracological analysis in F. sylvatica, focusing on samples that date back to 4000 years before present, to better understand the drivers of beech presence and distribution during the Late Holocene (LH) in the Italian Peninsula. Then, we combined charcoal and spatial analyses to test the distribution of beech woodland at low elevation during LH in Italy and to evaluate the effect of climate change and/or anthrome on the disappearance of F. sylvatica from the lowlands. We collected 1383 charcoal fragments in Cetamura belonging to 21 woody taxa, with F. sylvatica being the most abundant species (28 %), followed by other broadleaved trees. We identified 25 sites in the Italian Peninsula with beech charcoals in the last 4000 years. Our spatial analyses showed a marked decrease in habitat suitability of F. sylvatica from LH to the present (ca. 48 %), particularly in the lowlands (0-300 m above sea level, a.s.l.) and in areas included between 300-600 m a.s.l. with a subsequent shift upwards of the beech woodland of ca. 200 m from the past to the present. In the lowland areas, where F. sylvatica has disappeared, anthrome alone and climate + anthorme had a main effect on beech distribution whitin 0-50 m a.s.l., while the climate from 50 to 300 m a.s.l. Furthermore, climate affect also the beech distrinution in the areas >300 m a.s.l., while climate + anthrome and antrhome alone were mainly focused on the lowland areas. Our results highlight the advantage of combining different approaches, such as charcoal analysis and spatial analyses, to explore biogeographic questions about the past and current distribution of F. sylvatica, with important implications for today's forest management and conservation policies.

A multifaceted field sampling approach for the management of extremely narrow endemic vascular plant species.

Extremely narrow endemic plant species (ENEs) are generally connected with microrefugia characterized by particular environmental conditions. In-depth knowledge of the ecological requirements of ENEs is fundamental to plan appropriate conservation measures. Using cross-cutting technology, this paper gives a multifaceted approach to collect on-site data on the ecology of ENEs, defines the protocols for a correct sampling design and describes the type of equipment, the time and expenditure needed. Our sampling approach is based on two orthogonal transects, long enough to extrapolate the whole ecological gradient across the area of occupancy of the target species. Microclimatic data are recorded all along the transects through iButton technology, plus a weather station installed at the intersection of the transects. Microtopographic data are recorded with high-resolution digital elevation model and sub-metric GPS. Edaphic data are recorded along the transects through standard soil analyses and on-site evaluation of the seasonal decomposition rate of organic matter. Additionally, vegetation sampling in 4 m2 plots and on-site germination tests allow to collect data on auto- and synecological factors that regulate the life cycle of the target species. Our approach has proved to be cost-effective and efficient in terms of time spent in the field against the data collected. The most demanding activities were the establishment of the transects and the vegetation sampling. The time spent downloading microclimatic data and testing seed germination was relatively short. Our sampling design allows: (i) to catch as much micro-topographic variability as possible, both within and out of the tolerance range of the target species, (ii) to minimize the risk of recording identical micro-topographic conditions compared with a random sampling scheme, and (iii) to ensure quick and relatively easy retrieval of the plots and the equipment both on a multi-seasonal and multi-annual basis.

Numerical simulation of transcatheter mitral valve replacement: The dynamic implication of LVOT obstruction in the valve-in-ring case.

Transcatheter mitral valve replacement (TMVR) has been used for "off-label" treatment when annuloplasty band ring for mitral repair fails. However, the complex anatomy and function of the mitral valve may lead to fatal complications as a result of the left ventricular outflow tract (LVOT) obstruction in TMVR. We report the structural and hemodynamic response of LVOT obstruction resulting from TMVR with the Edwards SAPIEN 3 Ultra (S3) device. We modified the original Living Heart Human Model (LHHM) to account for a failed mitral valve with an annuloplasty band ring and simulated the cardiac beating condition in the setting of S3 device implantation. Findings demonstrated a high dynamic behavior of the newly formed LVOT (neoLVOT) as confined by the displaced mitral valve and the interventricular septum. During the cardiac beat, the neoLVOT area oscillated from a maximum of 472.1 mm2 at early systole to the minimum of 183 mm2 at end-systole. The profile of both anchoring force and contact pressure revealed that the band ring serves as the anchoring zone while mitral valve is primally displaced by the deployed device. At early systole, computational flow dynamics highlighted hemodynamic disturbances associated with the LVOT obstruction, with a skewed flow towards the septum and a pressured drop of 4.5 mmHg between the left ventricular apex and the neoLVOT region. This study can lead to a more accurate assessment of the risk induced by the LVOT obstruction when stratifying patient anatomic suitability for TMVR.

