After undergoing surgery in late June to repair a torn left labrum in his left shoulder that required nine anchors to be inserted to keep everything in place, Zack Cozart is healthy and looking for a bounce-back season with the Angels.

The Angels announced their Minor League coaching staffs on Saturday, including former Major League catcher Lou Marson being named the new manager of Triple-A Salt Lake and former big leaguer David Newhan as the new skipper at Double-A Birmingham.

The Angels have a new closer in Cody Allen and there isn't any manager in baseball who knows him better than Indians skipper Terry Francona.

VOLUME 279 (2004) PAGES 33438–33446For Fig. 1B, the second, third, and fifth panels were mistakenly duplicated during article preparation as no yeast colonies were observed in these conditions. The corrected images are presented in the revised Fig. 1B. This correction does not affect the results or conclusions of the work. The authors apologize for the error.jbc;295/50/17382/F1F1F1Figure 1B.

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.

Higher Education in South Africa: Demands for Inclusion and the Challenges of Reform 17 October 2018 — 5:00PM TO 6:00PM Anonymous (not verified) 18 September 2018 Chatham House, London

South Africa After the Elections: Balancing Domestic and International Policy Priorities 16 May 2019 — 1:30PM TO 2:30PM Anonymous (not verified) 9 May 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

The government that emerges from the 8 May election in South Africa faces immediate domestic and international foreign policy demands. Attracting Foreign Direct Investment to stimulate job growth, accelerating anti-corruption and good governance efforts are at the forefront of the new government’s agenda.

International ambitions will be upgraded such as UN security council reform, maximizing South Africa’s G20, BRICS and IBSA membership and preparing for South Africa’s chairmanship of the African Union (AU) in 2020.

At this meeting, the speakers – Moeletsi Mbeki, deputy chairman of SAIIA and author with Nobantu Mbeki of A Manifesto for Social Change: How to Save South Africa, and Elizabeth Sidiropoulos, chief executive of SAIIA and currently co-editing a volume on A South African Foreign Policy for the 2020s which will be published in 2019 – will reflect on the election and discuss the new government’s domestic and international policy agenda. The meeting will be chaired by Ann Grant, former British High Commissioner to South Africa (2000-05) with past experience working for Oxfam, Standard Chartered Bank and Tullow Oil.

Hope, Peace and Reconciliation: Pope Francis in Mozambique Expert comment sysadmin 4 September 2019

A papal visit will highlight the importance of the recently signed peace agreement between the government and opposition.

Pope Francis’ visit to Mozambique on 4–6 September comes at a critical political moment. The theme for the papal Africa trip (which also includes Madagascar and Mauritius) is ‘pilgrim of hope, peace and reconciliation’. This is especially relevant for Mozambique, as this is the first week of the official campaign for Mozambique’s sixth national elections on 15 October.

It is also the one-month anniversary of the Maputo Accords for Peace and Reconciliation between the government and the armed opposition, RENAMO (and the fifth anniversary of the previous such agreement in 2014).

What is unusual is that the pope accepted to visit Mozambique just after a peace accord and in the run-up to national elections. Something similar has happened only once, when Pope John Paul II visited Angola in June 1992 (following the Bicesse Accords) prior to the country’s first ever national elections in September. Unfortunately Pope John Paul’s preaching of reconciliation and pluralism failed and civil war resumed some months later, following rejection of the preliminary election results. Angola’s civil war only finally ended a decade later in 2002.

The last papal visit to Mozambique was also by Pope John Paul II in 1988, when civil war was still ongoing, and the country was still a single party state. Despite the war, massive congregations attended and RENAMO reached local ceasefires and agreements to maintain electricity supply to honour the visit. Some of the seeds for the Rome peace process were laid during this trip – especially as it also represented a formal reconciliation of FRELIMO, the ruling party, with the Catholic Church.

This papal visit to Mozambique is equally anticipated, as was highlighted several times during speeches at the 6 August peace agreement signing in Maputo. When I was in Maputo last month, sales of papal-pictured capulanas (a Mozambican sarong) were brisk and Mozambican television carried countdown clocks on many programmes for the touchdown of Pope Francis on national soil.

The Catholic Church has played an instrumental role in promoting peace in Mozambique over the years. The 1977–92 civil war ended through negotiations hosted at the Sant’ Egidio lay community in Rome, and the current Archbishop of Bologna, Dom Matteo Zuppi (who led the Sant’ Egido negotiations in 1992 and is soon to be made a cardinal) was an official witness to 6 August accords signing.

When targeted armed conflict resumed in 2013, faith groups once more re-engaged and in 2016 Sant’ Egidio once more co-led mediation efforts, less successfully than in 1991–92. Sant’ Egidio (including during a presidential visit to Rome in July) contributed to convincing the Vatican that this papal visit should occur before the October elections.

President Filipe Nyusi anxiously wanted this visit to occur before the elections. He is seeking re-election for his second and final term and a papal visit should help win some votes. His party, FRELIMO, is also worried about securing a majority in the national assembly, as it has been weakened by patchy delivery of services and ongoing high-level corruption scandals.

This year, President Nyusi’s priorities have been to show that he can attract international investment (such as Andarko’s recently announced final investment decision on its gas project), a peace agreement with RENAMO (the August agreements) and a papal visit, so a successful trip would complete his goals.

The pope’s ‘hope, peace and reconciliation’ message of his visit is important. Twice previously, the FRELIMO-led government and RENAMO have reached definitive agreements, in Rome (1992) and Maputo (2014), but failed to fully end bloodshed. This new August 2019 agreement is the third attempt, and if it is to last, it will require political goodwill, compromise and an acceptance of more inclusive national politics by both parties.

