A hysteretic multiscale formulation for nonlinear dynamic analysis of composite materials

This article has been made available through the Brunel Open Access Publishing Fund.A new multiscale finite element formulation is presented for nonlinear dynamic analysis of heterogeneous structures. The proposed multiscale approach utilizes the hysteretic finite element method to model the microstructure. Using the proposed computational scheme, the micro-basis functions, that are used to map the microdisplacement components to the coarse mesh, are only evaluated once and remain constant throughout the analysis procedure. This is accomplished by treating inelasticity at the micro-elemental level through properly defined hysteretic evolution equations. Two types of imposed boundary conditions are considered for the derivation of the multiscale basis functions, namely the linear and periodic boundary conditions. The validity of the proposed formulation as well as its computational efficiency are verified through illustrative numerical experiments

A radiomics-based decision support tool improves lung cancer diagnosis in combination with the Herder score in large lung nodules

Background: Large lung nodules (≥15 mm) have the highest risk of malignancy, and may exhibit important differences in phenotypic or clinical characteristics to their smaller counterparts. Existing risk models do not stratify large nodules well. We aimed to develop and validate an integrated segmentation and classification pipeline, incorporating deep-learning and traditional radiomics, to classify large lung nodules according to cancer risk. Methods: 502 patients from five U.K. centres were recruited to the large-nodule arm of the retrospective LIBRA study between July 2020 and April 2022. 838 CT scans were used for model development, split into training and test sets (70% and 30% respectively). An nnUNet model was trained to automate lung nodule segmentation. A radiomics signature was developed to classify nodules according to malignancy risk. Performance of the radiomics model, termed the large-nodule radiomics predictive vector (LN-RPV), was compared to three radiologists and the Brock and Herder scores. Findings: 499 patients had technically evaluable scans (mean age 69 ± 11, 257 men, 242 women). In the test set of 252 scans, the nnUNet achieved a DICE score of 0.86, and the LN-RPV achieved an AUC of 0.83 (95% CI 0.77–0.88) for malignancy classification. Performance was higher than the median radiologist (AUC 0.75 [95% CI 0.70–0.81], DeLong p = 0.03). LN-RPV was robust to auto-segmentation (ICC 0.94). For baseline solid nodules in the test set (117 patients), LN-RPV had an AUC of 0.87 (95% CI 0.80–0.93) compared to 0.67 (95% CI 0.55–0.76, DeLong p = 0.002) for the Brock score and 0.83 (95% CI 0.75–0.90, DeLong p = 0.4) for the Herder score. In the international external test set (n = 151), LN-RPV maintained an AUC of 0.75 (95% CI 0.63–0.85). 18 out of 22 (82%) malignant nodules in the Herder 10–70% category in the test set were identified as high risk by the decision-support tool, and may have been referred for earlier intervention. Interpretation: The model accurately segments and classifies large lung nodules, and may improve upon existing clinical models. Funding This project represents independent research funded by: 1) Royal Marsden Partners Cancer Alliance, 2) the Royal Marsden Cancer Charity, 3) the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, 4) the National Institute for Health Research (NIHR) Biomedical Research Centre at Imperial College London, 5) Cancer Research UK (C309/A31316)

Macrophage enzyme and reduced inflammation drive brain correction of mucopolysaccharidosis IIIB by stem cell gene therapy

