Online Disinformation and Political Discourse: Applying a Human Rights Framework Research paper sysadmin 5 November 2019

Although some digital platforms now have an impact on more people’s lives than does any one state authority, the international community has been slow to hold to account these platforms’ activities by reference to human rights law.

This paper examines how human rights frameworks should guide digital technology.

Summary

• Online political campaigning techniques are distorting our democratic political processes. These techniques include the creation of disinformation and divisive content; exploiting digital platforms’ algorithms, and using bots, cyborgs and fake accounts to distribute this content; maximizing influence through harnessing emotional responses such as anger and disgust; and micro-targeting on the basis of collated personal data and sophisticated psychological profiling techniques. Some state authorities distort political debate by restricting, filtering, shutting down or censoring online networks.
• Such techniques have outpaced regulatory initiatives and, save in egregious cases such as shutdown of networks, there is no international consensus on how they should be tackled. Digital platforms, driven by their commercial impetus to encourage users to spend as long as possible on them and to attract advertisers, may provide an environment conducive to manipulative techniques.
• International human rights law, with its careful calibrations designed to protect individuals from abuse of power by authority, provides a normative framework that should underpin responses to online disinformation and distortion of political debate. Contrary to popular view, it does not entail that there should be no control of the online environment; rather, controls should balance the interests at stake appropriately.
• The rights to freedom of thought and opinion are critical to delimiting the appropriate boundary between legitimate influence and illegitimate manipulation. When digital platforms exploit decision-making biases in prioritizing bad news and divisive, emotion-arousing information, they may be breaching these rights. States and digital platforms should consider structural changes to digital platforms to ensure that methods of online political discourse respect personal agency and prevent the use of sophisticated manipulative techniques.
• The right to privacy includes a right to choose not to divulge your personal information, and a right to opt out of trading in and profiling on the basis of your personal data. Current practices in collecting, trading and using extensive personal data to ‘micro-target’ voters without their knowledge are not consistent with this right. Significant changes are needed.
• Data protection laws should be implemented robustly, and should not legitimate extensive harvesting of personal data on the basis of either notional ‘consent’ or the data handler’s commercial interests. The right to privacy should be embedded in technological design (such as by allowing the user to access all information held on them at the click of a button); and political parties should be transparent in their collection and use of personal data, and in their targeting of messages. Arguably, the value of personal data should be shared with the individuals from whom it derives.
• The rules on the boundaries of permissible content online should be set by states, and should be consistent with the right to freedom of expression. Digital platforms have had to rapidly develop policies on retention or removal of content, but those policies do not necessarily reflect the right to freedom of expression, and platforms are currently not well placed to take account of the public interest. Platforms should be far more transparent in their content regulation policies and decision-making, and should develop frameworks enabling efficient, fair, consistent internal complaints and content monitoring processes. Expertise on international human rights law should be integral to their systems.
• The right to participate in public affairs and to vote includes the right to engage in public debate. States and digital platforms should ensure an environment in which all can participate in debate online and are not discouraged from standing for election, from participating or from voting by online threats or abuse.

AI-driven Personalization in Digital Media: Political and Societal Implications Research paper sysadmin 2 December 2019

The fallout from disinformation and online manipulation strategies have alerted Western democracies to the novel, nuanced vulnerabilities of our information society. This paper outlines the implications of the adoption of AI by the the legacy media, as well as by the new media, focusing on personalization.

Summary

• Machine learning (ML)-driven personalization is fast expanding from social media to the wider information space, encompassing legacy media, multinational conglomerates and digital-native publishers: however, this is happening within a regulatory and oversight vacuum that needs to be addressed as a matter of urgency.
• Mass-scale adoption of personalization in communication has serious implications for human rights, societal resilience and political security. Data protection, privacy and wrongful discrimination, as well as freedom of opinion and of expression, are some of the areas impacted by this technological transformation.
• Artificial intelligence (AI) and its ML subset are novel technologies that demand novel ways of approaching oversight, monitoring and analysis. Policymakers, regulators, media professionals and engineers need to be able to conceptualize issues in an interdisciplinary way that is appropriate for sociotechnical systems.
• Funding needs to be allocated to research into human–computer interaction in information environments, data infrastructure, technology market trends, and the broader impact of ML systems within the communication sector.
• Although global, high-level ethical frameworks for AI are welcome, they are no substitute for domain- and context-specific codes of ethics. Legacy media and digital-native publishers need to overhaul their editorial codes to make them fit for purpose in a digital ecosystem transformed by ML. Journalistic principles need to be reformulated and refined in the current informational context in order to efficiently inform the ML models built for personalized communication.
• Codes of ethics will not by themselves be enough, so current regulatory and legislative frameworks as they relate to media need to be reassessed. Media regulators need to develop their in-house capacity for thorough research and monitoring into ML systems, and – when appropriate –proportionate sanctions for actors found to be employing such systems towards malign ends. Collaboration with data protection authorities, competition authorities and national electoral commissions is paramount for preserving the integrity of elections and of a political discourse grounded on democratic principles.
• Upskilling senior managers and editorial teams is fundamental if media professionals are to be able to engage meaningfully and effectively with data scientists and AI engineers.