A Population-Based 3D Atlas of the Pathological Lumbar Spine Segment.

The spine is the load-bearing structure of human beings and may present several disorders, with low back pain the most frequent problem during human life. Signs of a spine disorder or disease vary depending on the location and type of the spine condition. Therefore, we aim to develop a probabilistic atlas of the lumbar spine segment using statistical shape modeling (SSM) and then explore the variability of spine geometry using principal component analysis (PCA). Using computed tomography (CT), the human spine was reconstructed for 24 patients with spine disorders and then the mean shape was deformed upon specific boundaries (e.g., by ±3 or ±1.5 standard deviation). Results demonstrated that principal shape modes are associated with specific morphological features of the spine segment such as Cobb's angle, lordosis degree, spine width and height. The lumbar spine atlas here developed has evinced the potential of SSM to investigate the association between shape and morphological parameters, with the goal of developing new treatments for the management of patients with spine disorders.

Inversion of Left Atrial Appendage Will Cause Compressive Stresses in the Tissue: Simulation Study of Potential Therapy.

In atrial fibrillation (AF), thromboembolic events can result from the particular conformation of the left atrial appendage (LAA) bearing increased clot formation and accumulation. Current therapies to reduce the risk of adverse events rely on surgical exclusion or percutaneous occlusion, each of which has drawbacks limiting application and efficacy. We sought to quantify the hemodynamic and structural loads of a novel potential procedure to partially invert the "dead" LAA space to eliminate the auricle apex where clots develop. A realistic left atrial geometry was first achieved from the heart anatomy of the Living Heart Human Model (LHHM) and then the left atrial appendage inversion (LAAI) was simulated by finite-element analysis. The LAAI procedure was simulated by pulling the elements at the LAA tip and prescribing a displacement motion along a predefined path. The deformed configuration was then used to develop a computational flow analysis of LAAI. Results demonstrated that the inverted LAA wall undergoes a change in the stress distribution from tensile to compressive in the inverted appendage, and this can lead to resorption of the LAA tissue as per a reduced stress/resorption relationship. Computational flow analyses highlighted a slightly nested low-flow velocity pattern for the inverted LAA with minimal differences from that of a model without inversion of the LAA apex. Our study revealed important insights into the biomechanics of LAAI and demonstrated the inversion of the stress field (from tensile to compressive), which &can ultimately lead the long-term resorption of the LAA.

Left Ventricle Biomechanics of Low-Flow, Low-Gradient Aortic Stenosis: A Patient-Specific Computational Model.

This study aimed to create an imaging-derived patient-specific computational model of low-flow, low-gradient (LFLG) aortic stenosis (AS) to obtain biomechanics data about the left ventricle. LFLG AS is now a commonly recognized sub-type of aortic stenosis. There remains much controversy over its management, and investigation into ventricular biomechanics may elucidate pathophysiology and better identify patients for valve replacement. ECG-gated cardiac computed tomography images from a patient with LFLG AS were obtained to provide patient-specific geometry for the computational model. Surfaces of the left atrium, left ventricle (LV), and outflow track were segmented. A previously validated multi-scale, multi-physics computational human heart model was adapted to the patient-specific geometry, yielding a model consisting of 91,000 solid elements. This model was coupled to a virtual circulatory system and calibrated to clinically measured parameters from echocardiography and cardiac catheterization data. The simulation replicated key physiologic parameters within 10% of their clinically measured values. Global LV systolic myocardial stress was 7.1 ± 1.8 kPa. Mean stress of the basal, middle, and apical segments were 7.7 ± 1.8 kPa, 9.1 ± 3.8 kPa, and 6.4 ± 0.4 kPa, respectively. This is the first patient-specific computational model of LFLG AS based on clinical imaging. Low myocardial stress correlated with low ejection fraction and eccentric LV remodeling. Further studies are needed to understand how alterations in LV biomechanics correlates with clinical outcomes of AS.

Influence of taxonomic resolution on the value of anthropogenic pollen indicators.

The taxonomic resolution of palynological identification is determined by morphological criteria that are used to define pollen types. Different levels of taxonomic resolution are reached in palynology, depending on several factors such as the analyst's expertise, the palynological school, the aim of the study, the preservation of the pollen grains, the reference collections and the microscope facilities. Previous research has suggested that attaining pollen records with high taxonomic resolution is important to reconstruct correctly past land use and human impact. This is in turn central to disentangling past human activities from other drivers of long-term vegetation dynamics such as natural disturbance or climate variability. In this study, we assess the impact of taxonomic resolution on the indicative capacity of anthropogenic pollen types. To achieve this, we attribute the pollen types of sixteen sedimentary records, located along a latitudinal gradient spanning from Switzerland to Italy, to three levels of taxonomic resolution previously proposed at the European scale. Our results show that higher taxonomic resolution improves the identification of human impact by enhancing the indicative power of important pollen indicators widely used in the research field. Our results may contribute to the improvement of palynological reconstructions of land use and human impact by identifying key pollen types whose determination requires particular attention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00334-021-00838-x.

Patient-Specific Analysis of Ascending Thoracic Aortic Aneurysm with the Living Heart Human Model.

In ascending thoracic aortic aneurysms (ATAAs), aneurysm kinematics are driven by ventricular traction occurring every heartbeat, increasing the stress level of dilated aortic wall. Aortic elongation due to heart motion and aortic length are emerging as potential indicators of adverse events in ATAAs; however, simulation of ATAA that takes into account the cardiac mechanics is technically challenging. The objective of this study was to adapt the realistic Living Heart Human Model (LHHM) to the anatomy and physiology of a patient with ATAA to assess the role of cardiac motion on aortic wall stress distribution. Patient-specific segmentation and material parameter estimation were done using preoperative computed tomography angiography (CTA) and ex vivo biaxial testing of the harvested tissue collected during surgery. The lumped-parameter model of systemic circulation implemented in the LHHM was refined using clinical and echocardiographic data. The results showed that the longitudinal stress was highest in the major curvature of the aneurysm, with specific aortic quadrants having stress levels change from tensile to compressive in a transmural direction. This study revealed the key role of heart motion that stretches the aortic root and increases ATAA wall tension. The ATAA LHHM is a realistic cardiovascular platform where patient-specific information can be easily integrated to assess the aneurysm biomechanics and potentially support the clinical management of patients with ATAAs.

8,000 years of climate, vegetation, fire and land-use dynamics in the thermo-mediterranean vegetation belt of northern Sardinia (Italy).

