K Index in cerebrospinal fluid: a valid tool in multiple sclerosis diagnosis

Detection of oligoclonal IgG bands in cerebrospinal fluid by isoelectrocfocusing and immunodetection is the current gold standard to detect an inflammatory process in the central nervous system. It has been proposed that the presence of free light chains (FLCs) in CSF was associated with recent demyelination activity in MS and might be used as a prognosis marker. Our study’s objective is assessing the diagnostic accuracy of a new highly sensitive latex-enhanced nephelometric assay for k free light chain (kFLC) determination in CSF/serum as an alternative to traditional tests and its clinical application. Methods. kFLCs were measured in CSF/serum pairs from 80 patients by the use of a new highly sensitive latex-enhanced nephelometric automated immunoassay for detection of immunoglobulin FLC. The eighty patients were split into three groups according to the neurological diagnosis. In this study we confirm even more the use of the k Index as a diagnostic aid in multiple sclerosis. Results. kFLC Index seems to be more accurate parameter respect the determination of oligoclonal immunoglobulin bands (OCBs). We recalculate the K Index sensitivity and specificity respect the precedent published result. Two patients previously diagnosed with leukoencephalopathy have gone to group 3 as confirmed the diagnosis of MS. Conclusions. These new data reinforce even more the use of the k Index to diagnose MS in comparison to classical methods and to the reference method, the OCBs

Scheduling data flow program in xkaapi: A new affinity based Algorithm for Heterogeneous Architectures

Efficient implementations of parallel applications on heterogeneous hybrid architectures require a careful balance between computations and communications with accelerator devices. Even if most of the communication time can be overlapped by computations, it is essential to reduce the total volume of communicated data. The literature therefore abounds with ad-hoc methods to reach that balance, but that are architecture and application dependent. We propose here a generic mechanism to automatically optimize the scheduling between CPUs and GPUs, and compare two strategies within this mechanism: the classical Heterogeneous Earliest Finish Time (HEFT) algorithm and our new, parametrized, Distributed Affinity Dual Approximation algorithm (DADA), which consists in grouping the tasks by affinity before running a fast dual approximation. We ran experiments on a heterogeneous parallel machine with six CPU cores and eight NVIDIA Fermi GPUs. Three standard dense linear algebra kernels from the PLASMA library have been ported on top of the Xkaapi runtime. We report their performances. It results that HEFT and DADA perform well for various experimental conditions, but that DADA performs better for larger systems and number of GPUs, and, in most cases, generates much lower data transfers than HEFT to achieve the same performance

A novel POLR3A genotype leads to leukodystrophy type-7 in two siblings with unusually late age of onset

Background: Leukodystrophies are familial heterogeneous disorders primarily affecting the white matter, which are defined as hypomyelinating or demyelinating based on disease severity as assessed at MRI. Recently, a group of clinically overlapping hypomyelinating leukodystrophies (HL) has been associated with mutations in RNA polymerase III enzymes (Pol III) subunits. Case presentation: In this manuscript, we describe two Italian siblings carrying a novel POLR3A genotype. MRI imaging, genetic analysis, and clinical data led to diagnosing HL type 7. The female sibling, at the age of 34, is tetra-paretic and suffers from severe cognitive regression. She had a disease onset at the age of 19, characterized by slow and progressive cognitive impairment associated with gait disturbances and amenorrhea. The male sibling was diagnosed during an MRI carried out for cephalalgia at the age of 41. After 5 years, he developed mild cognitive impairment, dystonia with 4-limb hypotonia, and moderate dysmetria with balance and gait impairment. Conclusions: The present study provides the first evidence of unusually late age of onset in HL, describing two siblings with a novel POLR3A genotype which showed the first symptoms at the age of 41 and 19, respectively. This provides a powerful insight into clinical heterogeneity and genotype-phenotype correlation in POLR3A related HL

Parallel computation of echelon forms

International audienceWe propose efficient parallel algorithms and implementations on shared memory architectures of LU factorization over a finite field. Compared to the corresponding numerical routines, we have identified three main difficulties specific to linear algebra over finite fields. First, the arithmetic complexity could be dominated by modular reductions. Therefore, it is mandatory to delay as much as possible these reductions while mixing fine-grain parallelizations of tiled iterative and recursive algorithms. Second, fast linear algebra variants, e.g., using Strassen-Winograd algorithm, never suffer from instability and can thus be widely used in cascade with the classical algorithms. There, trade-offs are to be made between size of blocks well suited to those fast variants or to load and communication balancing. Third, many applications over finite fields require the rank profile of the matrix (quite often rank deficient) rather than the solution to a linear system. It is thus important to design parallel algorithms that preserve and compute this rank profile. Moreover, as the rank profile is only discovered during the algorithm, block size has then to be dynamic. We propose and compare several block decomposition: tile iterative with left-looking, right-looking and Crout variants, slab and tile recursive. Experiments demonstrate that the tile recursive variant performs better and matches the performance of reference numerical software when no rank deficiency occur. Furthermore, even in the most heterogeneous case, namely when all pivot blocks are rank deficient, we show that it is possbile to maintain a high efficiency

