Disease activity states, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

The advent of biologic medications has increased considerably the potential for treatment benefit in juvenile idiopathic arthritis (JIA), with clinical remission being now achievable in a substantial proportion of patients. However, there is a need of data from the real world of clinical practice to evaluate thoroughly the efficacy and safety profile of the biologic agents currently approved

Soluble CD40 ligand plasma levels in lung cancer

: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activatio

Giacomo Serpotta e il "pareggiamento delle arti": la decorazione degli oratori fra manipolazione vitalistica e vocazione classicista

ABSTRACT GIACOMO SERPOTTA AND THE “EQUALIZATION OF THE ARTS”: DECORATION OF THE ORATORIES BETWEEN VITALISTIC MANIPULATION AND CLASSICIST VOCATION Ettore Sessa The value of the whole of Giacomo Serpotta's artistic vision in the orchestration of the figu¬rative apparatuses of his oratories was certainly one of the principal primers of his historical-critical raising in the modernist period. In 1901 Mauceri and in 1911 Ricci and Basile heighten a profile of it, however synthetic, of angling and above all of different breath from the rediscovery realized in positivist age. Classifiable, in fact, among the eighteenth century precedents of Gesamtkunstwerk aesthetical plant (according to a rather diffused custom within the artistic historiography of modernist culturaI area or of decadentist origin, as in different formalistic demonstrations of the wealthiest society Belle Époque) the progress of Serpottas artistic way towards tangible expressions of the idea of «the whole work of art» has a unmistakable im¬print of his and, at the same time, a feasibility thanks to the plasticism of gestures and to the uni¬tary multiplicity of his modeled. In his oratories arrangements the "realist" component, not exempted from hedonistic sensual witty remarks, acts on a foundation of Hellenic taste (also in the use of profiles and architectural elements). With wise modulation and with dosing diversified for intensity, according the nature of the subjects, combines history (see the «teatrini» with perspective sceneries, among which the Lepanto battle), micro history (from feminine allegorical subjects, to attractive dames modernly adorned with ends and brocades, to "picciotti" proudly ragged and to the anecdotal of the daily life), mysticism (from the devotional subjects to the allegories of the virtues), obscurity (from numerological components to philosophical attributes) and, finally, mythology (from the allegorical correspondences between Christianity and paganism to classical simbology). Despite the actual halving of this group of oratories (was destroyed by traumatic events as earthquakes and war actions, or by villainous demolitions big part of Serpottas works, among which the SS. Sacrament oratories to Kalsa and those of Saint Maria del Ponticello), the comparison among the palermitan examples reached us entire allows the individualization of the characters of originality typical of the generaI composition, over that of those figurative unanimously accredited among the most valid of the late- Baroque European sculpture. The typical scheme of these oratories, places with a strong secular imprint (predisposed as for cultural reunions how as for the preclusive congregational assemblies, to which the only ones not admitted affiliate were the artists), has as constants: the hall with a rectangular plant; the skiff or pavilion vault with plaster decorations dissimulating the constructive geometry; the sculptural wall register above of a high plinth; windows on the greatest sides (in number of three); two doors in the counterfacade, originally with desk for the assemblies in central position, below the principal devotional allegorical composition. The first oratory to which Giacomo Serpotta imposes an unitary imprint, except the cappellone only defined between 1717 and the following year) is that of SS. Rosary in S. Cita; he has worked since 1685 to 1688 on behalf of SS. Rosary Company. Serpotta is twenty nine, but already since almost ten years, after the apprenticeship with subordinate roles, he showed himself almost beginning in mute with the decorations of Madonna of the Pity church in Monreale, where he operated like Procopio De' Ferrari's collaborator, and perhaps with his interventions in 1678 in the lateral walls of S. Mercurio oratory, to which follow the 1679 decoration works in the Charity oratory in St. Bartholomeo of the Incurable people (no more existing), perhaps S. Pietro and S. Paolo statues dating back to 1680 for the greatest altar in Gancia church, the marble model for Charles H's equestrian monument for Messina (then realized in 1684) and during the two years 1683-1684 the scenic decorations for the transept altars of Carmine Maggiore church (where he collaborates with his brother Giuseppe and realizes the couples of twisted columns gilded and commented by a theory of plaster miniature scenes disposed according to a spiral development). Immediately after S. Cita oratory he realized, between 1688 and 1691, the decorative apparatuses of the Sacrament oratory in S. Nicolò to Kalsa (destroyed because of 1823 earthquake). Only eight years after the completion of this work (about which it was hypothesized that it were an advancement in comparison to the intervention in S. Cita) Giacomo Serpotta is entrusted by S. Francesco from Assisi and S. Lorenzo Companies to realize the complex allegorical and explanatory cycle of the plasters of S. Lorenzo orato¬ry. He worked partly on Giacomo Amato's sketches (to which are probably owed the reform interventions that confer to this oratory a great architectural "squaring" in comparison to others), completing the presbytery within 1706, while already from 1701 he is busy in the definition of the walls. In 1703 he began the counter facade with the monumental wall framework and high-relief representation of St. Lorenzo Martyrdom

