We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures; however, the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored.
Aims
We aimed to explore the contributions of common genetic variation and copy number variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders.
Method
We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments and electronic healthcare records (EHRs). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed.
Results
The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report-based definitions.
Conclusions
Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.
Three years after the beginning of the COVID-19 pandemic, better knowledge on the transmission of respiratory viral infections (RVI) including the contribution of asymptomatic infections encouraged most healthcare centers to implement universal masking. The evolution of the SARS-CoV-2 epidemiology and improved immunization of the population call for the infection and prevention control community to revisit the masking strategy in healthcare. In this narrative review, we consider factors for de-escalating universal masking in healthcare centers, addressing compliance with the mask policy, local epidemiology, the level of protection provided by medical face masks, the consequences of absenteeism and presenteeism, as well as logistics, costs, and ecological impact. Most current national and international guidelines for mask use are based on the level of community transmission of SARS-CoV-2. Actions are now required to refine future recommendations, such as establishing a list of the most relevant RVI to consider, implement reliable local RVI surveillance, and define thresholds for activating masking strategies. Considering the epidemiological context (measured via sentinel networks or wastewater analysis), and, if not available, considering a time period (winter season) may guide to three gradual levels of masking: (i) standard and transmission-based precautions and respiratory etiquette, (ii) systematic face mask wearing when in direct contact with patients, and (iii) universal masking. Cost-effectiveness analysis of the different strategies is warranted in the coming years. Masking is just one element to be considered along with other preventive measures such as staff and patient immunization, and efficient ventilation.
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
Aims
Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
Method
As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
Results
We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
Conclusions
DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
The combination of double-sided laser heating in the diamond anvil cell and detailed chemical analysis of the recovered samples is a promising approach to explore the chemistry of the Earth’s deep interior from the lower mantle to the core. Routine recovery of laser-heated samples coupled with chemical and textural characterization at the submicron scale is the key to expand knowledge of chemical interactions and melting at extreme conditions, particularly in complex systems. Recent technical developments have allowed us to investigate element partitioning and melting relations at pressures approaching the Earth’s inner-core boundary. In this chapter, we review the techniques used for recovering tiny laser-heated samples and analyzing their chemical compositions and quenched textures, while highlighting key experiments that address silicate–metal element partitioning during mantle–core differentiation, silicate melting relations with applications to early magma ocean crystallization and deep mantle melting, and melting relations in iron-alloy systems relevant to the core. The results have drastically expanded our understanding of element redistribution at deep chemical boundaries and the chemical evolution of the deep mantle and the inner core. Finally, we emphasize the need for standardized protocols to obtain consistent, reproducible results and streamlined procedures to promote good practice and increase productivity. A broad collaboration with a systematic approach would further advance the field of high-pressure geochemistry.
The combination of double-sided laser heating in the diamond anvil cell and detailed chemical analysis of the recovered samples is a promising approach to explore the chemistry of the Earth’s deep interior from the lower mantle to the core. Routine recovery of laser-heated samples coupled with chemical and textural characterization at the submicron scale is the key to expand knowledge of chemical interactions and melting at extreme conditions, particularly in complex systems. Recent technical developments have allowed us to investigate element partitioning and melting relations at pressures approaching the Earth’s inner-core boundary. In this chapter, we review the techniques used for recovering tiny laser-heated samples and analyzing their chemical compositions and quenched textures, while highlighting key experiments that address silicate–metal element partitioning during mantle–core differentiation, silicate melting relations with applications to early magma ocean crystallization and deep mantle melting, and melting relations in iron-alloy systems relevant to the core. The results have drastically expanded our understanding of element redistribution at deep chemical boundaries and the chemical evolution of the deep mantle and the inner core. Finally, we emphasize the need for standardized protocols to obtain consistent, reproducible results and streamlined procedures to promote good practice and increase productivity. A broad collaboration with a systematic approach would further advance the field of high-pressure geochemistry.
Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.
The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.
