This article has been withdrawn by the authors. We discovered an error after this manuscript was published as a Paper in Press. Specifically, we learned that the structures of glycans presented for the PD-L1 peptide were drawn and labeled incorrectly. We wish to withdraw this article and submit a corrected version for review.

The glycoprotein spike (S) on the surface of SARS-CoV-2 is a determinant for viral invasion and host immune response. Herein, we characterized the site-specific N-glycosylation of S protein at the level of intact glycopeptides. All 22 potential N-glycosites were identified in the S-protein protomer and were found to be preserved among the 753 SARS-CoV-2 genome sequences. The glycosites exhibited glycoform heterogeneity as expected for a human cell-expressed protein subunit. We identified masses that correspond to 157 N-glycans, primarily of the complex type. In contrast, the insect cell-expressed S protein contained 38 N-glycans, completely of the high-mannose type. Our results revealed that the glycan types were highly determined by the differential processing of N-glycans among human and insect cells, regardless of the glycosites’ location. Moreover, the N-glycan compositions were conserved among different sizes of subunits. Our study indicate that the S protein N-glycosylation occurs regularly at each site, albeit the occupied N-glycans were diverse and heterogenous. This N-glycosylation landscape and the differential N-glycan patterns among distinct host cells are expected to shed light on the infection mechanism and present a positive view for the development of vaccines and targeted drugs.

Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.

The F-box protein MORE AXILLARY GROWTH 2 (MAX2) is a central component in the signaling cascade of strigolactones (SLs) as well as of the smoke derived karrikins (KARs) and the so far unknown endogenous KAI2 ligand (KL). The two groups of molecules are involved in overlapping and unique developmental processes, and signal-specific outcomes are attributed to perception by the paralogous α/β-hydrolases DWARF14 (D14) for SL and KARRIKIN INSENSITIVE 2/ HYPOSENSITIVE TO LIGHT (KAI2/HTL) for KAR/KL. Additionally, depending on which receptor is activated, specific members of the SUPPRESSOR OF MAX2 1 (SMAX1) – LIKE (SMXL) family control KAR/KL and SL responses. As proteins that function in the same signal transduction pathway often occur in large protein complexes, we aimed at discovering new players of the MAX2, D14 and KAI2 protein network by tandem affinity purification using Arabidopsis cell cultures. When using MAX2 as a bait, various proteins were co-purified among which general components of the Skp1-Cullin-F-box complex and members of the CONSTITUTIVE PHOTOMORPHOGENIC 9 signalosome. Here, we report the identification of a novel interactor of MAX2, a type 5 serine/threonine protein phosphatase, designated PHYTOCHROME-ASSOCIATED PROTEIN PHOSPHATASE 5 (PAPP5). Quantitative affinity purification pointed at PAPP5 as being more present in KAI2 rather than D14 protein complexes. In agreement, mutant analysis suggests that PAPP5 modulates KAR/KL-dependent seed germination in suboptimal conditions and seedling development. Additionally, a phosphopeptide enrichment experiment revealed that PAPP5 might dephosphorylate MAX2 in vivo independently of the synthetic strigolactone analog, rac-GR24. Together, by analyzing the protein complexes to which MAX2, D14 and KAI2 belong, we revealed a new MAX2 interactor, PAPP5, that might act through dephosphorylation of MAX2 to control mainly KAR/KL- related phenotypes and, hence, provide another link with the light pathway.

Giardia lamblia (G. lamblia) disease is a zoonosis with a-infection rate affecting the general population of the world. Despite the constant possibility of damage due to their own metabolism, G. lamblia have survived and evolved to adapt to various environments. However, research on energy-metabolism conversion in G. lamblia is limited. This study aimed to reveal the dynamic metabolism-conversion mechanism in G. lamblia under sugar starvation by detecting global lysine acetylation and 2-hydroxyisobutyrylation sites combined with quantitative proteome analyses. A total of 2999 acetylation sites on 956 proteins and 8877 2-hydroxyisobutyryl sites on 1546 proteins were quantified under sugar starvation. Integrated Kac and Khib data revealed that modified proteins were associated with arginine biosynthesis, glycolysis/gluconeogenesis, and alanine, aspartate, and glutamate metabolism. These findings suggested that lysine acetylation and 2-hydroxyisobutyrylation were ubiquitous and provided deep insight into the metabolism-conversion mechanism in G. lamblia under sugar starvation. Overall, these results can help understand the biology of G. lamblia infections and reveal the evolution rule from prokaryote to eukaryote.

Annual Review 2017-18 Other resource sysadmin 18 July 2018

Explore the institute’s output, activities and achievements from the past year examining how to make the world more secure in uncertain times; new thinking on how societies can flourish and be prosperous; and how to contribute to a more just society.

Director’s statement

I wrote a year ago that the world has entered one of the most politically turbulent periods in the modern era. This rings even more true now, as relations have seriously deteriorated between the US administration and its European allies, while instability persists across the Middle East, and China and Russia increase their strategic influence.

Over the past year, Chatham House has assessed these changes and proposed ways to manage the associated risks, while seeking out opportunities to expand prosperity and security across the world. Adam Ward, our deputy director, led the publication of the first Chatham House Expert Perspectives report on risks and opportunities in international affairs, to coincide with our fifth annual London Conference on 21–22 June 2018. The conference was attended by over 450 participants from 71 countries.

Furthermore, using our new simulation centre on the Stavros Niarchos Foundation (SNF) Floor, our research teams are ‘stress-testing’ their ideas in exercises involving both practitioners and experts. For example, in June 2017 the Centre on Global Health Security and the Africa Programme hosted our first scenario exercise, which explored how to respond to a humanitarian emergency that required landmine clearance. Since then, we have hosted other simulation and scenario planning exercises, including on cyberattacks, Brexit ‘futures’ and the rise of the populist parties in Europe.

We have also used the new facilities to host events supported by modern audiovisual systems; to stress-test our own communications strategy; and even to conduct a round of scenario-based interactive job interviews. The new media studio and editing facilities have led us to create more multimedia content, which has, in turn, enabled us to reach expanded and more diverse audiences for our work. The new SNF Floor has also provided staff with an open, multifunctional meeting area and has alleviated some of the space pressures which had been created by our growing staff numbers.

As you will read in the following pages, our research is currently centred around three themes: making the world more secure in uncertain times; offering new ideas on how societies can flourish and be prosperous; and contributing to a more just society. A growing number of cross-cutting projects enable us to address topics within each of these themes, including cyberthreats, transatlantic relations, the future of the EU–China economic relationship, regulating data, vulnerabilities in global food trade and implementing universal health coverage.

Our ability to do so has been enhanced by the appointment of several new senior research staff: Hans Kundnani as senior fellow in the Europe Programme; Champa Patel as head of the Asia- Pacific Programme; and Leslie Vinjamuri as head of the US and the Americas Programme and dean of the Queen Elizabeth II Academy for Leadership in International Affairs. In addition, Bernice Lee will take over as the new research director of our Global Economy and Finance Department, alongside her continuing role as executive director of the Hoffmann Centre for Sustainable Resource Economy.

During the coming months, we will lay the foundations to mark the institute’s centenary in the summer of 2020. In doing so, we will draw on our archives to acknowledge the institute’s unique achievements over the past 100 years, recognize those many individuals who have supported us along the way, and set out our objectives for the future. In preparation, we have already launched a series of members’ events with a historical focus, examining how the lessons from the past can inform international affairs and policy thinking today.

In closing, I would like to pay tribute and offer my sincere thanks to Stuart Popham, who steps down this year after six years as chair of the institute and 13 years between 2005 and 2018 as a member of Council. Stuart has been a tremendous support and guide to me, and to the institute as a whole, during this period. His measured advice to management and collegiate leadership of Council have been invaluable during a period in which the institute has more than doubled in size, and in which it has thrived despite the increasingly competitive environment for policy convening, analysis and ideas. We look forward to welcoming Stuart back to Chatham House as a highly engaged individual member, and wish him all the best for the future.

