Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: a case report

Ataxia-telangiectasia (A-T) is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM) gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children

Legal Status and the Criminal Activity of Immigrants

We exploit exogenous variation in legal status following the January 2007 European Union enlargement to estimate its effect on immigrant crime. We difference out unobserved time-varying factors by (i) comparing recidivism rates of immigrants from the “new” and “candidate” member countries; and (ii) using arrest data on for eign detainees released upon a mass clemency that occurred in Italy in August 2006. The timing of the two events allows us to setup a difference-in-differences strategy. Legal status leads to a 50 percent reduction in recidivism, and explains one-half to two-thirds of the observed differences in crime rates between legal and illegal immigrants

SESAR EXPLORATORY RESEARCH SAPIENT PROJECT OVERVIEW

The SESAR (Single European Sky ATM Research) Exploratory Research project called SAPIENT (Satellite and terrestrial architectures improving performance, security and safety in ATM) is a program of the SESAR Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreement 699328 [1][2]. It aims at defining Satellite and Terrestrial Architectures improving performance security and Safety in ATM (Air Traffic Management) through new and innovative functionalities for future CNS (Communication, Navigation and Surveillance) and ATM systems and future European RPAS (Remotely Piloted Air System) C2/C3 satellite Data Link (DL) for governmental initiatives (C2 states for Command and Control, while C3 states Command, Control and Communications). In this context it has been defined SAPIENT which is a novel cost-effective and performance-efficient system solution for aeronautical communications, aimed at adapting and optimizing the capacity and safety performance of aeronautical communication applications, e.g. CPDLC (Controller-Pilot Data Link Communications) and ADS-C (Automatic Dependent Surveillance – Contract), in view of the estimated ‘status’ of air ground ATM SoL (Safety of Life) terrestrial and satellite datalinks over actual flown trajectories. To meet these targets, SAPIENT exploits the information on actual 4D aircraft trajectories – in terms of dynamic position in space and time – and performance data of ATM Air Ground Datalinks, produced by aircraft and other elements of the ATM Communication Infrastructure [3]. The innovative aspects addressed in the SAPIENT Project are related to the TAS-I patent “System for Aeronautical Safety of Life Applications Providing Adaptation of Services and Communication Resources for Maximized Safety and Capacity Performance” [4] . Significant references for the ATM Datalink aspects are the activities undergong in SESAR on VDL2 (VHF Digital Link Mode 2) [5] and other new generation digital datalinks and in ESA on Iris [7]. The SAPIENT solution is a multilink/data link monitor and control system. It is aimed at providing information on the aircraft perception of the operational layout goodness in order to correct or operate more effectively with respect to the ATM communication goals. The main objectives are: - Support the multilink function during the selection of the optimal data link; - Foresee retroaction on the in-use data link, and change the resources during the flight, according to information obtained through it and according to the information collected from the other SAPIENT system actors; - Retroact on multilink function in order to change the priority between data links (i.e. need of load balancing in a common coverage area with traffic hot spots). The use of the SAPIENT system is expected to positively impact: - The efficiency of the data-links management in a multilink environment, resulting in less resources needed by ATM communication system elements, with main focus on effective and efficient use of RF spectrum The Communication issues in the ATM air/ground links minimizing the need of tactical interventions from ATC (Air Traffic Control) and pilots to de-conflict situations - Communication issues in the RPAS C3 satellite DL minimizing the use of RPAS safety procedure that will limit the execution of the RPAS missions - The Air Navigation Service providing a cost saving obtained by improving the Air navigation Service productivity and the frequency band usage The aim of this paper is to present the SAPIENT reference architecture and system boundaries, the SAPIENT protocol and the main SAPIENT simulation result

Enhanced Oil Spill Remediation by Adsorption with Interlinked Multilayered Graphene

