Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for primary cultured glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome datasets, 38 DEPs were organized; only 10 DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multi-sample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.

Deep proteome coverage in bottom-up proteomics requires peptide-level fractionation to simplify the complex peptide mixture before analysis by tandem mass spectrometry. By decreasing the number of co-eluting precursor peptide ions, fractionation effectively reduces the complexity of the sample leading to higher sample coverage and reduced bias towards high abundance precursors that are preferentially identified in data-dependent acquisition strategies. To achieve this goal, we report a bead-based off-line peptide fractionation method termed CIF or Carboxylate modified magnetic bead-based isopropanol gradient peptide fractionation. CIF is an extension of the SP3 (single-pot solid-phase-enhanced sample preparation) strategy and provides an effective but complementary approach to other commonly used fractionation methods including strong cation exchange (SCX) and reversed phase (RP)-based chromatography. We demonstrate that CIF is an effective offline separation strategy capable of increasing the depth of peptide analyte coverage both when used alone or as a second dimension of peptide fractionation in conjunction with high pH RP. These features make it ideally suited for a wide range of proteomic applications including the affinity purification of low abundance bait proteins.

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

Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches Research paper sysadmin 5 October 2018

Combating illegal wildlife trade and further pursuing conservation-development models could help generate considerable economic benefits for African countries, while ensuring the long-term preservation of Africa’s wealth of natural capital.

Summary

• The illegal wildlife trade (IWT) significantly impacts African economies by destroying and corroding natural, human and social capital stocks. This hinders the achievement of the Sustainable Development Goals (SDGs) and has an impact on national budgets. Illicit financial flows from IWT deny revenue to governments where legal wildlife product trade exists and perpetuate cash externalization. IWT diverts national budgets away from social or development programmes, increases insecurity and threatens vulnerable populations.
• In expanding wildlife economies and pursuing conservation-driven development models, governments can protect their citizens, derive revenue from wildlife products, and establish world class tourism offerings. The illegal exploitation of wildlife is often due to a failure to enforce rights over those resources, where rights are unclearly defined or not fully exercised. Southern African countries have defined these rights in various ways, contributing to regional differences in conservation practices and the socio-economic benefits derived from wildlife resources. Combating IWT is an important step towards allowing legitimate business and communities to develop livelihoods that incentivize stewardship and connect people to conservation.
• The Southern African Development Community (SADC) has several framework policies for the establishment of transfrontier conservation areas (TFCAs). These promote local stewardship across multiple land-use areas to conserve biodiversity and increase the welfare and socioeconomic development of rural communities. Private-sector partnerships also increase skills transfer, improve access to investment finance, and expand economic opportunities, including through the promotion of local procurement. The economic benefits of TFCAs extend beyond tourism.
• The economic value of African ecosystems is often under-recognized because they remain unquantified, partly due to the lack of available data on the broader economic costs of IWT. Improved monitoring and evaluation with key performance indicators would help governments and citizens to appreciate the economic value of combating IWT.

Adopting a Market-based Approach to Boost Energy Access in Displaced Contexts Research paper sysadmin 25 March 2019

This paper evaluates the market-based approaches adopted in the MEI projects in Kenya and Burkina Faso. It articulates how such commercial strategies can be applied to the delivery of energy in displacement settings and compares this to real world examples.

• Development of long-term energy solutions in displacement settings tends to be perceived as investment that falls outside the remit of emergency responses. In addition, when emergency energy supply measures are implemented they often result in expensive, unreliable and unhealthy energy provision for those in protracted or recurrent crises.
• There is widespread agreement among humanitarian and development experts that an effective refugee response should include long-term development solutions as well as emergency relief.
• The energy access imperative is more pronounced when considering the need for effective energy distribution in practically all camp activities and basic necessities: pumping and treatment of clean water; heating and cooling for food storage and cooking; energy for livelihood activities; and provision of light for schooling, hospitals and the prevention of violence against women and children.
• Minor shifts in household energy use to basic solar lighting options and non-wood fuels would save $303 million annually on refugee fuel costs.
• Within refugee contexts in Kenya and Burkina Faso, the MEI sought to examine opportunities to use market interventions, rather than in-kind distributions, to improve clean energy access over the long-term and test the delivery of market-based approaches.

