Personalising treatment in patients with carotid disease

Approximately 10-15% of all ischaemic strokes are caused by atherosclerotic stenosis of the carotid artery. Conventionally, carotid stenosis was treated by surgical removal of the atherosclerotic plaque (carotid endarterectomy). Since the introduction of carotid artery stenting as a less invasive treatment alternative almost 20 years ago, the choice of the optimal treatment for the individual patient with carotid stenosis has remained controversial. This PhD thesis consisted of three individual projects and aimed to enable personalised treatment decisions for individual patients with carotid disease and explore parameters specifically linked to the mechanisms of stroke occurring as a complication of both revascularisation procedures. The first project consisted of a systematic review and meta-analysis with the aim to compare short-term risks and long-term effects on stroke prevention between carotid stenting and endarterectomy in patients with symptomatic or asymptomatic carotid stenosis. To this end, we performed a systematic Cochrane Review of all published randomised trials comparing carotid stenting versus endarterectomy to obtain precise overall estimates of procedural risks and long-term stroke recurrence rates. We found that in patients with symptomatic carotid stenosis, stenting and endarterectomy are equally effective in preventing recurrent stroke in the long-term, while stenting is associated with a higher risk of procedure related stroke or death. In patients with asymptomatic carotid stenosis, there may be a small increase in the risk of procedure related stroke or death associated with stenting. However, more data from randomised trials are needed. Concerning the durability of carotid stenting in the long-term, only limited data are currently available for asymptomatic patients and the existing evidence does not yet allow any firm conclusions. The second project comprised the systematic assessment of the anatomy of all supra-aortic arteries and pre-defined stenosis characteristics in order to investigate the association between vascular anatomy and the occurrence of procedure-related cerebral ischaemia after carotid artery stenting or carotid endarterectomy in patients with symptomatic carotid stenosis. We identified complex vascular anatomy as an important predictor for cerebral ischaemia during stenting, but not during endarterectomy. The third and fourth projects consisted of an individual patient data meta-analysis of four randomised clinical trials comparing carotid artery stenting versus endarterectomy for treatment of symptomatic carotid stenosis. This work resulted in two separate manuscripts. Within the first, we investigated whether the temporal distribution of stroke or death occurring within 30 days of treatment differed between the two procedures. In the second, we investigated if the procedural risks associated with carotid stenting and carotid endarterectomy within the examined trials had decreased over time. Our analysis revealed that the excess occurrence of stroke or death associated with stenting is limited to the day of treatment. In our analysis of temporal trends in procedure related risks, we were able to show that carotid revascularisation procedures became safer over time within the examined trials. This decline in risk was particularly apparent for endarterectomy

Meanings in motion and faces: Developmental associations between the processing of intention from geometrical animations and gaze detection accuracy

Aspects of face processing, on the one hand, and theory of mind (ToM) tasks, on the other hand, show specific impairment in autism. We aimed to discover whether a correlation between tasks tapping these abilities was evident in typically developing children at two developmental stages. One hundred fifty-four normal children (6-8 years and 16-18 years) and 13 high-IQ autistic children (11-17 years) were tested on a range of face-processing and IQ tasks, and a ToM test based oil the attribution of intentional movement to abstract shapes in a cartoon. By midchildhood, the ability accurately and spontaneously to infer the locus of attention of a face with direct or averted gaze was specifically associated with the ability to describe geometrical animations using mental state terms. Other face-processing and animation descriptions failed to show the association. Autistic adolescents were impaired at both gaze processing and ToM descriptions. using these tests. Mentalizing and gaze perception accuracy are associated in typically developing children and adolescents. The findings are congruent with the possibility that common neural Circuitry underlies, at least in part, processing implicated in these tasks. They are also congruent with the possibility that autism may lie at one end of a developmental continuum with respect to these skills, and to the factor(s) underpinning them

REAPR: a universal tool for genome assembly evaluation.

