Diffusion Tensor Imaging for Diagnosing Root Avulsions in Traumatic Adult Brachial Plexus Injuries: A Proof-of-Concept Study

Cross-sectional MRI has modest diagnostic accuracy for diagnosing traumatic brachial plexus root avulsions. Consequently, patients either undergo major exploratory surgery or months of surveillance to determine if and what nerve reconstruction is needed. This study aimed to develop a diffusion tensor imaging (DTI) protocol at 3 Tesla to visualize normal roots and identify traumatic root avulsions of the brachial plexus. Seven healthy adults and 12 adults with known (operatively explored) unilateral traumatic brachial plexus root avulsions were scanned. DTI was acquired using a single-shot echo-planar imaging sequence at 3 Tesla. The brachial plexus was visualized by deterministic tractography. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for injured and avulsed roots in the lateral recesses of the vertebral foramen. Compared to healthy nerves roots, the FA of avulsed nerve roots was lower (mean difference 0.1 [95% CI 0.07, 0.13]; p < 0.001) and the MD was greater (mean difference 0.32 × 10−3 mm2/s [95% CI 0.11, 0.53]; p < 0.001). Deterministic tractography reconstructed both normal roots and root avulsions of the brachial plexus; the negative-predictive value for at least one root avulsion was 100% (95% CI 78, 100). Therefore, DTI might help visualize both normal and injured roots of the brachial plexus aided by tractography. The precision of this technique and how it relates to neural microstructure will be further investigated in a prospective diagnostic accuracy study of patients with acute brachial plexus injuries

Enhanced error estimator based on a nearly equilibrated moving least squares recovery technique for FEM and XFEM

In this paper a new technique aimed to obtain accurate estimates of the error in energy norm using a moving least squares (MLS) recovery-based procedure is presented. We explore the capabilities of a recovery technique based on an enhanced MLS fitting, which directly provides continuous interpolated fields, to obtain estimates of the error in energy norm as an alternative to the superconvergent patch recovery (SPR). Boundary equilibrium is enforced using a nearest point approach that modifies the MLS functional. Lagrange multipliers are used to impose a nearly exact satisfaction of the internal equilibrium equation. The numerical results show the high accuracy of the proposed error estimator

Potential application of mesh-free SPH method in turbulent river flows

A comprehensive review has been completed on the simulation of turbulent flow over rough beds using mesh-free particle models. Based on the outcomes of this review, an improved Smoothed Particle Hydrodynamics (SPH) method has been developed for open channel flows over a rough bed, in which a mixing length model is used for modeling the 2D turbulence and a drag force equation is proposed for treating the boundary shear. The proposed model was applied to simulate a depth-limited open channel flow over a rough bed surface. The results of the velocity profile and shear stress distribution show a good agreement with the experimental data and existing analytical solutions. This work reveals that in order to correctly model turbulent open channel flow over a rough bed, the treatment of both flow turbulence and bed roughness effect is equally important

Efficient recovery-based error estimation for the smoothed finite element method for smooth and singular linear elasticity