There are two immediate threats to this agreement. The first is the forthcoming 15 October elections and their conduct could make or break it. Accepting reconciliation and greater pluralism underpins this agreement, but RENAMO expects to increase its share of the parliamentary vote and win a majority in some provinces (and therefore indirectly elect their choice for governor).

A second threat is the ‘Military Junta’, a RENAMO splinter group that claims to be 500 strong, but probably accounts for 80 armed persons. It rejects the 6 August agreement and warns that it could disrupt the elections. This group has asked for mediation, and hopefully can be accommodated in a side deal to the main one agreed in August, which already provides for the reintegration of over 5,000 RENAMO supporters and combatants.

A recent Chatham House research paper on elite bargains in Mozambique concluded that the October elections will be the first immediate test of the August agreement. If the elections pass without significant electoral manipulation or violence and this August deal sticks on the third attempt, the domestic focus should then move onto poverty reduction, combating inequality, education and solving the new security crisis with Islamic militants in Cabo Delgado province.

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.

COVID-19 in South Africa: Leadership, Resilience and Inequality Expert comment sysadmin 7 May 2020

In a world looking for leadership, South Africa’s president Cyril Ramaphosa has been remarkable. One year after he carried the time-worn ANC through a national election, South Africans are crying out for more.

In the COVID-19 crisis so far, Cyril Ramaphosa has been widely praised for displaying the decisive leadership so many hoped for when they cast their ballot for him in May 2019. Buttressed by others such as health minister Dr Zweli Mkhize, and on a simple objective to prevent transmission, South Africa has been a lesson to the world. Act fast. Act hard.

Former president Thabo Mbeki’s disastrous response to the HIV crisis cast a long shadow over his legacy, and Ramaphosa has taken note. South Africa has had one of the tightest lockdowns in the world. No exercise. No cigarettes. No alcohol.

The lockdown was imposed when the country had only around 1,000 recorded cases and just two deaths. As a result, transmission from returning travellers has not yet led to an exponential infection rate within the community. The government’s swift reaction has bought much needed time with the peak now seemingly delayed to September or October.

Continental and national leadership

Ramaphosa has also emerged as a key focal point for Africa-wide responses. As current chair of the African Union (AU) he leads the continental engagement with the World Health Organization (WHO), and the various international finance institutions, while South African officials are working with the AU and the United Nations Economic Commission for Africa (UNECA) on a push for African debt restructuring.

He has also been active in trouble shooting to unlock external assistance to the continent, including from China and Russia. Appointing special envoys is typical of his boardroom-honed leadership style.

International and regional partnerships are vital for resilience and the arrival of 217 Cuban doctors to South Africa is strongly reminiscent of the liberationist solidarity of the Cold War era. And regional economies remain dependent on South Africa to protect their own vulnerable citizens. Following the 2008 financial crisis, it was South Africa’s regional trading relationships that remained robust, while trade with its main global partners in China and the US dropped.

Despite the plaudits, Ramaphosa remains vulnerable to challenge at home, notably around his failure to stimulate South Africa’s moribund economy. On the eve of lockdown, Moody’s joined its peers Standard and Poor’s and Fitch in giving South Africa a below investment grade credit rating. The move was a long time coming. Long mooted economic reforms were slow to materialise, and South Africa had fallen into recession.

Ramaphosa depends on a small core of close advisors and allies, initially united in apparent opposition to the kleptocratic rule of President Jacob Zuma and the deep patronage networks he created within both the party and the state. But this allegiance is being tested by economic reality. Support within the party was already drifting prior to the crisis.

Disagreements are not just technocratic – there are big ideological questions in play around the role of the state in the economy, the level of intervention, and its affordability, with key government figures sceptical of rapid market reforms. Energy minister and former union stalwart Gwede Mantashe is wary of job losses, and minister of public enterprises Pravin Gordhan protective of state-owned enterprises (SOEs). Before coronavirus hit, Ramaphosa seemed content to allow these policy disputes to play themselves out with little decisive intervention.

Slow progress on reform, against worsening economic performance, left Ramaphosa and his allies exposed. In January the president missed the UK’s African Investment Summit in order to assert control over a party meeting at which it was expected his detractors would seek to remove Gordhan.

COVID-19 has sharpened thinking

As the independently assertive - and eminently quotable - pro-market reformist finance minister Tito Mboweni stated, ‘you can’t eat ideology’. Accelerated reform and restructuring is required if the government turns to the International Monetary Fund (IMF) for assistance.

For the first time, Gordhan has been forced to deny a bailout to beleaguered state airline South African Airways (SAA), and the government’s lockdown bailout of R500 billion has been applauded by business. Much like the fiscal stimulus and recovery plan of 2018, it relies on smart spending, targeting sectors with high multiplier effects. It also includes significant reserve bank loans.

But it has been criticised for not doing enough to help the most vulnerable. There is considerable fear of what could happen when the virus takes hold in South Africa’s townships and informal settlements where social distancing is almost impossible, basic toilet facilities are shared, and HIV and TB rates high.

There are mounting concerns of the humanitarian cost of a prolonged lockdown, and the government has been faster than others in implementing a tiered lockdown system, trying to get people back to work and keep the economy afloat.

South Africa has been criticized by the UN for the use of lethal force by security forces in enforcing lockdown and, in a society plagued by corruption, there are fears legislation to stop the spread of false information could be used to restrict legitimate reporting on the virus response or other issues.

COVID-19 shines a spotlight on societies’ fault-lines worldwide. South Africa is often touted as having one of the highest levels of inequality in the world but, in a globalized economy, these divisions are international as much as they are local.

Resilience comes from within, but also depends on regional and global trading and financial systems. South Africans and international partners have long recognised Ramaphosa’s leadership qualities as an impressive voice for the global south.

But he must also be an advocate for South Africa’s poor. This crisis could accelerate implementation of his landmark pro-poor National Health Insurance and Universal Health Care programmes. Or the hit of COVID-19 on top of South Africa’s existing economic woes could see them derailed entirely. Ramaphosa must push through economic reforms at the same time as managing COVID-19 and rebuilding trust in his government.

Mozambique’s Peace and National Reconciliation Agreement: One Year On 6 August 2020 — 2:30PM TO 4:30PM Anonymous (not verified) 29 July 2020 Online

August 6, 2020 marks one year since the Peace and National Reconciliation Agreement was signed in Maputo. The agreement, signed by the President of Mozambique Filipe Nyusi and RENAMO leader Ossufo Momade, and witnessed by regional and international political and religious leaders, ended the return to conflict that started in 2013.

It also paved the way for Mozambique’s national elections in October 2019. Since the agreement, the Mozambique Liberation Front (FRELIMO) won a landslide victory in the elections, weakening RENAMO, and a splinter group has conducted targeted armed violence in Manica and Sofala provinces. Yet, the disarmament, demobilization, and reintegration (DDR) process has made progress.

At this event, senior figures reflect on the peace agreement and the key factors of its success. The event also draws upon insights from the authors of recent publications on the latest peace agreement in the context of longer term trends of democratization and peace-building in Mozambique.

A Chatham House Africa Programme research paper published in August 2019, Prospects for a Sustainable Elite Bargain in Mozambique: Third Time Lucky?, examined how the deal was achieved. The Portuguese version includes the full text of the peace accord. Read the research paper in Portuguese or English here.

Zimbabwe’s Economic Governance and Regional Integration 17 November 2020 — 12:00PM TO 1:30PM Anonymous (not verified) 6 November 2020 Online

Panellists discuss policy and governance for long-term economic prosperity in Zimbabwe, reflecting on the role of institutional change and regional integration in the context of the shocks caused by the coronavirus pandemic.

At this virtual event, panellists and participants will discuss policy and governance for long-term economic prosperity in Zimbabwe, reflecting on the role of institutional change and regional integration.

The government of Zimbabwe has emphasized its commitment to economic reform and its ambition to achieve upper-middle-income status by 2030, but there are considerable challenges to overcome.

The COVID-19 pandemic has exacerbated existing economic fragility. Improving the business climate to attract international private-sector investment will be contingent on clear, consistent and coherent policy and implementation, including targeting abuse and corruption.

Zimbabwe has, in recent years, successfully strengthened its regional trade integration, although some trade frictions remain. This is an important factor not only for catalysing economic growth in Zimbabwe, but for supporting regional prosperity and post-COVID recovery.

This webinar is the second in a series of events held in partnership with the Konrad Adenauer Stiftung on Zimbabwe’s economic reform and recovery.

Read a meeting summary

This event will also be broadcast live on the Africa Programme Facebook page.

South Africa’s foreign policy: Reflections on the United Nations Security Council and the African Union 20 January 2021 — 2:00PM TO 3:00PM Anonymous (not verified) 8 January 2021 Online

HE Dr Naledi Pandor, South Africa’s Minister of International Relations and Cooperation, discusses South Africa’s role in pursuing its regional and global goals.

To receive joining instructions, please finalise your registration by clicking the link below. Once you have registered you will receive a confirmation email from Zoom, which will include the unique joining link you will need to attend.

In 2019-2020, South Africa served its third term as a non-permanent member of the UN Security Council, seeking to strengthen its role as a bridge-builder and further justify a more permanent role for the country and continent on the body.

In February 2021, South Africa will also conclude its time as Chair of the African Union, having used its tenure to promote peace and security issues, including closer cooperation with the UNSC, and advance regional economic integration.

South Africa took up these roles at a time of global and regional upheaval. As COVID-19 tested countries’ commitment to cooperation over isolation, South Africa coordinated regional responses to address the challenges of stressed public health systems, vaccine strategies, and economic stimulus and debt support across Africa.

Its leadership has been further tested by ongoing and emerging insecurity in the Sahel, and in Cabo Delgado in neighbouring Mozambique. The crux of its regional strategy remains squaring the circle between promoting regional economic cooperation while protecting its own domestic economic priorities.

At this event, HE Dr Naledi Pandor, Minister of International Relations and Cooperation of the Republic of South Africa, reflects on the country’s two years on the UNSC and one year of chairing the AU, and discuss South Africa’s role in pursuing regional and global goals.

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

Read event transcript. 

Inclusion, agency and influence: The role of women in Zimbabwe’s economy 8 July 2021 — 3:00PM TO 4:30PM Anonymous (not verified) 2 July 2021 Online

Speakers discuss the changing role of women in Zimbabwe’s economic structures and the priorities for promoting greater economic inclusion, agency and influence of women.

Zimbabwe’s National Development Strategy of 2021-2025 highlights the importance of gender sensitivity in policymaking and of women’s economic participation in attaining the government’s Vision 2030.

However, women have been among the worst affected groups by the devastating effects that COVID-19 has had on Zimbabwe’s already floundering economy, which has exacerbated the challenges they face in economic life, such as access to credit, financial services and social security.

Leveraging existing structures such as women’s groups, micro-finance facilities, education and training, and national gender mechanisms, as well as supporting wider financial and digital inclusion in Zimbabwe, is central for the country’s sustained economic recovery.

This event also focuses on the differing impacts of COVID-19 on women’s economic activities across various sectors, as well as along rural-urban and formal-informal economy lines.

Read a meeting summary

This webinar is part of a series of events in partnership with the Konrad Adenauer Stiftung on Zimbabwe’s economic recovery and reform.

This event 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.

Expanding and enhancing the global cyber workforce 17 November 2022 — 5:00PM TO 6:00PM Anonymous (not verified) 5 October 2022 Chatham House and Online

How can we address the cybersecurity workforce shortage and skills gap?

Accelerated digital transformation and heightened geopolitical tensions on the international stage have increased the need for effective cybersecurity practices and policies as well as a skilled workforce. Despite this, the demand for cybersecurity professionals continues to outpace the supply for societies and businesses globally, resulting in a cybersecurity workforce gap.

To ensure that digital transformation is available, safe and beneficial to all, significant efforts are needed to encourage cyber workforce capacity-building and knowledge-sharing at both national and international levels.

This discussion, supported by (ISC)² and the UK Cyber Security Council, will explore how to effectively address the twin challenges of the global cyber workforce shortage and skills gap.

• What are the implications of the global cyber workforce and skills gaps for businesses and societies?

• What shape do these gaps take within society? Where are they most prevalent and how do they vary?

• What is the role of education and private-public partnerships in effectively addressing these gaps?

• How does the UK National Cyber Strategy seek to address these challenges? What are the key lessons from this strategy?

• What other efforts are being made internationally to bridge this gap? What opportunities are there for knowledge-sharing and capacity-building?

• What is the role of diversity, equity and inclusion in tackling these gaps?

As with all members events, questions from the audience drive the conversation. If you are not a member of Chatham House but would still like to attend the event please email Eleanor Macmillan-Fox to enquire about registration.

Read the transcript. 

Advanced technologies in the face of war 24 October 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 5 October 2022 Online

How is NATO strengthening its technological edge?

Russia’s invasion of Ukraine has brought with it a heavy focus on technology and weaponry, particularly as casualties mount and large numbers of equipment are lost on both sides. The conflict has highlighted how states and their militaries seek technological superiority and how access to advanced capabilities can help shape the course of the war.

Aiming to sharpen the Alliance’s technological edge, NATO is working to support the development of emerging and potentially disruptive technologies such as artificial intelligence (AI), autonomous systems, biotechnologies and quantum technologies that are seen as presenting both risks and opportunities for the Alliance.

As part of this work, NATO’s newly formed Defence Innovation Accelerator for the North Atlantic (DIANA), hosted by both the UK and Estonia, brings together academia, industry and government to support the development of critical technologies to deter and defend against existing and future threats.

Key questions to be considered by the panel include:

• How will the technologies that form the focus of DIANA’s efforts strengthen the Alliance and prepare it to better deal with threats to peace and security across the region?

• How will these technologies be applied and used in war?

• To what extent can a war be won by technology?

• Is Ukraine, and other future conflict zones, in danger of becoming a testing ground for emerging technologies?

• What has the war in Ukraine taught NATO about modern warfare and how should the Alliance respond to this?

• After the commotion of AUKUS, how will the Alliance manage the sharing of technologies and IP among member states?

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

Read the transcript. 

Who gains from artificial intelligence? 27 February 2023 — 5:30PM TO 6:30PM Anonymous (not verified) 6 February 2023 Chatham House and Online

What implications will AI have on fundamental rights and how can societies benefit from this technology revolution?

In recent months, the latest developments in artificial intelligence (AI) have attracted much media attention. These technologies hold a wealth of potential for a wide range of applications, for example, the recent release of OpenAI’s ChatGPT, a text generation model, has shed light on the opportunities these applications hold including to advance scientific research and discovery, enhance search engines and improve key commercial applications.

Yet, instead of generating an evidence-based public debate, this increased interest has also led to discussions on AI technologies which are often alarmist in nature, and in a lot of cases, misleading. They carry the risk of shifting public and policymakers’ attention away from critical societal and legal risks as well as concrete solutions.

This discussion, held in partnership with Microsoft and Sidley Austin LLP, provides an expert-led overview of where the technology stands in 2023. Panellists also reflect on the implications of implementing AI on fundamental rights, the enforcement of current and upcoming legislation and multi-stakeholder pathways to address relevant issues in the AI space.

More specifically, the panel explores:

• What is the current state of the art in the AI field?
• What are the opportunities and challenges presented by generative AI and other innovations?
• What are some of the key, and potentially most disruptive, AI applications to monitor in the near- and mid-term? 
• Which applications would benefit from greater public policy/governance discussions?
• How can current and future policy frameworks ensure the protection of fundamental rights in this new era of AI?
• What is the role of multi-stakeholder collaboration?
• What are the pathways to achieving inclusive and responsible governance of AI?

• How can countries around the world work together to develop frameworks for responsible AI that upholds democratic values and advance AI collaboration across borders?

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

Read the transcript.

Can diplomacy advance human rights? 25 April 2023 — 4:00PM TO 5:00PM Anonymous (not verified) 7 March 2023 Chatham House and Online

How is diplomacy contributing to advancing human rights through the multilateral system?

The international human rights system has come under significant pressure in recent years. Russia’s invasion of Ukraine and the US-China rivalry have created difficult political pressures, while major global challenges including climate change and global inequality demand answers. Effective diplomacy on human rights has become increasingly difficult, with incentives stacked against bold action.

The relationship between diplomacy and human rights is an uneasy one. Diplomacy is an art of negotiation, persuasion and compromise. Human rights are tightly defined and universal. The relationship between the two may seem paradoxical, but in the context of an unstable world order, it has never been more important.

In the 75th anniversary year of the Universal Declaration of Human Rights, this discussion will explore the critical role of diplomacy in advancing human rights in the future.

• What are the critical human rights challenges today? What is the role of diplomacy in addressing them?

• What is the impact of intensifying competition between the US and China on the human rights system?

• Is there an opening for more leadership emerging from the Global South?

• What is the future of the human rights system in the context of this polarized world?

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

The role of think tanks amid political uncertainty 9 May 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 13 April 2023 Chatham House and Online

Think tank leaders discuss how persistent and new forms of political uncertainty impact on their work and what can they do to counter it.  

Think tanks play a crucial role in supporting better public policy to address the most pressing global and local challenges. However, the recent rise in political turbulence poses a significant challenge to this work. Not only must the work of think tanks help counter political uncertainty but that uncertainty often threatens their ability to work effectively, and in some cases, their survival.

Polarized elections, regional instability, the rise of populism, shrinking civic space, eroding democracies, weakened institutions and public distrust are just some of the tricky contexts and issues raised by think tank leaders in the latest think tank state of the sector report. 

This event is being held in collaboration with On Think Tanks ahead of the On Think Tanks Conference.

Join us for a thought-provoking discussion at Chatham House on the major sources and consequences of political uncertainty in the world today and the critical role of think tanks in responding to and countering it. 

Key questions to be addressed during this discussion include:

• How does political uncertainty look like today?
• What can think tanks do to operate within uncertain contexts? 
• What are their roles: should they build the middle ground, support political parties, rally behind social demands?  
• Will think tanks be able to maintain their reliability and credibility in an increasingly polarized political environment?
• What can think tanks do to contribute to greater political stability?

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

A drinks reception will immediately follow this event.

Director’s breakfast briefing: Shifts in European foreign policy since 9/11 14 October 2021 — 8:00AM TO 9:15AM Anonymous (not verified) 4 October 2021 Chatham House

Former MI6 chief, Sir Alex Younger, discusses shifts in European foreign policy since 9/11.

Former MI6 chief Sir Alex Younger, discusses shifts in European foreign policy since 9/11.

The dramatic events surrounding the withdrawal from Afghanistan demonstrates a profound shift in European security priorities since the beginning of the ‘war on terror’. Against the backdrop of the 20th anniversary of 9/11, former MI6 chief, Sir Alex Younger, discusses recent shifts in European foreign policy.

How has the focus on counterterrorism changed over the last two decades particularly in light of new and evolving strategic challenges? Why were many long-term objectives in Afghanistan left unachieved? Has the threat of terrorism changed across Europe? How has cooperation between security and intelligence services across the world changed particularly across the Atlantic? And, 20 years on, is the ‘war on terror’ really over?

This event is only open to Chatham House Partners and Major Corporate Members as well as selected giving circles of Chatham House. If you would like to attend, please RSVP to Linda Bedford at RSVP@chathamhouse.org.

Reshaping NATO for an uncertain future The World Today mhiggins.drupal 25 May 2022

A Chatham House expert panel outlines the challenges for delegates at the Madrid summit where the roadmap for the transatlantic alliance will be created

This year had already been earmarked as pivotal for the shape and direction of European security even before Russia, a nuclear superpower, rolled its tanks into Ukraine.

On the agenda at the NATO summit in Madrid in June is the Strategic Concept, which sets out the alliance’s direction and priorities for the next decade. There is much to discuss. From shared values to the state of the security environment, the Strategic Concept will have a direct impact on the global security landscape.

Ten years ago, the world was a very different place. The United States had just withdrawn from its bloody war in Iraq and was still embroiled in Afghanistan fighting the Taliban. In China, Xi Jinping was poised to become the next president, while refugees escaping the vicious civil war in Syria were heading towards Europe. In Africa, Islamist activity in Mali was about to spread throughout the Sahel.

Now, Russia’s illegal war in Ukraine rages on NATO’s doorstep, spurring the once neutral countries of Sweden and Finland to seek membership. How will Russia’s aggression towards Ukraine affect the western security agenda and what will be the shape of the new NATO that emerges from these talks?  To help answer these questions, The World Today convened a panel of Chatham House experts to consider what the next 10 years holds for NATO.

Here is what they said.

Alice Billon-Galland
We shouldn’t expect a revolution, but more an adaptation of reforms that have taken place at NATO for quite a long time, especially since the Wales summit in 2014. NATO allies will have to decide on the Russian threat perception and decide how they want to reinforce their deterrence and defence posture in the East, and how this affects their ability to maintain a 360-degree approach and to carry out the ambitious NATO 2030 agenda.

Patricia Lewis
We need to understand how deterrence works far better and we should have better metrics by now. Russia and NATO do not wish to engage in conventional warfare with each other, which suggests that Nato’s conventional deterrence is working. That said, Putin’s nuclear threats have not been within the framework of deterrence. But nuclear deterrence has not worked in the way strategists imagined since the end of the Cold War, and we need a much clearer hard look at these weapons once this is all over.

Had we followed through on disarmament in the 1990s, Putin would have held very little sway today. Nuclear weapons and despots are not a good mix and with these weapons there are no small mistakes. We would be foolish to imagine that rationality will hold when it comes to nuclear decision-making.

It is time to put arms control back on the agenda and strengthen our efforts to prevent nuclear proliferation. We need to put the elimination of these weapons back on the UN Security Council agenda.

Andrew Dorman
Finland and Sweden coming into NATO completely transforms the Baltic. It makes the deployment of reinforcements to the Baltic states an awful lot easier. From the Kremlin’s point of view, the last thing they want is another border with NATO. Russia is already overly committed and hasn’t got enough forces to deal with Ukraine. Its border with Finland is enormous. And NATO would be gaining two very robust, well-organized military forces. You are seeing a lot more NATO assets starting to look at the high north.

Hans Kundnani
I am actually slightly less worried about the Russian threat to NATO countries than I was before February 24. The war has demonstrated how weak the Russian military is, and so the idea that it might present a threat to Finland and Sweden seems less plausible than before. It is not even clear to me that Russia could do very much in other south-eastern European countries. It already seems pretty overstretched. This should make us more relaxed, rather than more worried, about threats to other countries and in particular to NATO countries or to Finland and Sweden.

Leslie Vinjamuri
Sweden and Finland moving forward with their requests for membership is a sign of success for the West, but it also raises important questions for the future of European security. The possibility that we lock in a division that might suit Europe and the United States now does not bode well for a Russia maybe 10 years out or with a different leader.

Alice Billon-Galland
We need to avoid mission creep, but we also need to avoid going back to a position where NATO only focuses on Russia and then set an agenda for 10 years based on that threat assessment alone. We will risk missing out on the next big challenge if we go back on something too specific. We risk being reactive, whereas the Strategic Concept is an exercise that should be proactive and provide a space for transatlantic partners to share broader common security concerns.

Patricia Lewis
NATO is open to all countries in the transatlantic area, and it is even possible that Russia could join in the future should they wish to apply. But it is important to remember that NATO is a political-military alliance, and its politics are fundamental to its cohesion, far more than that of any weapon system or a specific enemy. It will continue to address a wider range of threats as it has in, for example, Afghanistan and many of those will be directly related to the impacts of climate change.

One thing to note, in light of Russia’s nuclear threats, is that NATO’s characterization of itself as a ‘nuclear alliance’ should be revised. NATO needs to be resilient to ebbs and flows of weapon systems and not become over-reliant on one system which has recently demonstrated severe negative impacts.

Hans Kundnani
During the Cold War, what held the alliance together was a shared perception of a threat from the Soviet Union – not a set of shared values. After all, there were authoritarian states in NATO. After the end of the Cold War that overwhelming sense of a shared threat from the Soviet Union disappeared and NATO tried to reinvent itself as a community alliance of democracies with shared values.

But we now once again have authoritarian states in NATO. So it was really in danger of being pulled apart. The war in Ukraine has refocused NATO on its original, historic mission: collective security in relation to Russia. In that sense it has given NATO a lifeline.

Creon Butler
Shared values are still an awful lot stronger as an element of what ties NATO together now than they were in the past. I think you now have the threat perception coming back full force. But I still think you have that very strong element of values, indeed the extra countries that are coming in are very strong democratic countries.

The interesting question is the out-of-area stuff – the Afghanistan-related stuff and counterterrorism more generally, and how important those threats remain. I guess there is an element to that which is a global kind of threat, counterterrorism, but there is also the out-of-area activity which obviously has been transformed following the withdrawal from Afghanistan.

Alice Billon-Galland
The crisis management mandate needs to be looked at again with some of the lessons learnt after Afghanistan and Libya, especially given what happened in Kabul, and all the discussion around cooperative security. The question is not only how do we work with partners and countries in the region, but how do we want to engage with China, for instance? How do we want to work on new technologies? How do we want to work with the European Union, with the United Nations?

The alliance must decide what it wants to do versus  what it wants to set aside and have other organizations do, while it refocuses on its core historic tasks.

Andrew Dorman
One of the sensitive, ongoing debates within NATO is whether it has a global role or whether it has a more transatlantic role. There are divisions within NATO about which is its focus. I think the answer, to a degree, is both. One of the real challenges for policymakers, particularly the Biden administration, is that they are going to be pushing for NATO to act as a global player.

This is one of the dilemmas that NATO faces. It could spend all its time focused purely on the short term – that is Russia –  and ignore China, and then suddenly need to think, ‘Oh heck’. What happens if , as a result of this, Russia is essentially dropped into the China camp and Putin becomes Xi Jinping’s poodle? That is a real dilemma, and why I think the US is going to focus on a global NATO.

Leslie Vinjamuri
NATO may have a role to play in Washington’s China strategy. But it won’t be the most important institution. The Biden administration is relying on multiple frameworks for engaging in the Indo-Pacific. For example, the Quad – a partnership between the US, Japan, India and Australia – is designed to secure India’s participation. Pulling India into the region where it has economic power, influence, military and security capabilities and can move the needle. It is both an intelligent and pragmatic strategy to have a number of groupings, a patchwork of overlapping partnerships, including existing alliances. That seems right to me.

Patricia Lewis
It is unlikely that the US would want to create a global NATO. The US and its allies in other regions may wish to model future alliances on NATO, that have strong relationships with it in areas such as political coherence, interoperability, and joint training and exercises and such. But political decision-making would be better suited to sit within specific regional contexts.

Washington has formal alliances in the Indo-Pacific region that commit the US to, for example, the defence of Australia through the Anzus security treaty, as well as Japan. As Washington increases its focus on the Pacific, the existing political-military relationships in the region could become more coherent. We might see a version of a Pacific-Asia Treaty Organization emerge – a Pato. All this depends on how China uses its power and how perspectives in the region evolve.

Creon Butler
I am not sure it is a problem that NATO does not have a specific focus on dealing with the China threat. It potentially has a role in dealing with those things that are seen by the membership as common threats. Which clearly is Russia now but has added terrorism in the past and may well include other things. China is not a common threat in the way that Russia is perceived to be. Of course, something could happen, not least something with Taiwan, which would change that, but that is not where NATO is at present.

Alice Billon-Galland
I think we should really avoid a false dichotomy between ‘NATO should do only Russia’ and ‘NATO should do everything’ because there are lots of activities in the middle where the alliance can bring some added value – and that is exactly what we should be discussing. The issue around China and NATO is being completely overblown. We need to be very clear that the purpose of NATO is to defend the Euro-Atlantic space, but that may include keeping an eye on ‘when China comes to us’, as NATO Secretary-General Jens Stoltenberg often says.

Hans Kundnani
None of the regional partners in Asia that you need to deal with the China challenge are in NATO – and can’t be – so it is just the wrong vehicle to deal with the Indo-Pacific. But there is also a bit of a tension here between Indo-Pacific and Euro-Atlantic. People in Asia also look at the different threat perceptions in completely different ways than we do in Europe. There are a number of reasons why people in India do not support the war in the Ukraine, but one of them is that they see China, not Russia, as the real threat.

Andrew Dorman
I think so much of the debate we have had so far is about political NATO as supposed to military NATO. One of its key roles is how military forces operate, engage and conduct operations, plan operations through deterrents and so forth. NATO as the template of the West does work. That is why it is in the interest of the US to keep this going. It is one of the ways of making sure, for example, the US Pacific fleet remains compatible with the US Atlantic fleet by forcing them to operate the same system, which is the NATO system.

It is one of the things the American forces learnt out of Afghanistan and Iraq. There is a NATO way which is a global footprint. NATO’s role within the African Union is as a template for peacekeeping operations. You have got the likes of Australia and South Korea and Japan very much integrated into NATO. It doesn’t have to be a formal political NATO, but it does strike me to be in the interest of the West to have them reach forces capable of operating with one another.

Patricia Lewis
One of the most interesting developments in the past year has been the creation of Aukus, the security pact between Australia, Britain and the United States. That grew out of the Five Eyes intelligence partnership which led to the need to develop new, interoperable equipment such as nuclear-powered submarines. We will have to see how it develops, but maybe it could be the start of a PATO in the region.  

Creon Butler
In the current situation, we have a crucial partnership between NATO and the EU over Russia, in terms of the long-term future they hold out for Ukraine, but also with the G7 because that is the place to organize the financial support for Ukraine and the economic and financial sanctions against Russia. They are different memberships but the combination of the EU, G7 and NATO is an absolutely crucial alliance of different alliances, with different memberships serving different purposes but having an overall impact that can potentially be very effective.

Leslie Vinjamuri
We work with the institutions that we have, but not always with a clear recognition of their limitations. We are facing a dark moment for the UN Security Council, with one of its founder members blatantly violating the UN’s most important norm. Yet many people in the rest of the world say, ‘Yes, but in 2003, the United States violated Iraq’s sovereignty …’ Where the West sees moral clarity, and so condemns Russia’s invasion of Ukraine, there is an assumption by much of the rest of the world of moral equivalence between these two invasions.

Working through the UN Security Council is going to be difficult for some time. This means that states are probably going to find different strategies for working around, rather than through, the Security Council.

Methods to shorten [¹⁸F]FDG Patlak PET imaging procedures ranging from 65–90 to 20–30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [¹⁸F]FDG Patlak imaging at 55–65 min after injection using a PIF combined with direct Patlak reconstructions to provide reliable quantitative accuracy of lung tumor uptake, compared with a full-duration 65-min acquisition using an IDIF. Methods: Patients underwent a 65-min dynamic PET acquisition on a long-axial-field-of-view (LAFOV) Biograph Vision Quadra PET/CT scanner. Subsequently, direct Patlak reconstructions and image-based (with reconstructed dynamic images) Patlak analyses were performed using both the IDIF (time to relative kinetic equilibrium between blood and tissue concentration (t*) = 30 min) and a scaled PIF at 30–60 min after injection. Next, direct Patlak reconstructions were performed on the system console using only the last 10 min of the acquisition, that is, from 55 to 65 min after injection, and a scaled PIF using maximum crystal ring difference settings of both 85 and 322. Tumor lesion and healthy-tissue uptake was quantified and compared between the differently obtained parametric images to assess quantitative accuracy. Results: Good agreement was obtained between direct- and image-based Patlak analyses using the IDIF (t* = 30 min) and scaled PIF at 30–60 min after injection, performed using the different approaches, with no more than 8.8% deviation in tumor influx rate value (K_i) (mean difference ranging from –0.0022 to 0.0018 mL/[min x g]). When direct Patlak reconstruction was performed on the system console, excellent agreement was found between the use of a scaled PIF at 30–60 min after injection versus 55–65 min after injection, with 2.4% deviation in tumor K_i (median difference, –0.0018 mL/[min x g]; range, –0.0047 to 0.0036 mL/[min x g]). For different maximum crystal ring difference settings using the scan time interval of 55–65 min after injection, only a 0.5% difference (median difference, 0.0000 mL/[min x g]; range, –0.0004 to 0.0013 mL/[min x g]) in tumor K_i was found. Conclusion: Ultrashort whole-body [¹⁸F]FDG Patlak imaging is feasible on an LAFOV Biograph Vision Quadra PET/CT system without loss of quantitative accuracy to assess lung tumor uptake compared with a full-duration 65-min acquisition. The ultrashort 10-min direct Patlak reconstruction with PIF allows for its implementation in clinical practice.

C-X-C motif chemokine receptor 4 (CXCR4)–directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [^99mTc]Tc-pentixatec in patients with PA. Methods: Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [^99mTc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. Results: Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52–1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. Conclusion: [^99mTc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [⁶⁸Ga]Ga-pentixafor PET.

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Methods: Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with ¹¹¹In to allow SPECT imaging. ¹¹¹In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non–p53-specific ¹¹¹In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. Results: In vivo SPECT imaging showed enhanced uptake of ¹¹¹In-anti-p53-TAT, versus ¹¹¹In-mIgG-TAT, in high-expression p53^R175H and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse–derived pancreatic ductal adenocarcinoma tumors. Imaging with ¹¹¹In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53^R172H pancreatic ductal adenocarcinoma tumors. Conclusion: We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.

Preclinical data have shown that ¹⁶¹Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their ¹⁷⁷Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose–response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE (agonist) and with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and β^– particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their ¹⁷⁷Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by ¹⁶¹Tb. When activity concentrations were considered, both [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with ¹⁷⁷Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose–response curves for [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE. [¹⁶¹Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [¹⁶¹Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by ¹⁶¹Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 than for the ¹⁷⁷Lu-labeled analogs. In contrast, [¹⁶¹Tb]Tb-DOTATATE showed no higher dose response than [¹⁷⁷Lu]Lu-DOTATATE, whereas for [¹⁶¹Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [¹⁶¹Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [¹⁶¹Tb]Tb-DOTATATE for labeling with ¹⁶¹Tb.

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.

Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [¹⁷⁷Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [¹⁷⁷Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (TBS) and changes in normalized peak count (nPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in TBS_second-first, TBS_third-first, and TBS_fourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [¹⁷⁷Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. –0.049, 0.08 vs. –0.116, and 0.109 vs. –0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). nPC_second-first showed significant group differences (mean, –0.107 vs. –0.282; P = 0.033); nPC_third-first and nPC_fourth-first did not reach statistical significance (mean, –0.122 vs. –0.312 and –0.183 vs. –0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, TBS_fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. TBS_second-first and TBS_third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. nPC_second-first, nPC_third-first, and nPC_fourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: TBS and nPC can predict [¹⁷⁷Lu]Lu-DOTATATE response by the second treatment session.

Unspecific bone uptake (UBU) related to [¹⁸F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [¹⁸F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [¹⁸F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUV_max, SUV_mean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HU_mean) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (n = 2) or more (n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (n = 178) as PCa metastases or not. Results: In total, 448 bone [¹⁸F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (P < 0.001) with determination of SUV_max (P < 0.001) and HU_mean (P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score’s AUC was significantly higher than that of HU_mean (AUC, 0.62) and remained high among lesions with HU_mean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [¹⁸F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging.

This analysis aimed to identify clinical factors associated with positivity on repeat ⁶⁸Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 ⁶⁸Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative ⁶⁸Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat ⁶⁸Ga-PSMA-11 PET/CT.

Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumors for which standardized diagnostic work-up fails to identify the primary site. We aimed to describe the Peter MacCallum Cancer Centre experience with ¹⁸F-FDG PET/CT in extracervical CUP with respect to detection of a primary site and its impact on management. A secondary aim was to compare overall survival (OS) in patients with and without a detected primary site. Methods: CUP patients treated between 2014 and 2020 were identified from medical oncology clinics and ¹⁸F-FDG PET/CT records. Information collated from electronic medical records included the suspected primary site and treatment details before and after ¹⁸F-FDG PET/CT. Clinicopathologic details and genomic analysis were used to determine the clinically suspected primary site and compared against 2 independent masked reads of ¹⁸F-FDG PET/CT images by nuclear medicine specialists to determine sensitivity, specificity, accuracy, and the rate of detection of the primary site. Results: We identified 147 patients, 65% of whom had undergone molecular profiling. The median age at diagnosis was 61 y (range, 20–84 y), and the median follow-up time was 74 mo (range, 26–83 mo). Eighty-two percent were classified as having an unfavorable CUP subtype as per international guidelines.¹⁸F-FDG PET/CT demonstrated a primary site detection rate of 41%, resulted in a change in management in 22%, and identified previously occult disease sites in 37%. Median OS was 16.8 mo for all patients and 104.7 and 12.1 mo for favorable and unfavorable CUP subtypes, respectively (P < 0.0001). Median OS in CUP patients when using ¹⁸F-FDG PET/CT, clinicopathologic, and genomic information was 19.8 and 8.5 mo when a primary site was detected and not detected, respectively (P = 0.016). Multivariable analysis of survival adjusted for age and sex remained significant for identification of a potential primary site (P < 0.001), a favorable CUP (P < 0.001), and an Eastern Cooperative Oncology Group status of 1 or less (P < 0.001). Conclusion: ¹⁸F-FDG PET/CT plays a complementary role in CUP diagnostic work-up and was able to determine the likely primary site in 41% of cases. OS is improved with primary site identification, demonstrating the value of access to diagnostic ¹⁸F-FDG PET/CT for CUP patients.