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Semi-automatically quantified tumor volume using Ga-68-PSMA-11-PET as biomarker for survival in patients with advanced prostate cancer

Prostate specific membrane antigen (PSMA) targeting Positron Emission Tomography (PET) imaging is becoming the reference standard for prostate cancer (PC) staging, especially in advanced disease. Yet, the implications of PSMA-PET derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be due to the fact that (semi-) automated quantification of whole-body tumor volume as PSMA-PET biomarker is an unmet clinical challenge. Therefore, a novel semi-automated software is proposed and evaluated by the present study, which enables the semi-automated quantification of PSMA-PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype (MI Whole Body Analysis Suite, v1.0, Siemens Medical Solutions USA, Inc., Knoxville, TN). PSMA accumulating foci were automatically segmented by a percental threshold (50% of local SUVmax). Neural networks were trained to segment organs in PET-CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semi-automatically excluded from the analysis. Pretherapeutic PSMA-PET-CTs of 40 consecutive patients treated with 177Lu-PSMA-617 therapy were evaluated in this analysis. The volumetric whole-body tumor volume (PSMATV50), SUVmax, SUVmean and other whole-body imaging biomarkers were calculated for each patient. Semi-automatically derived results were compared with manual readings in a sub-cohort (by one nuclear medicine physician using syngo.MM Oncology software, Siemens Healthineers, Knoxville, TN). Additionally, an inter-observer evaluation of the semi-automated approach was performed in a sub-cohort (by two nuclear medicine physicians). Results: Manually and semi automatically derived PSMA metrics were highly correlated (PSMATV50: R2=1.000; p<0.001; SUVmax: R2=0.988; p<0.001). The inter-observer agreement of the semi-automated workflow was also high (PSMATV50: R2=1.000; p<0.001; ICC=1.000; SUVmax: R2=0.988; p<0.001; ICC=0.997). PSMATV50 [ml] was a significant predictor of overall survival (HR: 1.004; 95%CI: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (HR: 1.004; 95%CI: 1.001-1.006 P = 0.004). Conclusion: PSMATV50 is a promising PSMA-PET biomarker that is reproducible and easily quantified by the proposed semi-automated software. Moreover, PSMATV50 is a significant predictor of overall survival in patients with advanced prostate cancer that receive 177Lu-PSMA-617 therapy.




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Radioiodine Ablation of Remaining Thyroid Lobe in Patients with Differentiated Thyroid Cancer Treated by Lobectomy. A systematic review and meta-analysis.

Purpose: We aimed to conduct a systematic review and meta-analysis of studies reporting the performance of radioactive iodine therapy (131-I therapy) in differentiating thyroid cancer (DTC) patients requiring a completion treatment following lobectomy. We also evaluated the response to 131-I therapy according to 2015ATA guidelines and the adverse events. Methods: A specific search strategy was designed to find articles evaluating the use of I-131 in patients with evidence of DTC after lobectomy. PubMed, CENTRAL, Scopus and Web of Science were searched. The search was updated until January 2020, without language restriction. Data were cross-checked and any discrepancy discussed. A proportion meta-analysis (with 95%CI) was performed using the random-effects model. Meta-regressions on I-131 success were attempted. Results: The pooled success ablation rate was 69% with better results in patients receiving a single administration of about 3.7 GBq; high heterogeneity was found (I2 85%), and publication bias was absent (Egger test: P = 0.57). Incomplete structural responses were recorded in only 14 of 695 (2%) patients enrolled in our analysis. Incomplete biochemical responses were observed in 8 to 24% of patients, with higher rates (24%) in patients receiving low radioiodine activities (~1.1 GBq) and lower rates (from 8 to 18%) in patients receiving higher activities of radioiodine (~3.7 Gbq). Neck pain due to thyroiditis was reported in up to 18% of patients but, in most cases, symptoms resolved after oral paracetamol or a short course of prednisone. Conclusion: Lobar ablation with 131-I is effective especially when high 131I activities are used. However, the rate of incomplete biochemical response to initial treatment appears to be slightly higher than the classical scheme of initial treatment of DTC. "Radioisotopic lobectomy" should be considered for patients with low-to-intermediate risk DTC requiring completion treatment after lobectomy due to specific individual risk factors and/or patient’s preferences.




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PET imaging quantifying 68Ga-PSMA-11 uptake in metastatic colorectal cancer

At diagnosis 22% of colorectal cancer (CRC) patients have metastases and 50% later develop metastasis. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-PSMA-617 is employed to treat metastatic prostate cancer (PC). 177Lu-PSMA-617 targets Prostate Specific Membrane Antigen (PSMA) a cell surface protein enriched in PC and the neovasculature of other solid tumors including CRC. We performed gallium-68 (68Ga)-PSMA-11 PET-CT imaging of ten metastatic CRC patients to assess metastasis avidity. Eight patients had lesions lacking avidity and two had solitary metastases exhibiting very low avidity. Despite expression of PSMA in CRC neovasculature, none of the patients exhibited tumor avidity sufficient to be considered for 177Lu-PSMA-617 PRRT.




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The Impact of Radiobiologically-Informed Dose Prescription on the Clinical Benefit of Yttrium-90 SIRT in Colorectal Cancer Patients

The purpose of this study was to establish the dose-response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to yttrium-90 (90Y). Methods: 23 mCRC patients with liver metastases refractory to chemotherapy were included. 90Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method. Baseline and follow-up CT scans were segmented to derive liver and tumor volumes. Mean, median, and D70 (minimum dose to 70% of tumor volume) values determined from dose maps were correlated with change in tumor volume and vRECIST response using linear and logistic regression, respectively. Radiosensitivity parameters determined by clonogenic assays of mCRC cell lines HT-29 and DLD-1 after exposure to 90Y or external beam radiotherapy (EBRT; 6MV photons) were used in biological effective dose (BED) calculations. Results: Mean administered radioactivity was 1469±428 MBq (847-2185 MBq), achieving a mean radiation absorbed tumor dose of 35.5±9.4 Gy and mean normal liver dose of 26.4±6.8 Gy. A 1.0 Gy increase in mean, median, and D70 absorbed dose was associated with reduction in tumor volume of 1.8%, 1.8%, and 1.5%, respectively, and increased probability of vRECIST response (odds ratio: 1.09, 1.09, and 1.10 respectively). Threshold mean, median and D70 doses for response were 48.3, 48.8, and 41.8 Gy respectively. EBRT-equivalent BEDs for 90Y are up to 50% smaller than those calculated by applying protraction-corrected radiobiological parameters derived from EBRT alone. Conclusion: Dosimetric studies have assumed equivalence between 90Y SIRT and EBRT, leading to inflation of BED for SIRT and possible under-treatment. Radiobiological parameters for 90Y were applied to a BED model, providing a calculation method that has the potential to improve assessment of tumor control.