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

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

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

Summary

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

Download a presentation of the survey’s main findings

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

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

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

Summary

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

Download a presentation of the survey’s main findings

• Belarusians’ views on the political crisis (PDF)

• Взгляды белорусов на политический кризис (PDF)

Political Opposition and Policy Alternatives in Zambia 31 October 2017 — 10:30AM TO 11:30AM Anonymous (not verified) 19 October 2017 Chatham House, London

In Zambia’s 2016 national election, the Patriotic Front (PF) was re-elected by a narrow margin. The PF’s Edgar Lungu secured 50.35 per cent of the vote according to the Electoral Commission of Zambia, narrowly avoiding a second round, while his main rival, Hakainde Hichilema, won 47.67 per cent. The UPND, led by Mr Hichilema, alleges electoral fraud and has challenged the result in the courts and through direct protests. Mr Hichilema was imprisoned for 100 days.

At this meeting, Hakainde Hichilema will discuss his UPND priorities, how to strengthen opposition parties and their role in Zambia’s democratic future.

Read transcript

Tsvangirai Leaves an Important Political Legacy in Southern Africa Expert comment sysadmin 21 February 2018

The story of Zimbabwe’s ‘people’s champion’ offers a powerful example to a region in need of new political compromises.

The death of Movement for Democratic Change (MDC) leader Morgan Tsvangirai is a loss for Zimbabwe. In nearly three decades of speaking truth to power, Tsvangirai helped to change his nation and the region.

Southern Africa’s new politics

His death marks a period of transition for regional governments and opposition parties alike. The Zuma era has ended in South Africa while Mozambique, Namibia and Angola have also seen political transitions, pushing modernization agendas to appeal to young citizenries that increasingly see politics in separate terms from the liberationist struggles of the previous generation.

Regional opposition movements also face winds of change: the longstanding opposition leader in the Democratic Republic of the Congo, Etienne Tshekedi, passed away in 2017, and Mozambique’s Afonso Dhlakama and Kenya’s Raila Odinga are both aging. These movements similarly need to appeal to a younger audience or risk losing relevance.

From trade unionist to opposition leader

Tsvangirai’s career is an eloquent illustration of these challenges. Born in Buhera in rural eastern Zimbabwe, Tsvangirai worked in textiles and mining before politics – diverse experience which gave him crucial exposure to the lives of ordinary people across the country. In his early years, he also worked for ZANU-PF, before leaving to forge his own political path. He became increasingly active in mining politics, rising to the executive of the National Mineworker’s Union and, in 1989, to secretary-general of the powerful Zimbabwe Congress of Trade Unions.

In the late 1990’s, Zimbabwe was riven by questions over land, war veterans, the Congo conflict, a shrinking economy and growing doubts about ZANU-PF itself. Opposition leaders of the time could not answer them; those such as Edgar Tekere and Margaret Dongo struggled to win support beyond their local constituencies, and liberation leader Joshua Nkomo’s ZAPU had been merged with ZANU-PF in the 1987 Unity Accord.

But in 2000, Zimbabwe’s ‘perfect storm’ of a divisive constitutional referendum, land redistribution and a June election made Tsvangirai and the newly minted MDC, formed in 1999, a national rival to ZANU-PF. Through subsequent national elections in 2002, 2005, 2008 and 2013, Zimbabwe remained polarized between competing visions of Zimbabwe future: ZANU-PF’s powerful black liberationist politics of identity and the opposition’s equally compelling liberal democracy agenda.

Tsvangirai’s achievement was to provide a credible alternative to liberation icon Robert Mugabe. Tsvangirai also resuscitated Zimbabwe’s tradition of urban nationalism, and was a successor to Benjamin Burombo and other mid-century Zimbabwean urban leaders. Tsvangirai would in turn be a touchstone for contemporary urban activists Evans Mawarire, Linda Masarira and others.

