Bearing damage characteristics of fibre-reinforced countersunk composite bolted joints subjected to quasi-static shear loading

This paper studies the progression of damage in carbon fibre-reinforced polymer (CFRP) countersunk composite bolted joints (CBJs) with neat-fit clearance, subjected to quasi-static loading. Damage mechanisms, comprising of fibre buckling and breakage, matrix damage, shear damage and inter-laminar delamination within the CFRP composite parts of the joints have been studied. Load-displacement curves, X-ray and optical microscopic images in single- and three-bolt CBJs were used to investigate damage and deformation characteristics. The observations were then employed to further investigate the type of failure and the extent of damage. The evolution of damage within the composite parts was correlated to the failure characteristics of the joints: It was found that the type and extension of damage is strongly correlated with the ultimate failure load point of the joint in single-bolt CBJs. A combined inter/intra-laminar damage consisting of fibre cluster breakage, extensive fibre buckling, debonding and delamination was observed at the ultimate failure load. This study was then extended to three-bolt CBJ where damage surrounding each bolt and its corresponding failure load was strongly correlated: The final study showed that the ultimate failure point in single-bolt CBJ and the first-bolt-failure point in three-bolt CBJ correspond to the composite plies undergoing intra-laminar damage with the size reaching to the edge of the countersunk head. This damage developed extensively through the thickness of the composite parts underneath the countersink, and in the direction opposite to the loading direction. Outside the countersunk head, debonding and delamination were found to be the dominant damage driving mechanisms. Finally, a new design rule has been proposed to predict the response of multi-bolt joints (damage area and failure load) by using the response in single-bolt CBJ as an initial baseline

Clinical and genetic characterization of leukoencephalopathies in adults

Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults

European Stroke Organisation expedited recommendation for the use of short-term dual antiplatelet therapy early after minor stroke and high-risk TIA

Prevention of early recurrent ischaemic stroke remains a priority in people with TIA or ischaemic stroke. A number of trials have recently been completed assessing the efficacy of short-term dual antiplatelet therapy (DAPT) versus single antiplatelet therapy early after minor or moderate stroke or high-risk TIA. We present an Expedited Recommendation for use of dual antiplatelet therapy early after ischaemic stroke and TIA on behalf of the ESO Guideline Board. We make a strong recommendation based on high quality of evidence for use of 21-days of dual antiplatelet therapy with aspirin and clopidogrel in people with a non-cardioembolic minor ischaemic stroke or high-risk TIA in the past 24 hours. We make a weak recommendation based on moderate quality evidence for 30-days of dual antiplatelet therapy with aspirin and ticagrelor in people with non-cardioembolic mild to moderate ischaemic stroke or high-risk TIA in the past 24 hours

White matter integrity correlates with cognition and disease severity in Fabry disease

Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42-81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects. We obtained average values of fractional anisotropy and mean diffusivity within the white matter and performed voxelwise analysis with tract-based spatial statistics. Using a standardized neuropsychological test battery, we assessed processing speed, executive function, anxiety, depression and disease severity. The mean age (% male) was 44.1 (45%) for patients with Fabry disease and 37.4 (53%) for the healthy control group. In patients with Fabry disease, compared to healthy controls the mean average white matter fractional anisotropy was lower in [0.423 (standard deviation, SD 0.023) versus 0.446 (SD 0.016), P = 0.002] while mean average white matter mean diffusivity was higher (749 × 10-6 mm2/s (SD 32 × 10-6) versus 720 × 10-6 mm2/s (SD 21 × 10-6), P = 0.004]. Voxelwise statistics showed that the diffusion abnormalities for both fractional anisotropy and mean diffusivity were anatomically widespread. A lesion probability map showed that white matter hyperintensities also had a wide anatomical distribution with a predilection for the posterior centrum semiovale. However, diffusion abnormalities in Fabry disease were not restricted to lesional tissue; compared to healthy controls, the normal appearing white matter in patients with Fabry disease had reduced fractional anisotropy [0.422 (SD 0.022) versus 0.443 (SD 0.017) P = 0.003] and increased mean diffusivity [747 × 10-6 mm2/s (SD 26 × 10-6) versus 723 × 10-6 mm2/s (SD 22 × 10-6), P = 0.008]. Within patients, average white matter fractional anisotropy and white matter lesion volume showed statistically significant correlations with Digit Symbol Coding Test score (r = 0.558, P = 0.001; and r = -0.633, P ≤ 0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r = -0.661, P ≤ 0.001), while average white matter mean diffusivity showed a strong correlation with plasma lyso-Gb3 levels (r = 0.559, P = 0.001). Our findings using DTI confirm widespread areas of microstructural white matter disruption in Fabry disease, extending beyond white matter hyperintensities seen on conventional MRI. Moreover, diffusion measures show strong correlations with cognition (processing speed), clinical disease severity and a putative plasma biomarker of disease activity, making them promising quantitative biomarkers for monitoring Fabry disease severity and progression

Therapeutic Decision Making in Acute Stroke due to Carotid Artery Dissection: A Potential Role for Percutaneous Vascular Intervention following Intravenous Thrombolysis

Internal carotid artery dissection (ICAD) is an important cause of acute ischemic stroke in younger patients. Potential acute treatments include anticoagulation, intravenous thrombolysis (IVT), and endovascular thrombectomy (ET). We report a case where the use of IVT followed by ET resulted in a good clinical outcome in a patient with tandem internal carotid and middle cerebral artery occlusion following ICAD

RBCK1‐related disease: A rare multisystem disorder with polyglucosan storage, auto‐inflammation, recurrent infections, skeletal, and cardiac myopathy—Four additional patients and a review of the current literature

In this article, we report four new patients, from three kindreds, with pathogenic variants in RBCK1 and a multisystem disorder characterised by widespread polyglucosan storage. We describe the clinical presentation of progressive skeletal and cardiac myopathy, combined immunodeficiencies and auto‐inflammation, illustrate in detail the histopathological findings in multiple tissue types, and report muscle MRI findings

Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies

Background Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. Methods We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. Findings In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio [OR] 3·8, 95% CI 2·1–7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8–5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6–8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I (c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). Interpretation Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness

Reduction in Early Stroke Risk in Carotid Stenosis With Transient Ischemic Attack Associated With Statin Treatment

Background and purposeStatins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis.MethodsWe analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded.ResultsIn patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P&lt;0.0001; 90-day risks 17.8% and 5.7% [P&lt;0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8-2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054).ConclusionsIn acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required