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177Lu-EB-PSMA radioligand therapy with escalating doses in patients with metastatic castration-resistant prostate cancer

Purpose: This study is designed to assess the safety and therapeutic response to 177Lu-EB-PSMA treatment with escalating doses in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: With institutional review board approval and informed consent, patients were randomly divided into three groups: Group A (n = 10) were treated with 1.18 ± 0.09 GBq/dose of 177Lu-EB-PSMA. Group B (n = 10) were treated with 2.12 ± 0.19 GBq/dose of 177Lu-EB-PSMA. Group C (n = 8) were treated with 3.52 ± 0.58 GBq/dose of 177Lu-EB-PSMA. Eligible patients received up to three cycles of 177Lu-EB-PSMA therapy, at eight-week intervals. Results: Due to disease progression or bone marrow suppression, 4 out of 10, 5 out of 10, and 5 out of 10 patients completed three cycles therapy as planned in Groups A, B, and C, respectively. The prostate-specific antigen (PSA) response was correlated with treatment dose, with PSA disease control rates in Group B (70%) and C (75%) being higher than that in Group A (10%) (P = 0.007), but no correlation between Group B and Group C was found. 68Ga-PSMA PET/CT showed response in all the treatment groups, however, there was no significant difference between the three groups. Hematologic toxicity study found that platelets in Group B and Group C decreased more than those in Group A, and that Grade 4 thrombocytopenia occurred in 2 (25.0%) patients in Group C. No serious nephritic or hepatic side effects were observed. Conclusion: This study demonstrates that 2.12 GBq/dose of 177Lu-EB-PSMA seems to be safe and adequate in tumor treatment. Further investigations with increased number of patients are warranted.




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Impact of 68Ga-PSMA-11 PET on the Management of recurrent Prostate Cancer in a Prospective Single-Arm Clinical Trial

Introduction: Prostate-specific membrane antigen ligand positron emission tomography (PSMA PET) induces management changes in patients with prostate cancer. We aim to better characterize the impact of PSMA PET on management of recurrent prostate cancer in a large prospective cohort. Methods: We report management changes following PSMA PET, a secondary endpoint of a prospective multicenter trial in men with prostate cancer biochemical recurrence. Pre-PET (Q1), Post-PET (Q2) and Post-Treatment (Q3) questionnaires were sent to referring physicians recording site of recurrence, intended (Q1 to Q2 change) and implemented (Q3) therapeutic and diagnostic management. Results: Q1/Q2 response was collected for 382/635 (60%, intended cohort), Q1/Q2/Q3 for 206 patients (32%, implemented cohort). Intended management change (Q1/2) occurred in 260/382 (68%) patients. Intended change (Q1/2) was considered major in 176/382 (46%) patients. Major changes occurred most often for patients with PSA of 0.5 to <2.0 ng/mL (81/147, 55%). By analysis of stage-groups, management change was consistent with PET disease location, i.e. majority of major changes towards active surveillance (47%) for unknown disease site (103/382, 27%), towards local/focal therapy (56%) for locoregional disease (126/382, 33%), and towards systemic therapy (69% M1a; 43% M1b/c) for metastatic disease (153/382, 40%). According to Q3 responses, intended management was implemented in 160/206 (78%) patients. A total of 150 intended diagnostic tests, mostly CT (n = 43, 29%) and bone Scans/NaF-PET (n = 52, 35%), were prevented by PSMA PET; 73 tests, mostly biopsies (n = 44, 60%) as requested by the study protocol, were triggered (Q1/2). Conclusion: According to referring physicians, sites of recurrence were clarified by PSMA PET and disease localization translated into management changes in more than half of patients with biochemical recurrence of prostate cancer.




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Unexplained Hyperthyroglobulinemia in Differentiated Thyroid Cancer Patients Indicates Radioiodine Adjuvant Therapy: A Prospective Multicenter Study

Background: The management for totally thyroidectomized differentiated thyroid cancer (TT-DTC) patients with unexplained hyperthyroglobulinemia remains indeterminate due to evidence scarcity. This multicenter study aimed at prospectively evaluating the response to radioiodine (131I) adjuvant therapy (RAT) and its potential role in risk stratification and causal clarification. Methods: TT-DTC patients with stimulated serum thyroglobulin (Tgoff) levels > 10 ng/mL but no structurally evident disease were consecutively enrolled in five tertiary care institutions. After the administration of 5.55 GBq of 131I, the risk of presence of persistent/recurrent/metastatic DTC (prmDTC) was compared to that before RAT. The causes of hyperthyroglobulinemia were explored and the response to RAT was assessed 6-12 months post RAT. The change in suppressed thyroglobulin (Tgon) level was reported. Results: A cohort of 254 subjects with a median Tgoff of 27.1 ng/mL was enrolled for the analyses. Immediately after RAT, low-, intermediate-, and high-risk were identified in 5.9%, 88.6%, and 5.5% patients, respectively, with no significant difference in risk stratification compared with that before RAT (P = 0.952). During the follow-up (median, 10.6 months), hyperthyroglobulinemia was ultimately attributed to thyroid remnant, biochemical disease, and structural/functional disease in 17.3%, 54.3%, and 28.3% of subjects, respectively. In addition, excellent, indeterminate, biochemical incomplete, and structural/functional incomplete responses were achieved in 18.1%, 27.2%, 36.2%, and 18.5% of patients, respectively. Notably, distribution for either cause of hyperthyroglobulinemia or response to RAT was comparable among the three postoperative risk groups. Tgon levels in patients who merely received RAT declined significantly over time. Conclusion: Our study demonstrated that over 90% of TT-DTC patients with unexplained hyperthyroglobulinemia are stratified as intermediate-high risk, and RAT using 5.55 GBq of 131I reveals biochemical/functional/structural disease and yields non-structural/functional incomplete response in more than 80% patients, suggesting TT-DTC patients with unexplained hyperthyroglobulinemia as explicit candidates for RAT.




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The effects of monosodium glutamate on PSMA radiotracer uptake in men with recurrent prostate cancer: a prospective, randomized, double-blind, placebo-controlled intra-individual imaging study.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [18F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [18F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.




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The Relevance of Intergovernmental Organizations to African States: The International Organization of La Francophonie

Research Event

6 November 2019 - 10:00am to 11:15am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Louise Mushikiwabo, Secretary General, Organisation Internationale de la Francophonie (OIF)
Chair: Bob Dewar CMG, Associate Fellow, Africa Programme, Chatham House

African states are well represented in intergovernmental organizations linked by official language and colonial history such as the Organisation Internationale de la Francophonie (OIF), the Comunidade dos Países de Língua Portuguesa (CPLP) and the Commonwealth. These organizations aim to provide support in addressing matters of mutual interest – in addition to responding to significant policy challenges such as improving sustainable growth prospects and opportunities to young populations – and citizens are increasingly vocal on key issues such as democracy, human rights and the rule of law. This event series examines the importance of these intergovernmental organizations in working with their members to responsibly and sustainably respond to policy challenges in Africa.

