mp

In It Together: A Conversation With Anna Houseman '21

The Sanford C. Bernstein & Co. Center for Leadership and Ethics spoke with Anna Houseman '21 about her daily routine, personal ethics, and staying productive during the pandemic. 




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A World of Hurt: The Impact of COVID-19 On Retail

Director of Retail Studies Mark Cohen offers his view on the changes coming to large retailers, many of which had already seen declining sales and store closures before the pandemic hit.




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Competition Policy

Conference

Need for a paradigm shift?

23 May 2019 - 9:30am to 5:30pm

Chatham House, London

Overview

Agenda

Speakers

Pricing and booking information

Sponsors

Media partners and supporting organizations

Venue and accommodation

Press registration

Contact us

Models for antitrust policy and competition regulation have traditionally been guided by principles that have prioritized consumer welfare standards, albeit according to varied interpretations, and antitrust has often been seen as disconnected from mainstream public interest and political debate. But what can lawmakers and regulators do to meet the challenges of the political trend of populism that is prevailing in many developed economies? What should competition regulators do in response to the idea that the consumer welfare standard should be replaced – or supplemented – with another standard, or more broadly interpreted to allow consideration of consumer welfare effects that go beyond price, including the surrender by consumers of their personal data?  

In this context the annual Chatham House Competition Policy conference will assess how a range of public interest considerations — such as unemployment, discrimination or protection of small businesses — and rapidly evolving marketplaces, are reshaping thinking on antitrust policy and the regulation of markets to the extent that changes to the scope and nature of the consumer welfare standard are being advocated.

Discussion themes include:

  • A consumer welfare approach versus market regulation
  • Potential changes to the consumer welfare approach to encompass concerns other than price-related effects
  • Advances in technology and the rise of new and unseen competition concerns 
  • The realities of AI and big data for competition and market regulation
  • What do these potential changes and new market realities mean for the consistency and predictability of antitrust decisions and business certainty
  • To what extent do public interest considerations and wider trade issues impact on international cooperation between antitrust regulators

Continuing Professional Development 
6 CPD hours are available for delegates attending this event, as per the Bar Standards Board’s CPD Provider Accreditation Scheme. For professionals regulated by the Solicitors Regulation Authority, 6 CPD hours are available for delegates that remain opted into the 16 hours annual CPD requirement.

The Chatham House Rule 
To enable as open a debate as possible, this conference will be held under the Chatham House Rule.

Twitter 
@CH_Events
#CHCompetition

Thursday 23 May
0930

Welcome and Chair's opening remarks
Howard Shelanski, Professor of Law, Georgetown University; Partner, Davis Polk & Wardwell   

Session One | Competition Policy and Regulation: Pressures in a Globalised Economy
1000-1110

This opening session will assess the current political and economic dynamics that are shaping the decision-making environment for competition policy and regulation, and how in the context of the ongoing globalisation of the world economy, the pressures and expectations of populist movements along with rising trade tensions may influence the principles of competition policy and regulation across developed and developing countries.

Chair
Howard Shelanski, Professor of Law, Georgetown University; Partner, Davis Polk & Wardwell   

Speakers
Andreas Mundt, President, Bundeskartellamt
Rebecca Slaughter, Commissioner, Federal Trade Commission
Sarah Cardell, General Counsel, Competition and Markets Authority
Liyuan Wang, State Administration for Market Regulation, China

Questions and discussion

1110 – 1130 Refreshments

Session Two | Merger Control in an Environment of Trade Tensions and Populist Challenges
1130–1300

  • How should competition authorities react to growing calls for them to take a tougher stance in relation to mergers and acquisitions in the face of increasing market concentration and the rise of common ownership?
  • Do big businesses cause problems beyond their effects on competition?  If so, are antitrust laws the cure?
  • To what extent should competition authorities have greater ability to intervene to protect smaller companies, or prevent their acquisition, where competition is not (yet) threatened?
  • Where competition authorities do intervene, how should they ensure that they do not stifle investment or discourage innovation?
  • Should competition authorities assess mergers on public interest grounds, including how mergers impact on labour markets or national security?  Should they be asking whether mergers will reduce competition for employees?
  • How should competition authorities respond to calls for the promotion of national champions or other protectionist tendencies?

Chair
Jorge Padilla, Senior Managing Director and Head, Compass Lexecon Europe

Speakers
Cecilio Madero Villarejo, Deputy Director-General, DG Competition, European Commission
Amelia Fletcher, Professor of Competition Policy, Centre for Competition Policy, University of East Anglia
Aaron Hoag, Chief, Technology and Financial Services Section, Antitrust Division, U.S. Department of Justice
Wolfgang Heckenberger, Chief Counsel Competition, Siemens
Alex Nourry, Partner, Clifford Chance

Questions and discussion

1300 – 1400 Lunch

Session Three | Antitrust Tools and the Challenges of the Digital Economy
1400–1540

  • Does the current antitrust framework need to be supplemented by regulation, inter alia to ensure common standards on transparency and fairness of online platforms?
  • Is there a risk that undue intervention by competition authorities or regulation will hurt innovation and destroy incentives for new entrants to emerge capable of challenging incumbents?
  • Does the possession of so-called Big Data give rise to barriers to entry or more efficient and innovative markets?
  • Whilst the use of pricing algorithms can benefit consumers, how concerned should competition authorities be about the possibility that algorithms might facilitate collusive outcomes and lead to higher prices for consumers?
  • Is there any reason to be concerned about the ability of firms to innovate without fear of undue enforcement, particularly given the special duty ascribed to dominant companies as regards their competitors and consumers?

Chair
Thomas Vinje, Partner, Chairman, Global Antitrust Group, Clifford Chance

Speakers
Jason Furman, Professor of the Practice of Economic Policy, Harvard Kennedy School
Tommaso Valletti, Chief Competition Economist, European Commission
Heike Schweitzer, Professor, Humboldt University
David Sevy, Executive Vice President, Compass Lexecon
Horacio Gutierrez, General Counsel, VP Business & Legal Affairs, Spotify

Questions and discussion

1540 – 1610 Afternoon refreshments

Session Four | International Co-operation Between Competition Authorities: Ensuring Consistent and Effective Enforcement in Interconnected Economy
1600–1730

  • How can the compatibility of procedural and substantive competition rules be maintained, along with legal certainty and predictability, in the face of the growing divergence in trade and industrial policies and conflicting public interest goals?
  • To what extent, if any, could the promotion of best practices and substantive convergence in competition enforcement through multi-lateral organisations such as the OECD and the ICN be enhanced?
  • What other steps could be taken to increase co-operation and coordination in the enforcement of the competition rules such as, for example, the development of international standards for comity, systems of mutual recognition of decisions of other authorities or deference to a lead authority?
  • Is bi-lateral and multi-lateral cooperation sufficient to ensure effective and consistent enforcement or is there a greater need for supra-national authorities, at least, regionally, if not internationally?
  • Can or should WTO rules play a greater role in ensuring a level playing field and thereby removing the incentives for divergence in the scope and enforcement of the competition rules?

Chair
Sean Ennis, Director, Centre for Competition Policy and Professor of Competition Policy, University of East Anglia

Speakers
Isolde Goggin, Chairperson of the Competition and Consumer Protection Commission, Ireland
João Paulo Resende, Commissioner, Administrative Council for Economic Defense, Brazil 
Gabriel Harnier, Head of Law, Patents & Compliance, Bayer
Avaantika Kakkar, Partner, Head of Competition Practice, Cyril Amarchand Mangaldas

Questions and discussion

1730 Close of conference and drinks reception

© The Royal Institute of International Affairs 2019

Speakers

Sarah Cardell

General Counsel, CMA

Sean Ennis

Director, Centre for Competition Policy and Professor of Competition Policy, University of East Anglia

Amelia Fletcher

Professor of Competition Policy at the Centre for Competition Policy, University of East Anglia

Jason Furman

Professor of the Practice of Economic Policy, Harvard Kennedy School

Isolde Goggin

Chairperson, Competition and Consumer Protection Commission, Ireland

Horacio Gutierrez

General Counsel and VP Business & Legal Affairs, Spotify

Gabriel Harnier

General Counsel, Bayer

Wolfgang Heckenberger

Senior Competition Advisor, Siemens

Aaron Hoag

Chief, Technology and Financial Services Section, Antitrust Division, U.S. Department of Justice

Avaantika Kakkar

Partner, Head of Competition Practice, Cyril Amarchand Mangaldas

Andreas Mundt

President, Bundeskartellamt

Alex Nourry

Partner, Clifford Chance

Dr Jorge Padilla

Senior Managing Director and Head, Compass Lexecon Europe

João Paulo Resende

Commissioner, Administrative Council for Economic Defense, Brazil

Heike Schweitzer

Professor of Competition, Humboldt University

David Sevy

Executive Vice President, Compass Lexecon

Howard Shelanski

Professor of Law, Georgetown University; Partner, Davis Polk & Wardwell LLP

Rebecca Slaughter

Commissioner, Federal Trade Commission

Tommaso Valletti

Chief Competition Economist, European Commission

Cecilio Madero Villarejo

Deputy Director-General, DG Competition, European Commission

Thomas Vinje

Partner and Chairman, Global Antitrust Group, Clifford Chance

Liyuan Wang

Deputy Director, State Administration for Market Regulation, China

General Counsel of major companies may register at the standard government department rate.