Methods to reliably assess the accuracy of genome sequence data are lacking. Currently completeness is only described qualitatively and mis-assemblies are overlooked. Here we present REAPR, a tool that precisely identifies errors in genome assemblies without the need for a reference sequence. We have validated REAPR on complete genomes or de novo assemblies from bacteria, malaria and Caenorhabditis elegans, and demonstrate that 86% and 82% of the human and mouse reference genomes are error-free, respectively. When applied to an ongoing genome project, REAPR provides corrected assembly statistics allowing the quantitative comparison of multiple assemblies. REAPR is available at http://www.sanger.ac.uk/resources/software/reapr/

Calling for User-Centric VR Design Research in Hospitality and Tourism

VR has enjoyed a steep growth in awareness in society in recent years and is regarded a promising tool for the design and enhancement of experiences. However, as research and use cases in the hospitality context are expanding rapidly, it is crucial to define a clearer research direction that aligns the number of scattered studies across various fields. It is time to overcome the boundaries of the technological dimension and explore methods for purposeful VR design. This research note calls for more user-centric VR studies and developments to define the future direction of VR implementations in the hospitality and tourism industry. To achieve this, the authors recommend the use of design methodology with a focus on the first steps in the design process to clearly identify and understand issues concerning the customer. The customer needs and desires need to be analyzed at the core independent of VR technology. The need to shift the focus from technology to the purpose for the user is identified

Creating Opportunities for Digital Writing: Multimodality in Argument Writing Tasks

Writing students need opportunities in their language arts classrooms to develop the global skills that are paramount in today’s digital world. Students should not only be prepared to communicate in traditional forms but also through multiple literacies as well. Secondary ELA teachers and first-year composition instructors can build interest in writing tasks by including digital writing and multimodal elements that appeal to Gen Z students while also developing skills that transfer to other disciplines, civic life, and career goals. A digital writing sample unit for secondary ELA and FYC is included

The set-shifting profiles of anorexia nervosa and autism spectrum disorder using the Wisconsin Card Sorting Test: a systematic review and meta-analysis

Difficulties in set-shifting are commonly reported in both autism spectrum disorder (ASD) and anorexia nervosa (AN) populations. Despite this, it is not known whether this cognitive profile persists across different ages, or whether the profiles seen in ASD and AN are comparable. This systematic review and meta-analyses aimed to compare the set-shifting profiles, as measured by the Wisconsin Card Sorting Test (WCST) in adults and younger people with either ASD or AN, relative to healthy controls (HCs) and to statistically compare performance on the WCST between ASD and AN. In all, 24 studies on ASD and 22 studies on AN were identified. In ASD, there were significant differences between the clinical group and HCs, with the ASD group making significantly more perseverative errors, indicating greater difficulty in set-shifting [pooled effect size of d = 0.67, 95% confidence interval (CI) 0.53-0.81, p ⩽ 0.001]. This effect was consistent across the age span. For AN studies, there was a significant difference between adults with AN and HCs (d = 0.52, 95% CI 0.36-0.68, p ⩽ 0.001) but a non-significant effect in child studies (d = 0.25, 95% CI -0.05 to 0.55, z = 1.66, p = 0.096). Meta-regression indicated no effect of diagnosis (AN or ASD) on performance in adult studies but there was a non-significant trend (p = 0.053) towards children with ASD performing worse than children with AN. While difficulties with set-shifting appear to be stable in ASD, there may be differences between children and adults with AN, which warrant further investigation

