Patch-wise Quadrature of Trimmed Surfaces in Isogeometric Analysis

This work presents an efficient quadrature rule for shell analysis fully integrated in CAD by means of Isogeometric Analysis (IGA). General CAD-models may consist of trimmed parts such as holes, intersections, cut-offs etc. Therefore, IGA should be able to deal with these models in order to fulfil its promise of closing the gap between design and analysis. Trimming operations violate the tensor-product structure of the used Non-Uniform Rational B-spline (NURBS) basis functions and of typical quadrature rules. Existing efficient patch-wise quadrature rules consider actual knot vectors and are determined in 1D. They are extended to further dimensions by means of a tensor-product. Therefore, they are not directly applicable to trimmed structures. The herein proposed method extends patch-wise quadrature rules to trimmed surfaces. Thereby, the number of quadrature points can be signifficantly reduced. Geometrically linear and non-linear benchmarks of plane, plate and shell structures are investigated. The results are compared to a standard trimming procedure and a good performance is observed

Novel targeted strategies to overcome resistance in small-cell lung cancer: focus on PARP inhibitors and rovalpituzumab tesirine

ABSTRACTIntroduction: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour, and its outcome is strongly conditioned by the rapid onset of resistance to conventional chemothera..

Is there a role for dacomitinib, a second-generation irreversible inhibitor of the epidermal-growth factor receptor tyrosine kinase, in advanced non-small cell lung cancer?

Introduction: Non-small cell lung cancer (NSCLC) is a highly lethal disease. During the past 20 years, the epidermal growth factor receptor (EGFR) has been a relevant target for anticancer drug-design, and a large family of EGFR tyrosine kinase inhibitors (TKI) were designed, which improved therapeutic outcomes compared to conventional chemotherapy in NSCLC patients with specific EGFR mutations. However, resistance to these inhibitors occurs; therefore, the debate on which inhibitor should be used first is still open. Dacomitinib was approved in 2018 for the first-line treatment of NSCLC with EGFR activating mutations. Areas covered: This manuscript reviews the properties of dacomitinib, including the current information from clinical trials and its potential application as stand-alone therapy, or in combination. Expert opinion: Dacomitinib is a second-generation EGFR-TKI that has demonstrated significant improvement in overall survival in a phase III randomized study compared with gefitinib, a first-generation TKI. However, the rapid development and approval of a new generation of TKIs (osimertinib), with better clinical profiles, raises the question of which role can dacomitinib play in NSCLC. Further studies are required to evaluate the efficacy of this drug on brain metastases, as a second-line treatment after third-generation TKIs, or in combination with other types of treatments

Surface composition of mixed self-assembled monolayers on Au by infrared attenuated total reflection spectroscopy

Abstract Self-assembled monolayers (SAMs) of N-(2-hydroxyethyl)-3-mercaptopropanamide (NMPA) were synthesized directly on the surface of electron-beam evaporated Au films, starting from 3-mercaptopropionic acid (3MPA) via ethyl-3-(3-dimethylamino-propyl)carbodiimide/N-hydroxysulfosuccinimide sodium salt (EDC/NHSS) coupling with ethanolamine hydrochloride. The influence on the reaction yield of the acidity of EDC/NHSS solutions (pH = 5.6 or 4.8) was assessed by exploiting the high surface sensitivity of infrared attenuated total reflection spectroscopy. The light-matter interaction was modeled in the framework of a matrix formalism considering the complete multi-layer sample structure. A comparison between the relative intensity of the main absorption bands, associated with amide I and carbonyl stretching of carboxylic acid or amide II vibrations, with a calibration curve obtained from the measurement of mixed 3MPA/NMPA SAMs, show that the more acid solution is 16% more efficient. This is mostly due to the higher protonation of the 3MPA

The right immune-modulation at the right time: thymosin α1 for prevention of severe COVID-19 in cancer patients

