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Mental Health Bill promises more tailored and dignified treatment for people detained




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Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis




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Moderate alcohol intake is linked to lower risk of ischaemic stroke, study finds




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Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study




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NICE recommends implantable monitor to identify atrial fibrillation after stroke




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Artificial pancreases for type 1 diabetes: Better access is “watershed moment”—but delivery is key




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Scarlett McNally: Preventing obesity is different from curing it—and even more urgent




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FDA approves first over-the-counter blood glucose monitor for diabetes




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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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American democracy in 2022: Trump, insurrection, and midterm elections

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

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

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

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

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

Key questions discussed include:

  • What has been learned from the January 6 Committee?

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

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

  • What are the broader ramifications of the Trump era?

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

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

Read the transcript. 




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The Commonwealth reimagined

The Commonwealth reimagined 8 November 2022 — 6:00PM TO 7:00PM Anonymous (not verified) 18 October 2022 Chatham House and Online

Ghana’s minister of foreign Affairs, the Hon. Shirley Ayorkor Botchwey, discusses her vision for a modern Commonwealth and how it can evolve and match demands from its members.

The death of HM Queen Elizabeth II has focused attention on the future of the Commonwealth. The Commonwealth is an expanding voluntary organization of 56 independent countries in Africa, Asia, the Americas, Europe, and the Pacific.

Its appeal is increasingly beyond the circle of former British colonies – ex-French colonies Togo and Gabon officially joined in October 2022 and the ex-Portuguese colony, Angola, has applied. The Commonwealth Secretariat, established in 1965, is its main intergovernmental agency, which coordinates and carries out much of the Commonwealth’s work, supported by a network of more than 80 organizations.

King Charles III now heads the Commonwealth, which is focused on shared goals of prosperity, democracy and peace. However, the future of the Commonwealth and its purpose are unclear, and the organization needs to develop a sharper agenda on what its international contribution can be across its 56 state members and their peoples.

The minister discusses key questions including:

  • What should a modern Commonwealth look like and how can it best operate?

  • How can the organization impact policies and actions at a country level?

  • What role will young people play in the future of the Commonwealth?

  • How can the organization harness collective resources and technology to tackle major global issues such as climate change?

  • Can the issue of mobility and immigration among member states be managed?




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What’s next in UK monetary policy?

What’s next in UK monetary policy? 4 November 2022 — 4:00PM TO 5:30PM Anonymous (not verified) 19 October 2022 Chatham House and Online

A panel of leading experts discuss the future direction of UK monetary policy.

The UK’s so-called ‘mini-budget’ on 23 September led to a severe market reaction and a wave of criticism at home and abroad that ultimately forced the sacking of UK chancellor Kwasi Kwarteng and contributed to the downfall of Liz Truss’s government.

The new chancellor Jeremy Hunt is due to deliver what will essentially be an entirely new budget in mid-November, with a full assessment from the Office of Budget Responsibility. This will follow the meeting of the Bank of England’s interest rate setting Monetary Policy Committee (MPC) on Thursday 3 November.

Given rising inflationary pressures worldwide, it seems highly likely that the MPC will increase interest rates once again, but by how much and how far there will have to be an additional premium linked to the government’s fiscal strategy is far from clear.

Chatham House’s Global Economy and Finance programme is pleased to partner with Fathom Consulting to host a special session of Fathom’s Monetary Policy Forum.

A presentation of Fathom’s latest economic outlook, fully updated to take account of the previous day’s MPC decision, will be followed by a discussion among four of the MPC’s original former external members. Key questions will include:

  • How far has the government been able to restore its fiscal credibility?
  • Did the MPC make the right decision on 3 November?
  • What is the likely pace and extent of monetary tightening in the UK going forward?
  • What will be the long-term consequences for the UK economy of the past month’s policy experiment?
  • What are the international implications?

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

This event is in partnership with Fathom Consulting.




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Chatham House Primer: Social media and democracy

Chatham House Primer: Social media and democracy 21 March 2023 — 6:00PM TO 6:45PM Anonymous (not verified) 23 February 2023 Chatham House

From the Arab Spring to the 2016 Trump election win, how have democracies benefited and suffered from the impact of social media? 

With social media now a well-entrenched, yet still recent, component of societies, democracies are still grappling with the impact bought about by this new form of communication and promotion.

