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Craniomaxillofacial surgery has been experiencing a deep conceptual change in surgical planning over the last decade, with virtual reality technologies becoming widely adopted. The high demand has led to an exponential increase in available software. The aim of this review was to outline the current literature and provide evidence on the most used software for virtual surgical planning (VSP), and also to define contemporary knowledge on which procedures are more ready candidates for VSP. A search was performed in the major databases, and screening of the results according to the PRISMA statement identified 535 articles reporting the implementation of preoperative VSP during the years 2010-2020. A total of 77 different software programs were identified. The surgical procedures were assigned a standardized nomenclature and further simplified into 10 categories for analysis: temporomandibular joint (TMJ), implants (IMPL), malformations (MALF), reconstruction (REC), oncology (ONCO), oral surgery (ORAL), orthognathic surgery (ORTH), cranial surgery (CRANIO), trauma (TRAUMA), miscellaneous (OTHER). The journals they were reported in and the sample size of each study were also investigated. The results showed that the Materialise suite was the most widespread tool for VSP, with a prevalence of 36.3%, followed by the Geomagic family. Several packages were found to be associated with a specific type of surgical procedure. This review offers a synopsis of the array of VSP software reported in the literature and sets the basis for an informed, evidence-based use of this software in craniomaxillofacial surgery.

The European Programme Copernicus is one of the main sources of free and open Earth Observation (EO) data and information services, aimed at sustaining important social and economic advancements to the European Union with Remote Sensing (RS) practices. To achieve these goals User Uptake initiatives have been undertaken: aimed at increasing Copernicus awareness, dissemination and competences, thus supporting the development of downstream applications. The paper introduces the ongoing activity of the EO-UPTAKE project, funded by Liguria Region, aiming to bridge the skills gap between intermediate and end-users involved in the downstream sectors and promoting the use and integration of Copernicus data and services. It presents an overview of the Copernicus Programme and the European User Uptake initiatives, and provides a survey about the downstream applications based on academic literature, by outlining thematic sectors involved, the developed applications, their users, and data integration practices. Benefits and obstacles are discussed.

Background Massive hemoptysis is a serious complication in Cystic Fibrosis (CF), occurring commonly in older patients. Bronchial artery embolization (BAE) can be performed to stop the bleeding. BAE is generally safe and effective, but can sometimes lead to serious complications. We report the first case of temporary unilateral diaphragmatic paralysis associated to lung consolidation following BAE in a pediatric CF female patient. This complication worsened the lung function of the patient who underwent lung transplantation after 9 months. Case presentation A 14 years old female CF patient followed by the CF center of Florence presented low-grade fever, cough increase and recurrent episodes of major hemorrhages such as to carry out a BAE. Within 24 h the patient started to complain of severe thoracic pain in the right hemithorax, increased dyspnea and fever. A computed tomographic angiography and a dynamic fluoroscopic evaluation revealed the right diaphragmatic paralysis, not present before the procedure. After 4 days the clinical condition and radiological imaging had improved with restored mobility of the right hemidiaphragm. Nine months later, she required mechanical ventilation, and subsequently the initiation of extracorporeal membrane oxygenation (ECMO) for a pulmonary exacerbation with septic shock. Lung transplantation in ECMO was performed with success. Conclusion Clinicians should be aware of the possibility of phrenic nerve injury with BAE in pediatric CF patients.

Background: Novel strategies aimed to overcome trastuzumab (Tz) resistance of HER2+ breast cancer (BC) are needed. Recently, we demonstrated a novel immune evasion strategy used by BC where tumor necrosis factor alpha (TNF) induces upregulation of the transmembrane glycoprotein mucin 4 (MUC4) via NF-kB activation to impair Tz binding that prevents antibody mediated killing of BC cells. Etanercept, a non-selective inhibitor of soluble and transmembrane TNF (sTNF, tmTNF), downregulated MUC4 expression and sensitized de novo Tz-resistant BC xenografts to Tz. Moreover, we showed that MUC4 expression is an independent predictor of poor disease-free survival in patients treated with Tz in the adjuvant setting (Clin Cancer Res 2017, 23:636). Etanercept is immunosuppressive due to off-target effects on tmTNF while selective inhibition of sTNF improves the immune response to the tumor (Cancer Immunol Res 2016, 4:441). Because of the immunosuppressive properties of etanercept, we wanted study if the dominant negative-TNF protein XPro1595 (DN-TNF; also known as INB03) that neutralizes sTNF without affecting tmTNF is able to downregulate MUC4 to inhibit Tz-resistant tumor growth and improve innate antitumor immune response. Methods: To assess the effect of DN-TNF on Tz-resistant HER2+ tumor growth, JIMT-1 cells were s.c. injected in nude mice. When tumors were established, animals were treated with IgG, DN-TNF, Tz or DN-TNF+Tz, i.p. twice a week for one month. Innate immune response was determined by flow cytometry analysis of NK cells activation and degranulation and myeloid-derived suppressor cells (MDSC) subtypes in tumor microenvironment (TME) and in spleen. Tz-dependent NK cells degranulation was assessed in splenocytes using HER2+, Tz-sensitive cell line BT-474 as the target. MUC4 and phospho NF-kB expression was determined by Western blot. Results: Treatment with Tz or DN-TNF had no impact on JIMT-1 tumor growth. However, co-treatment with DN-TNF and Tz resulted in significantly less growth. At day 21st, tumor volume was 75mm3 in DN-TNF+Tz vs 300mm3 control groups. DN-TNF+Tz treatment showed a decrease in myeloid cell infiltration and MDSC phenotype was enriched in the granulocytic-MDSC vs monocytic-MDSC suggesting a less immunosuppressive TME. DN-TNF+Tz administration significantly increased activation and degranulation of tumor infiltrating NK cells. In addition, spleen NK cells from these animals exhibited enhanced Tz-dependent degranulation vs control groups. MUC4 expression was downregulated in tumors treated with DN-TNF and NF-kB phosphorylation was inhibited (all comparisons p Conclusion: These results suggest that targeting sTNF together with Tz treatment improves antitumor immune response reducing tumor burden. Activated NK cells can more effectively attack the tumor due to a less suppressive TME and decreased MUC4 expression enhancing Tz binding in Tz-resistant HER2+ BC. Patients with increased levels of TNF expressing MUC4 in their tumors could be eligible for a combined therapy with DN-TNF and Tz to overcome/avoid resistance to therapy. These results can be translated quickly into the clinic. Citation Format: Schillaci R, Bruni S, De Martino M, Mercogliano MF, Inurrigarro G, Frahm I, Proietti CJ, Elizalde PV. Neutralizing soluble tumor necrosis factor alpha overcomes trastuzumab-resistant breast cancer immune evasion by downregulating mucin 4, improving NK cell function and decreasing myeloid-derived suppressor cells in tumor microenvironment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-20-14.

Morphometric and hydrological variables of a river basin are fundamental tools for water quality management within the basin. The paper aims to provide a method for the calculation of morphometric and hydrological variables based on a sub-basins agglutination strategy. The agglutination respects the topology of the existing drainage network within the hydrographic basin according to Shreve's stream order. Preliminary results are provided: TerraHidro system developed at INPE is used to assess a set of variables, in particular, the morphometric variable Gradient Factor and the hydrological variable Maximum Drainage Order of Strahler. An exemplified application is provided considering the Brazilian Brumadinho dam basin

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease. © 2021 BioScientifica Ltd.. All rights reserved.

Il programma Europeo Copernicus (www.copernicus.eu) è una delle principali fonti di dati open sull'Osservazione della Terra (EO) ed è volto a sostenere importanti progressi sociali ed economici verso l'Unione Europea. Copernicus fornisce una vasta quantità di dati satellitari acquisiti da sei missioni Sentinel, e sei tipologie di servizi che forniscono informazioni pronte per l'uso su diverse tematiche: atmosfera (CAMS), terra (CLMS), clima (C3S), oceani (CMEMS) e sicurezza (CSS). L'articolo descrive le attività preliminari del progetto EO-UPTAKE finanziato dalla Regione Liguria, iniziato nel 2019. Il progetto, coordinato dall' Istituto IMATI del CNR e da GISIG, ha come fine primario lo sviluppo e la diffusione delle competenze rivolte a migliorare l'accesso e la fruizione delle risorse Copernicus e la loro integrazione nei Sistemi Informativi Territoriali e nelle infrastrutture di dati open (e.g. dati.gov.it). Ciò prevede la formazione di un giovane ricercatore per acquisire tali competenze, finalizzata al trasferimento tecnologico nel settore EO. Il progetto si inserisce nel patrimonio informativo del territorio, del settore pubblico e del tessuto produttivo della Regione Liguria: lo scopo è stimolare nuove opportunità di business ed affrontare le attuali sfide sociali, promuovendo al contempo l'attività di ricerca.

BackgroundGlucocorticoids (GCs) are still the mainstay of treatment of Giant Cell Arteritis (GCA), while Tocilizumab (TCZ) has been licensed as the first biologic treatment for GCA. Although GCs are highly effective in GCA, it is well documented the high burden of toxicity of GCs as well as the disease relapse during GC tapering. Therefore, patients with GCA may benefit from GC-sparing treatments[1].ObjectivesThe aim is to compare the efficacy as steroid-sparing agents of Tocilizumab (TCZ) or Methotrexate (MTX) in GCA.MethodsA single-center retrospective study included 39 patients with newly diagnosed GCA confirmed by temporal artery biopsy, temporal artery ultrasound, or TC-PET. Patients were collected from December 2010 to December 2020. The inclusion criterion was the initiation of treatment with MTX or TCZ as GC-sparing agent within the first year of disease, whereas the exclusion criterion was previous treatment with other immunosuppressive agents.Results11 patients received TCZ (162mg/week), while 28 patients MTX (up to 20mg/week) as a GC-sparing agent. Baseline characteristics were reported in Table 1.Table 1.Baseline characteristics of 39 newly diagnosed GCA patients.Median (IQR) or n (%)TCZ (n=11)MTX (n=28)All (n=39)P valueAge, years66 (57-77)72 (66-76)71 (65-76)0.125Female9 (81.8)20 (71.4)29 (74.4)0.504ESR, mm/h89.5 (71-116)51.5 (39.5-88.5)72 (46-92)0.026CRP, mg/L102 (79-169)43.9 (20.8-68)54 (27-102)0.006Fibrinogen, mg/dL605 (381-897)680 (539-800)680 (492-808)0.760≥3 ACR criteria5 (45.5)10 (35.7)15 (38.5)0.718AION3 (27.3)0 (0)3 (0.8)0.018Fever8 (72.7)13 (46.4)21 (53.8)0.138Extra-cranial symptoms7 (63.6)17 (60.7)24 (61.5)1.000TAB positive6 (54.5)13 (46.4)19 (48.7)1.000Halo sign positive5 (45.5)6 (21.4)11 (28.2)0.234TC-PET positive6 (54.5)12 (42.9)18 (46.2)0.676Comorbidities*5 (45.5)15 (53.6)20 (51.3)0.648*Presence of at least one among diabetes mellitus, hypertension, ischaemic heart disease, obesity, or osteoporosis.The follow-up time between groups was 20 (IQR 18.5-24.5) months vs 36 (IQR 24-60.5) months, respectively. At the last medical examination, all patients were in sustained remission, 6/11 (54.5%) and 17/28 (60.7%) had discontinued GCs. The prednisone equivalent dosage of 5 mg/day was achieved at 5 (IQR 2.75-5.5) and 7 (IQR 5-10) months (p-value 0.078), respectively, while discontinuation of GCs was achieved at 7.5 (IQR 6.25-11) and 19 (IQR 14-24) months (p-value 0.015), respectively. No differences were observed as concerns GC-related adverse events at 1 year after the onset of GCA (1 event in 11 patients [9.1%] vs 3 events in 28 patients [10.7%]). In details, GC-related adverse events were development of diabetes (2/4), hypertension (1/4), or osteoporosis (1/4). Two patients in the first group (18.2%) and 9 in the second one (32.1%) experienced at least one relapse (median time to relapse was 6.5 [IQR 5.75-7.25] and 18 [IQR 12-24] months). Relapses required the association of MTX with TCZ (1/11 [9.1%]) or start of TCZ (1/11 [9.1%] in the former group, while they required an increase in steroid dosage (7/11 [63.6%]), switch from MTX to TCZ (1/11 [9.1%]), or reinstatement of MTX therapy after its discontinuation (1/11 [9.1%]) in the latter.Overall, both drugs were well tolerated. 1/11 (9.1%) and 5/28 (17.9%) had discontinued TCZ and MTX, respectively, due to mild and reversible drug-related adverse events (4/6 general malaise or discomfort, 1/6 gastrointestinal symptoms, or 1/6 abnormal liver function tests). No serious infections were observed.ConclusionTCZ showed a faster steroid-sparing effect than MTX. Both immunosuppressants are safe, effective and allow the discontinuation of GCs.References[1]Quartuccio, L.; Isola, M.; Bruno, D.; Treppo, E.; Gigante, L.; Angelotti, F. et al. Treatment Strategy Introducing Immunosuppressive Drugs with Glucocorticoids Ab Initio or Very Early in Giant Cell Arteritis: A Multicenter Retrospective Controlled Study. J. Transl. Autoimmun.2020, 3, 100072, doi:10.1016/j.jtauto.2020.100072.Disclosure of InterestsNone declared

BackgroundThe ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire is a 29-item disease-specific PRO measure for AAV[1]. The Italian version of the AAV-PRO questionnaire (AAV-PRO_ita) was translated in collaboration with Oxford and Bristol University (UK) and was preliminarily tested on a single-center Italian cohort[2].ObjectivesThe main objective of this multicentric study was to assess the internal consistency, feasibility, and reliability of the AAV-PRO_ita in a large cohort of Italian AAV patients. The secondary objective was to investigate the clinical characteristics of AAV patients associated with AAV-PRO_ita domains.MethodsThe AAV-PRO_ita is describes the following disease domains: (1) organ-specific and systemic symptoms and signs (SSS); (2) physical function (PF); (3) social and emotional impact (SEI). In this study, Italian-speaking AAV patients were recruited from Italian Centres (N=13) with a large experience in the diagnosis and treatment of systemic vasculitis, belonging to the Vasculitis Study Group of the Italian Society of Rheumatology. Inclusion criteria were: a confirmed diagnosis of GPA, MPA, or EGPA; ANCA positivity in at least once occasion or biopsy-proven AAV; and age ≥18 years old. Participants completed the AAV-PRO_ita at three different time-points: baseline, after 5-7 days, and at month 3.Results229 AAV-patients (56.3% women) with a median age of 61 (IQR 51-72) were recruited and completed the questionnaires. The subtype of AAV was mainly GPA (131, 57.2%), followed by EGPA (58, 25.3%), and MPA (40, 17.5%). Median BVASv3 at baseline was 0 (IQR 0-3), whereas the median BVASv3 at the onset of disease was 14 (IQR 9-20). Participants had a median duration of disease of 67 (IQR 24-126) months. Patients who experienced at least one relapse, one hospitalization, and one severe infection were 40.2%, 53.3%, and 24%, respectively. 83% of the patients were on immunosuppressant therapy and 71.6% were still receiving glucocorticoids (GC).AAV-PRO_ita questionnaire had good internal consistency (Cronbach’s Alpha range 0.81-0.93) and good test-retest reliability (ICCs range 0.93-0.96). Item response rates were high overall (maximum 0.87% missing data), supporting the feasibility of the questionnaire.Concerning the domains of the questionnaire, female AAV patients scored higher (i.e. worse) in all three domains, especially in the SEI domain (p-value0.3, p-valueConclusionThe AAV-PRO_ita questionnaire is a new 29-item, disease-specific PRO measure for use in AAV in the Italian language. It is a self-administered Italian questionnaire with good internal consistency, feasibility, and reliability. AAV-PRO_ita proved to be a useful tool to explore the AAV patient’s perception of quality of life, and it could become an important way of measuring the unmet needs of AAV patients.References[1]Robson, J.C. et al. Validation of the ANCA-Associated Vasculitis Patient-Reported Outcomes (AAV-PRO) Questionnaire. Ann. Rheum. Dis.2018, 77, 1157–1164, doi:10.1136/annrheumdis-2017-212713.[2]Treppo, E.; Palese, A.; Vita, S.D.; Quartuccio, L. AB0392 PRELIMINARY VALIDATION OF THE ITALIAN VERSION OF ANCA-ASSOCIATED VASCULITIS PATIENT-REPORTED OUTCOME (AAV-PRO_ita) QUESTIONNAIRE: FATIGUE AND CHRONIC PAIN AS UNMET NEEDS BY CURRENT TREATMENTS. Ann. Rheum. Dis.2021, 80, 1224–1224, doi:10.1136/annrheumdis-2021-eular.2123.AcknowledgementsWe thank the Italian Study Group on Systemic Vasculitis.Disclosure of InterestsNone declared

We report a 3-month-old male with Down syndrome (DS), prolonged jaundice and poor weight gain, that showed biliary lithiasis and undiagnosed congenital hypothyroidism (CH).CH should be considered in DS, especially in presence of gastrointestinal symptoms or malformations. Clinicians should be aware of the increased risk of gallstones in hypothyroid children with DS, even in neonatal age.

The management of latent tuberculosis (LTBI) in children represents an important issue for paediatricians because of the disease burden, the lack of a gold standard for the diagnosis and the high annual risk of progression to active disease. Areas covered: A review of English language articles on LTBI in children, published between the 1st of January 2010 and the 1st of July 2016, was conducted using multiple keywords and standardized terminology in PubMed database. This review provides an updated overview of the available tests for LTBI diagnosis in children, management strategies and treatment options. Expert commentary: Two tests are available for LTBI diagnosis: tuberculin skin test and interferon-gamma release assays, both with a suboptimal specificity and sensitivity, and both with the lack of capability in distinguishing between infection and disease. Several new markers have been identified but further studies are needed. Among all treatment regimes, because of the high safety and efficacy profile showed and to avoid the poor completion rate, the treatment with a three-month course of isoniazid and rifampicin is currently recommended. New vaccines are needed because of the spread of the disease despite BCG vaccination in high risk countries. Currently, 15 new vaccines are in the pipeline.

Round table debate “Transformation of political values in the EU: pros and cons” was held on February 13 2017 on the Faculty of the humanities and social sciences of Peoples’ Friendship University of Russia (RUDN University). The “Round-table” debate has been realized in the frame of the project “Transformation of the social and political values: the EU practice” (project number: 575361-EPP-1-2016-1-RU-EPPJMO-MODULE), Erasmus+ Jean Monnet Actions. Jean Monnet Module “Transformation of the social and political values: the EU practice”.

Human error is as old as humanity itself and occurs on a daily basis, whatever we are doing. Recognising our fallibility is the first step to understanding error and ways to reduce it. The term "never event" is, therefore, a misnomer as these serious adverse incidents can never be eliminated completely. Up to 1 in 20 hospital admissions includes some form of error, and while many have little detrimental effect on patients' care (such as forgetting to write a discharge summary), 6% are serious. Many medical errors could have been prevented through the understanding and application of human factors (HF) including (but not exclusively) better team working, situational awareness, and the lowering of authority gradients. In this article we provide an overview of error and introduce the concept of threat and error management (TEM) which is used in other, high-reliability organisations, and provides three layers of defence to reduce the effect or severity of any error. We discuss how to try and avoid medical error in the first place (the first line of defence), trap errors when they occur, and mitigate the consequences of any error to help further safeguard our patients.

Aims: Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. Methods: MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. Stakeholders: Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. Results: MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU grants (2018): MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). Lessons learnt: (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases. © 2019 The Author(s).

The generation of regular and irregular inflected verb-forms has been taken as a crucial test between models of inflection in the mental lexicon, namely approaches which invoke different mechanisms for regular and irregular forms (rule-based procedures vs. recovery of whole forms stored in an associative network) and accounts which postulate a single procedure for all forms. An alternative hypothesis suggests that inflectional processes are explained by membership of words to clusters, for instance, Italian inflectional classes (conjugations). In a behavioural and a rapid event-related fMRI experiment, participants overtly generated the past participle of verbs from the three Italian conjugations. Results showed that the cognitive operations and the neural substrate underlying inflectional processes rely on specific properties of inflectional classes. Different patterns of cortical activations elicited by verbs from different conjugations were detected for the first time in the left middle frontal gyrus, left pre-supplementary motor area and left anterior cingulate cortex.

SUMMARYTo evaluate measles incidence and its relevant changes over a 14-year period (2000–2014), we analysed data from the regional hospital discharge database on children and adults hospitalized in Tuscany, Italy. A total of 181 paediatric and 413 adult cases were identified. Despite all the efforts towards regional measles elimination, we observed that the overall measles hospitalization rates for children and adults living in Tuscany globally increased from 0·45 to 0·85/100 000 during the study period (P = 0·001) showing fluctuations due to periodic measles outbreaks. Data stratified by age group showed that the hospitalization rate significantly increased in young adults over the study period, confirming an increase in susceptibility to measles in this subpopulation. Conversely, no statistically significant difference was observed in the hospitalization rate in the other age groups. However, children aged

Background Nontuberculous mycobacteria (NTM) are pathogens that commonly affect the paediatric population and its most frequent manifestation is a cervicofacial lymphadenopathy. With the improvement of technologies, new species have been recently identified. Case presentation We report the first case of NMT lymphadenitis in a child caused by Mycobacterium marseillense, a newly described species belonging to Mycobacterium avium complex. Conclusions Improving the identification of these newly discovered mycobacteria, further information will be available about their clinical involvement and their best treatment.

mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary. © 2018 The Author(s).

Artemisia vulgaris L and Artemisia annua L (Chinese: qinghao) are similar plants of the Asterbaceae family. Artesunate, a semi-synthetic derivate of artemisin which is the active principle extract of the plant qinghao, has antimalarial properties. Some cases of severe allergic reactions to artesunate have been described. The purpose of this study was to evaluate the association between positive skin tests to Artemisia vulgaris L allergen and a preparation of injectable artesunate. A total of 531 children were skin prick tested with inhalants (including Artemisia vulgaris L), foods, and artesunate. Among the 59 patients positive to Artemisia vulgaris L only one child was also positive to artesunate. No child was positive to artesunate in those negative to Artemisia vulgaris L. We conclude that Artemisia vulgaris L sensitization is not associated with sensitization to artesunate; consequently, skin test to artesunate should not be carried out before using the drug considering the rare allergic reactions.

In recent decades, urban sprawl became a serious European-wide problem, not only due to total land taken, but also due to its spatial distribution patterns and quality of the land consumed. Land use efficiency is becoming a prime political objective at both European and city level, and the EU Land Communication aims to establish “zero net land take” across the EU by 2050. Land is a finite resource and therefore the sprawl has to be regulated. This can be realized through careful management of urban land, applying the concept of urban land transformation. The other main concern of sustainable city panning is the preservation and improvement of the Green Infrastructure in the cities. Only such approaches can assure sustainable development of European urban and suburban landscape as well as of quality of environment and life in the cities in the long term perspective. The EU funded URBIS project (ICT PSP 2014-17) targets these issues and focuses on investigation of open space potential in urban areas, and the opportunities for inner development, as well as on investigation of urban green systems. URBIS delivers EO based methodologies and tools to provide accurate up-to-date intelligence that is comparable across European cities to support the definition and implementation of sustainable planning and governance strategies in cities and city-regions throughout Europe. The present paper focuses on the role, within the URBIS methodologies and products, of remote sensing image analysis. Classification, feature extraction, and multitemporal analysis approaches are combined to characterize open, green, and sealed areas within large urban zones.

The three Americas have 46% of all the world fresh water. South America has 60% of three Americas fresh water regarding 27.6% of world fresh wa-ter. Brazil has 28% of America's fresh water and 12% of world fresh water. The existence of this huge amount of water is directly related to various situations of floods, occurring in cities and in rural areas, at fast or slows pace. Those floods, which can cause major social and economic damage, must be studied and whenever possible prevented. This work aims to illustrate the planned activity of a bilateral collaboration between two Brazil (INPE) and Italian (CNR-IMATI) Institutions aiming at identifying methodologies fostering drainage data sharing, use and re-usage at different stages of the data processing pipelines in order to create a seamless cross-sectorial data "provider/consumer" chain. In particular, it illustrates the preliminary results of the research activities aiming at making available South America drainage network data and the Amazonian basin. Such data, produced by the TerraHidro tool developed by INPE, is going to be published as Open Data, thus addressing the implementation of the Bra-zilian e-government initiative about data transparencies according to Law no. 12.527, of November 18, 2011. The strategy of Brazil and the European Commission about "free and open public access of information" are also take into account. Moreover, the Implementing Rules of INSPIRE are considered in order to meet the scientific and technological policy between Brazil and European Commission. The approach aims at producing, publishing and reusing territorial infor-mation created by INPE about drainage resources. In a medium-long term, this methodology aimed at establishing a consolidated point of access of territorial interlinked maps and geo-localized data and metadata-related information. The implemented strategy foresees: o"Documentation of data with proper metadata needed for third party application", by covering issues such as provenance, quality, versioning (e.g., GEO-DCAT-AP, W3C-DQV, W3C-PROV); o"Fostering the data publication on the Web according to the (Linked) Open Data initiative", by adopting W3C best practices for (Spatial) Data on the Web; o"Data semantic enrichment" considering Linked Data and ontology as lightweight Semantic Web tools for the semantic enrichment of the Drainage Data. The expected result is an enrichment of drainage datasets, and in particular of Amazonia with 5m resolution produced by INPE, enhancing data dissemination among the different communities working on cross-target discipline (e.g. climate change, water.

BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P

Background SS and LC contributed equally to this manuscript. Hypovitaminosis D is common in the general population. Although many studies on 25-hydroxyvitamin D (25(OH)D) are available on systemic lupus erythematosus (SLE), few data are reported in juvenile-onset SLE (JSLE) patients. Design This study aimed to assess serum 25(OH)D levels in JSLE patients and to identify risk factors for vitamin D deficiency in this population. Methods Forty-five Caucasian JSLE patients (36 females, nine males; mean age 18.9 ± 6.3 years) and 109 age- and sex-matched healthy controls entered the study. Dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine, serum calcium and phosphate, bone-specific alkaline phosphatase (BSAP), parathyroid hormone (PTH), and 25(OH)D were assessed. The data were compared with an age- and sex-matched control group including 109 Caucasian healthy subjects. Results JSLE patients exhibited lower 25(OH)D levels than controls ( p Conclusions Patients with JSLE have significantly lower 25(OH)D levels than controls. Therefore, vitamin D supplementation may be useful to normalize bone mass and quality in subjects with JSLE.

Allergic reactions associated to the use of macrolides are uncommon; in particular only two cases of anaphylaxis with erithromycin and clarithromycin have been reported to date. The aim of this study was to investigate macrolide-induced anaphylaxis. Between December 2007 and December 2011, 136 consecutive children were referred to the Allergy Unit of A. Meyer Children's Hospital because of a past history of reactions to macrolides. Allergy work-ups were carried out according to the European Network for Drug Allergy protocol. Anaphylaxis was diagnosed according to the clinical criteria proposed by Sampson et al. and graded according to Brown SGA et al. Sixty-six out of 136 patients completed the allergologic work-up and among them we investigated three cases of anaphylaxis due to azithromycin which included one child with anaphylaxis to both clarithromycin and azithromycin. In two of the children with anaphylaxis, the diagnosis was only confirmed with the skin prick test, the third was positive to the Intradermal Test. The azithromycin allergy shows a surprisingly high sensitivity to the in-vivo tests. Moreover, this study shows that cross-reactivity may occur between different macrolidic molecules; it has even been suggested that macrolide allergies are unlikely to be class allergies.

Macrophage activation syndrome is a potentially fatal clinical syndrome caused by an excessive activation and proliferation of macrophages and T cells, leading to an exaggerated inflammatory reaction. It is well known that it can complicate the course of different conditions, especially autoimmune, lympho-proliferative, infectious diseases and drugs. Many infective pathogens can trigger the syndrome but the association with malaria has rarely been described, especially in children. We report a child with severe malaria complicated by MAS, in whom the clinical appearance of this syndrome could be considered as worsening of malaria itself. Furthermore, the use of steroids as first choice drugs in this complication, but arguable in malaria, has been highlighted. Clinicians should be aware of this syndrome when malaria does not respond to conventional therapy, since early diagnosis and prompt treatment may dramatically reduce the mortality associated with this condition.

Presentiamo le attivit`a del gruppo di ricerca denominato "Shape and Semantics Modelling" operante presso la sezione di Genova dell'Istituto di Matematica Applicata e Tecnologie Informatiche "E. Magenes" del Consiglio Nazionale delle Ricerche.

La missione dell'Istituto di Matematica Applicata e Tecnologie Informatiche "E. Magenes" (IMATI), con le sue tre sezioni di Pavia, Milano e Genova, è quella di fornire le conoscenze e le infrastrutture per lo sviluppo e la diffusione della matematica applicata e dell'informatica come strumenti per affrontare le sfide provenienti dalle applicazioni in campi diversi come la medicina e la biologia, l'ingegneria, le scienze sociali, il clima e l'ambiente e i beni culturali.

Business archives are of utmost importance for the cultural development of a country and represent valued sources for historical research; however, their preservation and access remain a challenge to be faced. The archive content description has to take into account that its understanding might be difficult for users with different cultural background and skill levels. The paper proposes a replicable methodology for the definition of a knowledge model aimed at providing a common understanding of the content of historical industrial archives for a diverse user community. The knowledge model has been formalized in ontology to support tools for data searching.

The role of interferon-gamma release assays (IGRAs) for immunologic diagnosis of tuberculosis in children is under debate. We carried out a narrative review on the studies on IGRAs in paediatric populations. A literature search was conducted using multiple keywords and standardized terminology in Medline, EMBASE and Cochrane databases, up to January 27th, 2011. Study quality was assessed using the MOOSE checklist and results of relevant studies were summarized. Sixty-seven paediatric studies (study population ranging from 14 to 5,244 children) were identified. Non-commercial ELISPOT assay (by means of ESAT-6 and CFP-10 antigens) had been carried out in 11 studies. QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-tube (QFT-G-IT), and T-SPOT.TB assays had been performed in 10, 44 and 18 studies, respectively. Most studies reported higher specificity of IGRA than tuberculin skin test (TST), but interpretation of the results is complicated by the fact that a gold standard for the diagnosis of latent TB is lacking. The reported sensitivity for active TB ranged from 51-93 percent for QFT-G/QFT-G-IT and 40-100 percent for ELISPOT assays, suggesting that a negative IGRA result may not exclude tuberculosis. Combining TST and IGRA results increased the diagnostic sensitivity. Rates of indeterminate results largely varied (0 to 35 percent). Most of the studies on young (less than 5 years) or immune-compromised children reported a proportion of indeterminate results exceeding 4 percent. Agreement among TST and IGRA, assessed by the k statistics, ranged from -0.03 to 0.87. Higher rates of discordance were reported in BCG-vaccinated than in non-BCG-vaccinated children. Studies on children less than 5 years and immunocompromised children reported conflicting results, as did studies on serial IGRA determinations. Despite the large amount of literature data, the role of IGRA in the pediatric population is still unclear, especially in young children. Combined use of TST/IGRA may increase diagnostic sensitivity but interpretation of discordant results remains a challenging issue.

We report the case of a primary metastatic renal solitary fibrous tumour (SFT) and present a cumulative analysis of the literature. A 68-year-old woman presenting with a history of flank pain was diagnosed with a 7 cm renal mass. Further staging showed liver, lung and bone metastases. The patient underwent radical nephrectomy. Microscopically, the tumour consisted of pleomorphic, high-grade spindle cells with high mitotic activity, tumour necrosis and dense collagenous bands. Immunohistochemistry showed the strong expression of CD34 and vimentin, a weak expression of bcl-2 and CD99, and no expression of smooth muscle actin, desmin, S-100, pan-cytokeratin, and epithelial membrane antigen. These findings are consistent with an SFT. For the cumulative analysis, a total of 46 renal SFTs from 35 reports were analysed. Median age at the time of surgery was 52 years and 63% of the patients were female. Sixty-two percent of the tumours were symptomatic, most commonly with flank / back pain (24%). Median tumor size was 6.4 cm. Histologically, 91% of the SFTs were benign and 9% were malignant. One patient died of the disease, while 90% are alive without evidence of disease.

In vivo exposure to microorganisms resident in the oral cavity is considered as a possible cause of Kawasaki disease (KD), and some epitopes derived from streptococci display homology with Factor H of Complement. Additionally, calprotectin, a major calcium binding protein released by neutrophils and activated monocytes, could be directly involved in endothelial damage occurring in KD. The aim of our study is to evaluate the percentages of IFN-γ+ and/or TNF-α+ lymphocytes and double positive calprotectin/TNF-α monocytes (CD14+) after in vitro stimulation with streptococcal- and/or Factor H-derived peptides, in patients with acute KD. Peripheral Blood Mononuclear Cells (PBMCs) obtained from KD patients and febrile controls were stimulated in vitro with peptides. After culture, cells were collected, stained with fluorochrome-labelled monoclonal antibodies against CD3, CD14, calprotectin, IFN-γ and TNF-α, and cytofluorimetric analyses were performed. Our results showed increased percentages of TNF-α+/IFN-γ+ lymphocytes in KD patients in respect to controls when PBMCs were stimulated with streptococcal or Factor H-derived epitopes. In addition, also calprotectin+/TNF-α+ monocytes from KD patients were activated after PBMC in vitro stimulation. These findings lead us to speculate that some peptides, derived from oral streptococci and cross-reactive with the human Factor H of Complement, could induce lymphocyte and monocyte activation potentially involved in the pathogenesis of KD. Our results should be confirmed by further studies enrolling more patients and controls than those analyzed in our study.

Background The genetic background, transmissibility and virulence of MRSA have been poorly investigated in the cystic fibrosis (CF) population. The aim of this multicentre study was to analyse MRSA strains isolated from CF patients attending nine Italian CF care centres during a two-year period (2004–2005). All CF patients infected by MRSA were included. Method Antibiotic susceptibility testing, SCC mec typing, Panton–Valentine Leukocidin (PVL) production, and Multi Locus Sequence Typing (MLST) analysis were carried out on collected isolates (one strain per patient). Results One hundred and seventy-eight strains isolated from 2360 patients attending the participating centres were analysed. We detected 56 (31.4%) SCC mec IV PVL-negative strains, with a resistance rate of 80.3% to clindamycin and of 14.5% to trimethoprim/sulphamethoxazole. MLST analysis showed that many isolates belonged to known epidemic lineages. The largest clone grouping of 29 isolates from 6 centres had the genetic background (ST8-MRSA-IV) of the American lineages USA300 and USA500, thus demonstrating the diffusion of these strains in a population considered at risk for hospital associated infections. Conclusions Known MRSA epidemic clones such as USA600, USA800, USA1100, and UK EMRSA-3 were described for the first time in Italy. The diffusion of MRSA strains with high pathogenic potential in the CF population suggests that analysis of the MRSA strains involved in pulmonary infections of these patients is needed.

Objective To define normal values for respiratory resistance (R(rs)) and reactance (X(rs)) and bronchodilator response (BDR) in a population of healthy Italian preschool children using a commercially available forced oscillation device Methods R(rs) and X(rs) were measured in kindergartens in Viterbo Italy Regression analysis was performed taking into account height weight age gender and reference equations calculated The coefficient of repeatability (CR) between two tests performed 15 min apart was calculated in a subset of children BDR was assessed by repeating the measurements 15 min after the administration of 200 mu g of inhaled salbutamol and calculated as an absolute change in R(rs) and X(rs) at 8 Hz as a percent change in baseline and as a change in Z score calculated from the reference equations Results Lung function was attempted in 175 healthy children and successful in 163 (81 male median age 4 8 range 2 9-6 1 years) R(rs) and X(rs) at 6 8 and 10 Hz were related to height but not other variables The CR was 1 53 hPa s L(-1) for R(rs8) and 091 hPa s L(-1) for X(rs8) The 5th percentile for absolute R(rs8) BDR was -3 16 hPa s L(-1) whereas the 95th percentile for absolute X(rs8) BDR was 2 25 hPa s L(-1) These cut off values corresponded to a change in the Z score of -1 88 and 2 48 respectively Conclusions We have established reference equations for R(rs) and X(rs) in healthy Italian preschool children using forced oscillations We recommend a change in Z score of -1 88 for R(rs8) and 2 48 for X(rs8) as cut off values for a positive BDR Pediatr Pulmonol 2010, 45 1086-1094 (C) 2010 Wiley Liss Inc

We conducted a cross-sectional study on 43 Italian perinatally human immunodeficiency virus-type 1 (HIV-1) infected children receiving highly active antiretroviral therapy (HAART) and 26 age-matched healthy controls to explore CD1d-restricted NKT subsets. CD4+CD1d-rectricted natural killer (NKT) cell depletion was evidenced in 26 HIV-1 infected children with active viral replication despite HAART. Conversely, no alteration was evidenced in 17 children with undetectable viral load, suggesting full recovery in both CD4+ and CD4− CDld-rectricted NKT cell subsets. The loss of CD4+ NKT cells in unresponsive children may have clinical consequences, including autoimmune disorders or cancer development. Future therapeutic perspectives are suggested.