scholarly journals The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases

2020 ◽  
Author(s):  
Francesco Mazzarotto ◽  
Megan H. Hawley ◽  
Matteo Beltrami ◽  
Leander Beekman ◽  
Antonio de Marvao ◽  
...  
Keyword(s):  
Association Analysis ◽  
Genetic Architecture ◽  
Left Ventricular ◽  
Myocardial Wall ◽  
Genetic Landscape ◽  
The Subject ◽  
The Uk ◽  
The Relationship ◽  
Population Controls ◽  
Secondary Phenotype

AbstractBackgroundLeft ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. We sought to investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies.MethodsWe performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases.ResultsWe observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants in MYH7, ACTN2 and PRDM16 may represent a distinct LVNC aetiology. MYH7 truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Individuals with MYH7 truncating variants identified in the UK Biobank and cohorts of healthy volunteers also displayed significantly greater non-compaction compared to matched controls, with 50% meeting the diagnostic criteria for LVNC. Additionally, structural variants (exon deletions) in RYR2 and missense variants in the transmembrane region of HCN4 were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes.ConclusionsWe demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVNC/arrhythmia phenotypes. These results underline the complex genetic landscape of LVNC and inform how genetic testing in LVNC cases should be pursued and interpreted.

scholarly journals The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Walsh ◽  
F Mazzarotto ◽  
M Hawley ◽  
M Beltrami ◽  
L Beekman ◽  
...  
Keyword(s):  
Association Analysis ◽  
Rare Variant ◽  
Genetic Architecture ◽  
Left Ventricular ◽  
Myocardial Wall ◽  
Genetic Landscape ◽  
The Subject ◽  
The Relationship ◽  
Population Controls ◽  
Secondary Phenotype

Abstract Background Left ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. Purpose To investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies. Methods We performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases. Results We observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants in MYH7, ACTN2 and PRDM16 may represent a distinct LVNC aetiology. MYH7 truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Additionally, structural variants (exon deletions) in RYR2 and missense variants in the transmembrane region of HCN4 were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes. Conclusions We demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVNC/arrhythmia phenotypes. These results underline the complex genetic landscape of LVNC and inform how genetic testing in LVNC cases should be pursued and interpreted. Cardiomyopathy rare variant frequencies Funding Acknowledgement Type of funding source: None

scholarly journals Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies

2021 ◽  
Author(s):  
Francesco Mazzarotto ◽  
Megan H. Hawley ◽  
Matteo Beltrami ◽  
Leander Beekman ◽  
Antonio de Marvao ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Large Scale ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Large Scale Assessment ◽  
Genetic Overlap ◽  
The Uk ◽  
Population Controls ◽  
Secondary Phenotype

Abstract Purpose To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases. Methods We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Results We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants in MYH7, ACTN2, and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC etiology. In particular, MYH7 truncating variants (MYH7tv), generally considered nonpathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7tv heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater noncompaction compared with matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes. Conclusion LVNC is characterized by substantial genetic overlap with DCM/HCM but is also associated with distinct noncompaction and arrhythmia etiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological noncompaction.

Public opinion attitudes towards the European Union and its future in the United Kingdom. Study based on the results of Eurobarometer surveys in the UK and Poland

2014 ◽  
pp. 116-131
Author(s):  
Beata Słupek
Keyword(s):  
European Union ◽  
The European Union ◽  
Main Research ◽  
The United Kingdom ◽  
The Future ◽  
The Subject ◽  
The Uk ◽  
The Relationship ◽  
British People ◽  
The Eu

The subject of this publication is the scepticism regarding the future of the European Union in the UK. The research is based on Eurobarometer surveys conducted over the period of five years. A purpose of the research is to show the relationship between the results of the Eurobarometer survey on the future of the EU, and the eurosceptic views in the UK. The main research questions is: is the UK sceptical about the future of the EU? Hypothesis of this publication is that the UK is sceptical about the future of the European Union. The reasons for such attitudes are not analysed here – the article is merely an attempt to present the societal attitudes. The research method employed is the comparative critical analysis of quantitative data. The conclusion is that Great Britain is not significantly eurosceptic. British people are, however, less enthusiastic about what is happening at present in the EU, and also are showing greater anxieties when it comes to the future of the EU.

13. Corporate management

Company Law ◽  
2020 ◽  
pp. 275-320
Author(s):  
Alan Dignam ◽  
John Lowry
Keyword(s):  
Board Of Directors ◽  
General Meeting ◽  
Company Law ◽  
Corporate Management ◽  
Strategic Decisions ◽  
The Board Of Directors ◽  
The Subject ◽  
The Uk ◽  
And Control ◽  
The Relationship

Titles in the Core Text series take the reader straight to the heart of the subject, providing focused, concise, and reliable guides for students at all levels. This chapter deals with corporate management, focusing on those individuals who are responsible for making key strategic decisions within the company, namely the members of the board of directors. It begins by tracing the emergence of the professional managerial organ, with emphasis on the separation of ownership and control and the recognition of directorial autonomy. It then considers the relationship between directors and the general meeting, how directors are appointed, categories of directors, principle and policy governing directors’ remuneration, and the fiduciary nature of the office. The issues surrounding corporate governance are also examined, along with the approach of company law in the UK with regards to the structure and functions of the board of directors. Finally, the chapter discusses vacation, removal from office, and disqualification of directors as well as recent statutory reforms (the Small Business, Enterprise and Employment Act 2015) aimed at bolstering the disqualification regime.

The Politics and Ideology of Planning

2020 ◽  
Author(s):  
Tim Marshall
Keyword(s):  
Political Activity ◽  
The Political ◽  
Political Forces ◽  
Legal Thinking ◽  
The Media ◽  
The Subject ◽  
The Uk ◽  
Relationship Of ◽  
The Relationship

The present time is one of considerable political and ideological turmoil. This affects urban planning, like all areas of public policy. This book sets out to analyse the political and ideological dimensions of planning, focusing on the UK and particularly on England. These have been underplayed or obscured in the past, partly because professional planners have wished to present themselves as apolitical and non-ideological actors. The book proposes that good planning practice will be helped by a more explicit engagement with how planning is affected by political activity and by ideological thinking. The book therefore takes a series of cuts into the subject, starting with a survey of recent planning literature and proceeding to a historical overview of the relationship of planning to ideological currents, including a brief study of one recent UK government. There is then a survey of the main ideological composites active in Britain. There follows a chapter on the relationships between technical work, law and planning, to establish to what degree the political forces allow autonomy for technical skill and the force of legal thinking. Three chapters deal with dimensions of politics and ideology as they operate within government, pressure politics and the media, as well as the place of public deliberation in planning. Two chapters examine different facets and fields of planning, to identify variation across sub-fields of planning work. The final chapter explores some paths to improving the relationship between politics and planning, in current circumstances.

The Police Informer/Handler Relationship: Is it Really Unique?

2003 ◽  
Vol 5 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Roger Billingsley
Keyword(s):  
Criminal Justice ◽  
Law Enforcement ◽  
Justice System ◽  
Law Enforcement Agencies ◽  
Common Assumption ◽  
Police Service ◽  
The Subject ◽  
The Veil ◽  
The Uk ◽  
The Relationship

The use of informers by the police service in the UK has been the subject of recent research, even though the police service in this country has been protective towards this particular investigative method. It has been revealed from this research that there is a common assumption that the use of informers is quite unique among police relationships. This paper examines whether in fact the relationship between an informer and the police is really that unique, or whether it is the secrecy which surrounds it that provokes such an assumption. The paper relies heavily on a comparison with other relationships, starting with typical professional partnerships, then examining other police relationships. The factors which emerge from these relationships have been compared to police/informer relationships to determine how dissimilar they are. The paper suggests there are in fact many similarities between a police/ informer relationship and other professional partnerships, and concludes that it is probably the secrecy which the police have maintained that has created the assumption that the relationship is unique. It is suggested by the author that if the police/informer relationship became more transparent and accountable then this may lead to law enforcement agencies being less able to hide behind the veil of secrecy, which may help the concept of openness within the criminal justice system.

scholarly journals Migrating architectures: Palladio’s legacy from Calcutta to New Delhi