From opposition to coalition

The political struggle for Zimbabwe became global, with Mugabe and Tsvangirai both winning support from rival international power blocs. In March 2007, pictures of a beaten and bloodied Tsvangirai helped to galvanize support for the MDC in the 2008 elections. But the disputed result and violent subsequent run-off between Tsvangirai and Mugabe led the regional community to push both men into a coalition government, with Tsvangirai as prime minister.

Despite continuous ructions, the Government of National Unity (GNU) held, and stabilized Zimbabwe’s collapsed economy, until 2013. Although often politically out-manoeuvred by Mugabe, Tsvangirai deserves credit for getting the opposition a share of political power and for holding his nerve against many who wanted to collapse the GNU.

Tsvangirai was no saint; his complicated love life, and tacit approval of violent attacks on party dissenters, do him no credit. More importantly, the MDC neglected its grassroots supporters during the GNU, and paid the price in its comprehensive 2013 electoral defeat. But although diminished, Tsvangirai remained Zimbabwe’s most popular opposition politician, and the MDC’s new leaders will have quite a task ahead of them, even if they have been planning since his courageous 2016 public admission of colon cancer.

The MDC after Tsvangirai

Nelson Chamisa, one of the three MDC vice presidents, has now been appointed as acting president by the party’s national committee. Chamisa inherits a fractured and fractious party, and one which has also fallen out with the Tsvangirai family. The other two vice presidents, Thokozani Khupe and Elias Mudzuri, have also set their sights on party leadership.

At 40, Chamisa, an orator with grassroots appeal, has a huge task. With general elections due by July, he has to unite the party, counter Zimbabwe’s rising ethno-politics, prove himself as leader of a broader opposition coalition and take on a resurgent President Emmerson Mnangagwa and ZANU-PF.

Electorally, the opposition’s strongest card has always been the urban vote and the economy. But Mnangagwa has fast forwarded a comprehensive economic reform and internationalist agenda. This, and Mugabe’s exit, have forced Chamisa, Joice Mujuru and other opposition leaders to play catch-up. Zimbabwe’s elections, the first since 2000 without Mugabe and Tsvangirai as contenders, will be of global interest as the country navigates the new political dynamics.

The people’s champion

Morgan Tsvangirai’s resilience earned him respect from friends and foes alike, with Zimbabwe’s President Mnangagwa and Vice President Constantino Chiwenga visiting him at home a few weeks ago. A former nominee for the Nobel Peace Prize, Tsvangirai, popularly known by his totem of ‘Save’ and also called mudhara [the old man] deserves national hero status. He will certainly be remembered as the ‘people’s champion’, and a pioneer in bridging the generational and ideological fissures that have shaped Southern Africa’s politics.

With their leader now gone, the turbulent MDC will undoubtedly be hoping for a ‘remembrance vote’ in his memory to carry them through the elections. But beyond that, his story offers a powerful example to a region in need of new political compromises.

Zimbabwe Ahead of the Elections: Political and Economic Challenges 8 May 2018 — 10:00AM TO 11:00AM Anonymous (not verified) 3 May 2018 Chatham House, London

The upcoming elections in Zimbabwe will be the first since 2000 in which former president Robert Mugabe and long-time opposition leader Morgan Tsvangirai are not on the ballot paper. A key electoral issue for many voters will be the economy: recent years have been marked by high unemployment rates, chronic cash shortages and mounting public debt. Although this has traditionally been a strong campaigning issue for the opposition, President Emmerson Mnangagwa has fast-tracked comprehensive economic reforms.

At this event, Nelson Chamisa, MDC Alliance presidential candidate, will discuss his efforts to build a united opposition coalition with a strong message, the steps needed to ensure a free and fair election can take place, and the role that international partners can play in Zimbabwe’s democratic process.

Political Reform in Angola: Challenges and Priorities for Elected Officials 31 October 2018 — 4:00PM TO 5:00PM Anonymous (not verified) 26 October 2018 Chatham House, London

Angola’s reformulated National Assembly has passed a series of legislative reforms since elections in August 2017, in which the ruling MPLA won a majority of 150 seats to the 51 held by the UNITA leading opposition party.

Many of the changes have targeted the revitalization of an underperforming economy and improved governance: in June 2018 parliament approved a new private investment law aimed at diversifying Angola’s fiscal base beyond oil revenues while new legislation in May mandated the return of illicitly exported capital of over $100,000.

