Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population

Background Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians. Methods A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV ≥ 12 m/s. Results In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals. Conclusions These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.

Contribution to assessing the stiffness reduction of structural elements in the global stability analysis of precast concrete multi-storey buildings

This study deals with the reduction of the stiffness in precast concrete structural elements of multi-storey buildings to analyze global stability. Having reviewed the technical literature, this paper present indications of stiffness reduction in different codes, standards, and recommendations and compare these to the values found in the present study. The structural model analyzed in this study was constructed with finite elements using ANSYS® software. Physical Non-Linearity (PNL) was considered in relation to the diagrams M x N x 1/r, and Geometric Non-Linearity (GNL) was calculated following the Newton-Raphson method. Using a typical precast concrete structure with multiple floors and a semi-rigid beam-to-column connection, expressions for a stiffness reduction coefficient are presented. The main conclusions of the study are as follows: the reduction coefficients obtained from the diagram M x N x 1/r differ from standards that use a simplified consideration of PNL; the stiffness reduction coefficient for columns in the arrangements analyzed were approximately 0.5 to 0.6; and the variation of values found for stiffness reduction coefficient in concrete beams, which were subjected to the effects of creep with linear coefficients from 0 to 3, ranged from 0.45 to 0.2 for positive bending moments and 0.3 to 0.2 for negative bending moments.

The role of wake stiffness on the wake-induced vibration of the downstream cylinder of a tandem pair

When a pair of tandem cylinders is immersed in a flow the downstream cylinder can be excited into wake-induced vibrations (WIV) due to the interaction with vortices coming from the upstream cylinder. Assi, Bearman & Meneghini ( J. Fluid Mech. , vol. 661, 2010, pp. 365–401) concluded that the WIV excitation mechanism has its origin in the unsteady vortex–structure interaction encountered by the cylinder as it oscillates across the wake. In the present paper we investigate how the cylinder responds to that excitation, characterising the amplitude and frequency of response and its dependency on other parameters of the system. We introduce the concept of wake stiffness , a fluid dynamic effect that can be associated, to a first approximation, with a linear spring with stiffness proportional to Re and to the steady lift force occurring for staggered cylinders. By a series of experiments with a cylinder mounted on a base without springs we verify that such wake stiffness is not only strong enough to sustain oscillatory motion, but can also dominate over the structural stiffness of the system. We conclude that while unsteady vortex–structure interactions provide the energy input to sustain the vibrations, it is the wake stiffness phenomenon that defines the character of the WIV response

Importance of footing-soil separation on dynamic stiffness of piled embedded footings

[EN]Different phenomena such a soil consolidation, erosion, and scour beneath an embedded footing supported on piles may lead to loss of contact between soil and the pile cap underside. The importance of this separation on the dynamic stiffness and damping of the foundation is assessed in this work.

Dynamic stiffness of deep foundations with inclined piles.

[EN]The influence of inclined piles on the dynamic response of deep foundations and superstructures is still not well understood and needs further research. For this reason, impedance functions of deep foundations with inclined piles, obtained numerically from a boundary element-finete element coupling model, are provided in this paper.

Influence of chain stiffness on structure and dynamics of polymers in the melt

Die vorliegende Arbeit beschaeftigt sich mit der Untersuchung vonPolymeren mit intrinsischer Steifigkeit. Es werden vor allem lokale statische unddynamische Eigenschaften anhand zweier verschiedener Simulationsmodellebetrachtet: Ein generisches Polymermodell, bei dem nur dieSteifigkeit als ein das spezifische Polymer charakterisierenden Parametereingeht und ein atomistisches Modell fuer trans-Polyisopren. Mit Hilfe des ersten Modells koennen Statik und Dynamik wurmartiger Kettenbeobachtet werden. Das Blob-Konzept ist eine angemessene statischeBeschreibung. Lokale Orientierungen haengen schwach von derSteifigkeit ab. Das Reptationsmodell kann die beobachtete Dynamik fuer lange Kettennicht mehr angemessen beschreiben. Lange Ketten bewegen sich, als obsie in Roehren gezwaengt waeren; jedoch ist die Bewegung starkabhaengig von der Steifigkeit. Fuer Ketten dieser Art konntequalitativ das Verhalten reproduziert werden, das in NMR-Experimentenbeobachtet wird. Eine Verhakungslaenge laesst sich fuer solche Kettenkaum mehr definieren. Dynamische Strukturfunktionen und insbesonderedie direkte Visualisierung der Ketten verdeutlichen die effektiv aufeine Roehre beschraenkte Bewegung. Das atomistische Polyisoprenmodell wurde mit verschiedenen Experimenten,verglichen. In den Simulationen bei konnten qualitativ undsemiquantitativ experimentelle Ergebnisse reproduziert werden. Zuletzt wurden die Laengen- und Zeitskalen der beiden Modelleerfolgreich aufeinander abgebildet.

Combined Evaluation of ST-segment Elevation in lead AVR and ST-segment Depression in other Leads Enhances Prediction of in-hospital Cardiovascular Death in Patients with Non ST-segment Elevation Acute Coronary Syndrome

Objective: To investigate the prognostic significance of ST-segment elevation (STE) in aVR associated with ST-segment depression (STD) in other leads in patients with non-STE acute coronary syndrome (NSTE-ACS). Background: In NSTE-ACS patients, STD has been extensively associated with severe coronary lesions and poor outcomes. The prognostic role of STE in aVR is uncertain. Methods: We enrolled 888 consecutive patients with NSTE-ACS. They were divided into two groups according to the presence or not on admission ECG of aVR STE≥ 1mm and STD (defined as high risk ECG pattern). The primary and secondary endpoints were: in-hospital cardiovascular (CV) death and the rate of culprit left main disease (LMD). Results: Patients with high risk ECG pattern (n=121) disclosed a worse clinical profile compared to patients (n=575) without [median GRACE (Global-Registry-of-Acute-Coronary-Events) risk score =142 vs. 182, respectively]. A total of 75% of patients underwent coronary angiography. The rate of in-hospital CV death was 3.9%. On multivariable analysis patients who had the high risk ECG pattern showed an increased risk of CV death (OR=2.88, 95%CI 1.05-7.88) and culprit LMD (OR=4.67,95%CI 1.86-11.74) compared to patients who had not. The prognostic significance of the high risk ECG pattern was maintained even after adjustment for the GRACE risk score (OR = 2.28, 95%CI:1.06-4.93 and OR = 4.13, 95%CI:2.13-8.01, for primary and secondary endpoint, respectively). Conclusions: STE in aVR associated with STD in other leads predicts in-hospital CV death and culprit LMD. This pattern may add prognostic information in patients with NSTE-ACS on top of recommended scoring system.

Seismic mitigation of existing masonry structures by means of added damping and stiffness

In this work seismic upgrading of existing masonry structures by means of hysteretic ADAS dampers is treated. ADAS are installed on external concrete walls, which are built parallel to the building, and then linked to the building's slab by means of steel rod connection system. In order to assess the effectiveness of the intervention, a parametric study considering variation of damper main features has been conducted. To this aim, the concepts of equivalent linear system (ELS) or equivalent viscous damping are deepen. Simplified equivalent linear model results are then checked respect results of the yielding structures. Two alternative displacement based methods for damper design are herein proposed. Both methods have been validated through non linear time history analyses with spectrum compatible accelerograms. Finally ADAS arrangement for the non conventional implementation is proposed.

Changes in tumor stiffness for early prediction of tumor response to sorafenib: a proof-of-concept study with elastosonography in an animal model of Hepatocellular Carcinoma (HCC)