Robin Niblett CMG

New Frontiers in Gender-responsive Governance: Five Years of the W20 Research paper sysadmin 2 November 2018

After five years of the W20, women and gender equality remain at the margin of the G20. There is a real risk of the W20 representing a one-off territorial gain at a frontier that could easily be pushed back again.

Summary

• 2018 marks the fifth anniversary of the first grouping of the W20, the engagement group of the G20 that focuses on gender-inclusive economic growth and advocates for gender equality across the G20 agenda. Formally launched under the Turkish G20 presidency in 2015, the W20 is made up of women from business, international organizations, civil society, think-tanks and academia across the G20 member states.
• This paper takes stock of the critical steps in the development of the W20 over the last five years, examining its background, rationale and foundations, and identifying the areas of economic governance where it has so far contributed the most – and those where more action is needed. The W20 has filled a gap, it but needs to carefully assess its coherence with the UN agencies, the private sector, the G7 and other G20 engagement groups.
• The establishment of the W20 has contributed to defining new frontiers for economic governance and shifting the traditional approach from gender-neutral to gender-responsive. Whereas in 2013 gender in the G20 was considered a marginal issue better dealt with by ministers for equal opportunities, now gender equality and women’s economic empowerment are part of the mainstream economic dialogue. The next step is to ensure more structural and monitored policy reforms at the G20 level.
• Already, the W20 can count among its achievements the ‘25 by 25’ female labour force participation commitment adopted at the G20’s Brisbane summit in 2014, and the Women Entrepreneurs Finance Initiative (We-Fi) and Business Women Leaders’ Taskforce, both agreed at the Hamburg summit in 2017.
• The W20 is constrained in its policy impact by limited engagement with the finance track and a lack of consistent resourcing levels. Addressing these issues would strengthen its role as a credible player in shifting global economic governance while contributing to good gender-responsive domestic policies.
• Progress on gender equality has been too slow and too peripheral to drive change in the relatively short term – over one generation, for example. G20 governments must therefore embrace active, credible policies to bring more women into the labour market, improve access to education and finance, close the pay gap, invest in social infrastructure – especially childcare and assistance for the elderly – and support female entrepreneurs. These domestic policies need to be internationally coordinated so that action and benefits can be widespread.
• A feminist, inclusive agenda at the G20 level should highlight the current empirical evidence of women’s exclusion from the benefit of their economic activity, both in G20 members and beyond. The W20 should also focus on efforts to remedy the lack of women’s representation in G20 processes and in economic governance as a whole.

Annual Review 2018-19 Other resource sysadmin 24 July 2019

Explore the institute’s output, activities and achievements from the past year examining how to make the world more stable in uncertain times, new thinking on how societies can promote prosperity, and how to contribute to a more just society.

Chair’s statement

I was delighted to be elected chair of Chatham House last year. It is an honour to lead such a remarkable institution and to have the opportunity to build on the legacy left by Stuart Popham, who stepped down last year as chair and whom I thank and pay tribute to.

My ambition is to ensure that the institute has an even better future than its illustrious past. We are living in unpredictable times, and I want us to be at the centre of the drive to guide the world to a healthier place both politically and economically.

Chatham House possesses world-leading convening power, which – when combined with our capacity to deliver leading, cross-cutting research – gives us a unique advantage in the field of international relations. I want us to harness these assets and better combine the strengths of our research teams so that we can address the big global challenges around economic growth; avoiding geopolitical tensions; and developing new governance systems (as outlined on page 7). This will enable us to improve our impact and effect more policy change.

I also want Chatham House to be an exciting place that attracts younger, more diverse, international audiences. We need to drive more engagement with the next generation of members and others to draw on their enthusiasm, energy and ideas. Our Common Futures Conversations project, for example, is engaging young people from 13 countries across Africa and Europe to identify their shared concerns, and is enabling them to work together to identify solutions via online communities.

This initiative, and indeed all of our activities, would not be possible without funding and support. As noted in more detail in the Honorary Treasurer’s report (page 32), 2018/19 was a challenging year financially, with income totalling £16,381,000, slightly below the level recorded in 2017/18.

Although total net assets at 31 March 2019 were 3 per cent down year on year, the balance sheet remain strong and there was an inflow of cash, with the level of forward income received and pledged increasing significantly.

In this context, I am delighted to note the award of the transformational £10 million grant to facilitate the creation of the Stavros Niarchos Foundation Wing, which will help facilitate research, host our Queen Elizabeth II Academy for Leadership in International Affairs and establish a new collaboration space – the ‘CoLab’ – for engaging our new audiences. All of Chatham House’s supporters, and not least our members, remain indispensable to our success. Without their engagement, enthusiasm and input, the institute could not fulfil its mission.

I am indebted to my colleagues on Council for their support, engagement and expertise. I can say with confidence that they are actively involved in their governance responsibilities at this time when the operational, as well as financial, pressures on all charitable institutions are more intense than ever.

I would like to pay tribute to Alistair Burnett, Martin Fraenkel and Barbara Ridpath, who step down from Council this year after a total of 15 years’ service. I would also like to thank and acknowledge Robin Niblett and his team for their dedication and hard work. Some of the outcomes of their labours are highlighted on the following pages.

Lord Jim O’Neill

Belarusians’ views on the political crisis - April 2021 Other resource NCapeling 11 June 2021

Results of a public opinion poll conducted between 20 and 30 April 2021.

Chatham House surveyed a total of 937 respondents between 20 and 30 April 2021. Our survey sample corresponds to the general structure of Belarus’s urban population and is corrected and weighted by gender, age, size of respondents’ town of residence and education level.

Summary

• After Lukashenka, the most known political figures in Belarus are pro-protest politicians: Tsikhanouskaya, Babaryka, Tsikhanouski, Kalesnikava, Tsapkala and Latushka. Viktar Babaryka is the most popular presidential candidate among Belarusian urban citizens, and Lukashenka comes second to him.
• State organizations and bodies are still mistrusted by more than half the population, while the army is slightly more popular than other bodies. Independent media, labour unions and human rights organizations are trusted far more than state ones.
• Russia leads when it comes to positive attitudes to foreign states: one in three Belarusians feel very positive about their neighbour and 79 per cent feel positive in general. 71 per cent Belarusians feel positive about China, which is the next highest indicator. Despite propaganda efforts, Ukraine, Lithuania, Poland and EU states in general are still perceived positively by more than 60 per cent of Belarusians, with fewer than 20 per cent feeling negative about them.
• The position on Russian interference in the Belarusian political crisis is consolidated enough: 58 per cent think that Russia should remain neutral. The rest are almost equally divided between those who think Russia should support the protest movement (19 per cent) and those who think Russia should support Lukashenka (23 per cent).
• 40 per cent have changed their attitude to the Russian government since it supported Lukashenka in the crisis, and 73 per cent are sure that Russia is his sole support.
• While 32 per cent of Belarusians see union with Russia as the most appropriate foreign policy, 46 per cent would like to be in a union with both Russia and the EU simultaneously.
• Almost half the population thinks that Belarusian foreign policy in the event of a pro-protest government coming to power would be oriented toward friendship and cooperation with both Russia and the West, which correlates with how the majority thinks it should be. Although 42 per cent expect foreign policy would lean toward the EU in that situation, which is less acceptable: only 25 per cent think it ‘should’.
• The proportion of respondents who think Belarus should remain in the Collective Security Treaty Organization is 58 per cent, while 35 per cent would like to see Belarus not belonging to any military bloc and a small share (seven per cent) would prefer Belarus to join NATO.
• Almost half of the population considers Lukashenka to be the major obstacle for political stability and economic development and is sure he does not care about, and in fact is a threat to, independence.
• In general, most Belarusians have a consolidated opinion that the authorities should start negotiating with opponents and free all political prisoners.
• More than half of Belarusians think that Lukashenka must leave immediately or before the end of 2021, while 27 per cent think he should leave when his term ends in 2025. The opinion that Lukashenka should rule for another term beginning in 2025 is marginal – only ten per cent support this.
• Expectations are not so optimistic though: only 26 per cent believe he will leave office this year. One in three thinks he will leave in 2025; a further 19 per cent say that he will stay on for further terms in office.
• If Lukashenka doesn’t leave, people expect an increase in emigration and unemployment, the continuation of repression in all areas of life, falling exchange rates and the tightening of dependency on Russia.
• Opinion on abortions is still consolidated, with only 19 per cent thinking they should be banned in most or all cases. The same applies to Lukashenka’s infamous statement that society in Belarus is not ready to have a female president: only 20 per cent agree with the opinion.
• 52 per cent don’t think there is a problem of wage inequality between men and women in Belarus, while 37 per cent do see an issue.