As the appetite for measurable progress across all sectors of society remains high, and with newly constituted municipal elections scheduled for 2020, inclusive and accountable political debate will remain critical to Angola’s future.

At the event, a cross-party delegation discuss the role of the National Assembly in affecting political change and the importance of maintaining open dialogue among opposing voices to address the challenges facing Angola.

Zambia’s political and economic reform and recovery 5 November 2021 — 11:30AM TO 12:30PM Anonymous (not verified) 2 November 2021 Chatham House and Online

At this event, HE Hakainde Hichilema, president of the Republic of Zambia, discusses his vision for Zambia’s development and long-term political and economic reform and recovery.

Zambia’s new administration, following the general elections of August 2021, faces a daunting challenge of reversing economic contraction, lowering income-eroding inflation, and addressing the unsustainable national debt.

The country has been one of the few to seek debt restructuring under the G20’s new Common Framework for Debt Treatments, and its immediate priorities include a prospective agreement with the International Monetary Fund (IMF).

Young Zambians are eager for jobs and improved living standards. But the government’s ambition to create more jobs and achieve middle-income status will depend on both attracting new investment into its copper sector and pursuing a programme of economic diversification supporting growth beyond the mining industry.

Addressing these economic concerns will also need to be supported by a programme of political reform and rehabilitation of citizens’ trust in the state.

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

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

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

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

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

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

Key questions to be addressed during this discussion include:

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

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

A drinks reception will immediately follow this event.

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.

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.

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 SUV_max of these lesions was 19.6 (range, 2.7–95.3), and the mean SUV_mean 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 SUV_mean, <1.6), with a continuous decline to 4 h after administration (mean SUV_mean, 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 SUV_max 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.

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

Single-domain antibodies (sdAbs) demonstrate favorable pharmacokinetic profiles for molecular imaging applications. However, their renal excretion and retention are obstacles for applications in targeted radionuclide therapy (TRT). Methods: Using a click-chemistry–based pretargeting approach, we aimed to reduce kidney retention of a fibroblast activation protein α (FAP)–targeted sdAb, 4AH29, for ¹⁷⁷Lu-TRT. Key pretargeting parameters (sdAb-injected mass and lag time) were optimized in healthy mice and U87MG (FAP⁺) xenografts. A TRT study in a pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (PDX) model was performed as a pilot study for sdAb-based pretargeting applications. Results: Modification of 4AH29 with trans-cyclooctene (TCO) moieties did not modify the sdAb pharmacokinetic profile. A 200-µg injected mass of 4AH29-TCO and an 8-h lag time for the injection of [¹⁷⁷Lu]Lu-DOTA-PEG₇-tetrazine resulted in the highest kidney therapeutic index (2.0 ± 0.4), which was 5-fold higher than that of [¹⁷⁷Lu]Lu-DOTA-4AH29 (0.4 ± 0.1). FAP expression in the tumor microenvironment was validated in a PDAC PDX model with both immunohistochemistry and PET/CT imaging. Mice treated with the pretargeting high-activity approach (4AH29-TCO + [¹⁷⁷Lu]Lu-DOTA-PEG₇-tetrazine; 3 x 88 MBq, 1 injection per week for 3 wk) demonstrated prolonged survival compared with the vehicle control and conventionally treated ([¹⁷⁷Lu]Lu-DOTA-4AH29; 3 x 37 MBq, 1 injection per week for 3 wk) mice. Mesangial expansion was reported in 7 of 10 mice in the conventional cohort, suggesting treatment-related kidney morphologic changes, but was not observed in the pretargeting cohort. Conclusion: This study validates pretargeting to mitigate sdAbs’ kidney retention with no observation of morphologic changes on therapy regimen at early time points. Clinical translation of click-chemistry–based pre-TRT is warranted on the basis of its ability to alleviate toxicities related to biovectors’ intrinsic pharmacokinetic profiles. The absence of representative animal models with extensive stroma and high FAP expression on cancer-associated fibroblasts led to a low mean tumor-absorbed dose even with high injected activity and consequently to modest survival benefit in this PDAC PDX.

Turkey Needs Radical New Direction to Save the Economy Expert comment NCapeling 23 November 2020

Turkey should emulate the reformist approach it adopted after the 2001 crisis to prevent an economic and financial breakdown - but this looks highly unlikely.