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.

Subsidies and Sustainable Agriculture: Mapping the Policy Landscape Research paper sysadmin 10 December 2019

Agricultural subsidies shape production and consumption patterns, with potentially significant effects on poverty, nutrition and other sustainability concerns. This paper maps the different types of support provided by governments to the agricultural sector, and highlights some of the complex political economy dynamics that underpin the relevant policies.

Summary

• Agricultural subsidies, a mainstay of government policy, have a large part in shaping production and consumption patterns, with potentially significant effects as regards poverty, food security, nutrition, and other sustainability concerns such as climate change, land use practices and biodiversity.
• There are multiple types of direct and indirect support provided by governments to various actors in the agricultural sector; and in terms of political economy, there are complex dynamics underpinning the policies that sustain these subsidies.
• Overall, subsidies targeting producers have the most significant effect on production, and the greater trade-distorting effect. These subsidies promote domestic production and discourage imports, leading to overproduction that is largely disposed of on the international market, with the help of export subsidies. This can tend to intensify negative environmental agricultural practices, such as cultivating marginal land, unsustainable types of intensification, or incentivizing excessive pesticide and fertilizer use.
• On the other hand, producer subsidies that are not tied to output of a specific commodity (i.e. delinked) have far fewer distorting impacts and could help to deliver sustainable outcomes. For example, this type of subsidies can require crop diversification or be linked to conservation of permanent grassland.
• Subsidies that enable transfers to consumers, for example through food stamp programmes, also serve to delink production from consumption, can foster healthier diets, can play an important role in delivering food accessibility and security among low-income groups, and can represent one of the less trade-distorting subsidies.
• If subsidies are to be reformed to help promote healthier diets and encourage more sustainable production, it is essential to understand not only the type and amount of support that key countries provide, but also the domestic dynamics that can shape such policies.
• While price support, input subsidies or investment aids remain the central pillars of programmes in large developing countries such as Brazil, China or India, other economies – notably including the EU and Japan – focus on direct payments, support for general services and set-aside schemes, as well as significant border protection. The US, for its part, has tended to focus on subsidized insurance schemes and food programmes for poorer consumers.
• If subsidies are to deliver policy objectives, their design and implementation should delink production from consumption. For example, consumer subsidies designed to deliver nutrition and food security, or payments for environmental services to enable more environmentally friendly production systems, could prove to be the most effective, least trade-distorting means of achieving more sustainable and equitable agricultural production.
• The political economy of food means that the removal of subsidies is often highly sensitive, and tends to be met with significant resistance. However, reform that delinks support from production through a gradual transition process could ultimately prove successful in delivering effective subsidy schemes.
• Effective subsidy schemes must by design be truly result- and performance-based, supported by robust and objective indicators. At the same time, engaging multiple actors along key commodity value chains – including leading importing and exporting countries, traders and transporters – could lead to the development of international, commodity-specific arrangements that are able to deliver effective nutrition and sustainability goals.

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

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

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

Key findings

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

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

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

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

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

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

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

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

Read the full analysis

Gabe Kapler is trying to keep the focus on his players in 2019, but it might be an impossible task.

Phillies manager Gabe Kapler has a little advice for the players who could be impacted most if the team signs Bryce Harper or Manny Machado.

Ramaphosa Has Won the Battle. But Can He Win the War? Expert comment sysadmin 21 December 2017

Cyril Ramaphosa is taking charge of South Africa’s ruling party, the ANC, at its weakest point in post-apartheid history. Expectations couldn’t be higher.

Ramaphosa ran for the leadership of the ANC on a platform of party renewal, economic recovery, and building the capacity of the state. But Jacob Zuma remains the President of South Africa and, under the constitution, can stay in office until elections in 2019. Therefore, meeting expectations on economic recovery will depend on Ramaphosa taking the presidency – and he has a number of political battles to face before that becomes reality.