Knowledge about the vegetation history of Sardinia, the second largest island of the Mediterranean, is scanty. Here, we present a new sedimentary record covering the past ~ 8,000 years from Lago di Baratz, north-west Sardinia. Vegetation and fire history are reconstructed by pollen, spores, macrofossils and charcoal analyses and environmental dynamics by high-resolution element geochemistry together with pigment analyses. During the period 8,100-7,500 cal bp, when seasonality was high and fire and erosion were frequent, Erica arborea and E. scoparia woodlands dominated the coastal landscape. Subsequently, between 7,500 and 5,500 cal bp, seasonality gradually declined and thermo-mediterranean woodlands with Pistacia and Quercus ilex partially replaced Erica communities under diminished incidence of fire. After 5,500 cal bp, evergreen oak forests expanded markedly, erosion declined and lake levels increased, likely in response to increasing (summer) moisture availability. Increased anthropogenic fire disturbance triggered shrubland expansions (e.g. Tamarix and Pistacia) around 5,000-4,500 cal bp. Subsequently around 4,000-3,500 cal bp evergreen oak-olive forests expanded massively when fire activity declined and lake productivity and anoxia reached Holocene maxima. Land-use activities during the past 4,000 years (since the Bronze Age) gradually disrupted coastal forests, but relict stands persisted under rather stable environmental conditions until ca. 200 cal bp, when agricultural activities intensified and Pinus and Eucalyptus were planted to stabilize the sand dunes. Pervasive prehistoric land-use activities since at least the Bronze Age Nuraghi period included the cultivation of Prunus, Olea europaea and Juglans regia after 3,500-3,300 cal bp, and Quercus suber after 2,500 cal bp. We conclude that restoring less flammable native Q. ilex and O. europaea forest communities would markedly reduce fire risk and erodibility compared to recent forest plantations with flammable non-native trees (e.g. Pinus, Eucalyptus) and xerophytic shrubland (e.g. Cistus, Erica).

Transcatheter Heart Valve Implantation in Bicuspid Patients with Self-Expanding Device.

Bicuspid aortic valve (BAV) patients are conventionally not treated by transcathether aortic valve implantation (TAVI) because of anatomic constraint with unfavorable outcome. Patient-specific numerical simulation of TAVI in BAV may predict important clinical insights to assess the conformability of the transcathether heart valves (THV) implanted on the aortic root of members of this challenging patient population. We aimed to develop a computational approach and virtually simulate TAVI in a group of n.6 stenotic BAV patients using the self-expanding Evolut Pro THV. Specifically, the structural mechanics were evaluated by a finite-element model to estimate the deformed THV configuration in the oval bicuspid anatomy. Then, a fluid-solid interaction analysis based on the smoothed-particle hydrodynamics (SPH) technique was adopted to quantify the blood-flow patterns as well as the regions at high risk of paravalvular leakage (PVL). Simulations demonstrated a slight asymmetric and elliptical expansion of the THV stent frame in the BAV anatomy. The contact pressure between the luminal aortic root surface and the THV stent frame was determined to quantify the device anchoring force at the level of the aortic annulus and mid-ascending aorta. At late diastole, PVL was found in the gap between the aortic wall and THV stent frame. Though the modeling framework was not validated by clinical data, this study could be considered a further step towards the use of numerical simulations for the assessment of TAVI in BAV, aiming at understanding patients not suitable for device implantation on an anatomic basis.

On the Left Ventricular Remodeling of Patients with Stenotic Aortic Valve: A Statistical Shape Analysis.

The left ventricle (LV) constantly changes its shape and function as a response to pathological conditions, and this process is known as remodeling. In the presence of aortic stenosis (AS), the degenerative process is not limited to the aortic valve but also involves the remodeling of LV. Statistical shape analysis (SSA) offers a powerful tool for the visualization and quantification of the geometrical and functional patterns of any anatomic changes. In this paper, a SSA method was developed to determine shape descriptors of the LV under different degrees of AS and thus to shed light on the mechanistic link between shape and function. A total of n=86 patients underwent computed tomography (CT) for the evaluation of valvulopathy were segmented to obtain the LV surface and then were automatically aligned to a reference template by rigid registrations and transformations. Shape modes of the anatomical LV variation induced by the degree of AS were assessed by principal component analysis (PCA). The first shape mode represented nearly 50% of the total variance of LV shape in our patient population and was mainly associated to a spherical LV geometry. At Pearson's analysis, the first shape mode was positively correlated to both the end-diastolic volume (p<0.01, R=0.814) and end-systolic volume (p<0.01, and R=0.922), suggesting LV impairment in patients with severe AS. A predictive model built with PCA-related shape modes achieved better performance in stratifying the occurrence of adverse events with respect to a baseline model using clinical demographic data as risk predictors. This study demonstrated the potential of SSA approaches to detect the association of complex 3D shape features with functional LV parameters.