Generation of tuneable 589nm radiation as a Na guide star source using an optical parametric amplifier

We describe a 5.5W 589nm source based on a passively modelocked Nd:YVO4 laser and a multi-stage Lithium Triborate optical parametric amplifier seeded by a tuneable semiconductor laser. We show this system can produce rapidly tuneable, transform-limited pulses in near diffraction-limited beams at 589nm, useful for Na guide star applications. The attraction of this scheme is that it can be assembled from commercially available hardware and is readily scalable to high average powers

WMH and long-term outcomes in ischemic stroke

Objective To investigate the relationship between baseline white matter hyperintensities (WMH) in patients with ischemic stroke and long-term risk of dementia, functional impairment, recurrent stroke, and mortality. Methods Following the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42018092857), we systematically searched Medline and Scopus for cohort studies of ischemic stroke patients examining whether MRI- or CT-assessed WMH at baseline are associated with dementia, functional impairment, recurrent stroke, and mortality at 3 months or later poststroke. We extracted data and evaluated study quality with the Newcastle–Ottawa scale. We pooled relative risks (RR) for the presence and severity of WMH using random-effects models. Results We included 104 studies with 71,298 ischemic stroke patients. Moderate/severe WMH at baseline were associated with increased risk of dementia (RR 2.17, 95% confidence interval [CI] 1.72–2.73), cognitive impairment (RR 2.29, 95% CI 1.48–3.54), functional impairment (RR 2.21, 95% CI 1.83–2.67), any recurrent stroke (RR 1.65, 95% CI 1.36–2.01), recurrent ischemic stroke (RR 1.90, 95% CI 1.26–2.88), all-cause mortality (RR 1.72, 95% CI 1.47–2.01), and cardiovascular mortality (RR 2.02, 95% CI 1.44–2.83). The associations followed dose-response patterns for WMH severity and were consistent for both MRI- and CT-defined WMH. The results remained stable in sensitivity analyses adjusting for age, stroke severity, and cardiovascular risk factors, in analyses of studies scoring high in quality, and in analyses adjusted for publication bias. Conclusions Presence and severity of WMH are associated with substantially increased risk of dementia, functional impairment, stroke recurrence, and mortality after ischemic stroke. WMH may aid clinical prognostication and the planning of future clinical trials

White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Background; Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM. Methods; We used post‐mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro‐caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles. Results; The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P < 0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P < 0.01), with most prominent axonal abnormalities observed in the frontal WM (P < 0.05). The SIs of arterioles in CADASIL were increased by 25–45% throughout the regions assessed, with the highest change in the mid‐frontal region (P = 0.000). Conclusions; Our results suggest disruption of either cortico‐cortical or subcortical‐cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures

The Primacy Effect in Amnestic Mild Cognitive Impairment: Associations with Hippocampal Functional Connectivity

Background: The “primacy effect,” i.e., increased memory recall for the first items of a series compared to the following items, is reduced in amnestic mild cognitive impairment (aMCI). Memory task-fMRI studies demonstrated that primacy recall is associated with higher activation of the hippocampus and temporo-parietal and frontal cortical regions in healthy subjects. Functional magnetic resonance imaging (fMRI) at resting state revealed that hippocampus functional connectivity (FC) with neocortical brain areas, including regions of the default mode network (DMN), is altered in aMCI. The present study aimed to investigate whether resting state fMRI FC between the hippocampus and cortical brain regions, especially the DMN, is associated with primacy recall performance in aMCI. Methods: A number of 87 aMCI patients underwent resting state fMRI and verbal episodic memory assessment. FC between the left or right hippocampus, respectively, and all other voxels in gray matter was mapped voxel-wise and used in whole-brain regression analyses, testing whether FC values predicted delayed primacy recall score. The delayed primacy score was defined as the number of the first four words recalled on the California Verbal Learning Test. Additionally, a partial least squares (PLS) analysis was performed, using DMN regions as seeds to identify the association of their functional interactions with delayed primacy recall. Results: Voxel-based analyses indicated that delayed primacy recall was mainly (positively) associated with higher FC between the left and right hippocampus. Additionally, significant associations were found for higher FC between the left hippocampus and bilateral temporal cortex, frontal cortical regions, and for higher FC between the right hippocampus and right temporal cortex, right frontal cortical regions, left medial frontal cortex and right amygdala (p < 0.01, uncorr.). PLS analysis revealed positive associations of delayed primacy recall with FC between regions of the DMN, including the left and right hippocampus, as well as middle cingulate cortex and thalamus (p < 0.04). In conclusion, in the light of decreased hippocampus function in aMCI, inter-hemispheric hippocampus FC and hippocampal FC with brain regions predominantly included in the DMN may contribute to residual primacy recall in aMCI

Neuronal correlates of serial position performance in amnestic mild cognitive impairment.