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pilar Maria Guerrieri
Keyword(s):  
Thomas Jefferson ◽  
New Delhi ◽  
Archival Material ◽  
The Us ◽  
The World ◽  
The Subject ◽  
The Common ◽  
Eighteenth And Nineteenth Centuries ◽  
The Uk ◽  
The Relationship

AbstractPalladianism, which originated in Italy, is a style of architecture which spread widely across the world and has been extensively studied. It is known that it migrated to the UK during the eighteenth century at the same time as it did to Germany through Georg Knobelsdorff, to Russia through the work of Charles Cameron and Giacomo Quarenghi, to the US through Thomas Jefferson between the eighteenth and nineteenth centuries, and was adopted in Poland, Sweden, and elsewhere. Palladianism became a tool of politicians and a status symbol for the elites to differentiate themselves from the common man. There are a few studies on the migration and adoption of Palladianism in India, primarily in relation to Calcutta’s architecture between the eighteenth and nineteenth centuries. In particular, there is specific research focusing on Lord Wellesley’s Palladian building programme, frequently highlighting the relationship between Government House, Calcutta and Kedleston Hall in Derbyshire. This essay focuses on the subject of the migration of Palladian architecture and, in particular, on its adoption by the capitals of India, Calcutta and Delhi, on the basis of primary archival material.

Language, Labels and Lived Identity in Debates about Science, Religion and Belief

2019 ◽  
pp. 55-78
Author(s):  
Tom Kaden ◽  
Stephen H. Jones ◽  
Rebecca Catto ◽  
Grace Davie
Keyword(s):  
Science And Religion ◽  
Structured Interviews ◽  
The Public ◽  
The Subject ◽  
Social Scientific ◽  
The Uk ◽  
New Atheism ◽  
The Relationship ◽  
Scientific Treatment

In public discussion and polling on the subject of science and belief people’s views are often subsumed under identity labels such as ‘Creationism’, ‘Darwinism’, ‘New Atheism’, ‘Intelligent Design’ and ‘Theistic Evolutionism’. Often, these labels are held to accurately represent people’s views both by public figures and by social scientific researchers. In this chapter, Kaden, Jones and Catto make the case for a reassessment of the role of labels and the knowledge connected to them in popular and social scientific treatment of the relationship between science and belief. They argue that there are considerable problems in identifying people’s views using the majority of commonly used analytic labels. Drawing on 123 semi-structured interviews with scientists and members of the public in the UK and Canada from a range of religious and non-religious positions, the authors then show that such categories of belief are creatively interpreted. The authors highlight the limited salience of popular concepts in science and religion debates, showing that such terms are frequently unfamiliar to British and Canadian publics. Based on their analysis, they argue that naive application of labels contributes to misperceptions and prejudices, especially relating to religious people’s beliefs about human origins. Finally, they conclude that to limit such misperceptions attention needs to be paid by scholars to whether, how and why individuals relate their fundamental beliefs to aspects of science.

13. Corporate management

2016 ◽  
Author(s):  
Alan Dignam ◽  
John Lowry
Keyword(s):  
Board Of Directors ◽  
General Meeting ◽  
Company Law ◽  
Corporate Management ◽  
Strategic Decisions ◽  
The Board Of Directors ◽  
The Subject ◽  
The Uk ◽  
And Control ◽  
The Relationship

Titles in the Core Text series take the reader straight to the heart of the subject, providing focused, concise, and reliable guides for students at all levels. This chapter deals with corporate management, focusing on those individuals who are responsible for making key strategic decisions within the company, namely the members of the board of directors. It begins by tracing the emergence of the professional managerial organ, with emphasis on the separation of ownership and control and the recognition of directorial autonomy. It then considers the relationship between directors and the general meeting, how directors are appointed, categories of directors, principle and policy governing directors’ remuneration, and the fiduciary nature of the office. The issues surrounding corporate governance are also examined, along with the approach of company law in the UK with regards to the structure and functions of the board of directors. Finally, the chapter discusses vacation, removal from office, and disqualification of directors as well as recent statutory reforms (the Small Business, Enterprise and Employment Act 2015) aimed at bolstering the disqualification regime.

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