The group of five articles forming this special section of Brill Open Law is a selection of the papers presented at the Workshop on "Global Public Goods, Global Commons, Fundamental Values: the Responses of International Economic Law," organized by the Interest Group (ig) on International Economic Law (iel) of the European Society of International Law (esil) in Naples on September 6th, 2017. The mission of the esil iel ig is to promote research in the field of International Economic Law, endorsing exchange of views among young and experienced scholars, as well as supporting debate and discussion with practitioners, lawyers and officials from international organizations and national administrations working in the fields of international trade and investments and International Financial Law. The articles appearing in this Section are all devoted to International Investment Law, the first work being the opening speech to the Naples Workshop by Professor Pavel Šturma on "Public Goods and International Investment Law: Do the New Generation of iias Better Protect Human Rights?", while the subsequent four essays are all dedicated to the recent case-law developed in international arbitration proceedings dealing with the right to water and the right to human health. Professor Šturma provides a synthetic effective reconstruction of the way in which International Investment Law now interacts with International Human Rights Law. Starting from the description of the situation in the first generation of Bilateral Investment Treaties (bits), establishing the rights of investors and the obligations of States, the author then goes on exposing the differences with human rights treaties, and analyzes the significant developments in relation to the new generation of investment treaties. The relevant clauses concerning the exceptions to investment protection, or the right to regulate of the host State, expressed by the new generation of International Investment Agreements (iias), such as the eu-Canada Comprehensive Economic Trade Agreement (ceta), the now-abandoned Transatlantic Trade and Investment Partnership (ttip), or the bit models of Norway, Canada, Austria, or the Czech Republic, are therefore considered, stressing their relevance to guide interpreters and arbitrators when having to combine investment protection with human rights. Due attention is then given to the role of private parties with reference to human rights, underlining the introduction of the concept of Corporate Social Responsibility (csr) in the new iias encouraging economic operators to conduct their business in compliance with the relevant international soft law codes inspired by the principle of sustainable development – requiring that economic development be constantly combined with environmental protection and social progress. The article also emphasizes the role that the principle of systemic integration in treaty interpretation, as codified in Article 31, para. 3(c) of the Vienna Convention on the Law of Treaties, may play when arbitrators have to combine human rights, environmental protection and bits, illustrating the relevance of the case-law of international investment disputes in order to strike a fair balance between non-economic considerations and investors' rights. The analysis by Pavel Šturma opens the door to the subsequent four articles. Professor Ursula Kriebaum, in her work on "The Right to Water Before Investment Tribunals," provides a complete overview of the case-law developed in international investment arbitration proceedings with reference to the right to water. She presents the constantly rising relevance that the human right to water has been given by the Arbitral Tribunals while discussing the respect of the investors' prerogatives enshrined in the various bits invoked by the claimants. Professor Kriebaum thus emphasizes that the Arbitrators never denied that they have an obligation to take into consideration human rights while interpreting bits. On the contrary, international awards concluded that national measures introduced in order to protect the environment against the pollution of water resources, and the termination of concessions as a consequence of inadequate performance of an investment contract on the part of the investor involved in water distribution services cannot be automatically considered as infringements of bits by the States benefitting from the foreign investments. Furthermore, Ursula Kriebaum stressed the highly relevant developments reached by the Arbitral Tribunal in the Urbaser case, where it was held in an obiter that investors have to abstain from acts which may violate the human right to water by endangering access to water. The Urbaser case is at the center of the analysis by Dr Edward Guntrip and Dr Patrick Abel. In his work on "Private Actors, Public Goods and Responsibility for the Right to Water in International Investment Law: An Analysis of Urbaser v. Argentina," Dr Guntrip considers how the Arbitral Tribunal allocated responsibility for compliance with the right to water between the host State and the foreign investor while being asked to settle the dispute over privatized water services in Greater Buenos Aires. The author underlined that the Arbitrators chose to follow the scheme defined by the un Committee on Economic, Social and Cultural Rights (cescr). Pursuant to that, human rights obligations in relation to economic, social and cultural rights, which include the right to water, have to be broken down into obligations to respect, protect and fulfil. Edward Guntrip criticizes the Tribunal's decision to limit the duties of the investor to the obligation to respect only, i.e. not to interfere with the enjoyment of the right to water. In fact, such a limitation makes the human right to water vulnerable for the right holders trying to hold a foreign investor responsible. Dr Patrick Abel manifests further perplexities on the counterclaim raised by Argentina in relation to the existence of an international investor obligation under the human right to water, for the first time accepted as possible in international investment arbitration proceedings. While stressing the importance of the novelty of the Urbaser award -i.e. the possibility of holding investors accountable for a breach of an international human rights obligation- Patrick Abel highlights the flaws in the legal reasoning of the Tribunal, which he considers unclear in the way it perceives the integration of human rights obligations as a source of international law external to the relevant bit invoked in the investment arbitration. Last but not least, Professor Pei-Kan Yang, in his article on "The Margin of Appreciation Debate over Novel Cigarette Packaging Regulations in Philipp Morris v. Uruguay," explores the legal reasoning of the Arbitrators in the case brought by the famous tobacco multinational company against the Latin-American State. The majority of the Tribunal, applying the "margin of appreciation" doctrine as originally developed by the European Court of Human Rights (ECtHR), found that Uruguay's tobacco legislation did not violate the Switzerland – Uruguay bit as the Latin-American State enjoyed a substantial degree of discretion in choosing the regulatory means to achieve its public health objectives among various options of effective measures. Pei-Kan Yang analyzes both the majority conclusions and the dissenting opinion by Gary Born, and identifies lacunae in each of the two approaches, suggesting an adjustment of the concept of the margin of appreciation in order to better accommodate the right to regulate of the host State for public health purposes and balance it against the investor's private rights. We do hope that the proposed set of articles may represent a welcome perspective of analysis of some recent developments concerning treaties and case-law in the field of International Investment Law. Enjoy the reading!
1. Objectif : étudier la participation protéiforme Le changement de discours qui accompagne les transformations actuelles des prises de décision dans les démocraties européennes passe par la valorisation assez systématique de certains thèmes tels que la discussion, le débat, la concertation, la consultation, le partenariat, la participation ou la gouvernance. Au niveau européen, comme ailleurs, les institutions proposent une série de dispositifs participatifs, consultatifs ou dialogiques. Cette thèse prend comme objet l'un d'entre eux, l'Initiative Citoyenne Européenne, mise en place par la Commission européenne en 2012. Une initiative citoyenne européenne est une invitation qui peut être faite à la Commission de présenter une proposition législative dans un domaine dans lequel l'UE est habilitée à légiférer. Partant du constat que le terme « participation » est utilisé très largement pour décrire des réalités diverses et que dans la définition de la participation, la dimension expressive et symbolique des comportements a été revalorisée, j'ai formulé l'hypothèse que l'émergence de formes nouvelles de participation politique bouscule les frontières entre expression, engagement, participation et mobilisation. L'objectif était donc d'étudier, par les pratiques des acteurs des initiatives, en quoi la participation citoyenne renvoie à des dispositifs et à des expériences variées qui sollicitent la participation des individus et des associations à un exercice qui, de façon plus ou moins intégrée, semble partager information, communication, expression, délibération – et parfois décision. Par de l'observation participante, j'ai identifié différents types de pratiques que les acteurs des initiatives reconnaissent comme relevant de la participation citoyenne. En effet, pour les acteurs des initiatives, « participer » se décline en différentes formes d'engagement et d'action : prendre part à un dispositif participatif institutionnel (l'ICE), débattre en interne des associations ou comité d'initiatives, organiser ou contribuer à des débats en externe, contribuer à l'espace public par la diffusion d'idées, partager des ressources entre acteurs, se mobiliser autour d'actions militantes très diversifiées, communiquer des messages au grand public, convaincre des individus de signer la proposition d'initiative, ou encore plaider auprès des élus politiques. Cette recherche met donc en lumière les pratiques composites, élargies, protéiformes de la participation citoyenne au travers des initiatives et des pratiques de leurs acteurs (et non du point de vue institutionnel). J'ai fait le choix de penser structuralement les actions autour de l'ICE, c'est-à-dire de ne pas étudier tel type d'engagement ou d'action indépendamment des autres moyens et instruments d'action utilisés par les acteurs des initiatives. 2. Cadrage théorique : une approche interactionniste de l'action des acteurs d'initiatives L'ancrage communicationnel vis-à-vis de l'objet et des objectifs de la recherche se justifient notamment en raison de l'enjeu communicationnel de la participation citoyenne dont la portée et les effets sur l'espace public permettent de comprendre que des processus d'information-communication, institués par les pouvoirs publics, et, dans le cas des initiatives par les associations, jouent un rôle majeur dans l'évolution des représentations et des pratiques socio-politiques collectives. Ce processus de médiation publique entraîne avec lui une série de repositionnements des modes organisationnels et de régulation des activités. Porter un regard communicationnel sur ce dispositif permet d'analyser plusieurs éléments qui restent souvent dans l'angle mort des recherches sur la participation : le cadrage interprétatif d'une proposition politique (ici d'une initiative), les formats et modes d'expression des acteurs, l'importance des processus d'intercompréhension, les stratégies de communication instrumentales qui infiltrent la participation (de la part des insti ; The composite participation : Extensions and variations of citizen participation through the lens of the European Citizens' Initiative practices 1. Objective: Studying multifaceted participation The change in discourses that accompanies the current transformations of decision making in European democracies through the fairly systematic valuation of certain themes such as discussion, debate, dialogue, consultation, partnership, participation or governance. At European level, as elsewhere, the institutions offer a series of participatory, advisory or dialogical mechanisms. This thesis takes as its subject one of them, the European Citizens' Initiative, set up by the European Commission in 2012. European citizens' initiative is an invitation that can be made to the Commission to present a legislative proposal in area in which the EU can legislate. Noting that the term "participation" is used very broadly to describe different realities and that the definition of participation, expressive and symbolic behavior was upgraded, I hypothesized that the emergence of new forms of political participation pushes the boundaries of expression, engagement, participation and mobilization. The objective was to study the practices of initiatives actors, how citizen participation refers to devices and varied experiences that engage individuals and associations in an exercise that, more or less integrated, appears to share information, communication, expression, deliberation - and sometimes decision. By participant observation, I identified different types of practices that initiatives actors recognize as belonging to citizen participation. In fact, for the initiatives actors, "participate" comes in various forms of engagement and action: take part in a participatory institutional device (ECI), debating internally in associations or initiatives organizing committee or contribute to debates externally contribute to public space through the dissemination of ideas, sharing of resources among actors to mobilize around highly diversified militant actions, communicate messages to the general public, convince people to sign proposed initiative, or advocate to elected politicians. This research therefore highlights the composite practice expanded, multifaceted citizen participation through initiatives and practices of their players (and not from the institutional point of view). I made the choice to think structurally about the actions of ICE, that is to say not to study such kind of commitment or action independently of other means and policy instruments used by initiatives actors. 2. Theoretical framework: an interactionist approach to the action of the initiatives actors Anchoring communicative regarding the purpose and research objectives are justified in particular because of the communicative challenge of citizen participation, the scope and effects on the public space for understanding that process information-communication, established by the government, and, in the case of initiatives by associations, play a major role in the evolution of representations and collective socio-political practices. This public mediation process brings with it a series of repositioning the organizational modes and regulation of activities. Wear communicational look at this device can analyze several elements which often remain in the blind spot of research on participation: the interpretive framing of a policy proposal (here an initiative), formats and modes of expression of the actors, the importance of mutual understanding processes, instrumental communication strategies that infiltrate the participation (of the institutions but also of participants). This allows particularly communicative anchor to uncover how the communication comes to subsume the various practices. The communicative approach to participation allowed to specifically examine the interactions of different types of stakeholders in participatory practices, pay attention to trade, the process of mutua ; (Faculté de sciences économiques, sociales et politiques) -- FUSL, 2016
1. Objectif : étudier la participation protéiforme Le changement de discours qui accompagne les transformations actuelles des prises de décision dans les démocraties européennes passe par la valorisation assez systématique de certains thèmes tels que la discussion, le débat, la concertation, la consultation, le partenariat, la participation ou la gouvernance. Au niveau européen, comme ailleurs, les institutions proposent une série de dispositifs participatifs, consultatifs ou dialogiques. Cette thèse prend comme objet l'un d'entre eux, l'Initiative Citoyenne Européenne, mise en place par la Commission européenne en 2012. Une initiative citoyenne européenne est une invitation qui peut être faite à la Commission de présenter une proposition législative dans un domaine dans lequel l'UE est habilitée à légiférer. Partant du constat que le terme « participation » est utilisé très largement pour décrire des réalités diverses et que dans la définition de la participation, la dimension expressive et symbolique des comportements a été revalorisée, j'ai formulé l'hypothèse que l'émergence de formes nouvelles de participation politique bouscule les frontières entre expression, engagement, participation et mobilisation. L'objectif était donc d'étudier, par les pratiques des acteurs des initiatives, en quoi la participation citoyenne renvoie à des dispositifs et à des expériences variées qui sollicitent la participation des individus et des associations à un exercice qui, de façon plus ou moins intégrée, semble partager information, communication, expression, délibération – et parfois décision. Par de l'observation participante, j'ai identifié différents types de pratiques que les acteurs des initiatives reconnaissent comme relevant de la participation citoyenne. En effet, pour les acteurs des initiatives, « participer » se décline en différentes formes d'engagement et d'action : prendre part à un dispositif participatif institutionnel (l'ICE), débattre en interne des associations ou comité d'initiatives, organiser ou contribuer à des débats en externe, contribuer à l'espace public par la diffusion d'idées, partager des ressources entre acteurs, se mobiliser autour d'actions militantes très diversifiées, communiquer des messages au grand public, convaincre des individus de signer la proposition d'initiative, ou encore plaider auprès des élus politiques. Cette recherche met donc en lumière les pratiques composites, élargies, protéiformes de la participation citoyenne au travers des initiatives et des pratiques de leurs acteurs (et non du point de vue institutionnel). J'ai fait le choix de penser structuralement les actions autour de l'ICE, c'est-à-dire de ne pas étudier tel type d'engagement ou d'action indépendamment des autres moyens et instruments d'action utilisés par les acteurs des initiatives. 2. Cadrage théorique : une approche interactionniste de l'action des acteurs d'initiatives L'ancrage communicationnel vis-à-vis de l'objet et des objectifs de la recherche se justifient notamment en raison de l'enjeu communicationnel de la participation citoyenne dont la portée et les effets sur l'espace public permettent de comprendre que des processus d'information-communication, institués par les pouvoirs publics, et, dans le cas des initiatives par les associations, jouent un rôle majeur dans l'évolution des représentations et des pratiques socio-politiques collectives. Ce processus de médiation publique entraîne avec lui une série de repositionnements des modes organisationnels et de régulation des activités. Porter un regard communicationnel sur ce dispositif permet d'analyser plusieurs éléments qui restent souvent dans l'angle mort des recherches sur la participation : le cadrage interprétatif d'une proposition politique (ici d'une initiative), les formats et modes d'expression des acteurs, l'importance des processus d'intercompréhension, les stratégies de communication instrumentales qui infiltrent la participation (de la part des insti ; The composite participation : Extensions and variations of citizen participation through the lens of the European Citizens' Initiative practices 1. Objective: Studying multifaceted participation The change in discourses that accompanies the current transformations of decision making in European democracies through the fairly systematic valuation of certain themes such as discussion, debate, dialogue, consultation, partnership, participation or governance. At European level, as elsewhere, the institutions offer a series of participatory, advisory or dialogical mechanisms. This thesis takes as its subject one of them, the European Citizens' Initiative, set up by the European Commission in 2012. European citizens' initiative is an invitation that can be made to the Commission to present a legislative proposal in area in which the EU can legislate. Noting that the term "participation" is used very broadly to describe different realities and that the definition of participation, expressive and symbolic behavior was upgraded, I hypothesized that the emergence of new forms of political participation pushes the boundaries of expression, engagement, participation and mobilization. The objective was to study the practices of initiatives actors, how citizen participation refers to devices and varied experiences that engage individuals and associations in an exercise that, more or less integrated, appears to share information, communication, expression, deliberation - and sometimes decision. By participant observation, I identified different types of practices that initiatives actors recognize as belonging to citizen participation. In fact, for the initiatives actors, "participate" comes in various forms of engagement and action: take part in a participatory institutional device (ECI), debating internally in associations or initiatives organizing committee or contribute to debates externally contribute to public space through the dissemination of ideas, sharing of resources among actors to mobilize around highly diversified militant actions, communicate messages to the general public, convince people to sign proposed initiative, or advocate to elected politicians. This research therefore highlights the composite practice expanded, multifaceted citizen participation through initiatives and practices of their players (and not from the institutional point of view). I made the choice to think structurally about the actions of ICE, that is to say not to study such kind of commitment or action independently of other means and policy instruments used by initiatives actors. 2. Theoretical framework: an interactionist approach to the action of the initiatives actors Anchoring communicative regarding the purpose and research objectives are justified in particular because of the communicative challenge of citizen participation, the scope and effects on the public space for understanding that process information-communication, established by the government, and, in the case of initiatives by associations, play a major role in the evolution of representations and collective socio-political practices. This public mediation process brings with it a series of repositioning the organizational modes and regulation of activities. Wear communicational look at this device can analyze several elements which often remain in the blind spot of research on participation: the interpretive framing of a policy proposal (here an initiative), formats and modes of expression of the actors, the importance of mutual understanding processes, instrumental communication strategies that infiltrate the participation (of the institutions but also of participants). This allows particularly communicative anchor to uncover how the communication comes to subsume the various practices. The communicative approach to participation allowed to specifically examine the interactions of different types of stakeholders in participatory practices, pay attention to trade, the process of mutua ; (Faculté de sciences économiques, sociales et politiques) -- FUSL, 2016
1. Objectif : étudier la participation protéiforme Le changement de discours qui accompagne les transformations actuelles des prises de décision dans les démocraties européennes passe par la valorisation assez systématique de certains thèmes tels que la discussion, le débat, la concertation, la consultation, le partenariat, la participation ou la gouvernance. Au niveau européen, comme ailleurs, les institutions proposent une série de dispositifs participatifs, consultatifs ou dialogiques. Cette thèse prend comme objet l'un d'entre eux, l'Initiative Citoyenne Européenne, mise en place par la Commission européenne en 2012. Une initiative citoyenne européenne est une invitation qui peut être faite à la Commission de présenter une proposition législative dans un domaine dans lequel l'UE est habilitée à légiférer. Partant du constat que le terme « participation » est utilisé très largement pour décrire des réalités diverses et que dans la définition de la participation, la dimension expressive et symbolique des comportements a été revalorisée, j'ai formulé l'hypothèse que l'émergence de formes nouvelles de participation politique bouscule les frontières entre expression, engagement, participation et mobilisation. L'objectif était donc d'étudier, par les pratiques des acteurs des initiatives, en quoi la participation citoyenne renvoie à des dispositifs et à des expériences variées qui sollicitent la participation des individus et des associations à un exercice qui, de façon plus ou moins intégrée, semble partager information, communication, expression, délibération – et parfois décision. Par de l'observation participante, j'ai identifié différents types de pratiques que les acteurs des initiatives reconnaissent comme relevant de la participation citoyenne. En effet, pour les acteurs des initiatives, « participer » se décline en différentes formes d'engagement et d'action : prendre part à un dispositif participatif institutionnel (l'ICE), débattre en interne des associations ou comité d'initiatives, organiser ou contribuer à des débats en externe, contribuer à l'espace public par la diffusion d'idées, partager des ressources entre acteurs, se mobiliser autour d'actions militantes très diversifiées, communiquer des messages au grand public, convaincre des individus de signer la proposition d'initiative, ou encore plaider auprès des élus politiques. Cette recherche met donc en lumière les pratiques composites, élargies, protéiformes de la participation citoyenne au travers des initiatives et des pratiques de leurs acteurs (et non du point de vue institutionnel). J'ai fait le choix de penser structuralement les actions autour de l'ICE, c'est-à-dire de ne pas étudier tel type d'engagement ou d'action indépendamment des autres moyens et instruments d'action utilisés par les acteurs des initiatives. 2. Cadrage théorique : une approche interactionniste de l'action des acteurs d'initiatives L'ancrage communicationnel vis-à-vis de l'objet et des objectifs de la recherche se justifient notamment en raison de l'enjeu communicationnel de la participation citoyenne dont la portée et les effets sur l'espace public permettent de comprendre que des processus d'information-communication, institués par les pouvoirs publics, et, dans le cas des initiatives par les associations, jouent un rôle majeur dans l'évolution des représentations et des pratiques socio-politiques collectives. Ce processus de médiation publique entraîne avec lui une série de repositionnements des modes organisationnels et de régulation des activités. Porter un regard communicationnel sur ce dispositif permet d'analyser plusieurs éléments qui restent souvent dans l'angle mort des recherches sur la participation : le cadrage interprétatif d'une proposition politique (ici d'une initiative), les formats et modes d'expression des acteurs, l'importance des processus d'intercompréhension, les stratégies de communication instrumentales qui infiltrent la participation (de la part des insti ; The composite participation : Extensions and variations of citizen participation through the lens of the European Citizens' Initiative practices 1. Objective: Studying multifaceted participation The change in discourses that accompanies the current transformations of decision making in European democracies through the fairly systematic valuation of certain themes such as discussion, debate, dialogue, consultation, partnership, participation or governance. At European level, as elsewhere, the institutions offer a series of participatory, advisory or dialogical mechanisms. This thesis takes as its subject one of them, the European Citizens' Initiative, set up by the European Commission in 2012. European citizens' initiative is an invitation that can be made to the Commission to present a legislative proposal in area in which the EU can legislate. Noting that the term "participation" is used very broadly to describe different realities and that the definition of participation, expressive and symbolic behavior was upgraded, I hypothesized that the emergence of new forms of political participation pushes the boundaries of expression, engagement, participation and mobilization. The objective was to study the practices of initiatives actors, how citizen participation refers to devices and varied experiences that engage individuals and associations in an exercise that, more or less integrated, appears to share information, communication, expression, deliberation - and sometimes decision. By participant observation, I identified different types of practices that initiatives actors recognize as belonging to citizen participation. In fact, for the initiatives actors, "participate" comes in various forms of engagement and action: take part in a participatory institutional device (ECI), debating internally in associations or initiatives organizing committee or contribute to debates externally contribute to public space through the dissemination of ideas, sharing of resources among actors to mobilize around highly diversified militant actions, communicate messages to the general public, convince people to sign proposed initiative, or advocate to elected politicians. This research therefore highlights the composite practice expanded, multifaceted citizen participation through initiatives and practices of their players (and not from the institutional point of view). I made the choice to think structurally about the actions of ICE, that is to say not to study such kind of commitment or action independently of other means and policy instruments used by initiatives actors. 2. Theoretical framework: an interactionist approach to the action of the initiatives actors Anchoring communicative regarding the purpose and research objectives are justified in particular because of the communicative challenge of citizen participation, the scope and effects on the public space for understanding that process information-communication, established by the government, and, in the case of initiatives by associations, play a major role in the evolution of representations and collective socio-political practices. This public mediation process brings with it a series of repositioning the organizational modes and regulation of activities. Wear communicational look at this device can analyze several elements which often remain in the blind spot of research on participation: the interpretive framing of a policy proposal (here an initiative), formats and modes of expression of the actors, the importance of mutual understanding processes, instrumental communication strategies that infiltrate the participation (of the institutions but also of participants). This allows particularly communicative anchor to uncover how the communication comes to subsume the various practices. The communicative approach to participation allowed to specifically examine the interactions of different types of stakeholders in participatory practices, pay attention to trade, the process of mutua ; (Faculté de sciences économiques, sociales et politiques) -- FUSL, 2016
ÖZETMısır Arap Cumhuriyeti, Afrika'nın Kuzey Doğusunda 997,739 km2 alanı, 68,5 milyon nüfusu vardır. Yıllık nüfus artışı % 2,3 tür ve nüfus yoğunluğu 58,2 kişi/km2 dir. Erkler ayrılığı ilkesine dayanan başkanlık sitemi ve çok partili demokratik sistem ile yönetilmektedir. Mısır Arap Cumhuriyeti 1922 yılında bağımsızlığına kavuşmuştur. Ülke bulunduğu bölge nedeniyle dünyanın başlıca güçlerinin çekişme alanı olmuş ve bu yüzden yıllarca istikrara kavuşamamıştır. Mısır Arap Cumhuriyeti' de bağımsızlığından sonra İsrail ile savaşa girmiştir. 1978 yılında İsrail ile Camp Davit barış anlaşmasını imzalamıştır. İmzalanan anlaşma ile Arap Dünyasının tepkisini almasına rağmen ABD' nin tam desteğini arkasına almıştır. Batı Dünyası ile iyi ilişkiler kurarak ve ılımlı politikalar izleyerek istikrarlı bir dönem sürdürmektedir. Mısır Arap Cumhuriyeti'nin 2000 yılında 92,6 milyar Dolar Gayri Safi Milli Hasılası ile 3,4 reel büyüme gerçekleştirmiştir. Yıllık enflasyon 2000 yılında 2,7 olmuştur. Toplam dış borcu 29,5 milyar Dolardır. Bir Mısır Poundu 3,47 ABD Dolarına eşittir.Ülke 1990 yılından sonra kalkınma programlarına önem vermektedir ve bunun için çeşitli reformlar uygulamaktadır. Uygulamış olduğu mali politikalarda harcamaları kısıtlama, ithalatı azaltma ve ihracatı artırmak için çaba sarf etmektedir. Özelleştirme bütün kalkınmakta olan ülkelerin temel sorunu olduğu gibi beklenen hızın altında devam etmektedir. Fiyatlar serbest ekonomi kurallarına uygun olarak belirlenmektedir. 14 milyar dolar döviz rezervi bulunmaktadır. Üç aylık bono faiz oranları % 10 civarında seyretmektedir. Borsa 2000 yılını düşük bir trendle geçirmiştir. Çalışma hayatında nüfusun çoğunluğu tarımla uğraşmaktadır. İşsizlik oranı oldukça yüksektir. Tarım alanlarının yetersizliği nedeniyle Nis nehrinin sularıyla sulama alanları için projeler geliştirilmektedir. Ülkenin en önemli tarım ürünü pamuktur. İhracatta pamuk ve pirinç en önemli tarım ürünüdür.madencilikte petrol üretimi ve doğal gaz üretimi mevcuttur. Büyük miktarda doğal gaz rezervlerine sahiptir. Turizm sektörü ülkenin en önemli gelir kaynaklarındandır. Ülke turizminin en önemlisi ünlü Mısır piramitleridir. Turizm için önemli yatırımlarda bulunulmaktadır. Ulaşımda Nil nehri önemli bir yere ve gelire sahiptir. Nil nehrinde üzerinden büyük gemilerin geçişi için genişletme çalışmaları devam etmektedir. Sanayide, otomotiv sanayi başı çekmektedir. Uluslar arası büyük otomotiv üreticisi firmaların üretim ve montaj üssü olarak görülebilir. İmalat sanayiinde tekstil ürünleri üretimi yapılmaktadır. İnşaat sektöründe yeni yerleşim bölgeleri, otoyollar ve çimento fabrikaları ilk baştaki yatırımlarıdır. Mısır Arap Cumhuriyetinin 2000 yılında 4,689 milyon Dolar ihracatı, 14,010 milyon Dolar ithalatı vardır. İhracatında başlıca ürünleri, petrol ürünleri, tekstil ürünleri ve tarım ürünleri yer almaktadır. Başlıca ihracat yaptığı ülkelerin başında ABD. İtalya ve Hollanda gelmektedir. İthalatında ihracatının üç katına yakındır. İthalatta en önemli payı makineler, elektrikli aletler, taşıt araçları, gıda maddeleri ve petrol mamulü ürünler almaktadır. Ayrıca ithalatta sınai ve yatırım malları önemli yer tutmaktadır. Başlıca ithalat yaptığı ülkeler ABD, Almanya, İtalya'dır. Türkiye ile Mısır Arap Cumhuriyeti arasında ticari ilişkiler en son olarak Türkiye'nin 1/95 sayılı protokolde kendisin bağlayan anlaşmalar arasında olan, Mısır ile Avrupa Topluluğu arasında imzalanmış olan "Avrupa - Akdeniz ortaklık anlaşmasına" istinaden yürütülmektedir. İki ülke arasında ticaret hacmi 517,427 bin dolara ulaşmıştır. Türkiye' nin 2000 yılında Mısır Arap Cumhuriyetine ihracatı 376,7 milyon dolar olarak gerçekleşmiştir. Türkiye'nin Mısır Arap Cumhuriyetine ihraç ettiği ürünlerin başında motorlu kara taşıtları ve bunların parçaları, örülmemiş giyim eşyaları, demir ve çelik ürünleri ilk sıraları alır. Türkiye'nin Mısır Arap Cumhuriyetinden ithalatı 2000 yılında 140,7 milyon dolar olarak gerçekleşmiştir. Türkiye'nin Mısır Arap Cumhuriyetinden ithal ettiği ürünlerin bayında: petrol ürünleri, doğal gaz, pamuk ve pirinç ilk sıraları almaktadır. Türkiye ve Mısır Arap Cumhuriyetinin 1990 yılından itibaren artan miktarlarda bir ticaret hacmi gerçekleşmektedir. Bu artış her iki ülkenin faydasınadır. ABSTRACTARABIAN REPUCLIC OF EGYPT'S ECONOMY AND TURKEY - EGPYT ECONOMIC RELATIONSHIPSArabian republic of Egypt is located at the northeast of Africa covering 997,739 km2 with a population of 68,5 million. Annual population increase is % 2,3 and its density is 58,2 people per km2 . The country has been ruled by presidential system, based on principles of powers separations, and a democratic parliamentary. Arabian republic of Egypt had won her independence in 1922 due to her strategical importance, great powers of the world tried to dominate the region so the county became unsuccessfull to balance her economical and politikal stability for years. After her idebendence, Arabian republic of Egypt declared war on Israel. In 1978 the wor en ded with Camp David peace negotion signature for the sides. Although Arabic world's reactions against. This negotiation, Egypt is now continuing a normal period by establishing good relationships and following friendly political strategies with west. Arabian republic of Egypt obtained 92,6 milyard USD national income beside 3,4 percent real growthy in the year of 2000. statistics show that yearly infilation was % 2,7 in 2000. Total external debt is 29,5 milliard USD. An Egyption pound equals to 3,47 USD.Arabian republic of Egypt has been giving priority to development programmes and adapting various reforms since 1990. It is strived to restrict the spendings, to increase exportation but to decrease importation by means of practised financial politics. Privatization is the main similar problem of all developing countries like in Egypt; therefore it is going along under estimated speed. Prices are determined according to free economics rules. There is 14 milliard USD foreign exchange reserve 3 monthly bond interest rates are about % 10. Stock exchance closed the year of 2000 with a low trend.Majority population of working class are busy with agriculture. Unemployment rate is pretty high. It is tried to improve irrigation projects by using Nile River's water because of unsufficient agricultural gields cotton is the most important agricultural produce. Cotton and rice are the important items for exportation. Petroleum and natural gas production take place in the mining sector. The country has a huge natural gas rezerves. Tourism sector is one of the most essential income resorces of the Egypt. Egypt pyramids are among the famous touristic places. It's made big investments for transportation of large ships are continuing. Automotiv is the leader sector in country' industry. The country can be seen as an assembly and production base of international automotive manifacturers.Textille is produced for production industry.Hiyways,new centres of population and cement factories are the privileyed investment areas in construction industry.Figures show that Eygpt's exportation was 4,689 million USD while her impoctation was 14,010 million USD in 2000. petroleum, textile and agriculturel products can be calculated as country's main exportation goods. Holland, USA and Italy are Egypt's chiefly economical partners for her export. Importation has approximately tripled of exportation. The lion's share of importation are machines, electrical tools, vehicles, food staffs and made of petroleum products. In addition above, investment and industrial goods are playing important role for the country's importation. USA, Germany and Italy are her main importation partners.Turkey- Arabian republic of Egypt's economic relation are based on " European - mediterranen ded of partnership" signed between egypt and European union. This agreement is binding Turkey with a protocol number of 1/95 signed between Turkey and EU. And Turkey - Egypt relations are countinuing in this frame. Trading volume between Turkey and Egypt has reached 517 million USD. Turkey's exportation to Egypt was 376,7 million USD in 2000, Essetial exportation of Turkey to Egypt are vehicles and their spare parts, not knitted garments and iron-steel products. Turkey's importation from Egypt was 140,7 million USD in 2000. Turkey imports petroloum products, naturel gas, cotton and rice from Egypt.Turkey and Egypt economic relations has been tending to increase since 1990. It is benifical for both country.
One of the most intriguing and indeed progressive features of the Labour government is its willingness to have itself judged against a wide range of targets, as set out in the Public Service Agreements (PSAs) which accompanied the Comprehensive Spending Review (CSR) in 1998.The second Comprehensive Spending Review due in summer 2000 will be accompanied by a revised set of PSAs negotiated between the Treasury and individual departments. This second round of PSAs will rightly concentrate on the key policy outcomes which departments are aiming to deliver. The several hundred targets which assess the managerial effectiveness of the government machine will be covered by a separate series of Service Delivery Agreements. However, ironically the remarks by the Prime Minister on health service funding appear to undermine the whole CSR process, and threaten to turn the debate back to a focus on how much money gets spent on the public services, rather than the welcome focus on outcomes implied by the PSAs.The PSAs in effect set out in detail the government's strategy, which immediately raises the question of whether they should signal more clearly the government's priorities across the many different policy outcomes. Several of the articles in this issue of New Economy focus on the key areas of policy which should be central to the agenda of a centre‐left government: restoring full employment, eliminating child poverty and putting sustainable development at the heart of government strategy rather than at its margins. Matthew Taylor leads off by discussing the tensions which lie at the heart of the PSA process. Performance targets can have perverse outcomes if they are not designed carefully. The PSA process is highly centralising and may sti?e local initiative. It is not clear that modern government is best delivered by the Treasury telling everyone what to do.In an act of modest self‐indulgence the editor contributes an article to this issue which argues that a commitment to the attainment of full employment alongside a commitment to eliminating child poverty would represent a really powerful and radical agenda for the Government. Less weight should be given to closing the productivity gap, which is less of a problem than usually thought. Lisa Harker takes up the issues raised by the government's anti‐poverty strategy noting the absence of any debate about which of the poverty indicators the government intends to track should be given priority. She also notes that adopting a clear measure of income poverty brings challenges for government, raising the question of how far it should explicitly address poverty through higher bene?ts to provide 'security for those who cannot work'.The urgency of tackling child poverty is given weight by the chilling conclusion set out by John Micklewright and Kitty Stewart that on three key measures of child well‐being – child poverty, children in workless households and the teenage birth rate – the UK's performance is the worst in the EU. It is this 'child poverty gap' with our European partners which should make us ashamed not the productivity gap. Fran Bennett and Chris Roche argue for genuinely participatory approaches to the development of indicators of poverty and social exclusion which focus not just on what is measured, but also on who decides which indicators are important. This approach features heavily in debates in the developing world, but the OECD countries could learn from this experience. Chris Hewett and Matthew Rayment note discouragingly that seven major government departments made no reference to sustainable development in their aims and objectives as set out in the PSAs in 1998. By and large, the key environmental issues are still seen as only a priority for the DETR and no one else. It is not clear that any relationship between the PSAs and the government's sustainable development strategy is evidence of joined up government or merely coincidental overlapping government.The original PSAs made little or no reference to the goal of securing greater racial equality and Sarah Spencer takes up this omission by looking at a range of areas of public policy where a focus on outcome based measures relating to racial equality are needed. The achievement of race equality objectives necessitates a contribution from each of the key Whitehall departments responsible for domestic policy, and from all departments in relation to their own employment practices. Damian Tambini discusses the 'Ulysees Effect' by which the announcing of targets amid great fanfare forces the government to nail its colours to the mast. In the area of electronic service delivery, targets have so far been quite successful in jolting government agencies into taking action. If potential problems relating to data protection and social exclusion do not emerge, targets in this area will be seen as a useful tool of radical modernisation. However, if the negative effects of electronic service delivery do become more severe, then the government will have to face some difficult choices: abandon the targets, fudge the ?gures, or push them through despite the negative consequences. Andrea Westall discusses four recently published IPPR reports relating to business or industrial policy. A common theme is that government has a role as a market maker and catalyst by bringing players together to encourage the formation of innovative solutions rather than intervening in a broad and possibly blunt way. This role requires an element of risk and 'letting go' rather than devising programmes with clearly de?ned outcomes and targets – somewhat anathema to the Treasury with its emphasis on performance targets as set out in the PSAs. Rebecca Harding looks at the establishment of regional venture capital funds, arguing that in the north of England the main problem may be the lack of demand for venture capital, so that it may not be the correct tool for supporting innovative small businesses in all regions. Robert Atkinson explodes some of the myths held about the emerging 'new economy'. This includes the notion that technological change is destroying employment (preposterous when viewed against the tremendous jobs growth in the US economy) or that economic change calls into question the continued viability of large corporations or the role of the state.Finally David Osmon offers a different model from the government's proposed public private partnership for achieving a more efficient London Underground. The combined infrastructure and operations of some underground lines could be leased to the private sector which could then compete with the publicly operated lines. If the private companies achieved efficiency savings they could then bid for further franchises and in the meantime those lines still in public ownership would be subject to competitive pressures to increase their efficiency. With all the uncertainty surrounding the current PPP this idea is worthy of consideration.
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Previously posted on May 10/22 and Jan 30/23 Kissinger in Washington, May 7, 2022Henry Kissinger will be one hundred years old in a few weeks and has published five books since he turned ninety. Along with President Nixon, he futilely prolonged and escalated the Vietnam War for four years when defeat was already inevitable. But he also received the Nobel Peace Prize precisely for negotiating the ceasefire for that same war. His doctrine also has these two faces. On the one hand, he conceives international politics as the interaction between states seeking power. On the other hand, he favors the balance of powers so that no one is able to fully impose its dominance on the others. In the academic literature, Kissinger's approach is called "realism" and is widely accepted. The main alternative is the so-called "liberal" approach, which trusts in the ability of institutions to prevent wars and keep peace. From there arose the League of Nations, which failed, and the United Nations and its specialized organizations, which have had significant success on many issues, but are also currently showing their insufficiency. The most accurate postulate of the realists is that the world is more peaceful when there are multiple powers than when there are only two, as in the Cold War, or a single super-dominant one, as seemed to be the case with the United States after the dissolution of the Soviet Union. The success of the formula requires that the multilateral equilibrium could only be overthrown by an effort of a magnitude too difficult to mount. As a historical example, Kissinger has analyzed and praised the so-called Concert of Europe that was formed, after the defeat of Napoleon's France, by Great Britain, Russia, Prussia, Austria, and also recovered France. According to his interpretation, the Concert "came close to constituting the government of Europe" and achieved a long period without European-wide wars. The balance was upset by the unification of Germany at the end of the 19th century and its consequent aggressive expansionism, which led to the absurd and catastrophic First World War. Taking a similar approach, Kissinger continues to praise the construction of the European Union, which has prevented new general wars on the continent. During his time in government, the biggest concern was that communism would end up dominating the world according to the domino theory, whereby the fall of a piece like Indochina would be followed by Burma and Thailand, as well as Indonesia (which, in fact, was very close), and from there, India, Japan, the Middle East... That's why the Vietnam war extended to Laos and Cambodia. But this is also the reason for the diplomatic opening to China, to break the Sino-Soviet bloc and achieve a certain multilateral balance. The current interest of the discussion is that the role of the United States as the only superpower may be less exclusive and exclusionary than it seemed. A version of political realism in academia tends to analyze international relations "after hegemony" as a ground for "anarchy", that is, destructive conflicts and wars. However, the changes around the Ukrainian war can be read as a new opportunity for multilateral cooperation. The United States has the initiative and many economic and military resources, but, paradoxically, it may have a good opportunity to expand pluralism. In the new situation of divided government between the Presidency and Congress, the most ambitious projects in domestic policy are paralyzed, so Joe Biden can focus on foreign policy, where he has more power, and expand multilateral cooperation. The European Union is beginning to develop, for the first time, a spirited common international policy, in contrast to the dissent during the Iraq war, when the governments of Britain and Spain were on one side and those of France and Germany on the other. The rulers of China and India, which are rivals to each other, have told Russia that the world is not ready for war. This configuration with more than three major powers points to a balance of powers capable of avoiding polarization, since, otherwise, a coalition of two-to-one preludes conflict. Specifically, the Group of Seven, which is the nucleus of a latent world government, needs to work more closely with some members of the Group of Twenty, which includes India and China, so that its decisions are widely accepted and effective. Negotiations between the US and the EU for the Transatlantic Trade and Investment Partnership (TTIP), in which substantive agreements had been reached, were paralyzed by Trump, and could now be revived. The Trans-Pacific Agreement for Economic Cooperation was also abandoned by Trump, but the other eleven initial countries went ahead on their own and ended up signing the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), to which China has presented its candidacy. Many in the United States are clamoring for re-entry in what had been its own initiative. And after the war in Ukraine, a new international structure will have to be defined, especially for Central and Eastern Europe, in which, as Kissinger said in a recent interview, "Russia should find a place." Realism shows that the seeking for power explains many things, and the balance of power can prevent a general war. But when there is neither a single dominant power nor a confrontation between two, "liberal" rules and institutions may be the best mechanism for peace and multilateral cooperation.Also in Spanish in the daily La Vanguardia-click While President Biden is not clear, and sometimes he is confusing about how the war in Ukraine could end, some other voices in Washington can speak and suggest more clearly. Several of them did it a few days ago at the Financial Times Weekend Festival, which was held, for the first time outside England, at the Kennedy Center for the Performing Arts in Washington.The first surprisingly constructive intervention was from William J. Burns, the current CIA Director. Just a year ago, he came from retirement after a long career as a diplomat, and as such, in his presentation, the conversation with an FT journalist, and the dialogue with the audience, he showed a broader vision than the usual spies. When he was Ambassador in Boris Yeltsin's Moscow in the mid-1990s, Burns already felt that the NATO expansion until the borders of Russia was "premature at best, and needlessly provocative at worst." More specifically, to push for NATO membership of Ukraine and Georgia was "a serious strategic mistake that did indelible damage" –an opinion that at the time was shared by the governments of France and Germany. In an official encounter, Putin had told him that Ukraine in NATO "would be a hostile act toward Russia."Burns emphasized, of course, that there is "absolutely no justification for the invasion of Ukraine." Yet, he resumed that kind of strategic explanation while dismissing the ideological elaborations that pretend either justify or condemn the attack. In short: Russia has "pushed back" after Ukraine moved westward away from Russian influence.In his view, nevertheless, Putin miscalculated regarding the power of the Russian Army (which was sent to a "special operation" not planned by its generals), about Ukrainian resistance, and with the supposition that the West would be distracted by elections in Germany and France. He tried to explain the recent candidacies of Sweden and Finland to NATO as a deterrent against Putin's other potential attacks in the future. But the Director of the CIA did not utter a word that could be interpreted as supporting Ukraine's NATO membership.Even more thrilling was the participation of Henry Kissinger on "the new world disorder." The former Secretary of State is 99 years old this month, announced a new book of immediate publication, and for nearly one hour was focused, clear, and insightful, also in a dialogue with the audience. Kissinger started by using his academic background and remarking that the foreign policy's main priority of Russia, which is the largest country in the world, has always been to protect its huge territory from invasions. From this perspective, after the Cold War, the country's leadership was "offended" by NATO's absorption of Eastern Europe.Now –he noted— public discussion on Ukraine is all about confrontation, but by reflecting on the previous failures of the several governments he advised, he lamented that, again, nobody knows where we are going. Kissinger had already opposed Ukraine's candidacy to NATO when President Bush and Vice-president Cheney launched it in 2008. Six years later, at the Russian occupation of Crimea, he warned that Ukraine should not join either the East or the West, but it should function as "a bridge" between the two. He had predicted that otherwise, "the drift toward confrontation would accelerate."Most striking was his warning about the use of nuclear weapons. "I would not make Ukraine's membership to NATO a key issue," he remarked at the Kennedy Center. It would be "unwise to take an adversarial position," mainly because of the horrible danger of a nuclear war. His approach was certainly in contrast with that in the 1970s, of which he was reminded, when the gibberish theory of the "domino" was used to attack one country after another. Bush and Cheney still used that approach in the early 2000s to justify "preventive wars." I got the impression that with aging, intelligent people like Kissinger may feel that it is not worth trying to deceive himself again, and despite his physical frailness (or perhaps because of that), his more mature brain moves in the direction of more honest and clear thinking. His main argument was that in the past, although confrontation was addressed to "preserve the balance of power" between the US and the Soviet Union, at the same time, he also promoted agreements for nuclear arms reduction and control. Nowadays, modern technology would produce much worse destruction, so he claimed for a "new era" in which the governments should take more care about the consequences of nuclear arms and favor diplomacy above all. Kissinger reminded the audience that, in the past, nuclear countries such as the Soviet Union and the United States accepted military defeats from non-nuclear countries, such as in Vietnam and (both) in Afghanistan. Even more now, "we have to deescalate to conventional arms and learn to live with adversarial relations." Kissinger has met Putin more than twenty times and asserted that "there is still room for negotiation" with him. In Spanish in the daily La Vanguardia
Publisher's version (útgefin grein) ; Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd. ; Research reported in this publication was supported by the Bill & Melinda Gates Foundation; the University of Melbourne; Queensland Department of Health, Australia; the National Health and Medical Research Council, Australia; Public Health England; the Norwegian Institute of Public Health; St Jude Children's Research Hospital; the Cardiovascular Medical Research and Education Fund; the National Institute on Ageing of the National Institutes of Health (award P30AG047845); and the National Institute of Mental Health of the National Institutes of Health (award R01MH110163). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. The authors alone are responsible for the views expressed in this Article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated, the National Health Service (NHS), the National Institute for Health Research (NIHR), the UK Department of Health and Social Care, or Public Health England; the United States Agency for International Development (USAID), the US Government, or MEASURE Evaluation; or the European Centre for Disease Prevention and Control (ECDC). This research used data from the Chile National Health Survey 2003, 2009-10, and 2016-17. The authors are grateful to the Ministry of Health, the survey copyright owner, for allowing them to have the database. All results of the study are those of the authors and in no way committed to the Ministry. The Costa Rican Longevity and Healthy Aging Study project is a longitudinal study by the University of Costa Rica's Centro Centroamericano de Poblacion and Instituto de Investigaciones en Salud, in collaboration with the University of California at Berkeley. The original pre-1945 cohort was funded by the Wellcome Trust (grant 072406), and the 1945-55 Retirement Cohort was funded by the US National Institute on Aging (grant R01AG031716). The principal investigators are Luis Rosero-Bixby and William H Dow and co-principal investigators are Xinia Fernandez and Gilbert Brenes. The accuracy of the authors' statistical analysis and the findings they report are not the responsibility of ECDC. ECDC is not responsible for conclusions or opinions drawn from the data provided. ECDC is not responsible for the correctness of the data and for data management, data merging and data collation after provision of the data. ECDC shall not be held liable for improper or incorrect use of the data. The Health Behaviour in School-Aged Children (HBSC) study is an international study carried out in collaboration with WHO/EURO. The international coordinator of the 1997-98, 2001-02, 2005-06, and 2009-10 surveys was Candace Currie and the databank manager for the 1997-98 survey was Bente Wold, whereas for the following surveys Oddrun Samdal was the databank manager. A list of principal investigators in each country can be found on the HBSC website. Data used in this paper come from the 2009-10 Ghana Socioeconomic Panel Study Survey, which is a nationally representative survey of more than 5000 households in Ghana. The survey is a joint effort undertaken by the Institute of Statistical, Social and Economic Research (ISSER) at the University of Ghana and the Economic Growth Centre (EGC) at Yale University. It was funded by EGC. ISSER and the EGC are not responsible for the estimations reported by the analysts. The Palestinian Central Bureau of Statistics granted the researchers access to relevant data in accordance with license number SLN2014-3-170, after subjecting data to processing aiming to preserve the confidentiality of individual data in accordance with the General Statistics Law, 2000. The researchers are solely responsible for the conclusions and inferences drawn upon available data. Data for this research was provided by MEASURE Evaluation, funded by USAID. The authors thank the Russia Longitudinal Monitoring Survey, conducted by the National Research University Higher School of Economics and ZAO Demoscope together with Carolina Population Center, University of North Carolina at Chapel Hill and the Institute of Sociology, Russia Academy of Sciences for making data available. This paper uses data from the Bhutan 2014 STEPS survey, implemented by the Ministry of Health with the support of WHO; the Kuwait 2006 and 2014 STEPS surveys, implemented by the Ministry of Health with the support of WHO; the Libya 2009 STEPS survey, implemented by the Secretariat of Health and Environment with the support of WHO; the Malawi 2009 STEPS survey, implemented by Ministry of Health with the support of WHO; and the Moldova 2013 STEPS survey, implemented by the Ministry of Health, the National Bureau of Statistics, and the National Center of Public Health with the support of WHO. This paper uses data from Survey of Health, Ageing and Retirement in Europe (SHARE) Waves 1 (DOI:10.6103/SHARE. w1.700), 2 (10.6103/SHARE.w2.700), 3 (10.6103/SHARE.w3.700), 4 (10.6103/SHARE.w4.700), 5 (10.6103/SHARE.w5.700), 6 (10.6103/SHARE.w6.700), and 7 (10.6103/SHARE.w7.700); see Borsch-Supan and colleagues (2013) for methodological details. The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193, COMPARE: CIT5-CT-2005-028857, SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N degrees 211909, SHARE-LEAP: GA N degrees 227822, SHARE M4: GA N degrees 261982) and Horizon 2020 (SHARE-DEV3: GA N degrees 676536, SERISS: GA N degrees 654221) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2, P01_AG005842, P01_AG08291, P30_AG12815, R21_AG025169, Y1-AG-4553-01, IAG_BSR06-11, OGHA_04-064, HHSN271201300071C), and from various national funding sources is gratefully acknowledged. This study has been realised using the data collected by the Swiss Household Panel, which is based at the Swiss Centre of Expertise in the Social Sciences. The project is financed by the Swiss National Science Foundation. The United States Aging, Demographics, and Memory Study is a supplement to the Health and Retirement Study (HRS), which is sponsored by the National Institute of Aging (grant number NIA U01AG009740). It was conducted jointly by Duke University and the University of Michigan. The HRS is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan. This paper uses data from Add Health, a program project designed by J Richard Udry, Peter S Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due to Ronald R Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website. No direct support was received from grant P01-HD31921 for this analysis. The data reported here have been supplied by the United States Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. Collection of data for the Mozambique National Survey on the Causes of Death 2007-08 was made possible by USAID under the terms of cooperative agreement GPO-A-00-08-000_D3-00. This manuscript is based on data collected and shared by the International Vaccine Institute (IVI) from an original study IVI conducted. L G Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Brazil; finance code 001) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, a Brazilian funding agency). I N Ackerman was supported by a Victorian Health and Medical Research Fellowship awarded by the Victorian Government. O O Adetokunboh acknowledges the South African Department of Science and Innovation and the National Research Foundation. A Agrawal acknowledges the Wellcome Trust DBT India Alliance Senior Fellowship. S M Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. M Ausloos, C Herteliu, and A Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. A Badawi is supported by the Public Health Agency of Canada. D A Bennett was supported by the NIHR Oxford Biomedical Research Centre. R Bourne acknowledges the Brien Holden Vision Institute, University of Heidelberg, Sightsavers, Fred Hollows Foundation, and Thea Foundation. G B Britton and I Moreno Velasquez were supported by the Sistema Nacional de Investigacion, SNI-SENACYT, Panama. R Buchbinder was supported by an Australian National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship. J J Carrero was supported by the Swedish Research Council (2019-01059). F Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. A R Chang was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK106515. V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundacao para a Ciencia e Tecnologia, IP, under the Norma Transitaria DL57/2016/CP1334/CT0006. A Douiri acknowledges support and funding from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South London at King's College Hospital NHS Foundation Trust and the Royal College of Physicians, and support from the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. B B Duncan acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. H E Erskine is the recipient of an Australian NHMRC Early Career Fellowship grant (APP1137969). A J Ferrari was supported by a NHMRC Early Career Fellowship grant (APP1121516). H E Erskine and A J Ferrari are employed by and A M Mantilla-Herrera and D F Santomauro affiliated with the Queensland Centre for Mental Health Research, which receives core funding from the Queensland Department of Health. M L Ferreira holds an NHMRC Research Fellowship. C Flohr was supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust. M Freitas acknowledges financial support from the EU (European Regional Development Fund [FEDER] funds through COMPETE POCI-01-0145-FEDER-029248) and National Funds (Fundacao para a Ciencia e Tecnologia) through project PTDC/NAN-MAT/29248/2017. A L S Guimaraes acknowledges support from CNPq. C Herteliu was partially supported by a grant co-funded by FEDER through Operational Competitiveness Program (project ID P_40_382). P Hoogar acknowledges Centre for Bio Cultural Studies, Directorate of Research, Manipal Academy of Higher Education and Centre for Holistic Development and Research, Kalaghatagi. F N Hugo acknowledges the Visiting Professorship, PRINT Program, CAPES Foundation, Brazil. B-F Hwang was supported by China Medical University (CMU107-Z-04), Taichung, Taiwan. S M S Islam was funded by a National Heart Foundation Senior Research Fellowship and supported by Deakin University. R Q Ivers was supported by a research fellowship from the National Health and Medical Research Council of Australia. M Jakovljevic acknowledges the Serbian part of this GBD-related contribution was co-funded through Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. P Jeemon was supported by a Clinical and Public Health intermediate fellowship (grant number IA/CPHI/14/1/501497) from the Wellcome Trust-Department of Biotechnology, India Alliance (2015-20). O John is a recipient of UIPA scholarship from University of New South Wales, Sydney. S V Katikireddi acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_12017/13, MC_UU_12017/15), and the Scottish Government Chief Scientist Office (SPHSU13, SPHSU15). C Kieling is a CNPq researcher and a UK Academy of Medical Sciences Newton Advanced Fellow. Y J Kim was supported by Research Management Office, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/00010). K Krishan is supported by UGC Centre of Advanced Study awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar was supported by K43 TW 010716 FIC/NIMH. B Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. J V Lazarus was supported by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III [ISCIII]/ESF, the EU [CP18/00074]). K J Looker thanks the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol, in partnership with Public Health England, for research support. S Lorkowski was funded by the German Federal Ministry of Education and Research (nutriCARD, grant agreement number 01EA1808A). R A Lyons is supported by Health Data Research UK (HDR-9006), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. J J McGrath is supported by the Danish National Research Foundation (Niels Bohr Professorship), and the Queensland Health Department (via West Moreton HHS). P T N Memiah acknowledges support from CODESRIA. U O Mueller gratefully acknowledges funding by the German National Cohort Study BMBF grant number 01ER1801D. S Nomura acknowledges the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). A Ortiz was supported by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. S B Patten was supported by the Cuthbertson & Fischer Chair in Pediatric Mental Health at the University of Calgary. G C Patton was supported by an aNHMRC Senior Principal Research Fellowship. M R Phillips was supported in part by the National Natural Science Foundation of China (NSFC, number 81371502 and 81761128031). A Raggi, D Sattin, and S Schiavolin were supported by grants from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4-Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). P Rathi and B Unnikrishnan acknowledge Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. A L P Ribeiro was supported by Brazilian National Research Council, CNPq, and the Minas Gerais State Research Agency, FAPEMIG. D C Ribeiro was supported by The Sir Charles Hercus Health Research Fellowship (#18/111) Health Research Council of New Zealand. D Ribeiro acknowledges financial support from the EU (FEDER funds through the Operational Competitiveness Program; POCI-01-0145-FEDER-029253). P S Sachdev acknowledges funding from the NHMRC of Australia Program Grant. A M Samy was supported by a fellowship from the Egyptian Fulbright Mission Program. M M Santric-Milicevic acknowledges the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract number 175087). R Sarmiento-Suarez received institutional support from Applied and Environmental Sciences University (Bogota, Colombia) and ISCIII (Madrid, Spain). A E Schutte received support from the South African National Research Foundation SARChI Initiative (GUN 86895) and Medical Research Council. S T S Skou is currently funded by a grant from Region Zealand (Exercise First) and a grant from the European Research Council under the EU's Horizon 2020 research and innovation program (grant agreement number 801790). J B Soriano is funded by Centro de Investigacion en Red de Enfermedades Respiratorias, ISCIII. R Tabares-Seisdedos was supported in part by the national grant PI17/00719 from ISCIII-FEDER. N Taveira was partially supported by the European & Developing Countries Clinical Trials Partnership, the EU (LIFE project, reference RIA2016MC-1615). S Tyrovolas was supported by the Foundation for Education and European Culture, the Sara Borrell postdoctoral programme (reference number CD15/00019 from ISCIII-FEDER). S B Zaman received a scholarship from the Australian Government research training programme in support of his academic career. ; "Peer Reviewed"
Publisher's version (útgefin grein) ; Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10− 9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes. ; 1000BRAINS: 1000BRAINS is a population-based cohort based on the Heinz-Nixdorf Recall Study and is supported in part by the German National Cohort. We thank the Heinz Nixdorf Foundation (Germany) for their generous support in terms of the Heinz Nixdorf Study. The HNR study is also supported by the German Ministry of Education and Science (FKZ 01EG940), and the German Research Council (DFG, ER 155/6-1). The authors are supported by the Initiative and Networking Fund of the Helmholtz Association (Svenja Caspers) and the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement 7202070 (Human Brain Project SGA1; Katrin Amunts, Sven Cichon). This work was further supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e:Med Program (grant 01ZX1314A to M.M.N. and S.C.), and by the Swiss National Science Foundation (SNSF, grant 156791 to S.C.). 16p.11.2 European Consortium: B.D. is supported by the Swiss National Science Foundation (NCCR Synapsy, project grant Nr 32003B_159780) and Foundation Synapsis. LREN is very grateful to the Roger De Spoelberch and Partridge Foundations for their generous financial support. This work was supported by grants from the Simons Foundation (SFARI274424) and the Swiss National Science Foundation (31003A_160203) to A.R. and S.J. Betula: The relevant Betula data collection and analyses were supported by a grant from the Knut & Alice Wallenberg (KAW) to L. Nyberg. Brainscale: the Brainscale study was supported by the Netherlands Organization for Scientific Research MagW 480-04-004 (Dorret Boomsma), 51.02.060 (Hilleke Hulshoff Pol), 668.772 (Dorret Boomsma & Hilleke Hulshoff Pol); NWO/SPI 56-464-14192 (Dorret Boomsma), the European Research Council (ERC-230374) (Dorret Boomsma), High Potential Grant Utrecht University (Hilleke Hulshoff Pol), NWO Brain and Cognition 433-09-220 (Hilleke Hulshoff Pol). Brain Imaging Genetics (BIG): This work makes use of the BIG database, first established in Nijmegen, The Netherlands, in 2007. This resource is now part of Cognomics (www.cognomics.nl), a joint initiative by researchers of the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud university medical centre and the Max Planck Institute for Psycholinguistics in Nijmegen. The Cognomics Initiative has received supported from the participating departments and centres and from external grants, i.e., the Biobanking and Biomolecular Resources Research Infrastructure (the Netherlands) (BBMRI-NL), the Hersenstichting Nederland, and the Netherlands Organisation for Scientific Research (NWO). The research leading to these results also receives funding from the NWO Gravitation grant 'Language in Interaction', the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreements n° 602450 (IMAGEMEND), n°278948 (TACTICS), and n°602805 (Aggressotype) as well as from the European Community's Horizon 2020 programme under grant agreement n° 643051 (MiND) and from ERC-2010-AdG 268800-NEUROSCHEMA. In addition, the work was supported by a grant for the ENIGMA Consortium (grant number U54 EB020403) from the BD2K Initiative of a cross-NIH partnership. COBRE: This work was supported by a NIH COBRE Phase I grant (1P20RR021938, Lauriello, PI and 2P20GM103472, Calhoun, PI) awarded to the Mind Research Network. We wish to express our gratitude to numerous investigators who were either external consultants to the Cores and projects, mentors on the projects, members of the external advisory committee and members of the internal advisory committee. Decode: The research leading to these results has received financial contribution from the European Union's Seventh Framework Programme (EU-FP7/2007–2013), EU-FP7 funded grant no. 602450 (IMAGEMEND) as well as support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no.115300 (EUAIMS). DemGene: Norwegian Health Association and Research Council of Norway. Dublin: Work was supported by Science Foundation Ireland (SFI grant 12/IP/1359 to Gary Donohoe and SFI08/IN.1/B1916-Corvin to Aidan C Corvin) and the European Research Council (ERC-StG-2015-677467). EPIGEN-UK (SMS, CL): The work was partly undertaken at UCLH/UCL, which received a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centres funding scheme. We are grateful to the Wolfson Trust and the Epilepsy Society for supporting the Epilepsy Society MRI scanner, and the Epilepsy Society for supporting CL. Haavik: The work at the K.G.Jebsen center for neuropsychiatric disorders at the University of Bergen, Norway, was supported by Stiftelsen K.G. Jebsen, European Community's Seventh Framework Program under grant agreement no 602805 and the H2020 Research and Innovation Program under grant agreement numbers 643051 and 667302. HUNT: The HUNT Study is a collaboration between HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health. HUNT-MRI was funded by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Norwegian National Advisory Unit for functional MRI. IMAGEN: The work received support from the European Union-funded FP6Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant 'STRATIFY' (Brain network based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), the FP7 projects IMAGEMEND (602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300), the Medical Research Council Grant 'c-VEDA' (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-1, SM 80/7-2, SFB 940/1). Further support was provided by grants from: ANR (project AF12-NEUR0008-01—WM2NA, and ANR-12-SAMA-0004), the Fondation de France, the Fondation pour la Recherche Médicale, the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. MCIC: This work was supported primarily by the Department of Energy DE-FG02-99ER62764 through its support of the Mind Research Network and the consortium as well as by the National Association for Research in Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award (to SE) as well as through the Blowitz-Ridgeway and Essel Foundations, and through NWO ZonMw TOP 91211021, the DFG research fellowship (to SE), the Mind Research Network, National Institutes of Health through NCRR 5 month-RR001066 (MGH General Clinical Research Center), NIMH K08 MH068540, the Biomedical Informatics Research Network with NCRR Supplements to P41 RR14075 (MGH), M01 RR 01066 (MGH), NIBIB R01EB006841 (MRN), R01EB005846 (MRN), 2R01 EB000840 (MRN), 1RC1MH089257 (MRN), as well as grant U24 RR021992. NCNG: this sample collection was supported by grants from the Bergen Research Foundation and the University of Bergen, the Dr Einar Martens Fund, the K.G. Jebsen Foundation, the Research Council of Norway, to SLH, VMS and TE. The Bergen group was supported by grants from the Western Norway Regional Health Authority (Grant 911593 to AL, Grant 911397 and 911687 to AJL). NESDA: Funding for NESDA was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10-000-1002); the Center for Medical Systems Biology (CSMB, NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University's Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health.Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. NTR: The NTR study was supported by the Netherlands Organization for Scientific Research (NWO), MW904-61-193 (Eco de Geus & Dorret Boomsma), MaGW-nr: 400-07- 080 (Dennis van 't Ent), MagW 480-04-004 (Dorret Boomsma), NWO/SPI 56-464-14192 (Dorret Boomsma), the European Research Council, ERC-230374 (Dorret Boomsma), and Amsterdam Neuroscience. OATS: OATS (Older Australian Twins Study) was facilitated by access to Twins Research Australia, which is funded by a National Health and Medical Research Council (NHMRC) Enabling Grant 310667. OATS is also supported via a NHMRC/Australian Research Council Strategic Award (401162) and a NHMRC Project Grant (1045325). DNA extraction was performed by Genetic Repositories Australia, which was funded by a NHMRC Enabling Grant (401184). OATS genotyping was partly funded by a Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund Grant. PAFIP: PAFIP data were collected at the Hospital Universitario Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Carlos III Health Institute PIE14/00031 and SAF2013-46292-R and SAF2015-71526-REDT. We wish to acknowledge IDIVAL Neuroimaging Unit for imaging acquirement and analysis.We want to particularly acknowledge the patients and the BioBankValdecilla (PT13/0010/0024) integrated in the Spanish National Biobanks Network for its collaboration. QTIM: The QTIM study was supported by grants from the US National Institute of Child Health and Human Development (R01 HD050735) and the Australian National Health and Medical Research Council (NHMRC) (486682, 1009064). Genotyping was supported by NHMRC (389875). Lachlan Strike is supported by an Australian Postgraduate Award (APA). AFM is supported by NHMRC CDF 1083656. We thank the twins and siblings for their participation, the many research assistants, as well as the radiographers, for their contribution to data collection and processing of the samples. SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, 01ZZ0403 and 01ZZ0701), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network 'Greifswald Approach to Individualized Medicine (GANI_MED)' funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. Whole-body MR imaging was supported by a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. StrokeMRI: StrokeMRI has been supported by the Research Council of Norway (249795), the South-Eastern Norway Regional Health Authority (2014097, 2015044, 2015073) and the Norwegian ExtraFoundation for Health and Rehabilitation. TOP: TOP is supported by the Research Council of Norway (223273, 213837, 249711), the South East Norway Health Authority (2017-112), the Kristian Gerhard Jebsen Stiftelsen (SKGJ‐MED‐008) and the European Community's Seventh Framework Programme (FP7/2007–2013), grant agreement no. 602450 (IMAGEMEND). We acknowledge the technical support and service from the Genomics Core Facility at the Department of Clinical Science, the University of Bergen ; Peer Reviewed
In 2017, the Central American Agricultural Council (CAC), with the support of CCAFS, CIAT, IICA, FAO, ECLAC and CATIE, formulated and adopted the Climate Smart Agriculture Strategy (EASAC) for the Central American Integration System (SICA) region. This regional strategy aims at promoting climate-smart agriculture (CSA) at scale and is an original example of regional policy. This communication presents the first results of an assessment process of the EASAC outcomes three years after its launch. We carried out a methodology mobilizing the theory-based assessment (Delahais and Toulemonde 2012; Lemire, et al. 2012, Maine, 2008) applied to a policy innovation, in this case, the EASAC. Theory-based approaches have been designed to provide systematic, robust approaches to understand whether the intended outcomes of an intervention have been achieved (or not), and the importance of the intervention's contribution under consideration, relative to that of other alternative causes. This assessment process encompasses three steps: (i) the formulation of the EASAC Theory of Change (ToC), (ii) the identification of changes aligned with the ToC and (iii) the analysis of EASAC's contribution to some of these identified changes. In this communication, we present the results of the two first above mentioned steps. To establish the EASAC ToC, we first reformulated the EASAC into a ToC vocabulary/thinking starting from the policy document (CAC, 2017) and adjusting it through an iterative process of consultation and validation with 8 key actors (EASAC formulators). Once the ToC validated, we conducted 44 semi-directed interviews with actors involved in CSA related actions or interventions at regional and national level of the 8 countries of SICA. The objective of these interviews was to understand what expected changes identified in the EASAC ToC have occurred so far. Finally, the changes were analyzed and compared across and among countries. The EASAC ToC is structured along four routes: (1) policy route, (2) institutional, (3) financing and (4) communication. The four routes aim through the formulation and implementation of CSA policies (policy route); the creation and promotion of spaces for CSA dialogue and partnerships and the strengthening of CSA capacities of actors (institutional route); the development of a portfolio of CSA projects to apply to competitive international funds (financial route); the implementation of communication campaigns to foster the implementation of the EASAC (communication route) to a final outcome: the adoption of CSA practices, services and technologies by local farmers and thus achieve a great impact focused on a more productive, adapted and resilient agriculture in the face of climate change (CC). Results related to the identification of changes aligned with the ToC show that, although the EASAC was launched only 3 year ago, 252 changes related to the four EASAC ToC routes were identified in all countries of SICA and at the regional level to date, attesting of a great dynamic toward CSA scaling in the region. A total of 225 changes occurred in the eight countries in the SICA region. Costa Rica and Guatemala stand out with the highest number of changes identified. Honduras, El Salvador and Nicaragua show with an average progress, and finally Panamá, the Dominican Republic and Belize exhibit the lowest number of changes observed. The remaining 27 identified changes were exclusively at the regional level. The policy route is the strongest and most profuse as it concentrates the largest number of changes identified (182 changes) that mostly (98) correspond to the formulation and implementations of CSA conducive policies at regional, national and/or subnational levels concentrated in Costa Rica, Guatemala, Honduras and El Salvador. The remaining changes (84) are local implemented CSA conducive projects that respond to regional programs (sometimes 'jumping' the national level) such as EUROCLIMA+, FAO-EU FLEGT - Latin America, REDD+, RECLIMA, RELIVE, BIOCLIMA, ARAUCLIMA, AGROINNOVA, PROCAGICA, among others. However, the CSA approach has yet to be incorporated further into the planning, research, monitoring and evaluation processes of the agricultural sector at both the regional and national levels. The institutional route, although less developed than the policy route, presents a total of 45 changes distributed in three dimensions: i) the creation and promotion of coordination initiatives, alliances and CSA dialogue spaces at regional and national levels, ii) the strengthening of CSA capacities of governments, research actors and extension systems at national level and iii) financial services designed and implemented through specific programs, mainly supported by regional cooperation (ECLAC). Most of the changes in this route corresponds to CSA dialogue spaces and alliances mainly in Costa Rica, Guatemala and El Salvador. However, there is a gap between countries in the creation and diversification of coordination initiatives, alliances and spaces for dialogue for the promotion and follow-up of the CSA approach. Moreover, there is a lack of institutionalization of the programs for research actors, public officials and extensionists to strengthen their capacities to formulate and implement CSA practices, services and technologies. The financing route has been strengthened mainly through technical and financial support from international cooperation agencies with 25 changes identified at the regional and national levels mostly impulse by a regional initiative from FAO in partnership with the Central American Bank for Economic Integration (CABEI) that seeks to facilitate access to climate finance and strengthen the national capacities of the countries to create a portfolio of CSA projects in the region. Even though there are advances in this route, some aspects pointed out in the EASAC are still missing or are partly implemented. A consolidated portfolio of CSA projects and an updated database on sources of climate financing need to be consolidated. Besides, more work must be done on the creation of alliances to promote financial services and, to consolidate a common agenda of CSA climate action in Central America. Finally, regarding the communication route, no changes were observed so far. Considering the orientation of changes both at regional and country levels, the emphasis of the changes has been oriented more towards adaptation to CC (137) than mitigation (36), although the CSA approach integrate both adaptation and mitigation. The agricultural sectors most prioritized have been cattle raising (73), coffee (44), and some basic grains: corn (15), rice (14) and beans (13). In addition, the predominant issues on the sector's policy agenda in the countries have been water resource sustainability (45), food and nutritional security (FNS) and family agriculture (95). Finally, it is worth noting that the changes identified tends to be geographically concentrated in the Central American Dry Corridor, although the aim of the intervention is to expand the scope of these measures to other areas of the region. The first results of the evaluation of the effect to date of the EASAC provides original insights to the discussion on the effectiveness of scaling up CSA through a regional policy framework, on the effectiveness of EASAC ToC and its implementation features. To go deeper into this, a rigorous and systematic analysis must be conducted in a second phase of this study to assess the degree of contribution of the EASAC to these identified changes. However, these first results of the assessment process is of interest to regional and national stakeholders in particular CAC executive secretariats well as scholars and practitioners as they enable to draw preliminary recommendations to support the implementation of EASAC in the region and lessons learned for strengthening enabling policy environments to achieve CSA goals in the region and other parts of the world.
Background There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. ; AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N. 340541. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK, Genome Quebec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Quebec Sante (FRQS). TN is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Quebec Ministry of Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research Scholarship. Support from Calcul Quebec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London. The Biobanque Quebec COVID19 is funded by FRQS, Genome Quebec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Quebec Sante. These funding agencies had no role in the design, implementation or interpretation of this study. The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of Excellence 2167 Precision Medicine in Chronic Inflammation (PMI) (DFG Grant: EXC2167). The COVID19-Host(a)ge study was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). Genotyping in COVID19-Host(a)ge was supported by a philantropic donation from Stein Erik Hagen. The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia and also by the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by Consejeria de Salud y Familias of the Andalusian Government. DMM is currently funded by the the Andalussian government (Proyectos Estrategicos-Fondos Feder PE-0451-2018). The Columbia University Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Columbia University. The SPGRX study was supported by the Consejeria de Economia, Conocimiento, Empresas y Universidad #CV20-10150. The GEN-COVID study was funded by: the MIUR grant Dipartimenti di Eccellenza 2018-2020 to the Department of Medical Biotechnologies University of Siena, Italy; the Intesa San Paolo 2020 charity fund dedicated to the project NB/2020/0119; and philanthropic donations to the Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by Tuscany Region Bando Ricerca COVID-19 Toscana grant to the Azienda Ospedaliero Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA consortium for providing computational resources; the Network for Italian Genomes (NIG) (http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for managing specimens. Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the Dolce&Gabbana Fashion Firm is gratefully acknowledged. Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione IRCCS Ca Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- Liver Investigation: Testing Marker Utility in Steatohepatitis, Programme Photonics under grant agreement 101016726 for the project REVEAL: Neuronal microscopy for cell behavioural examination and manipulation, Fondazione Patrimonio Ca' Granda Liver Bible PR-0361. DP was supported by Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, CV PREVITAL Strategie di prevenzione primaria nella popolazione Italiana Ministero della Salute, and Associazione Italiana per la Prevenzione dell'Epatite Virale (COPEV). Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the Fonds Erasme. The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2) study was supported by grants from Fondation Leon Fredericq and from Fonds de la Recherche Scientifique (FNRS). The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones Cientificas. KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project grant to Michael Hultstrom (KAW 2020.0182) and the Swedish Research Council to Robert Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus Bergvalls Stiftelse. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland. ; No
In: Jensen , M B 2016 , Environmental assessment of biowaste management in the Danish-German border region . Technical University of Denmark, DTU Environment , Kgs. Lyngby .
De seneste år har der været et øget politisk fokus på behandling af organisk husholdningsaffald, der samtidigt behandles forskelligt fra land til land. I Danmark og Tyskland har behandlingen af organisk husholdningsaffald taget en meget anderledes drejning i det sidste århundrede. I Danmark indsamles det organiske husholdningsaffald som en del af restaffaldet, som primært forbrændes, og biologisk behandling er kun forsøgt i begrænset omfang. Tyskland derimod har fokuseret kraftigt på kildesortering med efterfølgende biologisk behandling og en blanding af forbrænding og mekanisk-biologisk behandling af det organiske husholdningsaffald i restaffaldet. Danmark har i de senere år øget fokus på at bevæge sig væk fra affaldsforbrænding og i stedet øge materialegenanvendelse, både på eget initiativ, men også drevet af EU's mål på 50% genanvendelse i 2020. Dette fokus omfatter genanvendelse af organisk husholdningsaffald samt tørre affaldsfraktioner. Dette ph.d.-projekt blev gennemført som et partnerskab mellem Danmark Tekniske Universitet og fem affaldshåndteringsselskaber på tværs af den dansk-tyske grænse, tre i Danmark og to i Tyskland, alle med ønsket om at øge kildesortering og adskilt behandling af det organiske husholdningsaffald. Den nuværende praksis på det danske område omfatter ikke kildesortering, og alt organisk husholdningsaffald forbrændes som en del af restaffaldet. Den tyske region har allerede en veletableret kildesortering, men ønsker at øge denne. Gennem livscyklusvurderinger og eksperimentelt arbejde på et kombineret biogas- og komposteringsanlæg, er resultatet af projektet blevet en anbefaling til affaldsselskaberne vedrørende øget genanvendelse af det organiske husholdningsaffald. En stor del af ph.d.-studiet var indsamling af data om alle aspekter af affaldshåndteringskæden. Alt fra affaldsmængder over indsamling og transport til behandling og endelig bortskaffelse blev analyseret. Den mest detaljerede analyse fandt sted på et kombineret biogas- og komposteringsanlæg, hvor faste og flydende prøver blev taget og diffuse luftemissioner blev målt. Livscyklusvurdering vurderer håndteringen af det organiske husholdningsaffald i den dansk-tyske grænseregion. Det vigtigste resultat af livscyklusvurderingen viser store forskelle i de miljømæssige effekter af de to forskellige regioner, hvor den danske region klarer sig bedst i de fleste påvirkningskategorier. Desuden er betydningen af energisystemerne undersøgt og viser, at resultaterne i høj grad er afhængige af det omgivende energisystem. Udover at sammenligne de to regioners aktuelle miljøpåvirkning med hinanden, blev de sammenlignet med fire fremtidsscenarier med øget kildesortering og forskellige biologiske behandlinger. Denne livscyklusvurdering er i dette tilfælde brugt som et planlægningsværktøj for det fremtidige affaldshåndteringssystem og til at identificere miljømæssige hotspots for både nuværende og mulige fremtidige systemer. I alle tilfælde viser resultaterne, at lokale forhold spiller en stor rolle for, hvordan systemet kan forbedres; konklusioner på et for overordnet niveau (alle fem affaldsselskaber sammen) kan føre til dårlige beslutninger, og det er vigtigt at se på hver affaldshåndteringsvirksomhed for sig. Vigtigst for de biologiske behandlingsanlæg er en høj produktion af biogas og lave emissioner (diffuse og direkte) af metan, lattergas og ammoniak. De diffuse emissioner målt ved et kombineret biogas- og komposteringsanlæg var meget væsentlige og en livscyklusvurdering førte til at anlægget, går fra at være en miljømæssig gevinst til en belastning i miljøpåvirkningskategorien "Global opvarmning". I sidste ende er øget kildesortering af organisk dagrenovation for de fem affaldsselskaber en realistisk mulighed, hvis fokus for virksomhederne er fleksibelt brændstof (biogas), kompostproduktion og deraf følgende ressourcebesparelser. Men billedet er ikke krystalklart, da den nuværende affaldsbehandling, hovedsagligt forbrænding, allerede fungerer godt, og i nogle tilfælde udkonkurrerer den biologiske behandling. ; The treatment of organic waste from households has gained significant interest in recent years. Each country in the EU and the rest of the world treat their organic waste in many different ways, and Denmark and Germany are no exemption in this regard. The treatment of household organic waste in these two countries has taken a very different turn in the last century. Denmark has been incinerating organic household waste as part of a residual waste policy for more than a century, but it has only attempted biological treatment to a limited extent. Germany, on the other hand, has focused intensely on source separation followed by biological treatment and a mixture of incineration and mechanical and biological treatment for any organic matter remaining in residual waste. In recent years, Denmark has increased its focus on moving away from incineration and increasing material recycling, both on its own initiative and also incentivised by the EU's 50% recycling target for 2020. This focus includes recycling organic waste from households as well as dry recyclable waste fractions. This PhD project was carried out as a cross-border partnership with five waste management companies, three located in Denmark and two in Germany, all with the wish to increase the source separation and treatment of organic household waste. The current practice in the Danish border region does not include source separation, and all organic household waste is incinerated as part of the residual waste. The German region already has a well-established source separation system, but it wants to increase its efficiency. The main aim of this Ph.D. thesis was to compare current organic waste management systems across the Danish-German border with future scenarios intended for the treatment of organic waste using LCA. The outcome of the project was a recommendation to waste management companies through life cycle assessment and experimental work at a biological treatment plant. A major part of the PhD study was collecting data on all aspects of the waste management chain. Waste generation through to collection, transportation, treatment and final disposal were analysed. The most detailed analysis took place at a combined biogas and composting plant, where solid and liquid samples were taken and air emissions measured through whole-site fugitive emissions. The assessments were done by using a combination of material flow analysis, substance flow analysis, life cycle inventories and life cycle assessments, using the EASETECH modelling software. The life cycle assessment assessed the management of organic household waste in the Danish-German border region. The main output was a life cycle assessment showing large differences in the environmental performance of the two different regions, with the Danish region performing better in most impact categories. Furthermore, the importance of the energy systems was investigated, showing that a large influence on the results was the surrounding energy system. Besides comparing the two regions' current performances to each other, they were compared to four future scenarios featuring increased source separation and different biological treatments. In this case the life cycle assessment was used as a planning tool for a future waste management system where environmental hotspots could be identified for both current and possible future systems. In all cases, the results showed that local conditions can play a major role in where the system can be improved, and conclusions made on an overall level (all five waste management companies together) can lead to suboptimal decisions; it is therefore important to look at each waste management company individually. Major differences in environmental performance were seen when changing from incineration or mechanical and biological treatment to biological treatment, such as increased savings of phosphorous and increased loadings of ammonia. Most important for the environmental performance of the biological treatment facilities were high biogas production and low fugitive methane, nitrous oxide and ammonia emissions. Fugitive emissions measured at a combined biogas and composting plant were very significant and led to a turnaround in the environmental performance of the plant, going from a saving in greenhouse gas potential to a loading when including the measured emissions and applying the life cycle assessment principles. Ultimately, increasing the source separation of organic household waste for the five waste management companies is a viable option, if the focus of the companies is on flexible fuel (biogas), compost production and subsequent resource savings. However, the picture is not clear, as the current waste management system (mainly incineration) is already working well, and in some cases it outperforms the biological treatment option.
AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N. 340541. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS). TN is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London. The Biobanque Québec COVID19 is funded by FRQS, Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé. These funding agencies had no role in the design, implementation or interpretation of this study. The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of Excellence 2167 "Precision Medicine in Chronic Inflammation (PMI)" (DFG Grant: "EXC2167"). The COVID19-Host(a)ge study was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). Genotyping in COVID19-Host(a)ge was supported by a philantropic donation from Stein Erik Hagen. The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"and also by the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by "Consejeria de Salud y Familias" of the Andalusian Government. DMM is currently funded by the the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018). The Columbia University Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Columbia University. The SPGRX study was supported by the Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150. The GEN-COVID study was funded by: the MIUR grant "Dipartimenti di Eccellenza 2018-2020" to the Department of Medical Biotechnologies University of Siena, Italy; the "Intesa San Paolo 2020 charity fund" dedicated to the project NB/2020/0119; and philanthropic donations to the Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by Tuscany Region "Bando Ricerca COVID-19 Toscana" grant to the Azienda Ospedaliero Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA consortium for providing computational resources; the Network for Italian Genomes (NIG) (http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for managing specimens. Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the Dolce&Gabbana Fashion Firm is gratefully acknowledged. Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione IRCCS Cà Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- "Liver Investigation: Testing Marker Utility in Steatohepatitis", Programme "Photonics" under grant agreement "101016726" for the project "REVEAL: Neuronal microscopy for cell behavioural examination and manipulation", Fondazione Patrimonio Ca' Granda "Liver Bible" PR-0361. DP was supported by Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, CV PREVITAL "Strategie di prevenzione primaria nella popolazione Italiana" Ministero della Salute, and Associazione Italiana per la Prevenzione dell'Epatite Virale (COPEV). Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the "Fonds Erasme". The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2) study was supported by grants from Fondation Léon Fredericq and from Fonds de la Recherche Scientifique (FNRS). The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones Científicas. KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project grant to Michael Hultström (KAW 2020.0182) and the Swedish Research Council to Robert Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus Bergvalls Stiftelse. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland. These funding agencies had no role in the design, implementation or interpretation of this study. ; Background: There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. ; Academy of Finland Fellow grant N. 323116 ; Academy of Finland for PREDICT consortium N. 340541. ; Canadian Institutes of Health Research (CIHR) (365825 and 409511) ; Lady Davis Institute of the Jewish General Hospital ; Canadian Foundation for Innovation (CFI) ; NIH Foundation ; Cancer Research UK ; Genome Québec ; Public Health Agency of Canada ; McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS) ; Japan Society for the Promotion of Science for Young Scientists ; CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship ; FRQS Clinical Research Scholarship ; Calcul Québec ; Compute Canada ; Welcome Trust ; Medical Research Counc ; European Union ; National Institute for Health Research-funded BioResource ; Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust ; King's College London ; Genome Québec ; Public Health Agency of Canada ; McGill Interdisciplinary Initiative in Infection and Immunity ; Fonds de Recherche Québec Santé ; (DFG Grant: "EXC2167") ; (CompLS grant 031L0165) ; Stein Erik Hagen ; "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia" ; Instituto de Salud Carlos III (CIBERehd and CIBERER) ; COVID-19-GWAS ; COVID-PREMED initiatives ; "Consejeria de Salud y Familias" of the Andalusian Government ; Andalusian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018) ; Columbia University ; National Center for Advancing Translational Sciences ; NIH Grant Number UL1TR001873 ; Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150 ; MIUR grant "Dipartimenti di Eccellenza 2018-2020" ; "Intesa San Paolo 2020 charity fund" dedicated to the project NB/2020/0119 ; Tuscany Region "Bando Ricerca COVID-19 Toscana" ; CINECA consortium ; Network for Italian Genomes (NIG) ; COVID-19 Host Genetics Initiative ; Genetic Biobank of Siena ; EuroBioBank ; RD-Connect ; Ricerca Corrente (Italian Ministry of Health) ; Fondazione Humanitas per la Ricerca ; Banca Intesa San Paolo ; Dolce&Gabbana Fashion Firm ; COVID-19 Biobank ; Fondazione IRCCS Cà Granda Milano ; MyFirst Grant AIRC n.16888 ; Ricerca Finalizzata Ministero della Salute RF-2016-02364358 ; Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico ; European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) ; "Photonics" "101016726" ; Fondazione Patrimonio Ca' Granda "Liver Bible" PR-0361 ; CV PREVITAL "Strategie di prevenzione primaria nella popolazione Italiana" Ministero della Salute, and Associazione Italiana per la Prevenzione dell'Epatite Virale (COPEV) ; "Fonds Erasme" ; Fondation Léon Fredericq ; Fonds de la Recherche Scientifique (FNRS) ; Consejo Superior de Investigaciones Científicas ; German Research Foundation (LU 1944/3-1) ; SciLifeLab/KAW national COVID-19 research program project (KAW 2020.0182) ; Swedish Research Council (2014-02569 and 2014-07606) ; Jeansson Stiftelser, Magnus Bergvalls Stiftelse ; Technical University of Munich, Munich, Germany ; Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland
ENIGMA-CNV working group. ; Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function. ; 1000BRAINS: The 1000BRAINS study was funded by the Institute of Neuroscience and Medicine, Research Center Juelich, Germany. We thank the Heinz Nixdorf Foundation (Germany) for the generous support of the Heinz Nixdorf Recall Study on which 1000BRAINS is based. We also thank the scientists and the study staff of the Heinz Nixdorf Recall Study and 1000BRAINS. Funding was also granted by the Initiative and Networking Fund of the Helmholtz Association (Caspers) and the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement 945539 (Human Brain Project SGA3; Amunts, Caspers, Cichon). Brainscale: The Brainscale study was supported by the Netherlands Organization for Scientific Research MagW 480-04-004 (Dorret I. Boomsma), 51.02.060 (Hilleke E. Hulshoff Pol), 668.772 (Dorret I. Boomsma and Hilleke E. Hulshoff Pol); NWO/SPI 56-464-14192 (Dorret I. Boomsma), the European Research Council (ERC-230374) (Dorret I. Boomsma), High Potential Grant Utrecht University (Hilleke E.Hulshoff Pol) and NWO Brain and Cognition 433-09-220 (Hilleke E.Hulshoff Pol). Betula: The Betula study was funded by the Knut and Alice Wallenberg (KAW) foundation (Nyberg). The Freesurfer segmentations on the Betula sample were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at HPC2N (in Umeå, Sweden), partially funded by the Swedish Research Council through grant agreement no. 2018-05973. Brain Imaging Genetics (BIG): This work makes use of the BIG database, first established in Nijmegen, The Netherlands, in 2007. This resource is now part of Cognomics (www.cognomics.nl), a joint initiative by researchers from the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud University Medical Centre and the Max Planck Institute for Psycholinguistics in Nijmegen. The Cognomics Initiative has received support from the participating departments and centres and from external grants, that is, the Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL), the Hersenstichting Nederland and the Netherlands Organization for Scientific Research (NWO). The research leading to these results also receives funding from the NWO Gravitation grant 'Language in Interaction', the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement nos. 602450 (IMAGEMEND), 278948 (TACTICS) and 602805 (Aggressotype), as well as from the European Community's Horizon 2020 programme under grant agreement no. 643051 (MiND) and from ERC-2010-AdG 268800-NEUROSCHEMA. In addition, the work was supported by a grant for the ENIGMA Consortium (grant number U54 EB020403) from the BD2K Initiative of a cross-NIH partnership. deCODE genetics: deCODE genetics acknowledges support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nos. 115008 (NEWMEDS) and 115300 (EUAIMS), of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union's Seventh Framework Programme (EU-FP7/2007-2013), EU-FP7-funded grant agreement no. 602450 (IMAGEMEND) and EU-funded FP7-People-2011-IAPP grant agreement no. 286213 (PsychDPC). Dublin: This work was supported by Science Foundation Ireland (SFI grant 12/IP/1359 to Gary Donohoe and grant SFI08/IN.1/B1916-Corvin to Aidan C. Corvin). ECHO-DEFINE: The ECHO study acknowledges funding from a Medical Research Council (MRC) Centre Grant to Michael J. Owen (G0801418), the Wellcome Trust (Institutional Strategic Support Fund (ISSF) to van den Bree and Clinical Research Training Fellowship to Joanne L. Doherty), the Waterloo Foundation (WF 918-1234 to van den Bree), the Baily Thomas Charitable Fund (2315/1 to van den Bree), National Institute of Mental Health (NIMH 5UO1MH101724 to van den Bree and Michael J. Owen), the IMAGINE-2 study (funded by the MRC (MR/T033045/1) to van den Bree, Jeremy Hall and Michael J. Owen), the IMAGINE-ID study (funded by MRC (MR/N022572/1) to Jeremy Hall, van den Bree and Owen). The DEFINE study was supported by a Wellcome Trust Strategic Award (100202/Z/12/Z) to Michael J. Owen. ENIGMA: ENIGMA is supported in part by NIH grants U54 EB20403, R01MH116147 and R56AG058854. NIA T32AG058507; NIH/NIMH 5T32MH073526. EPIGEN-Dublin: The EPIGEN-Dublin cohort was supported by a Science Foundation Ireland Research Frontiers Programme award (08/RFP/GEN1538). EPIGEN-UK (Sisodiya): The work was partly undertaken at UCLH/UCL, which received a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centres funding scheme. We are grateful to the Wolfson Trust and the Epilepsy Society for supporting the Epilepsy Society MRI scanner. GAP: This work was supported by the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, Psychology and Neuroscience, King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. GOBS: The GOBS study data collection was supported in part by the National Institutes of Health (NIH) grants: R01 MH078143, R01 MH078111 and R01 MH083824, with work conducted in part in facilities constructed under the support of NIH grant C06 RR020547. GSP: Data were in part provided by the Brain Genomics Superstruct Project (GSP) of Harvard University and Massachusetts General Hospital (MGH) (Principal Investigators: Randy Buckner, Jordan Smoller and Joshua Roffman), with support from the Center for Brain Science Neuroinformatics Research Group, Athinoula A. Martinos Center for Biomedical Imaging, Center for Genomic Medicine and Stanley Center for Psychiatric Research. Twenty individual investigators at Harvard and MGH generously contributed data to the overall project. We would like to thank Randy Buckner for insightful comments and feedback on this work. HUBIN: The HUBIN study was financed by the Swedish Research Council (K2010-62X-15078-07-2, K2012-61X-15078-09-3, 521-2014-3487 K2015-62X-15077-12-3, 2017-00949), the regional agreement on medical training and clinical research between Stockholm County Council and the Karolinska Institutet. HUNT: The HUNT study is a collaboration between HUNT Research Centre (Faculty of Medicine and Movement Sciences, NTNU—Norwegian University of Science and Technology), Nord-Trøndelag County Council, Central Norway Health Authority and the Norwegian Institute of Public Health. HUNT-MRI was funded by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Norwegian National Advisory Unit for functional MRI. IMAGEN: This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant 'STRATIFY' (Brain network based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), Human Brain Project (HBP SGA 2, 785907),the FP7 projects IMAGEMEND(602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EUAIMS (115300-2), the Medical Research Council Grant 'c-VEDA' (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152, 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL 01EE1406A, 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants, SM 80/7-2, SFB 940/2), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1). Further support was provided by grants from: ANR (project AF12-NEUR0008-01—WM2NA, ANR-12-SAMA-0004), the Eranet Neuron (ANR-18-NEUR00002-01), the Fondation de France (00081242), the Fondation pour la Recherche Médicale (DPA20140629802), the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012, the Fondation de l'Avenir (grant AP-RM-17-013), the Fédération pour la Recherche sur le Cerveau; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1) and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Lifespan: The study is funded by the Research Council of Norway (230345, 288083 and 223273). NCNG: NCNG sample collection was supported by grants from the Bergen Research Foundation and the University of Bergen, the Dr Einar Martens Fund, the Research Council of Norway, to le Hellard, Steen and Espeseth. The Bergen group was supported by grants from the Western Norway Regional Health Authority (Grant 911593 to Arvid Lundervold, Grant 911397 and 911687 to Astri Johansen Lundervold). NTR: The NTR cohort was supported by the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organisation for Health Research and Development (ZonMW) grants 904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004,463-06-001, 451-04-034, 400-05-717, Addiction-31160008, 016-115-035, 481-08-011, 056-32-010, Middelgroot-911-09-032, OCW_NWO Gravity programme—024.001.003, NWO-Groot 480-15-001/674, Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007 and 184.033.111); Spinozapremie (NWO-56-464-14192), KNAW Academy Professor Award (PAH/6635) and University Research Fellow grant (URF) to Dorret I. Boomsma; Amsterdam Public Health research institute (former EMGO+), Neuroscience Amsterdam research institute (former NCA); the European Science Foundation (ESF, EU/QLRT-2001-01254), the European Community's Seventh Framework Programme (FP7- HEALTH-F4-2007-2013, grant 01413: ENGAGE and grant 602768: ACTION); the European Research Council (ERC Starting 284167, ERC Consolidator 771057, ERC Advanced 230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the National Institutes of Health (NIH, R01D0042157-01A1, R01MH58799-03, MH081802, DA018673, R01 DK092127-04, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995); the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by NWO through grant 2018/EW/00408559, BiG Grid, the Dutch e-Science Grid and SURFSARA. OATS: The OATS study has been funded by a National Health & Medical Research Council (NHMRC) and Australian Research Council (ARC) Strategic Award Grant of the Ageing Well, Ageing Productively Programme (ID No. 401162) and NHMRC Project Grants (ID Nos. 1045325 and 1085606). This research was facilitated through Twins Research Australia, a national resource in part supported by an NHMRC Centre for Research Excellence Grant (ID No.: 1079102). We thank the participants for their time and generosity in contributing to this research. We acknowledge the contribution of the OATS research team (https://cheba.unsw.edu.au/project/older-australian-twins-study) to this study. OATS genotyping was partly funded by a Commonwealth Scientific and Industrial Research Organization Flagship Collaboration Fund Grant. Osaka: Osaka study was supported by the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS: Grant Number JP18dm0207006), Brain/MINDS& beyond studies (Grant Number JP20dm0307002) and Health and Labour Sciences Research Grants for Comprehensive Research on Persons with Disabilities (Grant Number JP20dk0307081) from the Japan Agency for Medical Research and Development (AMED), Grants-in-Aid for Scientific Research (KAKENHI; Grant Numbers JP25293250 and JP16H05375). Some computations were performed at the Research Center for Computational Science, Okazaki, Japan. PAFIP: The PAFIP study was supported by Instituto de Salud Carlos III, FIS 00/3095, 01/3129, PI020499, PI060507, PI10/00183, the SENY Fundació Research Grant CI2005-0308007 and the FundaciónMarqués de Valdecilla API07/011. Biological samples from our cohort were stored at the Valdecilla Biobank and genotyping services were conducted at the Spanish 'Centro Nacional de Genotipado' (CEGEN-ISCIII). MCIC/COBRE: The study is funded by the National Institutes of Health studies R01EB006841, P20GM103472 and P30GM122734 and Department of Energy DE-FG02-99ER62764. PING: Data collection and sharing for the Paediatric Imaging, Neurocognition and Genetics (PING) Study (National Institutes of Health Grant RC2DA029475) were funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. A full list of PING investigators is at http://pingstudy.ucsd.edu/investigators.html. QTIM: The QTIM study was supported by the National Institute of Child Health and Human Development (R01 HD050735) and the National Health and Medical Research Council (NHMRC 486682, 1009064), Australia. Genotyping was supported by NHMRC (389875). Medland is supported in part by an NHMRC fellowship (APP1103623). SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grant nos. 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide single-nucleotide polymorphism typing in SHIP and MRI scans in SHIP and SHIP-TREND have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. StrokeMRI: StrokeMRI was supported by the Norwegian ExtraFoundation for Health and Rehabilitation(2015/FO5146), the Research Council of Norway (249795, 262372), the South-Eastern Norway Regional Health Authority (2014097, 2015044, 2015073) and the Department of Psychology, University of Oslo. Sydney MAS: The Sydney Memory and Aging Study (Sydney MAS) is funded by National and HealthMedical Research Council (NHMRC) Programme and Project Grants (ID350833, ID568969 and ID109308). We also thank the Sydney MAS participants and the Research Team. SYS: The SYS Study is supported by Canadian Institutes of Health Research. TOP: Centre of Excellence: RCN #23273 and RCN #226971. Part of this work was performed on the TSD (Tjeneste for Sensitive Data) facilities, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo, IT-Department (USIT) (tsd-drift@usit.uio.no). The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement no. 609020—Scientia Fellows; the Research Council of Norway (RCN) #276082—A lifespan perspective on mental illness: toward precision medicine using multimodal brain imaging and genetics. Ida E. Sønderby and Rune Bøen are supported by South-Eastern Norway Regional Health Authority (#2020060). Ida E. Sønderby and Ole A. Andreassen have received funding from the European Union's Horizon 2020 Research and Innovation Programme under Grant agreement no. 847776 (CoMorMent project) and the KG Jebsen Foundation (SKGJ-MED-021). UCLA_UMCU: The UCLA_UMCU cohort comprises of six studies which were supported by National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) (20244 to Prof. Hillegers), The Netherlands Organisation for Health Research and Development (ZonMw) (908-02-123 to Prof. Hulshoff Pol), and Netherlands Organisation for Scientific Research (NWO 9120818 and NWO-VIDI 917-46-370 to Prof. Hulshoff Pol). The GROUP study was funded through the Geestkracht programme of the Dutch Health Research Council (ZonMw, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly and Janssen Cilag) and universities and mental health care organizations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ inGeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord-Holland-Noord. Groningen: University Medical Center Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia Psycho-medical Center, The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh, voor Geestelijke Gezondheid, Mondriaan, Virenzeriagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-JozefKortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Center Utrecht and the mental health institutions: Altrecht, GGZ Centraal and Delta.). UK Biobank: This work made use of data sharing from UK Biobank (under project code 27412). Others: Work by Pierre Vanderhaeghen was funded by Grants of the European Research Council (ERC Adv Grant GENDEVOCORTEX), the EOS Programme, the Belgian FWO, the AXA Research Fund and the Belgian Queen Elizabeth Foundation. Ikuo K. Suzuki was supported by a postdoctoral fellowship of the FRS/FNRS. ; Peer reviewed