Background and aims: Sorafenib is the reference therapy for advanced Hepatocellular Carcinoma (HCC). No method exists to predict in the very early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography a new ultrasound based technique allows assessment of tissue stiffness, we investigated the role of elastonography in the very early prediction of tumor response to sorafenib in a HCC animal model. Methods: HCC (Huh7 cells) subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle or treatment with sorafenib when tumor size was 5-10 mm. Elastosonography (Mylab 70XVG, Esaote, Genova, Italy) of the whole tumor mass on a sagittal plane with a 10 MHz linear transducer was performed at different time points from treatment start (day 0, +2, +4, +7 and +14) until mice were sacrified (day +14), with the operator blind to treatment. In order to overcome variability in absolute elasticity measurement when assessing changes over time, values were expressed in arbitrary units as relative stiffness of the tumor tissue in comparison to the stiffness of a standard reference stand-off pad lying on the skin over the tumor. Results: Sor-treated mice showed a smaller tumor size increase at day +14 in comparison to vehicle-treated (tumor volume increase +192.76% vs +747.56%, p=0.06). Among Sor-treated tumors, 6 mice showed a better response to treatment than the other 4 (increase in volume +177% vs +553%, p=0.011). At day +2, median tumor elasticity increased in Sor-treated group (+6.69%, range –30.17-+58.51%), while decreased in the vehicle group (-3.19%, range –53.32-+37.94%) leading to a significant difference in absolute values (p=0.034). From this time point onward, elasticity decreased in both groups, with similar speed over time, not being statistically different anymore. In Sor-treated mice all 6 best responders at day 14 showed an increase in elasticity at day +2 (ranging from +3.30% to +58.51%) in comparison to baseline, whereas 3 of the 4 poorer responders showed a decrease. Interestingly, these 3 tumours showed elasticity values higher than responder tumours at day 0. Conclusions: Elastosonography appears a promising non-invasive new technique for the early prediction of HCC tumor response to sorafenib. Indeed, we proved that responder tumours are characterized by an early increase in elasticity. The possibility to distinguish a priori between responders and non responders based on the higher elasticity of the latter needs to be validated in ad-hoc experiments as well as a confirmation of our results in humans is warranted.

Responsive Bürstenpolymere

'Responsive' Bürstenpolymere Bürstenpolymere sind definiert verzweigte Makromoleküle, die aus einer Hauptkette und vielen darauf (kovalent) gepfropften Seitenketten bestehen; ist der Pfropfungsgrad hoch und die Hauptkette wesentlich länger als die Seitenketten, dann haben sie die Form semiflexibler molekularer Zylinder. Lassen sich Form bzw. Ausdehnung eines solchen Zylinders gezielt ansteuern, dann könnten diese Moleküle entweder als (Nano-)Sensoren für die entsprechende Umgebungsbedingung oder als molekulare Motoren eingesetzt werden. Die Idee responsiver Bürstenpolymere beruht auf folgender Überlegung: Die gestreckte Konformation der Hauptkette ist entropisch gegenüber einem entsprechenden Knäuel benachteiligt, weshalb sie ,molekulare Federn‘ darstellen, die auf Änderung der repulsiven Wechselwirkung zwischen den Seitenketten reagieren. Dies wurde für den Wechsel zwischen gutem und schlechtem Lösungsmitteln untersucht. Ein zweites Konzept zur Änderung der Molekülform beruht auf der intramolekularen Phasentrennung (,Segmentbildung‘) miteinander unverträglicher Seitenketten in selektiven Lösungsmitteln, da die Hauptkette durch Ausbildung von Mikrophasen entlang des Moleküls ebenfalls aus ihrer gestreckten Form gebracht werden sollte. Die dritte Möglichkeit zur Änderung der Konformation ist die intramolekulare Vernetzung von Seitenketten, die ebenfalls zu verringerter Abstoßung und damit zur Verkürzung der Zylinder führen sollte. Eine weitere wichtige Untersuchung der Arbeit war der Übergang einer geknäuelten Hauptkette zu einer gestreckten Bürste als Funktion der Pfropfdichte. Zur Beantwortung dieser Fragestellungen wurden zylindrische Bürstenpolymere durch ,Grafting Trough‘ und ,Grafting Onto‘ synthetisiert (PS bzw. PI/PS und PnBMA/PMAA mit Kern/Schale- und ,Segment‘-Architektur) und systematisch Pfropfdichte, Vernetzungsgrad (Vernetzung durch gamma-Bestrahlung) und Lösungsbedingungen verändert. Die Möglichkeit gezielter Ansteuerung der Konformationsänderung durch Vernetzung konnte nach polymeranaloger Modifikation von PI/PS-Bürstenpolymeren durch Photovernetzung und vernetzende Komplexierung erfolgreich bestätigt werden. Zur Untersuchung der Probenreihen wurden AFM, Licht- und Neutronenstreuung herangezogen. Die Analysen bestätigten konsistent die Änderung von Steifigkeit, Zylinderquerschnitt und Streckung der Hauptkette durch Variation von Pfropfdichte, Vernetzung und Lösungsmittelqualität. Für die Änderung der Pfropfdichte gehorchen die Parameter dabei Potenzgesetzen.