For all that social media has bought people closer together and brought government, business and civic leaders, it has also been said to have fuelled divisions and hate. Governments and businesses are now drawing battle lines on the legal responsibilities required of social media platforms as we slowly determine the role they play in our society.

This Primer will discuss key questions including:

  • What are the current legal responsibilities of social media companies? What sort of laws and regulations must they abide by?
  • How are governments looking to change to this?
  • How have some countries manipulated social media to monitor and censor their populations?
  • Can social media truly tackle harmful and dangerous content?
  • Is it possible to combat disinformation and what role should social media platforms play?
  • How can we make social media best fit our society in the future?
  • How should we govern online space?

A drinks reception will follow this event.

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




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Memory politics: the challenge of commemoration in post-Soviet Eastern Europe and the Caucasus

Memory politics: the challenge of commemoration in post-Soviet Eastern Europe and the Caucasus 5 October 2021 — 1:00PM TO 2:30PM Anonymous (not verified) 21 September 2021 Online

This event explores how to address memory and commemoration in the former Soviet states, considering their role in political processes and violent conflict. 

How the past is remembered and commemorated plays a large role – perhaps too large – in contemporary political debates and in how conflicts are negotiated.

Perceptions of history influence people’s actions and are used to judge or dismiss the actions of others. Nowhere is this more so than in the political, territorial and social debates and disputes across the former Soviet Union.
 
This event examines how to address the problems caused by entrenched memory debates – and proposes a framework for ‘ethical political commemoration’ for use across historical enquiry, political processes, and conflict transformation initiatives.

The speakers explore the topic through the context of Turkey and the Armenian genocide, as well as more broadly through their own experiences in conflict transformation and peace processes.




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How do Eurasian kleptocracies earn and use their money?

How do Eurasian kleptocracies earn and use their money? 9 November 2021 — 1:00PM TO 2:30PM Anonymous (not verified) 22 October 2021 Chatham House and Online

This event explores the presence of corrupt funds from Eurasia in Western democracies, what they are used for, and how they can be constrained.

The Pandora Papers once again shone the spotlight on the UK being home to corrupt funds from kleptocracies, where the ruling elite abuse their political power for private gain.

In recent years much focus has been placed on this term, and the possible effects such money could have on Western democracies.

  • How do such states create this wealth in the first place?
  • How do these funds make their way to the UK?
  • Is the term kleptocracy appropriate for the majority of countries in Eurasia?
  • What evidence is there that such funds are ‘weaponized’ to achieve foreign policy goals?

This event discusses the term, how it can be applied, and the differences between how ’grey’ funds are used by various countries. It also highlights how the UK and the wider international community can counteract these flows, both from a legal point of view, and via other methods.




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Here we go again: Russia’s energy ‘diplomacy’ in Moldova

Here we go again: Russia’s energy ‘diplomacy’ in Moldova Expert comment LJefferson 6 December 2021

The gas crisis shows that while the new Moldovan government may wish for geopolitics to go away, they are a weapon Russia will deploy at will.

In October, Moldova came under the spotlight when Russia, its primary provider of gas, slashed supplies by a third and refused to extend the existing contract.

The crisis was resolved at the end of October when Russia and Moldova signed a new contract, in which Moscow has used Moldova’s gas dependence to extract geopolitical concessions, weaken the new pro-western Chisinau government and drive a wedge between the EU and Moldova.

A chronic failure to reform

Moldova became a classic case of state capture when political elites – including nominally pro-European political elites – engaged in massive rent-extraction.

Up until 2020, when pro-reform forces came to power, Moldovan politics offered rapid route to riches for both the nominally pro-European parties and the pro-Russian Socialist Party; each was responsible for playing up ethnic and geopolitical cleavages in the country to mobilize votes and shore up legitimacy.

These predatory elites hollowed out Moldova economically and politically by a chronic failure to reform, in particular the energy sector which became a major source of rent.

However, this started to change when the pro-reform forces came to power as a result of the 2020 presidential and then 2021 parliament elections. The pro-reformist Maia Sandu defeated the incumbent president Igor Dodon (58 per cent to 42 per cent) in November of that year. And then her party got 58 per cent of the vote in the parliamentary elections which followed in July 2021.

The Party of Action’s winning formula was to focus on corruption and domestic reforms – rather than playing the ‘geopolitical’ card, a favourite strategy of their predecessors.