To begin with, Ramaphosa and his supporters did not win a total victory at the elective conference. The presidency was only one position in the senior cadre – the co-called ‘top six’ – that was elected. This body is now split evenly between Ramaphosa and his allies, and those that supported his opponent Dr Nkosazana Dlamini-Zuma - Jacob Zuma’s preferred successor. This creates two centres of power in the ANC, limiting what Ramaphosa will be able to achieve from within the party.

Although there is significant pressure from the electorate to remove Zuma from national office, actually doing so will be difficult. Zuma’s predecessor Thabo Mbeki was removed from the national presidency before his term was up when the National Executive Committee (NEC) of the party recalled him from office following Zuma’s assumption of party leadership. But this option may not be available to Ramaphosa. The split within the ‘top six’ and new NEC will make it difficult to present an ultimatum to Zuma. His loyalists will not want a witch hunt within the party.

Corruption and elitism within the party

Much of the tension centres on questions of corruption, the dominant political issue in South Africa at the moment. In the build up to the elective conference Gwede Mantashe - now national chairperson - admitted that “The biggest challenge from where we’re sitting is the image and the reputation of the ANC. The ANC is seen as equal to corruption and looting.” Ramaphosa made anti-corruption initiatives a centrepiece of his campaign, including the establishment of a judicial commission and rapid action to investigate and prosecute the guilty.

But the split within the party may undermine the credibility of these promises. Ramaphosa’s problem is that some of the new ‘top six’ - including Deputy President David Mabuza, and Secretary General Ace Magashule – would be high on the list of those the electorate want to see investigated. Party resistance may restrict the extent to which Ramaphosa can demonstrate a comprehensive break from the past.

Corruption within the party goes far deeper than the headline cases of ‘state capture’ and expropriation. At a branch level, access to political power has become the primary means of access to economic resource. It is a process of selective patronage that differentiates between those who are ‘in’ from those who aren’t. At its broadest, this type of corruption has created a mistrust of the ANC and the new economic elite that the party has created around it – including Ramaphosa himself.

Having lost out to Mbeki in the fight to succeed Mandela despite being the favourite for the job, Ramaphosa spearheaded the ANC’s deployment of cadres in business. He has become one of the country’s richest men, and a highly sought after board member by South Africa’s largest companies across mining, telecoms, and logistics.

One of his biggest challenges will be to remove the perception of elitism as his senior position within the party and economy has given rise to mistrust from a grass roots level. The political tussle at the conference was also largely driven by a small number of the party elite being able to control large groups of delegate votes. The nature of political competition within the party is symptomatic of the ANCs electoral dominance in the early days of the nation’s democracy. But this support is now far less certain, and the party cannot afford to become complacent.

Resetting the relationship with business

Ramaphosa’s business dealings may mean he has to walk a fine line in censuring his colleagues for making money from politics. But it may also be a significant opportunity for the party to reset its relationship with the private sector. Under Mbeki, relations between the ANC and business were distant, but characterized by recognition of mutual dependence.

Under Zuma this relationship deteriorated, and the President demonstrated he was willing to make decisions to boost his political power irrespective of economic consequences. Ramaphosa could, for the first time, truly align the interests of business and government, without abandoning his transformative policy agenda.

At an ANC regional economic colloquium in Johannesburg in November Ramaphosa outlined his ten-point economic plan. It would deliver the party’s adopted mantra of ‘radical economic transformation’, but through broadly neo-liberal policies on private business development and state-owned enterprise reform to allow private capital to co-invest.

He took the ethos and principles of the Freedom Charter – the 1955 statement of core ANC principles – and applied them to a modernising economy. Talk of a ‘new deal’, productive partnerships in the mining sector, and an emphasis on job creation in manufacturing will woo investors. The rand surged upon his election.

But Ramaphosa will not be able to deliver on the economic demands of the country until he is in the office of the presidency - and Zuma still holds many of the cards. Ramaphosa can promise his followers potential power and government positions in future, but Zuma can still offer them now.

