APEmille: a parallel processor in the teraflop range

APEmille is a SIMD parallel processor under development at the Italian National Institute for Nuclear Physics (INFN). APEmille is very well suited for Lattice QCD applications, both for its hardware characteristics and for its software and language features. APEmille is an array of custom arithmetic processors arranged on a tridimensional torus. The replicated processor is a pipelined VLIW device performing integer and single/double precision IEEE floating point operations. The processor is optimized for complex computations and has a peak performance of 528Mflop at 66MHz and of 800Mflop at 100MHz. In principle an array of 2048 nodes is able to break the Tflops barrier. A powerful programming language named TAO is provided and is highly optimized for QCD. A C++ compiler is foreseen. Specific data structures, operators and even statements can be defined by the user for each different application. Effort has been made to define the language constructs for QCD.Comment: Talk presented at LATTICE96(machines

Analysis of foot structural damage in rheumatoid arthritis: clinical evaluation by validated measures and serological correlations

Objective: To examine foot involvement in rheumatoid arthritis (RA) and to characterize structural alterations in patients with anti-cyclic citrullinated peptide (CCP) antibody-positive and -negative disease. Methods: Seventy-eight patients with RA with foot pain were consecutively enrolled. The Manchester Hallux Valgus (MHV) rating scale was used to evaluate the hallux valgus deformity degree. The Foot Posture Index (FPI6), a novel, foot-specific outcome measure, was adopted in order to quantify variation in the position of the foot. The findings were correlated with disease duration and presence or absence of anti-CCP antibodies. Results: About 84.6% patients had different degrees of hallux valgus and 65.4% subjects had a pronated foot. These two foot alterations were prevalently found in patients with long-standing disease and circulating anti-CCP antibodies. On the contrary, RA patients without anti-CCP and early disease essentially displayed a supinated foot without relevant hallux valgus deformity. Conclusion: Our findings allowed to identify different anatomic foot alterations in RA patients according to disease duration and negative prognostic factors such as anti-CCP antibodies. Our findings support the role of an accurate analysis of foot structural damage and may suggest the usefulness of a correct plantar orthosis prescription also in early phases of the disease

Matched filters for coalescing binaries detection on massively parallel computers

We discuss some computational problems associated to matched filtering of experimental signals from gravitational wave interferometric detectors in a parallel-processing environment. We then specialize our discussion to the use of the APEmille and apeNEXT processors for this task. Finally, we accurately estimate the performance of an APEmille system on a computational load appropriate for the LIGO and VIRGO experiments, and extrapolate our results to apeNEXT.Comment: 19 pages, 6 figure

The clinical spectrum of primary Sjögren's syndrome: beyond exocrine glands

Although primary Sjögren's syndrome (pSS) is a mild indolent chronic disease mainly characterized by mucosal dryness in the majority of cases, a consistent subgroup of patients display extra-glandular manifestations. Virtually any organs and systems can be affected, leading to a more serious disease prognosis. Therefore, the prompt identification of patients at higher risk of extra-glandular manifestations is necessary to start a thorough follow up and an aggressive treatment. The aim of this review article is to provide an overview of epidemiological, clinical and serological features of extra-glandular manifestations in pSS as well as current knowledge about putative biomarkers useful in clinical practice

The onset site of rheumatoid arthritis: the joints or the lung?

The etiopathogenesis of rheumatoid arthritis (RA) is not yet fully elucidated and the site of inflammation onset is still a matter of debate. The presence of autoantibodies as well as clinical manifestations, such as interstitial lung disease, before the onset of arthritis seems to be in favour of the hypothesis that initial pathogenic events take place in tissues other than the joint. In this review article we summarize the most recent literature on extra-synovial autoimmunity triggers eventually leading to RA, with particular focus on the role of the lung. To date, anti-cyclic citrullinated peptide antibodies (ACPAs) are considered central players in RA pathogenesis and represent the gold-standard for disease diagnosis. Lungs and mucosae are exposed to environmental stimuli such as dusts and smoke which have been shown to foster citrullination of peptides in lungs thereby triggering the production of ACPA. In addition, other mechanisms of disease pathogenesis independent of citrullination play an important role. Deeper knowledge of these processes could represent a huge step forward in the management of RA, with dramatic impact on diagnosis, prevention, prognostic stratification and treatment of the disease

[Glucocorticoid induced TNFR-related protein (GITR) as marker of human regulatory T cells: expansion of the GITR(+)CD25⁻ cell subset in patients with systemic lupus erythematosus].