Portal hypertension: a comparison between portal-venous pressure measurement and ARFI measurement of liver and spleen stiffness

PURPOSE. Portal pressure is measured invasively as Hepatic Venous Pressure Gradient (HVPG) in the angiography room. Liver stiffness measured by Fibroscan was shown to correlate with HVPG values below 12 mmHg. This is not surprising, since in cirrhosis the increase of portal pressure is not directly linked with liver fibrosis and consequently to liver stiffness. We hypothesized that, given the spleen’s privileged location upstream to the whole portal system, splenic stiffness could provide relevant information about portal pressure. Aim of the study was to assess the relationship between liver and spleen stiffness measured by Virtual Touch™ (ARFI) and HVPG in cirrhotic patients. METHODS. 40 consecutive patients (30 males, mean age 62y, mean BMI=26, mean Child-Pugh A6, mean platelet count=92.000/mmc, 19 HCV+, 7 with ascites) underwent to ARFI stiffness measurement (10 valid measurements in right liver lobe both surface and centre, left lobe and 20 in the spleen) and HPVG, blindly to each other. Median ARFI values of 10 samplings on every liver area and of 20 samplings on spleen were calculated. RESULTS. Stiffness could be easily measured in all patients with ARFI, resulting a mean of 2,61±0,76, 2,5±0,62 and 2,55±0,66 m/sec in the liver areas and 3.3±0,5 m/s in the spleen. Median HPVG was 14 mmHg (range 5-27); 28 patients showed values ≥10 mmHg. A positive significant correlation was found between spleen stiffness and HPVG values (r=0.744, p<0.001). No significant correlation was found between all liver stiffness and HVPG (p>0,05). AUROC was calculated to test spleen stiffness ability in discriminating patients with HVPG ≥10. AUROC = 0.911 was obtained, with sensitivity of 69% and specificity of 91% at a cut-off of 3.26 m/s. CONCLUSION. Spleen stiffness measurement with ARFI correlates with HVPG in patients with cirrhosis, with a potential of identifying patients with clinically significant portal hypertension.

A Design Method for Flexure-Based Compliant Mechanisms on the Basis of Stiffness and Stress Characteristics

Geometric nonlinearities of flexure hinges introduced by large deflections often complicate the analysis of compliant mechanisms containing such members, and therefore, Pseudo-Rigid-Body Models (PRBMs) have been well proposed and developed by Howell [1994] to analyze the characteristics of slender beams under large deflection. These models, however, fail to approximate the characteristics for the deep beams (short beams) or the other flexure hinges. Lobontiu's work [2001] contributed to the diverse flexure hinge analysis building on the assumptions of small deflection, which also limits the application range of these flexure hinges and cannot analyze the stiffness and stress characteristics of these flexure hinges for large deflection. Therefore, the objective of this thesis is to analyze flexure hinges considering both the effects of large-deflection and shear force, which guides the design of flexure-based compliant mechanisms. The main work conducted in the thesis is outlined as follows. 1. Three popular types of flexure hinges: (circular flexure hinges, elliptical flexure hinges and corner-filleted flexure hinges) are chosen for analysis at first. 2. Commercial software (Comsol) based Finite Element Analysis (FEA) method is then used for correcting the errors produced by the equations proposed by Lobontiu when the chosen flexure hinges suffer from large deformation. 3. Three sets of generic design equations for the three types of flexure hinges are further proposed on the basis of stiffness and stress characteristics from the FEA results. 4. A flexure-based four-bar compliant mechanism is finally studied and modeled using the proposed generic design equations. The load-displacement relationships are verified by a numerical example. The results show that a maximum error about the relationship between moment and rotation deformation is less than 3.4% for a flexure hinge, and it is lower than 5% for the four-bar compliant mechanism compared with the FEA results.

