We consider the wind-forced nonlinear Schrödinger (NLS) equation obtained in the potential flow framework when the Miles growth rate is of the order of the wave steepness. In this case, the form of ...the wind-forcing terms gives rise to the enhancement of the modulational instability and to a band of positive gain with infinite width. This regime is characterised by the fact that the ratio between wave momentum and norm is not a constant of motion, in contrast to what happens in the standard case where the Miles growth rate is of the order of the steepness squared.
•We start from the nonlinear Schrödinger equation (NLSE) for fast-growing waves.•The wind-forcing terms give rise to the enhancement of the modulational instability.•In this regime the ratio between wave momentum and norm is not conserved in time.
To assess the association of the degree of severity of motor impairment to that of cognitive impairment in a large cohort of patients with amyotrophic lateral sclerosis (ALS).
This is a ...population-based cross-sectional study on patients with ALS incident in Piemonte, Italy, between 2007 and 2015. Cognitive status was classified according to the revised ALS-FTD Consensus Criteria. The King system and the Milano Torino Staging system (MiToS) were used for defining the severity of motor impairment.
Of the 797 patients included in the study, 163 (20.5%) had ALS-frontotemporal dementia (FTD), 38 (4.8%) cognitive and behavioral impairment (ALScbi), 132 (16.6%) cognitive impairment (ALSci), 63 (7.9%) behavioral impairment (ALSbi), 16 (2.0%) nonexecutive impairment, and 385 (48.2%) were cognitively normal. According to King staging, the frequency of cases with ALS-FTD progressively increased from 16.5% in stage 1-44.4% in stage 4; conversely, the frequency of ALSci, ALSbi, and ALScbi increased from King stage 1 to King stage 3 and decreased thereafter. A similar pattern was observed with the MiToS staging. ALS-FTD was more frequent in patients with bulbar involvement at time of cognitive testing. Patients with
expansion (n = 61) showed more severe cognitive impairment with increasing King and MiToS stages.
Our findings suggest that ALS motor and cognitive components may worsen in parallel, and that cognitive impairment becomes more pronounced when bulbar function is involved. Our data support the hypothesis that ALS pathology disseminates in a regional ordered sequence, through a cortico-efferent spreading model.
In the wind-driven wave regime, the Miles mechanism gives an estimate of the growth rate of the waves under the effect of wind. We consider the case where this growth rate, normalised with respect to ...the frequency of the carrier wave, is of the order of the wave steepness. Using the method of multiple scales, we calculate the terms which appear in the nonlinear Schrödinger (NLS) equation in this regime of fast-growing waves. We define a coordinate transformation which maps the forced NLS equation into the standard NLS with constant coefficients, that has a number of known analytical soliton solutions. Among these solutions, the Peregrine and the Akhmediev solitons show an enhancement of both their lifetime and maximum amplitude which is in qualitative agreement with the results of tank experiments and numerical simulations of dispersive focusing under the action of wind.
•We derive the nonlinear Schrödinger equation (NLSE) for fast growing waves.•The wind-forced NLSE is mapped into the standard NLSE with constant coefficients.•Lifetime and maximum amplitude of Peregrine and Akhmediev solutions are enhanced under wind action.•This enhancement is observed in tank experiments of dispersive focusing waves.
To assess the burden of rare genetic variants and to estimate the contribution of known amyotrophic lateral sclerosis (ALS) genes in an Italian population-based cohort, we performed whole genome ...sequencing in 959 patients with ALS and 677 matched healthy controls.
We performed genome sequencing in a population-based cohort (Piemonte and Valle d'Aosta Registry for ALS PARALS). A panel of 40 ALS genes was analyzed to identify potential disease-causing genetic variants and to evaluate the gene-wide burden of rare variants among our population.
A total of 959 patients with ALS were compared with 677 healthy controls from the same geographical area. Gene-wide association tests demonstrated a strong association with
, whose rare variants are the second most common cause of disease after
expansion. A lower signal was observed for
, proving that its effect on our cohort is driven by a few known causal variants. We detected rare variants in other known ALS genes that did not surpass statistical significance in gene-wise tests, thus highlighting that their contribution to disease risk in our cohort is limited.
We identified potential disease-causing variants in 11.9% of our patients. We identified the genes most frequently involved in our cohort and confirmed the contribution of rare variants in disease risk. Our results provide further insight into the pathologic mechanism of the disease and demonstrate the importance of genome-wide sequencing as a diagnostic tool.
Background
Amyotrophic lateral sclerosis (ALS) is characterized by a spectrum of phenotypes, but only a few studies have addressed the presence of parkinsonian (PK) symptoms. The aim of our study was ...to investigate the occurrence of PK features in a prospective population-based cohort of ALS patients, determining their demographic, clinical, neuropsychological and genetic characteristics, and identifying their morphological and functional imaging correlates.