Although Ankara has witnessed what appears to be an abrupt change of its top economic team with two fresh appointments to key positions – Naci Ağbal as governor of the central bank and Lütfi Elvan as finance and treasury minister – a cardinal rule of thumb in Turkish politics is that the more drama one sees, the less policy change there will actually be.

Financial markets reacted positively to the moves in the expectation they will signal a change of Turkey’s overall economic approach, but the reality is Turkish president Recep Tayyip Erdoğan is simply putting loyalists into key bureaucratic positions to help ensure the primary role of these functions becomes ‘selling’ his policies more effectively, rather than altering them.

The hope from the markets – which saw the beleaguered Turkish lira appreciate against the US dollar at the news – is that Turkey adopts substantial interest rate increases as well as measures to repress liquidity expansion in order to temper its controversial so-called ‘Triple C’ approach of using cheap credit to stimulate growth with an unsustainable consumption and construction boom.

But instead, Erdoğan’s declaration after the appointments were made indicates the new restrictions in which they will now operate, saying ‘we are in a historic struggle against those who want to force Turkey into modern capitulations through the shackles of interest rates, foreign exchange rates and inflation’.

Learn from past successes

To resolve its current underlying economic problems, Turkey should actually be looking to its recent past and aiming to emulate the approach pursued by former prime minister Bülent Ecevit during the 2001 financial crisis when he recruited Kemal Derviş, a senior World Bank official with extensive experience and international contacts in economic, financial, and monetary affairs.

As economy minister with a broad mandate to spearhead a durable economic recovery plan, Dervis established independent market regulatory agencies covering banking, telecommunications, energy, and other key sectors, and strengthened the competition authority.

He also either liquidated or merged insolvent banks, granted central bank autonomy to guarantee price stability, and ensured recruitment was based on competence, expertise, and meritocracy. Crucially, his productivity-enhancing restructuring blueprint was designed in Turkey rather than being imposed by the International Monetary Fund (IMF) or another external agency.

Ecevit also turbocharged reforms motivated in part by a desire to join the EU with constitutional, political and legal modernization which widened personal freedom, significantly curtailed capital punishment, liberalized the cultural environment for Kurds, and fortified the rule of law. And one of his coalition partners in that work, the right-wing pro-Turkish National Action Party (MHP), is now allied with the current ruling Justice and Development Party (AKP).

His foreign minister Ismail Cem also enhanced Turkey’s relations with both Europe and the US, initiated the so-called ‘earthquake diplomacy’ with his Greek counterpart George Papandreou after twin tragedies struck both nations in 1999, and largely avoided entanglement in Middle Eastern conflicts.

The net result of all these actions was that Turkey emerged from the crisis with greater resilience, a more robust regulatory framework, upgraded political and economic institutions, rapidly decreasing inflation, a credible central bank, a stronger financial system, closer relations with the EU and US, and heightened domestic and foreign investor confidence.

But now that similar woes are engulfing Turkey anew, is Erdogan and the AKP/MHP alliance able – and willing – to repeat the Ecevit recipe? Present signs indicate they are highly unlikely to as they are too committed to entrenching the Triple C model.

Although this model will likely further consolidate their power, it will also empty the civil service of qualified professionals, restrict civil liberties and freedoms, and create more ideological politics, affecting Turkey’s foreign policy.

Such a stubborn refusal to shift direction is increasing the inevitability of a deep economic and financial breakdown and so, unless Turkey undertakes a serious policy departure instead of continuing to resort to the quick fix approach, there is real likelihood it will simply accelerate towards disaster.

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

HANOVER, Md., Nov. 5, 2024 — Ciena has announced that its optical and routing and switching innovations will once again support the SCinet network at SC24, taking place November 17–22 […]

The post Ciena Powers SC24’s SCinet with High-Speed Connectivity and Advanced Optical Solutions appeared first on HPCwire.

In AI, time is money. Top AI players are spending billions to create computing infrastructures to satisfy that need for speed. However, these companies are bottlenecked by computing constraints at […]

The post Ayar Labs CEO: Optical Chiplets Coming to SOCs Soon appeared first on HPCwire.

This banner year for elections worldwide may witness the arrival of advertising tailored to your personality

Nov. 1, 2024 — NCC France & NCC Slovakia announce a free online training on Numerical Computing With Rust on CPU. The training is spread over three days, from November […]

The post NCC France & NCC Slovakia Announce Numerical Computing With Rust on CPUs Training appeared first on HPCwire.

