ON THE STABILITY OF VARIABLE HELIX MILLING TOOLS

One of the main aims of the manufacturing industry has been to maximise the material removal rate of machining processes. However, this goal can be restricted by the appearance of regenerative chatter vibrations. In milling, one approach for regenerative chatter suppression is the implementation of variable-helix cutters. However, these tools can lead to isolated unstable regions in the stability diagram. Currently, variable-helix unstable islands have not been extensively researched in the literature. Therefore, the current thesis focuses on studying and experimentally validating these islands. For the validation, an experimental setup that scaled not only the structural dynamics but also the cutting force coefficients was proposed. Therefore, it was possible to attain larger axial depths of cut while assuming linear dynamics. The variable-helix process stability was modelled using the semi-discretization method and the multi-frequency approach. It was found that the variable helix tools can further stabilise a larger width of cut due to the distributed time delays that are a product of the tool geometry. Subsequently, a numerical study about the impact of structural damping on the variable-helix stability diagram revealed a strong relationship between the damping level and instability islands. The findings were validated by performing trials on the experimental setup, modified with constrained layer damping to recreate the simulated conditions. Additionally, a convergence analysis using the semi-discretization method (SDM) and the multi-frequency approach (MFA) revealed that these islands are sensitive to model convergence aspects. The analysis shows that the MFA provided converged solutions with a steep convergence rate, while the SDM struggled to converge. In this work, it is demonstrated that variable-helix instability islands only emerge at relatively high levels of structural damping and that they are particularly susceptible to model convergence effects. Meanwhile, the model predictions are compared to and validated against detailed experimental data that uses a specially designed configuration to minimise experimental error. To the authors' knowledge, this provides the first experimentally validated study of unstable islands in variable helix milling, while also demonstrating the importance of accurate damping estimates and convergence studies within the stability predictions

The Effect of Extensive Reading on Vocabulary Knowledge of First Level University Students

The objective of the research was to analyze how extensive reading or reading for pleasure can improve the development of vocabulary in a sample of 48 first-level university students of the Universidad Tecnológica Indoamérica in the city of Ambato. It was an experimental, bibliographic, descriptive, field and correlational research. To determine the correlation between the two study variables, a deep and thorough investigative analysis of books, journals and research was carried out. An intervention plan was applied through the use of a handbook of 19 vocabulary activities and to measure the knowledge of the vocabulary in the students, an observation card was used in order to measure attitudes and behavior towards extensive reading. A questionnaire of twelve questions related to word knowledge and the word form with its meaning was used as well. The research contains the sociodemographic statistical analysis of the participants and an analysis of the results of the evaluation of reading knowledge and vocabulary to know the descriptive aspects. Furthermore, the descriptive analysis of the vocabulary knowledge assessment from a global point of view and the aspects of word knowledge was carried out; to finally perform the analysis of the presence and degree of correlation between extensive reading and vocabulary knowledge, using the Pearson coefficient. Thus, it allowed to determine that, the existence of the correlation between the two variables investigated. That is to say, the results indicated that the use of extensive reading influences the development of students' vocabulary by raising interest and improving vocabulary

Valve hemodynamic performance and myocardial strain after implantation of a third-generation, balloon-expandable, transcatheter aortic valve

Background: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS); however, transcatheter aortic valve implantation (TAVI) may positively affect LV mechanics. Assessed herein is the performance of the SAPIEN 3 transcatheter heart valve (THV) and the effect of TAVI on LV function recovery, as assessed by global longitudinal strain (GLS). Methods: A subset of patients from the SOURCE 3 registry (n = 276) from 16 European centers received SAPIEN 3 balloon-expandable THV. Echocardiography was performed at baseline, postprocedure, and at 1 year, including assessment of GLS using standard two-dimensional images, and was analyzed in a core laboratory. Paired analyses between baseline and discharge, baseline and at 1 year were conducted. Results: Hemodynamic parameters were improved after TAVI and sustained to 1 year. At 1 year, the rate of moderate to severe paravalvular leaks (PVL), and moderate to severe mitral and tricuspid regurgitations were 1.8%, 1.7%, and 8.0%, respectively. The discharge GLS (–15.6 ± 5.1; p = 0.004; n = 149) improved significantly from baseline (–15.1 ± 4.8) following TAVI. This improvement was sustained at 1 year compared with baseline (–17.0 ± 4.6, p < 0.001; n = 100). Conversely, LV ejection fraction (LVEF) did not significantly change following TAVI (p = 0.47). Conclusions: Following TAVI with a third-generation THV, valve performances were good at 1 year with low PVL rate. The LV mechanics improved immediately after the procedure and were maintained at 1 year. These findings demonstrate the benefit of TAVI on LV mechanics, and suggests that GLS may be superior to LVEF in assessing this benefit. Clinicaltrial.gov number: NCT0269895

