Pattern Dynamics of Vortex Ripples in Sand: Nonlinear Modeling and Experimental Validation

Vortex ripples in sand are studied experimentally in a one-dimensional setup with periodic boundary conditions. The nonlinear evolution, far from the onset of instability, is analyzed in the framework of a simple model developed for homogeneous patterns. The interaction function describing the mass transport between neighboring ripples is extracted from experimental runs using a recently proposed method for data analysis, and the predictions of the model are compared to the experiment. An analytic explanation of the wavelength selection mechanism in the model is provided, and the width of the stable band of ripples is measured.Comment: 4 page

Evaluating Therapies to Prevent Future Stroke in Patients with Patent Foramen Ovale-Related Strokes : The SCOPE Study

Note: The material presented in this section previously appeared in the following peer-reviewed publication: Kent DM, Saver JL, Kasner SE, et al. .. Heterogeneity of treatment effects in an analysis of pooled individual patient data from randomized trials of device closure of patent foramen ovale after stroke. JAMA. 2021;326(22):2277-2286. doi:10.1001/jama.2021.20956 Background: Patent foramen ovale (PFO)-associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. Despite the overall beneficial effects of closure device placement in patients with a first PFO-associated cerebral ischemic event, the best treatment option for any individual patient encountered in routine clinical practice is often quite unclear. Objective: The objective of this study was to evaluate the heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems. Methods: Individual patient data were pooled from 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, which involved a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017. Comparisons were made between PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) score (a 10-point score in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) algorithm, which combines the RoPE score with high-risk PFO features (either an atrial septal aneurysm or a large shunt) to classify patients into 3 categories of causal relatedness: “unlikely,” “possible,” and “probable.” The main outcome was ischemic stroke. Results: Over a median follow-up of 57 months (interquartile range, 24-64 months), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09% (95% CI, 0.88%-1.36%) and with device closure was 0.47% (95% CI, 0.35%-0.65%); the adjusted hazard ratio (HR) was 0.41 (95% CI, 0.27-0.60). Subgroup analyses showed statistically significant interaction effects. Patients with low vs high RoPE score had HRs of 0.61 (95% CI, 0.37-1.00) and 0.21 (95% CI, 0.11-0.42), respectively (P for interaction = .02). Patients classified under PASCAL as unlikely, possible, and probable had HRs of 1.14 (95% CI, 0.53-2.46), 0.38 (95% CI, 0.22-0.65), and 0.10 (95% CI, 0.03-0.35), respectively (P for interaction = .003). The 2-year absolute risk reduction was −0.7% (95% CI, −4.0% to 2.6%), 2.1% (95% CI, 0.6%-3.6%), and 2.1% (95% CI, 0.9%-3.4%) in the unlikely, possible, and probable PASCAL categories, respectively. Device-associated adverse events were generally higher among patients classified as unlikely; the absolute risk increases in atrial fibrillation beyond day 45 postrandomization with device were 4.41% (95% CI, 1.02%-7.80%), 1.53% (95% CI, 0.33%-2.72%), 0.65% (95% CI, −0.41% to 1.71%) in the unlikely, possible, and probable PASCAL categories, respectively. Conclusions: Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO. Application of these classification systems has the potential to guide individualized decisions regarding the selection of device closure vs medical therapy, supporting patient-centered decision-making for patients with PFO-associated cerebral ischemic events. Limitations: Some limitations of the study were the following: data were missing with respect to functional outcomes with recurrent stroke; trials had heterogenous definitions of key variables; the original PASCAL classification could not be evaluated; and several questions remain unaddressed, such as the best type of antithrombotic therapy, the role of new PFO devices, and the role of closure for patients older than 60 years

A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis.

Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1, which codes for a signal-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher VAV1 messenger RNA expression. VAV1 expression was increased in individuals with multiple sclerosis and correlated with tumor necrosis factor and interferon-gamma expression in peripheral blood and cerebrospinal fluid cells. We conclude that VAV1 plays a central role in controlling central nervous system immune-mediated disease and proinflammatory cytokine production critical for disease pathogenesis