The 99th percentile of reference population for cTnI and cTnT assay: Methodology, pathophysiology and clinical implications

According to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision â\u89¤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population "healthy"), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in "their quest to define normality". In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines

Die italienische Energiewende im Mehrebenensystem: Zwischen sich gegenseitig verstärkender Dynamiken und institutionellen Zwängen

The article analyses drivers as well as coordination mechanisms and instruments for the energy transition in Italy from a multilevel governance perspective. It addresses the structural constraints that influenced the decision-making processes and organisation of the Italian energy sector and the socio-technical challenges opened up by enhancing renewables. The current energy system is making the move from a centralised, path-dependent institutional and organisational structure to a more fragmented and pluralistic one. Renewables and decentralised patterns of production and consumption are key elements of this paradigmatic shift, which is paralleled by a multiplication of decision-making arenas and actors. These actors follow different interests, problem understandings and green growth narratives, increasing the complexity of governing the energy transition. Against this background, community-based renewable energy policy is assuming a very important role and Italy is putting efforts to establish an enabling framework in line with the requirements of the European Union. The goal of this strategy is to foster a positive link between acceptance of the energy transition and decentralised local activities. In the conclusion we address problems and barriers to new modes of governance, and discuss possible approaches to improved cooperation.Der Artikel analysiert Treiber sowie Koordinationsmechanismen und Instrumente für die Energiewende in Italien aus einer Multi-Level-Governance-Perspektive. Er befasst sich mit den strukturellen Barrieren, welche die Entscheidungsprozesse und die Organisation des italienischen Energiesektors beeinflusst haben sowie mit den sozio-technischen Herausforderungen, die sich durch den Ausbau der erneuerbaren Energien ergeben. Das derzeitige Energiesystem befindet sich auf dem Weg von einer zentralisierten, pfadabhängigen institutionellen und organisatorischen Struktur zu einer stärker fragmentierten und pluralistischen Struktur. Erneuerbare Energien und dezentrale Produktions- und Konsummuster sind Schlüsselelemente dieses Paradigmenwechsels, der mit einer Vervielfachung der Entscheidungsarenen und Akteure einhergeht. Diese Akteure folgen unterschiedlichen Interessen, Problemverständnissen und grünen „Wachstumsnarrativen“, was die Steuerungskomplexität der Energiewende erhöht. Vor diesem Hintergrund nehmen die Bürgerenergie im allgemeinen und Erneuerbare-Energie-Gemeinschaften im Besonderen eine wichtige Rolle ein. Derzeit unternimmt die Regierung Italiens Anstrengungen, einen Förderrahmen zu schaffen, der den Anforderungen der Europäischen Union entspricht. Das Ziel dieser Strategie ist, eine positive Verbindung zwischen der Akzeptanz der Energiewende und dezentralen lokalen Aktivitäten zu fördern. In der Schlussfolgerung gehen wir auf Probleme und Barrieren für neue Formen der Governance ein und diskutieren mögliche Ansätze für eine verbesserte Kooperation

The Italian energy transition in a multilevel system: between reinforcing dynamics and institutional constraints

The article analyses drivers as well as coordination mechanisms and instruments for the energy transition in Italy from a multilevel governance perspective. It addresses the structural constraints that influenced the decision-making processes and organisation of the Italian energy sector and the socio-technical challenges opened up by enhancing renewables. The current energy system is making the move from a centralised, path-dependent institutional and organisational structure to a more fragmented and pluralistic one. Renewables and decentralised patterns of production and consumption are key elements of this paradigmatic shift, which is paralleled by a multiplication of decision-making arenas and actors. These actors follow different interests, problem understandings and green growth narratives, increasing the complexity of governing the energy transition. Against this background, community-based renewable energy policy is assuming a very important role and Italy is putting efforts to establish an enabling framework in line with the requirements of the European Union. The goal of this strategy is to foster a positive link between acceptance of the energy transition and decentralised local activities. In the conclusion we address problems and barriers to new modes of governance, and discuss possible approaches to improved cooperation