Coronary Obstruction Following Transcatheter Aortic Valve Implantation for Degenerative Bioprosthetic Surgical Valves: a Systematic Literature Review

ABSTRACTBackgroundVery few data exist on coronary obstruction following transcatheter aortic valve implantation (TAVI) for degenerative bioprosthetic valves (valve-in-valve [ViV]). The present trial evaluated, through a systematic review of the literature, the clinical characteristics, management and clinical outcomes of patients with coronary obstruction after ViV-TAVI.MethodsStudies published between 2002 and 2013 evaluating coronary obstruction as a complication of ViV-TAVI were identified using a systematic electronic search. Data on the clinical and procedural characteristics, management of the complication, and clinical outcomes were analyzed.ResultsA total of four publications describing seven patients were identified. Most patients (71%) were women, with mean age of 82±5 years, and STS-PROM score of 9.4±2.6%. Mean left coronary artery (LCA) ostium height and aortic root width were 8.8±1.5mm and 28.0±5.0mm, respectively. Most patients had stented bioprosthetic valves with externally mounted leaflets or stentless aortic bioprosthesis, and the LCA was involved in all patients. Percutaneous coronary intervention (PCI) was attempted in all patients and was successful in four (57%). In-hospital mortality was 42.9% (three cases), all of them after failed PCI.ConclusionsCoronary obstruction following ViV-TAVI occurred more frequently in women with stented bioprosthetic valves with externally mounted leaflets or with stentless bioprosthesis. The LCA was involved in all cases and PCI was successful in 60% of them. Continued efforts may help identify the factors associated with this complication so that appropriate prevention measures may be implemented

Impact of Low Flow on the Outcome of High-Risk Patients Undergoing Transcatheter Aortic Valve Replacement

ObjectivesThis study sought to assess the impact of baseline left ventricular (LV) outflow, LV ejection fraction (LVEF), and transvalvular gradient on outcomes following transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis (AS).BackgroundLow flow (i.e., reduced stroke volume index [SVi]) can occur with both reduced and preserved LVEF. Low flow is often associated with low gradient despite severe stenosis and with worse outcomes following surgical aortic valve replacement. However, there are few data about the impact of low flow on outcomes following TAVR.MethodsWe retrospectively analyzed the clinical, Doppler-echocardiographic, and outcome data prospectively collected in 639 patients who underwent TAVR for symptomatic severe AS in 2 Canadian centers.ResultsIn this cohort, 334 (52.3%) patients had a low flow (SVi <35 ml/m2) and these patients had increased 30-day mortality (11.4 vs. 5.9%, p = 0.01), 2-year all-cause mortality (35.3 vs. 30.9%, p = 0.005), and 2-year cardiovascular mortality (25.7 vs. 16.8%, p = 0.01) compared with patients with normal flow. Reduced flow was an independent predictor of 30-day mortality (odds ratio: 1.94, p = 0.026), cumulative all-cause mortality (hazard ratio: 1.27 per 10 ml/m² SVi decrease, p = 0.016), and cumulative cardiovascular mortality (hazard ratio: 1.29 per 10 ml/m² decrease, p = 0.04). Despite significant association in univariable analyses, low LVEF and low mean gradient were not found to be independent predictors of outcomes in multivariable analyses.ConclusionsLow flow but not low LVEF or low gradient is an independent predictor of early and late mortality following TAVR in high-risk patients with severe AS. SVi should be integrated in the risk stratification process of these patients

Incidence, predictive factors and haemodynamic consequences of acute stent recoil following transcatheter aortic valve implantation with a balloon-expandable valve