Download a presentation of the survey’s main findings

Impact report 2020–21 Other resource dora.popova 14 July 2021

Explore our policy impact in the past year, including through our research, convening and next generation initiatives, in a revised format annual review.

Chair’s statement

It has been an extraordinary year of change for us all. The COVID-19 pandemic is the greatest challenge to the world for generations. Millions have lost their lives or suffered devastating impacts on their health, both from COVID-19 itself and because health systems have been unable to deliver treatments for other conditions. The pandemic has also caused the greatest shock to the global economy since the 1930s, setting back the progress of recent years in eliminating poverty, getting more children into education and improving global health.

This means Chatham House is needed more than ever. Our world-leading convening and cutting-edge research on the major challenges facing the world, from building more sustainable economic growth and tackling climate change to easing geopolitical tensions, has continued despite the challenges of lockdown. For that I pay tribute to the resilience and ingenuity of the staff who have found innovative solutions to the obstacles presented by the pandemic, all while working largely from home.

This year I am also delighted to note the exceptional gift of £10 million from the MAVA Foundation to enable us to launch the Sustainability Accelerator. This initiative builds on the Hoffmann Centre’s last five years of innovative convening and activity. And it puts sustainability at the core of the institute’s work in this critical year for addressing climate change and biodiversity.

So, as I prepare to step down from my three years as chair of the institute, I would like to thank my fellow Council members and Robin Niblett and his team for their hard work and ambition to deliver on Chatham House’s mission. I have also been especially pleased to see how we are engaging younger, more diverse audiences through the next generation initiatives, including our Panel of Young Advisers, the Common Futures Conversations project, the QEII Academy Ambassadors, our Internship Programme and the Chatham House-SNF CoLab.

I am particularly pleased about the Chatham House Summer School, where 16–18-year-olds can now engage with experts on international affairs and get an insight into careers within the charity and not-for-profit sector.

It has been an honour to lead this extraordinary institution and I look forward to continuing my involvement with Chatham House in new ways.

Lord Jim O’Neill

COP26: What happened, what does this mean, and what happens next? Chatham House briefing NCapeling 15 November 2021

Analysing a crucial opportunity for enhancing ambitions on climate finance, adaptation, and ‘loss and damage’, and the implementation of the Paris Agreement.

Key findings

Raising the ambition of national emission reduction targets (nationally determined contributions – NDCs) was a critical task for COP26. On this front, governments fell short: although over 120 parties have submitted new or updated NDCs, the new targets only narrow the gap to 1.5°C by 15–17 per cent, and are, if fully implemented (and this is far from certain), projected to result in warming of 2.4°C by the end of the century.

If warming is to be limited to 1.5°C above pre-industrial levels, additional emissions reductions before 2030, over and above current NDC pledges, will need to equate to reducing emissions by the equivalent of two years of current annual emissions. To keep warming to 2°C, the equivalent reductions would be needed of one year’s total emissions.

The Glasgow Climate Pact – the main political outcome of COP26 – requests governments to revisit and strengthen their NDCs before the end of 2022 to bring these in line with the Paris Agreement’s temperature goal. To keep 1.5°C within reach, it will be absolutely essential that governments return to the table with significantly enhanced offers ahead of COP27, which will take place at Sharm El-Sheikh, Egypt, in 2022.

Another key feature of the Glasgow Climate Pact is the reference to ‘accelerating efforts towards the phasedown of unabated coal power and phase-out of inefficient fossil fuel subsidies’. Although the language was watered down over the course of the negotiations, COP26 marks the first time ever reducing fossil fuels is mentioned in a COP decision.

Discussions around climate finance, adaptation, and loss and damage were centre stage in Glasgow, and were critical points of contention. Although the Glasgow Climate Pact urges developed countries to ‘fully’ deliver on the $100 billion annual climate finance pledge through to 2025, it remains unclear when this sum will actually be raised in full – and if a total of $500 billion will be mobilized between 2020 and 2025 to make up for initial shortfalls.

And while the Pact urges developed countries to double their adaptation finance by 2025, and establishes a dialogue on loss and damage finance, much more will need to be done to address the needs of climate-vulnerable developing countries. 

COP26 saw a flurry of plurilateral deals on key issues such as phasing out various forms of fossil fuels and ending deforestation. These initiatives have the potential to accelerate decarbonization, but monitoring their implementation and holding governments and other institutions to account will be critical. Future COPs provide a platform for doing this, and governments should seek to incorporate the pledges made outside the formal remits of the UNFCCC process in their NDCs.

While some progress was made at COP26, the next 12 months will be crucial in determining if the formal agreements reached in Glasgow provide grounds for optimism that 1.5°C remains firmly in sight, and are sufficient to build trust between countries and between citizens and governments.

Read the full analysis

Belarusians’ views on the political crisis - Nov 2021 Other resource NCapeling 20 January 2022

Results of a public opinion poll conducted between 1 and 10 November 2021.

Chatham House surveyed a total of 767 respondents between 1 and 10 November 2021. Our survey sample corresponds to the general structure of Belarus’s urban population and is adjusted by gender, age, education level and the size of respondents’ place of residence.

Summary

• After Aliaksandr Lukashenka, the most well-known political figures in Belarus are the protest leaders: Sviatlana Tsikhanouskaya, Viktar Babaryka, Siarhei Tsikhanouski, Valery Tsapkala, Marya Kalesnikava and Pavel Latushka.
• Lukashenka and Babaryka have the highest popularity ratings among Belarus’s urban population. At the same time, Lukashenka has a high negative rating: half of the city residents surveyed say that they would never vote for him. Babaryka has one of the lowest negative ratings in the country.
• The popularity ratings of pro-government politicians are low, and their negative ratings remain extremely high, although the latter have decreased slightly in comparison with July 2021. The popularity ratings of protest leaders are significantly higher than those of politicians who support the current government.
• Trust in state and independent organizations is polarized along political lines. Thus, respondents classed as hardcore protesters do not trust state structures and do trust independent ones, while Lukashenka’s supporters hold the opposite positions.
• Belarusians’ geopolitical orientations remain stable. The most widely preferred option for a geopolitical union is simultaneous integration with the EU and Russia.
• Belarusians have become increasingly negative about the possibility that Russian airbases could be established on Belarusian territory (48 per cent in November 2021, compared to 39 per cent in July 2021).
• Belarusians are now feeling more strongly that the situation concerning the COVID-19 pandemic has worsened: in November, more than half were beginning to respond that Belarus is unable to cope with the spread of coronavirus.
• Sanctions against Lukashenka and those around him are supported more widely than sanctions against state enterprises.
• Belarusians feel there is acute social tension in their country: almost everyone surveyed states that social tension exists, while one in every five respondents considers the situation catastrophic. A perception that there is social tension is closely related to many factors, with the strongest of all being a sense of a lack of personal safety.
• Only one-third of Belarusians are prepared to call the state built under Lukashenka their own. Most of the survey respondents do not trust this state to some degree, and do not believe that the state protects the interests of Belarusian citizens.

Download a presentation of the survey’s main findings

• Belarusians’ views on the political crisis (PDF)

• Взгляды белорусов на политический кризис (PDF)

Annual Review 2021–22 Other resource NCapeling 11 July 2022

Explore highlights from our work over the past year, including research, events, and next generation initiatives.

Chair’s statement

The past 12 months have seen new levels of instability injected into international affairs. The consequences of the COVID-19 pandemic, the continued fracturing of the international system and Russia’s war on Ukraine, which triggered the largest movement of refugees since the Second World War, have had severe impacts on trade, prices and people around the world.

Chatham House’s Russia and Eurasia Programme and its Ukraine Forum have advised allied governments on their response to the war on Ukraine, and secured the participation of Ukrainian president Volodymyr Zelenskyy in the most watched event of the institute’s history.

The challenge now is to ensure Chatham House can bring together its diverse areas of research and offer influential ideas on how to respond to the uncertain future. Council has supported the push to define clear priorities for the institute’s work, and the launch of two new research centres covering sustainability and global governance.

Drawing out the best from the institute’s expertise in the changed geopolitical landscape will be a top priority for Bronwen Maddox when she takes over as director at the end of August. Council is delighted to have found such a worthy successor to Robin Niblett. Robin’s 15 years of inspiring leadership have seen the institute more than triple in size of staff and budget. New areas of research under his tenure include cyber policy, digital governance, global health, the US and the Americas, and the UK in the world post-Brexit.

Robin also launched the Queen Elizabeth II Academy for Leadership in International Affairs, providing the base for many initiatives to engage the next generation. He also leaves the institute with a rebuilt balance sheet after securing some major long-term gifts; expanded and renovated premises; and a strong communications and digital infrastructure that has raised the profile of Chatham House with our audiences.

Council places on record the institute’s debt to Robin and to his wife, Trisha de Borchgrave. Chatham House’s supporters around the world were delighted to see Robin awarded a knighthood in HM The Queen’s Birthday Honours 2022.

I pay tribute also to my predecessor, Jim O’Neill, and I am grateful to Simon Fraser, deputy chair, and to the other four retiring members of Council (Mimi Ajibadé, Heide Baumann, Kenneth Cukier and Tim Willasey-Wilsey) for their dedication and counsel.

Council will continue to focus on strengthening the impact of the institute’s work and on improving governance, as well as providing continuity during the leadership transition. We will act as a strategic partner for Bronwen as she takes Chatham House forward. Central to this will be implementing the institute’s plan to strengthen equality, diversity and inclusion across the board. Finally, I thank the staff for their commitment through this period of transformation.

Sir Nigel Sheinwald GCMG

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

The origin recognition complex (ORC), composed of six subunits, ORC1–6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2–7, the minichromosome maintenance protein complex, around DNA and initiate DNA replication. We previously reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a reduction in the number of origins firing. Here, using CRISPR-Cas9–mediated mutations, we report that human HCT116 colon cancer cells also survive when ORC5 protein expression is abolished via a mutation in the initiator ATG of the ORC5 gene. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2–7 and initiate replication from a similar number of origins as WT cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells, rendering both ORC5 and ORC2 proteins undetectable in the same cells and destabilizing the ORC1, ORC3, and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2–7 normally to chromatin, and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2–7 to initiate DNA replication, or human cell lines can sometimes recruit MCM2–7 to origins independent of ORC.

Homologous recombination (HR) repairs DNA double-strand breaks using intact homologous sequences as template DNA. Broken DNA and intact homologous sequences form joint molecules (JMs), including Holliday junctions (HJs), as HR intermediates. HJs are resolved to form crossover and noncrossover products. A mismatch repair factor, MLH3 endonuclease, produces the majority of crossovers during meiotic HR, but it remains elusive whether mismatch repair factors promote HR in nonmeiotic cells. We disrupted genes encoding the MLH3 and PMS2 endonucleases in the human B cell line, TK6, generating null MLH3−/− and PMS2−/− mutant cells. We also inserted point mutations into the endonuclease motif of MLH3 and PMS2 genes, generating endonuclease death MLH3DN/DN and PMS2EK/EK cells. MLH3−/− and MLH3DN/DN cells showed a very similar phenotype, a 2.5-fold decrease in the frequency of heteroallelic HR-dependent repair of restriction enzyme–induced double-strand breaks. PMS2−/− and PMS2EK/EK cells showed a phenotype very similar to that of the MLH3 mutants. These data indicate that MLH3 and PMS2 promote HR as an endonuclease. The MLH3DN/DN and PMS2EK/EK mutations had an additive effect on the heteroallelic HR. MLH3DN/DN/PMS2EK/EK cells showed normal kinetics of γ-irradiation–induced Rad51 foci but a significant delay in the resolution of Rad51 foci and a 3-fold decrease in the number of cisplatin-induced sister chromatid exchanges. The ectopic expression of the Gen1 HJ re-solvase partially reversed the defective heteroallelic HR of MLH3DN/DN/PMS2EK/EK cells. Taken together, we propose that MLH3 and PMS2 promote HR as endonucleases, most likely by processing JMs in mammalian somatic cells.

Timely repair of DNA double-strand breaks (DSBs) is essential to maintaining genomic integrity and preventing illnesses induced by genetic abnormalities. We previously demonstrated that the E3 ubiquitin ligase SMURF2 plays a critical tumor suppressing role via its interaction with RNF20 (ring finger protein 20) in shaping chromatin landscape and preserving genomic stability. However, the mechanism that mobilizes SMURF2 in response to DNA damage remains unclear. Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. We demonstrate that a SMURF2 mutant with an S384A substitution has reduced capacity to ubiquitinate RNF20 while promoting Smad3 ubiquitination unabatedly. More importantly, mouse embryonic fibroblasts expressing the SMURF2 S384A mutant show a weakened ability to sustain the DSB response compared with those expressing WT SMURF2 following etoposide treatment. These data indicate that SMURF2-mediated RNF20 ubiquitination and degradation controlled by ataxia telangiectasia mutated–induced phosphorylation at Ser384 constitutes a negative feedback loop that regulates DSB repair.

Jake Arrieta on Thursday offered an unexpected explanation for his second-half struggles in 2018: he pitched much of last season with an injured left knee.

Odubel Herrera smiled and patted his stomach. The paunch that he carried into Spring Training 2018 is no longer there. Herrera has reported to camp leaner and, as he said Friday morning at Spectrum Field, motivated to bounce back from the worst season of his four-year career.

Spring Training is imminent, Opening Day is within sight and the big league season isn't complete for fans without a subscription to MLB.TV. The most comprehensive streaming service in professional sports is now available for the 2019 season.

POSTPONED: Zimbabwe Futures 2025: Financial Sector Expansion and Policy Priorities 15 November 2017 — 9:00AM TO 11:30AM Anonymous (not verified) 6 November 2017 Harare, Zimbabwe 

This roundtable will draw on current best practice and senior level expertise to identify policy options for financial stability and sector growth. A depoliticized analysis of the development agenda will highlight requisite conditions and prospective policies for a business-driven roadmap to the economic recovery of Zimbabwe, with a specific focus on the financial sector.

Participants will discuss macro-economic policy and stability, retail banking products and services, fintech, mobilizing domestic finance for national infrastructure and balancing consumer price index and inflation.

This event is being held in partnership with the Zimbabwe Business Club.

PLEASE NOTE, THIS EVENT HAS BEEN POSTPONED UNTIL FURTHER NOTICE.

