Rational use of anti-tuberculosis drugs in the EU: better patient care and less drug resistance

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Improving the TB case management: The International Standards for Tuberculosis Care.

Tuberculosis (TB) is currently the leading cause of death from a curable infectious disease. The World Health Organization (WHO) estimates that 8.9 million new TB cases occurred in 2004 (of which 3.9 million were sputum smear positive), although only about half of the estimated number were reported by public health systems. Whilst the highest TB incidence rate is in sub-Saharan Africa (estimated to be 356 new cases per 100,000 population per yr), in most countries of the former Soviet Union the estimated incidence rate exceeds 100 new cases per 100,000 population per yr. Although the rate of increase in the TB incidence rate is decreasing, the global TB notification grew by 1% between 2003 and 2004, the last year for which data are available. This continued increase is largely the result of the striking increase in cases in sub-Saharan Africa and, to a lesser extent, in the former USSR. Whilst the worsening of the TB incidence in Africa is due to the HIVepidemic compounded by an insufficient health infrastructure, it is due to different causes in Eastern Europe, including economic decline, increased poverty, social disruption and sub-standard health services. In addition, as a result of these factors, .10% of new TB cases in the Baltic states and in some parts of Russia are multidrug-resistant (MDR-TB), i.e. resistant to at least isoniazid and rifampicin. In the European region, 445,000 new TB cases and nearly 70,000 deaths were estimated to have resulted from TB in 2004. In the Eastern part of the region, the levels of directly observed treatment, short-course (DOTS) strategy coverage and case detection are the lowest among the world regions, and the overall treatment success rate is the second lowest (75%) after Africa

ms-van3t: An integrated multi-stack framework for virtual validation of V2X communication and services

The automotive field is evolving towards high levels of automation, requiring seamless data exchange between vehicles through Vehicle-to-Everything (V2X) communications. Direct V2X technology is already being deployed on commercial vehicles, and it has the potential to deliver a range of safety and efficiency benefits on the road. However, the deployment of V2X-based applications is a complex process that demands extensive testing before these systems can be widely used by the public; indeed, high costs and safety concerns are among the main hurdles to overcome before applications leveraging V2X communication can become a reality. It is thus critical to reliably validate through simulation and emulation both the V2X technologies and the applications in realistic scenarios, before performing large-scale road tests. To address this pressing need, we present an open source framework for the virtual validation of V2X-based applications, amenable to the development and testing not only of different access technologies within the same environment (IEEE 802.11p, LTE-V2X, 5G NR-V2X, and LTE), but also of any kind of V2X-based application using ETSI-compliant messages. Our framework, called ms-van3t, is based on the ns-3 and SUMO (Simulation of Urban MObility) simulators, it implements a full ETSI C-ITS stack for CAM, DENM and IVIM messages, and it provides several novel features not found elsewhere. Further, ms-van3t enables the testing of V2X-based applications in HIL (Hardware-In-the-Loop) scenarios, thanks to a dedicated emulation mode, and it allows users to easily select different physical and MAC layer models, seamlessly collecting performance statistics. To showcase the capabilities of the framework, we present three sample applications as well as the performance results we obtained in terms of both application-related and network-related key performance indicators

S-LDM: Server Local Dynamic Map for 5G-based Centralized Enhanced Collective Perception

The automotive field is undergoing significant technological advances, which includes making the next generation of autonomous vehicles smarter, greener and safer through vehicular networks, which are often referred to as Vehicle-to-Everything (V2X) communications. Together with V2X, centralized maneuver management services for autonomous vehicles are increasingly gaining importance, as, thanks to their complete view over the road, they can optimally manage even the most complex maneuvers targeting L4 driving and beyond. These services face the challenge of strictly requiring a high reliability and low latency, which are tackled with the deployment at orchestrated Multi-Access Edge Computing (MEC) platforms. In order to properly manage safety-critical maneuvers, these services need to receive a large amount of data from vehicles, even though the useful subset of data is often related to a specific context on the road (e.g., to specific road users or geographical areas). Decoding and post-processing a large amount of raw messages, which are then for the most part filtered, increases the load on safety-critical services, which should instead focus on meeting the deadlines for the actual control and management operations. On this basis, we present an innovative open-source, 5G & MEC enabled service, called Server Local Dynamic Map (S-LDM). The S-LDM is a service that collects information about vehicles and other non-connected road objects using standard-compliant messages. Its primary purpose is to create a centralized dynamic map of the road that can be shared efficiently with other services managing L4 automation, when needed. By doing so, the S-LDM enables these services to widely and precisely understand the current situation of sections of the road, offloading them from the need of quickly processing a large number of messages. After a detailed description of the service architecture, we validate it through extensive laboratory and pilot trials, involving the MEC platforms and production 5G networks of three major European network operations and two Stellantis vehicles equipped with V2X On-Board Units (OBUs). We show how it can efficiently handle high update rates and process each messages in less than few tenths of microseconds. We also provide a complete scalability analysis with details on deployment options, providing insights on where new instances should be created in practical 5G-based V2X scenarios

Cooperative Localization Enhancement through GNSS Raw Data in Vehicular Networks

The evolution and integration of communication networks and positioning technologies are evolving at a fast pace in the framework of vehicular systems. The mutual dependency of such two capabilities can enable several new cooperative paradigms, whose adoption is however slowed down by the lack of suitable open protocols, especially related to the positioning and navigation domain. In light of this, the paper introduces a novel vehicular message type, namely the Cooperative Enhancement Message (CEM), and an associated open protocol to enable the sharing of Global Navigation Satellite Systems (GNSS) raw measurements among connected vehicles. The proposed CEM aims at extending existent approaches such as Cooperative Awareness Messages (CAM) and Collective Perception Messages (CPM) by complementing their paradigms with a cooperative enhancement of the localization accuracy, precision, and integrity proposed by state-of-the-art solutions. Besides the definition of CEMs and a related protocol, a validation of the approach is proposed through a novel simulation framework. A preliminary analysis of the network performance is presented in the case where CEM and CAM transmissions coexist and are concurrently used to support cooperative vehicle applications

del (3) (q13.11q21.1): descrizione di un nuovo caso

La delezione interstiziale della regione prossimale del braccio lungo del cromosoma 3 (q11-q21) \ue8 un\u2019alterazione cromosomica molto rara ed \ue8 stata descritta solo in 13 pazienti. Riportiamo il caso di un bambino di 8 mesi nato con parto eutocico da genitori sani non consanguinei. Il cariotipo da sangue periferico ha mostrato la presenza di un\u2019ampia delezione sul braccio lungo del cromosoma 3: 46,XY,del(3)(q12q21) confermata per mezzo di FISH. L\u2019Array-CGH ha evidenziato che la delezione \ue8 pari a 18,97 Mb e si estende da q13.11 a q21.1 consentendo di definire in modo pi\uf9 preciso il cariotipo: 46,XY,del(3)(q13.11q21.1) Il cariotipo normale di entrambi i genitori ha confermato l\u2019insorgenza de novo della delezione. Il bambino presenta tratti dismorfici del volto (fronte ampia, epicanto bilaterale, radice nasale a sella, ipoplasia della parte mediana del volto, padiglioni auricolari a basso impianto), ipotono assiale con ritardo moderato nell\u2019acquisizione delle tappe di sviluppo, plagiocefalia, ipoplasia del corpo calloso, assottigliamento della sostanza bianca in sede peritrigonale bilaterale, anomala conformazione del tronco encefalico per lieve ipoplasia del ponte, tendenza all\u2019inversione della fisiologica lordosi cervicale, criptorchidismo sinistro ed ernia inguinale sinistra Per quanto riguarda la correlazione genotipo-fenotipo il gene CBLB (3q13.11) sembra responsabile delle alterazioni craniofacciali, il gene BOC (3q13.2) dell\u2019ipotonia muscolare, il gene DRD3 (3q13.3) del ritardo dello sviluppo. La comparazione delle caratteristiche cliniche del nostro paziente con quelle dei pazienti descritti in letteratura conferma che la delezione della regione prossimale del braccio lungo del cromosoma 3 determina un fenotipo eterogeneo che comprende dismorfismi a carico del volto, ipotonia, ritardo di sviluppo, difetti cardiaci, anomalie celebrali, anomalie scheletriche e genitourinarie. L\u2019espressivit\ue0 variabile del fenotipo potrebbe essere dovuta all\u2019ampiezza della delezione variabile per differenti punti di rottura e alla presenza in questa regione di geni sensibili al dosaggio e o allo smascheramento di alleli recessivi, che a seguito della delezione si troverebbero in una condizione di emizigosi

Pediatric Moyamoya Disease and Syndrome in Italy: A Multicenter Cohort

Background: Moyamoya is a rare progressive cerebral arteriopathy, occurring as an isolated phenomenon (moyamoya disease, MMD) or associated with other conditions (moyamoya syndrome, MMS), responsible for 6–10% of all childhood strokes and transient ischemic attacks (TIAs). Methods: We conducted a retrospective multicenter study on pediatric-onset MMD/MMS in Italy in order to characterize disease presentation, course, management, neuroradiology, and outcome in a European country. Results: A total of 65 patients (34/65 women) with MMD (27/65) or MMS (38/65) were included. About 18% (12/65) of patients were asymptomatic and diagnosed incidentally during investigations performed for an underlying condition (incMMS), whereas 82% (53/65) of patients with MMD or MMS were diagnosed due to the presence of neurological symptoms (symptMMD/MMS). Of these latter, before diagnosis, 66% (43/65) of patients suffered from cerebrovascular events with or without other manifestations (ischemic stroke 42%, 27/65; TIA 32%, 21/65; and no hemorrhagic strokes), 18% (12/65) of them reported headache (in 4/12 headache was not associated with any other manifestation), and 26% (17/65) of them experienced multiple phenotypes (≥2 among: stroke/TIA/seizures/headache/others). Neuroradiology disclosed ≥1 ischemic lesion in 67% (39/58) of patients and posterior circulation involvement in 51% (30/58) of them. About 73% (47/64) of patients underwent surgery, and 69% (45/65) of them received aspirin, but after diagnosis, further stroke events occurred in 20% (12/61) of them, including operated patients (11%, 5/47). Between symptom onset and last follow-up, the overall patient/year incidence of stroke was 10.26% (IC 95% 7.58–13.88%). At last follow-up (median 4 years after diagnosis, range 0.5–15), 43% (26/61) of patients had motor deficits, 31% (19/61) of them had intellectual disability, 13% (8/61) of them had epilepsy, 11% (7/61) of them had behavioral problems, and 25% (13/52) of them had mRS > 2. The proportion of final mRS > 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (p = 0.021). Onset age <4 years and stroke before diagnosis were significantly associated with increased risk of intellectual disability (p = 0.0010 and p = 0.0071, respectively) and mRS > 2 at follow-up (p = 0.0106 and p = 0.0009, respectively). Conclusions: Moyamoya is a severe condition that may affect young children and frequently cause cerebrovascular events throughout the disease course, but may also manifest with multiple and non-cerebrovascular clinical phenotypes including headache (isolated or associated with other manifestations), seizures, and movement disorder. Younger onset age and stroke before diagnosis may associate with increased risk of worse outcome (final mRS > 2)