24 research outputs found
multiaxial fatigue behavior of additive manufactured ti 6al 4v under in phase stresses
Abstract The development and application of additive manufacturing (AM) technologies is constantly increasing. However, in many applications, AM parts are subjected to multiaxial loads, arising from operating conditions and/or complex geometries. These make AM components serious candidates for crack initiation and propagation mechanisms. Therefore, a deep understanding of the multiaxial fatigue behavior of AM parts is essential in many applications where durability and reliability are core issues. In this study, multiaxial fatigue of Ti6Al4V thin-walled tubular specimens, made by Selective Laser Melting (SLM) process, was investigated by combined axial-torsional loads. Infrared thermography (IR) was also used to investigate the temperature evolution during fatigue tests. Results highlighted different damage mechanisms and failure modes in the low- and high-cycle fatigue regimes
Multiaxial fatigue behavior of additively manufactured Ti6Al4V alloy: Axial–torsional proportional loads
Additive manufacturing (AM) techniques are under constant development and selective laser melting (SLM) is among the most promising ones. However, widespread use of AM techniques in many industries is limited by the different/unusual mechanical properties of AM metallic parts, with respect to traditionally processed ones, especially when dealing with complex fatigue loading conditions. In fact, crack formation and propagation mechanisms are mainly affected by the development of internal defects, residual stresses, and microstructural changes. This is actually one of the major issues the materials engineering community is facing today. In many applications, AM components are subjected to multiaxial fatigue loads, arising from operating conditions and/or from complex geometries, that unavoidably generate crack initiation and propagation mechanisms. The aim of this study is to investigate the multiaxial fatigue behavior of additively manufactured Ti6Al4V samples, made by SLM. Fatigue tests, combining proportional axial and torsional loads, were performed on thin-walled tubular specimens. Full-field measurement techniques, such as the infrared thermography and digital image correlation, were also used to capture temperature and strain evolutions, at both local scales and global scales. Fatigue results highlighted damage mechanisms, and failure modes are strongly related to the applied stress level
Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males
The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor
An explainable model of host genetic interactions linked to COVID-19 severity
We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to
genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility
and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component.
Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci
(eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene),
including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform
genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer
SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the
diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types
Shape Memory Alloy—Polymer Composites: Static and Fatigue Pullout Strength under Thermo-Mechanical Loading
This work was carried out within the context of an R&D project on morphable polymer matrix composites (PMC), actuated by shape memory alloys (SMA), to be used for active aerodynamic systems in automotives. Critical issues for SMA–polymer integration are analyzed that are mostly related to the limited strength of metal–polymer interfaces. To this aim, materials with suitable thermo-mechanical properties were first selected to avoid premature activation of SMA elements during polymer setting as well as to avoid polymer damage during thermal activation of SMAs. Nonstandard samples were manufactured for both static and fatigue pullout tests under thermo-mechanical loading, which are made of SMA wires embedded in cylindrical resin blocks. Fully coupled thermo-mechanical simulations, including a special constitutive model for SMAs, were also carried out to analyze the stress and temperature distribution in the SMA–polymer samples as obtained from the application of both mechanical loads and thermal activation of the SMA wires. The results highlighted the severe effects of SMA thermal activation on adhesion strength due to the large recovery forces and to the temperature increase at the metal–polymer interface. Samples exhibit a nominal pullout stress of around 940 MPa under static mechanical load, and a marked reduction to 280 MPa was captured under simultaneous application of thermal and mechanical loads. Furthermore, fatigue run-out of 5000 cycles was achieved, under the combination of thermal activation and mechanical loads, at a nominal stress of around 200 MPa. These results represent the main design limitations of SMA/PMC systems in terms of maximum allowable stresses during both static and cyclic actuation
Risk of surgical site infections following hip and knee arthroplasty. Results of the ischia-gisio study
Introduzione. L'infezione del sito chirurgico (SSI) è una delle principali complicanze a seguito dell'inserimento della protesi dell'anca o del ginocchio. Lo scopo del presente studio era di descrivere i tassi di SSI e i fattori di rischio associati durante le procedure di protesi dell'anca e del ginocchio negli ospedali italiani.
Metodi. Gli ospedali italiani sono stati invitati a unirsi al progetto ISChIA (Infezioni del sito chirurgico in chirurgia di artroplastica) e hanno partecipato allo studio su base volontaria. La sorveglianza SSI è stata eseguita in base al protocollo SSI di collegamento ospedaliero per il controllo delle infezioni attraverso la sorveglianza (HELICS). La popolazione dello studio era composta da tutti i pazienti che avevano avuto una protesi protesica del ginocchio o dell'anca tra marzo 2010 e febbraio 2011. Sono state incluse solo operazioni elettive.
Risultati. Sono stati inclusi un totale di 14 ospedali e 1285 procedure chirurgiche. L'incidenza cumulativa di SSI è stata di 1,3 per 100 anca e 2,4 per 100 interventi chirurgici al ginocchio; una tendenza positiva significativa delle incidenze SSI è stata osservata con l'aumento dell'indice di rischio SSI. Nell'analisi multivariata, considerando le procedure dell'anca, il singolo fattore di rischio indipendente associato alla SSI era la lunghezza dell'operazione (RR: 4,54; IC al 95%: 1,06-19,48). Per le procedure al ginocchio, non è stato identificato alcun fattore di rischio significativo.
Conclusioni. Nel presente studio, l'incidenza cumulativa SSI era nell'intervallo di dati europei. Tuttavia, è necessario un numero maggiore di operazioni per stimare meglio le tariffe SSI. È già stata condotta una seconda edizione del progetto ISChIA e i risultati dei due sondaggi forniranno nuove conoscenze per approfondire le nostre conoscenze per il controllo delle infezioni.Background. Surgical Site Infection (SSI) is one of the major complications following insertion of hip or knee prosthesis. The aim of the present study was to describe rates of SSIs and associated risk factors during hip and knee prosthesis procedures in Italian hospitals.
Methods. Italian hospitals were invited to join the ISChIA (Surgical Site Infections in Arthroplasty Surgery) project and participated in the study on a voluntary basis. SSI surveillance was performed according to the Hospitals in Europe Link for Infection Control through Surveillance (HELICS)-SSI protocol. The study population consisted of all patients who had a prosthetic knee or hip joint replacement between March 2010 and February 2011. Only elective operations were included.
Results. A total of 14 hospitals and 1285 surgical procedures were included. SSI cumulative incidence was 1.3 per 100 hip and 2.4 per 100 knee surgical procedures; a significant positive trend of SSI incidences was observed with increasing SSI risk index. In multivariate analysis, considering hip procedures, the single independent risk factor associated to SSI was operation length (RR: 4.54; 95%CI: 1.06-19.48). For knee procedures, no significant risk factor was identified.
Conclusions. In the present study, SSI cumulative incidence was in the range of European data. However, a larger number of operations is needed to better estimate SSI rates. A second edition of the ISChIA project has been already conducted and results of the two surveys will provide new insight to further our knowledge for infection control