Is Going Beyond Rasch Analysis Necessary to Assess the Construct Validity of a Motor Function Scale?

Objective

To examine whether a Rasch analysis is sufficient to establish the construct validity of the Motor Function Measure (MFM) and discuss whether weighting the MFM item scores would improve the MFM construct validity.

The FBN2 gene: new mutations, locus-specific database (Universal Mutation Database FBN2), and genotype-phenotype correlations

Congenital contractural arachnodactyly (CCA) is an extremely rare disease, due to mutations in the FBN2 gene encoding fibrillin-2. Another member of the fibrillin family, the FBN1 gene, is involved in a broad phenotypic continuum of connective-tissue disorders including Marfan syndrome. Identifying not only what is in common but also what differentiates these two proteins should enable us to better comprehend their respective functions and better understand the multitude of diseases in which these two genes are involved. In 1995 we created a locus-specific database (LSDB) for FBN1 mutations with the Universal Mutation Database (UMD) tool. To facilitate comparison of identified mutations in these two genes and search for specific functional areas, we created an LSDB for the FBN2 gene: the UMD-FBN2 database. This database lists 26 published and six newly identified mutations that mainly comprise missense and splice-site mutations. Although the number of described FBN2 mutations was low, the frequency of joint dislocation was significantly higher with missense mutations when compared to splice site mutations.     

English Cross-Cultural Translation and Validation of the Neuromuscular Score: A System for Motor Function Classification in Patients With Neuromuscular Diseases

Objective

To develop and validate an English version of the Neuromuscular (NM)-Score, a classification for patients with NM diseases in each of the 3 motor function domains: D1, standing and transfers; D2, axial and proximal motor function; and D3, distal motor function.

Design

Validation survey.

Setting

Patients seen at a medical research center between June and September 2013.

Participants

Consecutive patients (N=42) aged 5 to 19 years with a confirmed or suspected diagnosis of congenital muscular dystrophy.

Interventions

Not applicable.

Main Outcome Measures

An English version of the NM-Score was developed by a 9-person expert panel that assessed its content validity and semantic equivalence. Its concurrent validity was tested against criterion standards (Brooke Scale, Motor Function Measure [MFM], activity limitations for patients with upper and/or lower limb impairments [ACTIVLIM], Jebsen Test, and myometry measurements). Informant agreement between patient/caregiver (P/C)-reported and medical doctor (MD)-reported NM scores was measured by weighted kappa.

Results

Significant correlation coefficients were found between NM scores and criterion standards. The highest correlations were found between NM-score D1 and MFM score D1 (ρ=−.944, P<.0001), ACTIVLIM (ρ=−.895, P<.0001), and hip abduction strength by myometry (ρ=−.811, P<.0001). Informant agreement between P/C-reported and MD-reported NM scores was high for D1 (κ=.801; 95% confidence interval [CI], .701–.914) but moderate for D2 (κ=.592; 95% CI, .412–.773) and D3 (κ=.485; 95% CI, .290–.680). Correlation coefficients between the NM scores and the criterion standards did not significantly differ between P/C-reported and MD-reported NM scores.

Conclusions

Patients and physicians completed the English NM-Score easily and accurately. The English version is a reliable and valid instrument that can be used in clinical practice and research to describe the functional abilities of patients with NM diseases.     

A Lattice Boltzmann Model to Study Sedimentation Phenomena in Irrigation Canals

Fresh water is one of the most significant resources for human activities and survival, and irrigation is among the most important uses of water. The sustainibility and performance of irrigation canals can be greatly affected by sediment transport and deposition. In our previous works, we proposed a Lattice Boltzmann model for simulating a free surface flow in an irrigation canal, as an alternative to more traditional models mainly based on shallow water equations. Here we introduce the sedimentation phenomenon into our model by adding a new algorithm, based on the earlier work by B. Chopard, A. Dupuis and A. Masselot [9, 11, 12, 27]. Transport, erosion, deposition and toppling of sediments are taken into account and enable the global sedimentation algorithm to simulate different transport modes such as bed load and suspended load. In the present work, we study both the behaviour of a sediment deposit located at an underflow submerged gate (depending on the gate opening and the flow discharge) and the influence of the presence of such a deposit on the flow. Both numerical and experimental validations have been performed. The experiments were realized on the micro-canal of the LCIS laboratory at Valence, France. The comparisons between simulations and experiments give good qualitative agreement.     

Spécificités des néphropathies du sujet âgé

In our aging population, kidney disease management needs to take into account the frailty of the elderly. Standardized geriatric assessments can be proposed to help clinicians apprehend this dimension in their daily practice. These tools allow to better identify frail patients and offer them more personalized and harmless treatments. This article aims to focus on the kidney diseases commonly observed in elderly patients and analyze their specific nephrogeriatric care modalities. It should be noticed that all known kidney diseases can be also observed in the elderly, most often with a quite similar clinical presentation. This review is thus focused on the diseases most frequently and most specifically observed in elderly patients (except for monoclonal gammopathy associated nephropathies, out of the scope of this work), as well as the peculiarities of old age nephrological care.     

A new locus-specific database (LSDB) for mutations in the TGFBR2 gene: UMD-TGFBR2

The implication of mutations in the TGFBR2 gene, known to be involved in cancers, in Marfan syndrome (MFS) and later in Loeys-Dietz syndrome (LDS) and Familial Thoracic Aortic Aneurysms and Dissections (TAAD2) gives a new example of the complexity of one gene involved in multiple diseases. To date, known TGFBR2 mutations are not disease-specific and many mutations have to be accumulated before genotype-phenotype relationships emerge. To facilitate mutational analysis of the TGFBR2 gene, a locus-specific database has been set up with the Universal Mutation Database (UMD) software. The version of the computerized database contains 85 entries. A total of 12 mutations are reported to be involved in MFS, six in incomplete MFS, 30 in LDS type I, 10 in LDS type II, seven in TAAD2, and 20 in various cancers. The database is accessible online at http://www.umd.be (last accessed: 3 July 2007).     

Meta-analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection.

PURPOSE: Analyses of the pattern of p53 mutations have been essential for epidemiologic studies linking carcinogen exposure and cancer. We were concerned by the inclusion of dubious reports in the p53 databases that could lead to controversial analysis prejudicial to the scientific community. EXPERIMENTAL DESIGN: We used the universal mutation database p53 database (21,717 mutations) combined with a new p53 mutant activity database (2,300 mutants) to perform functional analysis of 1,992 publications reporting p53 alterations. This analysis was done using a statistical approach similar to that of clinical meta-analyses. RESULTS: This analysis reveals that some reports of infrequent mutations are associated with almost normal activities of p53 proteins. These particular mutations are frequently found in studies reporting multiple mutations in one tumor, silent mutations, or lacking mutation hotspots. These reports are often associated with particular methodologies, such as nested PCR, for which key controls are not satisfactory. CONCLUSIONS: We show the importance of accurate functional analysis before inferring any genetic variation. The quality of the p53 databases is essential in order to prevent erroneous analysis and/or conclusions. The availability of functional data from our new p53 web site (http://p53.free.fr and http://www.umd.be:2072/) will allow functional prescreening to identify potential artifactual data.