Cerebrospinal fluid levels of L-glutamate signal central inflammatory neurodegeneration in multiple sclerosis

Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179 MS patients (relapsing remitting, RR, N = 157; secondary progressive/primary progressive, SP/PP, N = 22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1 year follow-up, was assessed using the Expanded Disability Status Scale (EDSS). CSF concentrations of lactate and of a large set of pro-inflammatory and anti-inflammatory molecules were explored. CSF levels of L-Glu were slightly reduced in MS patients compared to controls. In RR-MS patients, L-Glu levels correlated with EDSS after 1 year follow-up. Moreover, in MS patients, significant correlations were found between L-Glu and both CSF levels of lactate and the inflammatory molecules interleukin (IL)-2, IL-6, and IL-1 receptor antagonist. Altered expression of L-Glu is associated with disability progression, oxidative stress, and inflammation. These findings identify CSF L-Glu as a candidate neurochemical marker of inflammatory neurodegeneration in MS. (Figure presented.)

Cerebrospinal fluid levels of L-glutamate signal central inflammatory neurodegeneration in multiple sclerosis

Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179 MS patients (relapsing remitting, RR, N = 157; secondary progressive/primary progressive, SP/PP, N = 22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1 year follow-up, was assessed using the Expanded Disability Status Scale (EDSS). CSF concentrations of lactate and of a large set of pro-inflammatory and anti-inflammatory molecules were explored. CSF levels of L-Glu were slightly reduced in MS patients compared to controls. In RR-MS patients, L-Glu levels correlated with EDSS after 1 year follow-up. Moreover, in MS patients, significant correlations were found between L-Glu and both CSF levels of lactate and the inflammatory molecules interleukin (IL)-2, IL-6, and IL-1 receptor antagonist. Altered expression of L-Glu is associated with disability progression, oxidative stress, and inflammation. These findings identify CSF L-Glu as a candidate neurochemical marker of inflammatory neurodegeneration in MS. (Figure presented.)

INTEGRAL/SPI data segmentation to retrieve sources intensity variations

International audienceContext. The INTEGRAL/SPI, X/γ-ray spectrometer (20 keV–8 MeV) is an instrument for which recovering source intensity variations is not straightforward and can constitute a difficulty for data analysis. In most cases, determining the source intensity changes between exposures is largely based on a priori information.Aims. We propose techniques that help to overcome the difficulty related to source intensity variations, which make this step more rational. In addition, the constructed “synthetic” light curves should permit us to obtain a sky model that describes the data better and optimizes the source signal-to-noise ratios.Methods. For this purpose, the time intensity variation of each source was modeled as a combination of piecewise segments of time during which a given source exhibits a constant intensity. To optimize the signal-to-noise ratios, the number of segments was minimized. We present a first method that takes advantage of previous time series that can be obtained from another instrument on-board the INTEGRAL observatory. A data segmentation algorithm was then used to synthesize the time series into segments. The second method no longer needs external light curves, but solely SPI raw data. For this, we developed a specific algorithm that involves the SPI transfer function.Results. The time segmentation algorithms that were developed solve a difficulty inherent to the SPI instrument, which is the intensity variations of sources between exposures, and it allows us to obtain more information about the sources’ behavior

Trend in potassium intake and Na/K ratio in the Italian adult population between the 2008 and 2018 CUORE project surveys

Background and aims: Low potassium intake, in addition to high sodium, has been associated with higher risk of hypertension and CVD. The Study assessed habitual potassium intake and sodium/potassium ratio of the Italian adult population from 2008 to 2012 to 2018–2019 based on 24-h urine collection, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU’ SALUTE national surveys. Methods and results: Data were from cross-sectional surveys of randomly selected age-and-sex stratified samples of resident persons aged 35–74 years in 10 (out of 20) Italian regions. Urinary electrolyte and creatinine measurements were performed in a central laboratory. Analyses considered 942 men and 916 women, examined in 2008–2012, and 967 men and 1010 women, examined in 2018–2019. In 2008–2012, the age-standardized mean of potassium intake (urinary potassium accounts for 70% of potassium intake) was 3147 mg (95% CI 3086–3208) in men and 2784 mg (2727–2841) in women, whereas in 2018–2019, it was 3043 mg (2968–3118) and 2561 mg (2508–2614) respectively. In 2008–2012, age-adjusted prevalence of persons with an adequate potassium intake (i.e. ≥ 3510 mg/day) was 31% (95% CI 28–34%) for men and 18% (16–21%) for women; in 2018–2019, it was 26% (23–29%) and 12% (10–14%) respectively. The sodium/potassium ratio significantly decreased both in men and women. Conclusions: The average daily potassium intake of the Italian general adult population remains lower than the WHO and EFSA recommended level. These results suggest the need of a revision to strengthen initiatives for the promotion of an adequate potassium intake at the population level

Trend of salt intake measured by 24-h urine collection in the Italian adult population between the 2008 and 2018 CUORE project surveys

