Summary Juvenile idiopathic arthritis is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age. This term encompasses ...several disease categories, each of which has distinct methods of presentation, clinical signs, and symptoms, and, in some cases, genetic background. The cause of disease is still poorly understood but seems to be related to both genetic and environmental factors, which result in the heterogeneity of the illness. Although none of the available drugs has a curative potential, prognosis has greatly improved as a result of substantial progresses in disease management. The most important new development has been the introduction of drugs such as anticytokine agents, which constitute a valuable treatment option for patients who are resistant to conventional antirheumatic agents. Further insights into the disease pathogenesis and treatment will be provided by the continuous advances in understanding of the mechanisms connected to the immune response and inflammatory process, and by the development of new drugs that are able to inhibit selectively single molecules or pathways.
Summary Juvenile idiopathic arthritis is a heterogeneous group of diseases characterised by arthritis of unknown origin with onset before age of 16 years. Pivotal studies in the past 5 years have led ...to substantial progress in various areas, ranging from disease classification to new treatments. Gene expression profiling studies have identified different immune mechanisms in distinct subtypes of the disease, and can help to redefine disease classification criteria. Moreover, immunological studies have shown that systemic juvenile idiopathic arthritis is an acquired autoinflammatory disease, and have led to successful studies of both interleukin-1 and interleukin-6 blockade. In other forms of the disease, synovial inflammation is the consequence of a disturbed balance between proinflammatory effector cells (such as T-helper-17 cells), and anti-inflammatory regulatory cells (such as FOXP3-positive regulatory T cells). Moreover, specific soluble biomarkers (S100 proteins) can guide individual treatment. Altogether these new developments in genetics, immunology, and imaging are instrumental to better define, classify, and treat patients with juvenile idiopathic arthritis.
To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and ...routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases.
The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria.
In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor-positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody-positive JIA. The other forms were gathered under the term "others." These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities.
An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical term
. These preliminary criteria will be formally validated with a dedicated project.
Strain Modal Testing (SMT), based on strain sensors signal processing, is an unconventional approach to perform Experimental Modal Analysis which is typically based on data measured by ...accelerometers. SMT is still mainly restricted to academia and requires additional investigation for a successful transition towards industry. This paper critically reviews why the automotive sector can benefit from this relatively new approach for a variety of reasons. Moreover, a case study representative of the automotive field is analyzed and discussed. Specifically, an SMT methodology is applied to evaluate the modal properties of a reinforced composite roof belonging to a racing solar powered vehicle. In the experimental activity, signals from Fiber Bragg Grating (FBG) sensors, strain gauges, and accelerometers were simultaneously acquired and further processed. The advantages of using optical fibers were discussed, together with their weaknesses and ongoing challenges. The FBG results were compared with the conventional analysis performed with the accelerometers, emphasizing the main similarities and discrepancies.
This article aims to describe the Belle II experiment, its status and physics prospects for the next several years. Belle II is situated in Japan, at the KEK laboratory and it is the upgraded version ...of the Belle experiment. It uses a new collider named SuperKEKB, a second generation of B-factory based on the innovative Nano-Beam scheme technique, which is expected to collect an integrated luminosity of 50 ab
-1
. Using this amount of data, together with improved detector performances, it will be possible to provide important contributions about several flavour physics topics (
i.e.
CKM matrix elements, FCNC processes, quarkonium states etc..) through high precision measurements. The main aim of Belle II is to investigate new physics scenarios and validate highly suppressed SM predictions. The experiment is almost completely assembled; it already took the first data without the vertex detector installed while the data taking will start in February 2019.
Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA.
We randomly assigned 112 ...children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension.
At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology ACR core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 85% vs. 9 of 37 24%, P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range.
Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00642460.).
Reducing losses in water distribution networks is a worldwide challenge and all utilities are developing proper strategies for the active control of leaks. Temporary or permanent grids of units for ...the continuous monitoring of pipelines through vibro-acoustic measurements are probably the most commonly adopted leak detection systems. Such systems generally rely on the definition of proper thresholds to detect increments in the vibration levels associated with leaks. Since the thresholds are strongly dependent on the local boundary conditions of the monitored network, the initial setup is costly and time consuming, and the risk of undetected leaks or false alarms increases. This work aims to investigate leak detection methods based on the inherent properties of the measured signals instead of their relative amplitude. In particular, the possibility of detecting water leaks in small-diameter plastic pipes by analyzing the autocorrelation function of vibro-acoustic signals is assessed. An experimental campaign is conducted in a full-scale test facility that simulates the actual network. The measurements concerning artificially generated leaks are attained by two accelerometers and one hydrophone. The experimental results confirm the effectiveness of the proposed approach, which is therefore proven as a promising tool for leak detection.
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