The performances of an innovative material based on graphene multilayers in a 3D structure similar to expanded graphite, Grafysorber\uae G+ (Directa Plus), have been tested via in field applications on a real contaminated site. Several experimental tests were performed using Grafysorber\uae inside adsorbent devices (booms and pillows) to treat waters polluted by oil. The experimental campaign was carried out with the aim of comparing the performances of Grafysorber\uae with those of polypropylene (PP), which is the material used worldwide in case of water oil spill clean-up activities. The results achieved have confirmed a considerably higher selective adsorption capacity of Grafysorber\uae compared to PP, and configure the new material as a promising alternative to standard materials in enhancing oil spill remediation by selective adsorption

Migraine patients with and without neck pain:Differences in clinical characteristics, sensitization, musculoskeletal impairments, and psychological burden

Aims: This study aims to assess differences in clinical characteristics across healthy controls and migraine patients with (MNP) and without (MwoNP) neck pain.Method: This study assessed: headache frequency; headache disability index (HDI); central sensitization inventory (CSI); Hospital Anxiety (HADS-A) and Depression (HADS-D) scale; active range of motion (AROM); flexion rotation test (FRT); activation pressure score (APS); number of active/latent myofascial trigger points (MTrPs) in head/neck muscles; number of positive cervical vertebral segments (C1/C2) who reproduce migraine pain; wind-up ratio (WUR); mechanical pain threshold (MPT) and static pressure pain threshold (sPPT) over the trigeminal area; sPPT and dynamic PPT (dPPT) over the cervical area; sPPTs and MPT over the hand.Results: Compared to controls, MNP had: worse CSI, HADS-A, and HADS-D (all, p < 0.002); reduced AROM (flexion, extension, left lateral-flexion, and right-rotation), FRT, APS, and a higher number of MTrPs and positive cervical vertebral segments (all, p < 0.020); reduced trigeminal MPT and sPPT, cervical sPPT and dPPT, hand MPT and sPPT (all, p < 0.006). Compared to controls, MwoNP had: worse CSI, and HADS-A (all, p < 0.002); reduced AROM (flexion, and left lateral-flexion), FRT, APS, and a higher number of MTrPs and positive cervical vertebral segments (all, p < 0.017); reduced trigeminal MPT and cervical dPPT (all, p < 0.007). Compared to MwoNP, MNP had higher headache frequency, worse HDI and CSI (all, p < 0.006); reduced AROM (flexion, and right rotation) (all, p < 0.037); reduced cervical dPPT (all, p < 0.002).Conclusion: MNP had worse headache characteristics, more pronounced cervical musculoskeletal impairments, enhanced signs and symptoms related to sensitization, and worse psychological burden compared to MwoNP

Management of pericarditis

Pericarditis is an inflammatory syndrome involving pericardium, which is a double-walled sac consisting of two leaves, a serous visceral layer in contact with the myocardium (pericardium) and a parietal fibrous one, delimiting a cavity (pericardial cavity) containing pericardial fluid. Pericarditis may occur isolated or as a manifestation of a systemic disorder. Diagnosis and correct management of pericarditis can be difficult and its natural history is often characterized by a lot of relapses. Treatment of acute pericarditis should target the underlying etiology. The diagnosis is based on characteristic clinical findings, electrocardiogram, and echocardiography. The goals of treatment are relief of pain, resolution of inflammation (and, if present, pericardial effusion), and prevention of recurrence. Despite a significant impairment of the quality of life, pericarditis usually has good long-term outcomes

Case report: Neonatal-onset inflammatory bowel disease due to novel compound heterozygous mutations in DUOX2

Very Early Onset Inflammatory Bowel Disease (VEO-IBD) is potentially associated with genetic disorders of the intestinal epithelial barrier or inborn errors of immunity (IEI). Dual oxidase 2 (DUOX2), an H2O2-producing NADPH oxidase expressed at apical enterocyte membranes, plays a crucial role in innate defense response. Biallelic DUOX2 mutations have been described only in two patients with VEO-IBD to date. We report the case of a 1-month-old female infant who presented persistent high C-reactive protein (CRP) levels from birth and anemia. Positive occult blood and very high calprotectin in the stool were detected and abdominal ultrasound showed thickened last ileal loop. Full endoscopy evaluation revealed important colon stenosis with multiple pseudo-polyploidy formations that resulted refractory to steroid therapy, requiring a partial colic resection. Histological examination of biopsy samples showed morphological features of IBD. Whole Exome Sequencing (WES) disclosed compound heterozygous variants in the DUOX2 gene: the pathogenic c.2524C>T; p.Arg842Ter and the variant of uncertain significance (VUS) c.3175C>T; p.Arg1059Cys. Molecular and functional studies showed the presence of mutant DUOX2 in the intestinal epithelium of the patient, albeit with at least 50% decreased catalytic activity. In conclusion, we describe the third patient to date with compound heterozygous variants of DUOX2, responsible for monogenic neonatal-IBD. This case expands the knowledge about Mendelian causes of VEO-IBD and DUOX2 deficiency. We suggest that DUOX2 should be part of the diagnostic evaluation of patients with suspected monogenic VEO-IBD

The first interim analysis of Italian patients enrolled in the real-world, Pan-European, prospective, observational, phase 4 PEARL study of fremanezumab effectiveness

Introduction: In 2020, the Italian Medicines Agency (AIFA) approved the reimbursement of calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs), including fremanezumab, in patients with a Migraine Disability Assessment Scale (MIDAS) score ≥ 11, with prescription renewals for up to 12 months in patients with ≥ 50% reduction in MIDAS score at Months 3 and 6. In this sub-analysis of the Pan-European Real Life (PEARL) study, we provide real-world data on fremanezumab use in Italian routine clinical practice (EUPAS35111). Methods: This first interim analysis for Italy was conducted when 300 enrolled adult patients with episodic or chronic migraine (EM, CM) completed 6 months of treatment with fremanezumab. The primary endpoint is the proportion of patients achieving ≥ 50% reduction in monthly migraine days (MMD) across the 6 months post-fremanezumab initiation. Secondary endpoints include: proportion of patients achieving ≥ 50% reduction in MIDAS score at Months 3 and 6, and mean change from baseline across Months 1-6 in MMD and headache-related disability. Safety was assessed through adverse events (AEs) reported. Results: Of 354 patients enrolled at Italian centers, 318 (EM, 35.5%, CM, 64.5%) were included in the effectiveness analysis. Of patients with available data, 109 (61.2%) achieved the primary endpoint. 61.0% and 65.1% achieved ≥ 50% reduction in MMDs at Months 3 and 6, respectively; 79.9% and 81.0% experienced ≥ 50% reduction in MIDAS at the same timepoints. Conclusion: Fremanezumab was effective and well-tolerated over the first 6 months of treatment, with approximately 80% of patients meeting Italian criteria for treatment continuation at Months 3 and 6

The Inborn Errors of Immunity—Virtual Consultation System Platform in Service for the Italian Primary Immunodeficiency Network: Results from the Validation Phase

purposeInborn errors of immunity (IEI) represent a heterogeneous group of rare genetically determined diseases. In some cases, patients present with complex or atypical phenotypes, not fulfilling the accepted diagnostic criteria for IEI and, thus, at high risk of misdiagnosis or diagnostic delay. this study aimed to validate a platform that, through the opinion of immunologist experts, improves the diagnostic process and the level of care of patients with atypical/complex IEI.MethodsHere, we describe the functioning of the IEI-Virtual consultation system (VCS), an innovative platform created by the italian Immunodeficiency network (IPINet). resultsIn the validation phase, from January 2020 to June 2021, 68 cases were entered on the IEI-VCS platform. a final diagnosis was achieved in 35/68 cases (51%, 95% CI 38.7 to 64.2). In 22 out of 35 solved cases, the diagnosis was confirmed by genetic analysis. In 3/35 cases, a diagnosis of secondary immunodeficiency was made. In the remaining 10 cases, an unequivocal clinical and immunological diagnosis was obtained, even though not substantiated by genetic analysis. conclusionFrom our preliminary study, the VCS represents an innovative and useful system to improve the diagnostic process of patients with complex unsolved IEI disorders, with benefits both in terms of reduction of time of diagnosis and access to the required therapies. these results may help the functioning of other international platforms for the management of complex cases