Background and aims: The WHO Global Action Plan for the Prevention of non-communicable diseases (NCDs) recommends a 30% relative reduction in mean population salt/sodium intake. The study assessed the trend in the habitual salt intake of the Italian adult population from 2008 to 2012 to 2018–2019 based on 24-h urinary sodium excretion, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU’ SALUTE national surveys. Methods and results: Data were from cross-sectional surveys of randomly selected age and sex–stratified samples of resident persons aged 35–74 years in 10 (out of 20) Italian Regions distributed in North, Centre and South of the Country. Urinary sodium and creatinine measurements were carried out in a central laboratory. The analyses included 942 men and 916 women examined in 2008–2012, and 967 men and 1010 women examined in 2018–2019. The age-standardized mean daily population salt (sodium chloride) intake was 10.8 g (95% CI 10.5–11.1) in men and 8.3 g (8.1–8.5) in women in 2008–2012 and respectively 9.5 g (9.3–9.8) and 7.2 g (7.0–7.4) in 2018–2019. A statistically significant (p<0.0001) salt intake reduction was thus observed over 10 years for both genders, and all age, body mass index (BMI) and educational classes. Conclusions: The average daily salt intake of the Italian general adult population remains higher than the WHO recommended level, but a significant reduction of 12% in men and 13% in women has occurred in the past ten years. These results encourage the initiatives undertaken by the Italian Ministry of Health aimed at the reduction of salt intake at the population level

A pipeline structure for the block QR update in digital signal processing

[EN] There exist problems in the field of digital signal processing, such as filtering of acoustic signals that require processing a large amount of data in real time. The beamforming algorithm, for instance, is a process that can be modeled by a rectangular matrix built on the input signals of an acoustic system and, thus, changes in real time. To obtain the output signals, it is required to compute its QR factorization. In this paper, we propose to organize the concurrent computational resources of a given multicore computer in a pipeline structure to perform this factorization as fast as possible. The pipeline has been implemented using both the application programming interface OpenMP and GrPPI, a library interface to design parallel applications based on parallel patterns. We tackle not only the performance challenge but also the programmability of our idea using parallel programming frameworks.This work was supported by the Spanish Ministry of Economy and Competitiveness under MINECO and FEDER projects TIN2014-53495-R and TEC2015-67387-C4-1-R.Dolz, MF.; Alventosa, FJ.; Alonso-Jordá, P.; Vidal Maciá, AM. (2019). A pipeline structure for the block QR update in digital signal processing. The Journal of Supercomputing. 75(3):1470-1482. https://doi.org/10.1007/s11227-018-2666-1S14701482753Huang Y, Benesty J, Chen J (2006) Acoustic MIMO signal processing (signals and communication technology). Springer, BerlinRamiro C, Vidal AM, González A (2015) MIMOPack: a high performance computing library for MIMO communication systems. J Supercomput 71:751–760Alventosa FJ, Alonso P, Piñero G, Vidal AM (2016) Implementation of the Beamformer algorithm for the NVIDIA Jetson. In: Actas de la Conferencia, Granada, Spain, pp 201–211. ISBN 978-3-319-49955-0Alventosa FJ, Alonso P, Vidal AM, Piñero G, Quintana-Ortí ES (2018) Fast block QR update in digital signal processing. J Supercomput. https://doi.org/10.1007/s11227-018-2298-5del Rio D, Dolz MF, Fernández J, García JD (2017) A generic parallel pattern interface for stream and data processing. Concurr Comput Pract Exp 29(24):e4175Benesty J, Chen J, Huang Y, Dmochowski J (2007) On microphone-array Beamforming from a MIMO acoustic signal processing perspective. IEEE Trans Audio Speech Lang Process 15(3):1053–1065Lorente J, Piñero G, Vidal AM, Belloch JA, González A (2011) Parallel implementations of Beamforming design and filtering for microphone array applications. In: 19th European Signal Processing Conference (EUSIPCO), Barcelona, Spain, pp 501–505Belloch JA, Ferrer M, González A, Martínez-Zaldívar FJ, Vidal AM (2013) Headphone-based virtual spatialization of sound with a GPU accelerator. J Audio Eng Soc 61:546–561Belloch JA, González A, Martínez-Zaldívar FJ, Vidal AM (2011) Real-time massive convolution for audio applications on GPU. J Supercomput 58(3):449–457Golub GH, Van Loan CF (2013) Matrix computations. Johns Hopkins studies in the mathematical sciences. Johns Hopkins University Press, BaltimoreGunter BC, van de Geijn RA (2005) Parallel out-of-core computation and updating the QR factorization. ACM Trans Math Softw 31(1):60–78Buttari A, Langou J, Kurzak J, Dongarra J (2009) A class of parallel tiled linear algebra algorithms for multicore architectures. Parallel Comput 35(1):38–53Dolz MF, Alventosa FJ, Alonso-Jordá P, Vidal AM (2018) A pipeline for the QR update in digital signal processing. In: Proceedings of the 18th International Conference on Computational and Mathematical Methods in Science and Engineering (CMMSE 2018), Rota, Cádiz, Spain, pp 1–5Quintana-Ortí G, Quintana-Ortí ES, Van De Geijn RA, Van Zee FG, Chan E (2009) Programming matrix algorithms-by-blocks for thread-level parallelism. ACM Trans Math Softw 36(3):14:1–14:2