Removing Zuma will require skilful internal party politicking, and Ramaphosa will need to limit the fallout – he cannot afford to further damage the credibility of the party before it faces the electorate in 2019. He has won the battle, but the outcome of the war is far from certain.

Ramaphosa Must Act Fast With New Mandate in South Africa Expert comment sysadmin 23 May 2019

In the wake of South Africa’s election, political constraints will ebb momentarily. The president should seize the opportunity to deliver meaningful change.

On 25 May, Cyril Ramaphosa will be inaugurated as president of South Africa, having dragged the African National Congress (ANC) over the line in the 8 May election. The ANC gained a 57 per cent majority, its lowest vote since 1994, its status as national liberator deeply eroded by successive corruption scandals. Only Ramaphosa’s personal popularity stopped it haemorrhaging more support.

His sustained action against corrupt public servants and promises of job-creating economic growth has attracted support from beyond the ANC’s base, including a significant minority of white voters, and generated significant international goodwill. Ramaphosa now has a short window of opportunity to reset social democracy in South Africa before the political cycle of municipal, party and national elections from 2021 to 2024 forces his attention back to party politics.

Defining ‘Ramaphosa-ism’

But personal popularity is fickle, and goodwill alone will not turn around the ailing economy. To attract investment and keep the electorate on side, Ramaphosa’s government needs to move beyond pragmatic crisis responses and articulate a clear, shared vision for how market intervention can allow the economy to grow while simultaneously delivering social transformation.

Growth will be hard to achieve in the short term. The economy is expected to grow 1.2% in 2019 and 1.5% in 2020, according to the IMF. Consumer confidence remains subdued, and a decade of declining GDP per capita and increasing inequality has put a strain on households. A ‘fiscal stimulus’ in 2018 delivered very little new government spending, and over the past 10 years, the government wage bill has increased three times higher than the rate of inflation.

Eskom, the state electricity provider, has debts equating to the GDP of Latvia and is not the only state-owned enterprise (SOE) that has required bailing out by the government. There are plans to break up Eskom into three separate entities but calls for deeper reform – or even privatization – are growing.

The president’s responses to these challenges will go a long way to defining ‘Ramaphosa-ism’ and the role of government in pursuing equitable economy growth.

Economic expectations under Ramaphosa

Ramaphosa was a champion of the introduction of a minimum wage and a proponent of the National Development Plan, which relies on growth to drive job creation. His support for land reform is an individual conviction as much as it is a party line, although his views are softer than many in the party, with state-owned land being the initial target.

Investor uncertainty on land tenure and regulations in mining will need to be addressed through passing key pieces of legislation on land reform and the revised Mining and Petroleum Resources Development Act.

Where Ramaphosa differs from his predecessors is his links with business. Thabo Mbeki enjoyed a relationship of mutual respect with business; this disintegrated under Jacob Zuma. Ramaphosa, however, is part of South Africa’s business community, having founded the Shanduka Group, with investments in multiple sectors including retail, telecoms and extractives, and served as chairman of MTN and Bidvest. As president, he has surrounded himself with close economic advisers from business and banking.

In the short term, anti-corruption measures and competent appointments will ease investor woes. In the long term, there is a need to improve the ease of doing business, including labour market reforms, and to make South Africa a more competitive business environment by reducing the hold of large conglomerates on the economy. Ramaphosa may also make greater use of public-private partnerships for large projects.

Political constraints

Ramaphosa faces few immediate political challenges. The ANC is still deeply divided, but although Ramaphosa does not enjoy the ideological support of the entire party, his opponents are leaderless post-Zuma, and have been unable to offer a coherent alternative. ANC Secretary General Ace Magashule has fallen into the role of interim figurehead of this faction, and allegations of corruption would make it difficult for him to aspire to national leadership.

The need to avoid splits before the election meant Ramaphosa had to make concessions, and his first cabinet in February 2018 included opponents and those accused of corruption or incompetence, such as Malusi Gigaba and Bathabile Dlamini. Such concessions to political opponents are unlikely to continue after the election.