At this event, Louise Mushikiwabo, secretary general of the Organisation Internationale de la Francophonie (OIF), will discuss the organisation’s relevance to African states and the future of the organization on the continent.

THIS EVENT IS NOW FULL AND REGISTRATION HAS NOW CLOSED.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Diversity and Unity: African Agency in International Affairs

22 November 2019

Professor Carlos Lopes

Associate Fellow, Africa Programme
More and more, African countries are able to act in concert to stand up for the interests of the continent.

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Delegates leave the plenary hall of the Africa Union headquarters in Addis Ababa in January 2018. Photo: Getty Images.

The conventional wisdom is that Africa is at the periphery of international affairs, and the perpetual subject – or victim – of decisions by powerful political or economic actors from outside the continent. The argument then goes on that the diversity of African countries, their atomization and fragmentation, further weakens the ability of the continent to act as a unified whole. As with much cliché about Africa, it does not tell the whole story. 

Soft vs hard power

There is no denying that the structure of international affairs, built on foundations which preceded the independence of the vast majority of African states, places limits on the continent’s ability to independently shape the course of its development and its international engagements. African countries lack the hard power that would typically allow them to be bolder in the global scene.

But Africa has long found softer approaches to exercise its agency, through international institutions and diplomatic arrangements. The collective mobilization at the level of the UN, leading up to the successful 1969 declaration by the General Assembly of apartheid as a crime against humanity, is a good example of early post-independence collective influence.

The last two decades have further empowered African countries, as economic development has been translated into increased diplomatic capacity, and socioeconomic potential has given weight to a more assertive leadership.

There are many examples, including: the successful integration of African priorities in the Sustainable Development Goals, notably financing for development; the push to include a substantial climate financing component for developing countries in the Paris Agreement; enhanced coordination between African non-permanent members of the UN Security Council; the condemnation of the International Criminal Court; or the solid resistance to reversals of the Doha Round at the World Trade Organization.

A fragmented unity?

It is also correct to note that individual African countries are quite diverse. Today, there are 55 member states of the African Union (AU); 30 are middle income economies with the rest towards the bottom of various indexes measuring progress and wellbeing. Socioeconomic and political divergences undeniably exist within the continent. But these factors have not prevented the continent from demonstrating some impressive feats of collective agency.

The internal processes put in place by the AU have created a level of continental diplomacy which is more coordinated than any other continental block bar the EU. African countries have also proved adept at using other diplomatic alliances to exercise collective agency, for instance as the most powerful voice within the G77, a coalition of developing nations.

Africa’s Future in a Changing Global Order: Agency in International Relations

HE Jakaya Kikwete, former president of the Republic of Tanzania, addresses a Chatham House conference on the role that African states and citizens play in international relations.

This has allowed Africa to build tactical alliances with countries and blocs from across the globe, resisting being drawn into any one sphere of influence. It has thus retained ultimate control of decision-making, even on issues of traditional ‘hard’ politics, notably the establishment of the African Peace and Security Architecture and the subsequent building of African capacity to collectively manage its peace and security efforts.

Among other things, this collective political will has powered African opposition to a formal permanent presence of US Africa Command (AFRICOM) and helped resolve conflicts from West Africa to Zimbabwe and Lesotho.

Another extraordinary example of collective political resistance can be observed in the trade discussions taking place between Africa and Europe. The EU is Africa's number-one trading partner. It designed and aggressively promoted new bilateral economic partnership agreements (EPAs) at a time when Africans were busy putting together a continental free-trade area. The apparent imbalance between the collective weight of the EU and the weakness of African states seemed likely to end African aspirations to continental integration.

But, to the surprise of many, the majority of African countries were able to resist pressure to sign the EPAs. Almost 20 years into the negotiations, only 15 countries have signed them, with 5 of these being interim agreements. Comparatively, 54 African countries signed the African Continental Free Trade Area agreement in 2018, and 28 have so far ratified.

The ongoing debate between Europe and Africa on migration is an equally useful illustration of how the continent has become more protective of its interests. Despite pressure, the continent has collectively resisted attempts to externalize the EU’s internal migration management challenges to Africa. Rather, it has emphasized finding solutions that would also benefit its nationals through a mobility framework that privileges the management of intra-Africa migration.   

Diversity and unity

There are of course different levels of agency at work. The power of African countries is uneven both vis-à-vis the international community and within the continent itself, where development pathways are increasingly divergent. Achieving collective positions and joint action demands the careful balancing of regional and bilateral objectives and assuaging multiple – and sometimes contradictory – concerns. It is not easy in Africa, like for any other region.

However, there is no denying that Africans have realized the need for bolder action in the international arena, and the importance of unity in achieving their goals. The call by Africa’s leaders for the reform of their continental organization, the AU, demonstrates their recognition of its current limitations. This must now go beyond good intentions.

This article is the first of a series on African agency in international affairs.




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Can the New European Commission Deliver on Its Promises to Africa?

4 December 2019

Fergus Kell

Projects Assistant, Africa Programme

Damir Kurtagic

Former Academy Robert Bosch Fellow, Africa Programme
Familiar promises of equal partnership must be backed by bolder action, including an expanded budget, internal reform and a rethink of its approach to trade negotiations.

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Jutta Urpilainen, new EU commissioner for international partnerships, at the European Parliament in Brussels in October. Photo: Getty Images.

The new European Commission, headed by Ursula von der Leyen, assumed office on 1 December, and there are early signs that Africa will begin near the top of their foreign policy priorities. Policy towards Africa under the new EU administration is yet to be fully defined, but its contours are already visible in the selection of commissioners and assignment of portfolios.  

Although rumours of a dedicated commissioner for Africa were unfounded, the appointment of Jutta Urpilainen to the new role of commissioner for international partnerships – replacing the former post of development commissioner – is a strong signal of ongoing change in EU development thinking, away from bilateral aid towards trade and investment, including by the private sector. 

This may have significant consequences for the EU’s relationship with Africa. In her mission letter to Urpilainen in September, von der Leyen listed the first objective as a new ‘comprehensive strategy for Africa’. Urpilainen, Finland’s finance minister before being posted to Ethiopia as special representative on mediation, has also described her appointment as an opportunity to move on from traditional measures of aid delivery. 

Ambition or incoherence? 

However, this ambition may be at odds with other EU priorities and practices, notably managing migration and institutions and instruments for governing EU–Africa relations that remain rooted in a ‘traditional’ model of North–South development cooperation rather than equitable partnership.

Another newly created post will see Margaritis Schinas assume the role of vice-president for promoting the European way of life – formerly ‘protecting our European way of life’ before a backlash saw it changed – a reminder that migration will remain high on the EU’s foreign policy agenda. The new high representative for foreign and security policy and chief EU diplomat, Josep Borrell, has highlighted the need for bilateral partnership with countries of origin and transit, mainly in Africa. 

