A reduced order variational multiscale approach for turbulent flows

The purpose of this work is to present different reduced order model strategies starting from full order simulations stabilized using a residual-based variational multiscale (VMS) approach. The focus is on flows with moderately high Reynolds numbers. The reduced order models (ROMs) presented in this manuscript are based on a POD-Galerkin approach. Two different reduced order models are presented, which differ on the stabilization used during the Galerkin projection. In the first case, the VMS stabilization method is used at both the full order and the reduced order levels. In the second case, the VMS stabilization is used only at the full order level, while the projection of the standard Navier-Stokes equations is performed instead at the reduced order level. The former method is denoted as consistent ROM, while the latter is named non-consistent ROM, in order to underline the different choices made at the two levels. Particular attention is also devoted to the role of inf-sup stabilization by means of supremizers in ROMs based on a VMS formulation. Finally, the developed methods are tested on a numerical benchmark. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Assessing non-Mendelian inheritance in inherited axonopathies

PURPOSE: Inherited axonopathies (IA) are rare, clinically and genetically heterogeneous diseases that lead to length-dependent degeneration of the long axons in central (hereditary spastic paraplegia [HSP]) and peripheral (Charcot–Marie–Tooth type 2 [CMT2]) nervous systems. Mendelian high-penetrance alleles in over 100 different genes have been shown to cause IA; however, about 50% of IA cases do not receive a genetic diagnosis. A more comprehensive spectrum of causative genes and alleles is warranted, including causative and risk alleles, as well as oligogenic multilocus inheritance. METHODS: Through international collaboration, IA exome studies are beginning to be sufficiently powered to perform a pilot rare variant burden analysis. After extensive quality control, our cohort contained 343 CMT cases, 515 HSP cases, and 935 non-neurological controls. We assessed the cumulative mutational burden across disease genes, explored the evidence for multilocus inheritance, and performed an exome-wide rare variant burden analysis. RESULTS: We replicated the previously described mutational burden in a much larger cohort of CMT cases, and observed the same effect in HSP cases. We identified a preliminary risk allele for CMT in the EXOC4 gene (p value= 6.9 × 10-6, odds ratio [OR] = 2.1) and explored the possibility of multilocus inheritance in IA. CONCLUSION: Our results support the continuing emergence of complex inheritance mechanisms in historically Mendelian disorders

Charcot-Marie-Tooth neuropathy score and ambulation index are both predictors of orthotic need for patients with CMT

Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy with an estimated prevalence of 1 person affected on 2500. Frequent symptoms include distal weakness and muscle wasting, sensory loss, reduced deep tendon reflexes, and skeletal deformities, such as hammer toes and pes cavus. CMT is a progressive disease and patients\u2019 needs change over their lifetime. In particular, ambulation aids are increasingly needed to maintain ambulation and reduce the risk of falls. We performed a retrospective analysis of medical records from 149 patients with confirmed CMT to evaluate patients ambulation needs related to the severity of their CMT as measured by the CMT Neuropathy Score (CMTNS) and Ambulation Index (AI). Most patients required some form of orthotics (86.6%). The CMTNS and AI scores both differed significantly between patients with no orthotics compared to those who wore insoles/inserts. The CMTNS and AI also differed significantly between patients wearing insoles and those with ankle foot orthotics (AFOs). CMTNS and the AI were valid predictors of the type and choice of the orthotics. Both the CMTNS and AI can be effective tools to aid in the correct choice of orthotics in patients affected by CMT

The 6-min walk test as a new outcome measure in Amyotrophic lateral sclerosis.

