Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly: the Rotterdam study

BACKGROUND: Few studies have quantified the relation between carotid plaques and stroke in asymptomatic patients, and limited data exist on the importance of location of plaques or the association with subtypes of cerebral infarction. We investigated the relationship between carotid plaques, measured at different locations, and risk of stroke and subtypes of cerebral infarction in a population-based study. Methods and Results- The study was based on the Rotterdam Study and included 4217 neurologically asymptomatic subjects aged 55 years or older. Presence of carotid plaques at 6 locations in the carotid arteries was assessed at baseline. Severity was categorized according to the number of affected sites. After a mean follow-up of 5.2 years, 160 strokes had occurred. Data were analyzed using Cox proportional hazards regression. Plaques increased the risk of stroke and cerebral infarction approximately 1.5-fold, irrespective of plaque location. Severe carotid plaques increased the risk of nonlacunar infarction in anterior (RR 3.2 [95% CI, 1.1 to 9.7]) but not in posterior circulation (RR 0.6 [95% CI, 0.1 to 4.9]). A >10-fold increased risk of lacunar infarction was found in subjects with severe plaques (RR 10.8 [95% CI, 1.7 to 69.7]). No clear difference in risk estimates was seen between ipsilateral and contralateral infarction. CONCLUSIONS: Carotid plaques increase the risk of stroke and cerebral infarction, irrespective of their location. Plaques increase the risk of infarctions in the anterior but not in the posterior circulation. It is likely that carotid plaques in neurologically asymptomatic subjects are both markers of generalized atherosclerosis and sources of thromboemboli

Is carotid intima-media thickness useful in cardiovascular disease risk assessment? The Rotterdam Study

BACKGROUND AND PURPOSE: We determined the contribution of common carotid intima-media thickness (IMT) in the prediction of future coronary heart disease and cerebrovascular disease when added to established risk factors. METHODS: We used data from a nested case-control study comprising 374 subjects with either an incident stroke or a myocardial infarction and 1496 controls.

Discrete Variational Optimal Control

This paper develops numerical methods for optimal control of mechanical systems in the Lagrangian setting. It extends the theory of discrete mechanics to enable the solutions of optimal control problems through the discretization of variational principles. The key point is to solve the optimal control problem as a variational integrator of a specially constructed higher-dimensional system. The developed framework applies to systems on tangent bundles, Lie groups, underactuated and nonholonomic systems with symmetries, and can approximate either smooth or discontinuous control inputs. The resulting methods inherit the preservation properties of variational integrators and result in numerically robust and easily implementable algorithms. Several theoretical and a practical examples, e.g. the control of an underwater vehicle, will illustrate the application of the proposed approach.Comment: 30 pages, 6 figure

A genome-wide scan for microrna-related genetic variants associated with primary open-angle glaucoma

PURPOSE: To identify microRNAs (miRNAs) involved in primary open-angle glaucoma (POAG), using genetic data. MiRNAs are small noncoding RNAs that posttranscriptionally regulate gene expression. Genetic variants in miRNAs or miRNA-binding sites within gene 3’-untranslated regions (3’UTRs) are expected to affect miRNA function and con

Discrete Nonholonomic Lagrangian Systems on Lie Groupoids

This paper studies the construction of geometric integrators for nonholonomic systems. We derive the nonholonomic discrete Euler-Lagrange equations in a setting which permits to deduce geometric integrators for continuous nonholonomic systems (reduced or not). The formalism is given in terms of Lie groupoids, specifying a discrete Lagrangian and a constraint submanifold on it. Additionally, it is necessary to fix a vector subbundle of the Lie algebroid associated to the Lie groupoid. We also discuss the existence of nonholonomic evolution operators in terms of the discrete nonholonomic Legendre transformations and in terms of adequate decompositions of the prolongation of the Lie groupoid. The characterization of the reversibility of the evolution operator and the discrete nonholonomic momentum equation are also considered. Finally, we illustrate with several classical examples the wide range of application of the theory (the discrete nonholonomic constrained particle, the Suslov system, the Chaplygin sleigh, the Veselova system, the rolling ball on a rotating table and the two wheeled planar mobile robot).Comment: 45 page

CLES, Code Liegeois d'Evolution Stellaire

Cles is an evolution code recently developed to produce stellar models meeting the specific requirements of studies in asteroseismology. It offers the users a lot of choices in the input physics they want in their models and its versatility allows them to tailor the code to their needs and implement easily new features. We describe the features implemented in the current version of the code and the techniques used to solve the equations of stellar structure and evolution. A brief account is given of the use of the program and of a solar calibration realized with it.Comment: Comments: 8 pages, Astrophys. Space Sci. CoRoT-ESTA Volume, in the pres

