Recent advances in targeted proteomics for clinical applications

MS-based approaches using targeted methods have been widely adopted by the proteomics community to study clinical questions such as the evaluation of biomarkers. At present, the most widely used targeted MS method is the SRM technique typically performed on a triple quadrupole instrument. However, the high analytical demands for performing clinical studies in combination with the extreme complexity of the samples involved are a serious challenge. The segmentation of the biomarker evaluation workflow has only partially alleviated these issues by differently balancing the analytical requirements and throughput at different stages of the process. The recent introduction of targeted high-resolution and accurate-mass analyses on fast sequencing mass spectrometers operated in parallel reaction monitoring (PRM) mode offers new avenues to conduct clinical studies and thus overcome some of the limitations of the triple quadrupole instrument. This article discusses the attributes and specificities of the PRM technique, in terms of experimental design, execution, and data analysis, and the implications for biomarker evaluation. The benefits of PRM on data quality and the impact on the consistency of results are highlighted and the definitive progress on the overall output of clinical studies, including high throughput, is discussed.     

Child head injury criteria investigation through numerical simulation of real world trauma

Finite element modelling has been used for decades in the study of adult head injury biomechanics and determination of injury criteria. Interest is recently growing in investigation on pediatric head injury which requires elaboration of biofidelic models that take into account child's head particularities in terms of size, geometry, and mechanical properties. In this study, a finite element model of a 3-year-old child head is proposed. The model is reconstructed from real CT scan images and mechanical properties are extracted from available data in the literature. A large number of real accidents (25 falls) are reconstructed with proposed model using different brain constitutive relationships in order to investigate their influence on model response. Mechanical output parameters (HIC, pressure, shearing stress) are calculated from these simulations. Statistical analysis was performed in order to evaluate predictive capability of the parameters. Von Mises stress appears to be clearly the most predictive parameters, allowing clear distinction between injured and non-injured cases. To the authors' knowledge, this study proposes for the first time a statistically based neurological injury criterion for a pediatric population using finite element modelling.     

Partitioned and Implicit–Explicit General Linear Methods for Ordinary Differential Equations

Implicit–explicit (IMEX) time stepping methods can efficiently solve differential equations with both stiff and nonstiff components. IMEX Runge–Kutta methods and IMEX linear multistep methods have been studied in the literature. In this paper we study new implicit–explicit methods of general linear type. We develop an order conditions theory for high stage order partitioned general linear methods (GLMs) that share the same abscissae, and show that no additional coupling order conditions are needed. Consequently, GLMs offer an excellent framework for the construction of multi-method integration algorithms. Next, we propose a family of IMEX schemes based on diagonally-implicit multi-stage integration methods and construct practical schemes of order up to three. Numerical results confirm the theoretical findings.     

OCEAN,a flexible adaptive Network-On-Chip for dynamic applications

The dynamic and partial reconfiguration of FPGAs enables the dynamic placement of applicatives tasks in reconfigurable zones. However, the dynamic management of the tasks impacts the communications since they are not present in the FPGA during all computation time. So, the task manager should ensure the allocation of each new task and their interconnection which is performed by a flexible interconnection network. In this article, various interconnection networks are studied. Each architecture is evaluated with respect to its suitability for the paradigm of the dynamic and partial reconfiguration in FPGA implementations. This study leads us to propose the OCEAN network that supports the communication constraints into the context of dynamic reconfigurations. Thanks to a generic platform allowing in situ characterizations of network performances, fair comparisons of various Networks-On-Chip can be realized. The FPGA and ASICs implementations of the OCEAN network are also discussed.     

A K-nearest neighbours method based on imprecise probabilities

K-nearest neighbours algorithms are among the most popular existing classification methods, due to their simplicity and good performances. Over the years, several extensions of the initial method have been proposed. In this paper, we propose a K-nearest neighbours approach that uses the theory of imprecise probabilities, and more specifically lower previsions. We show that the proposed approach has several assets: it can handle uncertain data in a very generic way, and decision rules developed within this theory allow us to deal with conflicting information between neighbours or with the absence of close neighbour to the instance to classify. We show that results of the basic k-NN and weighted k-NN methods can be retrieved by the proposed approach. We end with some experiments on the classical data sets.