[EN] An error control technique aimed to assess the quality of smoothed finite element approximations is presented in this paper. Finite element techniques based on strain smoothing appeared in 2007 were shown to provide significant advantages compared to conventional finite element approximations. In particular, a widely cited strength of such methods is improved accuracy for the same computational cost. Yet, few attempts have been made to directly assess the quality of the results obtained during the simulation by evaluating an estimate of the discretization error. Here we propose a recovery type error estimator based on an enhanced recovery technique. The salient features of the recovery are: enforcement of local equilibrium and, for singular problems a ¿smooth + singular¿ decomposition of the recovered stress. We evaluate the proposed estimator on a number of test cases from linear elastic structural mechanics and obtain efficient error estimations whose effectivities, both at local and global levels, are improved compared to recovery procedures not implementing these features.Stephane Bordas would like to thank the partial financial support of the Royal Academy of Engineering and of the Leverhulme Trust for his Senior Research Fellowship Towards the next generation surgical simulators as well as the financial support for Octavio A. Gonzalez-Estrada and Stephane Bordas from the UK Engineering Physical Science Research Council (EPSRC) under grant EP/G042705/1 Increased Reliability for Industrially Relevant Automatic Crack Growth Simulation with the eXtended Finite Element Method. Stephane Bordas also thanks partial financial support of the European Research Council Starting Independent Research Grant (ERC Stg grant agreement No. 279578) and the FP7 Initial Training Network Funding under grant number 289361 "Integrating Numerical Simulation and Geometric Design Technology, INSIST". This work has been carried out within the framework of the research project DPI2010-20542 of the Ministerio de Ciencia e Innovacion (Spain). The financial support from Universitat Politecnica de Valencia, PROMETEO/2012/023 and Generalitat Valenciana are also acknowledged.González Estrada, OA.; Natarajan, S.; J.J. Ródenas; Nguyen-Xuan, H.; Bordas, S. (2013). Efficient recovery-based error estimation for the smoothed finite element method for smooth and singular linear elasticity. Computational Mechanics. 52(1):37-52. https://doi.org/10.1007/s00466-012-0795-6S3752521Liu GR, Dai KY, Nguyen TT (2006) A smoothed finite element method for mechanics problems. 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Commun Numer Methods Eng 25: 19–34Nguyen-Xuan H, Rabczuk T, Bordas S, Debongnie JF (2008) A smoothed finite element method for plate analysis. Comput Methods Appl Mech Eng 197: 1184–1203Nguyen NT, Rabczuk T, Nguyen-Xuan H, Bordas S (2008) A smoothed finite element method for shell analysis. Comput Methods Appl Mech Eng 198: 165–177Bordas SPA, Rabczuk T, Hung NX, Nguyen VP, Natarajan S, Bog T, óuan DM, Hiep NV (2010) Strain smoothing in FEM and XFEM. Comput Struct 88(23–24): 1419–1443. doi: 10.1016/j.compstruc.2008.07.006Bordas SP, Natarajan S, Kerfriden P, Augarde CE, Mahapatra DR, Rabczuk T, Pont SD (2011) On the performance of strain smoothing for óuadratic and enriched finite element approximations (XFEM/GFEM/PUFEM). Int J Numer Methods Biomed Eng 86: 637–666Liu G, Nguyen-Thoi T, Nguyen-Xuan H, Dai K, Lam K (2009) On the essence and the evaluation of the shape functions for the smoothed finite element method (SFEM). 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Eng Comput 29(8)Zienkiewicz OC, Zhu JZ (1987) A simple error estimator and adaptive procedure for practical engineering analysis. Int J Numer Methods Eng 24(2): 337–357Ródenas JJ, González-Estrada OA, Díez P, Fuenmayor FJ (2010) Accurate recovery-based upper error bounds for the extended finite element framework. Comput Methods Appl Mech Eng 199(37–40): 2607–2621Williams ML (1952) Stress singularities resulting from various boundary conditions in angular corners of plate in extension. J Appl Mech 19: 526–534Szabó BA, Babuška I (1991) Finite element analysis. Wiley, New YorkBarber JR. (2010) Elasticity. Series: solid mechanics and its application, 3rd edn. Springer, DordrechtChen JS, Wu CT, Yoon S, You Y (2001) A stabilized conforming nodal integration for Galerki mesh-free methods. Int J Numer Methods Eng 50: 435–466Yoo J, Moran B, Chen J (2004) Stabilized conforming nodal integration in the natural element method. Int J Numer Methods Eng 60: 861–890Zienkiewicz OC, Zhu JZ (1992) The superconvergent patch recovery and a posteriori error estimates. Part 1: The recovery technique. Int J Numer Methods Eng 33(7): 1331–1364Zienkiewicz OC, Zhu JZ (1992) The superconvergent patch recovery and a posteriori error estimates. Part 2: Error estimates and adaptivity. Int J Numer Methods Eng 33(7): 1365–1382Wiberg NE, Abdulwahab F (1993) Patch recovery based on superconvergent derivatives and eóuilibrium. Int J Numer Methods Eng 36(16): 2703–2724. doi: 10.1002/nme.1620361603Blacker T, Belytschko T (1994) Superconvergent patch recovery with eóuilibrium and conjoint interpolant enhancements. Int J Numer Methods Eng 37(3): 517–536Stein E, Ramm E, Rannacher R (2003) Error-controlled adaptive finite elements in solid mechanics. Wiley, ChichesterDuflot M, Bordas SPA (2008) A posteriori error estimation for extended finite elements by an extended global recovery. 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A Rapid Flp-In System for Expression of Secreted H5N1 Influenza Hemagglutinin Vaccine Immunogen in Mammalian Cells