A recent collaboration among researchers from HUN-REN Wigner Research Centre for Physics in Hungary and the Department of Energy’s Pacific Northwest National Laboratory (PNNL), along with industry collaborators SandboxAQ and […]

The post Collaboration Speeds Complex Chemical Modeling appeared first on HPCwire.

Background: Faced with the limits of synthetic antipyretic substances, in particular their involvement in the occurrence of numerous and often serious adverse effects; the challenge is in search of new antipyretics especially from the African traditional pharmacopoeia. The objective of this study was to evaluate the antipyretic activity of an aqueous extract and a formulation of Ceiba pentandra, with a view to designing an herbal antipyretic drug. Methods: Trials of formulation of an antipyretic syrup with leaves extract of Ceiba pentandra were carried out. The antipyretic activity was investigated by the bewer's yeast induced pyrexia. Physicochemical and microbiological stability tests were carried out on the syrup. Results: It was found with the extract an antipyretic activity at doses of 125 mg/kg and 150 mg/kg. The effect was greater for the 125 mg/kg dose with inhibition percentages ranging from 27.58% to 71.25%. This antipyretic activity was early (from 30 minutes) and was preserved during the four hours of the experiment. The syrup dosed at 125 mg/kg gave an activity similar to that of the extract by significantly reducing the hyperthermia in the rats. Regarding the stability tests, the syrup remained stable both physico-chemically and microbiologically throughout the study period (28 days) both when exposed to low temperature (5 °±3 ° C) and at high temperature (40°±2° C). Conclusions: Ceiba pentandra leaves have antipyretic activity and could be used for the development of an herbal antipyretic drug.

Can strawberries grown inside a building taste sweeter than those grown in a field? Farming entrepreneur Hiroki Koga explores how his team is combining solar-powered vertical farms with AI, robotics and indoor bee colonies to grow delicious strawberries year-round — and how this practice, if widely adopted, could deliver a harvest of benefits for the future of food.

When monarch butterflies migrate, they produce one of the most iconic wildlife spectacles in the world — and provide us with an important indicator of ecological health, says photographer Jaime Rojo. Telling a story about our relationship to the natural world, he shares his experience photographing these mesmerizing insects deep in their remote mountain habitats in Mexico, diving into the latest research into the mysteries of their multi-thousand-mile journey and sharing how each of us can join the growing movement to protect them.

Joel Bervell was one of the only Black students in his medical school program. After noticing how misconceptions about race were embedded in health care, he turned to social media to raise awareness about the harmful impact of biases in medicine. He unpacks the long history of race-based health care disparities — and shows what the medical field can do to better serve all patients.

Suboxone is a medicine prescribed to treat opioid use disorder. But in recent times, it has gained a poor reputation for contributing to severe side effects, such as dental damage and decay. Many patients have had to undergo costly dental repair surgery to treat the gum and tooth issues they faced. But the side effects […]

The post How To Cope With the Psychological Symptoms of Suboxone Withdrawal first appeared on What is Psychology?.

1. Do something “perspective expanding” either in terms of time or space. Examples: Time: look into the eyes of someone alive in the 1400s by visiting an art gallery. Space: A walk/coffee somewhere with an expansive view, a drive. Both time & space: A trip into the mountains (they’re giant & they’ve been there a […]

The post 5 Practical, Creative Tips for Soothing a Low Mood appeared first on Dr Alice Boyes.

This is for my kiwi readers – it’s freezing here at the moment! I got the idea to write this from an interview I did for the NZ Herald about weight gain during winter. 1. Eat at regular times, that are not too far apart. It will help you learn to recognize that if you […]

The post 10 Practical Tips for Avoiding Winter Weight Gain appeared first on Dr Alice Boyes.

The demand for substitute teacher positions is outpacing the supply, and the quality of those applying is a concern in many places.

Concerns about local school systems can pose recruitment and retention hurdles for the armed services as they seek to meet the needs of military families.

New Jersey is one of many states that have experienced problems with the online administering of standardized testing this year.

Former Republican Missouri Gov. Eric Greitens appointed enough board members to have Commissioner Margie Vandeven fired last year, but now that he's gone, the state board decided to hire her back.

In Arkansas, Ohio, and Wisconsin, educators and advocates will be on this year's ballot for governor, a position that will inevitably have an outsized role in shaping education policy.

Primary season is now upon us. Here are three ideas for teaching in the wake of the Iowa caucus fallout.

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