Methods
A consecutive series of ALS patients were enrolled and prospectively followed for 2 years. Patients were classified according to the presence (ALS-PK) or absence (ALS) of PK signs, and they underwent neuropsychological testing, genetic analysis for the main ALS and PD genes, brain MRI and
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F-FDG-PET. ALS-PK patients underwent
123
I-ioflupane SPECT.
Results
Out of 114 eligible patients, 101 (64 men; mean age at onset 65.1 years) were recruited. Thirty-one patients (30.7%) were classified as ALS-PK. Compared to ALS patients, ALS-PK patients were more frequently male, but did not differ for any other clinical, demographic or neuropsychological factors.
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I-ioflupane SPECT was normal in all but two ALS-PK patients. At
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F-FDG-PET, ALS-PK patients showed a relative hypometabolism in left cerebellum and a relatively more preserved metabolism in right insula and frontal regions; MRI fractional anisotropy was reduced in the sagittal stratum and increased in the retrolenticular part of the internal capsule.
Conclusions
In our study, about 30% of ALS patients showed PK signs. Neuroimaging data indicate that PK signs are due to the involvement of brain circuitries other than classical nigrostriatal ones, strengthening the hypothesis of ALS as a complex multisystem disease.
Abstract We recently reported that mutations in the valosin-containing protein (VCP) gene are a cause of 1%–2% of familial amyotrophic lateral sclerosis (ALS) cases, but their role in the ...pathogenesis of sporadic ALS is unclear. We undertook mutational screening of VCP in 701 sporadic ALS cases. Three pathogenic variants (p.Arg159Cys, p.Asn387Thr, and p.R662C) were found in three U.S. cases, each of whom presented with progressive upper and lower motor neuron signs consistent with definite ALS by El Escorial diagnostic criteria. Our data indicate that VCP mutations may underlie apparently sporadic ALS but account for <1% of this form of disease.
Abstract The common variant rs12608932, located within an intron of UNC13A gene on chromosome 19p13.3, has been suggested to influence susceptibility to amyotrophic lateral sclerosis (ALS), as well ...as survival, in patients of north European descent. To examine this possibility further, we evaluated the association of rs12608932 with susceptibility and survival in a population-based cohort of 500 Italian ALS patients and 1457 Italian control samples. Although rs12608932 was not associated with ALS susceptibility in our series ( p = 0.124), it was significantly associated with survival under the recessive model (median survival for AA/AC genotypes = 3.5 years interquartile range, 2.2–6.4; CC = 2.5 years interquartile range, 1.6–4.2; p = 0.017). Furthermore, rs12608932 genotype remained an independent prognostic factor in Cox multivariable analysis adjusting for other factors known to influence survival ( p = 0.023). Overall, minor allele carrier status of rs12608932 was strongly associated with an approximate 1-year reduction of survival in ALS patients, making it a significant determinant of phenotype variation. The identification of UNC13A as a modifier of prognosis among sporadic ALS patients potentially provides a new therapeutic target aimed at slowing disease progression.
We study a three-wave truncation of the high-order nonlinear Schrödinger equation for deep-water waves (also named Dysthe equation). We validate the model by comparing it to numerical simulation; we ...distinguish the impact of the different fourth-order terms and classify the solutions according to their topology. This allows us to properly define the temporary spectral upshift occurring in the nonlinear stage of Benjamin-Feir instability and provides a tool for studying further generalizations of this model.
We present coupled ocean–sea-ice simulations of the Middle Jurassic (∼165 Ma) when Laurasia and Gondwana began drifting apart and gave rise to the formation of the Atlantic Ocean. Since the opening ...of the Proto-Caribbean is not well constrained by geological records, configurations with and without an open connection between the Proto-Caribbean and Panthalassa are examined. We use a sea-floor bathymetry obtained by a recently developed three-dimensional (3D) elevation model which compiles geological, palaeogeographical and geophysical data. Our original approach consists in coupling this elevation model, which is based on detailed reconstructions of oceanic realms, with a dynamical ocean circulation model. We find that the Middle Jurassic bathymetry of the Central Atlantic and Proto-Caribbean seaway only allows for a weak current of the order of 2 Sv in the upper 1000 m even if the system is open to the west. The effect of closing the western boundary of the Proto-Caribbean is to increase the transport related to barotropic gyres in the southern hemisphere and to change water properties, such as salinity, in the Neo-Tethys. Weak upwelling rates are found in the nascent Atlantic Ocean in the presence of this superficial current and we discuss their compatibility with deep-sea sedimentological records in this region.
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