Ways to book:

  1. Online: Click here to complete the online registration form
  2. Phone: Call Boudicca Georgii Hellberg on +44 (0)20 7314 2785
  3. Email/Post: Download a PDF registration form, complete and return to Boudicca Georgii Hellberg via email or post: Chatham House, 10 St. James's Square, London, SW1Y 4LE

Check if your organization is a member of Chatham House here.

 RATE (+VAT):
Partners and major corporate members 
All organizations£595
Standard corporate members 
Commercial organizations£1,180
Government departments/agencies/intergovernmental organizations£700
NGOs/academic institutions/associations (including not for profits and registered charities)£460
Non-members 
Commercial organizations£1,295
Government departments/agencies/intergovernmental organizations£750
NGOs/academic insitutions/associations (including not for profits and registered charities)£510

Your delegate pass includes:

  • Conference attendance
  • Documentation
  • Lunch and refreshments

Travel and accommodation are not included.

If you are interested in becoming a sponsor for this event, please contact Kamil Hussain on +44 (0)20 7957 5783

If you are interested in becoming a media partner or supporting organization for this event, please contact Ayesha Arif on +44 (0)20 7957 5753

Chatham House
10 St James's Square
London
SW1Y 4LE
UK
conferences@chathamhouse.org

Telephone: +44 (0)20 7957 5643
Fax: +44 (0)20 7957 5710

If you wish to book the venue for your own event please phone +44 (0)20 7314 2764

Directions
The nearest tube station is Piccadilly Circus which is on the Piccadilly and the Bakerloo Underground lines. From Piccadilly follow Regent Street southwards towards Pall Mall and take the first road on the right called Jermyn Street. Duke of York Street is the second road on the left and leads to St James's Square. Chatham House is immediately on your right.

Map

Accommodation
Although we cannot book accommodation for delegates, we have arranged a reduced rate at some nearby hotels, where you can book your own accommodation. Please inform the hotel that you will be attending a conference at Chatham House (The Royal Institute of International Affairs) to qualify for the Institute's reduced rate.

Please note all rates are subject to availability.

Flemings Mayfair
13 Half Moon Street
Mayfair
London - W1J 7BH

Tel: + 44 (0)20 7499 2964
Fax: + 44 (0)20 7499 1817
reservations@flemings.co.uk

Classic Double without breakfast: £195 +VAT

The Cavendish London
81 Jermyn Street
London - SW1U 6JF

Tel: + 44 (0)20 7930 2111
Fax: + 44 (0)20 7839 2125
enquiry.cavendish@the-ascott.com 

Classic Room without breakfast: £195 +VAT

Book The Cavendish online

The Stafford London 
St James's Place
London - SW1A 1NJ

Tel: 020 7493 0111
Fax: 020 7493 7121
​reservations@thestaffordlondon.com

Classic Queen without breakfast: £247 +VAT
Quote Chatham House

This conference will be held under the Chatham House Rule. Information for journalists.

Press can request a press pass.

For enquiries relating to the conference agenda or sponsorship please call Kamil Hussain on +44 (0) 20 7957 5783

For registration enquiries please call Boudicca Georgii Hellberg on +44 (0)20 7314 2785

For general enquiries please email conferences@chathamhouse.org 

Department/project




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Human Rights Impact Assessment of Trade Agreements

Research Event

26 February 2019 - 6:00pm to 7:30pm

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

Event participants

James Harrison, Reader and Associate Professor, University of Warwick School of Law
Richard James, Evaluation Co-ordinator, Directorate-General for Trade European Commission
Jennifer Zerk, Associate Fellow, International Law Programme, Chatham House
Chair: Andrea Shemberg, Chair, Global Business Initiative on Human Rights

The idea that trade agreements should be subject to human rights impact assessment has been gathering momentum in recent years. This idea springs from concern – particularly on the part of trade unions and civil society organizations – that states are not presently doing enough to anticipate and address the human rights-related issues that arise from their trading arrangements with other countries.

This meeting will coincide with the launch of a research paper on human rights impact assessment by Dr Jennifer Zerk. It will bring together experts from law, trade policy, human rights impact assessment practice and civil society to take stock of progress so far and consider the future prospects for human rights impact assessment as a risk-analysis and policymaking tool in the trade context.  

The meeting will explore the key risks and benefits of the human rights impact assessment of trade agreements. What legal, political and practical challenges have been encountered so far? In what ways could communication, stakeholder consultation and follow-up of findings be improved? And what is needed to build political and stakeholder support for these kinds of processes?  

This meeting will be followed by a reception. 

Chanu Peiris

Programme Manager, International Law
+44 (0)20 7314 3686




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Power Politics Could Impede Progress on Responsible Regulation of Cyberspace

3 December 2019

Harriet Moynihan

Senior Research Fellow, International Law Programme
A new Chatham House paper examines the prospects of countries reaching agreement on issues of sovereignty and non-intervention in cyberspace in the face of persistent, low-level, state-to-state cyber attacks.

2019-11-29-Intl-Law-Cyberattacks.jpg

A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images.

In discussions to date about how international law applies in cyberspace, commentators have tended to focus their attention on how the rules on the use of force, or the law of armed conflict, apply to cyber activities conducted by states that give rise to physical damage, injury or death.

But in practice, the vast majority of state cyberattacks fall below this threshold. Far more common are persistent, low-level attacks that may leave no physical trace but that are capable of doing significant damage to a state’s ability to control its systems, often at serious economic cost.

Such cyber incursions might include network disruptions in the operation of another government’s websites; tampering with electoral infrastructure to change or undermine the result; or using cyber means to destabilize another state’s financial sector.

For these kinds of cyber operation, the principle of sovereignty, and the principle of non-intervention in another state’s internal affairs, are the starting point.

A UN Group of Government Experts (GGE) agreed in 2013 and 2015 that the principles in the UN Charter, including sovereignty and the prohibition on intervention in another state’s affairs, apply to states’ activities in cyberspace. The 2015 GGE also recommended eleven (non-binding) norms of responsible state behaviour in cyberspace.

However, states have not yet reached agreement on how to apply these principles. Until recently, there has also been very little knowledge of what states actually do in cyberspace, as they usually conduct cyber operations covertly and have been reluctant to put their views on record.

A new Chatham House research paper analyses the application of the principles of sovereignty and non-intervention to state cyberattacks that fall below the principle of use of force. As well as analysing the application of the law in this area, the paper also makes recommendations to governments on how they might best make progress in reaching agreement in this area.

Existing rules or new rules?

As the research paper makes clear, there is currently some debate, principally between countries in the West, about the extent to which sovereignty is a legally binding rule in the context of cyberspace and, if so, how it and the principle of non-intervention might apply in practice.

In the last few years, certain states have put on record how they consider international law to apply to states’ activities in cyberspace, namely the UK, Australia, France and the Netherlands. While there may be some differences in their approaches, which are discussed in the paper, there also remains important common ground: namely, that existing international law already provides a solid framework for regulating states’ cyber activities, as it regulates every other domain of state-to-state activity.

There is also an emerging trend for states to work together when attributing cyberattacks to hostile states, enabling them to call out malign cyber activity when it violates international law. (See, for example, the joint statements made in relation to the NotPetya cyber attack and malicious cyber activity attributed to the Russian government).

However, other countries have questioned whether existing international law as it stands is capable of regulating states’ cyber interactions and have called for ‘new legal instruments’ in this area.

This includes a proposal by the Shanghai Cooperation Organization (led by Russia and China) for an International Code of Conduct on Information Security, a draft of which was submitted to the UN in 2011 and 2015, without success. The UN has also formed a new Open-Ended Working Group (OEWG) under a resolution proposed by Russia to consider how international law applies to states’ activities in cyberspace.

The resolution establishing the OEWG, which began work earlier this year, includes the possibility of the group ‘introducing changes to the rules, norms and principles of responsible behaviour of States’ agreed in the 2013 and 2015 GGE reports. In the OEWG discussions at the UN in September, several countries claimed that a new legal instrument was needed to fill the ‘legal vacuum’ (Cuba) or ‘the gap of ungoverned areas’ (Indonesia).

It would be concerning if the hard-won consensus on the application of international law to cyberspace that has been reached at past GGEs started to unravel. In contrast to 2013 and 2015, the 2017 meeting failed to reach an agreement.