Negotiations also continue to stall on a replacement to the Cotonou Agreement, the 20-year partnership framework between the EU and the African, Caribbean and Pacific (ACP) group of states, which now looks certain to be extended for at least 12 months beyond its expiry in February 2020.

Ambiguities in the EU’s negotiating approach have certainly contributed to the delay: having pushed initially for a separate regional pillar for Africa that would be opened to the North African countries (who are not ACP members) and include a loosely defined role for the African Union, this would later be abandoned in favour of a dual-track process on separate new agreements with the AU and ACP respectively.

The EU also continues to pursue controversial economic partnership agreements under the aegis of Cotonou, despite their increasing appearance of incompatibility with the pathbreaking African Continental Free Trade Area (AfCFTA) – one of the clearest expressions to date of African agency.

The EU has so far attempted to gloss over this incoherence, claiming that EPAs can somehow act as the ‘building blocks’ for Africa-wide economic integration. But tensions are appearing between EU departments and within the commission, with the European External Action Service inclined to prioritize a more strategic continental relationship with the AU, while the Directorate-General for International Cooperation and Development remains committed to the ACP as the conduit for financial support and aid delivery.

And it is unlikely to get away with such incoherence for much longer. Change is now urgent, as numerous countries in sub-Saharan Africa continue to attract the strategic and commercial interests of the EU’s competitors: from established players such as China and potentially in future the UK, which is intent on remodelling its Africa ties post-Brexit, to emerging actors such as Turkey or Russia, which held its first Africa summit in October. 

The need for delivery

If the EU is serious about its rhetoric on equal partnership, it must therefore move beyond convoluted hybrid proposals. Delivering on the Juncker administration’s proposal to increase funding for external action by 30 per cent for 2021–27 would mark an important first step, particularly as this involves streamlining that would see the European Development Fund – the financial instrument for EU-ACP relations – incorporated into the main EU budget.

The new commission should therefore continue to exert pressure on the European Council and European Parliament to adopt this proposal, as negotiations on this financial framework have been repeatedly subject to delay and may not be resolved before the end of the year. 

Beyond this, proactive support for the AfCFTA and for structural transformation more broadly must be prioritized ahead of vague promises for a continent-to-continent free trade agreement, as held out by Juncker in his final State of the Union address in 2018. 

The significance of internal EU reforms for Africa should also not be discounted. The EU’s Common Agricultural Policy, for instance, has placed the African sector at a particular disadvantage and has made it harder to compete even in domestic markets, let alone in the distant EU export markets. EU efforts to stimulate inflows of private investments into the African agricultural sector, abolish import tariffs and offer technical support for African producers to satisfy EU health and safety regulations will be of little use if they are undermined by heavy subsidies across Europe.

Ultimately, changes to job titles alone will be insufficient. The new commission’s rhetoric, while ambitious, differs little from that of the previous decade – Africa has heard the promise of a ‘partnership of equals’ and of ‘shared ownership’ since before the advent of the Joint Africa–EU Strategy in 2007. Now is the time for truly bold steps to implement this vision.




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The African Continental Free Trade Area Could Boost African Agency in International Trade

10 December 2019

Tighisti Amare

Assistant Director, Africa Programme

Treasure Thembisile Maphanga

Director, Trade and Industry, African Union Commission (2012–19)
The agreement, which entered into force in May, could be a major step for Africa’s role in international trade, if the continent can overcome barriers to implementation.

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Delegates arrive at the closing ceremony of the African Union summit in Niger in July. Photo: Getty Images.

The entry into force of the African Continental Free Trade Area (AfCFTA) on 30 May, after only three years of negotiations, is an economic, political and diplomatic milestone for the African Union (AU) and its member states, crucial for economic growth, job creation, and making Africa a meaningful player in international trade. But the continent will have to work together to ensure that the potential benefits are fully realized.

A necessary innovation

With its advances in maintaining peace and security, abundant natural resources, high growth rates, improved linkages to global supply chains and a youthful population, Africa is emerging as a new global centre of economic growth, increasingly sought after as a partner by the world’s biggest economies. Governments from across Africa have been taking a more assertive role in international markets, including through proactive diversification of trading partners, and the continent remains a strong advocate for the multilateral trading system.

However, this is not yet reflected in outcomes. The African Union does not have observer status at the World Trade Organization, despite diplomatic efforts in the past decade. Africa has less than a three per cent share of global trade, and the growing trend towards protectionism across the global economy may only increase the vulnerability of a disunited Africa. Its fractured internal market means that trade within Africa is lower than for any other region on the globe, with intra-African trade just 18 per cent of overall exports, as compared to 70 per cent in Europe.

The AfCFTA is the continent’s tool to address the disparity between Africa’s growing economic significance and its peripheral place in the global trade system, to build a bridge between present fragmentation and future prosperity. It is an ambitious, comprehensive agreement covering trade in goods, services, investment, intellectual property rights and competition policy. It has been signed by all of Africa’s states with the exception of Eritrea.

It is the AU's Agenda 2063 flagship project, brought about by the decisions taken at the January 2012 African Union Summit to boost intra-African trade and to fast track the establishment of the Continental Free Trade Area. It builds upon ambitions enshrined in successive agreements including the Lagos Plan of Action and the Abuja Treaty. Access to new regional markets and reduced non-tariff barriers are intended to help companies scale up, driving job creation and poverty reduction, as well as attracting inward investment to even Africa’s smaller economies.

The signing in 2018 of the instruments governing the Single Air Transport Market and the Protocol on Free Movement of Persons, Right of Residence and Right of Establishment provided another step towards the gradual elimination of barriers to the movement of goods, services and people within the continent.

Tests to come

However, while progress is being made towards the ratification of the AfCFTA, much remains to be done before African countries can fully trade under its terms. The framework for implementation is still under development, and the creation of enabling infrastructure that is critical for connectivity will take time to develop and requires extensive investment.

Africa’s Future in a Changing Global Order: Africa’s Economic Diplomacy

Treasure Thembisile Maphanga talks about the international implications of the African Continental Free Trade Agreement (AfCFTA).

So, the first test for the AfCFTA will be the level to which Africa’s leaders make it a domestic priority, and whether a consensus can be maintained across the AU’s member states as the costs of implementation become clear.

There is no guarantee that the gains of free trade will be evenly distributed. They will mainly depend on the extent to which countries embrace industrialization, liberalization of their markets and opening of their borders for free movement of goods and people – policies that some incumbent leaders may be reluctant to implement. Political will to maintain a unified negotiating position with diverse stakeholders, including the private sector, will come under increasing stress.  

A second challenge is how the AfCFTA relates to already existing trade arrangements, notably with the EU.  The AU has long preferred to pursue a continent-to-continent trading arrangement instead of the bilateral Economic Partnership Agreements being sought by the EU under the African, Caribbean and Pacific (ACP) framework to which, with the exception of Algeria, Egypt, Libya, Morocco, Tunisia and South Africa, all African states belong. The signing of the AfCFTA is one important step towards making this possible.

But there are currently negotiations under the ACP to replace the Cotonou Accord (the framework governing trade between ACP members and the EU, including Economic Partnership Agreements [EPAs], that is due to expire in 2020). Negotiations on the African pillar of the accord are due to take place after the AfCFTA has entered into force. So African states and the AU will face the challenge of balancing their commitment to the ACP bloc with pursuing their own interests.

And though the AfCFTA should supersede any other agreements, the EPAs or their successors, will continue to govern day-to-day trading, in parallel to the new pan-African market. It is not yet clear how these contradictions will be reconciled.

A new role for the AU?

The AU will need to play an active role as the main interlocutor with Africa´s international trading partners, with the AfCFTA secretariat being the arbiter of internal tensions and trade disputes. The AU´s engagement at continental level has to date revolved mainly around headline political diplomacy, security and peacekeeping. With the continental free market becoming a reality, an effective pivot to economic diplomacy will be critical for growth and development.

With the AfCFTA, the AU has endeavoured to address Africa’s unsustainable position in global trade, to stimulate growth, economic diversification and jobs for its growing population. Much will depend on the commitment of African leaders to maintaining a unified negotiating position to implement the agreement and the AU’s capacity to effectively move from political to economic diplomacy.




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Can Liberation Movements Really Rid Southern Africa of Corruption?

17 December 2019

Christopher Vandome

Research Fellow, Africa Programme
Southern Africa’s national liberation movements have survived ‘end of decade’ elections across the region. Combating corruption has been at the heart of many of the campaigns, but the question is can they succeed?

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Supporters of the Namibian incumbent president and ruling party South West Africa People's Organisation (SWAPO) presidential candidate Hage Geingob cheer and dance. Photo by GIANLUIGI GUERCIA/AFP via Getty Images.

Swapo’s victory in Namibia two weeks ago was the last in a series of recent ‘end of decade’ elections that have returned dominant parties to power across Southern Africa. However, the “enduring appeal of liberation” is wearing thin.

Experiences across the region show that if governments are to deliver on their electoral promises, they must empower institutions, actively promote a culture of accountability and transparency within their party ranks and pursue economic reforms that untangle the web of party-state-business alliances. Such actions are critical for the survival of national liberation movements as the dominant force in the politics of Southern Africa – but will be difficult to implement.

Avoid political factionalism

South Africa, Botswana, Angola and Zimbabwe all saw new presidents take over just before elections. All used the rhetoric of anti-corruption to distance themselves from the tainted image of their predecessors. But acting on this requires a shift in mind-set in parties that have always preferred to deal with their problems behind closed doors. High profile adversaries from past regimes make tempting targets but could also drive party divisions.

In Angola, the transition of power was safeguarded by an agreement that former president José Eduardo dos Santos would be immune from prosecution. But this week his son faced corruption charges before the country’s supreme court, a high-profile example of a wave of anti-corruption cases across Southern Africa, driven by dominant parties wary of their future.

The allegations against José Filemino De Sousa Dos Santos, nickname ‘Zenu’, include a $500-million fraud involving the country’s central bank. Pressure is also mounting on Zenu’s sister Isabel — once prominent in Angola, she is now absent from public life.

Other leaders have had to tread more carefully. Immunity was a luxury Cyril Ramaphosa was neither willing nor politically able to grant Jacob Zuma in South Africa. Reliant on a few close allies at the top of the party, Ramaphosa lacks foot soldiers at the grassroots level, and his campaign against corruption within the ANC has faced persistent opposition.

Rebuilding institutions and empowering authorities takes time, and with few high-profile cases to point to, people are getting restless. This is also the case in Zimbabwe, where a worsening economic situation has left policy reformers politically isolated.

Party, state, and business

Long term incumbency has blurred the distinction between the party and the state. Liberation movements have created vast party-linked business empires. Political allegiance grants access to economic resources through appointments to lucrative positions in state-owned enterprises, preferential bids for tenders and licenses, and direct access to decision makers.

In Angola, this was fuelled by oil revenues. In South Africa, state capture flourished in an environment where the ANC and its constituent elements had significant power on the panels that chose leaders for state-owned enterprises (SOEs). In Namibia, an Icelandic fishing company paid backhanders to officials for fishing rights in what has become known as the ‘Fishrot’ scandal. Zanu-PF officials’ access to preferential foreign exchange rates present them with lucrative opportunities in Zimbabwe.

Ending this bureaucratic rent seeking goes beyond appointing ‘clean’ officials, which has been central to the anti-corruption campaigns in Angola and South Africa. Governments must also allow scrutiny of the state and empower those institutions designed for that role, such as the National Prosecuting Authority and the Public Protector in South Africa. Zimbabwe’s auditor general has published an in-depth report of the state of corruption in the country’s SOEs.

Companies must also be held to account for their role in aiding, and at worst directly benefitting, from state graft. International businesses have actively sought to benefit from corruption. They are now starting to face the consequences. A former Credit Suisse banker has pleaded guilty in the US over handling alleged kickbacks in Mozambique’s $2-billion “tuna bond” scandal. Global banks and consultancies continue to feel the squeeze for their complicity in state capture in South Africa.

Competition and pluralism

National liberation movements may only have a limited window within which to act. Across the region civil society campaigns and investigative journalists have shed light on some of the worst abuses of power. Anti-corruption campaigns are starting to bite. The state will continue to play a central role in Southern African economies, an important arbiter of economic transformation able to balance the region’s highly unequal and resource-dependent economies.

But opposition, civil society and the media are also critical for the progression towards democratic competition and pluralism in Southern Africa. Parliaments remain vital for holding rulers to account. Long used to unchallenged dominance, liberation movements have significant adjustments to make to rise to the challenge of a new era.

This article was originally published in the Mail and Guardian.




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African Agency Holds Power to Account in a Social Media Age

18 December 2019

Yusuf Hassan

Parliamentary and Media Outreach Assistant, Africa Programme

Waihiga Mwaura

News Anchor, Citizen TV Kenya
Structures to support more in-depth investigative journalism are vital in Africa because that seems to be the only thing those in power still truly fear.

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Broadcast technicians work in a control room during the official launch of the Digital Terrestrial Television (TNT) in February 2019 near Abidjan, Ivory Coast. Photo by ISSOUF SANOGO/AFP via Getty Images.

Africa’s media landscape has undergone a significant change over the last decade as digitalization and new forms of media consumption have weakened state control of information. Social media has provided an opportunity for African citizens and journalists to take agency over how the continent is presented to the wider world, and many emerging African voices bring clarity to this digitally disrupted marketplace. But significant external support is required to make these efforts sustainable.  

There is no one ‘African’ story. African media remains as diverse as the 55 states in the African Union, with each national media ecosystem dependent on patterns of culture and governance - most importantly the power gap between those in leadership and their voters.

