56 research outputs found

    Airways Disease in Sarcoidosis

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    Global Law as Intercontextuality and as Interlegality

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    Since the 1990s the effects of globalization on law and legal developments has been a central topic of scholarly debate. To date, the debate is however marked by three substantial deficiencies which this chapter seeks to remedy through a reconceptualization of global law as a law of inter-contextuality expressed through inter-legality and materialized through a particular body of legal norms which can be characterized as connectivity norms. The first deficiency is a historical and empirical one. Both critics as well as advocates of ‘non-state law’ share the assumption that ‘law beyond the state’ and related legal norms have gained in centrality when compared with previous historical times. While global law, including both public and private global governance law as well as regional occurrences such as EU law, has undergone profound transformations since the structural transformations which followed the de-colonialization processes of the mid-twentieth century, we do not have more global law relatively to other types of law today than in previous historical times. The second deficiency is a methodological one. The vast majority of scholarship on global law is either of an analytical nature, drawing on insights from philosophy, or empirically observing the existence of global law and the degree of compliance with global legal norms at a given moment in time. While both approaches bring something to the table they remain static approaches incapable of explaining and evaluating the transformation of global law over time. The third deficiency is a conceptual-theoretical one. In most instances, global law is understood as a unitary law producing singular legal norms with a planetary reach, or, alternatively, a radical pluralist perspective is adopted dismissing the existence of singular global norms. Both of these approaches however misapprehend the structural characteristics, function and societal effects of global law. Instead a third positon between unitary and radical pluralist perspectives can be adopted through an understanding of global law and its related legal norms as a de-centred kind of inter-contextual law characterised by inter-legality

    High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study

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    One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis

    Judging Inter-Legality

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    Sarcoidosis is not associated with BRAFV600E mutation

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    Purpose/Aim of the study: BRAFV600E is an oncogenic point mutation in the MAPK/ERK signaling pathway, which is important for cell proliferation and migration. It has been found to be associated with several malignancies and has also been found in significant proportions of patients with Langerhans cell histiocytosis. A recent mouse model which introduces the BRAFV600E mutations only into dendritic cell precursors results in a clinical picture very similar to human sarcoidosis. We therefore hypothesized that somatic BRAFV600E mutations may play a role in granuloma formation and/or maintenance in all or a subset of patients with sarcoidosis. Materials and methods: 28 diagnostic lymph node samples and 1 diagnostic lung parenchyma sample of patients with confirmed sarcoidosis were identified. Paraffin sections including positive and negative controls were stained using pre-diluted Ventana Medical Systems anti-BRAF V600E (VE1) mouse monoclonal antibody and processed on an automated Ventana Benchmark Ultra immunostainer. Slides were analyzed by two independent experts. Results: BRAFV600E immunostaining was negative in all 29 cases. Conclusions: Sarcoidosis is not associated with the BRAFV600E mutation and is very unlikely to be associated with other less common BRAF mutations not tested for in this study. Future studies addressing a potential role of other somatic mutations in cell proliferation and migration pathways are warranted
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