Effective Forchheimer Coefficient for Layered Porous Media

Inertial flow in porous media, governed by the Forchheimer equation, is affected by domain heterogeneity at the field scale. We propose a method to derive formulae of the effective Forchheimer coefficient with application to a perfectly stratified medium. Consider uniform flow under a constant pressure gradient Delta P/L in a layered permeability field with a given probability distribution. The local Forchheimer coefficient beta is related to the local permeability k via the relation beta = a/k(c), where a > 0 being a constant and c is an element of [0, 2]. Under ergodicity, an effective value of beta is derived for flow (i) perpendicular and (ii) parallel to layers. Expressions for effective Forchheimer coefficient, beta(e), generalize previous formulations for discrete permeability variations. Closed-form beta(e) expressions are derived for flow perpendicular to layers and under two limit cases, F << 1 and F >> 1, for flow parallel to layering, with F a Forchheimer number depending on the pressure gradient. For F of order unity, beta(e) is obtained numerically: when realistic values of Delta P/L and a are adopted, beta(e) approaches the results valid for the high Forchheimer approximation. Further, beta(e) increases with heterogeneity, with values always larger than those it would take if the beta - k relationship was applied to the mean permeability; it increases (decreases) with increasing (decreasing) exponent c for flow perpendicular (parallel) to layers. beta(e) is also moderately sensitive to the permeability distribution, and is larger for the gamma than for the lognormal distribution

Can prodromal symptoms predict recurrence of vasovagal syncope?

Background: Vasovagal syncope (VVS) is a common symptom with empirical therapy and high recurrence rate. Our goal was to determine whether the pattern of presyncopal prodromal symptoms can predict the recurrence probability of vasovagal syncope. Methods: Seventy-nine consecutive patients (male/female: 53/26) with history of VVS and positive tilt table test (TTT) were enrolled in the study and completed the follow-up time for one year. They all had normal electrocardiograms and cardiac echocardiography without underlying disease. All of them were evaluated meticulously for prodromal symptoms (diaphoresis, nausea, palpitation and blurred vision) and frequency of syncopal spells in their past medical history. They received metoprolol at maximum tolerated dose and were taught tilt training as an empirical therapy after TTT. Results: Fifty-four patients (68.4) reported at least one of the four main prodromal symptoms. Median syncopal ± presyncopal spells were 4 episodes. Forty-two patients (53.2) experienced recurrence of syncope or presyncope during the follow-up period. In recurrent symptomatic patients, diaphoresis had been more significantly reported in their past medical history (p = 0.018) and they had more syncopal spells before TTT (p = 0.001). Age, gender and type of TTT response did not have any effect on the recurrence of VVS. Conclusions: Patients with a history of diaphoresis as a prodromal symptom and more pre-tilt syncopal attacks experience more syncopal or presyncopal spells during follow-up. Copyright © 2008 Via Medica

Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration.

OBJECTIVE: To characterize clinically and molecularly an early-onset, variably progressive neurodegenerative disorder characterized by a cerebellar syndrome with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline affecting 11 individuals from 3 consanguineous families. METHODS: We used whole-exome sequencing (WES) (families 1 and 2) and a combined approach based on homozygosity mapping and WES (family 3). We performed in vitro studies to explore the effect of the nontruncating SQSTM1 mutation on protein function and the effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in vivo using zebrafish as a model. RESULTS: We identified 3 homozygous inactivating variants, including a splice site substitution (c.301+2T>A) causing aberrant transcript processing and accelerated degradation of a resulting protein lacking exon 2, as well as 2 truncating changes (c.875_876insT and c.934_936delinsTGA). We show that loss of SQSTM1 causes impaired production of ubiquitin-positive protein aggregates in response to misfolded protein stress and decelerated autophagic flux. The consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in zebrafish documented a variable but reproducible phenotype characterized by cerebellum anomalies ranging from depletion of axonal connections to complete atrophy. We provide a detailed clinical characterization of the disorder; the natural history is reported for 2 siblings who have been followed up for >20 years. CONCLUSIONS: This study offers an accurate clinical characterization of this recently recognized neurodegenerative disorder caused by biallelic inactivating mutations in SQSTM1 and links this phenotype to defective selective autophagy

Gray Matter Changes in Parkinson's and Alzheimer's Disease and Relation to Cognition

