Current seismic structural design makes use of a ground motion intensity that has a certain probability of being exceeded at a site of interest in a time interval or, equivalently, exceedance return ...period. The design intensities with the same return period are often collected in the form of maps deriving from probabilistic seismic hazard analysis (PSHA) for each of the sites of interest. Probability theory underlying PSHA dictates that, in any time interval, design intensities are expected to be exceeded in a fraction of sites that depends on the return period the map refers to. In the case of Italy, three different nationwide PSHA studies can be currently considered of relevance. In the study, the estimated areal fraction of the Italian territory exposed to exceedance of the design intensity from 2008 to 2019 was quantified for the three hazard models, based on ShakeMap data for instrumental earthquakes. In addition, the same fraction was calculated considering a sparse catalog of inferred ShakeMap for historical earthquakes that occurred over almost 1000 years. It was found that, despite the apparent differences in the hazard models, the estimated fraction of territory exposed to exceedance is comparable for all the considered hazard maps.
Abstract
Design ground motion intensities determine the actions for which structures are checked, in the conventional approach of seismic codes, not to fail the target performances. On the other ...hand, due to inherent characteristics of probabilistic seismic hazard analysis (PSHA), it is expected that site-specific design intensity based on PSHA is exceeded in the epicentral area of moderate-to-high magnitude earthquakes. In the context of regional seismic loss assessment and of the evolution of seismic codes from the regulator perspective, it is useful to gather insights about the extent of the zone around the earthquake source where code-conforming structures are expected to be systematically exposed to seismic actions larger than those accounted for in design. To assess such areal extent based on empirical evidence is the scope of the study presented in the paper. To this aim, peak ground acceleration ShakeMap data for Italian earthquakes from 2008 to 2020 were compared to the current design intensities in the same areas for which the maps are available. This allowed, first, to develop simple semi-empirical models of the exceedance area versus the magnitude of the earthquakes. Second, it allowed to model the probability that an earthquake of given magnitude causes exceedance of the design intensity via logistic regressions. Coupling the first and second class of models provides an approximation of the expected exceedance (logarithmic) area upon occurrence of an earthquake of given magnitude. Such an area can be of several thousand square kilometers for earthquakes occurring relatively frequently in countries such as Italy.
Abstract There is a thriving interest in the field of hereditary autoinflammatory disorders (HAID), a gamut of heterogeneous conditions deriving from an aberrant orchestration of innate immunity, ...unified by the common feature of seemingly unprovoked inflammation, which might be systemic or occur in localized niches of the organism. Recurrent fever and episodic inflammation in the joints, serosal membranes, skin, gut, and other organs are the common denominator of HAID. Mutations in the inflammasome-related genes have been associated with different HAID, showing the intimate link existing between interleukin-1 (IL-1)-structured inflammasome and their pathogenesis. Differential diagnosis of HAID can be challenging, as there are no universally accepted diagnostic protocols, and near half of patients may remain without any genetic abnormality identified. The use of IL-1-antagonists has been associated with beneficial effects in a large number of HAID associated with excessive IL-1 signalling, such as cryopyrin-associated periodic syndromes, familial Mediterranean fever, and deficiency of IL-1 receptor antagonist. This review will discuss about the key-clues of HAID which might guide for an early recognition and drive decisions for treatment.
Autoinflammatory diseases (AIDs) are heterogeneous disorders characterized by dysregulation in the inflammasome, a large intracellular multiprotein platform, leading to overproduction of ...interleukin-1(IL-1)β that plays a predominant pathogenic role in such diseases. Appropriate treatment is crucial, also considering that AIDs may persist into adulthood with negative consequences on patients' quality of life. IL-1β blockade results in a sustained reduction of disease severity in most AIDs. A growing experience with the human IL-1 receptor antagonist, Anakinra (ANA), and the monoclonal anti IL-1β antibody, Canakinumab (CANA), has also been engendered, highlighting their efficacy upon protean clinical manifestations of AIDs. Safety and tolerability have been confirmed by several clinical trials and observational studies on both large and small cohorts of AID patients. The same treatment has been proposed in refractory Kawasaki disease, an acute inflammatory vasculitis occurring in children before 5 years, which has been postulated to be autoinflammatory for its phenotypical and immunological similarity with systemic juvenile idiopathic arthritis. Nevertheless, minor concerns about IL-1 antagonists have been raised regarding their employment in children, and the development of novel pharmacological formulations is aimed at minimizing side effects that may affect adherence to treatment. The present review summarizes current findings on the efficacy, safety, and tolerability of ANA and CANA for treatment of AIDs and Kawasaki vasculitis with a specific focus on the pediatric setting.