The cardio-renal axis. Non ST-segment elevation myocardial infarction risk stratification according to renal dysfunction

Background: Chronic kidney disease (CKD) is one of the strongest risk factor for myocardial infarction (MI) and mortality. The aim of this study was to assess the association between renal dysfunction severity, short-term outcomes and the use of in-hospital evidence-based therapies among patients with non–ST-segment elevation myocardial infarction (NSTEMI). Methods: We examined data on 320 patients presenting with NSTEMI to Maggiore’s Emergency Department from 1st Jan 2010 to 31st December 2011. The study patients were classified into two groups according to their baseline glomerular filtration rate (GFR): renal dysfunction (RD) (GFR<60) and non-RD (GFR≥60 ml/min). Patients were then classified into four groups according to their CKD stage (GFR≥60, GFR 59-30, GFR 29-15, GFR <15). Results: Of the 320 patients, 155 (48,4%) had a GFR<60 ml/min at baseline. Compared with patients with a GFR≥60 ml/min, this group was, more likely to be female, to have hypertension, a previous myocardial infarction, stroke or TIA, had higher levels of uric acid and C-reactive protein. They were less likely to receive immediate (first 24 hours) evidence-based therapies. The GFR of RD patients treated appropriately increases on average by 5.5 ml/min/1.73 m2. The length of stay (mean, SD) increased with increasing CKD stage, respectively 5,3 (4,1), 7.0 (6.1), 7.8 (7.0), 9.2 (5.8) (global p <.0001). Females had on average a longer hospitalization than males, regardless of RD. In hospital mortality was higher in RD group (3,25%). Conclusions: The in-hospital mortality not was statically difference among the patients with a GFR value ≥60 ml/min, and patients with a GFR value <60 ml/min. The length of stay increased with increasing CKD stages. Despite patients with RD have more comorbidities then without RD less frequently receive guideline –recommended therapy. The GFR of RD patients treated appropriately improves during hospitalization, but not a level as we expected.

Accuracy of liver stiffness measurement using fibroscan ® to predict the response to antiviral therapy in patients with chronic hepatitis c viral infection

Introduction: Antiviral therapy can prevent disease progression in patients with chronic hepatitis C . Transient Elastografy (TE; Fibroscan) is an accurate surrogate marker to liver fibrosis, by measuring liver stiffness (LS). LS decrease has been associated with sustained virologic response (SVR). Aim: to assess the changes of LS measurments in CHC patients during and one year after Interferon (IFN)-based antiviral therapy (IFN/ribavirin) or (telaprevir+IFN/ribavirin). Methods: consecutive 69 CHC patients (53.6% females, mean age 57.9 ± 11.4) who underwent antiviral therapy for at least 20 weeks were enrolled. LS was measured using FibroScan at baseline, after three months, at the end of treatment and one year after treatment discontinuation. Fibrosis was graded using METAVIR score. Results: twenty patients treated with triple therapy and 49 with IFN/ribavirin. Fifty patients had SVR and 19 were non-responders. SVR patients: F0-F1, F2 and F3 patients (39.1%, 7.2% and 17.4%; respectively) showed no significant LS decrease (P= 0.186, 0.068 and 0.075; respectively). Conversely, in F4 patients (36.2%) LS was significantly decreased (P=0.015) after one year of treatment completion. In all patients with no SVR, no significant decrease in LS was observed. Interestingly, all Patients with F4 fibrosis (even non-responders) showed an initial significant decrease in LS (P=0.024) at 3 months after the start of treatment. However, this decrease was not predictive of SVR; area under the ROC curve 0.369 (CI %: 0.145-0.592) P= 0.265. Conclusion: Our study showed that initial decrease in LSM, especially in patients with higher baseline fibrosis score is unlikely to predict an SVR. In addition no significant association was found between clinical or virological parameters and fibrosis improvement. Further studies are needed to delineate the most appropriate clinical scenarios for the LSM by Fibroscan in chronic hepatitis C and its role in monitoring the response to antiviral treatment.

Feedback linearization of antagonistically actuated variable stiffness joints with twisted string actuators

The work of this thesis is on the implementation of a variable stiffness joint antagonistically actuated by a couple of twisted-string actuator (TSA). This type of joint is possible to be applied in the field of robotics, like UB Hand IV (the anthropomorphic robotic hand developed by University of Bologna). The purposes of the activities are to build the joint dynamic model and simultaneously control the position and stiffness. Three different control approaches (Feedback linearization, PID, PID+Feedforward) are proposed and validated in simulation. To improve the properties of joint stiffness, a joint with elastic element is taken into account and discussed. To the end, the experimental setup that has been developed for the experimental validation of the proposed control approaches.