Familial hypercholesterolemia in cardiac rehabilitation: a new field of interest

Familial hypercholesterolemia (FH) is a frequently undiagnosed genetic disease characterized by substantial elevations of low-density lipoprotein cholesterol (LDL-C). The prevalence of heterozygous FH (HeFH) in the general population is 1:500 inhabitants, while the prevalence of homozygous FH (HoFH) is 1:1,000,000. If FH is not identified and aggressively treated at an early age, affected individuals have a 20-fold increased lifetime risk of coronary heart disease compared with the general population. This narrative review provide a concise overview of recommendations for diagnosis and treatment of adults and children with FH, and discuss the utility of considering FH as a comorbidity at the entry of cardiac rehabilitation programme

Disconnection clauses: an inevitable symptom of regionalism?

‘Disconnection clauses’ are legal provisions inserted into multilateral conventions to ensure that certain parties to the convention are not required to apply the rules of the convention because other relevant rules have already been agreed to among themselves. A disconnection clause can also be described more generally as a ‘conflict clause’ because it signals to all parties that parallel and potentially conflicting treaty obligations exist. This paper presents a discussion of the disconnection clause which argues that while these clauses make it possible for a limited group of parties to enhance the objectives of a treaty by taking measures that correspond to their special circumstance, this practice also creates a possibility that the inter se agreement will undermine the original treaty regime. The actual impact of a particular disconnection clause depends on how the clause is crafted, along with the changing nature of the regime that it refers to. The potential for a disconnection clause to undermine the object and purpose of the original treaty can therefore be removed during its design. Nevertheless, without full disclosure when negotiating the convention, any clause that seeks to replace treaty provisions with an alternative regime that would be applicable only between certain parties may, at worst, be creating different standards for different parties and, at best, be opaque and incoherent. This paper first describes the various types of disconnection clause, focusing on their purpose and development. It then assesses the main legal and political controversies surrounding these clauses before assessing whether these clauses could potentially create more legal problems than they are intended to solve or whether they are simply a practical response to deepening regionalism

Small angle x-ray scattering with edge-illumination

Sensitivity to sub-pixel sample features has been demonstrated as a valuable capability of phase contrast x-ray imaging. Here, we report on a method to obtain angular-resolved small angle x-ray scattering distributions with edge-illumination- based imaging utilizing incoherent illumination from an x-ray tube. Our approach provides both the three established image modalities (absorption, differential phase and scatter strength), plus a number of additional contrasts related to unresolved sample features. The complementarity of these contrasts is experimentally validated by using different materials in powder form. As a significant application example we show that the extended complementary contrasts could allow the diagnosis of pulmonary emphysema in a murine model. In support of this, we demonstrate that the properties of the retrieved scattering distributions are consistent with the expectation of increased feature sizes related to pulmonary emphysema. Combined with the simplicity of implementation of edge-illumination, these findings suggest a high potential for exploiting extended sub-pixel contrasts in the diagnosis of lung diseases and beyond

Computing automorphic forms on Shimura curves over fields with arbitrary class number

We extend methods of Greenberg and the author to compute in the cohomology of a Shimura curve defined over a totally real field with arbitrary class number. Via the Jacquet-Langlands correspondence, we thereby compute systems of Hecke eigenvalues associated to Hilbert modular forms of arbitrary level over a totally real field of odd degree. We conclude with two examples which illustrate the effectiveness of our algorithms.Comment: 15 pages; final submission to ANTS I

The New Political Economy of EU State Aid Policy

Despite its importance and singularity, the EU’s state aid policy has attracted less scholarly attention than other elements of EU competition policy. Introducing the themes addressed by the special issue, this article briefly reviews the development of EU policy and highlights why the control of state aid matters. The Commission’s response to the current economic crisis notably in banking and the car industry is a key concern, but the interests of the special issue go far beyond. They include: the role of the European Commission in the development of EU policy, the politics of state aid, and a clash between models of capitalism. The special issue also examines the impact of EU policy. It investigates how EU state aid decisions affect not only industrial policy at the national level (and therefore at the EU level), but the welfare state and territorial relations within federal member states, the external implications of EU action and the strategies pursued by the Commission to limit any potential disadvantage to European firms, and the conflict between the EU’s expanding legal order and national

Keratoconus and granular dystrophy

Concurrent bilateral keratoconus and granular dystrophy is reported in a 32 year old patient with decreased vision. Initially contact lenses were attempted unsuccessfully to treat the conditions. There are a handful of other reports of these combined pathologies in the literature, and the likelihood of a chance cause or possible genetic linkage between the conditions is discussed

The Opinion procedure under Article 218(11) TFEU: Reflections in the light of Opinion 1/17

This paper explores aspects of Opinion 1/17, handed down by the Court of Justice on 30 April 2019, as an example of the specific procedure of Article 218(11) TFEU and the Court’s evolving practice. The prior Opinion procedure serves to prevent the complications that would arise, both internally and externally, if an international treaty were concluded by the EU and then subsequently found to be incompatible with primary EU law. Opinion 1/17 raised issues of institutional and substantive compatibility, in the form of the principle of autonomy and compliance with the Charter of Fundamental Rights. In handling both, the Court’s approach was characterised by its insistence on the reciprocal nature of the CETA relationship, the separation of the CETA system from EU law, the ability of the EU to engage with such independent and reciprocal dispute settlement processes, and its assessment of the way in which the agreement would be implemented. The Opinion represents an example of the explanatory or didactic form of reasoning typical of recent Opinions, as well as breaking new ground in its conception of an ‘envisaged’ agreement

Probabilistic and predictive performance-based approach for assessing reinforced concrete structures lifetime: The applet project

International audienceConcrete deterioration results in different damage extents, from cracking to concrete spalling, from losses of reinforcement cross-sections to bond losses. A relevant prediction of this performance is the basis for a successful management of the concrete structures. Conversely, the large amount of uncertainties related to parameters and models require a specific analysis in order to provide relevant results. The APPLET project intends to develop a probabilistic and predictive performance-based approach by quantifying the various sources of variability (material and structure), studying the interaction between environmental aggressive agents and the concrete material, ensuring a transfer of the physical-chemical models at the material scale towards models at the structure level, including and understanding in a better manner the corrosion process, integrating interface models between reinforcement and concrete, proposing relevant numerical models, integrating know-how from monitoring or inspection. To provide answers, a consortium of 19 partners has been established and has promoted a research project funded by the French Research Science Agency (ANR). Started in May 2007, the project has ended in November 2010. This paper will resume the most significant advances targeted by this research project

Peak shape clustering reveals biological insights

Background: ChIP-seq experiments are widely used to detect and study DNA-protein interactions, such as transcription factor binding and chromatin modifications. However, downstream analysis of ChIP-seq data is currently restricted to the evaluation of signal intensity and the detection of enriched regions (peaks) in the genome. Other features of peak shape are almost always neglected, despite the remarkable differences shown by ChIP-seq for different proteins, as well as by distinct regions in a single experiment. Results: We hypothesize that statistically significant differences in peak shape might have a functional role and a biological meaning. Thus, we design five indices able to summarize peak shapes and we employ multivariate clustering techniques to divide peaks into groups according to both their complexity and the intensity of their coverage function. In addition, our novel analysis pipeline employs a range of statistical and bioinformatics techniques to relate the obtained peak shapes to several independent genomic datasets, including other genome-wide protein-DNA maps and gene expression experiments. To clarify the meaning of peak shape, we apply our methodology to the study of the erythroid transcription factor GATA-1 in K562 cell line and in megakaryocytes. Conclusions: Our study demonstrates that ChIP-seq profiles include information regarding the binding of other proteins beside the one used for precipitation. In particular, peak shape provides new insights into cooperative transcriptional regulation and is correlated to gene expression