Journalists from Egypt, Eritrea and Cameroon - states in the 2019 global top 10 for putting their colleagues in prison - have different perspectives from those in other more liberal African countries.

This is most visible in traditional media where a business model based on advertising revenue has allowed African media houses to grow. But it is susceptible to manipulation from state and business actors holding outlets to ransom in exchange for editorial influence or control – a particularly acute problem in states where business and political elites are closely intertwined, and a middle-class consumer base to fund market-driven advertising has yet to develop.

Those African countries with relatively open borders, stronger passports and a more vibrant civil society also tend to have a more diverse and vibrant media environment. Open borders allow for easier movement, granting journalists the opportunity to travel, benchmark and participate in exchange programs.

The power of online networking

The advent of the social media age has begun to disrupt the links between governance and media health, as the large operations required by ‘serious’ media organizations have been replaced by mobile phone cameras and social media timelines.

Many African journalists are at the forefront of this innovation, unrestricted by historical perceptions of how journalism should be presented, and free to disrupt and change the established narratives to better engage with their ever-growing audiences.

And, far from replacing journalism, social media has actively empowered African journalists and media professionals. Instead of acting as sources for international media outlets as in the past, African journalists can publish their work on their own platforms, enabling greater ownership of how issues in their localities are globally framed. This local voice is often the key to avoiding the endemic oversimplifications and generalisations that have coloured much external coverage of the continent.

Obviously, these changes bring risks. Individual uploaders are largely free to publish what they like, and misinformation can - and often has - lead to devastating consequences, evident in recent violence across central Mali, South Africa and the middle belt of Nigeria.

But journalists on the African continent have an increasingly important role in preventing the spread of misinformation, not only as purveyors of news but also as fact-checkers, able to discern the difference between valid opinion and dubious rhetoric on social media, while new pan-African digital networks and discussion groups enable journalists to share knowledge, expertise, and story ideas, or quickly verify information from across the continent.

It is now possible to quickly find authentic voices for TV, radio or online commentary through digital platforms, present on the ground and able to speak with real authority. Many online networks also include Africa-focused journalists from outside the continent, and any biased or incorrect coverage of the African continent can be ‘called out’ and heavily critiqued, with challenges shared and solutions generated. While journalists remain independent, their working practices and professional standards are being shaped by the discourse in the groups like never before.

Online networking has also exposed the existence of lingering cultural differences between journalists of different national backgrounds, such as a hesitancy to discuss sensitive issues – the health of leaders for instance – for fear of being targeted by the authorities, or the level to which government statements are uncritically accepted.

While journalists search for truth, how they go about it is still very dependent on the state of democracy in their country. Though the cross-fertilisation of best practices and critical scrutiny can only improve the quality of journalism on the continent, in many places there remains a long way to go.

Drive for better resources

Across the world, digital media has struggled to create models which can provide news free at the point of access while also successfully monetizing content. This is even more palpable on the African continent, as the subscription-based models employed as a remedy elsewhere are not feasible on such a large scale in countries without a well-established middle-class.

African media needs resources to keep operating at a time when revenue is dwindling, and talented journalists are decamping to join the marketing, communication and sales sectors in search of better wages. Structures to support more in-depth investigative journalism are vital in Africa because that seems to be the only thing those in power still truly fear.

This means more training opportunities, fellowships, and exchange programs to allow the exchange of ideas and expertise. And, as social media has given a platform to talented local voices from across Africa, then an international community which truly wants to understand the nuances of the continent must hire them.   




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The Central African Republic: Security, Development and Responding to the Humanitarian Situation

Invitation Only Research Event

3 February 2020 - 2:00pm to 3:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Denise Brown, United Nations Deputy Special Representative of the Secretary-General, Resident and Humanitarian Coordinator in the Central African Republic
Chair: Ben Shepherd, Consulting Fellow, Africa Programme, Chatham House

With two-thirds of the country’s population estimated to be in need of humanitarian aid and one-quarter either internally displaced or living as refugees in neighbouring countries, the Central African Republic (CAR) continues to face serious and complex humanitarian challenges. The country’s forthcoming presidential elections scheduled for December 2020 risk inflaming CAR’s volatile security situation particularly with the return of former leader, François Bozizé, ousted by the Séléka rebel coalition leader, Michel Djotodia, who has also returned from exile.

At this event, Denise Brown will discuss CAR’s current security, humanitarian and development situations and the role of actors such as the United Nations Multidimensional Integrated Stabilization Mission in the Central African Republic (MINUSCA). She will also discuss prospects for much-needed governance reform and reconciliation.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Hanna Desta

Programme Assistant, Africa Programme




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POSTPONED: Pursuing Economic Reform and Growth in South Africa: the view from the African National Congress

Research Event

18 March 2020 - 10:30am to 11:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Paul Mashatile, Treasurer General, African National Congress (ANC)

The government of South Africa is pursuing a programme of reform to revitalize the economy, strengthen institutions and combat corruption. The State of the Nation Address (SONA) on 13 February and the budget speech of 26 February represent the most significant articulation of the government’s economic strategy. Central to this is the government’s plans for the energy sector, which is fundamental for reviving the economy, and the reform of State Owned Enterprises (SOEs). But questions remain about possible divergence of the approach taken by government ministers from the policy position of the ruling party, the African National Congress (ANC), and what this might mean for the sustainability and progress of reform.  

At this event, Paul Mashatile, Treasurer General of the ANC, will discuss the party’s assessment of reform efforts to date and priorities for delivering on inclusive growth.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Webinar: Implications of the COVID-19 Pandemic for African Economies and Development

Research Event

21 April 2020 - 4:30pm to 5:30pm

Event participants

Dr Hafez Ghanem, Vice President for Africa, World Bank
Chair: Elizabeth Donnelly, Deputy Director, Africa Programme, Chatham House

Dr Hafez Ghanem discusses the implications of the COVID-19 pandemic for African economies and their development and poverty reduction efforts, and assesses the priorities and obstacles for establishing a comprehensive response to the crisis.
 
While the acute strain placed on health systems by the COVID-19 pandemic is already in evidence, the long-term economic fallout from the crisis is yet to fully manifest.
 
For Africa it is the economic impact that may leave the most enduring legacy: from the direct expense of measures to treat, detect and reduce the spread of the virus; to the indirect costs of domestic lockdown measures, global supply chain disruptions and plummeting commodity prices.
 
As decision-makers globally start to plan for the scale of this economic shock, strategizing in and on Africa to meet the challenge will require unprecedented planning and commitment - and will need to be matched by support from international partners to enable long-term recovery.
 