Meanwhile, opposition parties made some advances in the election, but where Zuma was an easy target, they are still grappling with how to confront Ramaphosa. The party with the biggest gains was the Economic Freedom Fighters, whose increase of just over 4 points from the last election gave it 11 per cent of the vote this time. They will likely continue to be an effective disruptor. Ramaphosa may also be challenged by trade unions on his reforms, notably over any break-up of SOEs.

But the biggest and most immediate external political challenge for Ramaphosa will be rebuilding trust between government and society, in a context where social protest has become an alternative form of political participation. A turnout of 65 per cent may be considered normal in Western democracies but is a notable drop for a country as politicized as South Africa, driven by frustration and a sense of exclusion as much as apathy. Turnout by young people was even lower.

Achieving the vision

South Africa has all the platforms it needs to project its renewal and attract vital external investment – it is a non-permanent member of the UN Security Council, it will take over as chair of the African Union in 2020, it is a member of BRICS and it is the only African member of the G20. But in the recent past, it has struggled to tell a coherent story about its vision for the future and offer to the world.

In the immediate wake of the election, internal and external political constraints will ebb. Ramaphosa must act fast to deliver results before the election cycle starts again. To attract much needed investment stimulus, he will not only need to articulate and market his vision for South Africa, but also outline how he plans to achieve it.

The security gap 7 March 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 24 February 2023 Chatham House and Online

With the increasingly significant role that women play in national defence, will perceptions change or are current attitudes towards women in uniform here to stay? 

Women have been part of armed conflicts for all of human history, serving alongside men, as well as in their own distinctive units.

More recently, scores of women are involving themselves in Kurdish resistance fighting, being deployed in Syria as fighter pilots for Israel’s Armed Forces and serving on Ukrainian frontlines.

Women have been integrated into militaries around the world including in the Canadian, Swedish and Norwegian armies to name a few.

This discussion aims to tackle some of the following questions:

• What are some of the challenges that more inclusive militaries bring and can these challenges be overcome?
• Can more inclusive militaries help solve the human resources problems that many modern militaries face?
• Are attitudes changing as more women serve in combat? 
• What are the opportunities for women in militaries and in wider defence efforts?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Here is what they said.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Russia's war: How will it shape the region's future? 1 December 2022 — 9:00AM TO 6:00PM Anonymous (not verified) 17 August 2022 Chatham House and Online

This conference takes a deep-dive into the implications of the war for the wider region.

You will receive an email in advance of the conference with further details on accessing the event.

The video on this page is of the opening session only. To view all the session videos, please visit the conference playlist on YouTube.

How will Russia’s war shape the region’s future?

Russia’s latest invasion of Ukraine is on such a scale that it will have a seismic effect on all the countries that once formed the Soviet empire. Vladimir Putin’s decisions have accelerated trends across the region leading to unintended consequences.

Now it is more crucial than ever – not only for those concerned with the region’s economic and democratic development, but for all those with a stake in the future security of Europe.

For some states, this will mean a faster break from the legacy of the USSR and from Russia’s ‘Geopathological embrace‘ while, for others, maybe even a fresh start at democracy and good governance.

In isolated cases, the war will conceivably hasten assimilation with Russia. But the two principal combatants, Ukraine and Russia, will diverge even further. Ukraine, though fighting for its survival now, will at least get the opportunity to ‘build back better’ if it achieves some form of victory.

Whatever the course of the war, however, Russia’s aspirations to be a global power again are doomed as it is gradually deglobalized from Western structures.

This conference analyses:

• How Russia’s war will affect the broader regional economy and whether this will hasten Vladimir Putin’s exit
• What to hope for, what to fear and the key trends that will dominate the region going forward.
• Unique expertise in an independent forum on what’s at stake for Europe. 

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.

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

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.

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.

Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. ⁶⁸Ga-labeled fibroblast activation protein inhibitor ([⁶⁸Ga]Ga-FAPI-04) PET/MRI, [¹⁸F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter’s sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [⁶⁸Ga]Ga-FAPI-04 PET/MRI and [¹⁸F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [⁶⁸Ga]Ga-FAPI-04 change in SUL_peak percentage, where SUL_peak is SUV_peak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [⁶⁸Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SUL_peak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.

As Nissan on Thursday reported a roughly half-billion- dollar revenue drop in 2024, the Japanese automaker said it will cut 9,000 jobs and reduce manufacturing capacity by 20%.

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

Mattel has apologized after inadvertently directing customers of its new line of Wicked dolls to a pornographic website, stating it is taking action to remove the misprinted toys' packaging.

Genetic-testing lab 23andMe plans to cut its workforce by 40% and end its therapeutics program in an effort to cut costs, the company announced Monday.

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

An American woman who was traveling in Hungary was killed in Budapest last week allegedly by a man she met on vacation.

Loopholes in international laws governing the use of incendiary weapons in warfare are allowing warring parties in Ukraine and the Middle East to exploit the use of such weapons without adequately protecting civilians.

The Japanese parliament on Monday re-elected Liberal Democratic Party chief Shigeru Ishiba as prime minister in a rare runoff vote after the ruling LDP lost its majority in the lower legislative chamber.

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

Zapata Computing, which was founded in 2017 as a Harvard spinout specializing in quantum software and later pivoted to an AI focus, is ceasing operations, according to an SEC filing […]

The post Zapata Computing, Early Quantum-AI Software Specialist, Ceases Operations appeared first on HPCwire.

Alex Ovechkin calmly slid into the right circle and sniped a snapshot past a blinded Juuse Saros to lead the Washington Capitals to a 3-2 triumph over the Nashville Predators.

Billy Napier will remain in place as head football coach at Florida, despite the Gators producing another lackluster campaign during his third season, athletic director Scott Stricklin announced Thursday.

Racing settles in for the winter season this weekend with the Breeders' Cup in the rearview mirror and the Dubai World Cup Carnival opening its tents Friday at Meydan Racecourse.

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.

Linebacker Quinton Bell and Miami Dolphins defenders deleted drives and put the Los Angeles Rams offense in quicksand, holding them without a touchdown to propel a primetime victory and snap a three-game losing streak.

Aug. 19, 2024 — SURF’s innovation department recently collaborated with Cornelis Networks to advance networking capabilities for high-performance computing (HPC) clusters. The collaboration marks a new step forward for SURF […]

The post Cornelis Networks Partners with SURF to Enhance HPC Cluster Networking Capabilities appeared first on HPCwire.

Last week NSF issued a request for the next round of proposals for its Quantum Leap Challenge Institutes (QLCI). First established in 2020, the QLCI program, as directed by National […]

The post NSF Seeks Proposals for Next Round of Quantum Leap Challenge Institutes appeared first on HPCwire.

The demand for high-performance computing (HPC) and artificial intelligence (AI) is rising dramatically as organizations rush to put their data to work. Several industries see a significant increase in HPC […]

The post Harness Insights with Cutting-edge AI Capabilities from HPE appeared first on HPCwire.

What can be achieved using applications such as AI/ML, Deep Learning, and Big Data Analytics has been revolutionized by Magnum IO GPUDirect Storage’s capabilities. Agencies have invested in these solutions […]

The post Accelerating GPU Based Applications with NVIDIA Validated Magnum IO GPUDirect Storage and Pavilion appeared first on HPCwire.

Oct. 31, 2024 — Giga Computing, a subsidiary of GIGABYTE and a leader in generative AI servers and advanced cooling technologies, will participate in today’s AI Accelerator Skyscraper Congress, hosted […]

The post GIGABYTE Joins AI Accelerator Skyscraper Congress to Highlight Sustainable Supercomputing Advances appeared first on HPCwire.

A zoo on England's Isle of Wight announced the saga of its escaped raccoons came to a happy ending with the final animal safely recaptured.

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.

A kangaroo that escaped from its Florida enclosure while fleeing from a bear has been safely returned home three weeks later.

Mattel has apologized after inadvertently directing customers of its new line of Wicked dolls to a pornographic website, stating it is taking action to remove the misprinted toys' packaging.