A complex web of dynamic relationships between innate and adaptive immunity is now evident for many autoinflammatory and autoimmune disorders, the first deriving from abnormal activation of innate ...immune system without any conventional danger triggers and the latter from self-/non-self-discrimination loss of tolerance, and systemic inflammation. Due to clinical and pathophysiologic similarities giving a crucial role to the multifunctional cytokine interleukin-1, the concept of autoinflammation has been expanded to include nonhereditary collagen-like diseases, idiopathic inflammatory diseases, and metabolic diseases. As more patients are reported to have clinical features of autoinflammation and autoimmunity, the boundary between these two pathologic ends is becoming blurred. An overview of monogenic autoinflammatory disorders, PFAPA syndrome, rheumatoid arthritis, type 2 diabetes mellitus, uveitis, pericarditis, Behçet’s disease, gout, Sjögren’s syndrome, interstitial lung diseases, and Still’s disease is presented to highlight the fundamental points that interleukin-1 displays in the cryptic interplay between innate and adaptive immune systems.
To compare the efficacy of adalimumab (ADA) and infliximab (IFX) in patients with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. Demographic, clinical, instrumental, and ...therapeutic data from patients enrolled were collected at the start of treatment, at 12-month follow-up, and at the last follow-up assessment. One hundred seven patients (46 females, 187 eyes) were enrolled, 66 (61.7%) treated with ADA and 41 (38.3%) with IFX. Bilateral involvement was observed in 80 cases. The mean follow-up was 26.45 ± 21.71 months for ADA patients and 56.60 ± 56.04 months for IFX patients. The overall decrease of uveitis frequency during the first 12 months of treatment was 66.7% in the IFX group and 84.2% in the ADA group, compared to the previous 12 months (
p
= 0.09). A significantly higher corticosteroid dosage was found among patients treated with ADA at the last follow-up visit (
p
= 0.008). The percentage of patients co-administered with corticosteroids was significantly higher among ADA patients both at the 12-month visit (
p
= 0.03) and at the last visit (
p
= 0.0004). The frequency of uveitic macular edema (UME) was significantly higher among patients treated with ADA compared to those treated with IFX at the 12-month assessment (
p
= 0.015) and at the last follow-up visit (
p
= 0.011); central macular thickness was significantly higher in ADA group compared to the IFX group at the last follow-up assessment (
p
= 0.04). ADA and IFX have shown a similar efficacy in controlling uveitis relapses, but IFX showed a more pronounced corticosteroid sparing effect and a significantly higher capacity in resolving UME compared to ADA.
In the state-of-the-art of structural engineering the actions for design or assessment of bridges should derive from a probabilistic (i.e., frequentist) characterization of the loads. Data from ...weigh-in-motion (WIM) systems can inform stochastic models for traffic loads. However, WIM is not widespread, and data of this kind are scarce in the literature and often not recent. Due to structural safety reasons, the 52 km long A3 highway in Italy, connecting the cities of Naples and Salerno, has been equipped with a WIM system which has been operational since the beginning of 2021. The system's measurements of each vehicle transiting over the WIM devices, impede overloads on the many bridges featured in the transportation infrastructure. By the time of this writing the WIM system has seen one year of uninterrupted operation, collecting more than thirty-six million datapoints in the meantime. This short paper presents and discusses these WIM measurements, deriving the empirical distributions of traffic loads and making the original data available for further research and applications.
The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet’s disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 ...selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12 months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (
p
< 0.0001). Similarly, BCVA improved if compared to baseline (7.4 ± 2.9 versus 8.5 ± 2.1,
p
= 0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27 ± 42.8 μm at the end of follow-up (
p
< 0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (
p
< 0.0001 and
p =
0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.
Recommendations related to ocular, mucosal and cutaneous involvement of Behçet's disease (BD) are mainly evidence-based, but in cases of vascular, neurological and gastrointestinal involvement there ...are no guidelines to define the best treatment strategy. We report three adult patients with BD, who received an interleukin-1β inhibitor by subcutaneous injections, canakinumab (at the dosage of 150 mg every 6 weeks), after failure shown by corticosteroids and different combinations of immunosuppressant agents. The prompt and sustained clinical efficacy demonstrated by canakinumab as a monotherapy supports the opportunity of using this specific anti-interleukin-1β agent as a valid therapeutic option for resistant or refractory BD. Open trials and observational studies should be performed to test canakinumab efficacy on a larger number of patients. The most appropriate dosage and intervals between administrations should be decided according to the individual patient, severity or recurrence of clinical manifestations and major organ involvement.
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