Confabulation in children with autism

Some children with high-functioning autistic spectrum conditions (ASC) have been noted clinically to produce accounts and responses akin to confabulations in neurological patients. Neurological confabulation is typically associated with abnormalities of the frontal lobes and related structures, and some forms have been linked to poor performance on source monitoring and executive function tasks. ASC has also been linked to atypical development of the frontal lobes, and impaired performance on source monitoring and executive tasks. But confabulation in autism has not to our knowledge previously been examined experimentally. So we investigated whether patterns of confabulation in autism might share similarities with neurologically-based confabulation. Tests of confabulation elicitation, source monitoring (reality monitoring, plus temporal and task context memory) and executive function were administered to four adolescents with ASC who had previously been noted to confabulate spontaneously in everyday life. Scores were compared to a typically developing (TD) and an ASC control group. One confabulating participant was significantly impaired at reality monitoring, and one was significantly worse at a task context test, relative to both the ASC and TD controls. Three of the confabulators showed impairment on measures of executive function (Brixton test; Cognitive Estimates test; Hayling Test B errors) relative to both control groups. Three were significantly poorer than the TD controls on two others (Hayling A and B times), but the ASC control group was also significantly slower at this test than the TD controls. Compared to TD controls, two of the four confabulating participants produced an abnormal number of confabulations during a confabulation elicitation questionnaire, where the ASC controls and TD controls did not differ from each other. These results raise the possibility that in at least some cases, confabulation in autism may be less related to social factors than it is to impaired source memory or poor executive function

Nonideal Solution Behavior in Forward Osmosis Processes Using Magnetic Nanoparticles

Despite the tremendous progress made toward the realization of wider application for forward osmosis (FO) technologies, lack of suitable draw solutes that provide high water flux, low reverse solute flux, and facile recovery has hindered commercial development. An extensive variety of osmotic agents have been investigated during the past decade, and while simple inorganic salts remain the most widely used, organic-coated magnetic nanoparticles (MNPs) offer exploitable properties that hold great promise. In addition to size-mitigated reverse flux and low-cost recovery via magnetic separation, devitalized MNPs provide enhanced osmotic performance when compared to that of the ungrafted coating material at similar concentration levels, a consequence of greater nonideal solution behavior. This nonideality has been assessed using a simple, semiempirical model and is largely attributable to the increased solvent-accessible surface area and enhanced hydration. When attached to MNPs, polymers appear to behave osmotically as much smaller molecules, providing higher osmotic pressures and improved FO performance

Comprehensive analysis of liver macrophage composition by flow cytometry and immunofluorescence in murine NASH

Recently, it has become evident that macrophage diversity increases in the liver during the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we provide a detailed protocol for the analysis of liver macrophage subsets in mice with non-alcoholic fatty liver disease (NAFLD) and early NASH using flow cytometry and immunofluorescence (IF). These methods can be used to assess the composition and localization of macrophage subsets during NASH. For complete details on the use and execution of this protocol, please refer to Daemen et al. (2021)

Autistic adults' personal experiences of navigating a social world prior to and during Covid-19 lockdown in Spain

BACKGROUND: The SARS-CoV-2 coronavirus pandemic brought significant movement restrictions and national lockdowns. These drastic changes impacted routines, social life and support networks for the autistic community. AIMS: This study investigated the lived experiences of autistic adults with social expectations before and during the first Covid-19 lockdown in Spain. METHODS: A qualitative Reflexive Thematic Analysis was applied to 10 Photo Elicitation Interviews using images provided by five autistic adults. Interviews were conducted at two time points, before the pandemic and during the first lockdown. FINDINGS: Three themes before the pandemic were identified: (1) everyday interactions, (2) finding sense of belonging, and (3) fractured wellbeing, which revealed the participants' eagerness to fit in socially whilst experiencing rejection, weakening their mental health. During the first Covid-19 lockdown, two master themes were identified: (1) daily, positive experiences, and (2) surfacing failures, which emphasised an increased lived stigma as well as an ineffective autism support network, contributing to a heightened anxiety. CONCLUSIONS: The current study provides further support to the recent findings highlighting lack of appropriate mental health support for the autistic communities during the pandemic, across the world. Future research should aim to provide more data on the experiences and needs of autistic communities when sudden societal changes are imposed