Angola Forum 2018: 30th Anniversary of the Battle of Cuito Cuanavale 23 March 2018 — 10:00AM TO 2:30PM Anonymous (not verified) 8 March 2018 Chatham House, London

Reflections on Southern Africa’s Turning Point

23 March 2018 marks the 30th anniversary of the final assault of what became known as the Battle of Cuito Cuanavale.

The confrontation between the Angolan army, supported by Cuba and the Soviet Union, and the armed opposition UNITA, supported by the South African Defence Force, is the largest land battle to have taken place in Africa since World War Two.

The battle was a watershed in Angolan and southern African history, but its significance continues to be contested. Today, although the battlefield has a monument and museum, it remains one of the most landmine-contaminated parts of Angola and this hinders development plans for international tourism.

This event brings together veterans and experts to contribute towards developing a deeper understanding of the battle. Discussions will further focus on the significance of the wider events around the battle, its regional implications, as well as the legacy of the battlefield.

Zimbabwe Futures 2030: Policy Priorities for Economic Expansion 28 February 2019 — 9:00AM TO 1:00PM Anonymous (not verified) 7 February 2019 Harare, Zimbabwe

This roundtable draws on current best practice and senior level expertise to identify policy options for long term economic expansion in Zimbabwe and pathways for inclusive development.

Participants discuss the necessary policies and business strategies to enable and support the effective implementation of the Transitional Stabilization Programme and longer term national development plans.

The discussions highlight requisite conditions for a business-driven and inclusive process towards Zimbabwe’s long-term economic recovery.

This event was held in partnership with the Zimbabwe Business Club and Konrad Adenauer Stiftung.

South Africa’s 2019 Election: Polling Data and Party Prospects 13 March 2019 — 12:30PM TO 1:30PM Anonymous (not verified) 7 March 2019 Chatham House, London

On 8 May 2019, South Africans will vote in their sixth national election. Incumbent President Cyril Ramaphosa is leading his ANC party campaign, which promises inclusive economic growth and social transformation, including through a sustainable land reform programme. However, public frustrations with the party’s record of service delivery and government corruption after 25 years in power could threaten the ANC’s electoral dominance especially in urban areas.

At this meeting, Professor David Everatt, head of the Wits School of Governance and political pollster, will present polling data and discuss the prospects and strategies of the main parties and their leaders ahead of the May election.

Attendance at this event is by invitation only.

Zimbabwe Futures 2030: Sector Priorities for Policy Implementation 4 June 2019 — 9:00AM TO 5:15PM Anonymous (not verified) 21 June 2019 Harare, Zimbabwe

Zimbabwe Futures 2030: Policy Priorities for Industrialization, Agri-Business and Tourism 6 June 2019 — 9:30AM TO 1:15PM Anonymous (not verified) 21 June 2019 Bulawayo, Zimbabwe

Zimbabwe Futures 2030: A Vision for Inclusive Long-Term Economic Recovery 10 October 2019 — 10:00AM TO 12:15PM Anonymous (not verified) 5 September 2019 Harare, Zimbabwe

In its Vision 2030, the government of Zimbabwe committed itself to facilitating an open market and stable economy through strategies such as the Transitional Stabilization Programme (TSP) and new industrialization policy. The private sector is pivotal to these objectives and creating an environment conducive to inclusive and job-creating economic growth. Economic growth can only be achieved with a conducive policy environment and government support to underpin markets with provision of public goods, entrepreneurial incentives and protect contract enforcement and dispute resolution mechanisms.

This event will launch a new Chatham House Africa Programme publication on Zimbabwe’s Vision 2030. The paper is the culmination of an inclusive research process that has drawn on senior private sector expertise, civil society, academics, technocratic elements of government and other experts to develop policy recommendations that will support inclusive economic growth in Zimbabwe.

This event is held in partnership with the Zimbabwe Business Club and Konrad Adenauer Stiftung (KAS). It is supported by KAS and the Dulverton Trust.

Angola Forum 2021: Policy options to support economic recovery in Angola 7 October 2021 — 2:00PM TO 5:00PM Anonymous (not verified) 22 September 2021 Online

Speakers discuss policy options to support economic recovery in Angola as the country transitions away from a state-led oil economy to a private-sector-led growth model.

The government of Angola has made some progress on a range of policies targeting macroeconomic stability and structural reform. However, the country has been suffering from a recurring economic recession for six consecutive years, with the last positive annual GDP growth rate posted in 2015 at 0.9 per cent.

The national budget remains dependent on oil revenue, leaving the country highly exposed to volatile oil prices particularly during the COVID-19 pandemic. While revenues collapsed, increased spending was needed to respond to the health crisis and estimates of Angola’s debt spike range from 130 to 150 per cent of its GDP by the close of 2020.

At this virtual Angola Forum, speakers discuss policy options to support economic recovery in Angola as the country transitions away from a state-led oil economy to a private-sector-led growth model.

The Forum launches the English translation of the Angola Economic Report 2019-20 by the Centro de Estudos de Investigação (CEIC) of the Catholic University of Angola in partnership with the Konrad-Adenauer-Stiftung (KAS), and the findings of Afrobarometer’s first ever survey in Angola, Ovilongwa – Estudos de Opinião Pública, which interviewed 2,400 adult Angolans and sampled individual perceptions on democracy and economic reform in Angola.

This event will be held in English and Portuguese with simultaneous interpretation.

The Forum will also be broadcast live on the Africa Programme Facebook page.

South Africa’s ANC party policy conference 2022: Outcomes and prospects 10 August 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 4 August 2022 Online

Paul Mashatile, Treasurer-General of the African National Congress (ANC), discusses the outcomes of the 6th ANC Policy Conference 2022.

The African National Congress (ANC) recently concluded its 6th National Policy Conference in Johannesburg, in the year that the ANC has declared ‘The Year of Unity and Renewal to Defend and Advance South Africa’s Democratic Gains’. The conference was a precursor to the party’s 55th National Elective Conference to be held in December.

The conference has come less than a year after municipal polls in which the ANC garnered less than 50 per cent of votes, its lowest since 1994. Many believe internal factionalism is impeding party reform and hampering its ability to address unemployment and entrenched inequality.

At this webinar, Paul Mashatile, Treasurer-General of the ANC, will discuss the outcomes of the ANC Policy Conference 2022, including measures to accelerate inclusive growth, job creation and a just energy transition.

This event will also be broadcast live on the Chatham House Africa Programme’s Facebook page.

Angola forum 2022: Prospects for Angola's social and economic future 15 December 2022 — 1:00PM TO 4:30PM Anonymous (not verified) 28 November 2022 Online

At this online Angola forum, experts will discuss Angola’s social and economic future, and what to expect from 2023.

At this virtual Angola Forum, speakers will discuss Angola’s social and economic future and what to expect from 2023.

Angola experienced positive economic momentum in 2022 allowing it to exit its six-year recession, with the economy taking centre stage in the August national multiparty elections. Increased oil prices and high levels of production have driven Angola’s economic growth and improved macroeconomic conditions, as well as helping the country to reduce its public debt to 56.5 per cent of Gross Domestic Product (down from 79.7 per cent in 2021).

However, a global economic downturn in 2023, with increased inflation, means Angola’s re-elected MPLA government will need to focus on job creation, greater economic inclusivity and diversifying away from an oil-led economy. It will also require Angola to navigate its international partnerships more effectively in this era of heightened geopolitical rivalries.  

At this online Angola forum, experts will discuss Angola’s social and economic future and what to expect from 2023. Speakers will reflect on the social and economic trends seen in 2021-22 and explore election trends, human rights and international relations.

This Angola Forum is supported by the Konrad-Adenauer-Stiftung.

American democracy in 2022: Trump, insurrection, and midterm elections 31 October 2022 — 2:00PM TO 3:00PM Anonymous (not verified) 7 October 2022 Online

How much has Donald Trump changed US politics and democracy, and will Trump and ‘Trumpism’ be more or less significant in the years ahead?

America’s democracy is divided, polarized and fragmenting. Inequality and internal division have a long history. But Trump’s lasting influence on the Republican party, and politics more broadly, continues to leave a mark. Repeated denials of President Joe Biden’s 2020 election win, wrapped in claims of electoral fraud, have eroded faith in the democratic institutions.

The memories of 6 January are still fresh, reminding all of the dangers posed by such actions. All told, America’s democracy has taken a beating in recent years.

To help make sense of the events over recent years and consequences for the coming mid-terms, Peter Baker and Susan Glasser (authors of The Divider: Trump in the White House 2017–2021) walk through in detail how the American politics of today has been arrived at.

Key questions discussed include:

• What has been learned from the January 6 Committee?

• Is there a likelihood of a similar event in the future?

• When and how will Trump lose his influence over the Republican party? 

• What are the broader ramifications of the Trump era?

• What did the events of 6 January mean for America’s relationships globally?

 As with all Chatham House member events, questions from members drive the conversation.

Read the transcript. 

The road to COP27: In conversation with US Special Presidential Envoy for Climate John Kerry 27 October 2022 — 3:00PM TO 4:00PM Anonymous (not verified) 20 October 2022 Chatham House and Online

What will progress on climate change look like at COP27?

With global attention zeroing in on COP27, policymakers and world leaders will meet in Egypt to take the next step in the fight against the climate crisis. The planet is on course to warm well beyond 1.5°C and climate hazards are increasing our exposure to climate risk. Violent and unpredictable weather events increasingly leave devastation among communities, particularly in vulnerable countries.

At the same time, the ripple effects of the conflict in Ukraine will have wide-ranging economic, social and geopolitical consequences for years to come. Whilst some finance is being made available, more is needed to properly address the damage caused by climate change and fund the transition to net zero worldwide. These challenges have become more acute as the world grapples with a growing energy crisis, the war in Ukraine and a troubling economic outlook.

Joined by US Special Presidential Envoy for Climate John Kerry, the following questions are considered:

• Is ‘1.5 degrees’ still on track?

• How can countries better collaborate to move to net zero faster?

• How can we achieve progress on adaptation, climate finance, and loss and damage?

As with all members events, questions from the audience drive the conversation.

Read the transcript. 

The Director’s Annual Lecture 2023 10 January 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 17 November 2022 Chatham House and Online

Bronwen Maddox looks ahead to the challenges of the year and sets out Chatham House’s recommendations for change.

Read a transcript of the event

A lecture and discussion on the year ahead in international relations with Bronwen Maddox, director and chief executive of Chatham House.

Although Russia’s war on Ukraine rightly dominated headlines in 2022, other challenges also grew, the climate became warmer, US/China competition intensified, deglobalization became a much-analysed theme, and the global economy suffered significant blows.

The UK has its third prime minister in less than one year as it grapples with its changing place in the world. And the world is still living in the shadow of COVID-19 and what the pandemic revealed about strengths and vulnerabilities, global inequity, and North/South divides.

This event examines how the forces that shaped 2022 may manifest in 2023, and what that means for progress in international relations:

• What will progress look like on the climate agenda?
• How will the new US Congress reposition America’s role in the world?
• What does the North/South divergence on Russia’s war in Ukraine tell us about shared values and prospects for working together?
• After a turbulent year, how will the UK recover its standing in Europe and beyond?

Nigeria's 2023 elections: Security, economic and foreign policy imperatives 5 December 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 23 November 2022 Chatham House and Online

Bola Ahmed Tinubu, presidential candidate for the All-Progressives Congress, discusses his vision and recently-unveiled manifesto for ‘renewing hope’ in Nigeria.

Nigeria is scheduled to hold presidential and national assembly elections on 25 February 2023 as well as governorship and other subnational elections on 11 March 2023.

The elections will end President Muhammadu Buhari’s two terms in office since his election in 2015 and will mark the first time that he is not engaging in a presidential poll since Nigeria’s transition to civilian rule in 1999 – an important marker in Nigeria’s trajectory of democratic consolidation.

Nigeria’s recently enacted Electoral Act has contributed to improved hope around the election process, reflected in the addition of 12.29 million new voters in Nigeria’s voter registration exercise across the federation’s 36 states and 1,491 constituencies.

Yet Nigeria stands at a critical juncture, having suffered from two recessions in the past six years, unprecedented levels of food insecurity, persistent fuel scarcity and high levels of crude oil theft.

Civic fatigue also remains an important challenge and President Muhammadu Buhari’s three main policy pillars of security, economy and corruption continue to be defining issues for citizens.

At this event, Bola Ahmed Tinubu, presidential candidate for the All-Progressives Congress, discusses his vision and recently unveiled manifesto for ‘renewing hope’ in Nigeria including his policy proposals for economic reform and revival and how to deliver secure and inclusive job opportunities for Nigerian citizens.

Download a transcript

This event is a members and Africa programme event and is part of a series of events and outputs examining Nigeria’s 2023 elections and political developments.

As with all Chatham House member events, questions from members drive the conversation.

Ten conflicts to watch in 2023 11 January 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 8 December 2022 Chatham House and Online

This event examines the most dangerous wars and crises through the lens of the International Crisis Group’s flagship annual report ‘10 Conflicts to watch in 2023’.

Each year, International Crisis Group compiles a list of the ten conflicts to watch that examines key conflicts across the globe. Please join us for this event at which Dr Comfort Ero, International Crisis Group president and CEO, discusses today’s and tomorrow’s most impactful wars and crises.

Key questions to consider include:

• What far-reaching repercussions and knock-on effects of Russia’s war on Ukraine will have for Europe and the rest of the world?

• Which crises beyond Ukraine warrant collective attention in the year ahead?

• How do rising tensions among major powers impact multilateral efforts to resolve these conflicts, impede progress on global challenges and impact institutions working on crisis prevention?

As with all members events, questions from the audience drive the conversation.

Read the transcript. 

I’m often asked if I miss working in the House of Commons. Of course I do; it’s one of the most amazing places in the world and remains the cockpit of our nation.There are obviously days I miss it more than others, usually around the big national moments. Whatever your view of Kim Leadbeater’s private member’s bill—the Terminally Ill Adults (End of Life) Bill—its second reading this month will be one of those big moments.Kim is a friend of mine, and we spoke before she decided to put her bill forward after it topped the private members’ ballot at the start of the new parliament. My advice was to proceed with great care, to remember that this will take over your career in many ways, and to read the report produced earlier this year by the Health and Social Care Committee, which I chaired, on the subject of assisted dying/assisted...

Europe's strategic choices 2021 4 November 2021 TO 5 November 2021 — 8:00AM TO 5:30PM Anonymous (not verified) 21 September 2021 Ritz Carlton Berlin

The 2021 conference will consider how Europe can navigate its political, economic and security challenges, in the context of the lasting effects of the coronavirus pandemic and an increasingly competitive geopolitical environment.

Registration is a two step process and you will receive a link to register on the conference virtually in advance. Please email if you wish to attend in-person.

The Eighth Annual Europe’s Strategic Choices conference, jointly developed and hosted by Chatham House, the Institute for Security Policy at the University of Kiel and the Konrad-Adenauer-Stiftung, aims to understand the complex set of challenges facing Europe in the areas of security, economic competitiveness, trade, technology, and global influence.

Set against the backdrop of a Europe emerging gradually from the COVID-19 pandemic, this annual forum brings together policymakers, and representatives from business, civil society and academia, to explore how European countries can best respond, individually and collectively to their common challenges in an increasingly competitive geopolitical environment.

The conference will be hosted in hybrid format to enable speakers and participants to join in person and allow others to engage virtually via the Conference Plus digital platform. This format ensures we can connect with a geographically diverse audience whilst incorporating important elements of in person engagement in accordance with German Federal government guidelines.

New research on 21st-century conflict 25 April 2022 — 5:00PM TO 6:00PM Anonymous (not verified) 11 April 2022 Online

This International Affairs webinar shares research on US special operations, urban warfare, and digital activism in recent conflicts.

Given the ongoing Russian invasion of Ukraine, and continuing conflicts in Myanmar, Yemen, and other countries, it is important to understand the changing nature of conflict in the 21st century.

In this webinar, authors from the March 2022 issue of International Affairs share research on the transformation of Western special forces, the impact of army size in urban warfare, and the use of social media and online activism in war.

The speakers in this event drew on the following research:

• US Special Forces transformation: post-Fordism and the limits of networked warfare (https://doi.org/10.1093/ia/iiab213)
• Urban insurgency in the twenty-first century: smaller militaries and increased conflict in cities (https://doi.org/10.1093/ia/iiac007)
• Diasporas as cyberwarriors: infopolitics, participatory warfare and the 2020 Karabakh war (https://doi.org/10.1093/ia/iiac015)

International Affairs was started at Chatham House in 1922 to communicate research to members who could not attend in person. Over the past 100 years, it has transformed into a journal that publishes academically rigorous and policy-relevant research. It is published for Chatham House by Oxford University Press. Read the latest issue here.

Polish-British Belvedere Forum 2022 7 July 2022 TO 8 July 2022 — 12:00PM TO 4:00PM Anonymous (not verified) 13 June 2022 Chatham House and Online

The Belvedere Forum is a leading annual British and Polish dialogue that seeks to strengthen the extensive social, economic and political partnership between the two countries.

Please note this event has reached full in-person capacity. You are welcome to join virtually via the Zoom link: https://chathamhouse.zoom.us/webinar/register/WN_QFwXsXb0RoSt-1ywkuPjfQ  

The video on this page is of the opening remarks from the Belvedere Forum, with addresses from Sir Robin Niblett KCMG, Dr Sławomir Dębski, Prof Zdzisław Krasnodębski, Sir Malcolm Rifkind KCMG QC, Ambassador Anna Clunes CMG OBE, Lord (Tariq) Ahmad of Wimbledon, Min Marcin Przydacz, and Ambassador Piotr Wilczek.

This and other session videos are available to watch on the Belvedere Forum 2022 playlist on YouTube. Photos by Mateusz Jozwiak, Zuzanna Nowak/PISM.

The Belvedere Forum is a leading annual British and Polish bilateral dialogue bringing together a diverse group of actors from civil society, politics, business, academia and NGOs.

It seeks to strengthen and deepen the extensive partnership between the two countries by exploring political, economic, social and cultural issues through debate and discussion.

The forum is an annual event alternating between the UK and Poland. Originally created in 2017 by the governments of the UK and Poland, the forum is now jointly organized by Chatham House and the Polish Institute of International Affairs (PISM) in Warsaw.

The forum brings together a diverse group of actors to debate and discuss not only current British-Polish relations, but also the British and Polish responses to key European and global challenges.

Issues to watch in 2023 The World Today mhiggins.drupal 29 November 2022

From nuclear proliferation to African debt, here are the issues six of our expert contributors expect to make the news in the year ahead.

Europe’s energy outlook

Mike Bradshaw, Professor of Global Energy, Warwick Business School

There is cautious optimism that Europe will endure this winter without an energy crisis. Gas prices have fallen, storage is 95 per cent full, and the autumn was mild. High summer gas prices cut industrial demand but domestic heating demand will be critical over the winter. Already, France’s problematic nuclear fleet and lower hydroelectric output mean Europe is using more gas to generate power. 

Russian pipeline gas supply to southern Europe has fallen by 55 per cent. While Asian demand has fallen, Europe has still paid record prices to secure additional liquefied natural gas (LNG), largely from America but also Russia. European demand for LNG this winter will push prices up, and these will rise even higher if China relaxes its Zero-Covid policy and demand recovers. However, with luck, Europe will avoid power cuts in early 2023. The problem is next winter. With less Russian pipeline gas and a tight LNG market, 90 per cent winter gas storage levels will be much harder to achieve. 

NATO’s resurgence

Alice Billon-Galland, Research Fellow, Europe Programme, Chatham House and one of 14 NATO Young Leaders

In response to Russia’s invasion of Ukraine, NATO adopted a new strategic concept. Member states will reinforce NATO battlegroups and bolster higher readiness forces from 40,000 troops to more than 300,000, while striving to avoid escalation with Russia. Turkey’s attempts to block Sweden and Finland’s NATO membership will preoccupy Jens Stoltenberg, the Secretary-General, until he leaves his post next autumn.

Expect arguments on defence spending in the run-up to the July summit in Vilnius. Although only nine of its 30 members are expected to meet the 2 per cent spending target, the debate is moving towards 3 per cent, in part to reduce dependency on American assets and hedge against the uncertainty of the 2024 US presidential election. Infrastructure vulnerabilities, such as the Nord Stream pipeline sabotage in the Baltic, will also be a focus. Otherwise, NATO ’s eyes will be on China: from its relations with Russia to the threat of cyberattacks.

Universal health reforms

Robert Yates, Executive Director, Centre for Universal Health, Chatham House

In response to the perma-crisis experienced by many populations this past year, some leaders are launching or extending universal health reforms. New left-wing leaders in Chile, Colombia and Brazil have promised to rebuild their publicly financed universal health systems. In Brazil, newly elected president Lula da Silva has pledged to increase public health spending and improve access to medicines. It is hoped Malaysia’s new coalition will carry forward its predecessor’s pledge to raise health spending to 5 per cent of GDP by 2027 to provide a universal package of free health services.

In September, world leaders will discuss universal health coverage at the UN General Assembly. There, Chatham House will publish its Commission for Universal Health report, identifying countries in which crises may trigger new national health programmes. Might this be when a US presidential candidate announces a platform to create a publicly financed health system?

Weapons of mass destruction

Patricia Lewis, Director of the International Security Programme, Chatham House

Since its illegal invasion of Ukraine, Russia has attacked civil nuclear power stations, falsely accused Ukraine of possessing bioweapons and radiological bombs, and threatened to use nuclear weapons. In contrast, NATO has instead demonstrated that deterrence can be highly effective with conventional weaponry. In the coming year, the Kremlin’s nuclear brinkmanship will still be a focus. Washington will try to restart bilateral nuclear negotiations with Moscow and similarly try to engage Beijing.

Following the failure of the nuclear Non-Proliferation Treaty Review Conference to reach consensus in August, the next review cycle will start by looking at strengthening the process. Iran’s nuclear capabilities remain a concern, and North Korea’s nuclear weapons programme is a growing threat. So, we are left with a question: will 2023 be the year of  nuclear conflict or the year when states get busy again on non-proliferation and disarmament?  

Africa’s mounting debt

Joseph Asunka, Chief Executive Officer, Afrobarometer

Inflation is at historic highs in several African economies. Meanwhile, many African countries including Nigeria, Zimbabwe and Democratic Republic of Congo will hold  elections in 2023, driving up public spending, increasing inflationary pressures and exacerbating poverty. According to Afrobarometer data, the proportion of Africans experiencing high levels of poverty has increased from 19 per cent in 2014/2015 to  26 per cent in 2021/2022.

Worse still, many of those countries holding elections are either, like Zimbabwe, in debt distress – that is unable to honour their obligations to creditors – or at high risk of debt distress, like Nigeria. This makes the elections in Zimbabwe and Nigeria critical. The expiration of the World Bank/IMF-backed debt service suspension initiative in 2021 has only amplified this risk. What are viable policy options to tackle this dire economic predicament? A debt service moratorium, debt cancellation and serious attention to fiscal discipline.

Feminist foreign policy

Daniela Philipson García, Co-founder of Internacional Feminista, and a PhD candidate, Monash University

Feminist Foreign Policy (FFP) is under threat. The war in Ukraine led to strengthened military budgets and alliances at odds with FFP’s human security and peace-centred approaches. Sweden’s new right-wing government reversed its FFP. In Mexico, the first Global South country to adopt an FFP, Congress has voted to expand the military’s role to curb cartel-related violence, in contradiction of its FFP. The second anniversary of the US withdrawal from Afghanistan will be a moment to assess how foreign policy, diplomacy and women’s and girls’ rights have been affected globally. 

There is hope. Germany, whose coalition government adopted an FFP in 2021, is to publish more guidelines in the spring. The governments of Colombia and Chile have announced their own FFPs. Colombia’s first National Action Plan on Women, Peace and Security, to be announced at the UN General Assembly in September, is expected to set a standard for a region submerged in violence. 

Virtual breakfast: The state of the EU in 2023 3 May 2023 — 8:30AM TO 9:30AM Anonymous (not verified) 5 April 2023 Online

In this breakfast discussion, we will explore the current state of play in the EU with one the most prominent experts on European politics.

While the European Union has come together in its response to the invasion of Ukraine, significant divisions remain on other issues. East-West tensions remain high and troublesome German-French relations are hampering the bloc’s traditional engine of integration.
 
Furthermore, the EU is pushing through legislation at breakneck speed, including in its attempts to kickstart green industrial policy with its responses to the American Inflation Reduction Act. At the same time, the main players within the EU continue to disagree on what the bloc’s fiscal rules should look like.

• What are the implications of the recent wave of protests in France against President Macron’s pension reforms?
• What is the outlook of EU-UK relations following the successful completion of the Windsor Framework?
• Where are the fiscal rules likely to land and when will they be back in place?
• Are we seeing the emergence of a new Central and Eastern European power bloc within the EU?

In short, despite having avoided an energy crisis over the winter, the EU continues to face significant challenges. In this breakfast event, we will explore the current state of play in the EU with one of the most prominent experts on European politics.

Fibroblast activation protein (FAP) is abundantly expressed in the stroma of most human solid tumors. Clinical-stage radiolabeled FAP ligands are increasingly used as tools for the detection of various cancer lesions. To unleash the full therapeutic potential of FAP-targeting agents, ligands need to remain at the tumor site for several days after administration. We recently described the discovery of OncoFAP, a high-affinity small organic ligand of FAP with a rapid accumulation in tumors and low uptake in healthy tissues in cancer patients. Trimerization of OncoFAP provided a derivative (named TriOncoFAP, or OncoFAP-23) with improved FAP affinity. In this work, we evaluated the tissue biodistribution profile and the therapeutic performance of OncoFAP-23 in tumor-bearing mice. Methods: OncoFAP-23 was radiolabeled with the theranostic radionuclide ¹⁷⁷Lu. Preclinical experiments were conducted on mice bearing SK-RC-52.hFAP (BALB/c nude mice) or CT-26.hFAP (BALB/c mice) tumors. ¹⁷⁷Lu-OncoFAP and ¹⁷⁷Lu-FAP-2286 were included in the biodistribution study as controls. Toxicologic evaluation was performed on Wistar rats and CD1 mice by injecting high doses of OncoFAP-23 or its cold-labeled counterpart, respectively. Results: ¹⁷⁷Lu-OncoFAP-23 emerged for its best-in-class biodistribution profile, high and prolonged tumor uptake (i.e., ~16 percentage injected dose/g at 96 h), and low accumulation in healthy organs, which correlates well with its potent single-agent anticancer activity at low levels of administered radioactivity. Combination treatment with the tumor-targeted interleukin 2 (L19-IL2, a clinical-stage immunocytokine) further expands the therapeutic window of ¹⁷⁷Lu-OncoFAP-23 by potentiating its in vivo antitumor activity. Proteomics studies revealed a potent tumor-directed immune response on treatment with the combination. OncoFAP-23 and ^natLu-OncoFAP-23 exhibited a favorable toxicologic profile, without showing any side effects or signs of toxicity. Conclusion: OncoFAP-23 presents enhanced tumor uptake and tumor retention and low accumulation in healthy organs, findings that correspond to a strongly improved in vivo antitumor efficacy. The data presented in this work support the clinical development of ¹⁷⁷Lu-OncoFAP-23 for the treatment of FAP-positive solid tumors.

Our purpose was to prospectively assess the distribution of NETPET scores in well-differentiated (WD) grade 2 and 3 gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and to determine the impact of the NETPET score on clinical management. Methods: This single-arm, institutional ethics review board–approved prospective study included 40 patients with histologically proven WD GEP NETs. ⁶⁸Ga-DOTATATE PET and ¹⁸F-FDG PET were performed within 21 d of each other. NETPET scores were evaluated qualitatively by 2 reviewers, with up to 10 marker lesions selected for each patient. The quantitative parameters that were evaluated included marker lesion SUV_max for each tracer; ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios; functional tumor volume (FTV) and metabolic tumor volume (MTV) on ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET, respectively; and FTV/MTV ratios. The treatment plan before and after ¹⁸F-FDG PET was recorded. Results: There were 22 men and 18 women (mean age, 60.8 y) with grade 2 (n = 24) or grade 3 (n = 16) tumors and a mean Ki-67 index of 16.1%. NETPET scores of P0, P1, P2A, P2B, P3B, P4B, and P5 were documented in 2 (5%), 5 (12.5%), 5 (12.5%) 20 (50%), 2 (5%), 4 (10%), and 2 (5%) patients, respectively. No association was found between the SUV_max of target lesions on ⁶⁸Ga-DOTATATE and the SUV_max of target lesions on ¹⁸F-FDG PET (P = 0.505). ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios were significantly lower for patients with low (P1–P2) primary NETPET scores than for those with high (P3–P5) primary NETPET scores (mean ± SD, 0.20 ± 0.13 and 1.68 ± 1.44, respectively; P < 0.001). MTV on ¹⁸F-FDG PET was significantly lower for low primary NETPET scores than for high ones (mean ± SD, 464 ± 601 cm³ and 66 ± 114 cm³, respectively; P = 0.005). A change in the type of management was observed in 42.5% of patients after ¹⁸F-FDG PET, with the most common being a change from systemic therapy to peptide receptor radionuclide therapy and from debulking surgery to systemic therapy. Conclusion: There was a heterogeneous distribution of NETPET scores in patients with WD grade 2 and 3 GEP NETs, with more than 1 in 5 patients having a high NETPET score and a frequent change in management after ¹⁸F-FDG PET. Quantitative parameters including ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios in target lesions and FTV/MTV ratios can discriminate between patients with high and low NETPET scores.

Understanding which patients with human epidermal growth factor receptor 2 (HER2)–negative or –low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on ⁸⁹Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. Methods: In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included. Metastasis HER2 status was determined by immunohistochemistry and in situ hybridization.⁸⁹Zr-trastuzumab uptake was quantified as SUV_max and SUV_mean. HER2 immunohistochemistry was related to the quantitative ⁸⁹Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, uptake heterogeneity, and qualitative scan evaluation. A prediction algorithm for HER2 immunohistochemistry positivity based on uptake was developed. Results: In 200 patients, ⁸⁹Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUV_max of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; P < 0.001). High uptake exceeding 14.6 (90th percentile) was observed in one third of patients with a HER2-negative or -low metastasis biopsy. The algorithm performed best when lesion site and size were incorporated (area under the curve, 0.86; 95% CI, 0.79–0.93). Conclusion: HER2 PET had good diagnostic performance in MBC, showing considerable whole-body HER2 heterogeneity and uptake above background in HER2-negative and -low MBC. This provides novel insights into HER2-negative and -low MBC compared with standard HER2 immunohistochemistry on a single biopsy.