Objectives: Delayed recall of the first words of a list - the primacy position – is thought to be particularly dependent on intact memory consolidation. Hippocampal volume has been suggested as the primary neuronal correlate of delayed primacy recall in cognitively normal elderly individuals. Here, we studied the association of hippocampal volume with primacy recall in individuals with amnestic mild cognitive impairment (aMCI). Methods: We investigated serial position performance in 88 subjects with aMCI using a 16-word list (CVLT). Primacy and recency performance were measured during learning and delayed recall. Hippocampal volumes were automatically determined from structural MRI scans. We conducted regression analyses with bilateral hippocampal volumes as predictors and serial position indices as outcomes. Results: After controlling for age, gender, and total intracranial volume, bilateral hippocampal volume was not associated with primacy recall either during learning or delayed recall. Primacy performance during learning was associated with the right inferior and middle temporal gyrus as well as the right inferior parietal cortex and supramerginal gyrus. During delayed recall, primacy performance was related to the bilateral supramarginal gyri. Conclusions: Our findings suggest a reduced primacy effect in aMCI already during learning, contrasting previous findings in normal cognitive aging. This might indicate impaired encoding and consolidation processes at an early stage of episodic memory acquisition. Furthermore, our data indicates that hippocampal volume may not be a relevant determinant of residual primacy performance in the stage of aMCI, which may rather depend on temporal and parietal neocortical networks

The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1&#8211;6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7&#8211;34 pathogenic variant

Purpose: CADASIL is a small-vessel disease caused by a cysteine-altering pathogenic variant in one of the 34 epidermal growth factor-like repeat (EGFr) domains of the NOTCH3 protein. We recently found that pathogenic variant in EGFr domains 7\u201334 have an unexpectedly high frequency in the general population (1:300). We hypothesized that EGFr 7\u201334 pathogenic variant more frequently cause a much milder phenotype, thereby explaining an important part of CADASIL disease variability. Methods: Age at first stroke, survival and white matter hyperintensity volume were compared between 664 CADASIL patients with either a NOTCH3 EGFr 1\u20136 pathogenic variant or an EGFr 7\u201334 pathogenic variant. The frequencies of NOTCH3 EGFr 1\u20136 and EGFr 7\u201334 pathogenic variant were compared between individuals in the genome Aggregation Database and CADASIL patients. Results: CADASIL patients with an EGFr 1\u20136 pathogenic variant have a 12-year earlier onset of stroke than those with an EGFr 7\u201334 pathogenic variant, lower survival, and higher white matter hyperintensity volumes. Among diagnosed CADASIL patients, 70% have an EGFr 1\u20136 pathogenic variant, whereas EGFr 7\u201334 pathogenic variant strongly predominate in the population. Conclusion: NOTCH3 pathogenic variant position is the most important determinant of CADASIL disease severity, with EGFr 7\u201334 pathogenic variant predisposing to a later onset of stroke and longer survival

Self-similar chain conformations in polymer gels

We use molecular dynamics simulations to study the swelling of randomly end-cross-linked polymer networks in good solvent conditions. We find that the equilibrium degree of swelling saturates at Q_eq = N_e**(3/5) for mean strand lengths N_s exceeding the melt entanglement length N_e. The internal structure of the network strands in the swollen state is characterized by a new exponent nu=0.72. Our findings are in contradiction to de Gennes' c*-theorem, which predicts Q_eq proportional N_s**(4/5) and nu=0.588. We present a simple Flory argument for a self-similar structure of mutually interpenetrating network strands, which yields nu=7/10 and otherwise recovers the classical Flory-Rehner theory. In particular, Q_eq = N_e**(3/5), if N_e is used as effective strand length.Comment: 4 pages, RevTex, 3 Figure

Tube Models for Rubber-Elastic Systems

In the first part of the paper we show that the constraining potentials introduced to mimic entanglement effects in Edwards' tube model and Flory's constrained junction model are diagonal in the generalized Rouse modes of the corresponding phantom network. As a consequence, both models can formally be solved exactly for arbitrary connectivity using the recently introduced constrained mode model. In the second part, we solve a double tube model for the confinement of long paths in polymer networks which is partially due to crosslinking and partially due to entanglements. Our model describes a non-trivial crossover between the Warner-Edwards and the Heinrich-Straube tube models. We present results for the macroscopic elastic properties as well as for the microscopic deformations including structure factors.Comment: 15 pages, 8 figures, Macromolecules in pres

Mechanical Properties of End-crosslinked Entangled Polymer Networks using Sliplink Brownian Dynamics Simulations

The mechanical properties of a polymeric network containing both crosslinks and sliplinks (entanglements) are studied using a multi-chain Brownian dynamics simulation. We coarse-grain at the level of chain segments connecting consecutive nodes (cross- or sliplinks), with particular attention to the Gaussian statistics of the network. Affine displacement of nodes is not imposed: their displacement as well as sliding of monomers through sliplinks is governed by force balances. The simulation results of stress in uniaxial extension and the full stress tensor in simple shear including the (non-zero) second normal stress difference are presented for monodisperse chains with up to 18 entanglements between two crosslinks. The cases of two different force laws of the subchains (Gaussian chains and chains with finite extensibility) for two different numbers of monomers in a subchain (no = 50 and no = 100) are examined. It is shown that the additivity assumption of slip- and crosslink contribution holds for sufficiently long chains with two or more entanglements, and that it can be used to construct the strain response of a network of infinitely long chains. An important consequence is that the contribution of sliplinks to the small-strain shear modulus is about &#8532; of the contribution of a crosslink

Kinetic models with randomly perturbed binary collisions

We introduce a class of Kac-like kinetic equations on the real line, with general random collisional rules, which include as particular cases models for wealth redistribution in an agent-based market or models for granular gases with a background heat bath. Conditions on these collisional rules which guarantee both the existence and uniqueness of equilibrium profiles and their main properties are found. We show that the characterization of these stationary solutions is of independent interest, since the same profiles are shown to be solutions of different evolution problems, both in the econophysics context and in the kinetic theory of rarefied gases