Hanna Desta

Programme Assistant, Africa Programme




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Webinar: Implications of the COVID-19 Pandemic for African Elections and Democracy

Research Event

6 May 2020 - 2:30pm to 3:30pm

Event participants

Dr Christopher Fomunyoh, Senior Associate and Regional Director for Central and West Africa, National Democratic Institute (NDI)
Chair: Elizabeth Donnelly, Deputy Director, Africa Programme, Chatham House
2020 was anticipated to be a year of landmark elections across Africa, including general elections scheduled in Somalia and Ethiopia – countries at critical junctures in their transitions to electoral democracy – as well as a re-run of annulled presidential elections in Malawi.
 
The COVID-19 pandemic has created new challenges for African countries seeking to hold elections or further democratization – including the practicalities of adapting containment measures to electoral processes in the context of strained financial and logistical resources. It may also be used as a pretext for the pursuit of repressive legislation and constitutional amendments to preclude elections or bolster authoritarianism, compounded by new constraints on accountability mechanisms such as election observation missions.
 
At this event, Dr Christopher Fomunyoh discusses the likely impact of the COVID-19 pandemic on elections and democracy in various African countries, as well as responses and measures to meet the multifaceted challenges posed.

Hanna Desta

Programme Assistant, Africa Programme




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How images frame China's role in African development

7 May 2020 , Volume 96, Number 3

George Karavas

Political leaders, policy-makers and academics routinely refer to development as an objective process of social change through the use of technical, value-free terms. Images of poverty and inequality are regularly presented as evidence of a world that exists ‘out there’ where development unfolds. This way of seeing reflects the value of scientific forms of knowledge but also sits in tension with the normative foundations of development that take European modernization and industrialization as the benchmark for comparison. The role images play in this process is often overlooked. This article argues that a dominant mode of visuality based on a Cartesian separation between subject and object, underpinning the ascendance of European hegemony and colonialism, aligns with the core premises of orthodox development discourse. An example of how visual representations of development matter is presented through images of Africa–China relations in western media sources. Using widely circulated images depicting China's impact on African development in western news media sources as an example of why visual politics matters for policy-making, the article examines how images play a role in legitimizing development planning by rendering associated forms of epistemological and structural violence ‘invisible to the viewer’.




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Upregulation of CD73 Confers Acquired Radioresistance and is Required for Maintaining Irradiation-selected Pancreatic Cancer Cells in a Mesenchymal State [Research]

The molecular mechanisms underlying exceptional radioresistance in pancreatic cancer remain elusive. In the present study, we established a stable radioresistant pancreatic cancer cell line MIA PaCa-2-R by exposing the parental MIA PaCa-2 cells to fractionated ionizing radiation (IR). Systematic proteomics and bioinformatics analysis of protein expression in MIA PaCa-2 and MIA PaCa-2-R cells revealed that several growth factor-/cytokine-mediated pathways, including the OSM/STAT3, PI3K/AKT, and MAPK/ERK pathways, were activated in the radioresistant cells, leading to inhibition of apoptosis and increased epithelial-mesenchymal plasticity. In addition, the radioresistant cells exhibited enhanced capabilities of DNA repair and antioxidant defense compared with the parental cells. We focused functional analysis on one of the most up-regulated proteins in the radioresistant cells, ecto-5'-nucleotidase (CD73), which is a cell surface protein that is overexpressed in different types of cancer. Ectopic overexpression of CD73 in the parental cells resulted in radioresistance and conferred resistance to IR-induced apoptosis. Knockdown of CD73 re-sensitized the radioresistant cells to IR and IR-induced apoptosis. The effect of CD73 on radioresistance and apoptosis is independent of the enzymatic activity of CD73. Further studies demonstrate that CD73 up-regulation promotes Ser-136 phosphorylation of the proapoptotic protein BAD and is required for maintaining the radioresistant cells in a mesenchymal state. Our findings suggest that expression alterations in the IR-selected pancreatic cancer cells result in hyperactivation of the growth factor/cytokine signaling that promotes epithelial-mesenchymal plasticity and enhancement of DNA repair. Our results also suggest that CD73, potentially a novel downstream factor of the enhanced growth factor/cytokine signaling, confers acquired radioresistance by inactivating proapoptotic protein BAD via phosphorylation of BAD at Ser-136 and by maintaining the radioresistant pancreatic cancer cells in a mesenchymal state.




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Site-specific N-glycan Analysis of Antibody-binding Fc {gamma} Receptors from Primary Human Monocytes [Research]

FcRIIIa (CD16a) and FcRIIa (CD32a) on monocytes are essential for proper effector functions including antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Indeed, therapeutic monoclonal antibodies (mAbs) that bind FcRs with greater affinity exhibit greater efficacy. Furthermore, post-translational modification impacts antibody binding affinity, most notably the composition of the asparagine(N)-linked glycan at N162 of CD16a. CD16a is widely recognized as the key receptor for the monocyte response, however the post-translational modifications of CD16a from endogenous monocytes are not described. Here we isolated monocytes from individual donors and characterized the composition of CD16a and CD32a N-glycans from all modified sites. The composition of CD16a N-glycans varied by glycosylation site and donor. CD16a displayed primarily complex-type biantennary N-glycans at N162, however some individuals expressed CD16a V158 with ~20% hybrid and oligomannose types which increased affinity for IgG1 Fc according to surface plasmon resonance binding analyses. The CD16a N45-glycans contain markedly less processing than other sites with >75% hybrid and oligomannose forms. N38 and N74 of CD16a both contain highly processed complex-type N-glycans with N-acetyllactosamine repeats and complex-type biantennary N-glycans dominate at N169. The composition of CD16a N-glycans isolated from monocytes included a higher proportion of oligomannose-type N-glycans at N45 and less sialylation plus greater branch fucosylation than we observed in a recent analysis of NK cell CD16a. The additional analysis of CD32a from monocytes revealed different features than observed for CD16a including the presence of a predominantly biantennary complex-type N-glycans with two sialic acids at both sites (N64 and N145).




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Combined EGFR and ROCK Inhibition in Triple-negative Breast Cancer Leads to Cell Death Via Impaired Autophagic Flux [Research]

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with very limited therapeutic options. We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell death, however, the underlying mechanisms remain unclear. To investigate this, here we applied a mass spectrometry-based proteomic approach to identify proteins altered on single and combination treatments. Our proteomic data revealed autophagy as the major molecular mechanism implicated in the cells' response to combinatorial treatment. We here show that EGFR inhibition by gefitinib treatment alone induces autophagy, a cellular recycling process that acts as a cytoprotective response for TNBC cells. However, combined inhibition of EGFR and ROCK leads to autophagy blockade and accumulation of autophagic vacuoles. Our data show impaired autophagosome clearance as a likely cause of antitumor activity. We propose that the inhibition of the autophagic flux on combinatorial treatment is attributed to the major cytoskeletal changes induced on ROCK inhibition, given the essential role the cytoskeleton plays throughout the various steps of the autophagy process.




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Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer [Research]

Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERβ) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERβ under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERβ in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERβ of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERβ association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERβ association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERβ in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners.