Continuing transmissions of highly pathogenic H5N1 viruses in poultry and humans underscores the need for a rapid response to potential pandemic in the form of vaccine. Recombinant technologies for production of immunogenic hemagglutinin (HA) could provide an advantage over the traditional inactivated vaccine manufacturing process. Generation of stably transfected mammalian cells secreting properly folded HA proteins is important for scalable controlled manufacturing.We have developed a Flp-In based 293 stable cell lines through targeted site-specific recombination for expression of secreted hemagglutinin (HA) proteins and evaluated their immunogenicity. H5N1 globular domain HA1(1-330) and HA0(1-500) proteins were purified from the supernatants of 293 Flp-In stable cell lines. Both proteins were properly folded as confirmed by binding to H5N1-neutralizing conformation-dependent human monoclonal antibodies. The HA0 (with unmodified cleavage site) was monomeric, while the HA1 contained oligomeric forms. Upon rabbit immunization, both HA proteins elicited neutralizing antibodies against the homologous virus (A/Vietnam/1203/2004, clade 1) as well as cross-neutralizing antibodies against heterologous H5N1 clade 2 strains, including A/Indonesia/5/2005. These results exceeded the human antibody responses against the inactivated sub-virion H5N1 vaccine.Our data suggest that the 293 Flp-In system could serve as a platform for rapid expression of HA immunogens in mammalian cells from emerging influenza strains

Three-dimensional mechanical evaluation of joint contact pressure in 12 periacetabular osteotomy patients with 10-year follow-up

Background and purpose Because of the varying structure of dysplastic hips, the optimal realignment of the joint during periacetabular osteotomy (PAO) may differ between patients. Three-dimensional (3D) mechanical and radiological analysis possibly accounts better for patient-specific morphology, and may improve and automate optimal joint realignment

Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin

Single nucleotide polymorphisms (SNPs) in the multiple drug resistance protein 1 (MRP1) and P-glycoprotein 1 (MDR1) genes modulate their ability to mediate drug resistance. We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and/or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin (PLD). The MRP1/R723Q polymorphism was found in five subjects among the 279 patient study population, all of whom received PLD + bortezomib. Its presence was associated with a longer time to progression (TTP; median 330 vs. 129 days; p = 0.0008), progression-free survival (PFS; median 338 vs. 129 days; p = 0.0006), and overall survival (p = 0.0045). MDR1/3435(C > T), which was in Hardy–Weinberg equilibrium, showed a trend of association with PFS (p = 0.0578), response rate (p = 0.0782) and TTP (p = 0.0923) in PLD + bortezomib patients, though no correlation was found in the bortezomib arm. In a recessive genetic model, MDR1/3435 T was significantly associated with a better TTP (p = 0.0405) and PFS (p = 0.0186) in PLD + bortezomib patients. These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and/or refractory myeloma patients treated with PLD + bortezomib. Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients

Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections.

Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families. We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was performed. We found five individuals with loss-of-function mutations in BGN encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early-onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. Fluorescent staining revealed an increase in TGF-β signaling, evidenced by an increase in nuclear pSMAD2 in the aortic wall. Our results are in line with those of prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture. In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD that is associated with preservation of elastic fibers and increased TGF-β signaling.Genet Med 19 4, 386-395