Mucopolysaccharidosis IIIB is a paediatric lysosomal storage disease caused by deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU), involved in the degradation of the glycosaminoglycan heparan sulphate. Absence of NAGLU leads to accumulation of partially degraded heparan sulphate within lysosomes and the extracellular matrix, giving rise to severe CNS degeneration with progressive cognitive impairment and behavioural problems. There are no therapies. Haematopoietic stem cell transplant shows great efficacy in the related disease mucopolysaccharidosis I, where donor-derived monocytes can transmigrate into the brain following bone marrow engraftment, secrete the missing enzyme and cross-correct neighbouring cells. However, little neurological correction is achieved in patients with mucopolysaccharidosis IIIB. We have therefore developed an ex vivo haematopoietic stem cell gene therapy approach in a mouse model of mucopolysaccharidosis IIIB, using a high-titre lentiviral vector and the myeloid-specific CD11b promoter, driving the expression of NAGLU (LV.NAGLU). To understand the mechanism of correction we also compared this with a poorly secreted version of NAGLU containing a C-terminal fusion to IGFII (LV.NAGLU-IGFII). Mucopolysaccharidosis IIIB haematopoietic stem cells were transduced with vector, transplanted into myeloablated mucopolysaccharidosis IIIB mice and compared at 8 months of age with mice receiving a wild-type transplant. As the disease is characterized by increased inflammation, we also tested the anti-inflammatory steroidal agent prednisolone alone, or in combination with LV.NAGLU, to understand the importance of inflammation on behaviour. NAGLU enzyme was substantially increased in the brain of LV.NAGLU and LV.NAGLU-IGFII-treated mice, with little expression in wild-type bone marrow transplanted mice. LV.NAGLU treatment led to behavioural correction, normalization of heparan sulphate and sulphation patterning, reduced inflammatory cytokine expression and correction of astrocytosis, microgliosis and lysosomal compartment size throughout the brain. The addition of prednisolone improved inflammatory aspects further. Substantial correction of lysosomal storage in neurons and astrocytes was also achieved in LV.NAGLU-IGFII-treated mice, despite limited enzyme secretion from engrafted macrophages in the brain. Interestingly both wild-type bone marrow transplant and prednisolone treatment alone corrected behaviour, despite having little effect on brain neuropathology. This was attributed to a decrease in peripheral inflammatory cytokines. Here we show significant neurological disease correction is achieved using haematopoietic stem cell gene therapy, suggesting this therapy alone or in combination with anti-inflammatories may improve neurological function in patients

Shaking table tests and numerical analyses on a scaled dry-joint arch undergoing windowed sine pulses

The damages occurred during recent seismic events have emphasised the vulnerability of vaulted masonry structures, one of the most representative elements of worldwide cultural heritage. Although a certain consensus has been reached regarding the static behaviour of masonry arches, still more efforts are requested to investigate their dynamic behaviour. In this regard, the present paper aims to investigate the performance of a scaled dry-joint arch undergoing windowed sine pulses. A feature tracking based measuring technique was employed to evaluate the displacement of selected points, shading light on the failure mechanisms and gathering data for the calibration of the numerical model. This was built according to a micro-modelling approach of the finite element method, with voussoirs assumed very stiff and friction interface elements. Comparisons with existing literature are also stressed, together with comments about scale effects.This work was partly financed by FEDER funds through the Competitivity Factors Operational Programme-COMPETE and by national funds through FCT-Foundation for Science and Technology within the scope of the Project POCI-01-0145-FEDER-007633.info:eu-repo/semantics/publishedVersio

Cyclic sulphur-nitrogen compounds and phosphorus reagents: Part XIII¹-Reactions of cyclic sulphur-nitrogen chlorides with Ph₃P-influences of tertiary base, Et₃N and the ring size of the cyclothiazyl chloride on the product formation

961-966Similar to the reactions with S4N3Cl and S3N3Cl3,triphenylphosphine reacts with five-membered cyclic sulphur-nitrogen chlorides namely, S3N2Cl and S3N2Cl2 to give triphenylphosphiniminium chloride, Ph3P=NHCl- as the major product. Maximum yield (ca. 90%) is obtained when triphenylphosphine is reacted with S3N2Cl in acetonitrile at room temperature in 2:1 molar ratio. Analogous reactions performed in presence of triethylamine afford two cyclothiazene products containing phosphinimino substituent. The ring size of the S-N chloride seems to determine the nature of phosphiniminocyclothiazenes formed. A rationalization of the results obtained has been attempted