Design aspects of a CMC coating-like system for hot surfaces of aero engine components

Ceramic Matrix Composite (CMC) is an emerging material system that can be a game changer in the aerospace industry, both civil and military. CMCs components are, in fact, lighter and less prone to fatigue failure in a high temperature environment. However, at high temperatures, the diffusion of oxygen and water vapour inside the CMC can have detrimental effects. Therefore, the presence of protective coating is necessary to extend the life of CMC components. In the present work, a three-layers coating, consisting of a silicon bond (BND), adhesively bonded to the CMC, an Environment Barrier Coating (EBC) and a softer layer 3 (LAY3), is investigated for a CMC component. An aero-engine high pressure turbine seal segment was considered. Two design aspects are covered: (i) creep law is determined and calibrated in environment Abaqus from the experimental data of each coating layer available in the open literature, to provide a suitable instrument for the creep relaxation analyses of hot components; (ii) thickness sensitivity study of each layer of the coating is conducted to minimise the interface stresses of coating with substrate in order to mitigate cracking and removal/spalling phenomena when exposed to temperature gradients and to increase their service life. These two different aspects are combined together to predict the coating stress field as a function of service time

FEM and BEM Analysis of a Human Mandible with Added Temporomandibular Joints

Mathematical modelling of human mandible and its temporomandibular joints (TMJs) is one of the most important steps for developing a powerful forecasting tool to analyse the stress/strain behaviour of a human masticatory system under occlusal loads. In this work the structural behaviour of a mandible with articular discs, undergoing a unilateral occlusion, is numerically analysed by means of both Finite Element Method (FEM) and Boundary Element Method (BEM). The mandible is considered as completely edentulous and its anisotropic and non-homogeneous bone material behaviour is modelled. The material behaviour of the articular discs was assumed to be either elastic or hyper-elastic. The loads applied to the mandible are related to the active muscle groups during a unilateral occlusion. The results of FEM and BEM analyses are presented mainly in terms of stress distribution on the mandible and on the articular discs. Due to the uncertainty in the determination of the biological parameters, a sensitivity analysis is provided, which demonstrates the impact of the variation of articular disc stiffness and TMJ friction coefficient on the mandible stress peaks and on the occlusal loads (for a given intensity of muscle loads). Moreover a comparison between the effectiveness of the BEM and FEM numerical approaches on this kind of problem is provided

Stress Analysis of an Endosseus Dental Implant by BEM and FEM

In this work the Boundary Element Method (BEM) and the Finite Element Method (FEM) have been used for an elastic-static analysis of both a Branemark dental implant and a generic conic threaded implant, modelled either in the complete mandible or in a mandibular segment, under axial and lateral loading conditions. Two different hypotheses are considered with reference to degree of osteo-integration between the implant and the mandibular bone: perfect and partial osteointegration. The BEM analysis takes advantage of the submodelling technique, applied on the region surrounding the implant. Such region is extracted from the overall mandible and the boundary conditions for such submodel are obtained from the stress analysis realised on the complete mandible. The obtained results provide the localisation of the most stressed areas at the bone-implant interface and at the mandibular canal (containing the alveolar nerve) which represent the most critical areas during mastication. This methodology, enriched with the tools necessary for the numerical mandible reconstruction, is useful to realise sensitivity analysis of the stress field against a variation of the localisation, inclination and typology of the considered implant, in order to assess the optimal implant conditions for each patient under treatment. Due to the high flexibility in the pre- and post-processing phase and accuracy in reproducing superficial stress gradients, BEM is more efficient than FEM in facing this kind of problem, especially when a linear elastic constitutive material law is adopted

Prevention of Dermatologic Side Effects of Bimatoprost 0.03% Topical Therapy

PURPOSE: To investigate the efficacy of reducing the drop-skin contact to prevent dermatologic side effects of bimatoprost 0.03% topical therapy. DESIGN: Prospective, randomized, single-blinded, internally controlled study. METHODS: Enrolled subjects started bimatoprost 0.03% therapy once at night in both eyes and were instructed to wipe selectively only one eye (eye 1) with an adsorbent pad during and after drops administration for four months. The fellow eye acted as the internal control. Eyelash growth, regional skin hypertrichosis, and pigmentation on the periocular skin were assessed at baseline and during the four months of follow-up. RESULTS: A lower incidence of eyelash growth and skin pigmentation in the inferonasal pericanthal region were observed in eye 1. The incidence of pigmentation in the inferotemporal skin region and skin hypertrichosis were similar in the two eyes. CONCLUSION: The reduction of the drop,skin contact affects the regional incidence and the extent of dermatologic skin changes that are related to bimatoprost 0.03% topical therapy

FEM sensitivity analyses on the stress levels in a human mandible with a varying ATM modelling complexity

Abstract: In this work the structural behaviour of a mandible considering a unilateral occlusion is numerically analysed by means of the Finite Element Method (FEM). The mandible, considered as completely edentolous, is modelled together with its articular disks, whose material behaviour is assumed as elastic or hyper-elastic. The mandible model is obtained by computer tomography scans. The anisotropic and non homogeneous bone material behaviour is considered and the loads applied to the mandible are those related to the active muscle groups during unilateral occlusion. The results of FEM analysis are presented mainly in terms of stress distribution on the mandible. Because of uncertainty on the determination of the adopted parameters, a sensitivity analysis is provided, showing the way in which the variation of articular disc stiffness and temporomandibular joint friction coefficient has an impact on the mandible stress peak and occlusal force

Hedgehog-GLI signalling promotes chemoresistance through the regulation of ABC transporters in colorectal cancer cells

Colorectal cancer (CRC) is a leading cause of cancer death. Chemoresistance is a pivotal feature of cancer cells leading to treatment failure and ATP-binding cassette (ABC) transporters are responsible for the efflux of several molecules, including anticancer drugs. The Hedgehog-GLI (HH-GLI) pathway is a major signalling in CRC, however its role in chemoresistance has not been fully elucidated. Here we show that the HH-GLI pathway favours resistance to 5-fluorouracil and Oxaliplatin in CRC cells. We identified potential GLI1 binding sites in the promoter region of six ABC transporters, namely ABCA2, ABCB1, ABCB4, ABCB7, ABCC2 and ABCG1. Next, we investigated the binding of GLI1 using chromatin immunoprecipitation experiments and we demonstrate that GLI1 transcriptionally regulates the identified ABC transporters. We show that chemoresistant cells express high levels of GLI1 and of the ABC transporters and that GLI1 inhibition disrupts the transporters up-regulation. Moreover, we report that human CRC tumours express high levels of the ABCG1 transporter and that its expression correlates with worse patients’ prognosis. This study identifies a new mechanism where HH-GLI signalling regulates CRC chemoresistance features. Our results indicate that the inhibition of Gli1 regulates the ABC transporters expression and therefore should be considered as a therapeutic option in chemoresistant patients

Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor

Until recently it was assumed that hereditary angioedema is a disease that results exclusively from a genetic deficiency of the C1 inhibitor. In 2000, families with hereditary angioedema, normal C1 inhibitor activity and protein in plasma were described. Since then numerous patients and families with that condition have been reported. Most of the patients by far were women. In many of the affected women, oral contraceptives, hormone replacement therapy containing estrogens, and pregnancies triggered the clinical symptoms. Recently, in some families mutations in the coagulation factor XII (Hageman factor) gene were detected in the affected persons

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P &lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.</p

High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case–control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46–0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48–0.89]; p = 0.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p = 0.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of ≥ 1 somatic DDR gene mutation was 20% and 24.5% (p = 0.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p = 0.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted