931 research outputs found

    Clinical and functional characterisation of a novel TNFRSF1A c.605T > A/V173D cleavage site mutation associated with tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), cardiovascular complications and excellent response to etanercept treatment.

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    Objectives: To study the clinical outcome, treatment response, T-cell subsets and functional consequences of a novel tumour necrosis factor (TNF) receptor type 1 (TNFRSF1A) mutation affecting the receptor cleavage site. Methods: Patients with symptoms suggestive of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and 22 healthy controls (HC) were screened for mutations in the TNFRSF1A gene. Soluble TNFRSF1A and inflammatory cytokines were measured by ELISAs. TNFRSF1A shedding was examined by stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol 12-myristate 13-acetate followed by flow cytometric analysis (FACS). Apoptosis of PBMCs was studied by stimulation with TNFa in the presence of cycloheximide and annexin V staining. T cell phenotypes were monitored by FACS. Results: TNFRSF1A sequencing disclosed a novel V173D/ p.Val202Asp substitution encoded by exon 6 in one family, the c.194–14G.A splice variant in another and the R92Q/p.Arg121Gln substitution in two families. Cardiovascular complications (lethal heart attack and peripheral arterial thrombosis) developed in two V173D patients. Subsequent etanercept treatment of the V173D carriers was highly effective over an 18-month follow-up period. Serum TNFRSF1A levels did not differ between TRAPS patients and HC, while TNFRSF1A cleavage from monocytes was significantly reduced in V173D and R92Q patients. TNFa-induced apoptosis of PBMCs and T-cell senescence were comparable between V173D patients and HC. Conclusions: The TNFRSF1A V173D cleavage site mutation may be associated with an increased risk for cardiovascular complications and shows a strong response to etanercept. T-cell senescence does not seem to have a pathogenetic role in affected patients

    Streamlined management of the built environment: the district and the building logbook as risk prevention tools

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    Management of information related to the real properties is a key topic both in private and public sector. In the Italian context, can be spotted an overall lack of organisation of the information concerning the real estate assets, from the building scale, to the neighbourhood, until the city and the territory. Moreover, management of the urban environment is characterised by the presence of different players asking for common needs in management and use of data. This research aims at proposing the Building Logbook and the District Logbook as tools for collection, organisation and management of information, in a perspective of streamlined real estate management process. Moreover, the Logbooks can be conceived as tools for risk management. They should be exploited especially in technical management phase of assets, as well as in the verification of compliance with laws, authorisations and licenses, since these issues often bear to disputes between public and private players. Often disputes concern that areas where the competences and responsibilities among different players are not clear (connections to system, property boundaries, licenses, occupation of public land etc.). In this situations, information management assumes a key role, since it could be a powerful mean to clarify responsibilities among players. Therefore, the scope of the research concerns the investigation on the relationships and related information flows among stakeholders in the real estate field. Altogether, it can be stated that the logbooks can streamline processes in the use phase of assets, despite they could be intended as rigid control tools. Through this paper these issues will deepened and clarified. The paper concludes with some considerations concerning the possible integration of the Logbooks in a digital environment, following the BIM approach

    The building materials’ and components’ database for an evidences-based design approach

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    The design process has always to meet, since the preliminary approaching step, every specific requirement which is foreseen for the building to realize. In a certain way, this operation represents an every time different prototype which varies according to the design demands for the considered room and the carried function, but also according to the used building materials: such an approach is already difficult by itself, but if we consider that at present the availability of technical information about building materials, components and systems is often incomplete or lost among many documents or even absent, it is evident that the designer’s activity becomes very uneven. That is the reason why, the definition of a database for building materials in which indicating each informative attribute to be considered becomes fundamental in order to: - provide a correct, univocal, clear and complete information for every building stakeholder; - help manufacturers to individualize the real needed information to join to their products, so to allow an easier comparison among products themselves and, as a consequence, to push towards a better quality of the entire building process (improving production, design, but also management). The paper deals with an analysis of the necessary information for designers and for maintenance planners, providing different levels of deepening according to the intended use. A particular attention will be paid on the so called “evidences-based design” which gives the opportunity to point out and to consider the most meaningful design matters, making an aware choice of building materials, components and systems. The International Service Life Data Base developed by CSTB with Politecnico di Milano will be reported as a tool for service life prediction, and buildings’ management

    Dynamic Facility Condition Index calculation for asset management

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    Aim of this research is to investigate the possibility of dynamically computing the Facility Condition Index (FCI) using a database of maintenance operations and costs of fabric and services components. This would lead to an instrument able to support decision making during asset and portfolio management because FCI is widely considered a good indicator for monitoring assets and portfolios conditions; so being able to efficiently calculate and update it is fundamental for a proper asset management. There are many ways to benchmark assets condition, but most of them are qualitative and lead to ratings in percentage, that need to be further elaborated to be connected to annual OM&R costs. The FCI can be considered an economic rating, based on money paid for maintenance, repair and replacement performed over the current asset value. The objective is to make an appraisal of the maintenance costs in a dynamic way, so to be able to examine multiple scenarios and make forecasts; the facility value comes from market appraisals with some coefficient applied, if need be. This calculation procedure, together with a maintenance operations and costs database developed by the authors (either forecasted or real costs), can be used by asset managers to support decisions about maintenance and repair actions to be undertaken. This paper shows preliminary results of this research, with the help of a case study. Further correlations should be investigated, even if this calculation procedure leads to an effective management. The calculation procedure and the database organization are an original work of the authors, as well as the case study used to show the results. In addition to this, connections among the indicators provided and BIM (Building Information Modelling) models are analyzed

    The maintenance paradox

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    This research will spot main features of servitization in real estate, placing main emphasis to current and future development of the trend. In manufacturing the servitization process has already been studied since the late 1980’s, whereas in real estate is a phenomenon not yet been clearly defined yet. Despite being a market characterised by low speed innovation, currently some changings in management of the built environment can be noticed: with new business models and financing structures, a shifting from a product-oriented market to a service-oriented one can be spotted. Therefore, through this research will be investigated the servitization process, with regard to maintenance management, no longer conceived as an optional non-core activity, after the transaction of the asset, but as part of the services included in the purchasing of the building and its facilities. Accordingly, the building is conceived more and more as a complex tangible and intangible entity, not only characterised by its production and location value, but also by its capability to offer provide users with a wide array of services to users. Thus, after a phase featured by the willingness to acquire legitimacy in the building process by the maintenance operators, we are witnessing to the maintenance paradox: the servitization of business model in real estate, leading to performing “the maintenance without maintenance”. The paper concludes with some considerations on future developments of the research and trends in the real estate marke

    Stéphane Mallarmés Raumkonzept in zeitgenössischen Positionen

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    Die Diplomarbeit behandelt das Gedicht „Un coup de Dés jamais n’abolira le Hasard“ des französischen Dichters Stéphane Mallarmé und dessen Einflüsse auf die zeitgenössische Kunst anhand von zwei Positionen wichtiger Künstler des 20. und 21. Jahrhunderts: Marcel Broodthaers (Belgien) und Edward Ruscha (Kalifornien). Das Gedicht erstreckt sich über zwölf Seiten und wird von Doppelseite zu Doppelseite gelesen, da die Zeilen über den Falz hinweg verlaufen. Das Gedicht legt erstmals mehr Wert auf Positionierung der Wörter, ihre lautbildlichen Qualitäten und das gesamte Layout des Buches als auf den Inhalt des Textes, der sekundär wird. Während sich Broodthaers in seinem Werk direkt und oft auf Mallarmé das Gedicht bezieht, erwähnt Ruscha Mallarmé nie als Einfluss, hat aber formale und ikonographische Elemente in seinem Werk, die auf Mallarmés Umgang mit dem Buch als Objekt und dem Wort als Objekt im Raum der Seite zurückgeführt werden können. Das hier vordergründig besprochene Werk von Broodthaers ist dessen Version des „Coup de Dés“ in der er den Text durch schwarze Balken ersetzte. Bei Ed Ruscha werden sowohl seine Ölgemälde von Worten und Sätzen in scheinbar leeren oft farbigen Hintergründen besprochen, als auch seine Künstlerbücher. An den beiden Positionen wird beispielhaft ergründet, warum das Gedicht zu einem Grundlagentext der Moderne und einer Inspirationsquelle für Künstler des 20. und 21. Jahrhunderts wurde und blieb.This thesis discusses the poem „Un coup de Dés jamais n’abolira le Hasard“ by french poet Stéphane Mallarmé. It’s influence on contemporary art is exemplified with two important artists of the 20th and 21st century: Marcel Broodthaers (Belgium) and Edward Ruscha (California). The poem is read on twelve double pages, with its lines crossing the fold of the book. For the first time the position of the words, their onomatopoeic quality and the overall layout of the book are much more important than the content of the text. While Broodthaers makes direct reference to Mallarmé and his poem, Ruscha, without mentioning Mallarmé as an influence, has formal and iconographic elements in his work that can be traces back to Mallarmé’s handling of the book as object and the word as object on the page. Broodthaers’ crucial work for this thesis is his version of the poem, where the text is substituted by black bars. As far as Ruscha is concerned, the thesis includes his canvases of words and phrases in apparently empty coloured space as well as his artist books. Both positions help to explain, why the poem is crucial text of modernism and a source of inspiration for the artists of the 20th and 21st century

    GeoBIM for built environment condition assessment supporting asset management decision making

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    The digital transformation in management of the built environment is more and more evident. While the benefits of location data, from Building Information Modelling or Geographical Information Systems, have been explored separately, their combination - GeoBIM - in asset management has never been explored. Data collection for condition assessment is challenging due to quantity, types, frequency and quality of data. We first describe the opportunities and challenges of GeoBIM for condition assessment. The theoretical approach is then validated developing an integrated GeoBIM model of the digital built environment, for a neighbourhood in Milan, Italy. Data are collected, linked, processed and analysed, through multiple software platforms, providing relevant information for asset management decision making. Good results are achieved in rapid massive data collection, improved visualisation, and analysis. While further testing and development is required, the case study outcomes demonstrated the innovation and the mid-term service-oriented potential of the proposed approach

    Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis

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    Antibodies directed against citrullinated vimentin are members of the family of autoantibodies reactive with citrullinated proteins and are among the most specific serological markers for the diagnosis of rheumatoid arthritis (RA). This study was performed to test the diagnostic value of a newly developed enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with a second-generation anti-cyclic citrullinated peptides (anti-CCP2) ELISA test system. Blinded sera from 631 patients (409 consecutive out-patients and 222 randomly selected stored sera) with RA (n = 164) and non-RA (osteoarthritis [n = 120], polymyalgia rheumatica/giant cell arteritis [n = 80], spondyloarthritis [n = 36], and other inflammatory rheumatic or non-inflammatory disease [n = 67]) were tested for the presence of anti-MCV and anti-CCP2 antibodies according to the manufacturers' instructions. The diagnostic performance of the anti-MCV was comparable with the anti-CCP2 assay for the diagnosis of RA according to the calculated area under the curve (0.824; 95% confidence interval (CI) 0.778–0.870 versus 0.818; 95% CI 0.767–0.869) as analysed by receiving operating characteristic curve. When categorised with a cutoff value of 20.0 U/ml (as recommended by the manufacturer), sensitivity and specificity of the anti-MCV ELISA were 69.5% (95% CI 61.9%–76.5%) and 90.8% (86.9%–93.8%), respectively, compared with 70.1% (62.5%–77.0%) and 98.7% (96.7%–99.6%) of the anti-CCP2 assay. Using the cutoff values of 19.0 U/ml and 81.5 U/ml for the anti-MCV test to obtain a sensitivity and specificity identical to the anti-CCP2 assay, showed a reduced specificity (89.8%; 85.8%–92.9%) and sensitivity (53.7%; 45.7%–61.5%), respectively, of the anti-MCV ELISA compared with the anti-CCP2 test. In conclusion, the serum ELISA testing for anti-MCV antibodies as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test

    BIM AND GIS INTEGRATION FOR INFRASTRUCTURE ASSET MANAGEMENT: A BIBLIOMETRIC ANALYSIS

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    The integration of Building Information Modelling (BIM) and Geographical Information Systems (GIS) is gaining momentum in digital built Asset Management (AM), and has the potential to improve information management operations and provide advantages in process control and delivery of quality AM services, along with underlying data management benefits through entire life cycle of an asset. Work has been carried out relating GeoBIM/AM to buildings as well as infrastructure assets, where the potential financial savings are extensive. While information form BIM maybe be sufficient for building-AM; for infrastructure AM a combination of GIS and BIM is required. Scientific literature relating to this topic has been growing in recent years and has now reached a point where a systematic analysis of current and potential uses of GeoBIM in AM for Infrastructure is possible. Three specific areas form part of the analysis – a review of BIM and Infrastructure AM and GIS and Infrastructure AM leads to a better understanding of current practice. Combining the two, a review of GeoBIM and Infrastructure AM allows the benefits of, and issues relating to, GeoBIM to be clearly identified, both at technical and operational levels. A set of 54 journal articles was selected for in-depth contents analysis according to the AM function addressed and the managed asset class. The analysis enabled the identification of three categories of issues and opportunities: data management, interoperability and integration and AM process and service management. The identified knowledge gaps, in turn, underpin problem definition for the next phases of research into GeoBIM for infrastructure AM

    Association of clinical, imaging and laboratory parameters with adverse effects of glucocorticoid therapy in patients with giant cell arteritis

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    BackgroundGiant cell arteritis (GCA) is characterized by inflammation of large and medium vessels. First-line therapy for the treatment of GCA are glucocorticoids, which are effective while potential adverse effects should be considered, especially during long-term use. The aim was to investigate the incidence of glucocorticoids’ adverse effects and potential predictors for them.Materials and methods138 GCA patients were retrospectively evaluated for newly developed glucocorticoid adverse effects in 2020. Potential predictors, defined as initial glucocorticoid pulse therapy, relapse of GCA and concomitant polymyalgia rheumatica as well as parameters of inflammation and endothelial dysfunction, including pulse-wave velocity and intima-media-thickness, were measured in 2012.ResultsPotential new glucocorticoid adverse effects per patient was 1 (25th-75th 0–3) of which chronic kidney disease progression (29%), bone fractures (23.2%), cataracts (18.1%), dementia, and arterial hypertension (each at 12.3%) were most commonly recorded. Significant associations were found between occurrence of any relapse and new diabetes mellitus and between initial glucocorticoid pulse therapy and new dementia (all with p < 0.05). In multivariate regression analysis, any relapse was a predictor for developing diabetes mellitus (OR 9.23 [95% CI 1.33–64.05], p = 0.025). However, no correlations were observed between endothelial dysfunction or inflammatory parameters and development of new glucocorticoid adverse effects.ConclusionGCA relapses may be associated for development of diabetes mellitus potentially by increasing glucocorticoid doses. Parameters of inflammation and endothelial dysfunction are not suited predictors for glucocorticoid adverse effects
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