On 9 December, a renewed GGE will meet in New York, but the existence of the OEWG exploring the same issues in a separate process reflects the fact that cyber norms have become an area of geopolitical rivalry.

Aside from the application of international law, states are also adopting divergent approaches to the domestic regulation of cyberspace within their own territory. The emerging trend towards a ‘splinternet’ – i.e. between states that believe the internet should be global and open on the hand, and those that favour a ‘sovereignty and control’ model on the other  – is also likely to make discussions at the GGE more challenging.

Distinct from the international law concept of sovereignty is the notion of ‘cybersovereignty’, a term coined by China to describe the wide-ranging powers it assumes under domestic law to regulate its citizens’ access to the internet and personal data within its territory. This approach is catching on (as reflected in Russia’s recently enacted ‘Sovereign Internet Law’), with other authoritarian states likely to follow suit.

The importance of non-state actors

In parallel with regional and UN discussions on how international law applies, a number of initiatives by non-state actors have also sought to establish voluntary principles about responsible state behaviour in cyberspace.

The Global Commission on the Stability of Cyberspace, a multi-stakeholder body that has proposed principles, norms and recommendations to guide responsible behaviour by all parties in cyberspace, recently published its final report. The Cybersecurity Tech Accord  aims to promote collaboration between tech companies on stability and resilience in cyberspace. President Macron’s ‘Paris Call for Trust and Security in Cyberspace’ has to date received the backing of 67 states, 139 international and civil society organizations, and 358 private-sector organizations.

It remains to be seen in the long term whether the parallel processes at the UN will work constructively together or be competitive. But notwithstanding the challenging geopolitical backdrop, the UN GGE meeting next week at the least offers states the opportunity to consolidate and build on the results of past meetings; to increase knowledge and discussion about how international law might apply; and to encourage more states to put their own views of these issues on the record.




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POSTPONED: Supporting Civic Space: The Role and Impact of the Private Sector

Invitation Only Research Event

16 March 2020 - 11:00am to 5:00pm

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

A healthy civic space is vital for an enabling business environment. In recognition of this, a growing number of private sector actors are challenging, publicly or otherwise, the deteriorating environment for civic freedoms.

However, this corporate activism is often limited and largely ad hoc. It remains confined to a small cluster of multinationals leaving potential routes for effective coordination and collaboration with other actors underexplored.

This roundtable will bring together a diverse and international group of business actors, civil society actors and foreign policy experts to exchange perspectives and experiences on how the private sector can be involved in issues around civic space. The meeting will provide an opportunity to explore the drivers of – and barriers to – corporate activism, develop a better understanding of existing initiatives, identify good practice and discuss practical strategies for the business community.

This meeting will be the first of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. 

Attendance at this event is by invitation only. 

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. 

Jacqueline Rowe

Programme Assistant, International Law Programme
020 7389 3287




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Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology]

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.




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The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis [Cell Biology]

Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype.




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HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV

Daniella H Hock
Apr 21, 2020; 0:RA120.002076v1-mcp.RA120.002076
Research




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Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation

Nora Linscheid
Apr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878
Research




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Immediate adaptation analysis implicates BCL6 as an EGFR-TKI combination therapy target in NSCLC

Yan Zhou Tran
Mar 31, 2020; 0:RA120.002036v1-mcp.RA120.002036
Research




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Characterization of signaling pathways associated with pancreatic {beta}-cell adaptive flexibility in compensation of obesity-linked diabetes in db/db mice

Taewook Kang
Apr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882
Research




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Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism

Xing-Huang Gao
May 1, 2020; 19:852-870
Research




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Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling

Samuel W Entwisle
Apr 6, 2020; 0:RA120.001946v2-mcp.RA120.001946
Research




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Selection of features with consistent profiles improves relative protein quantification in mass spectrometry experiments

Tsung-Heng Tsai
Mar 31, 2020; 0:RA119.001792v1-mcp.RA119.001792
Research




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Compliance Checklists No Longer Required at Initial Manuscript Submission

Alma L. Burlingame
Apr 1, 2020; 19:571-571
Editorial




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Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable, Isotopically Coded, and Mass Spectrometry-cleavable Chemical Crosslinker

Karl A. T. Makepeace
Apr 1, 2020; 19:624-639
Research




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An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics

Chia-Feng Tsai
May 1, 2020; 19:828-838
Research




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A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

Dorte B. Bekker-Jensen
Apr 1, 2020; 19:716-729
Technological Innovation and Resources




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The Implications of Drone Proliferation in Europe

Invitation Only Research Event

20 May 2019 - 9:30am to 21 May 2019 - 12:30pm

Chatham House, London

Several countries in Europe are currently developing, increasing or arming their drone capabilities. This increase in drone capability is taking place through procurement by individual states, bilateral projects – such as the French-German Future Combat Air Systems – and multinational efforts that include the development of the Eurodrone – a project by Germany, France, Italy and Spain – and the nEUROn which involves France, Greece, Italy, Spain, Sweden and Switzerland. In addition, the EU has recently approved the European Defence Fund which, along with funds for joint development of defence equipment and technology and for defence research, also includes direct funding to support the development of the Eurodrone.
  
Other recent developments include the UK obtaining the MQ−9B SkyGuardian – an updated variant of the MQ-9 Reaper – and Germany signing a leasing agreement for the Israeli-made Heron TP. Also, in March 2019, the US State Department approved the sale of the MQ-9B SkyGuardian to Belgium and announced the provision of MQ-9 Reaper drones to the Netherlands. While the UK and France are the only countries in Europe so far to possess armed drones, Italy is on track to acquire armed drones in the near future. However, out of the European countries currently seeking to obtain unarmed drones – including Spain, Poland and Greece – only Switzerland has so far ruled out weaponizing its drones in the future.
 
This Chatham House workshop will examine key issues pertaining to drone proliferation in Europe including: 
  • The risks and challenges of the increasing number and arming of drones. 
  • The risks for countries of not doing so in terms of geostrategic interests and the future battlefield.
  • Opportunities for developing common standards on drone transfers and deployment across EU member states.
  • Sharing and cooperation on drone use.
  • What legal and policy implications might arise for European states as a result.

With Brexit on the horizon, participants will also consider what impact this may have on future drone developments in Europe.

Attendance at this event is by invitation only.

Nilza Amaral

Project Manager, International Security Programme




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Protecting Children in Conflict: See Me Safe Symposium

Invitation Only Research Event

7 May 2019 - 10:00am to 5:00pm

Chatham House, London

Today there are 420 million children, or one-fifth of children worldwide, who live in conflict zones and are at risk of being killed or injured and denied access to education, healthcare and humanitarian assistance. From Myanmar and Syria, to South Sudan and Yemen, the impact of conflict on children and their families is devastating. With conflicts becoming more protracted and urbanized, and the undermining of international rules and norms, the risk to civilians is rapidly increasing. 
 
The impact of the crisis in civilian protection is not only devastating children’s lives and risking a lost generation, it threatens global stability and prosperity, contributing to the degradation of the international rules-based system and its institutions and undermining the ability to hold perpetrators accountable and prevent these atrocities from happening.
 
This symposium will bring together practitioners, policymakers, business leaders, philanthropists and academics for a day of panel discussions on the protection of children in conflict. The aim of the event is to generate an informed debate and to deepen engagement with issues around protecting children in conflict as well as to inspire support to help rebuild children’s lives.
 
This event will be followed by a reception from 17:00-18:30.
 
Attendance is by invitation only.
 
Celebrating its centenary in 2020, Chatham House is partnering with Save the Children on this core area of their work, in their anniversary year.

Nilza Amaral

Project Manager, International Security Programme




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Policy Implications of Armed Drone Use

This project brings together experts on the use of armed drones, including current and former military officials, academia, think-tanks and NGOs, to discuss and exchange perspectives based on their different experiences, with the aim of sharing knowledge and increasing understanding on these issues, and to inform and provide input into the European debate.

With the increased use of armed drones in recent years, ethical and legal concerns have been raised in regard to civilian casualties, secrecy and lack of transparency and accountability for drone strikes.

This project brings together experts on the use of armed drones, including current and former military officials, academia, think-tanks and NGOs, to discuss and exchange perspectives based on their different experiences, with the aim of sharing knowledge and increasing understanding on these issues, and to inform and provide input into the European debate. The experts explore the issues and controversies surrounding the use of drones outside formal armed conflict and study the broader policy implications in detail, particularly with regards to what this means for the UK and other European countries.

Building on the findings from the workshops, this project will hold a simulation exercise to stress test critical areas of concern around the use of armed drones that are relevant for the UK and other EU member states.

The discussions and the simulation exercise will provide opportunities for policy input on areas of mutual concern and feed into practical policy recommendations on the use of armed drones.

This project builds on previous work on armed drones by the International Security Department and is funded by the Open Society Foundations.

More on Policy Implications of Armed Drone Use




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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

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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.

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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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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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Predictions and Policymaking: Complex Modelling Beyond COVID-19

1 April 2020

Yasmin Afina

Research Assistant, International Security Programme

Calum Inverarity

Research Analyst and Coordinator, International Security Programme
The COVID-19 pandemic has highlighted the potential of complex systems modelling for policymaking but it is crucial to also understand its limitations.

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A member of the media wearing a protective face mask works in Downing Street where Britain's Prime Minister Boris Johnson is self-isolating in central London, 27 March 2020. Photo by TOLGA AKMEN/AFP via Getty Images.

Complex systems models have played a significant role in informing and shaping the public health measures adopted by governments in the context of the COVID-19 pandemic. For instance, modelling carried out by a team at Imperial College London is widely reported to have driven the approach in the UK from a strategy of mitigation to one of suppression.

Complex systems modelling will increasingly feed into policymaking by predicting a range of potential correlations, results and outcomes based on a set of parameters, assumptions, data and pre-defined interactions. It is already instrumental in developing risk mitigation and resilience measures to address and prepare for existential crises such as pandemics, prospects of a nuclear war, as well as climate change.

The human factor

In the end, model-driven approaches must stand up to the test of real-life data. Modelling for policymaking must take into account a number of caveats and limitations. Models are developed to help answer specific questions, and their predictions will depend on the hypotheses and definitions set by the modellers, which are subject to their individual and collective biases and assumptions. For instance, the models developed by Imperial College came with the caveated assumption that a policy of social distancing for people over 70 will have a 75 per cent compliance rate. This assumption is based on the modellers’ own perceptions of demographics and society, and may not reflect all societal factors that could impact this compliance rate in real life, such as gender, age, ethnicity, genetic diversity, economic stability, as well as access to food, supplies and healthcare. This is why modelling benefits from a cognitively diverse team who bring a wide range of knowledge and understanding to the early creation of a model.

The potential of artificial intelligence

Machine learning, or artificial intelligence (AI), has the potential to advance the capacity and accuracy of modelling techniques by identifying new patterns and interactions, and overcoming some of the limitations resulting from human assumptions and bias. Yet, increasing reliance on these techniques raises the issue of explainability. Policymakers need to be fully aware and understand the model, assumptions and input data behind any predictions and must be able to communicate this aspect of modelling in order to uphold democratic accountability and transparency in public decision-making.

In addition, models using machine learning techniques require extensive amounts of data, which must also be of high quality and as free from bias as possible to ensure accuracy and address the issues at stake. Although technology may be used in the process (i.e. automated extraction and processing of information with big data), data is ultimately created, collected, aggregated and analysed by and for human users. Datasets will reflect the individual and collective biases and assumptions of those creating, collecting, processing and analysing this data. Algorithmic bias is inevitable, and it is essential that policy- and decision-makers are fully aware of how reliable the systems are, as well as their potential social implications.

The age of distrust

Increasing use of emerging technologies for data- and evidence-based policymaking is taking place, paradoxically, in an era of growing mistrust towards expertise and experts, as infamously surmised by Michael Gove. Policymakers and subject-matter experts have faced increased public scrutiny of their findings and the resultant policies that they have been used to justify.

This distrust and scepticism within public discourse has only been fuelled by an ever-increasing availability of diffuse sources of information, not all of which are verifiable and robust. This has caused tension between experts, policymakers and public, which has led to conflicts and uncertainty over what data and predictions can be trusted, and to what degree. This dynamic is exacerbated when considering that certain individuals may purposefully misappropriate, or simply misinterpret, data to support their argument or policies. Politicians are presently considered the least trusted professionals by the UK public, highlighting the importance of better and more effective communication between the scientific community, policymakers and the populations affected by policy decisions.

Acknowledging limitations

While measures can and should be built in to improve the transparency and robustness of scientific models in order to counteract these common criticisms, it is important to acknowledge that there are limitations to the steps that can be taken. This is particularly the case when dealing with predictions of future events, which inherently involve degrees of uncertainty that cannot be fully accounted for by human or machine. As a result, if not carefully considered and communicated, the increased use of complex modelling in policymaking holds the potential to undermine and obfuscate the policymaking process, which may contribute towards significant mistakes being made, increased uncertainty, lack of trust in the models and in the political process and further disaffection of citizens.

The potential contribution of complexity modelling to the work of policymakers is undeniable. However, it is imperative to appreciate the inner workings and limitations of these models, such as the biases that underpin their functioning and the uncertainties that they will not be fully capable of accounting for, in spite of their immense power. They must be tested against the data, again and again, as new information becomes available or there is a risk of scientific models becoming embroiled in partisan politicization and potentially weaponized for political purposes. It is therefore important not to consider these models as oracles, but instead as one of many contributions to the process of policymaking.




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Iran Crisis: The Impact on Oil Markets

14 January 2020

Professor Paul Stevens

Distinguished Fellow, Energy, Environment and Resources Programme
The assassination of Qassem Soleimani has exacerbated the sensitivity of oil markets to political events and brought geopolitics back into global oil prices.

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Satellite image of the Strait of Hormuz. Photo: Getty Images.

The assassination of General Qassem Soleimani has created much speculation about the possible impact on oil markets and – although any impact will very much depend upon what happens next in terms of political and military responses – theoretically the potential exists for Iran to seriously destabilize oil markets, raising oil prices.

Arguably, it would be in Iran’s interest to do so. It would certainly hurt Trump’s possibility of a second term if higher prices were to last for some time as the 2020 presidential election gets underway. And it would also help shore up Iran’s failing economy. 

The assassination did initially cause oil prices to rise by a few dollars before quickly falling back, and the missile attacks by Iran produced a similar response. However, direct action by Iran to raise prices – for example by trying to close the Strait of Hormuz – is unlikely.

Around one-fifth of the world's oil supplies passes through the Strait of Hormuz, a narrow choke point between Iran and the Arabian Peninsula. Closing it would invite serious military action by the Americans and many of its allies who, so far, have been rather lukewarm over Trump’s actions. It would also possibly limit Iran’s own oil exports.

Similarly, overt attacks on American allies in the region such as Saudi Arabia and the UAE would probably invite too heavy a reaction, although this is uncertain given the lack of response after the alleged Iranian attacks on Abqaiq and Khurais in mid-September.

Indirect action by Iran to affect oil supplies is much more likely as they have many options by using their proxies to affect others’ oil production. This is especially true for Iraq, which is now an important source of global oil supply as Iraqi exports in 2019 averaged 3.53 million barrels per day (Mb/d), a significant amount.

Iraq’s future production has already been damaged as international oil companies are withdrawing staff for safety reasons, anticipating potential attacks by both Iraqi and Iranian sources. It is now very unlikely that the crucial ‘common seawater supply project’ being run by Exxon – essential for expanding production capacity – will go ahead in the near future.

However, one important consequence of the assassination that has attracted little attention is that it has almost fully restored the role of geopolitics into the determination of oil prices. Up to 2014, geopolitics played a key role in determining oil prices in the paper markets where perceptions and expectations ruled.

Prices determined in these markets – NYMEX in New York, ICE in London and other lesser futures markets throughout the world – then influence wet barrel markets where real barrels of oil are traded. 

In 2014, the world was so oversupplied with real oil barrels that the oil price collapsed – the price of Brent crude fell from $110.72 on 23 May to $46.44 eight months later. Thereafter, little if any attention was given to geopolitical events, and geopolitics became marginalized in the determination of crude oil prices.

This began to change in 2019. The market remained physically over-supplied but events in the Gulf began to attract attention. In June, there were a series of attacks on oil tankers close to the Gulf, followed by attacks on Saudi Arabia’s Abqaiq processing facility and the Khurais oil field in September.

The Americans claimed these attacks were launched by Iran, but no convincing evidence for the claim was provided. Both attacks produced an initial price response but it was surprisingly limited and short-lived. However, it did suggest that geopolitics might be creeping back into influencing oil prices.

This became ever more noticeable in the third and fourth quarters as rumours regarding the trade talks between China and US clearly began to affect price – talks going well meant higher oil demand, and prices rose; talks going badly meant lower oil demand, and prices fell.

Meanwhile, the oil market showed signs of tightening towards the end of 2019. Although there was much cheating on the OPEC+ agreement that was trying to restrain production and protect prices, the OPEC meeting last December saw both Iraq and Nigeria agreeing to restrain production. 

US stock levels also began to fall in December and the futures markets began to price in a tightening market towards the end of 2020. Significantly, the tighter the market appears, the greater attention is paid to the level of spare producing capacity.

Just before the attack on Abqaiq, the International Energy Agency (IEA) estimated there was 3.5 Mb/d spare capacity in OPEC which, historically, is quite comfortable. However, 2.5 of this was estimated to be in Saudi Arabia, so how much of this spare capacity still existed after the Abqaiq attack?

The Saudis claimed the Abqaiq capacity was quickly restored but technical experts greeted this with considerable skepticism, not least because the Abqaiq equipment was highly specialized. If spare capacity is tight, this makes the oil price vulnerable to geopolitical scares and rumours, real or imagined. 

Although the assassination of General Soleimani has exacerbated the sensitivity of oil markets to geopolitical events, this becomes irrelevant if a serious shooting war starts in the region. Saudi Arabia, the UAE and Iraq’s oil infrastructure remains highly vulnerable to attack either directly by Iran or one of its many proxies, suggesting oil prices will become increasingly volatile but, at the same time, benefit from a rising geopolitical premium.




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COVID-19 Impact on Refugees is Also Political

31 March 2020

Dr Lina Khatib

Director, Middle East and North Africa Programme
The spread of coronavirus in the Levant puts Syrian as well as other refugees and internally displaced people at particular risk because of the policies and practices of the authorities.

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The word Corona written in the sand on the beach in Lebanon's southern city of Saida. amid the spread of coronavirus in the country. Photo by MAHMOUD ZAYYAT/AFP via Getty Images.

As Lebanon strains to contain COVID-19, it is not clear which governmental public health policies apply to refugees. The government announced free testing for coronavirus in the public Rafiq Hariri University Hospital in Beirut but has not mentioned if refugees are eligible.

Lebanon’s coronavirus containment strategy is based on self-reporting and, given incidents of forced deportation and harassment of Syrian refugees from both the authorities and local communities, it is certainly less likely refugees would present themselves to the health authorities for fear of deportation.

Despite agreeing a Lebanon Crisis Response Plan with the UN for refugees, different ministries were left to implement it without coordination, just as Lebanese politicians from all sides started trying to rally popular support for ridding Lebanon from refugees - in particular from Syria, who Lebanese leaders say are causing a strain on the country’s already weak infrastructure.

This finger pointing is coupled with the leaders’ own complete disregard for the rampant corruption and lack of accountability within Lebanon’s political class, which contribute to the weakening of the country’s infrastructure.

For refugees who do find themselves back in Syria, there are different challenges according to which area they are in. In the north-east, the WHO and international NGOs (INGOs) negotiate with both Kurdish authorities as well as the government - each presenting its own hurdles.

Kurdish authorities in northeast Syria have closed the Semalka border with Iraqi Kurdistan, posing a serious dilemma for INGOs offering services in north-east Syria but concerned about their staff safety whose movement is now curtailed.

The government of Syria has stipulated all emergency response must go through its ministries. But this limits what the WHO can do in the country and gives Syrian authorities the ability to block ‘cross-line aid’ which goes from government-controlled to non-government areas.

Despite reports that doctors raised the alarm about suspected cases well before patient zero was confirmed, the government appears to be either covering up the actual extent of the spread of COVID-19 or failing to respond. Some limited testing kits have arrived but testing has barely started.

The WHO’s Syria plan is divided into three regions (north-west, north-east, and areas under government control). But concerns remain as to how workable such a decentralized plan is because of the government’s practices. In January, the UN Security Council did not renew the cross-border response resolution for the Yaroubiye border crossing between Syria and Iraq that the WHO was using to send medical supplies into north-east Syria.

Syrian authorities do not permit recently authorized ‘cross-line’ responders to engage with non-government authorities in areas outside regime control. This essentially voids the authorization to work cross-line as it is practically impossible to implement programs. The WHO has sought approval from the Syrian Ministry of Foreign Affairs to move medical supplies by land to north-east Syria.

While promising facilitation, the Ministry’s reply comes with conditions of seeking detailed approval for every shipment. When Eastern Ghouta was under siege, similar conditions led to certain supplies being removed from UN/ICRC convoys to Eastern Ghouta, and there is no guarantee this will not happen again.

Due to lack of capacity in north-east Syria, coronavirus tests conducted by the WHO there must be processed through the Central Public Health Laboratory in Damascus. Samples are transported twice a week from Qamishli to Damascus but no results were ever received from Damascus for those tests.

While the WHO is able to coordinate access to north-west Syria with the Turkish authorities, the prospective coronavirus testing capacity in the Idlib region is low – despite claims that thousands of kits are arriving, a lack of resource on the ground means potentially only 20 tests per day could be done in an area inhabited by an estimated three million people.

Following the recently announced ceasefire in the area, many internally displaced people are returning from the Turkish border to their homes in the north-west, but such mass movement increases the risk of coronavirus spreading. People also continue to move between Syria, Iraq, Turkey and Lebanon, posing a challenge to the WHO’s COVID-19 response in the Levant, as the WHO has distinct response plans for each country in the region and it is difficult to coordinate across these plans.

Challenges face refugees even if they head towards Europe due to the potential for conflation between migration control and coronavirus outbreak control. Aurelie Ponthieu, Coordinator for Forced Migration at Médecins Sans Frontières (MSF) says there is a risk some countries could use COVID-19 to impose draconian measures towards asylum seekers.

The crisis has also put a halt to search and rescue operations in the Mediterranean because European countries are not allowing boats carrying migrants to disembark under the pretext of limiting the spread of coronavirus. And for migrants who already made it - such as in Greece - they are now being put in collective quarantines in asylum centers, often with poor medical facilities.

Ponthieu also reports that migrants being quarantined on overcrowded navy ships docked in Greek ports, making social distancing impossible. And she is concerned the Greek authorities are imposing a curfew on asylum seekers but not on the local population.

UNHCR is stressing that people’s right of asylum must not be overruled by concerns about the spread of coronavirus, while local and international NGOs across the Levant are trying to coordinate their advocacy on lifting restrictions on freedom of movement for humanitarian workers and on other policies and practices by authorities in the region which are adversely affecting refugee and other vulnerable communities.

The international community must not lose sight of the impact of the crisis on refugees and migrants. It is not enough simply to supply humanitarian and medical assistance without paying attention to the policies and practices of the different authorities who have direct control over the fate of vulnerable communities.

The author would like to thank Aurelie Ponthieu and the two INGO field workers who all agreed to be interviewed to inform this analysis piece.




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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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COVID 19: Assessing Vulnerabilities and Impacts on Iraq

7 April 2020

Dr Renad Mansour

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

Dr Mac Skelton

Director, Institute of Regional and International Studies (IRIS), American University of Iraq, Sulaimani; Visiting Fellow, Middle East Centre, London School of Economics

Dr Abdulameer Mohsin Hussein

President of the Iraq Medical Association
Following 17 years of conflict and fragile state-society relations, the war-torn country is particularly vulnerable to the pandemic.

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Disinfecting shops in Baghdad's Bayaa neighbourhood as a preventive measure against the spread of COVID-19. Photo by AHMAD AL-RUBAYE/AFP via Getty Images.

Iraq is a country already in turmoil, suffering fallout from the major military escalation between the US and Iran, mass protests calling for an end to the post-2003 political system, and a violent government crackdown killing more than 600 and wounding almost 30,000 - all presided over by a fragmented political elite unable to agree upon a new prime minister following Adil abd al-Mehdi’s resignation back in November.

COVID-19 introduces yet another threat to the fragile political order, as the virus exposes Iraq’s ineffective public health system dismantled through decades of conflict, corruption and poor governance.

Iraqi doctors are making every effort to prepare for the worst-case scenario, but they do so with huge structural challenges. The Ministry of Health lacks enough ICU beds, human resources, ventilators, and personal protective equipment (PPE). Bogged down in bureaucracy, the ministry is struggling to process procurements of equipment and medications, and some doctors have made purchases themselves.

But individual efforts can only go so far as many Iraqi doctors are concerned the official numbers of confirmed COVID-19 cases do not reflect the complexity of the situation on the ground.

The ministry relies predominately upon patients self-presenting at designated public hospitals and has only just begun community-based testing in areas of suspected clusters. Reliance on self-presentation requires a level of trust between citizens and state institutions, which is at a historic low. This gap in trust – 17 years in the making – puts Iraq’s COVID-19 response particularly at risk.

Iraq’s myriad vulnerabilities

Certain social and political factors leave Iraq uniquely exposed to the coronavirus. The country’s vulnerability is tied directly to its social, religious and economic interconnections with Iran, an epicenter of the pandemic.

Exchanges between Iran and Iraq are concentrated in two regions, with strong cross-border links between Iraqi and Iranian Kurds in the north-east, and Iraqi and Iranian Shia pilgrims in the south. Cross-border circulation of religious pilgrims is particularly concerning, as they can result in mass ritual gatherings.

The high number of confirmed cases in the southern and northern peripheries of the country puts a spotlight on Iraq's failure in managing healthcare. The post-2003 government has failed to either rebuild a robust centralized healthcare system, or to pave the way for a federalized model.

Caught in an ambiguous middle between a centralized and federalized model, coordination across provinces and hospitals during the coronavirus crisis has neither reflected strong management from Baghdad nor robust ownership at the governorate level.

This problem is part of a wider challenge of managing centre-periphery relations and federalism, which since 2003 has not worked effectively. Baghdad has provided all 18 provinces with instructions on testing and treatment, but only a handful have enough resources to put them into practice. Advanced testing capacity is limited to the five provinces with WHO-approved centers, with the remaining 13 sending swabs to Baghdad.

But the greatest challenge to Iraq’s COVID-19 response is the dramatic deterioration of state-society relations. Studies reveal a profound societal distrust of Iraq’s public healthcare institutions, due to corruption and militarization of medical institutions. Numerous videos have recently circulated of families refusing to turn over sick members - particularly women - to medical teams visiting households with confirmed or suspected cases.

As medical anthropologist Omar Dewachi notes, the ‘moral economy of quarantine’ in Iraq is heavily shaped by a history of war and its impact on the relationship between people and the state. Although local and international media often interpret this reluctance to undergo quarantine as a matter of social or tribal norms, distrusting the state leads many families to refuse quarantine because they believe it resembles a form of arrest.

The management of coronavirus relies upon an overt convergence between medical institutions and security forces as the federal police collaborate with the Ministry of Health to impose curfews and enforce quarantine. This means that, troublingly, the same security establishment which violently cracked down on protesters and civil society activists is now the teeth behind Iraq’s COVID-19 response.

Without trust between society and the political class, civil society organizations and protest movements have directed their organizational structure towards awareness-raising across Iraq. Key religious authorities such as Grand Ayatollah Sistani have called for compliance to the curfew and mobilized charitable institutions.

However, such efforts will not be enough to make up for the lack of governance at the level of the state. In the short-term, Iraq’s medical professionals and institutions are in dire need of technical and financial support. In the long-term, COVID-19 is a lesson that Iraq’s once robust public healthcare system needs serious investment and reform.

COVID-19 may prove to be another catalyst challenging the ‘muddle through’ logic of the Iraqi political elite. International actors have largely been complicit in this logic, directing aid and technical support towards security forces and political allies in the interest of short-term stability, and neglecting institutions which Iraqis rely on for health, education, and well-being.

The response to the crisis requires cooperation and buy-in of a population neglected by 17 years of failed governance. This is a seminal event that may push the country to the brink, exposing and stirring underlying tensions in state-society relations.

This analysis was produced as part of the Iraq Initiative.




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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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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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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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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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Mapping prostate cancer lesions pre/post unsuccessful salvage lymph node dissection using repeat PSMA-PET

Introduction: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET). Material and Methods: 16 patients were included in this multicenter study. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Results: post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16) and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA-PET. About two thirds of patients had PET positive nodal disease after SLND already seen on pre-SLND PSMA-PET. Notably, about one quarter of patients had new lesions, not detected by pre-surgical PSMA-PET.




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18F-Fluorodeoxyglucose Positron Emission Tomography / Computed Tomography in Left-Ventricular Assist Device Infection: Initial Results Supporting the Usefulness of Image-Guided Therapy

Background: Accurate definition of the extent and severity of left-ventricular assist device (LVAD) infection may facilitate therapeutic decision making and targeted surgical intervention. Here, we explore the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for guidance of patient management. Methods: Fifty-seven LVAD-carrying patients received 85 whole-body 18F-FDG PET/CT scans for the work-up of device infection. Clinical follow-up was obtained over a period of up to two years. Results: PET/CT showed various patterns of infectious involvement of the 4 LVAD components: driveline entry point (77% of cases), subcutaneous driveline path (87%), pump pocket (49%) and outflow tract (58%). Driveline smears revealed staphylococcus or pseudomonas strains as the underlying pathogen in a majority of cases (48 and 34%, respectively). At receiver-operating characteristics analysis, an 18F-FDG standardized uptake value (SUV) >2.5 was most accurate to identify smear-positive driveline infection. Infection of 3 or all 4 LVAD components showed a trend towards lower survival vs infection of 2 or less components (P = 0.089), while involvement of thoracic lymph nodes was significantly associated with adverse outcome (P = 0.001 for nodal SUV above vs below median). Finally, patients that underwent early surgical revision within 3 months after PET/CT (n = 21) required significantly less inpatient hospital care during follow-up when compared to those receiving delayed surgical revision (n = 11; p<0.05). Conclusion: Whole-body 18F-FDG PET/CT identifies the extent of LVAD infection and predicts adverse outcome. Initial experience suggests that early image-guided surgical intervention may facilitate a less complicated subsequent course.




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Head to head prospective comparison of quantitative lung scintigraphy and segment counting in predicting pulmonary function of lung cancer patients undergoing video-assisted thoracoscopic lobectomy

Prediction of post-operative pulmonary function in lung cancer patients before tumor resection is essential for patient selection for surgery and is conventionally done with a non-imaging segment counting method (SC) or a two-dimensional planar lung perfusion scintigraphy (PS). The purpose of this study was to compare quantitative analysis of PS to single photon emission computed tomography/computed tomography (SPECT/CT) and to estimate the accuracy of SC, PS and SPECT/CT in predicting post-operative pulmonary function in patients undergoing lobectomy. Methods: Seventy-five non-small cell lung cancer (NSCLC) patients planned for lobectomy were prospectively enrolled (68% males, average age 68.1±8 years ). All patients completed pre-operative forced expiratory volume capacity (FEV1), diffusing capacity of the lung for carbon monoxide (DLCO), Tc99m-MAA lung perfusion scintigraphy with PS and SPECT/CT quantification. A subgroup of 60 patients underwent video-assisted thoracoscopic (VATS) lobectomy and measurement of post-operative FEV1 and DLCO. Relative uptake of the lung lobes estimated by PS and SPECT/CT were compared. Predicted post-operative FEV1 and DLCO were derived from SC, PS and SPECT/CT. Prediction results were compared between the different methods and the true post-operative measurements in patients who underwent lobectomy. Results: Relative uptake measurements differed significantly between PS and SPECT/CT in right lung lobes, with a mean difference of -8.2±3.8, 18.0±5.0 and -11.5±6.1 for right upper, middle and lower lobes respectively (p<0.001). The differences between the methods in the left lung lobes were minor with a mean difference of -0.4±4.4 (p>0.05) and -2.0±4.0 (p<0.001) for left upper and lower lobes respectively. No significant difference and strong correlation (R=0.6-0.76, p<0.001) were found between predicted post-operative lung function values according to SC, PS, SPECT/CT and the actual post-operative FEV1 and DLCO. Conclusion: Although lobar quantification parameters differed significantly between PS and SPECT/CT, no significant differences were found between the predicted post-operative lung function results derived from these methods and the actual post-operative results. The additional time and effort of SPECT/CT quantification may not have an added value in patient selection for surgery. SPECT/CT may be advantageous in patients planned for right lobectomies but further research is warranted.




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Positron lymphography via intracervical 18F-FDG injection for pre-surgical lymphatic mapping in cervical and endometrial malignancies

Rationale: The presence of metastasis in local lymph nodes (LNs) is a key factor influencing choice of therapy and prognosis in cervical and endometrial cancers; therefore, the exploration of sentinel LNs (SLNs) is highly important. Currently, however, SLN mapping requires LN biopsy for pathologic evaluation, since there are no clinical imaging approaches that can identify tumor-positive LNs in early stages. Staging lymphadenectomy poses risks, such as leg lymphedema or lymphocyst formation. Furthermore, in 80% to 90% of patients, the explored LNs are ultimately tumor free, meaning the vast majority of patients are unnecessarily subjected to lymphadenectomy. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG except one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG, except for one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Conclusion: This first-in-human study of PLG in women with uterine and cervical cancer demonstrates its feasibility and its ability to identify patients with nodal metastases, and warrants further evaluation in additional studies.




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Evaluation of 11C-NR2B-SMe and its Enantiomers as PET Radioligands for Imaging the NR2B Subunit within the NMDA Receptor Complex in Rats

[S-Methyl-11C](±)-7-methoxy-3-(4-(4-(methylthio)phenyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol (11C-NR2B-SMe) and its enantiomers were synthesized as candidates for imaging the NR2B subunit within the N-methyl-D-aspartate receptor with positron emission tomography (PET). Methods: Brains were scanned with PET for 90 min after intravenous injection of one of the candidate radioligands into rats. To detect any NR2B specific binding of radioligand in brain, various pre-blocking or displacing agents were evaluated for their impact on the PET brain imaging data. Radiometabolites from brain and other tissues were measured ex vivo and in vitro. Results: Each radioligand gave high early whole brain uptake of radioactivity, followed by a brief fast decline and then a slow final decline. 11C-(S)-NR2B-SMe was studied extensively. Ex vivo measurements showed that radioactivity in rat brain at 30 min after radioligand injection was virtually unchanged radioligand. Only less lipophilic radiometabolites appeared in plasma. High-affinity NR2B ligands, Ro-25-6981, ifenprodil, and CO10124, showed increasing preblock of whole brain radioactivity retention with increasing dose (0.01 to 1.25 mg/kg, i.v.). Five 1 antagonists (FTC146, BD1407, F3, F4, and NE100) and four 1 agonists ((+)-pentazocine, (±)-PPCC, PRE-084, (+)-SKF10047) were ineffective preblocking agents, except FTC146 and F4 at high dose. Two potent 1 receptor agonists, TC1 and SA4503, showed dose-dependent preblocking effects in the presence or absence of pharmacological 1 receptor blockade with FTC146. Conclusion: 11C-(S)-NR2B-SMe has adequate NR2B-specific PET signal in rat brain to warrant further evaluation in higher species. TC1 and SA4503 likely have off-target binding to NR2B in vivo.




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Impact of 68Ga-PSMA-11 PET/CT on Staging and Management of Prostate Cancer Patients in Various Clinical Settings: A Prospective Single Center Study

The impact of prostate specific membrane antigen (PSMA) PET/CT on management of prostate cancer (PCa) patients with biochemical recurrence (BCR) is well-established. However, whether and how PSMA PET/CT affects the management of patients undergoing scans for other clinical indications remains unknown. The goal of this study was to determine the impact of 68Ga-PSMA-11 PET/CT on initial and subsequent management decisions in a cohort of PCa patients referred for various indications ("basket trial") excluding the two main classical indications: BCR and presurgical staging. Methods: This was a prospective study of 197 patients that aimed to determine the impact of 68Ga-PSMA-11 PET/CT on PCa stage and management. Indications for PSMA PET/CT were: initial staging of non-surgical candidates (30 patients) and re-staging after definitive treatment (n = 168). The re-staging cohort comprised: patients re-staged with known advanced metastatic disease (n = 103), after androgen deprivation therapy only (n = 16), after surgery with serum PSA levels <0.2 ng/ml (n = 13), after radiation therapy (RT) not meeting the Phoenix criteria (n = 22) and after other primary local treatments [i.e. high-intensity focused ultrasound (HIFU), focal laser ablation, cryoablation, hyperthermia or irreversible electroporation] (n = 13). Patients with BCR and candidates for curative surgery were excluded. Impact on management was assessed using pre- and post-PET questionnaires completed by referring physicians, electronic chart review and/or patient telephone encounters. Results: PSMA PET/CT changed disease stage in 135/197 (69%) patients (38% up-stage, 30% down-stage and no changes in stage in 32%). Management was affected in 104/182 (57%) patients. Specifically, PSMA PET/CT impacted management of patients who were re-staged after RT without meeting the Phoenix criteria for BCR, after other definitive local treatments and with advanced metastatic disease in 13/18 (72%), 8/12 (67%) and 59/96 (61%), respectively. Conclusion: PSMA PET/CT has a profound impact on stage and management of PCa patients outside of the two main classical indications (BCR and presurgical staging) across all examined clinical scenarios.




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Projection-space implementation of deep learning-guided low-dose brain PET imaging improves performance over implementation in image-space

Purpose: To assess the performance of full dose (FD) positron emission tomography (PET) image synthesis in both image and projection space from low-dose (LD) PET images/sinograms without sacrificing diagnostic quality using deep learning techniques. Methods: Clinical brain PET/CT studies of 140 patients were retrospectively employed for LD to FD PET conversion. 5% of the events were randomly selected from the FD list-mode PET data to simulate a realistic LD acquisition. A modified 3D U-Net model was implemented to predict FD sinograms in the projection-space (PSS) and FD images in image-space (PIS) from their corresponding LD sinograms/images, respectively. The quality of the predicted PET images was assessed by two nuclear medicine specialists using a five-point grading scheme. Quantitative analysis using established metrics including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), region-wise standardized uptake value (SUV) bias, as well as first-, second- and high-order texture radiomic features in 83 brain regions for the test and evaluation dataset was also performed. Results: All PSS images were scored 4 or higher (good to excellent) by the nuclear medicine specialists. PSNR and SSIM values of 0.96 ± 0.03, 0.97 ± 0.02 and 31.70 ± 0.75, 37.30 ± 0.71 were obtained for PIS and PSS, respectively. The average SUV bias calculated over all brain regions was 0.24 ± 0.96% and 1.05 ± 1.44% for PSS and PIS, respectively. The Bland-Altman plots reported the lowest SUV bias (0.02) and variance (95% CI: -0.92, +0.84) for PSS compared with the reference FD images. The relative error of the homogeneity radiomic feature belonging to the Grey Level Co-occurrence Matrix category was -1.07 ± 1.77 and 0.28 ± 1.4 for PIS and PSS, respectively Conclusion: The qualitative assessment and quantitative analysis demonstrated that the FD PET prediction in projection space led to superior performance, resulting in higher image quality and lower SUV bias and variance compared to FD PET prediction in the image domain.




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Improved Alignment of PET and CT Images in Whole-Body PET/CT in Cases of Respiratory Motion During CT

Respiratory motion during the CT and PET parts of a PET/CT scan leads to imperfect alignment of anatomical features seen by the two modalities. In this work, we concentrate on the effects of motion during CT. We propose a novel approach for improving the alignment. Methods: Respiratory waveform data were gathered during the CT and PET parts of 28 PET/CT scans of cancer patients with 40 lesions up to 3 cm size in the lung or upper abdomen. PET list-mode data were reconstructed by three reconstruction methods: PET/static, PET/EX or end of expiration (OncoFreeze), and a novel PET/matched method that used both waveforms. The three methods were compared. The distance between tumor positions in PET and CT were characterized in visual interpretation by physicians as well as quantitatively. Tumor standardized uptake values (SUVmax and SUVpeak) were determined relative to SUV based on the static method. Image noise was evaluated in the liver and compared to PET/static. Results: In visual interpretation, the rate of good alignment was 13/21, 13/23 and 18/21 for PET/static, PET/EX and PET/matched methods, respectively, and the mean PET-CT distances were 3.5, 5.1 and 2.8 mm. In visual comparison with PET/EX, the rate of good alignment was increased in 1/10 and 7/10 cases for PET/static and PET/matched. SUVmax was on average 21% higher than PET/static when either PET/EX or PET/matched was used. SUVpeak was 12% higher. Image noise in the liver was 15% higher than static for the PET/EX method, and 40% higher for PET/matched; that is, noise was much lower than in gated PET. Conclusion: Acquiring respiratory waveforms both in PET (as in the current state of the art) and in CT (an unusual key step in this approach) has the potential to improve the alignment of PET and CT images. A proposed method for using this information was tested. Improved alignment was demonstrated.




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18F-FDG PET/CT in the Diagnostic and Treatment Evaluation of Pediatric Post-transplant Lymphoproliferative Disorders

We aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection of post-transplantation lymphoproliferative disorder (PTLD) in a pediatric population and explore its feasibility during response assessment. Methods: This retrospective study included 28 pediatric transplant recipients who underwent a total of 32 18F-FDG PET/CT scans due to clinical suspicion of PTLD within an 8-year period. Pathology reports and 2-year follow-up were used as reference standard. Twenty-one response assessment 18F-FDG PET/CT scans were re-evaluated according to the Lugano criteria. Results: The diagnosis of PTLD was established in 14 patients (49%). Sensitivity, specificity, positive predictive value, and negative predictive value of 18F-FDG PET/CT for the detection of PTLD in children with a clinical suspicion of this disease, was 50% (7/14), 100% (18/18), 100% (7/7), and 72% (18/25), respectively. False-negative results occurred in patients with PTLD in the Waldeyer’s ring, cervical lymph nodes or small bowel with either non-destructive or polymorphic PTLD. Two of 5 interim 18F-FDG PET/CT scans and 3 of 9 end-of-treatment 18F-FDG PET/CT scans were false-positive. Conclusion: 18F-FDG PET/CT had good specificity and positive predictive value but low to moderate sensitivity and negative predictive value for the detection of PTLD in a 28 pediatric patient cohort with a clinical suspicion of this disease. False-negative results were confirmed in the Waldeyer’s ring, cervical lymph nodes and small bowel with either non-destructive or polymorphic PTLD subtypes. 18F-FDG PET/CT appears to have a limited role in the response assessment setting of pediatric PTLD, given the observed high proportions of false-positives both at interim and end-of-treatment evaluations.




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FDG-PET/CT identifies predictors of survival in patients with locally advanced cervical carcinoma and para-aortic lymph node involvement to increase treatment

Introduction: To use positron emission tomography coupled with computed tomography (18FDG-PET/CT) to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy (EFR) between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynaecologic oncology reviewed all 18FDG-PET/CT scans. Metabolic parameters including maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were determined for the primary tumour, pelvic lymph nodes and PALN. Associations between these parameters and overall survival (OS) were assessed with Cox's proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% CI (40.8-68.0)). When adjusted for age, stage and histology, pelvic lymph node TLG, PALN TLG and PALN SUVmax were significantly associated with OS (p<0.005). Conclusion: FDG-PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed.