One of the issues highlighted in amyotrophic lateral sclerosis (ALS) clinical trials is the lack of appropriate outcome measures. The aim of this multicentric study was to evaluate the 6-min walk test (6MWT) as tool to monitor the natural history of a cohort of ALS patients followed up over a 6-month interval. Forty-four ambulant patients were assessed at baseline and after 1, 3 and 6 months. Eight out of forty-four lost the ability to walk before the end of the study. The 6MWT and the objective measures linked to motor function, such as 10 m walking test (10MWT) and Time-up and go (TUG), the ALSFRS-R and the ALSFRS-R items 7\u20139 showed a good responsiveness to change over the 6-month interval. There was a strong correlation between 6 and 10MWT, TUG, ALSFRS-R, ALSFRS-R items 7\u20139 and FVC% at baseline. There was no correlation with Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and Modified Borg Scale (MBS). The \u394 of 6MWT from T0 to T6 significantly correlated with the \u394s of 10MWT and TUG. There was no correlation with the \u394s of ALSFRS-R, ALSFRS-R items 7 9, ECAS, MBS and FVC%. The discordance between changes of the 6MWT and ALSFRS-R at 6 month highlights the different content validity among these instruments. The concordance among 6MWT, 10MWT and TUG indicates that the 6MWT is an objective, sensitive and robust tool to measure motor performances in a longitudinal setting. The main limitations of our study were the small sample size and the high percentage of patients (18%) lost at follow-up. Therefore, further studies on larger cohorts, and exploring the relation between 6MWT and need of ventilator support or survival could strengthen our results

Validation of the Italian version of the Charcot-Marie-Tooth disease Pediatric Scale

The Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) is a Rasch-built clinical outcome measure of disease severity. It is valid, reliable, and responsive to change for children and adolescents aged 3 to 20 years. The aim of this study was to translate and validate an Italian version of the CMTPedS using a validated framework of transcultural adaptation. The CMTPedS (Italian) was translated and culturally adapted from source into Italian by two experts in CMT with good English language proficiency. The two translations were reviewed by a panel of experts in CMT. The agreed provisional version was back translated into English by a professional translator. The definitive Italian version was developed during a consensus teleconference by the same panel. CMT patients were assessed with the final version of the outcome measure and a subset had a second assessment after 2 weeks to evaluate test-retest reliability. Seventeen patients with CMT aged 5 to 20 years (eight female) were evaluated with the CMTPedS (Italian), and test-retest was performed in three patients. The CMTPedS (Italian) showed a high test-retest reliability. No patient had difficulty in completing the scale. The instructions for the different items were clearly understood by clinicians and therefore the administration of the outcome measure was straight forward and easily understood by the children assessed. The CMTPedS (Italian) will be used for clinical follow-up and in clinical research studies in the Italian population. The data is fully comparable to that obtained from the English language version

Pescara benchmark: overview of modelling, testing andidentification

The 'Pescara benchmark' is part of the national research project 'BriViDi' (BRIdge VIbrations and DIagnosis) supported by the Italian Ministero dell'Universit e Ricerca. The project is aimed at developing an integrated methodology for the structural health evaluation of railway r/c, p/c bridges. The methodology should provide for applicability in operating conditions, easy data acquisition through common industrial instrumentation, robustness and reliability against structural and environmental uncertainties. The Pescara benchmark consisted in lab tests to get a consistent and large experimental data base and subsequent data processing. Special tests were devised to simulate the train transit effects in actual field conditions. Prestressed concrete beams of current industrial production both sound and damaged at various severity corrosion levels were tested. The results were collected either in a deterministic setting and in a form suitable to deal with experimental uncertainties. Damage identification was split in two approaches: with or without a reference model. In the first case f.e. models were used in conjunction with non conventional updating techniques. In the second case, specialized output- only identification techniques capable to deal with time-variant and possibly non linear systems were developed. The lab tests allowed validating the above approaches and the performances of classical modal based damage indicators

Pescara benchmark: overview of modelling, testing andidentification

The \u201cPescara benchmark\u201d is part of the national research project \u201cBriViDi\u201d (BRIdge VIbrations and DIagnosis) supported by the Italian Ministero dell\u2019Universit\ue0 e Ricerca. The project is aimed at developing an integrated methodology for the structural health evaluation of railway r/c, p/c bridges. The methodology should provide for applicability in operating conditions, easy data acquisition through common industrial instrumentation, robustness and reliability against structural and environmental uncertainties. The Pescara benchmark consisted in lab tests to get a consistent and large experimental data base and subsequent data processing. Special tests were devised to simulate the train transit effects in actual field conditions. Prestressed concrete beams of current industrial production both sound and damaged at various severity corrosion levels were tested. The results were collected either in a deterministic setting and in a form suitable to deal with experimental uncertainties. Damage identification was split in two approaches: with or without a reference model. In the first case f.e. models were used in conjunction with non conventional updating techniques. In the second case, specialized outputonly identification techniques capable to deal with time-variant and possibly non linear systems were developed. The lab tests allowed validating the above approaches and the performances of classical modal based damage indicators