Objectives: Regulatory T cells (TREG) represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/ inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR) is a well known marker of murine TREG cells, but little is known in humans. The aim of this study was to investigate the characteristics of TREG cells in systemic lupus erythematosus (SLE) and the potential role of GITR as marker of human TREG. Methods: Nineteen SLE patients and 15 sex- and age-matched normal controls (NC) were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies and real time polymerase-chain reaction (PCR) using TaqMan probes. Results: The CD25highGITRhigh subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05). On the opposite, the CD25-GITRhigh cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01). Interestingly, FoxP3 at mRNA level was expressed in both CD25- GITRhigh and CD25highGITRhigh cells, suggesting that both cell subsets have regulatory activity. Conclusions: CD4+CD25-GITRhigh cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset

FRI0565 PREVALENCE AND SIGNIFICANCE OF ANTIBODIES AGAINST CITRULLINATED ALPHA-ENOLASE (ANTI-CEP1) IN CONNECTIVE TISSUE DISEASES.

Background:Anti-cyclic citrullinated peptide (anti-CCP) auto-antibodies represent the current gold standard for the diagnosis of rheumatoid arthritis (RA). However, growing evidence suggests that a variety of other citrullinated self-proteins may act as autoantigens and lead to the production of autoantibodies (1). Furthermore, autoantibodies believed to be RA-specific have been detected also in patients with connective tissue diseases (CTDs). We recently demonstrated that antibodies against citrullinated alpha-enolase (anti-CEP1) are a biomarker of erosive disease and RA-associated interstitial lung disease (2).Objectives:The purpose of this study was to investigate the prevalence and possible prognostic value of anti-CEP-1 in patients with CTDs.Methods:Two hundred and twelve consecutive patients with CTDs (51 systemic lupus erythematosus (SLE), 85 primary Sjogren's syndrome (pSS) and 76 systemic sclerosis (SSc)) were studied and compared to 97 sex and age matched normal controls (NC) and 267 patients with RA. Anti-CEP1 IgG were detected in serum samples with a commercial ELISA kit (Euroimmun).Results:The overall prevalence of anti-CEP1 in CTDs was 7% (15/212 patients). In detail, these antibodies were detectable in 4 out of 85 pSS (5%), 5 out of 51 SLE (10%) and 6/76 SSc (8%). The prevalence and the titer of anti-CEP1 in CTDs was significantly higher compared to NC and significantly lower compared to RA. Anti-CEP1 positive patients did not display a specific clinical and serological picture. Unlike in RA, anti-CEP1 did not correlate with CTD-associated ILD.Conclusion:This is the first study assessing anti-CEP1 in a large cohort of patients with CTDs. We demonstrated that the association of these autoantibodies with ILD is specific for RA since it is not observed in SLE, pSS and SSc. Furthermore, although being significantly more prevalent and at higher titer compared to NC, anti-CEP1 do not allow to discriminate different patient subsets displaying peculiar clinical or serological phenotypes. Based on our results, the application of anti-CEP1 in CTDs is not advisable, however larger studies may possibly identify correlations not evident in our cohort.References:[1] Bonifacio AF, Alunno A, La Paglia GMC, Valentini E, Leone MC, Bartoloni E, Gerli R. Novel autoantibodies in rheumatoid arthritis. Reumatismo 2019;71(1):1-12[2] Alunno A, Bistoni O, Pratesi F, La Paglia GMC, Puxeddu I, Migliorini P, Gerli R. Anti-citrullinated alpha enolase antibodies, interstitial lung disease and bone erosion in rheumatoid arthritis. Rheumatology (Oxford). 2018;57(5):850-855Disclosure of Interests:Alessia Alunno: None declared, Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Onelia Bistoni: None declared, Matteo Antonucci: None declared, Elena Bartoloni Bocci: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer, Roberto Gerli: None declare