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Data-driven motion detection and event-by-event correction for brain PET: Comparison with Vicra

Head motion degrades image quality and causes erroneous parameter estimates in tracer kinetic modeling in brain PET studies. Existing motion correction methods include frame-based image-registration (FIR) and correction using real-time hardware-based motion tracking (HMT) information. However, FIR cannot correct for motion within one predefined scan period while HMT is not readily available in the clinic since it typically requires attaching a tracking device to the patient. In this study, we propose a motion correction framework with a data-driven algorithm, i.e., using the PET raw data itself, to address these limitations. Methods: We propose a data-driven algorithm, Centroid of Distribution (COD), to detect head motion. In COD, the central coordinates of the line of response (LOR) of all events are averaged over 1-sec intervals to generate a COD trace. A point-to-point change in the COD trace in one direction that exceeded a user-defined threshold was defined as a time point of head motion, which was followed by manually adding additional motion time points. All the frames defined by such time points were reconstructed without attenuation correction and rigidly registered to a reference frame. The resulting transformation matrices were then used to perform the final motion compensated reconstruction. We applied the new COD framework to 23 human dynamic datasets, all containing large head motions, with 18F-FDG (N = 13) and 11C-UCB-J (N = 10), and compared its performance with FIR and with HMT using the Vicra, which can be considered as the "gold standard". Results: The COD method yielded 1.0±3.2% (mean ± standard deviation across all subjects and 12 grey matter regions) SUV difference for 18F-FDG (3.7±5.4% for 11C-UCB-J) compared to HMT while no motion correction (NMC) and FIR yielded -15.7±12.2% (-20.5±15.8%) and -4.7±6.9% (-6.2±11.0%), respectively. For 18F-FDG dynamic studies, COD yielded differences of 3.6±10.9% in Ki value as compared to HMT, while NMC and FIR yielded -18.0±39.2% and -2.6±19.8%, respectively. For 11C-UCB-J, COD yielded 3.7±5.2% differences in VT compared to HMT, while NMC and FIR yielded -20.0±12.5% and -5.3±9.4%, respectively. Conclusion: The proposed COD-based data-driven motion correction method outperformed FIR and achieved comparable or even better performance as compared to the Vicra HMT method in both static and dynamic studies.




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Performance of digital PET compared to high-resolution conventional PET in patients with cancer

Recently introduced PET systems using silicon photomultipliers with digital readout (dPET) have an improved timing and spatial resolution, aiming at a better image quality, over conventional PET (cPET) systems. We prospectively evaluated the performance of a dPET system in patients with cancer, as compared to high-resolution (HR) cPET imaging. Methods: After a single FDG-injection, 66 patients underwent dPET (Vereos, Philips Healthcare) and cPET (Ingenuity TF, Philips Healthcare) imaging in a randomized order. We used HR-reconstructions (2x2x2 mm3 voxels) for both scanners and determined SUVmax, SUVmean, lesion-to-background ratio (LBR), metabolic tumor volume (MTV) and lesion diameter in up to 5 FDG-positive lesions per patient. Furthermore, we counted the number of visible and measurable lesions on each PET scan. Two nuclear medicine specialists blindly determined the Tumor Node Metastasis (TNM) score from both image sets in 30 patients referred for initial staging. For all 66 patients, these specialists separately and blindly evaluated image quality (4-point scale) and determined the scan preference. Results: We included 238 lesions that were visible and measurable on both PET scans. We found 37 additional lesions on dPET in 27 patients (41%), which were unmeasurable (n = 14) or invisible (n = 23) on cPET. SUVmean, SUVmax, LBR and MTV on cPET were 5.2±3.9 (mean±SD), 6.9±5.6, 5.0±3.6 and 2991±13251 mm3, respectively. On dPET SUVmean, SUVmax and LBR increased 24%, 23% and 27%, respectively (p<0.001) while MTV decreased 13% (p<0.001) compared to cPET. Visual analysis showed TNM upstaging with dPET in 13% of the patients (4/30). dPET images also scored higher in image quality (P = 0.003) and were visually preferred in the majority of cases (65%). Conclusion: Digital PET improved the detection of small lesions, upstaged the disease and images were visually preferred as compared to high-resolution conventional PET. More studies are necessary to confirm the superior diagnostic performance of digital PET.




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Interim PET assessment of advanced Hodgkin Lymphoma: is it sufficient?




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Benefit of improved performance with state-of-the art digital PET/CT for lesion detection in oncology

Latest digital whole-body PET scanners provide a combination of higher sensitivity and improved spatial and timing resolution. We performed a lesion detectability study on two generations of Siemens Biograph PET/CT scanners, the mCT and Vision, to study the impact of improved physical performance on clinical performance. Our hypothesis is that the improved performance of the Vision will result in improved lesion detectability, allowing shorter imaging times or equivalently, lower injected dose. Methods: Data were acquired with the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network torso phantom combined with a 20-cm diameter cylindrical phantom. Spherical lesions were emulated by acquiring spheres-in-air data, and combining it with the phantom data to generate combined datasets with embedded lesions of known contrast. Two sphere sizes and uptakes were used: 9.89 mm diameter spheres with 6:1 (lung) and 3:1 (cylinder) and 4.95 mm diameter spheres with 9.6:1 (lung) and 4.5:1 (cylinder) local activity concentration uptakes. Standard image reconstruction was performed: ordinary Poisson ordered subsets expectation maximization algorithm with point spread function and time-of-flight modeling and post-reconstruction smoothing with a 5 mm Gaussian filter. The Vision images were also generated without any post-reconstruction smoothing. Generalized scan statistics methodology was used to estimate the area under the localization receiver operating characteristic curve (ALROC). Results: Higher sensitivity and improved TOF performance of Vision leads to reduced contrast in the background noise nodule distribution. Measured lesion contrast is also higher on the Vision due to its improved spatial resolution. Hence, the ALROC values are noticeably higher for the Vision relative to the mCT. Conclusion: Improved overall performance of the Vision provides a factor of 4-6 reduction in imaging time (or injected dose) over the mCT when using the ALROC metric for lesions >9.89 mm in diameter. Smaller lesions are barely detected in the mCT, leading to even higher ALROC gains with the Vision. Improved spatial resolution of the Vision also leads to a higher measured contrast that is closer to the real uptake, implying improved quantification. Post-reconstruction smoothing, however, reduces this improvement in measured contrast, thereby reducing the ALROC values for small, high uptake lesions.




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A Prospective, Comparative Study of Planar and Single-photon Emission Computed Tomography Ventilation/Perfusion Imaging for Chronic Thromboembolic Pulmonary Hypertension

Objectives: The study compared the diagnostic performance of Planar Ventilation/perfusion (V/Q) and V/Q Single-photon computed tomography (SPECT), and determined whether combining perfusion scanning with low-dose computed tomography (Q-LDCT) may be equally effective in a prospective study of patients with chronic thromboembolic pulmonary hypertension (CTEPH) patients. Background: V/Q scanning is recommended for excluding CTEPH during the diagnosis of pulmonary hypertension (PH). However, Planar V/Q and V/Q SPECT techniques have yet to be compared in patients with CTEPH. Methods: Patients with suspected PH were eligible for the study. PH attributable to left heart disease or lung disease was excluded, and patients whose PH was confirmed by right heart catheterization and who completed Planar V/Q, V/Q-SPECT, Q-LDCT, and pulmonary angiography were included. V/Q images were interpreted and patients were diagnosed as instructed by the 2009 EANM guidelines, and pulmonary angiography analyses were used as a reference standard. Results: A total of 208 patients completed the study, including 69 with CTEPH confirmed by pulmonary angiography. Planar V/Q, V/Q-SPECT, and Q-LDCT were all highly effective for diagnosing CTEPH, with no significant differences in sensitivity or specificity observed among the three techniques (Planar V/Q [sensitivity/specificity]: 94.20%/92.81%; V/Q-SPECT: 97.10%/91.37%, Q-LCDT: 95.65%/90.65%). However, V/Q-SPECT was significantly more sensitive (V/Q-SPECT: 79.21%; Planar V/Q: 75.84%, P = 0.012; Q-LDCT: 74.91%, p<0.001), and Planar V/Q was significantly more specific (Planar V/Q: 54.14%; V/Q-SPECT 46.05%, p<0.001; Q-LDCT: 46.05%, P = 0.001) than the other two techniques for identifying perfusion defects in individual lung segments. Conclusion: Both Planar V/Q and V/Q-SPECT were highly effective for diagnosing CTEPH, and Q-LDCT may be a reliable alternative method for patients who are unsuitable for ventilation imaging.