Purpose of Review We summarize structural (s)MRI findings of gray matter (GM) atrophy related to cognitive impairment in Alzheimer's disease (AD) and Parkinson's disease (PD) in light of new analytical approaches and recent longitudinal studies results. Recent Findings The hippocampus-to-cortex ratio seems to be the best sMRI biomarker to discriminate between various AD subtypes, following the spatial distribution of tau pathology, and predict rate of cognitive decline. PD is clinically far more variable than AD, with heterogeneous underlying brain pathology. Novel multivariate approaches have been used to describe patterns of early subcortical and cortical changes that relate to more malignant courses of PD. New emerging analytical approaches that combine structural MRI data with clinical and other biomarker outcomes hold promise for detecting specific GM changes in the early stages of PD and preclinical AD that may predict mild cognitive impairment and dementia conversion

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'

Retaining wall optimization using interior search algorithm with different bound constraint handling

Along with the applicability of optimization algorithms, there are lots of features that can affect the functioning of the optimization techniques. The main purpose of this paper is investigating the significance of boundary constraint handling (BCH) schemes on the performance of optimization algorithms. To this end, numbers of deterministic and probabilistic BCH approaches are applied to one of the most recent proposed optimization techniques, named interior search algorithm (ISA). Apart from the implementing different BCH methods, a sensitivity analysis is conducted to find an appropriate setting for the only parameter of ISA. Concrete cantilever retaining wall design as one of the most important geotechnical problems is tackled to declare proficiency of the ISA algorithm, on the one hand, and benchmark the effect of BCH schemes on the final results, on the contrary. As results demonstrate, various BCH approaches have a perceptible impact on the algorithm performance. In like manner, the essential parameter of ISA can also play a pivotal role in this algorithm's efficiency. Copyright © 2017 John Wiley & Sons, Ltd

Inertial amplified resonators for tunable metasurfaces

In this work, we propose an inertial amplified resonator (IAR) as a building block of a tunable locally resonant metasurface. The IAR consists in a mass–spring resonator coupled with two inerters, realized by two inclined rigid links connected to an additional mass. The IAR has a static behaviour equivalent to that of a standard mass–spring oscillator whereas its dynamic response can be controlled by means of the geometrical configuration and mass of the inerters. We derive the dynamic amplification factor and the base force of the IAR for an imposed harmonic motion and perform a parametric study to unveil its peculiar dynamics. Next, we use an effective medium approach to derive the closed-form dispersion law of a metasurface consisting of IARs coupled to a semi-infinite elastic substrate. We show that the IAR enriches the dynamics of the metasurface providing the ability (1) to shift its bandgap frequency spectrum without changing the mass and stiffness of the resonators, (2) to design single frequency or multi-frequency (metawedges) metasurfaces, (3) to obtain a high-frequency behavior typical of an added dead mass layer (i.e., non-resonant), which confers to the metasurface additional filtering properties

Drainage of power-law fluids from fractured or porous finite domains

We develop a sharp-interface model that captures the coupled effect of spatial heterogeneity and fluid rheology on one-dimensional Newtonian and non-Newtonian buoyancy-driven flow spreading in fractured and porous media over a horizontal impermeable bed. We study the flow in three different geometries: (i) a constant uniform aperture, (ii) an aperture variable along the vertical axis, i.e. perpendicular to the direction of propagation and (iii) an aperture variable along the horizontal axis, i.e. parallel to the direction of propagation. The non-Newtonian rheology is described by the power-law equation of rheological index n and the aperture variation in both directions by a positive number r. The self-similar solutions of the flow obtained at late times allow the transformation of the nonlinear PDEs governing the spreading into nonlinear ODEs. The current shape is affected by the interplay between the rheological index and the spatial variability of the aperture. The residual liquid mass that remains in the fracture at any given time is computed from the current profiles, obtaining a negative power-law behavior in the time of exponent dependent on n and r. In addition, sensitivity analysis is performed to highlight the impact of the model parameters on the current profile and residual mass. The dimensionless analysis outcomes are compared to two real examples of flow within a uniform and a wedge-shaped aperture along the flow direction. The numerical results of the examples confirm that the proposed model can successfully capture the propagation of the gravity current, its profile, and drainage flow rate