Review of clinical practice guidelines relating to cognitive assessment in stroke

Purpose: To assess the content, quality, and supporting evidence base of clinical practice guidelines (CPGs) with reference to cognitive assessment in stroke. Materials and methods: We performed a systematic review to identify eligible CPGs pertaining to cognitive assessment in adult stroke survivors. We compared content and strength of recommendations. We used the AGREE-II (appraisal of guidelines for research and evaluation) tool to appraise the quality of the guideline. Results: Eight eligible guidelines were identified and seven were rated as high quality (i.e., appropriately addressing at least four domains of the AGREE-II tool including “rigor of development”). There was heterogeneity in the recommendations offered and limited guidance on fundamental topics such as which cognitive test to use or when to perform testing. Generally, the lowest quality of evidence (expert opinion) was used to inform these recommendations. Conclusions: Although assessment of cognition is a key aspect of stroke care, there is a lack of guidance for clinicians. The limited evidence base, in part, reflects the limited research in the area. A prescriptive approach to cognitive assessment may not be suitable, but more primary research may help inform practice

Serendipitous Geodesy from Bennu's Short-Lived Moonlets

The Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx; or OREx) spacecraft arrived at its target, near-Earth asteroid (101955) Bennu, on December 3, 2018. The OSIRIS-REx spacecraft has since collected a wealth of scientific information in order to select a suitable site for sampling. Shortly after insertion into orbit on December 31, 2018, particles were identified in starfield images taken by the navigation camera (NavCam 1). Several groups within the OSlRlS-REx team analyzed the particle data in an effort to better understand this newfound activity of Bennu and to investigate the potential sensitivity of the particles to Bennu's geophysical parameters. A number of particles were identified through automatic and manual methods in multiple images, which could be turned into short sequences of optical tracking observations. Here, we discuss the precision orbit determination (OD) effort focused on these particles at NASA GSFC, which involved members of the Independent Navigation Team (INT) in particular. The particle data are combined with other OSIRIS-REx tracking data (radiometric from OSN and optical landmark data) using the NASA GSFC GEODYN orbit determination and geodetic parameter estimation software. We present the results of our study, particularly those pertaining to the gravity field of Bennu. We describe the force modeling improvements made to GEODYN specifically for this work, e.g., with a raytracing-based modeling of solar radiation pressure. The short-lived, low-flying moonlets enable us to determine a gravity field model up to a relatively high degree and order: at least degree 6 without constraints, and up to degree 10 when applying Kaula-like regularization. We can backward- and forward-integrate the trajectory of these particles to the ejection and landing sites on Bennu. We assess the recovered field by its impact on the OSIRIS-REx trajectory reconstruction and prediction quality in the various mission phases (e.g., Orbital A, Detailed Survey, and Orbital B)

Research protocol – Assessing Post-Stroke Psychology Longitudinal Evaluation (APPLE) study : A prospective cohort study in stroke

Acknowledgements The following experts provided advice on the design and conduct of the APPLE study: Prof Jonathan Evans (University of Glasgow); Prof Gillian Mead (University of Edinburgh); Prof Sarah T Pendlebury (University of Oxford) Funding This work was supported by the Chief Scientist Office and Stroke Association (funders reference PPA 2015/01_CSO).Peer reviewedPublisher PD

Linking behaviour and climate change in intertidal ectotherms: insights from littorinid snails

A key element missing from many predictive models of the impacts of climate change on intertidal ectotherms is the role of individual behaviour. In this synthesis, using littorinid snails as a case study, we show how thermoregulatory behaviours may buffer changes in environmental temperatures. These behaviours include either a flight response, to escape the most extreme conditions and utilize warmer or cooler environments; or a fight response, where individuals modify their own environments to minimize thermal extremes. A conceptual model, generated from studies of littorinid snails, shows that various flight and fight thermoregulatory behaviours may allow an individual to widen its thermal safety margin (TSM) under warming or cooling environmental conditions and hence increase species’ resilience to climate change. Thermoregulatory behaviours may also buffer sublethal fitness impacts associated with thermal stresses. Through this synthesis, we emphasise that future studies need to consider not only animals' physiological limits but also their capacities to buffer the impact of climate change through behavioural responses. Current generalizations, made largely on physiological limits of species, often neglect the buffering effects of behaviour and may, therefore, provide an over-estimation of vulnerability, and consequently poor prediction of the potential impacts of climate change on intertidal ectotherms

De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies

Epileptic encephalopathies (EEs) are the most clinically important group of severe early-onset epilepsies. Next-generation sequencing has highlighted the crucial contribution of de novo mutations to the genetic architecture of EEs as well as to their underlying genetic heterogeneity. Our previous whole-exome sequencing study of 264 parent-child trios revealed more than 290 candidate genes in which only a single individual had a de novo variant. We sought to identify additional pathogenic variants in a subset (n = 27) of these genes via targeted sequencing in an unsolved cohort of 531 individuals with a diverse range of EEs. We report 17 individuals with pathogenic variants in seven of the 27 genes, defining a genetic etiology in 3.2% of this unsolved cohort. Our results provide definitive evidence that de novo mutations in SLC1A2 and CACNA1A cause specific EEs and expand the compendium of clinically relevant genotypes for GABRB3. We also identified EEs caused by genetic variants in ALG13, DNM1, and GNAO1 and report a mutation in IQSEC2. Notably, recurrent mutations accounted for 7/17 of the pathogenic variants identified. As a result of high-depth coverage, parental mosaicism was identified in two out of 14 cases tested with mutant allelic fractions of 5%–6% in the unaffected parents, carrying significant reproductive counseling implications. These results confirm that dysregulation in diverse cellular neuronal pathways causes EEs, and they will inform the diagnosis and management of individuals with these devastating disorders

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder