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GLP-1 receptor agonists: European drug regulator asks makers for evidence of self-harm




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GLP-1 agonist shortage will last until end of 2024, government warns




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Type 1 diabetes: Randox removes adverts after claims that it was using fear to sell genetic test




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GLP-1 shortages will not resolve this year, EMA warns, amid concern over off-label use




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Helen Salisbury: Weight loss treatment—available in theory but not in practice




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Diabetes: One in 10 patients on NHS’s “soups and shakes” diet plan went into remission




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Patient related outcome measures (PROMs) in long term conditions—is it time to bring them into routine clinical practice?




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A new transatlantic relationship?

A new transatlantic relationship? 4 October 2022 — 6:30PM TO 7:30PM Anonymous (not verified) 22 September 2022 Chatham House and Online

US senator Jeanne Shaheen examines the implications of new UK leadership, the war in Ukraine, and NATO expansion for the US–UK relationship.

In recent weeks, the UK has ushered in a new prime minister and a new monarch. The US will hold potentially power-shifting mid-term elections in November after nearly two years of the Biden presidency that promised to bring the US ‘back’ as a global leader in international affairs.

These leadership changes come at a time when Europe is at war, NATO is expanding and US–China competition is re-ordering long-held alliances. Old assumptions about foreign policy are in flux in the midst of huge international challenges.

Democratic senator Shaheen, a senior member of the Senate Foreign Relations Committee, explores how these changes might influence the US–UK ‘special’ relationship.

  • How will the trajectory of Russia’s war on Ukraine influence the bilateral relationship? What leadership is needed now?

  • What does Russia’s war on Ukraine mean for NATO in responding to other pressing security challenges?

  • What domestic constraints might limit the US’s power to reinsert itself as a global leader?

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

Read the transcript. 




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Black perspectives on international relations

Black perspectives on international relations 27 October 2022 — 5:00PM TO 6:00PM Anonymous (not verified) 4 October 2022 Chatham House and Online

How can black perspectives help the world tackle global challenges and expand our understanding of international relations?

As social boundaries change, the viewpoints of black academics, thought leaders and policymakers have grown in both influence and strength worldwide, challenging western and institutional norms. 

However, many institutions and organizations, long established with the exclusion of black voices, have to adapt if there is to be greater inclusion and diversity of thought when tackling major global issues.

Growing reflection on the legacy of colonialism and the importance of the power of diversity may be needed for today’s problems.

The search for global racial equality has seen a growing commitment to ensuring the black experience is at the heart of geopolitical discussions.

This panel discussion looks at what changes are occurring now and how is the conversation shifting. It also examines the challenges posed by the increasing politicization of race and culture issues in the current political environment.

Key questions discussed by the panel include:

  • What is the importance of black voices in international relations and where are the main challenges to greater incorporation?

  • What are some of the leading perspectives, approaches and beliefs within Africa and across the black diaspora regarding international relations?

  • To what extent are governments, businesses and leading global institutions making efforts to include more black voices in decision-making?

  • How are black academics changing wider geopolitical conversations and to what extent can deeper conversations lead to change?

  • Will an ‘African Century’ bring black perspectives on international relations to the fore of the geopolitical agenda?

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

Read the transcript. 




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What is Labour’s foreign policy?

What is Labour’s foreign policy? 24 January 2023 — 12:00PM TO 1:00PM Anonymous (not verified) 3 January 2023 Chatham House and Online

In conversation with David Lammy, the UK shadow foreign secretary.

David Lammy MP, shadow secretary of state for foreign, commonwealth and development affairs, outlines Labour’s plan for UK foreign policy if elected to government.

He addresses the UK’s strengths and opportunities in a world that has become more divided, more dangerous, and more unpredictable. He also offers a critique of the current UK government’s approach to foreign policy, particularly at strained relationships with allies and Britain’s economic woes.

The shadow foreign secretary explores the following key questions:

  • What would a future Labour government do to modernize Britain’s diplomacy and rebuild alliances to improve Britain’s global influence?

  • In a new age of warfare in Europe, how would Labour pursue security cooperation with allies?

  • How would Labour address high energy costs, energy security, and the climate crisis?

  • As Britain’s economy falters, how can foreign policy drive prosperity at home?

  • What is Labour’s plan for international development, following the UK government’s abandonment of the 0.7% commitment?

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

Read a transcript




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The future of the Russia-China relationship

The future of the Russia-China relationship 9 February 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 26 January 2023 Chatham House and Online

What lies ahead for the ‘unlimited friendship’ between Moscow and Beijing?

Russia’s invasion of Ukraine has raised new questions about the nature of the relationship between Russia and China, with the war seen as having the potential to shift Russia from a close ally to a liability in the eyes of the Chinese government.

This event explores the latest developments in extent of the relationship and interactions between the two: new convergences and divergences, energy links and limitations, declared alliances and private disagreements.

Experts on the panel explore:

  • How has the relationship changed since Russia’s 2022 invasion of Ukraine?
  • What do the Russian and Chinese people make of the relationship?
  • How could a war-weakened Russia be viewed by China?

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

Read the transcript.




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Russia’s aggression and a crisis for multilateralism

Russia’s aggression and a crisis for multilateralism 30 March 2023 — 1:00PM TO 2:00PM Anonymous (not verified) 23 March 2023 Chatham House and Online

In conversation with Dmytro Kuleba, minister of foreign affairs of Ukraine, about how multilateral organizations struggle to respond adequately to Russia’s full-scale invasion of Ukraine.

As a permanent member of the UN Security Council, Russia pursues this war in defiance of the umbrella organization’s multiple resolutions condemning the invasion, along with its war crimes, annexation of territory, deliberate targeting of civilian nuclear infrastructure, cultural extermination, and global disinformation campaign. 

This event explores the following questions: 

  • How should the response of the UN to Russian aggression be assessed? 
  • What can be done to uphold the guiding principles of the UN Charter? 
  • Is there a ‘UN problem’ or a ‘Russia problem’? 
  • How can trust and the legitimacy of multilateral cooperation be restored in times of strategic rivalry and rising global tensions?
  • Who can drive such an effort? 
  • Is post-Soviet transfer of the UN Security Council seat to Russia a cause of current impunity? 

This event features a live in-person audience in Kyiv as well as in London and online.




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The law as a tool for EU integration could be ending

The law as a tool for EU integration could be ending Expert comment NCapeling 15 October 2021

Poland is not the only EU member state challenging the supremacy of European law, as historic change is happening in how European integration functions.

The Polish Constitutional Tribunal’s ruling that several articles of the European treaties are incompatible with the Polish constitution is prompting much debate, especially in terms of both the similarities and differences between it and rulings by the German constitutional court which have also challenged the European Court of Justice (ECJ).

Pro-Europeans are keen to draw a sharp distinction between the reasoning deployed by the two courts. They see the Polish court’s challenge as an exceptional case which the European Union (EU) cannot ‘tolerate’ because it would lead to the ‘demolition of the EU’s legal order from within’ and argue the EU must take a tough approach to Poland by re-asserting the supremacy of EU law.

But this view misses a bigger long-term shift in the EU. Both the German and Polish cases illustrate some of the basic conflicts within the EU’s legal system for decades. What is being challenged increasingly openly – even since the UK left the EU – is the idea of the EU as a de facto federation in which non-majoritarian institutions such as the ECJ have final say about the quality of democracy in member states.

ECJ’s quiet revolution

Historically ‘integration through law’ was central to the European project and the ECJ was a key institution driving forward integration – usually benefiting from what Erik Stein called ‘benign neglect by the powers that be and the mass media’. Even when European integration in the form of treaties stalled in the 1960s and 1970s, ‘judicial integration’ through the ECJ continued, including its notable 1964 decision that EU law was supreme.

According to the German court’s theory of ‘constitutional pluralism’, there is in effect a constant dialogue and accommodation between the national and EU level rather than a simple primacy of EU law over national law

This self-empowerment of the ECJ – what another scholar of European constitutionalism Joseph Weiler calls ‘a quiet revolution’ – was possible because there was a ‘permissive consensus’ in member states which allowed judicial integration to continue largely unchallenged. But this has now changed as both politicians and national courts are more willing to challenge what they see as judicial overreach.

There are important differences between the approach of the German and the Polish constitutional courts. The Law and Justice Party has politicized the Polish court, packing it with judges sympathetic to that party, whereas the German court is more independent.

In addition, whereas the German court made qualified and subdued objections to measures taken in response to the euro crisis during the past decade and, in particular, the steps towards the mutualization of eurozone debt – but often backed down with ‘all bark and no bite’ as Christoph Schmid put it – the Polish court is driven by political considerations and has challenged the supremacy of EU law in a more direct and general way.

However, the German court has made it clear it is the guardian of the German constitution and seeks to impose limits on the ECJ’s self-empowerment by arguing Europe is not a federation. According to the German court’s theory of ‘constitutional pluralism’, there is in effect a constant dialogue and accommodation between the national and EU level rather than a simple primacy of EU law over national law.

The court sees itself as the ultimate arbiter of whether steps in European integration are consistent with the German constitution, and is likely to challenge any further steps in fiscal integration even if the ECJ deems them in accordance with the treaties – as it did with the European Central Bank’s quantitative easing programme.

Supremacy of EU law is under pressure

Right across Europe, courts and politicians are increasingly challenging the ECJ and questioning the supremacy of EU law. Michel Barnier called for France to regain ‘legal sovereignty’ and should no longer be subject to the judgments of the ECJ – an extraordinary demand from the EU Brexit negotiator who regularly lectured the UK about the sanctity of the EU’s legal order.

The Polish challenge is part of a historic change in how European integration functions – or does not function

Other possible French presidential candidates such as Valérie Pécresse and Eric Zemmour are also openly challenging the primacy of EU law. The UK, of course, is fighting its own battle with the EU about the ECJ’s role in the Northern Ireland Protocol.

It was not the current Polish government but the people of France and the Netherlands who blocked the attempt at explicit constitutionalisation of the EU in a referendum just one year after the 2004 enlargement. Whereas the Constitutional Treaty ‘would have codified the doctrine of EU legal supremacy’, that provision was dropped from its successor the Lisbon Treaty, again indicating consensus on EU legal supremacy is not as strong as is often claimed.




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Belarus-EU border crisis reveals wider security threat

Belarus-EU border crisis reveals wider security threat Expert comment NCapeling 8 December 2021

By engineering a crisis at the Belarus border, Lukashenka is attempting to exacerbate vulnerabilities within the EU. Securitizing migration is not the answer.

When thousands of migrants began freezing to death in the forests on the Belarus border with Poland, Belarusian leader Aliaksandr Lukashenka was forcing the European Union (EU) into a tough choice – either give in to blackmail and welcome migrants whose attempts to trespass the EU border were a result of his policy of luring them to Belarus to put pressure on the EU, or keep the borders closed and declare solidarity with Poland despite its known mistreatment and illegal pushbacks of potential asylum-seekers.

Lukashenka’s action was aptly exploiting three key pressure points of the EU – as a normative power where the human dignity of migrants is overlooked while the European border and coastguard agency Frontex stands by, as a geopolitical actor seeking to externalize its migration problem by signing readmission agreements with transit countries, and as a community of values with the EU-Poland dispute over rule of law.

Now is the time for a robust strategy aimed at preventing what is currently a rogue state from turning into an outright terrorist regime

His approach is typical ‘dictaplomacy’ and democracies which have confronted such a ‘continuation of war by other means’ in their past dealings with dictatorships know that blackmail mostly serves to divert attention away from a rogue leader’s misdemeanours towards his own population. But if this had been game of chess the EU would have been in check.

Thankfully checkmate was avoided – so far – as a compromise was found following weeks of heightened diplomatic efforts. Lukashenka was forced to back-pedal and take care of the migrants, and no humanitarian corridor was needed as the EU sent funds and took measures to support organizations providing shelter for the migrants in Belarus, while airlines and governments in the source countries were pressured to restrict flights to Minsk and started repatriating part of the migrants.

Causing a nuisance

‘Operation Gateway’ – the outline of which was allegedly drawn several years ago and tested by Russia in 2016 at its own borders with Norway and Finland – certainly caused a nuisance, but it ultimately backfired as Lukashenka now has to manage the remaining 2,000-5,000 migrants who refused to be flown back, as well as facing increased international sanctions. However, the fact that Angela Merkel had to personally call him made it look as if Lukashenka did not back down for nothing.

The EU and NATO, including the UK, only reacted collectively to this crisis once it was already out of hand, leaving questions over whether this experience of Lukashenka’s dictaplomacy is a wake-up call to boost resilience against rogue warfare, and to upgrade strategic assessments of the ‘Lukashenka problem’ too.

Back in June, the Belarus ministry of foreign affairs (MFA) announced its withdrawal from the Eastern Partnership and the visa facilitation and readmission agreement with the EU, while Lithuania sent early warnings about a ‘hybrid attack’ at its own border with Belarus. In August, Der Spiegel reported details of an alleged smuggling scheme whereby Tsentr Kurort – a company closely linked to the Administration of the President of Belarus with offices in the Middle East – was handling the shipping, accommodation, and relocation of migrants.

The EU and NATO, including the UK, only reacted collectively to this crisis once it was already out of hand, leaving questions over whether this experience of Lukashenka’s dictaplomacy is a wake-up call to boost resilience against rogue warfare

The smuggling of migrants was entirely predictable as Lukashenka has hinted many times Belarus could stop ‘protecting the EU from armed migrants’ seeking to enter it illegally. He has upped his rhetoric beyond notions of hybrid warfare by saying he needs Russian nuclear-capable bombers to ‘help him navigate the migrant crisis’, even hinting Belarus could station both Russian nuclear weapons and S-400 anti-aircraft missile systems. This shows Lukashenka is feeling increasingly cornered – which could lead to more unpredictable security crises.

Russia and Belarus are deepening relations

Although there is no smoking gun pointing to direct Russian involvement in orchestrating the hybrid attack at the EU’s borders, a new step in the military rapprochement between the two countries came when Putin and Lukashenka approved a new Military Doctrine of the Union-State of Russia and Belarus – a non-public document including a joint concept of migration policy. Lukashenka has also come off the fence over Crimea by openly accepting the legality of the peninsula’s integration with Russia.

Given Russia is also sabre-rattling over Ukraine, the risk of an accidental escalation into armed conflict is increasing in what feels like a return to classic Cold War logic, with the difference that the East is now offensively using the South for confronting the West. In recognition of the threat, the UK has joined the US, Canada, and the EU in the fresh sanctions on Belarus.




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Review: Islam's role in shaping Europe

Review: Islam's role in shaping Europe The World Today rsoppelsa.drupal 1 February 2022

Maryyum Mehmood on a work that recasts the role of Muslim minorities

Muslims and the Making of Modern Europe
Emily Greble, Oxford University Press, £26.99

When discussing the historical role of Muslims in Europe, most authors focus on Muslims in the western part of the continent, many of whom arrived as immigrant settlers from Muslim-majority nations. As a result, Muslims are easily identifiable as a foreign ‘other’. 

Emily Greble takes a different trajectory. In Muslims and the Making of Modern Europe, Greble centres her analysis on south-eastern European Muslims who are native to the region and, despite this fact, have still been subject to continuous stigmatization. 

In light of the present-day political tensions and targeted attacks on Muslims in Bosnia, which has seen inter-ethnic and religious hostility at its worst in 30 years, Greble’s nuanced retelling of the region’s social and political landscape has renewed urgency. Her work serves as a refreshing intervention to the literature on various fronts. It subverts stereotypical assumptions promulgated by the ‘Eastern Question’, whereby Muslims are portrayed as a simple ethnic minority living under colonial rule. Instead, Greble shows how they are a marginalized indigenous group that is by no means a monolithic, homogeneous entity. 

By uncovering the history of the region through the lens of Muslims, Greble highlights their capabilities as agents of change. Muslims were not just passive subjects but active citizens whose engagement was vital in the framing of social norms, political, ethical and legislative structures. 

By uncovering the history of the region through the lens of Muslims, Greble highlights their capabilities as agents of change

Greble’s neatly crafted thesis serves as a counterpunch to a decades-long clash-of-civilizations discourse, which pits Muslims of the region as Ottoman outsiders to be scapegoated as and when deemed necessary. 

The author offers a proposition that while secularism was the overarching aim of the new European state-project, the role of religion, especially marginalized or ‘othered’ religious communities cannot be overlooked or relegated to a simple ‘minority’ issue. 

This argument is laid out in three historical parts, beginning with the post-Ottoman transition of power (1878-1921), to the Yugoslav nation-building project (1918-1941) and finally to the political overhaul in a post-Second World War Europe (1941-1949).

Most historical analyses of the region focus on state actions towards Muslim minorities. Greble points out that such an approach is lacking because it is riddled with institutional biases from the very sources and methods used to understand them. 

Instead, the author takes Muslims, their lived realities and agency as her starting point and effectively manages to avoid such pitfalls.

What is most remarkable about this book is Greble’s self-reflective approach to confronting such a sensitive topic with great care.

The reader is shown how Muslims affected change and steered the trajectory of democracies in Europe at key historical junctures

Almost every chapter begins with an insightful and deeply personal historical account from a Muslim from the region which sets the scene for Greble’s assessment of key social, political and legal struggles.

With an enriching methodology, Greble explores the topic through first and second-hand accounts of how Muslims manoeuvred in both the secular realm and within religious spaces, such as madrasas (Islamic seminaries), waqfs (local community funds), muftis and ulemas (religious scholar), and the shariah courts. As a result, the reader is shown how Muslims affected change and steered the trajectory of constitutional democracies in Europe at key historical junctures. 

By taking this lens, Greble does not just offer another retelling of the significance of the 1878 Congress of Berlin, which enabled the demarcation of new territorial boundaries in a post-Ottoman world, but also conveys the story of how Muslims contributed to the emerging narratives around citizenship. 

Crucially, we are exposed to Muslim leadership as more than just a docile, homogenous grouping, but a defining entity that shaped the European citizenship project by refashioning both imperial secular norms, as well as Islamic jurisprudential rulings to suit their unique context, as opposed to a remnant of bygone Ottoman rule. 

A fundamental difference that sets this book apart from other contemporary work on the topic is that the author brings forth multiple intra-faith complexities found within Muslim groups of the region, from revivalist to reformists, and all else in between. The fluctuating relationship between the traditionalist ulema, muftis and qadis (religious scholars, clergy and judges) and the secular state powers is intricately captured across most chapters in this book. 

At times, the ulema would be seen to bandy with the state to acculturate Muslims to the emerging polities of the region. As Greble shows, muftis in 1914 travelled across southern Serbia giving dawah (missionary work) to locals to encourage them to support the Serbian state. Similarly, qadis in Montenegro in 1902 reassured local Muslims that by following the law of the land, they would be guaranteed their ‘shariah rights’, which were loosely defined by the Muslim clergy. 

This created a paradox for the states: the role of nation-building and liberalizing orthodox religious communities was given to conservative clerics who, in turn, were gatekeepers setting the boundaries and thus interpreted and applied Islam to preserve their position of power. The consequences were twofold. As Greble suggests, ‘instead of becoming more tied to secular structures of state and society – through centralized law, conscription, political representation – Muslims in formerly Ottoman lands were becoming more deeply bound to Islam’. 

Simultaneously, the rhetoric used further embedded Muslims firmly as a minority. 

Ironically in contrast, it was the liberal reformist thinkers who, sometimes, stood in opposition to the state regimes. Such internal divisions within Muslim spaces became more overtly discernible under communist rule, wherein members of the same Muslim community fought in different camps. 

The author offers a complex perspective not only of Balkan Muslims and their lived experiences, but also, their impact upon wider society and the states themselves

For instance, the author notes how some were aligned with the communist regime, while others were fighting with the allied forces and many were still backing revivalist Islamic groups. In light of this, what is perhaps most intriguing is how the communist takeover in 1945 managed to tear down any seemingly progressive movement that benefited the region’s Muslims. And it brought them back to square one, with the scrapping of shariah law and the removal of a mufti-led judiciary. Such crackdowns caused greater frenzy among the region’s Muslims and led to resistance movements in the form of activism and insurgencies. 

Ultimately, the author offers a complex perspective not only of Balkan Muslims and their lived experiences, but also, the implications of this upon wider society and the states themselves.

Greble’s remapping of the historical underpinnings of the tale of Muslims and the Making of Modern Europe is not just a clear example of how Muslims are not a foreign entity to the region, but a call to overturn the entrenched Great Replacement theory which uses this foreign ‘othering’ to further prejudice and calls for the ousting of Muslims and other minorities from Europe, a land which has forever been their home.
 




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Why a no-fly zone risks escalating the Ukraine conflict

Why a no-fly zone risks escalating the Ukraine conflict Expert comment NCapeling 13 March 2022

The US rejection of Poland’s offer to send fighter jets as a boost to Ukraine’s air defence shows just how uneasy nations are about direct combat with Russia.

The Pentagon’s decision to turn down the proposal by its fellow NATO member Poland to put Russian-made MiG-29 jets at its disposal demonstrates again how keen the US and allies are to avoid risking major confrontation with Russian forces.

The US Department of Defense says the offer to locate jets at bases in Germany was ‘not tenable’ as this risks flying into contested airspace over Ukraine – a non-NATO member – raising ‘serious concerns for the entire NATO alliance’ and echoing the continuing rejection of calls to implement no-fly zones (NFZs) as a way of easing the devastation being faced by trapped Ukraine civilians.

NFZs restrict any aircraft, including drones, from flying over a pre-defined region and can be used for both military and civilian purposes. But the implementation of NFZs is difficult to enforce and – most significantly – is unlikely to achieve the intended effect on the ground.

In the long-term, under the terms of a ceasefire agreement, it may be possible to include a NFZ under a UN or joint OSCE-UN peace terms

In conflict situations, they are usually implemented under the remit of United Nations (UN) peace support operations, requiring authorization under Article 42 of the UN Charter. This details that if all possible methods have proven ineffective in responding to a threat, countries ‘may take such action by air, or land forces as may be necessary to maintain or restore international peace and security’.

Protection but with limitations

NFZs provide both protection from attack and surveillance but do have limitations. They must be monitored and enforced which requires committing to fighter jet patrols with the explicit task of defending the area from the air by whatever means necessary.

This could mean jets firing upon Russian planes and drones so, if NATO allies and partners were to enforce a NFZ, it would represent an escalation of measures which is a step that would most likely provoke an unpredictable Vladimir Putin into further escalation – in short, it is highly likely to be seen as an act of war.

UK defence secretary Ben Wallace – among others – has repeatedly dispelled the idea, saying that enforcing NFZs would mean deploying ‘British fighter jets directly against Russian fighter jets’. In relation to moves such as the Polish jets, the Kremlin has warned that any countries offering airfields to Ukraine for attacks on Russia may be viewed as having entered the conflict.

There have only been three past instances of military NFZs. In Bosnia, as part of Operation Deny Flight from 1993-1995, a NFZ was enforced as part of a strategy which also including the provision of close air support and approved air strikes.

In Iraq, an NFZ endured for 12 years from 1991 and was succcesful in preventing Saddam Hussein from attacking Kurdish and Shia Muslim civilians. And in Libya in 2011, a NFZ was deployed to prevent the destruction of military infrastructure and the Libyan regime – although this quickly morphed into the provision of close air support.

So it is unclear just how successful NFZs are at providing protection. In Iraq and Libya, NFZ cover protection was provided but neither Saddam Hussein or Colonel Gaddafi were able to effectively target victims through their ground forces whereas, in Bosnia, Slobodan Milosevic infamously used ground troops to slaughter 8,000 Bosnian men and boys at Srebrenica.

Putin would still be able to continue to use both ground forces and artillery to assault Ukrainian cities with or without a NFZ – in fact, his sparse use of his Russian Aerospace Forces (VKS) has been one of the surprising features of the war so far. Under a NFZ, missile attacks could also continue, there is nothing in the record of no-fly zones to suggest the provision of safe areas for non-combatants would work.

And NFZs have only been successful against vastly inferior forces such as in Iraq, Bosnia, and Libya. But Russia has an air force second only in size to the US and has a vast range of defences including the potent S-400 Triumf at its disposal. Not only would an NFZ be ineffective, it might also not be possible to enforce without risking significant losses to the peace operations force.

It is due to a combination of these reasons that NFZs have not been used more in previous conflicts. The most recent consideration for a NFZ was in Syria but President Bashar al-Assad’s Syrian forces, protected by Russian air cover, could still have targeted their intended victims despite air policing so a NFZ was not used.

If NATO allies and partners were to enforce a NFZ, it would represent an escalation of measures which is a step that would most likely provoke an unpredictable Vladimir Putin into further escalation

In the long-term, under the terms of a ceasefire agreement, it may be possible to include a NFZ under a UN or joint OSCE-UN peace terms. However, the forces involved should exclude NATO allies and partners or any states with Russian alliances to avoid further conflict.

This leaves few suitable countries with the capacity, willingness, and political stance to be called on. Two of the world’s most militarily capable states – China and India – abstained in the Uniting for Peace vote in the UN General Assembly (UNGA). Whether another willing state with the military capability – such as a Gulf state – could be considered acceptable to all sides remains to be tested.

Notable successes with SAMs

Many military commentators also note that currently Ukrainian forces are having notable success without jets, downing Russian aircraft using sophisticated surface-to-air missiles (SAMs) such as Stinger and Javelin, and NATO countries continue to supply those in their thousands.




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Interview: Sviatlana Tsikhanouskaya

Interview: Sviatlana Tsikhanouskaya The World Today mhiggins.drupal 25 May 2022

Belarus’s exiled democratic opposition leader tells Roxanne Escobales about her unexpected political career and President Lukashenka’s wavering support for Putin

Sviatlana Tsikhanouskaya is the face of the Belarusian democratic movement. In 2020, she stood as a presidential candidate against Aliaksandr Lukashenka after her husband, an anti-corruption campaigner and the main opposition candidate, was arrested on the campaign trail and imprisoned. Lukashenka, autocratic ruler of Belarus for more than 30 years, was re-elected. Since then, Sviatlana has lived in exile in Lithuania meeting with western leaders and calling for regime change in her native land. Her husband Sergey remains in prison serving an 18-year sentence.

You have said in the past that there will be no free Belarus without a free Ukraine. How is the fate of the two countries connected?

The Kremlin wants to drag our countries into the past, and we are looking into a future which we want to choose for ourselves. The Kremlin doesn’t recognize Ukraine or Belarus as independent countries – it sees them as part of Russia. While the current regime is in our country, there will be a constant threat of aggression from Russia. But we are absolutely independent countries with our own languages, cultures and so on.

The fate of Belarus depends a lot on the outcome of the war in Ukraine, it is evident. When Ukraine wins – and they definitely will win – it will mean the Kremlin is weak and that Lukashenka is weak. Every day we create multiple points of pressure on the regime from within the country, from outside the country. For countries like Ukraine and Belarus the support of strong democracies is very important.

The support between the Kremlin and Lukashenka has always been situational – it is not a real friendship


It is very important for European society to understand that it is not just a war between Russia and Ukraine. It is a war between democratic values and dictatorship on the territory of Ukraine. It is very important for democracy to have a strong voice at the moment.

Recently Lukashenka said the war was taking too long. Do you think he understood what he was getting into when he supported Vladimir Putin by allowing his illegal invasion to be launched from Belarus?

The support between the Kremlin and Lukashenka has always been situational – it is not a real friendship. Lukashenka got huge political and economic support in 2020 after the protests, and now he owes a debt to the Kremlin and had to show his loyalty.

And we see how his rhetoric is changing because the situation in Ukraine is changing. At the beginning Lukashenka always said that, ‘Me and Putin will take Ukraine in three days’, and when this blitzkrieg failed, now he wants to get out of the situation. Now he wants to say, ‘Look, we are for peace. We didn’t have any intention to invade Ukraine.’ He wants to act like he is a peacemaker.

He only cares about his own interest, not his country or its people. He just wants to keep his power.

You have been living in exile in Lithuania for two years, and a lot has happened in that time. What is the state of the Belarusian democratic movement now?

We have been a grassroots movement since the first day. There is no leader who says you have to do this or that. My role is to work on the political level. My task is to go to the European Union, to the United States, and ask for packages to assist civil society. With this technical assistance from our democratic partners, we have managed to build structures in exile, and people in Belarus have managed to build structures inside the country.

Another task of mine is to inspire people, and to explain to the international community what is going on and to show them that Belarus is not just Lukashenka’s regime – it is people who want change.

I communicate with Belarusian people almost every day, especially those who are in the country. We have to keep close ties. It is important to understand how dangerous it is in Belarus to communicate on different channels like Telegram or even to subscribe to some media sources. But people do this. They understand the threats and the consequences, but their energy is still so alive.

I send short messages to my [imprisoned] husband once a week through my lawyer

We have to keep this energy strong and to give this assurance to people that in case something happens to them, or their families, they will get help from outside. This is how it works.

This struggle has come at a very personal cost to you and your husband, Sergey, who is in prison for his political activities. How is he doing?

I communicate with my husband through his lawyer, who visits him once a week. It has to be short messages because there is no privacy. Our children can send him letters and they receive letters back from him.

There are thousands of people like Sergey, and we have to take care of all of them. The treatment of political prisoners is much worse than criminals because they are like Lukashenka’s personal enemies. That is why it is so important to support human rights organizations who provide lawyers to political prisoners. It is important to fund support for them and for families of political prisoners.

I didn’t have any political experience – I was an ordinary woman and wife

You were a teacher when you took over your husband’s presidential campaign. If you could go back in time, what advice would you give yourself?

I would wish I could have had more confidence. I didn’t have any political experience – I was an ordinary woman and wife, the same as millions of other Belarusians. At the beginning, I didn’t feel confident because I didn’t know about politics. I didn’t know how to communicate with the political leaders of different countries. I was scared.

What motivated you to step into your husband’s shoes?

It was an accidental choice. It was terrible for my husband. But I saw millions of people on the streets, and when you see people standing shoulder to shoulder it inspires you. Every day thousands of people call me who want to help, and I understand that we are not alone. This motivates me.

Also, the fact that thousands of children want to see their mothers and fathers who are in jail gives me strength. When sometimes you think you can’t do this any more because it is so difficult, you think about those who haven’t seen their children for two years. It is awful.

So, every day, you find something that gives you a small energy and it doesn’t let you give up.




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Gorbachev's complex legacy is beyond the popular belief

Gorbachev's complex legacy is beyond the popular belief Expert comment NCapeling 3 September 2022

The last major figure with a decisive Cold War role, Mikhail Gorbachev was not as bad as Putin’s Russia portrays him, but also not as heroic as the West thinks.

Arguably the worst year of the Cold War since the Cuban Missile Crisis was 1983, with three major incidents which escalated East-West tensions – and any one of them could have led to a full-scale war.

The first was the Korean Airline KAL007 being shot down by an SU15 fighter aircraft for straying into Soviet airspace, killing all 269 passengers and crew. Then came the identification of signals from Soviet satellites as being incoming US intercontinental ballistic missiles – Colonel Stanislav Petrov, going against all protocols, thankfully decided to report them as a false alarm before he could be sure.

The third was perhaps the most dangerous, being the misinterpretation of a live-fire NATO exercise which was believed by some in both East Germany and Russia to be a front for an imminent attack.

The greatest disappointment in Gorbachev’s legacy was he completely believed the USSR could be reformed and still survive as an entity while others, such as Boris Yeltsin and Ronald Reagan, understood it had to be dismantled

All three incidents occurred in the few months following the infamous March 1983 ‘Star Wars’ speech by US president Ronald Reagan, in which he talked about nuclear arms control and laid out the US case for a ballistic missile defence programme.

At that time Mikhail Sergeyevich Gorbachev was the youngest serving member of the USSR Politburo, known to be a favourite of Soviet leader Yuri Andropov, and it is highly likely he had been aware of these close calls and was part of discussions within Kremlin decision-making circles.

A changemaker both inside and outside the USSR

Following the deaths of Andropov in 1984 and his replacement Konstantin Chernenko in 1985, Gorbachev’s appointment as general secretary of the Communist Party saw him immediately begin to change the Soviet Union from within – and also change relationships with the major Western powers, especially the US, Germany, and the UK.

His policies of glasnost (openness) and perestroika (restructuring) were primarily aimed at internal reforms but translated into a major reset of international relations and international security. During his six years as leader, Gorbachev initiated many arms control negotiations which resulted in treaties and increased both the transparency and the confidence between the USSR and the US.

These included the 1986 Stockholm Accord which emanated from the Helsinki Process and allowed for the observation and inspection of large-scale military exercises, the 1985 resumption of the Strategic Arms Reduction Talks which lead to START I, and the 1987 INF Treaty in which the USSR ‘out-yessed’ the US – the most open and transparent disarmament treaty in terms of notification and verification measures ever agreed.

There was also a reciprocal moratorium on nuclear weapons tests starting from 1985 – which laid the groundwork for the 1996 CTBT – the 1991 Chemical Weapons Convention, and the 1990 Conventional Forces in Europe (CFE) Treaty.

The most dramatic moment of all was when Gorbachev and Reagan met at a summit in Reykjavik and came close to deciding to eliminate nuclear weapons – but the initiative failed to reach agreement, mainly because Reagan could not drop his commitment to ballistic missile defences and Gorbachev could not accept the offer of joint development.

Nonetheless, all these nuclear arms control treaties led the way for their descendants which have kept nuclear weapons in check ever since and are still in place in the form of the New START agreement.

During his six years as leader, Gorbachev initiated many arms control negotiations which resulted in treaties and increased both the transparency and the confidence between the USSR and the US

But despite these outstanding achievements, Gorbachev had blind spots – such as enabling rather than destroying the USSR bioweapons programme, unlike the US which had dismantled its own bioweapons offensive capability by 1973.

And it is now known that, despite negotiating the Chemical Weapons Convention, Russia withheld information on new chemical weapons agents – Novichoks – which have since been used to lethal effect by Russia in Salisbury and against figures opposing the current regime.

His misguided faith in a Soviet future

Gorbachev was markedly different to his predecessors as secretary general. He was neither as decrepit nor as hardline, and he understood from the outset that the Soviet Union was, by the 1980s, finally dying.

Using the intellectual abilities of Aleksandr Yakovlev, he forced through the reforms which simultaneously captured the imagination of the free world and liberated his countrymen and women.

But although he built solid relationships – even friendships – with the world’s major heads of state and improved the USSR’s human rights, releasing dissidents such as Andrei Sakharov, but many – especially Ukrainian dissidents – continued to languish in camps.

The greatest disappointment in Gorbachev’s legacy was he completely believed the USSR could be reformed and still survive as an entity while others, such as Boris Yeltsin and Ronald Reagan, understood it had to be dismantled.

This shortcoming is especially uncomfortable as today’s Russia continues to insist it has a given right to control other former Soviet states, to the extent it is willing to destroy them if they do not concede.




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Culture notes: Will the EU find its voice at last?

Culture notes: Will the EU find its voice at last? The World Today mhiggins.drupal 30 January 2023

Russia’s invasion of Ukraine has galvanized the bloc, but doubt remains about how it can capitalize on this moment, writes Catherine Fieschi.

Despite its reticence to believe that Russia would attack Ukraine, once Vladimir Putin’s tanks rolled across the Donbas, the European Union finally grasped the momentous nature of the events unfolding on its eastern flank. The immediate reaction of Europe’s member states was one of unity, resolve and uncharacteristically rapid decision-making, at least on sanctions and energy policy.

That they would need to act in concert across a concatenation of crises that would be either triggered (energy), worsened (inflation) or heightened (geopolitical instability) by Putin’s move was obvious. And so, Europe’s collective narrative of this past year slid into place, and it goes something like this: We gave Russia the benefit of every doubt, including after their invasion of Crimea when we still tried to bring them back to the negotiating table, but Putin has made the fundamental choice of turning away from democracy and the rule of law.

Europe had long been in need of an arc to follow

Now, the narrative goes on, we have to treat them as enemies and give ourselves the means to become resilient in the face of aggression as Ukraine is all that stands – both symbolically and geographically – between us and the chaos of a Europe-wide war.

Like any good narrative, it is anchored in previous trials and exploits. Having learnt from its failure to coordinate action during the eurozone crisis and then the migration crisis, Europe was keen to make the most of its resilience in the face of the Covid pandemic in the form of the joint vaccine purchases and a massive recovery plan.

The Russian invasion of Ukraine is an added – albeit dramatic and costly – opportunity to pursue further collective action and discover the next chapter of its shared purpose, as a political and perhaps even a defence alliance.

Europe had long been in need of an arc to follow. In the aftermath of the Second World War, peace and prosperity seemed enough. But the new multipolar world that emerged from the ashes of the Cold War and then 9/11 were more difficult to navigate for a largely commercial and regulatory alliance.

Could the EU, then, ever find its political voice?

David vs Goliath

While Brexit and Covid created rallying points, the shock and tragedy of the invasion delivered everything the EU needed in narrative terms: a David and Goliath story, with the opportunity to feature on Team David in European terms while allying with the United States, and a ‘band of brothers’ element to shore up a union bruised by the defection of a key but troubled member. Above all, the appearance of an arch-villain in the form of Vladimir Putin put Europe back into the familiar and mythical territory of the 1940s and then the Cold War.

When on May 28, 2016, Putin seated himself on the throne of the Byzantine emperors in Mount Athos’ Protaton Church in Greece in a scene truly worthy of Game of Thrones, the writing should have been on the wall. That day he explicitly laid out his aim to appoint himself as the new Eastern emperor who would fight the decadence of the West.

‘Today,’ Putin told the world, ‘we restore the values of patriotism, historical memory and traditional culture.’ Later, he cited Ukraine as the biggest unfinished mission of his years in power. That Europe – and Germany in particular – had taken so long to decipher Putin’s dark designs only adds to the narrative’s epic quality, positioning Europe as a victim of its own good faith and open heart.

Cracks in the narrative

But the narrative is not free from cracks. The Baltic states would argue that they had long warned of Putin’s nefarious intentions; and Poland has always been convinced of the threat posed by its neighbour.




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Review: Rediscovering Milan Kundera’s European tragedy

Review: Rediscovering Milan Kundera’s European tragedy The World Today mhiggins.drupal 28 March 2023

The Czech writer’s 40-year-old essay on the roots of Russia’s empire-building, ‘A Kidnapped West’, reads all too presciently, writes Stefan Auer.

A Kidnapped West: The Tragedy of Central Europe
Milan Kundera, Faber, £10

‘In November 1956, the director of the Hungarian News Agency, shortly before his office was flattened by artillery fire, sent a telex to the entire world with a desperate message announcing that the Russian attack against Budapest had begun. The dispatch ended with these words: “We are going to die for Hungary and for Europe.”’ Thus, Milan Kundera began his 1983 essay for the French journal Le Débat, reflecting on the 1956 Hungarian Uprising.

A seminal essay

The Czech author might well have written a near-identical passage about the fraught hours immediately after Russia’s invasion of Ukraine in 2022. In the event, Russian tanks failed to occupy Kyiv, unlike Budapest in 1956. Nevertheless, Faber has chosen this moment, 40 years later, to republish Kundera’s seminal essay on Europe and Russian aggression in its original translation for the New York Review of Books by Edmund White. How salient are its observations today?

Thanks to the Cold War, the countries of Central Europe were denied their true destiny, Kundera thought, in the democratic West

The essay’s original French title, ‘Un Occident kidnappé ou la tragédie de l’Europe centrale’ (The Kidnapped West, or the Tragedy of Central Europe), described the fate of Hungary, Czechoslovakia in 1968 and, to an extent, Poland in 1980-81 at the hands of the Soviet Union. Owing to the Cold War division of Europe, the countries of Central Europe were denied their true destiny, Kundera thought, to be an integral part of the liberal, democratic West. Kundera himself fled Czechoslovakia for France in 1975.

The author of The Unbearable Lightness of Being might no longer be as well-known as he was at the height of his fame in the 1980s, but his novels and essays still deserve attention. So, it is pleasing to see Kundera’s masterpiece republished, even as it is awful to witness the enduring relevance of the questions it raises.

What did the Hungarian journalist mean when he declared his willingness to die for Europe, Kundera asked? That ‘Russians, in attacking Hungary, were attacking Europe itself. He was ready to die so that Hungary might remain Hungary and European’. The journalist did indeed die in the uprising.

It is a line that President Volodymyr Zelenskyy and his supporters abroad have echoed time and again: that Ukrainian soldiers are not just dying for their country, they are dying for Europe at large.

Kundera’s suspicion of Russia has been validated. His frustration about the indifference of the West less so

The ‘tragedy’ in Kundera’s essay was that the West didn’t care. ‘Europe hasn’t noticed the disappearance of its cultural home,’ Kundera wrote, ‘because Europe no longer perceives its unity as a cultural unity.’

In other words, as the cultural sphere in Central Europe continued to defy the political restrictions imposed by the Soviet empire, it embodied the western values of freedom and democracy more than the West itself did. The extent to which this analysis remains relevant today will prove decisive for Europe’s future.

As timely as ever

Kundera’s essay is as timely as ever but in ways that both vindicate and challenge his key arguments. His suspicion of Russia has been validated. His frustration about the indifference of the West less so. But the true tragedy of Ukraine would be if the West has not changed sufficiently. So far, the West appears to be doing enough to enable Ukraine to defend itself, but not enough to defeat the aggressor.

[A small nation] is one whose very existence can be put in question at any moment; a small nation can disappear and it knows it

Milan Kundera

Faber has made an excellent decision in combining The Tragedy of Central Europe with a lesser-known text by Kundera: his 1967 speech to the Czech Writers’ Congress given the year before the ill-fated Prague Spring. In it, Kundera addressed what was to become a lifelong preoccupation: the fate of small nations. ‘For Czechs’, Kundera wrote, ‘nothing has ever constituted an indisputable possession – neither their language nor their belonging to Europe.’

Rather than reflecting the size of its territory or population, a small nation ‘is one whose very existence can be put in question at any moment; a small nation can disappear, and it knows it.’ In this way Ukraine, Europe’s largest country, apart from Russia, is fighting to avoid the fate of Kundera’s ‘small nation’.

Historically, the ‘small’ nations of Central Europe were threatened by both Germany and Russia. But after the Second World War, the threat was from the Soviet Union, which for Kundera was indistinguishable from Russia (tacitly including Ukraine). In its expansiveness, Russia was the opposite of Central Europe. While the latter was based on the principle of ‘the greatest variety within the smallest space’, the former represented ‘the smallest variety within the greatest space’.

Kundera was criticized for observations that smack of civilizational racism, yet his bleak view of Russia remains prescient

In this sense, authoritarian communism was the fulfilment of Russian history, Kundera argued, writing that ‘Russian communism vigorously reawakened Russia’s old anti-western obsessions and turned it brutally against Europe’. Vladimir Putin’s Russia appears to build on these same pernicious impulses.

Kundera was widely criticized for observations in his essay that smack of civilizational racism (including by me) describing Russians as fundamentally different from us: ‘Russia knows another (greater) dimension of disaster, another image of space (a space so immense that entire nations are swallowed up in it), another sense of time (slow and patient), another way of laughing, living, and dying’.




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Independent Thinking: Sweden, Finland, and NATO

Independent Thinking: Sweden, Finland, and NATO Audio NCapeling 31 March 2023

Episode 21 of our weekly podcast examines the latest developments relating to Sweden and Finland’s proposed accession to NATO.

The Hungarian parliament has finally ratified Finland’s membership to the NATO alliance, two weeks after President Erdogan in Turkey gave his seal of approval following a meeting with the Finnish president.

Sweden however remains trapped in limbo, with both Turkey and Hungary delaying Stockholm’s membership and Erdogan in particular asking for more concessions.

The panel discusses why Turkey and Hungary took issue with Sweden and Finland, what the strategic situation in the Baltic looks like now with only Finland joining NATO, and the challenges facing Sweden amid its fraught ties with President Erdogan.

We also look ahead to Turkey’s presidential election in May as recent opinion polls point to a neck-and-neck race, with some polls even showing President Erdogan falling behind the opposition. The panel examines what the sentiment is like in Turkey ahead of the election, and how the world would respond if there was a change in power in Ankara for the first time in 20 years.

Joining Bronwen Maddox on the podcast this week is Henri Vanhanen, research fellow with the Finnish Institute of International Affairs, and Galip Dalay, associate fellow with our Middle East and North Africa programme.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.




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[68Ga]Ga-PSMA-11 PET/CT-Positive Hepatic Inflammatory Pseudotumor: Possible PSMA-Avid Pitfall in Nuclear Imaging




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Ultrashort Oncologic Whole-Body [18F]FDG Patlak Imaging Using LAFOV PET

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 (Ki) (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 Ki (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 Ki 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.




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Design, Synthesis, and Preclinical Evaluation of a High-Affinity 18F-Labeled Radioligand for Myocardial Growth Hormone Secretagogue Receptor Before and After Myocardial Infarction

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with 18F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with 18F a quinazolinone derivative ([18F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [18F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [18F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [13N]NH3 PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [18F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [18F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [18F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [18F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.




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Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT

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 p53R175H 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 p53R172H 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.




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Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177Lu-Labeled Radiohapten

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic - and β-emitting isotope 177Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [177Lu]Lu-Gemini was prepared with no-carrier-added 177LuCl3 to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-177Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [177Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [177Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([177Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [177Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [177Lu]Lu-Gemini behaved similarly to [177Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [177Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor–to–normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [177Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [177Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [177Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [177Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [177Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered 177Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).




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[68Ga]Ga-RAYZ-8009: A Glypican-3-Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging--A First-in-Human Case Series

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [68Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [68Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with 68Ga from a 68Ge/68Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [68Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non–tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor–to–healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUVmax of these lesions was 19.6 (range, 2.7–95.3), and the mean SUVmean was 10.1 (range, 1.0–49.2) at approximately 60 min after administration. Uptake in non–tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUVmean, <1.6), with a continuous decline to 4 h after administration (mean SUVmean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUVmax of 31.3) and decreased gradually afterward. Conclusion: [68Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [68Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.




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1,090 Publications and 5 Years Later: Is FAP-Targeted Theranostics Really Happening?




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The Rise of Molecular Image-Guided Robotic Surgery

Following early acceptance by urologists, the use of surgical robotic platforms is rapidly spreading to other surgical fields. This empowerment of surgical perception via robotic advances occurs in parallel to developments in intraoperative molecular imaging. Convergence of these efforts creates a logical incentive to advance the decades-old image-guided robotics paradigm. This yields new radioguided surgery strategies set to optimally exploit the symbiosis between the growing clinical translation of robotics and molecular imaging. These strategies intend to advance surgical precision by increasing dexterity and optimizing surgical decision-making. In this state-of-the-art review, topic-related developments in chemistry (tracer development) and engineering (medical device development) are discussed, and future scientific robotic growth markets for molecular imaging are presented.