Her Party of Action’s (PAS) winning formula was to focus on corruption and domestic reforms – rather than playing the ‘geopolitical’ card, a favourite strategy of their predecessors. As Sandu put it, the elections marked ‘the end of the reign of thieves in Moldova’.

A gas crisis is initiated  

Russia’s response to these results was to initiate a gas crisis. Up until the victory of the pro-reform forces, Russia had annually renewed a gas contract signed in 2007. However, in September 2021, Russia refused to renew the contract as it had done many times before and instead insisted on a new contract, which allowed Russia to create linkages between energy prices, debt settlement, a halt on energy market reforms and, it can be logically inferred, further integration with the EU.

Moldova’s national energy company, Moldovgaz, is 63.5 per cent de facto owned by Gazprom with the Moldovan government owning the remaining 35.5 per cent. (Moldova was forced to give Gazprom a controlling stake when faced with a cut in supplies in January 2006). It is therefore hardly surprising that no efforts were made to de-monopolise the sector and diversify energy supplies.

This lack of modernization can be explained by the somewhat surreal fact that in any negotiations and planning, Moldovagaz – majority owned by Gazprom – represents the Moldovan side in negotiations with Gazprom. So, when it came to signing of the new five-year contract in October 2021, Russia, through Gazprom, was able to institute a contract which made gas prices conditional on various geopolitical conditions.

It is noteworthy that Moldova’s original 2007 gas contract had been renewed annually despite the supposed accrual of debt. However, the very nature of this debt is suspect. While Moldova’s debt is said to be approximately $700 million, the debt of the much smaller breakaway Transnistria was around $7.3 billion.

The exact level and source of the debt remain murky. Russia appears to be making Moldova liable to repay at least some of Transnistria’s debt while only demanding the debt settlement with Moldova, but not with Transnistria.

High stakes for Moscow

Moreover, the contract is used to derail liberalisation of the energy market in line with EU’s energy market rules (through the so-called unbundling of supplies and distribution) which Moldova had committed itself to since the country joined the Energy Community in 2010.

Referring to ‘the non-application of forced reorganization and sanctions against Moldovagaz’, the new gas contract forces Moldova to postpone implementing the unbundling of supplies and distribution by making it conditional on resolving the energy debt.

Furthermore, Moldova ominously agreed to create an ‘intergovernmental commission on economic cooperation’ with Russia, which effectively blocks Moldova’s economic integration with the EU. (This demand is hardly new as Russia previously requested, and was granted, a seat at the negotiating table on a bilateral trade agreement between the EU and Ukraine. The trilateral EU-Ukraine-Russia negotiations have made it clear that Russia is seeking a veto over European integration of all neighbouring countries.)  

Targeting Moldova’s new reformist government reflects high personal stakes for Moscow. Moldova’s caretaker (kurator) in the Kremlin is Dimitrii Kozak, who in 2003 masterminded the so-called ‘Kozak Memorandum’. This sought to reintegrate breakaway Transnistria into a Moldova-Transnistria federation.

It was thwarted at the last minute but the Russian leadership has not given up on its plan. Now using his position as the deputy head of Presidential Administration, Kozak is masterminding Russia’s rehashed policy towards Moldova and has attempted to bring back his Memorandum as a political blueprint for a ‘settlement’.

Russia’s heavy-handed energy ‘diplomacy’

The new Moldovan government is caught in a crossfire of domestic expectations and Russian geopolitical demands. The gas crisis shows that while the new government may wish for geopolitics to go away, they are a weapon Russia will deploy at will.

The new Moldovan government is caught in a crossfire of domestic expectations and Russian geopolitical demands.

The Moldovan government is brand new so it has relatively little experience of dealing with Russia’s heavy-handed ‘energy diplomacy’. But the EU has been on the receiving end of this before – this is a direct replica of Russia’s strategy toward Armenia and Ukraine – and neither ended well for the target countries or for the EU.

So, Russia’s plans for Moldova are likely to have similar consequences for the EU’s latest attempts to be a convincing foreign policy actor. 




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Limited expectations as Scholz heads to Kyiv and Moscow

Limited expectations as Scholz heads to Kyiv and Moscow Expert comment NCapeling 14 February 2022

After heavy criticism for an initially timid response, the approach of Germany’s new government to the Ukraine crisis is improving as its position on Russia evolves.

Olaf Scholz is a famously quiet and cautious communicator and, as concerns mounted in Washington and London about the possibility of a Russian invasion of Ukraine, the new German chancellor remained silent.