The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
Methods
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
Results
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Conclusions
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Congress is the centerpiece institution of Madison’s Republic. Article I of the Constitution starts with Congress, enumerating an impressive list of specific powers given to government because they are vested in the national legislature. And, if we have a republic, it is because the Congress somehow represents the national interest. It does this, as the above quote from Federalist 10 suggests, by bringing into government the range of interests in society. This is necessarily a messy business. The “necessary and ordinary operations of government” involve the range of factions in society? No wonder there is so much conflict, noise, frustration, posturing, and gridlock in Washington. Congressional politics, in other words, is untidy by design.
For James Madison, self-interest is the problem. It is the problem because it is an immutable part of human nature and because its consequences in politics are potentially devastating. People act for their own gain without thinking of the interests of others, or of the larger public good. Although everyone benefits in the long run from a stable social order, people may pursue their short-run interests in ways that harm or even destroy that order. This consequence of self-interest – social instability and chaos – is relatively easily managed. The problem is complicated because the governments created to protect against instability and disorder are themselves subject to self-interest. This problem is the possibility of tyranny. The people with power naturally use it to pursue their own interests, without concern for the interests of others or for the larger public good. Those with power often have a compelling interest in avoiding instability and chaos, but stability is not enough. Great care must be taken to avoid tyranny – by a majority over the minority, or by the government over the governed.
This book critically examines the following claim: Self-interest is the problem; it is also the only possible solution. The problem with what? The solution to what? This is a book about American government and politics, and both the problem and the solution are concerned with how best to conduct our politics. The title to this introduction states a paradox: The thing that causes the predicament – self-interest – also gets us out of it. To put it more precisely (and optimistically): All that is required in a well-ordered political system for the public good to be achieved is for everyone – politicians, citizens, leaders of special interest groups – to pursue their own selfish interests. The political system does not require anyone to set aside his or her interests in the name of the public good for that good to be achieved. We describe in detail the source of this claim in Chapter 2 and devote the rest of the book to some critical questions about whether the claim that self-interest is sufficient to resolve the problems it creates in politics fits with the reality of American politics today.
Setting aside Donald Trump’s typical braggadocio, when he claimed he alone could fix the mess that was America after eight years under Democratic President Barack Obama, he was following a long-standing political tradition in at least two ways: Presidential candidates from the party not currently in power emphasize what is wrong in American national life, not what is going well, and presidential candidates of both parties promise more than they can deliver. Whether it was Jimmy Carter promising independence from foreign oil, Ronald Reagan promising to balance the budget, cut taxes, and increase spending on the military, or Barack Obama promising healthcare reform that would require little inconvenience or change from those satisfied with their insurance coverage, presidential candidates assume the mantle of responsibility for the nation’s well-being well beyond their constitutional capacity to deliver.
Before beginning in earnest our exposition of Madison’s Republic in the next chapter, we spell out some key concepts and questions that help to give context to the next chapter and the rest of the book. We discuss concepts such as the meaning of democracy, the principal–agent problem, and collective action because these concepts relate directly to an understanding of how theories relate to the world of politics. We also introduce basic ideas about how political scientists approach the study of politics especially by using models that simplify some important aspect of the political world under study.
Citizen participation in politics is a good place to begin our analysis of the Republic. Madison expected self-interested participation by citizens to be the foundation of the system. Political participation can be defined as any attempt to influence what the political system does. Madison’s theory expects everyone in the Republic to be self-interested, and citizens who become involved in politics to compel political leaders to respond to their interests.
On the first Monday in October and continuing into late June or early July of the following year, the US Supreme Court sits in session. Unlike the executive and legislative branches of government, the day-to-day business of the Court is largely removed from public view. The nine justices who serve on the bench give interviews only sparingly, and television cameras are not allowed in the courtroom when hearings or deliberations are taking place. When appearing at formal public events, such as the annual State of the Union address given to Congress or the swearing in of a president, a justice is easy to spot because of his or her unusual attire – a black silk robe worn over a business suit.