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Navigating the Future of Prostate Cancer Care: AI-Driven Imaging and Theranostics Through the Lens of RELAINCE




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How to Explain Turkey's Early Elections

How to Explain Turkey's Early Elections 14 June 2018 — 12:30PM TO 1:30PM Anonymous (not verified) 29 May 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

On 24 June 2018 Turkey will go to the polls to vote in early presidential and parliamentary elections. Following a constitutional referendum last spring and against the backdrop of Turkey’s continued intervention in Syria and rising economic problems, President Erdogan has argued that an early election would help reduce uncertainty and set the country on a course to greater prosperity. The elections, likely to be held under the state of emergency in place since the attempted coup in July 2016, will also mark the country’s transformation from a parliamentary democracy to one with a powerful executive presidency.

In this session, the speaker will discuss what other factors led President Erdogan to call for an early election, what the state of the opposition is and what we can expect from Turkey should Erdogan win another term.

Attendance at this event is by invitation only.




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Turkey-Russia Relations: A Marriage of Convenience?

Turkey-Russia Relations: A Marriage of Convenience? 26 November 2020 — 12:00PM TO 1:30PM Anonymous (not verified) 17 November 2020 Chatham House

Speakers discuss the complex but, so far, durable ties between Putin and Erdogan and the perspectives of each leader. Other issues will include the impact of the Biden presidency and the unfolding situation in Nagorny Karabakh.

This is an online only event

Russia-Turkey relations are governed by a unique dynamic between presidents Vladimir Putin and Recep Tayyip Erdogan. They pursue contrasting objectives in Libya, the Eastern Mediterranean, Caucasus and Ukraine; yet they have managed to compartmentalize their differences to avoid any spill-over into diplomatic, military and economic cooperation.

Erdogan purchased the Russian S400 missile defence system at the cost of ejection from the US-led fourth generation F35 stealth fighter programme; and at the risk of sanctions by Washington. Russia is also proceeding with the construction of the Akkuyu Nuclear Power Plant near Turkey’s Mediterranean coast.




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Planet Fitness makes second bid to buy out Blink Fitness chain in bankruptcy

Planet Fitness is seeking to further grow its number of locations in a second bid for the Blink Fitness chain of workout facilities, according to new reports.




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Stellantis trimming 1,100 jobs at its Toledo Jeep Gladiator plant

About 1,100 workers will be laid off indefinitely in January from the Jeep Gladiator plant in Toledo, Ohio, Stellantis officials announced Wednesday.




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Australia to legislate social media ban for those under 16

Australian Prime Minister Anthony Albanese said Thursday his government will introduce legislation to ban children under 16 years of age from social media.




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Qantas flight lands safely at Sydney after suffering engine failure during takeoff

A Qantas airlines flight made an emergency landing at Sydney Airport on Friday afternoon after suffering engine failure shortly after takeoff, the company said.




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Tesla regains $1 trillion in market capitalization in post-election surge

Tesla Friday reached a $1 trillion market capitalization value for the first time since 2022 in a post-election stock rally.




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SS United States to be towed from Phila., launching transition into artificial reef

The historic ocean liner SS United States, whose fate had been in limbo for years, will begin its transition into the world's largest sunken artificial reef beginning this week in Philadelphia, its owner says.




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Five additional monkeys from S.C. research lab recovered; 13 remain at large

An additional five rhesus macaque monkeys that escaped from a South Carolina research facility last week have been recovered, meaning about a dozen of the rhesus macaque primates remain at large.




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Shell wins appeal against landmark court-ordered emissions reductions in The Hague

Oil giant Shell emerged victorious Tuesday from a Dutch court where it was appealing a ruling ordering it to slash its global carbon emissions by 45% by the end of the decade in line with the Paris climate agreement.




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Costco recalls nearly 80,000 pounds of butter due to possible mislabeling

Costco voluntarily recalled 79,200 pounds of two types of its store-brand butter over the past month because their labels may not have said the products contain milk.




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Supermicro Introduces JBOF Storage Platform Powered by NVIDIA BlueField-3 for Scalable AI and HPC

SAN JOSE, Calif., Oct. 16, 2024 — Supermicro, Inc. is launching a new optimized storage system for high performance AI training, inference and HPC workloads. This JBOF (Just a Bunch […]

The post Supermicro Introduces JBOF Storage Platform Powered by NVIDIA BlueField-3 for Scalable AI and HPC appeared first on HPCwire.




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Xsight Labs Launches E1 SoC Built on TSMC’s 5nm Tech for AI Workloads

Oct. 16, 2024 — Xsight Labs, a leading fabless semiconductor company providing end-to-end connectivity solutions for next-generation hyperscale, edge, and AI data center networks, has announced the tape-out of the […]

The post Xsight Labs Launches E1 SoC Built on TSMC’s 5nm Tech for AI Workloads appeared first on HPCwire.




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NextSilicon Launches Maverick-2, Introducing Software-Defined Acceleration for HPC Workloads

TEL AVIV, Israel and MINNEAPOLIS, Oct. 30, 2024 — NextSilicon, a pioneer in high-performance computing (HPC) innovation, today announced its emergence from stealth with the launch of Maverick-2, the industry’s first […]

The post NextSilicon Launches Maverick-2, Introducing Software-Defined Acceleration for HPC Workloads appeared first on HPCwire.




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Ukraine blasts Russia with massive overnight drone strike

Ukraine launched a massive drone attack on Moscow overnight, the largest on the Russian capital since the Russian invasion more than two years ago, forcing three airports to divert traffic and causing casualties.




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Strong earthquakes strike Cuba, causing damage and landslides

A pair of strong earthquakes has struck off the southern coast of Cuba, inflicting damage and causing landslides.




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Starmer, Macron reaffirm 'ironclad' support for Ukraine amid uncertainty around Trump

French President Emmanuel Macron was joined in Paris on Monday by British Prime Minister Keir Starmer for Armistice Day commemorations after a meeting at which both leaders reaffirmed "unwavering" support for Ukraine.




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North Korea ratifies landmark defense pact with Russia

North Korea ratified a defense treaty with Russia, state media reported Tuesday, formally deepening military cooperation that has seen Pyongyang send thousands of troops to help Moscow in its war against Ukraine.




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Shell wins appeal against landmark court-ordered emissions reductions in The Hague

Oil giant Shell emerged victorious Tuesday from a Dutch court where it was appealing a ruling ordering it to slash its global carbon emissions by 45% by the end of the decade in line with the Paris climate agreement.




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PNNL-Microsoft Collaborate on Cloud Computing for Chemistry, More to Come

RICHLAND, Wash.—Some computing challenges are so big that it’s necessary to go all in. That’s the approach a diverse team of scientists and computing experts led by the Department of Energy’s […]

The post PNNL-Microsoft Collaborate on Cloud Computing for Chemistry, More to Come appeared first on HPCwire.



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