We presented the rationale for the use of thymosin alpha1 as prophylaxis of severe COVID-19 in cancer patients undergoing active treatment, constituting the background for the PROTHYMOS study, a prospective, multicenter, open-label, Phase II randomized study, currently in its start-up phase(Eudract no.2020-006020-13). We aim to offer new hope for this incurable disease, especially to frail patient population, such as patients with cancer. The hypothesis of an effective prophylactic approach to COVID-19 would have immediate clinical relevance, especially given the lack of curative approaches. Moreover, in the 'COVID-19 vaccine race era' both clinical and biological results coming from the PROTHYMOS trials could even support the rationale for future combinatorial approaches, trying to rise vaccine efficacy in frail individuals

Collective behavior and self-organization in neural rosette morphogenesis

Neural rosettes develop from the self-organization of differentiating human pluripotent stem cells. This process mimics the emergence of the embryonic central nervous system primordium, i.e., the neural tube, whose formation is under close investigation as errors during such process result in severe diseases like spina bifida and anencephaly. While neural tube formation is recognized as an example of self-organization, we still do not understand the fundamental mechanisms guiding the process. Here, we discuss the different theoretical frameworks that have been proposed to explain self-organization in morphogenesis. We show that an explanation based exclusively on stem cell differentiation cannot describe the emergence of spatial organization, and an explanation based on patterning models cannot explain how different groups of cells can collectively migrate and produce the mechanical transformations required to generate the neural tube. We conclude that neural rosette development is a relevant experimental 2D in-vitro model of morphogenesis because it is a multi-scale self-organization process that involves both cell differentiation and tissue development. Ultimately, to understand rosette formation, we first need to fully understand the complex interplay between growth, migration, cytoarchitecture organization, and cell type evolution

Adoption of Improved Reprocessing Decreased Microbiological Non-Compliance for Bronchoscopes

Background: In the past few decades, the inadequate reprocessing of bronchoscopes has been associated with several serious outbreaks caused by multidrug-resistant microorganisms. In this study we evaluated the improvement in the quality of reprocessing in a Bronchoscopy Unit (BU), after the introduction of a new procedure. Methods: In 2019, observational and clinical audits were conducted in the BU. After the introduction of an improved procedure in 2020, a microbiological surveillance plan was implemented in 2021. Results: In 2019, 13 of 22 bronchoscopes (59%) resulted as non-compliant, 18% as high concern organisms (HCO) and 36.4% as high microbial count (>= 100 CFU/all channels) and HCO. The most frequent microorganisms were Staphylococcus aureus (38.5%) and NDM-producing Klebsiella pneumoniae (15.4%). The bronchoscopes were stored inside their transport cases, which in some cases were found to be contaminated by the same strains isolated on the bronchoscopes (Enterobacter gergoviae and Vibrio alginolyticus). In 2021, all 31 bronchoscopes were sampled at least three times and 13/99 (13.1%) resulted as non-compliant, mostly K. pneumoniae (4.04%). Contamination level increases weakly in bronchoscopes in use for more than 14 years (R = 0.32). Conclusions: The adoption of an improved reprocessing procedure decreased the non-compliance of bronchoscopes, increasing the quality of the process and patient safety

Robust and Efficient Large Deformation Analysis of Kirchhoff–love Shells: Locking, Patch Coupling and Iterative Solution

Isogeometric Kirchhoff-Love elements have received an increasing attention in geometrically nonlinear analysis of thin walled structures. They make it possible to meet the C1requirement in the interior of surface patches, to avoid the use of finite rotations and to reduce the number of unknowns compared to shear flexible models. Locking elimination, patch coupling and iterative solution are crucial points for a robust and efficient nonlinear analysis and represent the main focus of this work. Patch-wise reduced integrations are investigated to deal with locking in large deformation problems discretized via a standard displacement-based formulation. An optimal integration scheme for third order C2NURBS, in terms of accuracy and efficiency, is identified, allowing to avoid locking without resorting to a mixed formulation. The Newton method with mixed integration points (MIP) is used for the solution of the discrete nonlinear equations with a great reduction of the iterative burden and a superior robustness with respect to the standard Newton scheme. A simple penalty approach for coupling adjacent patches, applicable to either smooth or non-smooth interfaces, is proposed. An accurate coupling, also for a nonmatching discretization, is obtained using an interface-wise reduced integration while the MIP iterative scheme allows for a robust and efficient solution also with very high values of the penalty parameter