Aims: The elastic behaviour (acute recoil) of a valve prosthesis stent following transcatheter aortic valve implantation (TAVI) is unknown. This study sought to determine the occurrence, severity, predictive factors and haemodynamic consequences of acute recoil following TAVI. Methods and results : A prospective angiographic analysis of the stent frame dimensions in 111 consecutive patients who underwent TAVI with a balloon-expandable valve (36 Edwards SAPIEN; 75 SAPIEN XT) was performed. Acute recoil was defined as the difference between minimal lumen diameter (MLD) at full balloon expansion and immediately after balloon deflation. MLD during balloon inflation was significantly larger than MLD after balloon deflation (23.40±2.31 mm vs. 22.29±2.21 mm, p<0.001), which represented an absolute and percent decrease in stent dimension of 1.10±0.40 mm and 4.70±1.76%, respectively. In the multivariate analysis, the predictors of larger recoil were a higher prosthesis/annulus ratio (r²=0.0624, p=0.015) and the SAPIEN XT prosthesis (r²=0.1276, p=0.001). No significant changes in haemodynamic performance were observed at discharge and follow-up in patients with larger recoil. Conclusions : TAVI with a balloon-expandable valve was systematically associated with a certain degree of valve stent recoil after balloon deflation. A higher degree of valve oversizing and the SAPIEN XT prosthesis predicted a larger degree of stent recoil

Molecular chaperone Hsp90 is a therapeutic target for noroviruses.

UNLABELLED: Human noroviruses (HuNoV) are a significant cause of acute gastroenteritis in the developed world, and yet our understanding of the molecular pathways involved in norovirus replication and pathogenesis has been limited by the inability to efficiently culture these viruses in the laboratory. Using the murine norovirus (MNV) model, we have recently identified a network of host factors that interact with the 5' and 3' extremities of the norovirus RNA genome. In addition to a number of well-known cellular RNA binding proteins, the molecular chaperone Hsp90 was identified as a component of the ribonucleoprotein complex. Here, we show that the inhibition of Hsp90 activity negatively impacts norovirus replication in cell culture. Small-molecule-mediated inhibition of Hsp90 activity using 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) revealed that Hsp90 plays a pleiotropic role in the norovirus life cycle but that the stability of the viral capsid protein is integrally linked to Hsp90 activity. Furthermore, we demonstrate that both the MNV-1 and the HuNoV capsid proteins require Hsp90 activity for their stability and that targeting Hsp90 in vivo can significantly reduce virus replication. In summary, we demonstrate that targeting cellular proteostasis can inhibit norovirus replication, identifying a potential novel therapeutic target for the treatment of norovirus infections. IMPORTANCE: HuNoV are a major cause of acute gastroenteritis around the world. RNA viruses, including noroviruses, rely heavily on host cell proteins and pathways for all aspects of their life cycle. Here, we identify one such protein, the molecular chaperone Hsp90, as an important factor required during the norovirus life cycle. We demonstrate that both murine and human noroviruses require the activity of Hsp90 for the stability of their capsid proteins. Furthermore, we demonstrate that targeting Hsp90 activity in vivo using small molecule inhibitors also reduces infectious virus production. Given the considerable interest in the development of Hsp90 inhibitors for use in cancer therapeutics, we identify here a new target that could be explored for the development of antiviral strategies to control norovirus outbreaks and treat chronic norovirus infection in immunosuppressed patients

Myocardial injury following transcatheter aortic valve implantation : insights from delayed-enhancement cardiovascular magnetic resonance

Aims: The aim of this study was to evaluate the presence, localisation and extent of myocardial injury as determined by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: A total of 37 patients, who underwent successful TAVI with a balloon-expandable valve (transapical [TA], n=11; non-TA, n=26), were included. Cardiac biomarker (CK-MB and cTnT) lev- els were determined at baseline and following TAVI. CMR was performed within a week before and within 30 days following TAVI. Some increase in cardiac biomarkers was detected in 97% of the patients as deter- mined by a rise in cTnT, and in 49% of the patients as determined by a rise in CK-MB. Following TAVI, no new myocardial necrosis defects were observed with the non-TA approach. Nonetheless, all patients who underwent TAVI through the TA approach had new focal myocardial necrosis in the apex, with a median myo-cardial extent and necrotic mass of 5% [2.0-7.0] and 3.5 g [2.3-4.5], respectively. Conclusions: Although some increase in cardiac biomarkers of myocardial injury was systematically detected following TAVI, new myocardial necrosis as evaluated by CMR was observed only in patients undergoing the procedure through the TA approach, involving ~5% of the myocardium in the apex