Thorough analysis of input physics in CESAM and CLES codes

This contribution is not about the quality of the agreement between stellar models computed by CESAM and CLES codes, but more interesting, on what ESTA-Task~1 run has taught us about these codes and about the input physics they use. We also quantify the effects of different implementations of the same physics on the seismic properties of the stellar models, that in fact is the main aim of ESTA experiments.Comment: 11 pages, 12 fig. Accepted for publication in ApSS CoRoT/ESTA Volu

Integrative and perturbation-based analysis of the transcriptional dynamics of TGFβ/BMP system components in transition from embryonic stem cells to neural progenitors

Cooperative actions of extrinsic signals and cell-intrinsic transcription factors alter gene regulatory networks enabling cells to respond appropriately to environmental cues. Signaling by transforming growth factor type β (TGFβ) family ligands (eg, bone morphogenetic proteins [BMPs] and Activin/Nodal) exerts cell-type specific and context-dependent transcriptional changes, thereby steering cellular transitions throughout embryogenesis. Little is known about coordinated regulation and transcriptional interplay of the TGFβ system. To understand intrafamily transcriptional regulation as part of this system's actions during development, we selected 95 of its components and investigated their mRNA-expression dynamics, gene-gene interactions, and single-cell expression heterogeneity in mouse embryonic stem cells transiting to neural progenitors. Interrogation at 24 hour intervals identified four types of temporal gene transcription profiles that capture all stages, that is, pluripotency, epiblast formation, and neural commitment. Then, between each stage we performed esiRNA-based perturbation of each individual component and documented the effect on steady-state mRNA levels of the remaining 94 components. This exposed an intricate system of multilevel regulation whereby the majority of gene-gene interactions display a marked cell-stage specific behavior. Furthermore, single-cell RNA-profiling at individual stages demonstrated the presence of detailed co-expression modules and subpopulations showing stable co-expression modules such as that of the core pluripotency genes at all stages. Our combinatorial experimental approach demonstrates how intrinsically complex transcriptional regulation within a given pathway is during cell fate/state transitions

ASTEC -- the Aarhus STellar Evolution Code

The Aarhus code is the result of a long development, starting in 1974, and still ongoing. A novel feature is the integration of the computation of adiabatic oscillations for specified models as part of the code. It offers substantial flexibility in terms of microphysics and has been carefully tested for the computation of solar models. However, considerable development is still required in the treatment of nuclear reactions, diffusion and convective mixing.Comment: Astrophys. Space Sci, in the pres

Exome sequencing and functional analyses suggest that SIX6 is a gene involved in an altered proliferation-differentiation balance early in life and optic nerve degeneration at old age

Primary open-angle glaucoma (POAG) is a hereditary neurodegenerative disease, characterized by optic nerve changes including increased excavation, notching and optic disc hemorrhages. The excavation can be described by the vertical cup-disc ratio (VCDR). Previously, genome-wide significant evidence for the association of rs10483727 in SIX1-SIX6 locus with VCDR and subsequent POAG was found. Using 1000 genomes-based imputation of four independent population-based cohorts in the Netherlands, we identified a missense variant rs33912345 (His141Asn) in SIX6 associated with VCDR (Pmeta = 7.74 × 10-7, n = 11 473) and POAG (Pmeta = 6.09 × 10-3, n = 292). Exome sequencing analysis revealed another missense variant rs146737847 (Glu129Lys) also in SIX6 associated with VCDR (P = 5.09 × 10-3, n = 1208). These two findings point to SIX6 as the responsible gene for the previously reported association signal. Functional characterization of SIX6 in zebrafish revealed that knockdown of six6b led to a small eye phenotype. Histological analysis showed retinal lamination, implying an apparent normal development of the eye, but an underdeveloped lens, and reduced optic nerve diameter. Expression analysis of morphants at 3 dpf showed a 5.5-fold up-regulation of cdkn2b, a cyclin-dependent kinase inhibitor, involved in cell cycle regulation and previously associated with VCDR and POAG in genome-wide association studies (GWASs). Since both six6b and cdkn2b play a key role in cell proliferation, we assessed the proliferative activity in the eye of morphants and found an alteration in the proliferative pattern of retinal cells. Our findings in humans and zebrafish suggest a functional involvement of six6b in early eye development, and open new insights into the genetic architecture of POAG