This time his silence reflected the fact that his government was unprepared for its first major foreign policy test, with marked divisions between the SPD and the Greens on how to manage a rapidly deteriorating relationship with Russia.

When he did speak, Scholz caused dismay in several NATO capitals by defending the controversial Nord Stream 2 pipeline. He called it ‘a purely private economic project’ even though the company building the pipeline is a subsidiary of Russia’s state-owned Gazprom.

Scholz has prepared the ground carefully for his visits to Kyiv and Moscow, extensively coordinating with NATO allies, such as France and Poland – as part of the Weimar Triangle – and the three Baltic states

The absence of crisis management from Berlin was a stark reminder of the gap left by Angela Merkel. Her knowledge of Russia and Ukraine, and her personal experience of dealing with Vladimir Putin, were key assets in 2014 in developing a unified western response to Russia’s annexation of Crimea and its destabilization of south-eastern Ukraine.

Germany has coordinated with its allies

Scholz has prepared the ground carefully for his visits to Kyiv and Moscow, extensively coordinating with NATO allies, such as France and Poland – as part of the Weimar Triangle – and the three Baltic states. His inaugural visit to Washington helped align positions on US-EU efforts to develop an economic deterrent against further Russian intervention in Ukraine.

Scholz has also repeated Merkel’s language from 2014 to signal to Moscow that Germany and its partners are ‘united and determined’ to stand their ground. And he has spoken of Germany’s continuing double strategy of ‘clear announcements’ to Moscow of the price it would pay for further aggression accompanied by a readiness to use all possible channels of dialogue to preserve peace.

The continuation of Germany’s established policy will not surprise Moscow. But under the surface Germany’s discourse on Russia is evolving as the political class internalizes the fact that the current Russian leadership is openly threatening to use military force to impose its will on Ukraine and re-configure Europe’s security arrangements.

Despite deep concerns about Germany’s dependence on Russian gas – more than half of the gas it consumes comes from Russia – there is broad acceptance that Nord Stream 2 cannot go ahead if Russia invades Ukraine. But typically, Scholz has not yet said as much publicly, limiting himself to stating ‘all options are on the table.’

Despite its mantra that there is no alternative to the Minsk Agreements, Berlin now admits these currently offer no prospect of resolving the war in Donbas

Robert Habeck, Germany’s vice-chancellor as well as economic affairs and climate action minister, says the ‘geopolitical situation’ requires Germany to diversify its gas supplies and infrastructure for importing gas. For years, a strong pro-Russian gas lobby has dominated the thinking of the Economics Ministry and one consequence is the complete absence of facilities to import liquefied natural gas.

The German debate on Russia is shifting

A public debate has also started about weapons deliveries to Ukraine, even though this runs counter to deeply embedded pacifist tendencies in German society. Some MPs, former diplomats, and experts have begun to make the case for Germany to supply weapons to Ukraine so it can exercise its right to self-defence and deter military attack.

Christoph Heusgen, a former long-standing foreign policy adviser in the Federal Chancellery, says Berlin’s decision not to deliver arms to Ukraine to avoid endangering the Minsk peace process requires revision now Moscow has abandoned the path of negotiation.

Despite its mantra that there is no alternative to the Minsk Agreements, Berlin now admits these currently offer no prospect of resolving the war in Donbas because Russia is not prepared to implement them properly.

Other taboos are also being broken inside Germany. Heavyweight left-of-centre Die Zeit published the first results of its investigation into the SPD’s links with Russia and their place in Russia’s channels of influence in Germany. And even the SPD’s Sigmar Gabriel, an outspoken champion of Nord Stream 2 during his time as a government minister, has raised the question of Germany terminating energy imports from Russia if there is a drastic deterioration of the security situation.




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President Maia Sandu on democracy and politics in Moldova

President Maia Sandu on democracy and politics in Moldova Video jon.wallace 4 July 2022

The president covers Moldova’s challenges as it seeks closer integration with the European Union.

President Maia Sandu discusses challenges to Moldovan democracy and society during an interview at Chatham House’s 2022 London Conference.

She covers issues including corruption, the presence of Russian troops in the Transnistria region, neutrality in Moldova’s constitution, popular support for EU membership and refugees from Russian aggression in Ukraine.




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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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C-X-C Motif Chemokine Receptor 4-Directed Scintigraphy Using [99mTc]Tc-Pentixatec in Primary Aldosteronism: A Proof-of-Concept Study

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.




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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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Preclinical Evaluation of 177Lu-OncoFAP-23, a Multivalent FAP-Targeted Radiopharmaceutical Therapeutic for Solid Tumors

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.




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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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Dual Somatostatin Receptor/18F-FDG PET/CT Imaging in Patients with Well-Differentiated, Grade 2 and 3 Gastroenteropancreatic Neuroendocrine 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 SUVmax for each tracer; 18F-FDG/68Ga-DOTATATE SUVmax 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 SUVmax of target lesions on 68Ga-DOTATATE and the SUVmax of target lesions on 18F-FDG PET (P = 0.505). 18F-FDG/68Ga-DOTATATE SUVmax 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 SUVmax ratios in target lesions and FTV/MTV ratios can discriminate between patients with high and low NETPET scores.




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Quantitative SPECT/CT Metrics in Early Prediction of [177Lu]Lu-DOTATATE Treatment Response in Gastroenteropancreatic Neuroendocrine Tumor Patients

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 TBSsecond-first, TBSthird-first, and TBSfourth-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). nPCsecond-first showed significant group differences (mean, –0.107 vs. –0.282; P = 0.033); nPCthird-first and nPCfourth-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, TBSfourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. TBSsecond-first and TBSthird-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. nPCsecond-first, nPCthird-first, and nPCfourth-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.




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Composite Prediction Score to Interpret Bone Focal Uptake in Hormone-Sensitive Prostate Cancer Patients Imaged with [18F]PSMA-1007 PET/CT

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 SUVmax, SUVmean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HUmean) 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 SUVmax (P < 0.001) and HUmean (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 HUmean (AUC, 0.62) and remained high among lesions with HUmean 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.




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Diagnostic Accuracy of [18F]FDG PET/MRI in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Metaanalysis

This study evaluates the diagnostic utility of PET/MRI for primary, locoregional, and nodal head and neck squamous cell carcinoma (HNSCC) through systematic review and metaanalysis. Methods: A systematic search was conducted using PubMed and Scopus to identify studies on the diagnostic accuracy of PET/MRI for HNSCC. The search included specific terms and excluded nonhybrid PET/MRI studies, and those with a sample size of fewer than 10 patients were excluded. Results: In total, 15 studies encompassing 638 patients were found addressing the diagnostic test accuracy for PET/MRI within the chosen subject domain. Squamous cell carcinoma of the nasopharynx was the most observed HNSCC subtype (n = 198). The metaanalysis included 12 studies, with pooled sensitivity and specificity values of 93% and 95% per patient for primary disease evaluation, 93% and 96% for locoregional evaluation, and 89% and 98% per lesion for nodal disease detection, respectively. An examination of a subset of studies comparing PET/MRI against PET/CT or MRI alone for evaluating nodal and locoregional HNSCC found that PET/MRI may offer slightly higher accuracy than other modalities. However, this difference was not statistically significant. Conclusion: PET/MRI has excellent potential for identifying primary, locoregional, and nodal HNSCC.




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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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This Month in JNM




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EU-Turkey Customs Union: Prospects for Modernization and Lessons for Brexit

EU-Turkey Customs Union: Prospects for Modernization and Lessons for Brexit 12 December 2018 — 12:30PM TO 1:30PM Anonymous (not verified) 26 November 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Turkey and the EU have been in a customs union since 1995. Both sides recognize that the current agreement is in need of modernization and have agreed to open negotiations to expand its scope to include services, public procurement, agriculture and other elements that would help bring it into the 21st century.

At the same time, the UK Parliament is debating whether to approve the agreement on the UK’s withdrawal from the EU. It includes a backstop which – if triggered – would keep the UK and the EU in a single customs territory which would limit the disruption of withdrawal but hamper Britain’s ability to pursue an independent trade policy. The political declaration proposes building on this customs arrangement as the basis for the future relationship.

In this context, the speaker will discuss the current EU-Turkey customs union arrangement and its shortcomings, examine the prospects for its modernization and share his insights on the lessons for the UK’s future trading relationship with the EU.

The event will launch the briefing paper ‘EU-Turkey Customs Union: Prospects for Modernization and Lessons for Brexit’.

Attendance at this event is by invitation only.




