Three-dimensional in situ XCT characterisation and FE modelling of cracking in concrete

Three-dimensional (3D) characterisation and modelling of cracking in concrete have been always of great importance and interest in civil engineering. In this study, an in situ microscale X-ray computed tomography (XCT) test was carried out to characterise the 3D microscale structure and cracking behaviour under progressive uniaxial compressive loading. The 3D cracking and fracture behaviour including internal crack opening, closing, and bridging were observed through both 2D tomography slices and 3D CT images. Spatial distributions of voids and cracks were obtained to understand the overall cracking process within the specimen. Furthermore, the XCT images of the original configuration of the specimen were processed and used to build microscale realistic 3D finite element (FE) models. Cohesive interface elements were inserted into the FE mesh to capture complicated discrete crack initiation and propagation. An FE simulation of uniaxial compression was conducted and validated by the in situ XCT compression test results, followed by a tension simulation using the same image-based model to investigate the cracking behaviour. The quantitative agreement between the FE simulation and experiment demonstrates that it is a very promising and effective technique to investigate the internal damage and fracture behaviour in multiphasic composites by combining the in situ micro XCT experiment and image-based FE modelling

Spatial variability in the mechanical properties of Gilsocarbon

The objective of this study is to investigate whether there is significant spatial variability in the mechanical properties of Gilsocarbon nuclear graphite at different sections of the billet; specifically the dynamic Poisson's ratio, dynamic shear modulus, dynamic Young's modulus and density. Similar studies have been done, usually in the context of manufacturing, to assess the quality of graphite components for nuclear reactors. In this new study, the measurements have been carried out at a much higher spatial resolution than previously. A Torness/Heysham B billet was machined into cubes so that measurements could be made across the circumference and height of the billet. ASTM standards were followed to assess the measurements of the samples. The spatial variability of material properties is described and analysed statistically. The study shows that material variability is present at different heights and circumferential locations of the billet. This discovery will have a significant impact on the structural integrity and through life performance predictions made in industry; both in current and future nuclear reactors. The computer modelling of graphite components may predict different outcomes to standard analyses (that use mean values) if this variability is incorporated into the analysis workflow; specifically through stochastic modelling

Fracture strength testing at the micron-scale on an ultra-fine grained WCr10- Ti2 alloy

The fracture strength of a W-Cr10-Ti2 alloy, manufactured through mechanical alloying and subsequent hot isostatic pressing, has been measured through means of micro-cantilever testing at the Culham Materials Research Facility. The material is a product of ongoing work into self-passivating Tungsten alloys at CEIT, Spain [1] and was chosen for this work due to its fine micro-structure (average grain size Heavy ion implantations to a depth of 3.5µm and an average damage of 0.7 and 7dpa were conducted at RBI, Zagreb in order to assess the effects of nuclear fusion relevant irradiation damage on the fracture strength of the material. Nano-indentation with pile-up correction showed an increase in hardness of 10% and 15% respectively. Results from micro-cantilever testing showed an apparent increase in the elastic modulus with implantation. This is not yet fully understood but similar effects have been reported in work on pure Tungsten previously [2]. A decrease in fracture strength by 10% was observed after implantation to 0.7dpa. For the 7dpa implanted material a slight increase in fracture strength was measured. This however changes to a decrease of 15% when normalized to the nano-indentation measured elastic modulus. Explanations for both the increase in the elastic modulus as well as the proportional effect on fracture strength measurements will be discussed

Effect of rhenium irradiations on the mechanical properties of tungsten for nuclear fusion applications

As-received and annealed tungsten samples were irradiated at a temperature of 400 °C with Re and W ions to peak concentrations of 1600 appm (atomic parts per million) and damage levels of 40 dpa (displacements per atom). Mechanical properties were investigated using nanoindentation, and the orientation and depth dependence of irradiation damage was investigated using Electron Back Scatter Diffraction (EBSD). Following irradiation there was a 13% increase in hardness in the as received sheet and a 23% increase in the annealed material for both tungsten and rhenium irradiation. The difference between the tungsten and rhenium irradiated samples was negligible, suggesting that for the concentrations and damage levels employed, the presence of rhenium does not have a significant effect on the hardening mechanism. Energy dependent EBSD of annealed samples provided information about the depth distribution of the radiation damage in individual tungsten grains and confirmed that the radiation damage is orientation dependant

Protocol for a double-blind placebo-controlled randomised controlled trial assessing the impact of oral semaglutide in amyloid positivity (ISAP) in community dwelling UK adults

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently marketed for type 2 diabetes and obesity, may offer novel mechanisms to delay or prevent neurotoxicity associated with Alzheimer’s disease (AD). The impact of semaglutide in amyloid positivity (ISAP) trial is investigating whether the GLP-1 RA semaglutide reduces accumulation in the brain of cortical tau protein and neuroinflammation in individuals with preclinical/prodromal AD. Methods and analysis: ISAP is an investigator-led, randomised, double-blind, superiority trial of oral semaglutide compared with placebo. Up to 88 individuals aged ≥55 years with brain amyloid positivity as assessed by positron emission tomography (PET) or cerebrospinal fluid, and no or mild cognitive impairment, will be randomised. People with the low-affinity binding variant of the rs6971 allele of the Translocator Protein 18 kDa (TSPO) gene, which can interfere with interpreting TSPO PET scans (a measure of neuroinflammation), will be excluded. At baseline, participants undergo tau, TSPO PET and MRI scanning, and provide data on physical activity and cognition. Eligible individuals are randomised in a 1:1 ratio to once-daily oral semaglutide or placebo, starting at 3 mg and up-titrating to 14 mg over 8 weeks. They will attend safety visits and provide blood samples to measure AD biomarkers at weeks 4, 8, 26 and 39. All cognitive assessments are repeated at week 26. The last study visit will be at week 52, when all baseline measurements will be repeated. The primary end point is the 1-year change in tau PET signal. Ethics and dissemination: The study was approved by the West Midlands—Edgbaston Research Ethics Committee (22/WM/0013). The results of the study will be disseminated through scientific presentations and peer-reviewed publications. Trial registration number: ISRCTN71283871

Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial

Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPTRx) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascending dose phase 1b trial evaluated the safety, pharmacokinetics and target engagement of MAPTRx. Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to intrathecal bolus administrations of MAPTRx or placebo every 4 or 12 weeks during the 13-week treatment period, followed by a 23 week post-treatment period. The primary endpoint was safety. The secondary endpoint was MAPTRx pharmacokinetics in cerebrospinal fluid (CSF). The prespecified key exploratory outcome was CSF total-tau protein concentration. Forty-six patients enrolled in the trial, of whom 34 were randomized to MAPTRx and 12 to placebo. Adverse events were reported in 94% of MAPTRx-treated patients and 75% of placebo-treated patients; all were mild or moderate. No serious adverse events were reported in MAPTRx-treated patients. Dose-dependent reduction in the CSF total-tau concentration was observed with greater than 50% mean reduction from baseline at 24 weeks post-last dose in the 60 mg (four doses) and 115 mg (two doses) MAPTRx groups. Clinicaltrials.gov registration number: NCT03186989

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.</p