159 research outputs found
Towards a consensus-based classification of childhood arterial ischemic stroke.
Background and purposeThe implementation of uniform nomenclature and classification in adult arterial ischemic stroke (AIS) has been critical for defining outcomes and recurrence risks according to etiology and in developing risk-stratified treatments. In contrast, current classification and nomenclature in childhood AIS are often overlapping or contradictory. Our purpose was to develop a comprehensive consensus-based classification system for childhood AIS.MethodsUsing a modified-Delphi method, members of the International Pediatric Stroke Study (IPSS) developed the Childhood AIS Standardized Classification And Diagnostic Evaluation (CASCADE) criteria. Two groups of pediatric stroke specialists from the IPSS classified 7 test cases using 2 methods each: (1) classification typical of the individual clinician's current clinical practice; and (2) classification based on the CASCADE criteria. Group 1 underwent in-person training in the utilization of the CASCADE criteria. Group 2 classified the same cases via an online survey, including definitions but without training. Inter-rater reliability (IRR) was assessed via multi-rater unweighted κ-statistic.ResultsIn Group 1 (with training), IRR was improved using CASCADE criteria (κ=0.78, 95% CI=[0.49, 0.94]), compared with typical clinical practice (κ=0.40, 95% CI=[0.11, 0.60]). In Group 2 (without training), IRR was lower than among trained raters (κ=0.61, 95% CI=[0.29, 0.77]), but higher than current practice (κ=0.23, 95% CI=[0.03, 0.36]).ConclusionsA new, consensus-based classification system for childhood AIS, the CASCADE criteria, can be used to classify cases with good IRR. These preliminary findings suggest that the CASCADE criteria may be particularity useful in the setting of prospective multicenter studies in childhood-onset AIS, where standardized training of investigators is feasible
Inter-Rater Reliability of the CASCADE Criteria: Challenges in Classifying Arteriopathies.
Background and purposeThere are limited data about the reliability of subtype classification in childhood arterial ischemic stroke, an issue that prompted the IPSS (International Pediatric Stroke Study) to develop the CASCADE criteria (Childhood AIS Standardized Classification and Diagnostic Evaluation). Our purpose was to determine the CASCADE criteria's reliability in a population of children with stroke.MethodsEight raters from the IPSS reviewed neuroimaging and clinical records of 64 cases (16 cases each) randomly selected from a prospectively collected cohort of 113 children with arterial ischemic stroke and classified them using the CASCADE criteria. Clinical data abstracted included history of present illness, risk factors, and acute imaging. Agreement among raters was measured by unweighted κ statistic.ResultsThe CASCADE criteria demonstrated a moderate inter-rater reliability, with an overall κ statistic of 0.53 (95% confidence interval [CI]=0.39-0.67). Cardioembolic and bilateral cerebral arteriopathy subtypes had much higher agreement (κ=0.84; 95% CI=0.70-0.99; and κ=0.90; 95% CI=0.71-1.00, respectively) than cases of aortic/cervical arteriopathy (κ=0.36; 95% CI=0.01-0.71), unilateral focal cerebral arteriopathy of childhood (FCA; κ=0.49; 95% CI=0.23-0.76), and small vessel arteriopathy of childhood (κ=-0.012; 95% CI=-0.04 to 0.01).ConclusionsThe CASCADE criteria have moderate reliability when used by trained and experienced raters, which suggests that it can be used for classification in multicenter pediatric stroke studies. However, the moderate reliability of the arteriopathic subtypes suggests that further refinement is needed for defining subtypes. Such revisions may reduce the variability in the literature describing risk factors, recurrence, and outcomes associated with childhood arteriopathy
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Research Data Management Principles, Practices, and Prospects
This report examines how research institutions are responding to data management requirements of the National Science Foundation, National Institutes of Health, and other federal agencies. It also considers what role, if any, academic libraries and the library and information science profession should have in supporting researchers’ data management needs. University of North Texas (UNT) Library Director Martin Halbert opens the report with an overview of the DataRes Project, a two-year investigation of data management practices conducted at UNT with colleagues Spencer D. C. Keralis, Shannon Stark, and William E. Moen. His introduction is followed by a series of papers that were presented at the DataRes Symposium that UNT organized in December 2012
Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study.
Background and purposePublished cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era.MethodsThe Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review.ResultsOf the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection.ConclusionsChildren with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed
Highly Volcanic Exoplanets, Lava Worlds, and Magma Ocean Worlds:An Emerging Class of Dynamic Exoplanets of Significant Scientific Priority
Highly volcanic exoplanets, which can be variously characterized as 'lava
worlds', 'magma ocean worlds', or 'super-Ios' are high priority targets for
investigation. The term 'lava world' may refer to any planet with extensive
surface lava lakes, while the term 'magma ocean world' refers to planets with
global or hemispherical magma oceans at their surface. 'Highly volcanic
planets', including super-Ios, may simply have large, or large numbers of,
active explosive or extrusive volcanoes of any form. They are plausibly highly
diverse, with magmatic processes across a wide range of compositions,
temperatures, activity rates, volcanic eruption styles, and background
gravitational force magnitudes. Worlds in all these classes are likely to be
the most characterizable rocky exoplanets in the near future due to
observational advantages that stem from their preferential occurrence in short
orbital periods and their bright day-side flux in the infrared. Transit
techniques should enable a level of characterization of these worlds analogous
to hot Jupiters. Understanding processes on highly volcanic worlds is critical
to interpret imminent observations. The physical states of these worlds are
likely to inform not just geodynamic processes, but also planet formation, and
phenomena crucial to habitability. Volcanic and magmatic activity uniquely
allows chemical investigation of otherwise spectroscopically inaccessible
interior compositions. These worlds will be vital to assess the degree to which
planetary interior element abundances compare to their stellar hosts, and may
also offer pathways to study both the very young Earth, and the very early form
of many silicate planets where magma oceans and surface lava lakes are expected
to be more prevalent. We suggest that highly volcanic worlds may become second
only to habitable worlds in terms of both scientific and public long-term
interest.Comment: A white paper submitted in response to the National Academy of
Sciences 2018 Exoplanet Science Strategy solicitation, from the NASA Sellers
Exoplanet Environments Collaboration (SEEC) of the Goddard Space Flight
Center. 6 pages, 0 figure
Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies
The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes
Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants
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