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

A green but also just transition? Variations in social and industrial policy responses to industrial decarbonisation in EU member states

The EU aims for net carbon neutrality by 2050. Since industry contributes substantially to carbon emissions, reforms to decarbonise industry are necessary to achieve this goal. However, these reforms may entail labour market costs in the form of unemployment, which may necessitate social policies to mitigate them. Our article provides a novel contribution to the existing literature by developing a framework to classify how these policy responses may vary across EU Member States and it also suggests sources for these variations. We analyse the planned social policy responses of four countries – Denmark, Germany, Spain and Poland – by comparing the emphasis on social investment relative to compensation; the emphasis on social relative to industrial policy; and the extent to which social policy is targeted. Our findings suggest that Danish plans will rely primarily on social investment, whereas Poland will rely on compensation. In Germany, there is a greater emphasis on industrial policy, and Spain’s planned responses differ between policies targeted at coal miners and policies for other workers

Systematic differences between BNP immunoassays: Comparison of methods using standard protocols and quality control materials

Background: Recent studies suggested that there are marked systematic differences among BNP immunoassays. In this study we compared the BNP data and clinical results obtained with different immunoassays, including a new method (ST-AIA-PACK, TOSOH Corporation). Methods: BNP was measured on plasma-EDTA samples of healthy subjects (HS, n = 126) and patients with heart failure (HF, n = 31 NYHA I, II; n = 46 NYHA III, IV) using the ST-AIA-PACK and the Triage Biosite (Beckman Coulter) methods. Control samples distributed in the CardioOrmoCheck external quality assessment were also measured with TOSOH and the most used BNP immunoassays in Italy. Results: TOSOH method showed a good correlation (R = 0.976; n = 327) but a mean bias (−46.9%) compared to Triage Biosite. On the base of the results obtained in 10 samples of the CardioOrmoCheck study, TOSOH method showed a strict agreementwith ADVIA Centaur, while it underestimated BNP in comparisonwith Triage (−52.5%) and ARCHITECT methods (−39.4%). The agreement of ST-AIA-PACK and Triage Biosite methods for classification of HF patients was tested using 100 ng/L of BNP; the positive agreement between methods was 65%, overall agreement was 73%. Conclusions: Our results confirm that there are marked differences in measured values among commercial methods for BNP assay

Head-to-head comparison of plasma cTnI concentration values measured with three high-sensitivity methods in a large Italian population of healthy volunteers and patients admitted to emergency department with acute coronary syndrome: A multi-center study

Abstract Background The study aim is to compare cTnI values measured with three high-sensitivity (hs) methods in apparently healthy volunteers and patients admitted to emergency department (ED) with acute coronary syndrome enrolled in a large multicentre study. Methods Heparinized plasma samples were collected from 1511 apparently healthy subjects from 8 Italian clinical institutions (mean age: 51.5 years, SD: 14.1 years, range: 18–65 years, F/M ratio:0.95). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests. Moreover, 1322 heparinized plasma sample were also collected by 9 Italian clinical institutions from patients admitted to ED with clinical symptoms typical of acute coronary syndrome. The reference study laboratory assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnI and ADVIA Centaur XPT methods. Principal Component Analysis (PCA) was also used to analyze the between-method differences among hs-cTnI assays. Results On average, a between-method difference of 31.2% CV was found among the results of hs-cTnI immunoassays. ADVIA Centaur XPT method measured higher cTnI values than Architect and Access methods. Moreover, 99th percentile URL values depended not only on age and sex of reference population, but also on the statistical approach used for calculation (robust non-parametric vs bootstrap). Conclusions Due to differences in concentrations and reference values, clinicians should be advised that plasma samples of the same patient should be measured for cTnI assay in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods

Evaluation of 99th percentile and reference change values of a high-sensitivity cTnI method: A multicenter study

Abstract Background The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method. Materials and methods Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease. Results and conclusions The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters