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Cyber Governance in the Commonwealth: Towards Stability and Responsible State Behaviour in Cyberspace

Invitation Only Research Event

7 October 2019 - 10:30am to 5:30pm

Addis Ababa, Ethiopia

This roundtable is part of a series under the project, 'Implementing the Commonwealth Cybersecurity Agenda', funded by the UK Foreign and Commonwealth Office (FCO). The roundtable aims to provide a multi-stakeholder, pan-Commonwealth platform to discuss how to implement the Commonwealth Cyber Declaration with a focus on its third pillar 'To promote stability in cyberspace through international cooperation'.

In particular, the roundtable focuses on points 3 and 4 of the third pillar which revolve around the commitment to promote frameworks for stability in cyberspace including the applicability of international law, agreed voluntary norms of responsible state behaviour and the development and implementation of confidence-building measures consistent with the 2015 report of the UNGGE. 

The workshop also focuses on the commitment to advance discussions on how existing international law, including the Charter of the United Nations and applicable international humanitarian law, applies in cyberspace.

The roundtable addresses the issue of global cyber governance from a Commonwealth perspective and will also include a discussion around the way forward, the needed capacity of the different Commonwealth countries and the cooperation between its members for better cyber governance.

Participants include UNGGE members from Commonwealth countries in addition to representatives to the UN Open-Ended Working Group from African countries as well as members from academia, civil society and industry.

Calum Inverarity

Research Analyst and Coordinator, International Security Department
+44 (0) 207 957 5751




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The Future of EU–US Cooperation in Space Traffic Management and Space Situational Awareness

29 August 2019

As more space activities develop, there is an increasing requirement for comprehensive space situational awareness (SSA). This paper provides an overview of the current landscape in SSA and space traffic management as well as possible scenarios for EU–US cooperation in this area. 

Alexandra Stickings

Research Fellow for Space Policy and Security, RUSI

2019-08-19-SpaceTrafficManagement.jpg

Deployment of the NanoRacks-Remove Debris Satellite from the International Space Station. Photo: Getty Images.

Summary

  • Space situational awareness (SSA) and space traffic management (STM) are essential for sustainable near-Earth orbit. International cooperation in SSA and STM is vital with the growing number of satellite operators and the increasingly complex space environment.
  • The various definitions of SSA and STM are ambiguous. Understanding the activities that fall under each term can better assist in finding areas for cooperation and collaboration.
  • SSA has historically been a military activity, leading to an incomplete public catalogue of its use and barriers to sharing information with other states and the commercial sector. The rise in private space actors has increased the number of commercial STM providers and, with plans in the US to move responsibility for STM to civilian control, there will likely be more opportunities for international collaboration, particularly through the EU Space Surveillance and Tracking (SST) programme.
  • Individual EU member states possess developed STM capabilities, but overall these are still some way behind those of allies such as the US. Further investment in STM infrastructure and programmes is required for the EU and individual European states to be an essential partner to the US and add value to the global effort.
  • There are worldwide challenges, both political and technical, to providing STM coverage, which may lead to a lack of collaboration and gaps in understanding of activities in orbit. Existing sensors have limitations in terms of the size of objects that can be detected and the precision with which their movements can be predicted. These capability gaps represent opportunities for the EU to contribute.
  • The EU can build on its tradition of support for openness and civil society by creating a system that fosters an environment of cooperation and collaboration involving industry, commercial STM providers and the wider international community.
  • Although collaboration in STM is vital, the EU should also aim to tackle issues within the wider definition of SSA including space weather, intelligence and the security of ground stations.
  • The EU is well placed to become a global leader in SSA and STM. However, it needs to take into consideration the current political and technical landscape when making decisions regarding investment in capabilities and the pursuit of international partnerships.




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Examining Measures to Mitigate Cyber Vulnerabilities of Space-based Strategic Assets

Invitation Only Research Event

30 October 2019 - 9:30am to 4:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Beyza Unal, Senior Research Fellow, International Security Department, Chatham House
Patricia Lewis, Research Director, International Security Department, Chatham House

Strategic systems that depend on space-based assets, such as command, control and communication, early warning systems, weapons systems and weapons platforms, are essential for conducting successful NATO operations and missions. Given the increasing dependency on such systems, the alliance and key member states would therefore benefit from an in-depth analysis of possible mitigation and resilience measures.

This workshop is part of the International Security Department’s (ISD) project on space security and the vulnerability of strategic assets to cyberattacks, which includes a recently published report. This project aims to create resilience in NATO and key NATO member states, building the capacity of key policymakers and stakeholders to respond with effective policies and procedures. This workshop will focus on measures to mitigate the cyber vulnerabilities of NATO’s space-dependent strategic assets. Moreover, participants will discuss the type of resilience measures and mechanisms required.

Attendance at this event is by invitation only. 

Calum Inverarity

Research Analyst and Coordinator, International Security Department
+44 (0) 207 957 5751




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How Is New Technology Driving Geopolitical Relations?

Research Event

22 October 2019 - 6:00pm to 7:00pm

Chatham House, London

Event participants

Rt Hon Baroness Neville-Jones DCMG, Minister of State for Security and Counter Terrorism (2010-11)
Jamie Condliffe, Editor, DealBook Newsletter and Writer, Bits Tech Newsletter, The New York Times
Jamie Saunders, Partner, Wychwood Partners LLP; Visiting Professor, University College London
Chair: Dr Patricia Lewis, Research Director, International Security Department, Chatham House

New technology such as 5G, artificial intelligence, nanotechnology and robotics have become, now more than ever, intertwined with geopolitical, economic and trade interests. Leading powers are using new technology to exert power and influence and to shape geopolitics more generally.

The ongoing race between the US and China around 5G technology is a case in point. Amid these tensions, the impact on developing countries is not sufficiently addressed.

Arguably, the existing digital divide will increase leading developing countries to the early, if not hasty, adoption of new technology for fear of lagging behind. This could create opportunities but will also pose risks.

This panel discusses how new technology is changing the geopolitical landscape. It also discusses the role that stakeholders, including governments, play in the creation of standards for new technologies and what that means for its deployment in key markets technically and financially.

Finally, the panel looks at the issue from the perspective of developing countries, addressing the choices that have to be made in terms of affordability, development priorities and security concerns.

This event was organized with the kind support of DXC Technology.

Nicole Darabian

Research Assistant, Cyber Policy, International Security Department




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EU–US Cooperation on Tackling Disinformation

3 October 2019

Disinformation, as the latest iteration of propaganda suitable for a digitally interconnected world, shows no signs of abating. This paper provides a holistic overview of the current state of play and outlines how EU and US cooperation can mitigate disinformation in the future.

Sophia Ignatidou

Academy Associate, International Security Programme

2019-09-19-FakeNews.jpg

A congressional staff member displays print outs of social media posts during a hearing before the House Select Intelligence Committee 1 November 2017 in Washington, DC. Photo: Getty Images.
  • EU and US cooperation on tackling disinformation needs to be grounded in an international human rights framework in order to bridge the differences of both parties and include other countries facing this challenge.
  • The disinformation debate needs to be reformulated to cover systemic issues rather than merely technical or security concerns. A lag in regulatory development has led to systemic vulnerabilities. In this context, policymakers need to push for more evidence-based analysis, which is only attainable if technology companies engage in honest debate and allow meaningful access to data – as determined by government appointed researchers rather than the companies themselves – taking into account and respecting users’ privacy.
  • Data governance needs to be the focus of attempts to tackle disinformation. Data’s implications for information, market and power asymmetries, feed into and exacerbate the problem.
  • Policymakers should focus on regulating the distribution of online content rather than the subject matter itself, which may have implications for freedom of speech.
  • Disinformation is mainly the result of inefficient gatekeeping of highly extractive digital companies. The old gatekeepers, journalists and their respective regulators, need to be actively engaged in devising the new regulatory framework.
  • Legacy media need to urgently consider the issue of ‘strategic silence’ and avoid being co-opted by political actors aiming to manipulate the accelerated, reactive news cycle by engaging in divisive ‘clickbait’ rhetoric verging on disinformation and propaganda. When strategic silence is not an option, contextual analysis is fundamental.
  •  The EU delegation should assist the coordination of EU–US efforts to tackle disinformation by drawing on the work and expertise at the G7 Rapid Response Mechanism (RRM), the Transatlantic Commission on Election Integrity (TCEI), the European Centre of Excellence for Countering Hybrid Threats (Hybrid CoE), the High-level Panel on Digital Cooperation, and work with the International Telecommunication Union (ITU) to foster a long-term interdisciplinary forum to harness technological innovation to protect and support democracy from threats such as disinformation.
  • The EU and US must avoid rushed regulation that may condone enhanced surveillance or vilify journalism that scrutinizes those in power in the name of security.




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Who Runs the Internet: Internet Consolidation and Control

Research Event

10 December 2019 - 6:00pm to 7:15pm

Chatham House, London

Event participants

Andrew Sullivan, President and CEO, Internet Society
Jennifer Cobbe, Research Associate, Department of Computer Science and Technology, University of Cambridge
Jesse Sowell, Assistant Professor, Department of International Affairs, Bush School of Government and Public Service, Texas A&M University
Chair: Emily Taylor, Associate Fellow, International Security, Chatham House, Editor, Journal of Cyber Policy

In recent years, there has been a growing debate around the influence of a few large internet technology companies on the internet’s infrastructure and over the popular applications and social media platforms that we use every day.

The internet which was once widely viewed as a collective platform for limitless, permissionless innovation, competition and growth, is now increasingly viewed as a consolidated environment dominated by a few. Such market dominance threatens to undermine the internet’s fundamental benefits as a distributed network in which no single entity has control.  

The panel examines the risks of consolidation throughout the internet’s technology stack such as the impact on complex supply chains that support applications, including cloud provisions, ‘as a service’.

It also explores the potential benefits, for example, when building out essential infrastructure to support faster and cheaper internet services in developing economies, consolidation can create economies of scale that bring the resource-intensive building blocks of the internet economy within the reach of new start-ups and innovators.

The panel provides an interdisciplinary perspective exploring the relationship between consolidation and evolutions in the internet infrastructure as well as unpacking its policy implications.

This event supports a special issue of the Journal of Cyber Policy as part of a collaboration between Chatham House and the Internet Society which explores the impact of the consolidation on the internet’s fundamental architecture.

Nilza Amaral

Project Manager, International Security Programme




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EU–US Relations on Internet Governance

14 November 2019

As internet governance issues emerge in the wake of innovations such as the Internet of Things and advanced artificial intelligence, there is an urgent need for the EU and US to establish a common, positive multi-stakeholder vision for regulating and governing the internet.

Emily Taylor

Associate Fellow, International Security Programme

Stacie Hoffmann

Internet Policy and Cybersecurity Consultant, Oxford Information Labs

2019-11-14-EUUSInternet.jpg

Server room network cables in New York City, November 2014. Photo: Michael Bocchieri/Staff/Getty.
  • Political, economic, sociological and technological factors are poised to challenge EU and US ideological positions on internet governance, which will make it difficult to find consensus and common ground in the years to come.
  • The EU and US share core values and perspectives relating to internet governance, such as openness, freedom and interoperability, as well as a human rights framework for cybersecurity. There have been many examples of successful multi-stakeholder cooperation between the EU and US, including the Internet Assigned Numbers Authority (IANA) transition and the European Dialogue on Internet Governance (EuroDIG).
  • There are also subtle differences between the EU and US, and each has different reasons to support multi-stakeholderism. Cases that highlight growing tensions in EU–US coordination on internet governance include the controversies surrounding the EU General Data Protection Regulation (GDPR), the WHOIS system that governs domain name registration data, and the board of the Internet Corporation for Assigned Names and Numbers (ICANN), which undermined an independent cybersecurity review.
  • Internet governance is becoming more complex, with a multiplicity of actors and no obvious authority for important emerging issues. Additionally, the rise of China and its authoritarian vision for the future of the internet is a threat to the current internet governance institutions that have been shaped by and reflect Western values.
  • To bridge ideological gaps the EU and US should build capacity between likeminded stakeholders, create a taskforce on effective multi-stakeholder internet governance, and work through non-governmental stakeholders to improve participation.




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AI-driven Personalization in Digital Media: Political and Societal Implications

2 December 2019

The fallout from disinformation and online manipulation strategies have alerted Western democracies to the novel, nuanced vulnerabilities of our information society. This paper outlines the implications of the adoption of AI by the the legacy media, as well as by the new media, focusing on personalization.

Sophia Ignatidou

Academy Associate, International Security Programme

2019-12-02-AI-Driven-Personalization-small.jpg

The Reuters and other news apps seen on an iPhone, 29 January 2019. Photo: Getty Images.

Summary

  • Machine learning (ML)-driven personalization is fast expanding from social media to the wider information space, encompassing legacy media, multinational conglomerates and digital-native publishers: however, this is happening within a regulatory and oversight vacuum that needs to be addressed as a matter of urgency.
  • Mass-scale adoption of personalization in communication has serious implications for human rights, societal resilience and political security. Data protection, privacy and wrongful discrimination, as well as freedom of opinion and of expression, are some of the areas impacted by this technological transformation.
  • Artificial intelligence (AI) and its ML subset are novel technologies that demand novel ways of approaching oversight, monitoring and analysis. Policymakers, regulators, media professionals and engineers need to be able to conceptualize issues in an interdisciplinary way that is appropriate for sociotechnical systems.
  • Funding needs to be allocated to research into human–computer interaction in information environments, data infrastructure, technology market trends, and the broader impact of ML systems within the communication sector.
  • Although global, high-level ethical frameworks for AI are welcome, they are no substitute for domain- and context-specific codes of ethics. Legacy media and digital-native publishers need to overhaul their editorial codes to make them fit for purpose in a digital ecosystem transformed by ML. Journalistic principles need to be reformulated and refined in the current informational context in order to efficiently inform the ML models built for personalized communication.
  • Codes of ethics will not by themselves be enough, so current regulatory and legislative frameworks as they relate to media need to be reassessed. Media regulators need to develop their in-house capacity for thorough research and monitoring into ML systems, and – when appropriate –proportionate sanctions for actors found to be employing such systems towards malign ends. Collaboration with data protection authorities, competition authorities and national electoral commissions is paramount for preserving the integrity of elections and of a political discourse grounded on democratic principles.
  • Upskilling senior managers and editorial teams is fundamental if media professionals are to be able to engage meaningfully and effectively with data scientists and AI engineers.




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Trump’s Threat to Target Iran’s Cultural Heritage Is Illegal and Wrong

7 January 2020

Héloïse Goodley

Army Chief of General Staff Research Fellow (2018–19), International Security
Targeting cultural property is rightly prohibited under the 1954 Hague Convention.

2020-01-07-Trump.jpg

Donald Trump at Mar-a-Lago in December. Photo: Getty Images

As tensions escalate in the Middle East, US President Donald Trump has threatened to strike targets in Iran should they seek to retaliate over the killing of Qassem Soleimani. According to the president’s tweet, these sites includes those that are ‘important to Iran and Iranian culture’.

Defense Secretary Mark Esper was quick on Monday to rule out any such action and acknowledged that the US would ‘follow the laws of armed conflict’. But Trump has not since commented further on the matter.

Any move to target Iranian cultural heritage could constitute a breach of the international laws protecting cultural property. Attacks on cultural sites are deemed unlawful under two United Nations conventions; the 1954 Hague Convention for the Protection of Cultural Property during Armed Conflict, and the 1972 UNESCO World Heritage Convention for the Protection of the World Cultural and Natural Heritage.

These have established deliberate attacks on cultural heritage (when not militarily necessary) as a war crime under the Rome Statute of the International Criminal Court in recognition of the irreparable damage that the loss of cultural heritage can have locally, regionally and globally.

These conventions were established in the aftermath of the Second World War, in reaction to the legacy of the massive destruction of cultural property that took place, including the intense bombing of cities, and systematic plunder of artworks across Europe. The conventions recognize that damage to the cultural property of any people means ‘damage to the cultural heritage of all mankind’. The intention of these is to establish a new norm whereby protecting culture and history – that includes cultural and historical property – is as important as safeguarding people.

Such historical sites are important not simply as a matter of buildings and statues, but rather for their symbolic significance in a people’s history and identity. Destroying cultural artefacts is a direct attack on the identity of the population that values them, erasing their memories and historical legacy. Following the heavy bombing of Dresden during the Second World War, one resident summed up the psychological impact of such destruction in observing that ‘you expect people to die, but you don’t expect the buildings to die’.

Targeting sites of cultural significance isn’t just an act of intimidation during conflict. It can also have a lasting effect far beyond the cessation of violence, hampering post-conflict reconciliation and reconstruction, where ruins or the absence of previously significant cultural monuments act as a lasting physical reminder of hostilities.

For example, during the Bosnian War in the 1990s, the Old Bridge in Mostar represented a symbol of centuries of shared cultural heritage and peaceful co-existence between the Serbian and Croat communities. The bridge’s destruction in 1993 at the height of the civil war and the temporary cable bridge which took its place acted as a lasting reminder of the bitter hostilities, prompting its reconstruction a decade later as a mark of the reunification of the ethnically divided town.

More recently, the destruction of cultural property has been a feature of terrorist organizations, such as the Taliban’s demolition of the 1,700-year-old Buddhas of Bamiyan in 2001, eliciting international condemnation. Similarly, in Iraq in 2014 following ISIS’s seizure of the city of Mosul, the terrorist group set about systematically destroying a number of cultural sites, including the Great Mosque of al-Nuri with its leaning minaret, which had stood since 1172. And in Syria, the ancient city of Palmyra was destroyed by ISIS in 2015, who attacked its archaeological sites with bulldozers and explosives.

Such violations go beyond destruction: they include the looting of archaeological sites and trafficking of cultural objects, which are used to finance terrorist activities, which are also prohibited under the 1954 Hague Convention.

As a war crime, the destruction of cultural property has been successfully prosecuted in the International Criminal Court, which sentenced Ahmad Al-Faqi Al-Mahdi to nine years in jail in 2016 for his part in the destruction of the Timbuktu mausoleums in Mali. Mahdi led members of Al-Qaeda in the Islamic Maghreb to destroy mausoleums and monuments of cultural and religious importance in Timbuktu, irreversibly erasing what the chief prosecutor described as ‘the embodiment of Malian history captured in tangible form from an era long gone’.

Targeting cultural property is prohibited under customary international humanitarian law, not only by the Hague Convention. But the Convention sets out detailed regulations for protection of such property, and it has taken some states a lot of time to provide for these.

Although the UK was an original signatory to the 1954 Hague Convention, it did not ratify it until 2017, introducing into law the Cultural Property (Armed Conflicts) Act 2017, and setting up the Cultural Protection Fund to safeguard heritage of international importance threatened by conflict in countries across the Middle East and North Africa.

Ostensibly, the UK’s delay in ratifying the convention lay in concerns over the definition of key terms and adequate criminal sanctions, which were addressed in the Second Protocol in 1999. However, changing social attitudes towards the plunder of antiquities, and an alarming increase in the use of cultural destruction as a weapon of war by extremist groups to eliminate cultures that do not align with their own ideology, eventually compelled the UK to act.

In the US, it is notoriously difficult to get the necessary majority for the approval of any treaty in the Senate; for the Hague Convention, approval was achieved in 2008, following which the US ratified the Convention in 2009.

Destroying the buildings and monuments which form the common heritage of humanity is to wipe out the physical record of who we are. People are people within a place, and they draw meaning about who they are from their surroundings. Religious buildings, historical sites, works of art, monuments and historic artefacts all tell the story of who we are and how we got here. We have a responsibility to protect them.




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The Commonwealth Cyber Declaration: Achievements and Way Forward

Invitation Only Research Event

4 February 2020 - 9:15am to 5:30pm

Chatham House, London

In April 2018, the Commonwealth Heads of Government Meeting (CHOGM), held in London, saw the creation and the adoption of the Commonwealth Cyber Declaration. The declaration outlines the framework for a concerted effort to advance cybersecurity practices to promote a safe and prosperous cyberspace for Commonwealth citizens, businesses and societies. 

The conference will aim to provide an overview on the progress made on cybersecurity in the Commonwealth since the declaration was announced in 2018. In addition, it will examine future challenges and potential solutions going forward.

This conference is part of the International Security Programme's project on Implementing the Commonwealth Cybersecurity Agenda and will convene a range of senior Commonwealth representatives as well as a selection of civil society and industry stakeholders. This project aims to develop a pan-Commonwealth platform to take the Commonwealth Cyber Declaration forward by means of a holistic, inclusive and representative approach.

Please see below meeting summaries from previous events on Cybersecurity in the Commonwealth:  

Attendance at this event is by invitation only. 

Esther Naylor

Research Assistant, International Security Programme
+44 (0)20 7314 3628




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The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace

Invitation Only Research Event

12 May 2020 - 10:00am to 11:30am
Add to Calendar

Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria.
 
This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication.
 
Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation.

Nilza Amaral

Project Manager, International Security Programme




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Understanding NATO Obligations Under the NPT

The objective of the project is to understand Alliance obligations within the framework of nuclear non-proliferation and disarmament treaties.

Examining obligations under the Treaty on the Non-Proliferation of Nuclear Weapons (NPT), and exploring new approaches that NATO could adopt to reconcile strategic stability with nuclear disarmament policies which could be introduced at the 2020 NPT Review Conference (RevCon).

The project facilitates the reconciliation of different positions in advance of the RevCon by providing a platform for stakeholders to communicate their respective positions and engage in constructive dialogue. Key research findings and contemporary analysis will be disseminated to officials and the policy community.

Through dialogue and research, the project aims to reduce polarisation in the nuclear field and consequently lay a foundation for increased collaboration during the discussions. It also provides a unique opportunity for NATO countries to explore specific new approaches, including in relation to identifying and analysing relevant geopolitical conditions for nuclear disarmament measures that will inform their inputs into the RevCon and related policy framework discussions.

This project is supported by the Carnegie Corporation of New York.




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Nuclear Weapons: Innovative Approaches for the Complex International Security Environment

This programme of work addresses the conundrum of nuclear weapons as a wicked problem in a complex adaptive system.

Understanding the complexity and the wickedness of the situation allows analysts and strategic planners to approach these complex and intractable issues in new and transformative ways – with a better chance of coping or succeeding and reducing the divisions between experts.

Using complexity theory, a complex adaptive system representing the international system and its interaction with the environment can be represented through an interactive visualization tool that will aid thought processes and policy decision-making. 

Until recently, analysts did not have the tools to be able to create models that could represent the complexity of the international system and the role that nuclear weapons play. Now that these tools are available, analysts should use them to enable decision-makers to gain insights into the range of possible outcomes from a set of possible actions.

This programme builds on work by Chatham House on cyber security and artificial intelligence (AI) in the nuclear/strategic realms.

In order to approach nuclear weapons as wicked problems in a complex adaptive system from different and sometimes competing perspectives, the programme of work involves the wider community of specialists who do not agree on what constitutes the problems of nuclear weapons nor on what are the desired solutions.

Different theories of deterrence, restraint and disarmament are tested. The initiative is international and inclusive, paying attention to gender, age and other aspects of diversity, and the network of MacArthur Grantees are given the opportunity to participate in the research, including in the writing of research papers, so that the complexity modelling can be tested against a wide range of approaches and hypotheses.

In addition, a Senior Reference Group will work alongside the programme, challenging its outcome and findings, and evaluating and guiding the direction of the research.

This project is supported by the MacArthur Foundation.




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POSTPONED: What Impact of Sovereignty in the Internet?

Research Event

26 March 2020 - 6:00pm to 7:00pm

Chatham House

Event participants

Konstantinos Komaitis, Senior Director, Policy Development & Strategy, Internet Society
Gregory Asmolov, Leverhulme Early Career Fellow Russia Institute, King’s College London
Further speakers to be announced.
Chair: Joyce Hakmeh, Senior Research Fellow, International Security Programme, Chatham House and Co-Editor of the Journal of Cyber Policy.

 

Several governments have been moving towards a stronger sovereignty narrative when it comes to the internet with some trying to impose borders in cyberspace to extend their physical borders in cyberspace. From attempts to create isolatable domestic internets to data localization laws and to increased calls for sovereignty in the digital space, all these approaches are raising concerns regarding the fate of the internet.

While the impact of these approaches varies and the motivations behind them are arguably different too, all governments have been working towards the pursuit of greater technological independence and in some instances greater control.

The panellists will discuss the impact that these approaches have on the internet. They will address the question of whether the era of an 'open web' is drawing to an end and whether these territorialization efforts lead to a fragmentation of the internet, making a 'splinternet' inevitable?

This event is being organized with the kind support of DXC Technology.

This event will be followed by a reception. 

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Esther Naylor

Research Assistant, International Security Programme
+44 (0)20 7314 3628




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The Struggle for the State in Syria

Research Event

11 March 2020 - 9:00am to 6:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

This conference brings together policymakers, experts, academics and civil society leaders to explore the current condition of the state in Syria. It examines the structure, interrelations and importance of the regime’s core institutions and their interactions with international actors. It also highlights the regime’s different approaches in dealing with state institutions and non-state actors.

The speakers discuss governance dynamics in north-western Syria and the east Euphrates region and will analyse governance variations between regions within the regime-controlled areas after the dramatic changes in 2018 and 2019.

The conference also aims to evaluate the possibility for Syrians to move from a regime-led state to one that is accountable to its citizens and is governed by the rule of law.

 

Event attributes

Livestream

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Synergy in North Africa: Furthering Cooperation

21 January 2020

Discussions of North African integration have evoked ideas of a shared identity and a common destiny in the region. However, recent attempts to build regional blocs in North Africa have been unsuccessful. This paper examines the benefits of a ‘synergistic’ approach to North African cooperation. 

Dr Mohammed Masbah

Associate Fellow, Middle East and North Africa Programme

Mohamed El Dahshan

Associate Fellow, Middle East and North Africa Programme

2020-01-21-Market.jpg

A Tunisian vendor poses as he sells white truffles at a market in the town of Ben Guerdane, 40km west of the Libyan border, in February 2016. Photo: Getty Images.

Summary

  • North African integration is not a new idea. However, countries in the region have so far struggled to form a cohesive bloc with deep political, economic and social ties. Political instability has effectively deprioritized North African integration. A focus on thematic (political, economic and security) ‘synergies’ may provide a better framework for cooperation than seeking opportunities for all-encompassing ‘deep’ and ‘comprehensive’ integration.
  • Governments of North Africa dedicate considerable resources to domestic security. Much of their efforts are conducted at the national-level and directed towards threats from terrorists, insurgents and militias. Improved security cooperation would achieve better outcomes and economies of scale, including efforts to tackle human trafficking.
  • A new generation of jihadis has emerged in North Africa since 2011. Nearly 27 per cent of the 30,000 fighters who travelled to Syria are from the Maghreb. While government counterterrorism operations have been effective, countries have failed to address the root causes of radicalization.
  • Border economies have suffered as a consequence of a security focus on terrorism and smuggling, which has rendered many previously accepted cross-border trade activities illegal. States have struggled to provide alternative livelihoods for those who have lost this source of income. Border forces tend to lack the right combination of capacity, training and equipment to secure borders and often resort to heavy-handed tactics.
  • New thinking is required to develop a more human-centric and proactive approach to migration issues in the region, which continues to witness huge flows of migrants. The migration policy of Morocco, introduced through legislation in 2014, could be a model for North Africa.
  • The countries of North Africa have varying economic profiles, ranging from economically diverse Morocco to oil-and-gas-dependant Libya. However, they all face similar challenges including unemployment (particularly among the young), poor public-service delivery, low FDI levels, an oversized public sector, ineffective tax collection, and high informality.
  • Fostering entrepreneurship and the development of small and medium-sized enterprises (SMEs) are priorities for North African countries, particularly regarding job creation. Regulatory cooperation – such as harmonizing SME definitions, legislation and support institutions – across North Africa is an obvious area where further integration would encourage the development of start-ups and small businesses.
  • With the advent of the fourth industrial revolution, North African governments must address their technological gaps and work to improve public–private cooperation. In some sectors, such as the fintech industry, North African countries can build upon nascent synergies that have developed organically, such as those of start-up incubators and angel investors that work across the region.
  • Renewables, particularly solar energy production, are a promising development for North Africa. While regional initiatives, such as Desertec, have stalled due to political differences between countries, the sector has witnessed exponential growth in Tunisia, Egypt and Morocco, where the involvement of the private sector has proved successful.




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Local Pathways Towards De-escalation of Libya's Conflict

Invitation Only Research Event

28 January 2020 - 3:00pm to 4:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Usama Otman Essed, Libya Center for Strategic & Future Studies
Chair: Tim Eaton, Middle East and North Africa Programme, Chatham House

A shaky truce remains broadly in place among rival Libyan forces fighting for control of Tripoli. However, a durable ceasefire to bring an end to the current bout of conflict, which was initiated by Khalifa Haftar’s Libyan Arab Armed Forces’ (LAAF) offensive on the capital in April 2019, has not been reached. In recent weeks attention has focused on talks hosted in Moscow and Berlin, with the former aimed at agreeing a ceasefire and the latter seeking to reach agreement among international actors to bring an end to external military support for Libyan warring actors, and to craft a way forward for future intra-Libyan talks. Yet, there has been little emphasis on Libyan actors – beyond Haftar and prime minister Fayez al-Serraj – in this process.
 
This roundtable will bring together experts and policymakers to discuss means of de-escalating the conflict and seeking a lasting resolution through the development of interconnected intra-Libyan social and security negotiation tracks. Mr Usama Otman Essed of the Libya Center for Strategic and Future Studies (LCSFS) will present his research group’s ideas on these issues and discuss their ongoing efforts to promote dialogue among social and security actors.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Mohammed Abdalfatah

Asfari Foundation Academy Fellow

Biography

Mohammed’s research examines the potentials and the role of cities in driving inclusive sustainable development in the Gaza Strip and how cities can bring about innovative genuine solutions to encountered local and national challenges.

Before joining Chatham House and since 2006, Mohammed has been the director of international cooperation at the Municipality of Gaza, where he headed the planning team for the Gaza local development plan 2019-2022.

From 2002-06 he was international relations officer at the Municipality of Gaza and, prior to this, he held positions with UNDP and the Palestinian Ministry of Planning & International Cooperation.

He was a full time visiting research fellow at ICSR non-award research programme in the War Studies Department at King's College London from February-June 2014.

Mohammed holds a post-graduate diploma in Management of Local Development from the International Training Centre, ILO, Turin and earned his BA in Languages from Ain Shams University, Cairo.

Areas of expertise

  • Local development
  • Decentralized cooperation
  • International relations of the Middle East
  • Palestinian affairs with a particular focus on Gaza
  • Public policy and local governance

Past experience

2006-19Director of International Cooperation, Municipality of Gaza, Palestine
2014Visiting Research Fellow, ICSR, Department of War Studies at King's College London
2002-06International Relations Officer, Municipality of Gaza, Palestine
2001-02Programme Management Assistant, UNDP/PAPP, Gaza, Palestine
2000-01Desk Officer in Eastern Europe Dept., Palestinian Ministry of Planning & International Cooperation




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Iran Workshop Series: Domestic, Regional and International Outlook

Invitation Only Research Event

17 December 2019 - 10:00am to 3:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

After a summer of regional tensions and continued uncertainty regarding the future of the JCPOA, the Chatham House MENA Programme held a closed workshop to examine the impact of the Trump administration’s maximum pressure campaign.

Discussions focused on the domestic developments and challenges inside Iran, prospects for new negotiations with Iran, and the regional issues facing the country. Participants also considered the differences between American and European approaches towards Iran.

 

Event attributes

Chatham House Rule

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Conflict and the Water Crisis in Iraq

Invitation Only Research Event

9 March 2020 - 9:00am to 10:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Azzam Alwash, Founder & CEO, Nature Iraq
Peter Schwartzstein, Independent Journalist; Non-Resident Fellow, Centre for Climate Security
Discussant: Dr Jehan Baban, Founder & President, The Iraqi Environment and Health Society-UK
Chair: Dr Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Department, Chatham House

Water is a critical issue for Iraq’s future stability and prosperity. Only a few decades ago, the country was one of the most fertile in the region, with two major rivers flowing through it. Today, national and transboundary pollution, mismanagement, and debilitating cycles of conflict have contributed to a situation where only half of current water needs are being met, and where an 80% reduction in the flow of water down the Tigris and Euphrates rivers has led to the loss of millions of acres of formerly productive land and the displacement of rural communities.

Water scarcity can be a driver of violence and conflict. Tribal conflicts over water sources have erupted sporadically in the south and the contamination of municipal water which led to the hospitalization of some 118,000 citizens was a trigger for the large-scale protests in Basra in late 2018. Without concerted action by national and local governments, companies and international agencies, the situation will only worsen as higher temperatures and reduced rainfall drive rural-to-urban migration and increase the risk of drought, food insecurity and water-related diseases.

At this roundtable, part of the Chatham House Iraq Initiative, experts will discuss the domestic, regional and international factors that continue to exacerbate the water crisis in Iraq, and propose solutions, including technical innovation, public sector capacity-building and greater international cooperation, that might contribute to effective state-building, build resilience to the effects of climate change and reduce the risk of further conflict.

Event attributes

Chatham House Rule

Georgia Cooke

Project Manager, Middle East and North Africa Programme
+44 (0)20 7957 5740




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Expanding Sino–Maghreb Relations: Morocco and Tunisia

26 February 2020

Over the past two decades, China has increased its presence in North Africa in terms of trade and investment. This paper looks at China’s policy within the context of its Africa and Middle East policies to better understand its approach to Morocco and Tunisia.

Yahia H. Zoubir

Senior Professor of International Studies, KEDGE Business School, France and Visiting Fellow, Brookings Doha Center

2020-02-26-Xi-Jinping-King-Mohammed.jpg

Chinese President Xi Jinping and King Mohammed VI of Morocco wave during a welcoming ceremony outside the Great Hall of the People in Beijing on 11 May 2016. Photo: Getty Images.

Summary

  • China’s presence in the Maghreb has increased in recent years, raising concerns among Western powers. China has focused on bilateral relations with these countries while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF). However, this engagement has limited strategic value compared to relations China has with Saudi Arabia or the United Arab Emirates.
  • Since the launch of the Belt and Road Initiative (BRI) in 2013, China has shown greater interest in the Maghreb as an entry point to European and African markets. China has pursued commercial relations over political influence in the region. Morocco and Tunisia are still dependent on France, their former colonial power, and the European Union, which exert great political, economic, security and cultural influence over the two countries.
  • The Maghreb countries’ economic relations with China have grown exponentially, with Algeria forming the closest relationship. However, Morocco and Tunisia are keen to attract China’s investment and involvement in major construction and infrastructure projects to boost industrial and economic development. While China’s investments in Morocco and Tunisia remain at a low level, trade relations with both countries have grown steadily. Politically, China’s policy of noninterference in domestic affairs appeals to Maghreb states, which resent Western interference.
  • China’s influence in the Maghreb remains minimal. Its soft power push has struggled to promote advantages of strong relations with China beyond economics. Furthermore, Morocco and Tunisia’s populations have generally scant knowledge about China’s politics and culture. China has tried to address this lack of familiarity through the establishment of Confucius Institutes and other cultural activities. However, language and cultural barriers still impede the development of close relations, compared to those China has with other countries in Africa.




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POSTPONED: Libya: Political Fragmentation, War and Foreign Intervention

Members Event

24 March 2020 - 6:00pm to 7:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Wolfram Lacher, Senior Associate, German Institute for International and Security Affairs; Author, Libya's Fragmentation: Structure and Process in Violent Conflict
Chair: Maryam Nemazee, Anchor, Al Jazeera

Further speakers to be announced.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

 

Libya's third bout of civil war in a decade began when Khalifa Haftar's Libyan Arab Armed Forces (LAAF) launched an offensive on Tripoli in April 2019. Since then, a growing number of foreign states have intervened ever more deeply in the conflict. Warring Libyan armed factions, broadly aligned with either the internationally recognized Government of National Accord or the LAAF, have become increasingly reliant on foreign support to prosecute their war effort.  

Against this backdrop, the panellists will reflect on the forces that have shaped Libya’s trajectory since 2011. As the prospects for international mediation remain bleak, what motivations and grievances are driving the country’s warring parties? How can this war be explained beyond a scramble for the control of Libya’s oil wealth? And are Libyans at risk of being mere pawns in a proxy war?

 

Members Events Team




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Unpacking the role of religion in political transnationalism: the case of the Shi'a Iraqi diaspora since 2003

4 March 2020 , Volume 96, Number 2

Oula Kadhum

This article explores the role of religion in political transnationalism using the case of the Shi'a Iraqi diaspora since 2003. The article focuses on three areas that capture important trends in Shi'a transnationalism and their implications for transnational Shi'a identity politics. These include Shi'a diasporic politics, transnational Shi'a civic activism, and the cultural production of Iraqi Shi'a identity through pilgrimages, rituals and new practices. It is argued that understanding Shi'a Islam and identity formation requires adopting a transnational lens. The evolution of Shi'a Islam is not only a result of the dictates of the Shi'a clerical centres, and how they influence Shi'a populations abroad, but also the transnational interrelationships and links to holy shrine cities, Shi'i national and international politics, humanitarianism and commemorations and rituals. The article demonstrates that Shi'a political transnationalism is unexceptional in that it echoes much of the literature on diasporic politics and development where diaspora involve themselves from afar in the politics and societies of their countries of origin. At the same time, it shows the exceptionalism of Shi'a diasporic movements, in that their motivations and mobilizations are contributing to the reification of sectarian geographical and social borders, creating a transnationalism that is defined by largely Shi'a networks, spaces, actors and causes. The case of Shi'a political transnationalism towards Iraq shows that this is increasing the distance between Shi'is and Iraq's other communities, simultaneously fragmenting Iraq's national unity while deepening Shi'a identity and politics both nationally and supra-nationally.




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POSTPONED: Russia in MENA: An Update

Invitation Only Research Event

26 March 2020 - 9:30am to 11:00am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Nikolay Kozhanov, Research Associate Professor, Gulf Studies Center, Qatar University; Consulting Fellow, Russia and Eurasia Programme, Chatham House 
Chair: Sanam Vakil, Senior Research Fellow, Project Director, Future Dynamics of the Gulf, Middle East & North Africa Programme, Chatham House

Russia’s Middle East policy is driven by a complex mixture of traditional factors (such as the ongoing confrontation with the West) and new trends. The Kremlin is keen to maintain its position as an influential external broker. However, it is not confident Russia would be able to respond effectively if forced into a reactive mode by other regional players. The Kremlin therefore seeks to retain initiative and shape the agenda according to its needs and resources. This makes prediction of Moscow’s next moves in the region a challenging, but not impossible, task.

Nikolay Kozhanov will offer remarks on the changes that have taken place in Russia’s strategy since the publication of his research paper Russian Policy Across the Middle East: Motivations and Methods (2018).

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Event attributes

Chatham House Rule

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Webinar: The Environmental Crisis in the MENA Region – Impacts and Mitigation

Research Event

16 April 2020 - 11:30am to 12:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Programme, Chatham House
Greg Shapland, Associate Fellow, Middle East and North Africa Programme, Chatham House 
Moderator: Sanam Vakil, Deputy Director and Senior Research Fellow, Middle East and North Africa Programme, Chatham House

The event will be livestreamed on the MENA Programme Facebook page.

Climate and environmental issues have largely been marginalized in discussions about the Middle East and North Africa region and yet are critical to peace and security. In this webinar, experts will explore mounting pressures including those related to water (reduced, less reliable and more polluted sources), extreme temperatures, air pollution, land degradation and sea-level rise. Panelists will discuss the potential impact of worsening environmental conditions and what the region's governments can do to protect the health and livelihoods of their peoples.

This webinar is part of the Chatham House MENA Programme's Online Event Series and will be held on the record.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Webinar: Federalism in a Fragmented State: Rethinking Decentralization in Yemen

Research Event

15 April 2020 - 1:00pm to 2:00pm

Event participants

Osamah Al Rawhani, Deputy Director, Sana’a Center for Strategic Studies
Moderator: Nadim Houry, Executive Director, Arab Reform Initiative

Yemen suffered from the excessive control of the central government prior to the current conflict. Federalism has been put forward by many Yemeni political parties since the National Dialogue Conference (NDC) as the supposed magic cure for this significant problem. Today, Yemen is more fragmented than ever, its state central institutions have been scattered and lack leadership and the state has lost most of its sovereignty. The prevailing narrative that decentralization through federalism is Yemen’s inevitable path post-conflict often fails to acknowledge that there are prerequisites for effective local governance, beyond political will.  

In a recent article, Osamah Al Rawhani addressed how the weakness of central state institutions is the key challenge to proceeding with federalism in Yemen and highlighted prerequisites and contextual factors that need to be addressed before reforming the structure of the state. He argued that the viability of decentralization relies on the presence of a functioning, representative central government that is capable of devolving power but also able to keep the state from further fragmentation. 

In this webinar, part of the Chatham House project on The Future of the State in the Middle East and North Africa, the article’s author will discuss recent developments in Yemen, where shifting frontlines and regional divisions are fragmenting the country in new ways. The speaker will explore alternative approaches to pursue the path of federalism that recognize the current realities and the critical need for strong central institutions. He will also survey the internal and external factors that must be considered to rebuild a stable state in Yemen.

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Webinar: Reimagining the Role of State and Non-State Actors in (Re)building National Health Systems in the Arab World

Research Event

22 April 2020 - 1:00pm to 2:00pm

Event participants

Fadi El-Jardali, Professor of Health Policy and Systems, American University of Beirut
Moderator: Nadim Houry, Executive Director, Arab Reform Initiative

As new cases of COVID-19 continue to surge, countries around the world struggle to mitigate the public health and economic effects of the virus. It is becoming increasingly clear that an effective pandemic response requires a whole-of-government, whole-of-society approach. In the Arab world, where health systems are already strained by armed conflicts and displaced populations, a whole-of-society response to the pandemic is particularly critical as countries have become increasingly dependent on non-state actors, notably the private sector, for healthcare provision and any response that includes the state alone may not be sufficient to address the pandemic.

In a recent article, Fadi El-Jardali, argued that while the pandemic will have grave health and economic consequences for years to come, it brings with it a valuable opportunity to re-envision the role of state and non-state actors in strengthening health systems. The article addressed the need for increased collaboration between state and non-state actors, and the rethinking of existing cooperation models to provide quality healthcare services for all.  

In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, Dr El-Jardali will discuss how state and non-state actors can collaborate more effectively to address the shortcomings of national health care systems amidst the pandemic and beyond. The article’s author will share insights on the different capacities available in Arab societies that governments can draw upon to ensure that Universal Health Coverage, equity considerations and social justice are at the core of health systems.

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

 

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Same Old Politics Will Not Solve Iraq Water Crisis

15 April 2020

Georgia Cooke

Project Manager, Middle East and North Africa Programme

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative

Glada Lahn

Senior Research Fellow, Energy, Environment and Resources Programme
Addressing Iraq’s water crisis should be a priority for any incoming prime minister as it is damaging the country’s attempts to rebuild. But successive governments have allowed the problem to fester.

2020-04-15-Iraq-Water

Punting in the marshes south of the Iraqi city of Ammarah. Photo by Ghaith Abdul-Ahad/Getty Images.

Historically, Iraq lay claim to one of the most abundant water supplies in the Middle East. But the flow of the Tigris and Euphrates rivers has reduced by up to 40% since the 1970s, due in part to the actions of neighbouring countries, in particular Turkey, upstream.

Rising temperatures and reduced rainfall due to climate change are also negatively impacting Iraq’s water reserves. Evaporation from dams and reservoirs is estimated to lose the country up to 8 billion cubic metres of water every year.

A threat to peace and stability

Shortages have dried up previously fertile land, increasing poverty in agricultural areas. Shortages have also served to fuel conflict: communities faced with successive droughts and government inertia proved to be easy targets for ISIS recruiters, who lured farmers into joining them by offering money and food to feed their families. Economic hardship for those whose livelihoods relied upon river water has also driven rural to urban migration, putting significant strain on already over-populated towns and cities, exacerbating housing, job and electricity shortages, and widening the gap between haves and have-nots.

But scarcity isn’t the most crucial element of Iraq’s water crisis – contamination is. Decades of local government mismanagement, corrupt practices and a lack of regulation of dumping (it is estimated up to 70% of Iraq’s industrial waste is dumped directly into water) has left approximately three in every five citizens without a reliable source of potable water.

In 2018, 118,000 residents of Basra province were hospitalised with symptoms brought on by drinking contaminated water, which not only put a spotlight on the inadequacies of a crumbling healthcare system but sparked mass protests and a subsequent violent crackdown.

The water crisis is also undermining the stability of the country’s federal governance model, by occasionally sparking disputes between Baghdad and the Kurdistan Regional Government, as well as between governorates in the south.

The crisis is both a symptom and a cause of poor governance. Iraq is stuck in a cycle whereby government inaction causes shortages and contamination, which result in economic losses, reduced food supply, increased prices and widespread poor health. This in turn leads to increasing levels of poverty, higher demand on services and civil unrest, increasing the pressure on a weak, dysfunctional system of government.

What can be done?

The first priority should be modernising existing water-management infrastructure - a relic of a time when the problem was an excess rather than a shortage of water (the last time Iraq’s flood defences were required was 1968). Bureaucratic hurdles, widespread corruption and an endless cycle of other crises taking precedent prevent good initiatives from being implemented or scaled up.

Diversifying energy sources to improve provision is crucial. Baghdad has a sewage treatment plant that originally ran on its own electricity source, but this capacity was destroyed in 1991 and was never replaced. The city continues to suffer from dangerous levels of water pollution because the electricity supply from the grid is insufficient to power the plant. Solar energy has great potential in sun-drenched Iraq to bridge the gaping hole in energy provision, but successive governments have chosen to focus on fossil fuels rather than promoting investment to grow the renewables sector.

Heightened tension with upstream Turkey could turn water into another cause of regional conflict. But, if approached differently, collaboration between Iraq and its neighbour could foster regional harmony.

Turkey’s elevated geography and cooler climate mean its water reserves suffer 75% less evaporation than Iraq’s. Given that Turkey’s top energy priority is the diversification of its supply of imported hydrocarbons, a win-win deal could see Turkey exchange access to its water-management infrastructure for delivery of reduced cost energy supplies from Iraq.

German-French cooperation on coal and steel in the 1950s and the evolution of economic integration that followed might provide a model for how bilateral cooperation over one issue could result in cooperation with other regional players (in this case Iran and Syria) on a range of other issues. This kind of model would need to consider the future of energy, whereby oil and gas would be replaced by solar-power exports.

These solutions have been open to policymakers for years and yet they have taken little tangible action. While there are leaders and bureaucrats with the will to act, effective action is invariably blocked by a complex and opaque political system replete with vested interests in maintaining power and wealth via a weak state and limited services from central government.

Breaking the cycle

To break this cycle, Iraq needs a group of professional and able actors outside of government to work with willing elements of the state bureaucracy as a taskforce to pressure for action and accountability. Publishing the recommendations from a hitherto withheld report produced in the aftermath of Basra’s 2018 heath crisis would be a great start.

In time, this taskforce could champion the prioritisation of water on the national agenda, the implementation of infrastructure upgrades, and hold more productive conversations with neighbour states.

With such a high degree of state fragmentation and dysfunction in Iraq, looking to the central government to provide leadership will not yield results. Engagement with a coalition of non-state actors can begin to address the water crisis and also open a dialogue around new models of governance for other critical issues. This might even be a starting point for rewriting the tattered social contract in Iraq.

This piece is based on insights and discussion at a roundtable event, Conflict and the Water Crisis in Iraq, held at Chatham House on March 9 as part of the Iraq Initiative.




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Webinar: Idlib at Risk – Doctors and First Responders in Northwest Syria

Members Event Webinar

23 April 2020 - 5:00pm to 6:00pm

Online

Event participants

Dr Munzer al-Khalil, Head, Idlib Health Directorate
Raed Al Saleh, Director, Syria Civil Defence (The White Helmets)
Alaa Rajaa Mughrabieh, Child Protection Officer, Hurras Network
Chair: Dr Lina Khatib, Director, Middle East and North Africa Programme, Chatham House

 

In Syria, uncertainty about the safety of the ceasefire agreed between Russia and Turkey last month is inhibiting 1 million people who have been displaced since December 2019 from returning home.

The looming COVID-19 global health crisis threatens to further devastate those most vulnerable as the conditions in northwest Syria’s refugee camps make it hard to practice common social distancing guidelines. Added to this, the medical infrastructure in the region has been decimated after years of bombings which has disabled over 70 health facilities since April 2019.

This webinar highlights the potentially catastrophic risks of a coronavirus outbreak in Idlib and displacement camps in northwest Syria by speaking with medical and civil society actors working in the region. How are doctors and local humanitarian organizations scaling up their medical and prevention response to the COVID-19 outbreak?

What key supplies such as ventilators, testing kits and critical sanitary equipment are still lacking? And how can the international community step in to help mitigate the potentially devastating consequences of an outbreak in these refugee camps?

This event is run in collaboration with The Syria Campaign, a human rights organization working with Syrian civil society to raise the voices of those struggling for democracy, and support frontline activists and humanitarians.




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Webinar: Assessing the Twists and Turns in the US-Iran Stalemate

Research Event

28 April 2020 - 2:00pm to 3:30pm

Event participants

Esfandyar Batmanghelidj, Founder and Publisher, Bourse & Bazaar
Nasser Hadian, Professor of Political Sciences, Faculty of Law and Political Sciences, University of Tehran
Azadeh Zamirirad, Deputy Head, Middle East and Africa Division, SWP Berlin
Ariane Tabatabai, Middle East Fellow, Alliance for Securing Democracy, US German Marshall Fund; Adjunct Senior Research Scholar, SIPA
Moderator: Sanam Vakil, Deputy Head and Senior Research Fellow, Middle East and North Africa Programme, Chatham House
The webinar will be livestreamed on the MENA Programme Facebook page.

Since the start of 2020, Iran has been beset with multiple challenges including the spread of COVID-19, economic pressure from US sanctions, parliamentary elections in February, the killing of Qassem Soleimani and an increase in tensions in Iraq. The Trump administration interprets these domestic and regional challenges faces by Iran as evidence that its maximum pressure campaign is proving to be effective.

In this webinar, speakers will examine the economic and political impact of the Trump administration's policy towards Iran. Panelists will consider how these events are impacting internal dynamics in Iran and examine the economic impact of sanctions. They will also evaluate European diplomatic efforts to preserve the Iran nuclear agreement, and consider the future trajectory of US Iran policy and the potential for escalation in the region.
 
This webinar is part of the Chatham House Middle East and North Africa Programme's Online Event Series. The event will be held on the record.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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It's a man's world: carnal spectatorship and dissonant masculinities in Islamic State videos

7 May 2020 , Volume 96, Number 3

Manni Crone

Islamic State videos have often been associated with savage violence and beheadings. An in-depth scrutiny however reveals another striking feature: that female bodies are absent, blurred or mute. Examining a few Islamic State videos in depth, the article suggests that the invisibility of women in tandem with the ostentatious visibility of male bodies enable gendered and embodied spectators to indulge in homoerotic as well as heterosexual imaginaries. In contrast to studies on visual security and online radicalization which assert that images affect an audience, this article focuses on the interaction between video and audience and argues that spectators are not only rational and emotional but embodied and gendered as well. Islamic State videos do not only attract western foreign fighters through religious–ideological rhetoric or emotional impact but also through gendered forms of pleasure and desire that enable carnal imagination and identification. The article probes the analytical purchase of carnal aesthetics and spectatorship.




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Insulin-Like Growth Factor Dysregulation Both Preceding and Following Type 1 Diabetes Diagnosis

Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)+ compared with AAb relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre–type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb+ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb+ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction.




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Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors

Sodium–glucose cotransport 2 inhibitors (SGLT2i) lower plasma glucose but stimulate endogenous glucose production (EGP). The current study examined the effect of dapagliflozin on EGP while clamping plasma glucose, insulin, and glucagon concentrations at their fasting level. Thirty-eight patients with type 2 diabetes received an 8-h measurement of EGP ([3-3H]-glucose) on three occasions. After a 3-h tracer equilibration, subjects received 1) dapagliflozin 10 mg (n = 26) or placebo (n = 12); 2) repeat EGP measurement with the plasma glucose concentration clamped at the fasting level; and 3) repeat EGP measurement with inhibition of insulin and glucagon secretion with somatostatin infusion and replacement of basal plasma insulin and glucagon concentrations. In study 1, the change in EGP (baseline to last hour of EGP measurement) in subjects receiving dapagliflozin was 22% greater (+0.66 ± 0.11 mg/kg/min, P < 0.05) than in subjects receiving placebo, and it was associated with a significant increase in plasma glucagon and a decrease in the plasma insulin concentration compared with placebo. Under glucose clamp conditions (study 2), the change in plasma insulin and glucagon concentrations was comparable in subjects receiving dapagliflozin and placebo, yet the difference in EGP between dapagliflozin and placebo persisted (+0.71 ± 0.13 mg/kg/min, P < 0.01). Under pancreatic clamp conditions (study 3), dapagliflozin produced an initial large decrease in EGP (8% below placebo), followed by a progressive increase in EGP that was 10.6% greater than placebo during the last hour. Collectively, these results indicate that 1) the changes in plasma insulin and glucagon concentration after SGLT2i administration are secondary to the decrease in plasma glucose concentration, and 2) the dapagliflozin-induced increase in EGP cannot be explained by the increase in plasma glucagon or decrease in plasma insulin or glucose concentrations.




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The National Oncology PET Registry (NOPR): A monumental effort by a few leaders




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18F-DCFPyL PET/CT Imaging in Patients with Biochemical Recurrence Prostate Cancer after Primary Local Therapy

Objective: To investigate the lesion detection rate of 18F-DCFPyL-PET/CT, a prostate-specific membrane antigen (PSMA) targeted PET agent, in biochemical relapse prostate cancer patients after primary local therapy. Methods: This is a prospective institutional review board-approved study of 90 patients with documented biochemical recurrence (median PSA 2.5 ng/mL, range 0.21-35.5 ng/mL) with negative conventional imaging after primary local therapies, including radical prostatectomy (n = 38), radiation (n = 27) or combination (n = 25). Patients on androgen deprivation therapy were excluded. Patients underwent whole-body 18F-DCFPyL-PET/CT (299.9±15.5 MBq) at 2 h p.i. PSMA-PET lesion detection rate was correlated with PSA, PSA kinetics and original primary tumor grade. Results: Seventy patients (77.8%) showed a positive PSMA-PET scan, identifying a total of 287 lesions: 37 prostate bed foci, 208 lymph nodes, and 42 bone/organ distant sites; 11 patients had a negative scan and 9 patients showed indeterminate lesions, which were considered negative in this study. The detection rates were 47.6% (n = 10/21), 50% (n = 5/10), 88.9% (n = 8/9), and 94% (n = 47/50) for PSA >0.2 to <0.5, 0.5 to <1.0, 1 to <2.0, and ≥2.0 ng/mL, respectively. In post-surgical patients, PSA, PSAdt and PSAvel correlated with PET results but the same was not true for post-radiation patients. These parameters also correlated with the extent of disease on PET (intrapelvic vs. extrapelvic). There was no significant difference between the rate of positive scans in patients with higher grade vs lower grade primary tumors (Gleason score ≥4+3 vs <3+4). Tumor recurrence was histology confirmed in 40% (28/70) of patients. On a per-patient basis, positive predictive value was 93.3% (95% CI, 77.6-99.2%) by histopathologic validation, and 96.2% (95% CI, 86.3-99.7%) by the combination of histology and imaging/clinical follow-up. Conclusion: 18F-DCFPyL-PET/CT imaging offers high detection rates in biochemically recurrent prostate cancer patients; and is positive in about 50% of patients with PSA <0.5 ng/mL, which could substantially impact clinical management. In post-surgical patients, 18F-DCFPyL-PET/CT correlates with PSA, PSAdt and PSAvel suggesting it may have prognostic value. 18F-DCFPyL-PET/CT is highly promising for localizing sites of recurrent prostate cancer.




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3-year freedom from progression following 68GaPSMA PET CT triaged management in men with biochemical recurrence post radical prostatectomy. Results of a prospective multi-center trial.

Background: 68Ga PSMA PET CT (PSMA) is increasingly used in men with biochemical recurrence (BCR) post radical prostatectomy (RP), but its longer term prognostic / predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for 3 year freedom from progression (FFP) in men with BCR post RP undergoing salvage radiotherapy (sRT). Methods: This prospective multi-center study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA with rising PSA following RP. Management following PSMA was recorded but not mandated. PSMA protocols were standardised across sites and reported prospectively. Clinical, pathological and surgical information, sRT, timing and duration of androgen deprivation (ADT), 3 year PSA results and clinical events were documented. FFP was defined as a PSA rise ≤ 0.2ng/mL above nadir post sRT, with no additional treatment. Results: The median PSA was 0.26ng/mL (IQR 0.15 - 0.59) and follow-up 38 months (IQR 31-43). PSMA was negative in 34.6% (90/260), confined to prostate fossa 21.5% (56/260), pelvic nodes 26.2% (68/260), and distant disease 17.7% (46/260). 71.5% (186/260) received sRT, 38.2% (71/186) to the fossa only, 49.4% (92/186) fossa + pelvic nodes and 12.4% (23/186) nodes alone/SBRT. PSMA was highly predictive of FFP at 3 years following sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative/fossa confined vs. 45% (39/86) for extra fossa disease (p<0.0001). On logistic regression PSMA was more independently predictive of FFP than established clinical predictors, including PSA, T-stage, surgical margin status or Gleason score (P < 0.002). 32% of men with a negative PSMA PET did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59ng/mL over the 3 years. Conclusion: PSMA PET result is highly predictive of FFP at 3 years in men undergoing sRT for BCR following RP. In particular, men with negative PSMA PET or disease identified as still confined to the prostate fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional ADT than those with extra fossa disease.




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Head-to-head comparison of 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors: a prospective study

Purpose: 68Ga-DOTA-JR11 is an antagonist for somatostatin receptor used in neuroendocrine imaging. The purpose of this study is to compare 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: Patients with histologically-proven, metastatic and/or unresectable, well-differentiated neuroendocrine tumors were prospectively recruited in this study. They received an intravenous injection of 68Ga-DOTATATE (4.0 ± 1.3 mCi) on the first day and 68Ga-DOTA-JR11 (4.0 ± 1.4 mCi) on the second day. Whole-body PET/CT scans were performed at 40 to 60 minutes after injection on the same scanner. Physiologic uptake of normal organs, lesion numbers, and lesion uptake were compared. Results: Twenty-nine patients were prospectively enrolled in the study. The SUVmax of the spleen, renal cortex, adrenal glands, pituitary glands, stomach wall, normal liver parenchyma, small intestine, pancreas, and bone marrow were significantly lower on 68Ga-DOTA-JR11 than on 68Ga-DOTATATE PET/CT (P<0.001). 68Ga-DOTA-JR11 detected significantly more liver lesions (539 vs. 356, P = 0.002), but fewer bone lesions (156 vs. 374, P = 0.031, Figure 3) than 68Ga-DOTATATE. The tumor-to-background ratio of liver lesions was significantly higher on 68Ga-DOTA-JR11 (7.6 ± 5.1 vs. 3.4 ± 2.0, P<0.001). 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT showed comparable results for primary tumors and lymph node metastases based on either patient-based or lesion-based comparison. Conclusion: 68Ga-DOTA-JR11 performs better in the detection ability and TBR of liver metastases. However, 68Ga-DOTATATE outperforms 68Ga-DOTA-JR11 in the detection of bone metastases. The differential affinity of different metastatic sites provides key information for patient selection in imaging and peptide receptor radionuclide therapy.




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Can fluorescence-guided surgery help identify all lesions in unknown locations or is the integrated use of a roadmap created by preoperative imaging mandatory? A blinded study in prostate cancer patients.

Rationale: Lymphatic tracers can help visualize the lymphatic drainage patterns and sentinel nodes of individual prostate cancer patients. To determine the role of nuclear medicine, in particular the positional guidance of a SPECT/CT-based 3D imaging roadmap, in this process we studied to which extend fluorescence-guidance underestimated the number of target lesions. Methods: SPECT/CT imaging was performed after intraprostatic tracer administration of either ICG-99mTc-nanocolloid (hybrid tracer group) or 99mTc-nanocolloid to create a roadmap that depicted all sentinel nodes (SNs). Patients who received 99mTc-nanocolloid were injected with "free" ICG immediately prior to surgery ("free" ICG group). Before unblinding, fluorescence-guidance was used for intraoperative SN identification. This was followed by extended pelvic lymph node dissection (ePLND). Following unblinding of the SPECT/CT images, the number of missed SN’s were recorded and their resection was pursued when the anatomy allowed. Results: Preoperative SPECT/CT revealed no differences in the SN identification rate between ICG-99mTc-nanocolloid and 99mTc-nanocolloid. However, fluorescence-guidance only allowed intraoperative removal of all SNs in 40% of patients in the hybrid tracer group and in 20% of patients in the "free" ICG group. Overall, 75.9% of the intraoperatively resected SNs in the hybrid tracer group and 51.8% of the SNs in the "free" ICG group were removed solely under fluorescence-guidance. During ePLND 22 additional SNs were resected (7 in the hybrid tracer group and 15 in the "free" ICG group). After unblinding 18 remaining SNs were identified (6 in the hybrid group and 12 in the "free" ICG group). In the "free" ICG group, ex vivo evaluation of the excised specimens revealed that 14 SNs removed under ePLND or after unblinding contained radioactivity but no fluorescence. Conclusion: The preoperative imaging roadmap provided by SPECT/CT enhanced the detection of prostate SNs in more ectopic locations in 17 of the 25 patients and the hybrid tracer ICG-99mTc-nanocolloid was shown to outperform "free" ICG. Overall, fluorescence-guided pelvic nodal surgery underestimated the number of SNs in 60-80% of patients.




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Tau PET imaging with 18F-PI-2620 in patients with Alzheimer's disease and healthy controls: a first-in-human study

18F-PI-2620 is a positron emission tomography (PET) tracer with high binding affinity for aggregated tau, a key pathologic feature of Alzheimer’s disease (AD) and other neurodegenerative disorders. Preclinically, 18F-PI-2620 binds to both, 3R and 4R tau isoforms. The purpose of this first-in-human study was to evaluate the ability of 18F-PI-2620 to detect tau pathology in AD patients using PET imaging, as well as to assess its safety and tolerability of this new tau PET tracer. Methods: Participants with clinical diagnosis of probable AD and healthy controls (HC) underwent dynamic 18F-PI-2620 PET imaging for 180 min. 18F-PI-2620 binding was assessed visually and quantitatively using Distribution Volume Ratios (DVR) estimated from non-invasive tracer kinetics and standardized uptake value ratios (SUVR) measured at different time points post-injection (p.i.) with the cerebellar cortex as the reference region. Time-activity curves and SUVR were assessed in AD and HC, as well as DVR and SUVR correlations and effect size (Cohen’s d) over time. Results: 18F-PI-2620 showed peak brain uptake around 5 min p.i. and fast wash-out in non-target regions. In AD subjects, focal asymmetric uptake was evident in temporal and parietal lobes, precuneus, and posterior cingulate cortex. DVR and SUVR in these regions were significantly higher in AD compared to HC. Very low background signal was observed in HC. 18F-PI-2620 administration was safe and well tolerated. SUVR time activity curves in most regions and subjects achieved a secular equilibrium after 40 min p.i.. A strong correlation (R2 > 0.93) was found between non-invasive DVR and SUVR for all imaging windows starting >30 min p.i.. Similar effect sizes between AD and HC groups were obtained across the different imaging windows. 18F-PI-2620 uptake in neocortical regions was significantly correlated with the degree of cognitive impairment. Conclusion: Initial clinical data obtained in AD and HC demonstrate the high image quality with excellent signal-to-noise of 18F-PI-2620 PET for imaging tau deposition in AD subjects. Non-invasive quantification using DVR and SUVR for 30 min imaging windows between 30-90 min p.i., e.g. 45-75 min, provides robust and significant discrimination between AD and HC subjects. 18F-PI-2620 uptake in expected regions is highly correlated to neurocognitive performance.




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Evaluation of dosimetry, quantitative methods and test-retest variability of 18F-PI-2620 PET for the assessment of tau deposits in the human brain

18F-PI-2620 is a next generation tau positron emission tomography (PET)-tracer that has demonstrated ability to image the spatial distribution of suspected tau pathology. The objective of this study was to assess the tracer biodistribution, dosimetry and quantitative methods of 18F-PI-2620 in the human brain. Full kinetic modelling approaches to quantify tau load were investigated. Non-invasive kinetic modeling approaches and semi-quantitative methods were evaluated against the full tracer kinetics. Finally, the reproducibility of PET measurements from test and retest scans was assessed. Methods: Three healthy controls (HC) and 4 Alzheimer disease (AD) subjects underwent two dynamic PET scans including arterial sampling. Distribution volume ratio (DVR) was estimated using full tracer kinetics (2 Tissue Compartment (2TC) models, Logan Graphical Analysis (LGA)) and non-invasive kinetic models (Non-Invasive Logan Graphical Analysis (NI-LGA) and the multilinear reference tissue model (MRTM2)). Standardized uptake value ratio (SUVR) was determined at different imaging windows after injection. Correlation between DVR and SUVR, effect size (Cohen’s d) and test-retest variability (TRV) were evaluated. Additionally, 6 HC subjects received one tracer administration and underwent whole-body PET for dosimetry calculation. Organ doses and the whole-body effective dose were calculated using OLINDA 2.0. Results: Strong correlation was found across different kinetic models (R2 >0.97) and between DVR(2TC) and SUVRs between 30 to 90 min with R2>0.95. Secular equilibrium was reached around 40 min post injection (p.i.) in most regions and subjects. The TRV and effect size for the SUVR across different regions was similar at 30-60 min (TRV=3.8%, d=3.80), 45-75 min (TRV=4.3%, d=3.77) and 60-90 min (TRV=4.9%, d=3.73) and increased at later time points. Elimination was via the hepatobiliary and urinary system. The whole-body effective dose was determined to be 33.3±2.1 μSv/MBq for an adult female and 33.1±1.4 μSv/MBq for an adult male with a 1.5 hour urinary bladder voiding interval. Conclusion: 18F-PI-2620 exhibits fast kinetics, suitable dosimetry and low TRV. DVR measured using the 2TC model with arterial sampling correlated strongly with DVR measured by NI-LGA, MRTM2 and SUVR. SUVR can be used for 18F-PI-2620 PET quantification of tau deposits avoiding arterial blood sampling. Static 18F-PI-2620 PET scans between 45-75min p.i. provide excellent quantification accuracy, large effect size and low TRV.




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Combined Visual and Semi-quantitative Evaluation Improves Outcome Prediction by Early Mid-treatment 18F-fluoro-deoxi-glucose Positron Emission Tomography in Diffuse Large B-cell Lymphoma.

The purpose of this study was to assess the predictive and prognostic value of interim FDG PET (iPET) in evaluating early response to immuno-chemotherapy after two cycles (PET-2) in diffuse large B-cell lymphoma (DLBCL) by applying two different methods of interpretation: the Deauville visual five-point scale (5-PS) and a change in standardised uptake value by semi-quantitative evaluation. Methods: 145 patients with newly diagnosed DLBCL underwent pre-treatment PET (PET-0) and PET-2 assessment. PET-2 was classified according to both the visual 5-PS and percentage SUV changes (SUV). Receiver operating characteristic (ROC) analysis was performed to compare the accuracy of the two methods for predicting progression-free survival (PFS). Survival estimates, based on each method separately and combined, were calculated for iPET-positive (iPET+) and iPET-negative (iPET–) groups and compared. Results: Both with visual and SUV-based evaluations significant differences were found between the PFS of iPET– and iPET+ patient groups (p<0.001). Visually the best negative (NPV) and positive predictive value (PPV) occurred when iPET was defined as positive if Deauville score 4-5 (89% and 59%, respectively). Using the 66% SUV cut-off value, reported previously, NPV and PPV were 80 and 76%, respectively. SUV at 48.9% cut-off point, reported for the first time here, produced 100% specificity along with the highest sensitivity (24%). Visual and semi-quantitative SUV<48.9% assessment of each PET-2 gave the same PET-2 classification (positive or negative) in 70% (102/145) of all patients. This combined classification delivered NPV and PPV of 89% and 100% respectively, and all iPET+ patients failed to achieve or remain in remission. Conclusion: In this large consistently treated and assessed series of DLBCL, iPET had good prognostic value interpreted either visually or semi-quantitatively. We determined that the most effective SUV cut-off was at 48.9%, and that when combined with visual 5-PS assessment, a positive PET-2 was highly predictive of treatment failure.




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Initial studies with [11C]vorozole positron emission tomography detect over-expression of intra-tumoral aromatase in breast cancer

Introduction: Aromatase inhibitors are the mainstay of hormonal therapy in estrogen receptor positive, postmenopausal breast cancer, although response rate is just over 50%. The goal of the present study was to validate and optimize positron emission tomography (PET) with 11C-vorozole for measuring aromatase expression in postmenopausal breast cancer. Methods: Ten newly diagnosed, postmenopausal women with biopsy confirmed breast cancer were administered 11C-vorozole intravenously and PET emission data collected between 40 – 90 minutes post-injection. Tracer injection and scanning were repeated 2 hours after ingestion of 2.5mg letrozole p.o. Mean and maximal standard uptake values and ratios to non-tumor tissue (SUVs, SUVRs) were calculated for tumor and non-tumor regions at baseline and after letrozole. Biopsy specimens from the same tumors were stained for aromatase using immunohistochemistry and evaluated for stain intensity and the percentage of immune-positive cells. Results: Seven of the 10 women (70%) demonstrated increased focal uptake of tracer (SUVR>1.1) coinciding with the mammographic location of the lesion. The other 3 women (30%) did not show increased uptake in the tumor (SUVR <1.0). All of the cases with SUVR above 1.1 had SUVs above 2.4 and there was no overlap in SUV between the two groups, with mean SUV in tumors overexpressing aromatase (SUVR>1.1) ranging from 2.47 to 13.6, while tumors not overexpressing aromatase (SUVR<1) ranged from 0.8 to 1.8. Pretreatment with letrozole reduced tracer uptake in the majority of subjects; although the %blocking varied across and within tumors. Tumors with high SUV in vivo also showed high staining intensity on IHC. Conclusion: PET with 11C-vorozole is a useful technique for measuring aromatase expression in individual breast lesions, enabling a non-invasive quantitative measurement of baseline and post-treatment aromatase availability in primary tumors and metastatic lesions.




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SUV25 and {micro}PERCIST: Precision Imaging of Response to Therapy in Co-Clinical FDG-PET Imaging of Triple Negative Breast Cancer (TNBC) Patient-Derived Tumor Xenografts (PDX)

Numerous recent works highlight the limited utility of established tumor cell lines in recapitulating the heterogeneity of tumors in patients. More realistic preclinical cancer models are thought to be provided by transplantable, patient-derived tumor xenografts (PDX). Inter- and intra-tumor heterogeneity of PDX, however, present several challenges in developing optimal quantitative pipelines to assess response to therapy. The objective of this work was to develop and optimize image metrics of FDG-PET to assess response to combination docetaxel/carboplatin therapy in a co-clinical trial involving triple negative breast cancer (TNBC) PDX. We characterize the reproducibility of SUV metrics to assess response to therapy and optimize a preclinical PERCIST (µPERCIST) paradigm to complement clinical standards. Considerations in this effort included variability in tumor growth rate and tumor size; solid tumor vs. tumor heterogeneity and necrotic phenotype; and optimal selection of tumor slice versus whole tumor. A test-retest protocol was implemented to optimize the reproducibility of FDG-PET SUV thresholds, SUVpeak metrics, and µPERCIST parameters. In assessing response to therapy, FDG-PET imaging was performed at baseline and +4 days following therapy. The reproducibility, accuracy, variability, and performance of imaging metrics to assess response to therapy were determined. We defined an index—"Quantitative Response Assessment Score (QRAS)"—to integrate parameters of prediction and precision, and thus aid in selecting optimal image metrics of response to therapy. Our data suggests that a threshold value of 25% (SUV25) of SUVmax was highly reproducible (<9% variability). Concordance and reproducibility of µPERCIST were maximized at α=0.7 and β=2.8 and exhibited high correlation to SUV25 measures of tumor uptake. QRAS scores favor SUV25 followed by SUVP14 as optimal metrics of response to therapy. Additional studies are warranted to fully characterize the utility of SUV25 and µPERCIST SUVP14 as image metrics of response to therapy across a wide range of therapeutic regiments and PDX models.




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Long term follow-up and outcomes of re-treatment in an expanded 50 patient single-center phase II prospective trial of Lutetium-177 (177Lu) PSMA-617 theranostics in metastatic castrate-resistant prostate cancer

Objectives: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy. Methods: 50 patients with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Endpoints included PSA response (PCWG2), toxicity (CTCAE v4.03), imaging response, patient-reported health-related quality of life (QoL), progression-free and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including LuPSMA. Results: 75 men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 months) and extensive prior treatment including prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with ≥ 80% decrease. Of 27 patients with measurable soft tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to LuPSMA were self-limiting G1-2 dry mouth (66%), transient G1-2 nausea (48%), G3-4 thrombocytopenia (10%) and G3 anemia (10%). Brief pain inventory severity and interference scores decreased at all time points including at the 3 month follow-up with a decrease of -1.2 (95% CI -0.5 to -1.9, P = 0.001) and 1.0 (95% CI -0.2 to -0.18, P = 0.013), respectively. At a median follow-up of 31.4 months, median OS was 13.3 months (95% CI 10.5-18.7) with a significantly longer survival of 18.4 months (95% CI 13.8-23.8) in patients achieving a PSA decline ≥ 50%. At progression following prior response, further LuPSMA was administered to 15 (30%) patients (median 2 cycles commencing 359 days from enrolment) with PSA decline ≥ 50% in 11 patients (73%). 4 of 21 patients (19%) receiving other systemic therapies upon progression experienced PSA decline ≥ 50%. There were no unexpected adverse events with LuPSMA re-treatment. Conclusion: This expanded 50 patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity and improved QoL with LuPSMA radioligand therapy. Upon progression, re-challenge LuPSMA demonstrated higher response rates than other systemic therapies.




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Diagnostic value of 68Ga-PSMA PET/CT for detection of PTEN expression in prostate cancer: a pilot study

Purpose: To explore the value of 68Ga-PSMA-PET/CT for detection of phosphatase and tensin homolog (PTEN) - loss prostate cancer (PCa). Methods: We retrospectively enrolled 75 patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET/CT before radical prostatectomy. Lesions were outlined on pathological images and regions of interest were drawn on matched mpMRI and PET/CT images. Imaging parameters including average apparent diffusion coefficient (ADCmean) and maximum standardized uptake value (SUVmax) were derived. Immunohistochemical staining was carried out to evaluate the PTEN status. The diagnostic performance of imaging parameters was analyzed by receiver operating characteristics (ROC) analysis. A univariate logistic regression analyses were used to evaluate the association between clinical and imaging variables and PTEN status. Results: Totally, 103 lesions from 54 patients were analyzed. Of these lesions, 34 of 103 (33.0%) showed PTEN-loss status. Our study showed a strong association between SUVmax and PTEN-loss tumors both in the per-patient analysis (P < 0.01) and per-lesion analysis (P < 0.01), yielding the sensitivity and specificity of 0.80 and 0.77 in the per-patient analysis and 0.83 and 0.74 in the per-lesion analysis. Meanwhile, higher pathological PSMA expression was found in the PTEN-deficiency tumors. However, there was no significant difference between PTEN-loss tumors and PTEN-intact tumors using parameters including ADCmean (P > 0.05) and PI-RADS score (P > 0.05). Surprisingly, SUVmax was a significant predictor for detection of PTEN-loss tumors (odds ratio: 7.56, 95% confidence interval: 2.18-26.24, per-patient analysis; odds ratio: 13.66, 95% confidence interval: 4.32-43.24, per-lesion analysis). Conclusion: 68Ga-PSMA-PET/CT could effectively detect aggressive PTEN-loss tumors.




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Pre-treatment 18F-FDG PET/CT Radiomics predict local recurrence in patients treated with stereotactic radiotherapy for early-stage non-small cell lung cancer: a multicentric study

Purpose: The aim of this retrospective multicentric study was to develop and evaluate a prognostic FDG PET/CT radiomics signature in early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic radiotherapy (SBRT). Material and Methods: Patients from 3 different centers (n = 27, 29 and 8) were pooled to constitute the training set, whereas the patients from a fourth center (n = 23) were used as the testing set. The primary endpoint was local control (LC). The primary tumour was semi-automatically delineated in the PET images using the Fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. A total of 184 IBSI-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the four institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 (1.7 – 63.4) and 25.5 (7.7 – 57.8) months in training and testing sets respectively. In univariate analysis, none of the clinical variables, 2 PET and 2 CT features were significantly predictive of LC. The best predictive models in the training set were obtained by combining one feature from PET, namely information correlation 2 (IC2) and one from CT (Flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (IC2 and Strength), reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio (HR) (p<0.001). The latter model obtained an accuracy of 0.91 (sensitivity 100%, specificity 81%), with a HR undefined (P = 0.023) in the testing set, however other models relying on CT radiomics features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that two radiomic features derived from FDG PET were independently associated with LC in patients with NSCLC undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision-making.




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Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: a mechanistic perspective for FDG imaging of PSMA-suppressed tumors

Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by 18F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake.




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Comparison between 18F-FDG-PET- and CT-based criteria in non-small cell lung cancer (NSCLC) patients treated with Nivolumab

Due to their peculiar mechanism of action, the evaluation of radiological response to immune checkpoint inhibitors (ICI) presents many challenges in solid tumors. We aimed to compare the evaluation of first response to Nivolumab by means of CT-based criteria with respect to fluorodeoxyglucose positron emission tomography (FDG-PET) response criteria in non-small-cell lung cancer (NSCLC) patients. Methods: 72 patients with advanced NSCLC were recruited in a mono-institutional ancillary trial within the expanded access program (EAP; NCT02475382) for Nivolumab. Patients underwent CT scan and FDG-PET at baseline and after 4 cycles (first evaluation). In case of progressive disease (PD), an additional evaluation was performed after two further cycles in order to confirm progression. We evaluated the response to treatment with CT scan by means of response evaluation criteria in solid tumors (RECIST) 1.1 and Immuno-related Response Criteria (IrRC) and with FDG-PET by means of PERCIST and immunotherapy-modified-PERCIST (imPERCIST) criteria. The concordance between CT- and PET-based criteria and the capability of each method to predict overall survival (OS) were evaluated. Results: 48/72 patients were evaluable for first response assessment with both PET- and CT-based criteria. We observed low concordance between CT- and PET-based criteria (Kappa value of 0.346 and 0.355 and Kappa value of 0.128 and 0.198 between PERCIST and imPERCIST versus RECIST and irRC respectively). Looking at OS, IrRC were more reliable to distinguish responders from non-responders. However thanks to the prognostic value of partial metabolic response assessed by both PERCIST and Immuno-PERCIST, PET-based response maintained prognostic significant in patients classified as progressive disease on the basis of irRC. Conclusion: Even though the present study did not support the routine use of FDG-PET in the general population of NSCLC patients treated with ICI, it suggests the added prognostic value of the metabolic response assessment, potentially improving the therapeutic decision-making.




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Label-free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-guided Surgery by Photoacoustic Imaging

Objectives: The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of study is to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma in a very early stage and perform tumor resection by intraoperative photoacoustic image-guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a B16 melanoma hepatic metastasis mouse model (n = 10) was established to study the development of micrometastases in vivo. Next, the hepatic metastasis mice models were imaged by scalable PAI instrument, ultrasound, 9.4 T high-resolution magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT), and bioluminescence imaging. Photoacoustic images acquired with optical wavelengths spanning from 680 to 850 nm were spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in the signal-to-background ratios among different modalities were determined with the two-tailed paired t test. The diagnosis results were assessed with histologic examinations. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify tumor boundary. In vivo metastatic melanoma removal in surgery was precisely guided by the portable PAI system. Results: PAI achieved as small as ~400 µm hepatic melanoma detection at a depth up to 7 mm in vivo, which could early detect small melanoma compared with ultrasound and MRI in mouse models. The signal ratio of tumor-to-liver acquired with PAI in micrometastases at 8 days (4.2 ± 0.2, n = 6) and 14 days (9.2 ± 0.4, n = 5) were significantly higher than those obtained with PET/CT (1.8 ± 0.1, n = 5 and 4.5 ± 0.2, n = 5, P <0.001 for both). Functional PAI provided dynamic oxygen saturation changes during tumor growth. The limit of detection was measured to be approximately 219 cells per microliter in vitro. We successfully performed intraoperative photoacoustic image-guided surgery in vivo using the rapid portable PAI system. Conclusion: Our findings offer a rapid and effective tool to noninvasively detect micrometastases and guide intraoperative resection as a complementary clinical imaging application.




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Radiation Dosimetry in 177Lu-PSMA-617 Therapy Using a Single Post-treatment SPECT/CT: A Novel Methodology to Generate Time- and Tissue-specific Dose Factors

Calculation of radiation dosimetry in targeted nuclear medicine therapies is traditionally resource-intensive requiring multiple post-therapy SPECT acquisitions. An alternative approach is to take advantage of existing pharmacokinetic data from these smaller cohorts to enable dose computation from a single post-treatment scan in a manner that may be applied to a much broader patient population. Methods: In this work, a technical description for simplified dose estimation is presented and applied to assessment of 177Lu-PSMA-617 therapy (Prostate-Specific Membrane Antigen) for metastatic prostate cancer. By normalizing existing time-activity curves to a single measurement time, it is possible to calculate a mean and range of time-integrated activity values which relate to radiation absorbed dose. To assist with accurate pharmacokinetic modelling of the training cohort, a method for contour-guided image registration was developed. Results: Tissue-specific dose conversion factors for common post-treatment imaging times are reported along with a characterization of added uncertainty in comparison to a traditional serial imaging protocol. Single time point dose factors for tumor were determined to be 11.0, 12.1, 13.6, and 15.2 Gy per MBq/mL at image times of 24, 48, 72, and 96 hours, respectively. For normal tissues, parotid gland factors were 6.7, 9.4, 13.3, and 19.3 Gy per MBq/mL and kidneys were 7.1, 10.3, 15.0, and 22.0 Gy per MBq/mL at those times. Tumor dose estimates were most accurate using delayed scanning at times beyond 72 hours. Dose to healthy tissues is best characterized by scanning patients in the first two days of treatment owing to the larger degree of tracer clearance in this early phase. Conclusion: The work demonstrates a means for efficient dose estimation in 177Lu-PSMA-617 therapy. By providing methods to simplify and potentially automate radiation dosimetry we hope to accelerate the understanding of radiobiology and development of dose-response models in this unique therapeutic context.