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Medical supply company McKesson to pay more than $400K over discriminatory hiring

McKesson Medical-Surgical Inc. entered into an agreement with the Labor Department on Monday resolving employment discrimination issues involving nearly 900 Black, Hispanic, and White applicants at a distribution center




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FDA says commonly used decongestant 'not effective,' proposes removal

The U.S. Food and Drug Administration has determined commonly used oral phenylephrine is "not effective" and has proposed its removal from over-the-counter nasal decongestants.




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More than 500,000 space heaters sold on Amazon recalled

More than 500,000 space heaters from GoveeLife and GoveeSmart Electric are being recalled because of safety issues, according to the U.S. Consumer Product Safety Commission.




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Trump calls rumors he may sell $3.5B Trump Media stake 'illegal,' calls for investigation

President-elect Donald Trump wants legal authorities to investigate what he said were possibly illegal rumors he is going to sell his majority stock stake in Trump Media. He claims he won't sell.




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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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SDSC Leads Expansion of Open Storage Network to More Campus Computing Sites

Oct. 24, 2024 — The San Diego Supercomputer Center (SDSC), part of the School of Computing, Information and Data Sciences at UC San Diego, has been leading the Open Storage Network (OSN) program for years, and along […]

The post SDSC Leads Expansion of Open Storage Network to More Campus Computing Sites appeared first on HPCwire.




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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.



  • Features
  • Pacific Northwest National Laboratory

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Tagovailoa, Jones among 5 must-start fantasy football quarterbacks for Week 10

Tua Tagovailoa and Daniel Jones are among UPI senior sports writer Alex Butler's five must-start fantasy football quarterbacks for Week 10.




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Fantasy football: Gesicki, Smith among 4 must-start Week 10 tight ends

Mike Gesicki and Jonnu Smith are among UPI senior sports writer Alex Butler's four must-start fantasy football tight ends for Week 10.




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Tracy, Harris among 4 must-start Week 10 fantasy football running backs

Tyrone Tracy Jr. and Najee Harris are among UPI senior sports writer Alex Butler's four must-start fantasy football running backs for Week 10.




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Thomas, Williams among 4 must-start Week 10 fantasy football wide receivers

Brian Thomas Jr. and Jameson Williams are among UPI senior sports writer Alex Butler's four must-start wide receivers for Week 10 of the fantasy football campaign.




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Sam LaPorta, Tristan Wirfs, Dalton Kincaid among injured in NFL's Week 10

All-Pro left tackle Tristan Wirfs and tight ends Sam LaPorta and Dalton Kincaid were among key players injured in Week 10 of the NFL season.




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Fantasy football: Justin Herbert among top add/drops for Week 11

Justin Herbert, Russell Wilson and Quentin Johnston lead UPI senior sports writer Alex Butler's fantasy football waiver wire priority list for Week 11 of the 2024 NFL season.




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Speed up Innovation with performance gains of up to 42% on the most powerful HPC Cloud

About This Webinar Oracle’s next generation HPC architecture with Intel compute instance based on 3rd Generation Intel® Xeon® Scalable processors, code named “Ice Lake”, changes the game for HPC in […]

The post Speed up Innovation with performance gains of up to 42% on the most powerful HPC Cloud appeared first on HPCwire.




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Watch: British daredevil dragged behind motorcycle at 159 mph

A British daredevil was intentionally dragged behind his motorcycle at a speed of 159.52 mph to break a Guinness World Record.




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Watch: 43 monkeys on the loose after escaping South Carolina facility

Police in a small South Carolina town are warning residents to keep their doors and windows locked after 43 monkeys escaped from a research facility.




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Pet python missing for two months found at Chili's

A large ball python found slithering in the parking lot of a Chili's restaurant in North Carolina turned out to have been an escaped pet missing for two months.




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NSF Issues Next Solicitation and More Detail on National Quantum Virtual Laboratory

After percolating for roughly a year, NSF has issued the next solicitation for the National Quantum Virtual Lab program — this one focused on design and implementation phases of the […]

The post NSF Issues Next Solicitation and More Detail on National Quantum Virtual Laboratory appeared first on HPCwire.




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Quantum Motion and Goldman Sachs Identify Quantum Applications in Financial Services Project

LONDON, Nov. 1, 2024 — Quantum Motion, a UK-based quantum computing scale-up founded by Professor John Morton, University College London (UCL), and Professor Simon Benjamin, University of Oxford, has worked […]

The post Quantum Motion and Goldman Sachs Identify Quantum Applications in Financial Services Project appeared first on HPCwire.