Effects of eight neuropsychiatric copy number variants on human brain structure

peer reviewedMany copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. © 2021, The Author(s)

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

When adaptation increases energy demand: a systematic map of the literature

Adaptation is now a central component of climate policy, helping manage and reduce risks. Sometimes, however, adaptation to climate change may consume energy, threatening efforts to reduce greenhouse gas emissions. Examples are numerous, and include the use of air conditioning or water desalination. Nevertheless, so far, no clear view exists on how energy demand, globally, can be impacted by climate change: the information is scattered. Here, we systematically map the evidence on how and to what extent adaptation responses to climate change may impact energy demand. The literature is large, fast-growing and spans several disciplines, but we identify several research gaps. The literature focuses heavily on a few world regions, and on heating and cooling demand, while overlooking other potential sectors. Only a handful of papers -- most of them with a specific geographical scope -- consider that different adaptation possibilities may lead to different impacts on energy demand, which is an important prerequisite if the impact of adaptation on energy demand is to be lowered and maladaptation to be prevented. These papers study for the most part similar options, and most adaptation possibilities are conversely studied by just one or two papers

EPICEA Project [2008-2010], Multidisciplinary study of the impacts of climate change on the scale of Paris

International audienceThe EPICEA project is a joint collaboration between the City of Paris, the French Meteorological Office and the National Research Centre in Building to quantify the impact of climate change on Paris and the influence of building on urban climate and on adaptation strategy. First goal is to evaluate the evolution of the urban climate of Paris and its area with regard to climate change. Second goal is to realise a sharp analysis of the 2003 heatwave over Paris with simulations using a database of the Parisian urban cover. The ultimate goal is to assess the climatic impacts during heatwave periods that could result of actions on urban parameters. This information will allow the mapping of heatwave vulnerability

When adaptation increases energy demand: A systematic map of the literature

International audienceAdaptation is a central component of climate policy, helping manage and reduce risks. Sometimes,however, adaptation to climate change may consume energy, threatening efforts to reducegreenhouse gas emissions. Examples are numerous, and include the use of air conditioning orwater desalination. Nevertheless, no clear view exists on how energy demand globally can beimpacted by climate change. In this paper we systematically map existing evidence on how and towhat extent adaptation responses to climate change may impact energy demand. The literature islarge, fast-growing and spans several disciplines, but we identify several research gaps. First, theliterature focuses almost exclusively on heating and cooling demand, while overlooking otherpotential sectors. It also focuses heavily on a few world regions, while local specific climate andsocio-economic conditions may highly influence the impacts, and focuses largely on averagedemand, while often disregarding peak energy demand. Finally, and most importantly, only ahandful of papers—most of them with a specific geographical scope—consider that differentadaptation possibilities may lead to different impacts on energy demand, which is an importantprerequisite if the impact of adaptation on energy demand is to be lowered and maladaptation tobe avoided. The reviewed papers study for the most part similar options, and most adaptationpossibilities are conversely studied by just one or two papers

Strategies and scenarios to reduce energy consumption and CO2 emission in the urban, rural and sustainable neighbourhoods

peer reviewedThe building sector has become a major source of worldwide carbon emissions and energy consumption because of rapid population growth and a continuous environmental strain caused by humanity. A lack of consistent data on life-cycle carbon emissions and energy demand at the neighbourhood level has made it difficult to understand the origins of climate change at this scale. A sensitivity analysis brought clarity concerning the extent of environmental impacts on future climate evolution. From this perspective, the authors aimed to evaluate, analyse, compare, and provide recommendations to reduce carbon emissions, as well as the energy required by three types of neighbourhoods (urban, rural, and sustainable) located in and adapted to all countries worldwide. The most important parameters affecting carbon emission and energy consumption were analysed, including the energy mix of countries, local building materials and climate, technological solutions utilised, daily mobility, and occupied spaces. The results indicated that the highest levels of carbon dioxide emissions were produced by countries with prosperous economies, such as China, the United States, India, Germany, and Poland, because of high concentrations of coal in their energy mixes. Modernising cities through the construction of new ecodistricts and increasing the use of new techniques for substantial renovations of outdated buildings worldwide could mitigate the amount of greenhouse gases emitted by neighbourhoods 53–97 % by 2050. Moreover, by combining substantial building renovations with the installation of photovoltaic panels on roofs, the objective of ‘zero carbon’ at the neighbourhood level could be achievable by 2050 in rural neighbourhoods. Radical changes in the judicious choice of construction materials and use of green energy production represent targeted opportunities to resolve the future climate dilemma

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care

International audienceBackground: The relevance of registries as a key component for developing clinical research for rare diseases (RD) and improving patient care has been acknowledged by most stakeholders. As recent studies pointed to several limitations of RD registries our challenge was (1) to improve standardization and data comparability; (2) to facilitate interoperability between existing RD registries; (3) to limit the amount of incomplete data; (4) to improve data quality. This report describes the innovative concept of the DM-Scope Registry that was developed to achieve these objectives for Myotonic Dystrophy (DM), a prototypical example of highly heterogeneous RD. By the setting up of an integrated platform attractive for practitioners use, we aimed to promote DM epidemiology, clinical research and patients care management simultaneously.Results: The DM-Scope Registry is a result of the collaboration within the French excellence network established by the National plan for RDs. Inclusion criteria is all genetically confirmed DM individuals, independently of disease age of onset. The dataset includes social-demographic data, clinical features, genotype, and biomaterial data, and is adjustable for clinical trial data collection. To date, the registry has a nationwide coverage, composed of 55 neuromuscular centres, encompassing the whole disease clinical and genetic spectrum. This widely used platform gathers almost 3000 DM patients (DM1 n = 2828, DM2 n = 142), both children (n = 322) and adults (n = 2648), which accounts for > 20% of overall registered DM patients internationally. The registry supported 10 research studies of various type i.e. observational, basic science studies and patient recruitment for clinical trials.Conclusion: The DM-Scope registry represents the largest collection of standardized data for the DM population. Our concept improved collaboration among health care professionals by providing annual follow-up of quality longitudinal data collection. The combination of clinical features and biomolecular materials provides a comprehensive view of the disease in a given population. DM-Scope registry proves to be a powerful device for promoting both research and medical care that is suitable to other countries. In the context of emerging therapies, such integrated platform contributes to the standardisation of international DM research and for the design of multicentre clinical trials. Finally, this valuable model is applicable to other RDs

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care

International audienceBackground: The relevance of registries as a key component for developing clinical research for rare diseases (RD) and improving patient care has been acknowledged by most stakeholders. As recent studies pointed to several limitations of RD registries our challenge was (1) to improve standardization and data comparability; (2) to facilitate interoperability between existing RD registries; (3) to limit the amount of incomplete data; (4) to improve data quality. This report describes the innovative concept of the DM-Scope Registry that was developed to achieve these objectives for Myotonic Dystrophy (DM), a prototypical example of highly heterogeneous RD. By the setting up of an integrated platform attractive for practitioners use, we aimed to promote DM epidemiology, clinical research and patients care management simultaneously.Results: The DM-Scope Registry is a result of the collaboration within the French excellence network established by the National plan for RDs. Inclusion criteria is all genetically confirmed DM individuals, independently of disease age of onset. The dataset includes social-demographic data, clinical features, genotype, and biomaterial data, and is adjustable for clinical trial data collection. To date, the registry has a nationwide coverage, composed of 55 neuromuscular centres, encompassing the whole disease clinical and genetic spectrum. This widely used platform gathers almost 3000 DM patients (DM1 n = 2828, DM2 n = 142), both children (n = 322) and adults (n = 2648), which accounts for > 20% of overall registered DM patients internationally. The registry supported 10 research studies of various type i.e. observational, basic science studies and patient recruitment for clinical trials.Conclusion: The DM-Scope registry represents the largest collection of standardized data for the DM population. Our concept improved collaboration among health care professionals by providing annual follow-up of quality longitudinal data collection. The combination of clinical features and biomolecular materials provides a comprehensive view of the disease in a given population. DM-Scope registry proves to be a powerful device for promoting both research and medical care that is suitable to other countries. In the context of emerging therapies, such integrated platform contributes to the standardisation of international DM research and for the design of multicentre clinical trials. Finally, this valuable model is applicable to other RDs