Non-Malleable Codes for Decision Trees

We construct efficient, unconditional non-malleable codes that are secure against tampering functions computed by decision trees of depth $d = n^{1/4-o(1)}$. In particular, each bit of the tampered codeword is set arbitrarily after adaptively reading up to $d$ arbitrary locations within the original codeword. Prior to this work, no efficient unconditional non-malleable codes were known for decision trees beyond depth $O(\log^2 n)$. Our result also yields efficient, unconditional non-malleable codes that are $\exp(-n^{\Omega(1)})$-secure against constant-depth circuits of $\exp(n^{\Omega(1)})$-size. Prior work of Chattopadhyay and Li (STOC 2017) and Ball et al. (FOCS 2018) only provide protection against $\exp(O(\log^2n))$-size circuits with $\exp(-O(\log^2n))$-security. We achieve our result through simple non-malleable reductions of decision tree tampering to split-state tampering. As an intermediary, we give a simple and generic reduction of leakage-resilient split-state tampering to split-state tampering with improved parameters. Prior work of Aggarwal et al. (TCC 2015) only provides a reduction to split-state non-malleable codes with decoders that exhibit particular properties

A highly-compact and ultra-fast homogeneous electromagnetic calorimeter based on oriented lead tungstate crystals

Progress in high-energy physics has been closely tied to the development of high-performance electromagnetic calorimeters. Recent experiments have demonstrated the possibility to significantly accelerate the development of electromagnetic showers inside scintillating crystals typically used in homogeneous calorimeters based on scintillating crystals when the incident beam is aligned with a crystallographic axis to within a few mrad. In particular, a reduction of the radiation length has been measured when ultrarelativistic electron and photon beams were incident on a high-Z scintillator crystal along one of its main axes. Here, we propose the possibility to exploit this physical effect for the design of a new type of compact e.m. calorimeter, based on oriented ultra-fast lead tungstate (PWO-UF) crystals, with a significant reduction in the depth needed to contain electromagnetic showers produced by high-energy particles with respect to the state-of-the-art. We report results from tests of the crystallographic quality of PWO-UF samples via high-resolution X-ray diffraction and photoelastic analysis. We then describe a proof-of-concept calorimeter geometry defined with a Geant4 model including the shower development in oriented crystals. Finally, we discuss the experimental techniques needed for the realization of a matrix of scintillator crystals oriented along a specific crystallographic direction. Since the angular acceptance for e.m. shower acceleration depends little on the particle energy, while the decrease of the shower length remains pronounced at very high energy, an oriented crystal calorimeter will open the way for applications at the maximum energies achievable in current and future experiments. Such applications span from forward calorimeters, to compact beam dumps for the search for light dark matter, to source-pointing space-borne γ-ray telescopes, to decrease the size and the cost of the calorimeter needed to fully contain e.m. showers initiated by GeV to TeV particles

clinico pathological features treatments and survival of malignant insulinomas a multicenter study

Introduction Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. Aim of the study To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. Materials and methods Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. Results The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. Conclusions Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

Objective To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Results Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ = 0.76). Conclusion We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies

Expert consensus on dynamics of laboratory tests for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Objective: To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). Methods: A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre-MAS visit and at MAS onset, and the change in values between the two time points. The experts were asked to choose the 5 laboratory tests in which change was most important for the diagnosis of MAS and to rank the 5 selected tests in order of importance. The relevance of change in laboratory parameters was further discussed and ranked by the same experts at a consensus conference. Results: Platelet count was the most frequently selected test, followed by ferritin level, aspartate aminotransferase (AST), white cell count, neutrophil count, and fibrinogen and erythrocyte sedimentation rate. Ferritin was most frequently assigned the highest score. At the end of the process, platelet count, ferritin level and AST were the laboratory tests in which the experts found change over time to be most important. Conclusions: We identified the laboratory tests in which change over time is most valuable for the early diagnosis of MAS in sJIA. The dynamics of laboratory values during the course of MAS should be further scrutinised in a prospective study in order to establish the optimal cut-off values for their variation

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

PANDA Phase One - PANDA collaboration

The Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany, provides unique possibilities for a new generation of hadron-, nuclear- and atomic physics experiments. The future antiProton ANnihilations at DArmstadt (PANDA or P¯ANDA) experiment at FAIR will offer a broad physics programme, covering different aspects of the strong interaction. Understanding the latter in the non-perturbative regime remains one of the greatest challenges in contemporary physics. The antiproton–nucleon interaction studied with PANDA provides crucial tests in this area. Furthermore, the high-intensity, low-energy domain of PANDA allows for searches for physics beyond the Standard Model, e.g. through high precision symmetry tests. This paper takes into account a staged approach for the detector setup and for the delivered luminosity from the accelerator. The available detector setup at the time of the delivery of the first antiproton beams in the HESR storage ring is referred to as the Phase One setup. The physics programme that is achievable during Phase One is outlined in this paper