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Advances in Tools to Determine the Glycan-Binding Specificities of Lectins and Antibodies [Reviews]

Proteins that bind carbohydrate structures can serve as tools to quantify or localize specific glycans in biological specimens. Such proteins, including lectins and glycan-binding antibodies, are particularly valuable if accurate information is available about the glycans that a protein binds. Glycan arrays have been transformational for uncovering rich information about the nuances and complexities of glycan-binding specificity. A challenge, however, has been the analysis of the data. Because protein-glycan interactions are so complex, simplistic modes of analyzing the data and describing glycan-binding specificities have proven inadequate in many cases. This review surveys the methods for handling high-content data on protein-glycan interactions. We contrast the approaches that have been demonstrated and provide an overview of the resources that are available. We also give an outlook on the promising experimental technologies for generating new insights into protein-glycan interactions, as well as a perspective on the limitations that currently face the field.




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Integration of IgA and IgG Autoantigens Improves Performance of Biomarker Panels for Early Diagnosis of Lung Cancer [Research]

Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (i.e. BCL7A, and TRIM33 and MTERF4) and three IgG autoantigens (i.e. CTAG1A, DDX4 and MAGEC2) for diagnosis of early stage LC with 73.5% sensitivity at >85% specificity. In Phase III, the performance of this biomarker panel was confirmed with an independent cohort, comprised of 88 early stage LC patients, 18 LBL patients, and 36 healthy subjects. Finally, a blind test on 178 serum samples was conducted to confirm the performance of the biomarker panel. In summary, this study demonstrates for the first time that an integrated panel of IgA/IgG autoantigens can serve as valuable biomarkers to further improve the performance of early diagnosis of LC.




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Biosynthesis of depsipeptides with a 3-hydroxybenzoate moiety and selective anticancer activities involves a chorismatase [Metabolism]

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.




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Perturbation of phosphoglycerate kinase 1 (PGK1) only marginally affects glycolysis in cancer cells [Metabolism]

Phosphoglycerate kinase 1 (PGK1) plays important roles in glycolysis, yet its forward reaction kinetics are unknown, and its role especially in regulating cancer cell glycolysis is unclear. Here, we developed an enzyme assay to measure the kinetic parameters of the PGK1-catalyzed forward reaction. The Km values for 1,3-bisphosphoglyceric acid (1,3-BPG, the forward reaction substrate) were 4.36 μm (yeast PGK1) and 6.86 μm (human PKG1). The Km values for 3-phosphoglycerate (3-PG, the reverse reaction substrate and a serine precursor) were 146 μm (yeast PGK1) and 186 μm (human PGK1). The Vmax of the forward reaction was about 3.5- and 5.8-fold higher than that of the reverse reaction for the human and yeast enzymes, respectively. Consistently, the intracellular steady-state concentrations of 3-PG were between 180 and 550 μm in cancer cells, providing a basis for glycolysis to shuttle 3-PG to the serine synthesis pathway. Using siRNA-mediated PGK1-specific knockdown in five cancer cell lines derived from different tissues, along with titration of PGK1 in a cell-free glycolysis system, we found that the perturbation of PGK1 had no effect or only marginal effects on the glucose consumption and lactate generation. The PGK1 knockdown increased the concentrations of fructose 1,6-bisphosphate, dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, and 1,3-BPG in nearly equal proportions, controlled by the kinetic and thermodynamic states of glycolysis. We conclude that perturbation of PGK1 in cancer cells insignificantly affects the conversion of glucose to lactate in glycolysis.




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Targeting the polyamine pathway&#x2014;&#x201C;a means&#x201D; to overcome chemoresistance in triple-negative breast cancer [Cell Biology]

Triple-negative breast cancer (TNBC) is characterized by its aggressive biology, early metastatic spread, and poor survival outcomes. TNBC lacks expression of the targetable receptors found in other breast cancer subtypes, mandating use of cytotoxic chemotherapy. However, resistance to chemotherapy is a significant problem, encountered in about two-thirds of TNBC patients, and new strategies are needed to mitigate resistance. In this issue of the Journal of Biological Chemistry, Geck et al. report that TNBC cells are highly sensitive to inhibition of the de novo polyamine synthesis pathway and that inhibition of this pathway sensitizes cells to TNBC-relevant chemotherapy, uncovering new opportunities for addressing chemoresistance.




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Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy [Molecular Bases of Disease]

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.




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Canberra's north-south divided over internet surfing and the NBN

It's another front in the long-running rivalry beneath north and south in the nation's capital.




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From making scarves to building a $165 million tech start-up: Canva's Melanie Perkins

To say it has been a wild ride for Canva founder and CEO Melanie Perkins would be an understatement.




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ACT government defends seeking access to Canberrans' metadata

The ACT government has defended its right to seek access to Canberrans' private phone and internet records without a warrant.




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Government acknowledges poor internet in Canberra's south but sticks to NBN plan

Minister for Communications acknowledges some areas of Canberra's southern suburbs have poor internet access.




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Can the government really protect your privacy when it 'de-identifies' public data?

We don't really know to how to use big data and protect personal information at the same time.




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Faster NBN connections should go to all Canberra homes: Labor's Gai Brodtmann

Canberra Labor MP calls for fibre-to-the-curb and fibre-to-the-premises for whole of Canberra.




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Microsoft cloud targets critical government business in Canberra

Two new regions of Microsoft's Azure cloud will open in Canberra on Tuesday.




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Face scanning falls flat as part of digital credentials push

State government's facial recognition ID check is now required for those seeking solar rebates, but it failed 40 per cent of the time during the first two weeks.




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Can the World Economy Find a New Leader?

10 October 2019

This paper examines the governance problems in the monetary system and global trade and regulation. It then explores whether issues have arisen because the US has given up its dominant role, and if so how these might be rectified.

Alan Beattie

Associate Fellow, Global Economy and Finance Programme and Europe Programme

2019-10-07-RMB.jpg

An employee counts money at a branch of the Industrial and Commercial Bank of China, Anhui Province, on 26 July 2011. Photo: Getty Images.

Summary

  • Multilateralism may, in theory, put countries on an equal economic footing. But in practice the concept has often relied on an anchor government to create and preserve global norms. Under the presidency of Donald Trump, the US has accelerated its move away from leadership in global economic governance. This shift threatens the monetary and trading systems that have long underpinned globalization. Does the global economy need – and can it find – another leader to take America’s place?
  • In the monetary sphere, the US role in providing an internationalized currency has endured relatively well, even though the US’s formal anchoring of the global exchange rate system collapsed nearly half a century ago. Governance of the US dollar and of the dollar-based financial system has largely been left to competent technocrats.
  • Recent US political uncertainty has encouraged other governments, particularly in the eurozone and China, in their long-standing quest to supplant the dollar. But these economies’ internal weaknesses have prevented their respective currencies from playing a wider role. Arguments for a multipolar system exist, yet network effects plus the dollar’s superior institutions mean it has retained its dominance.
  • In trade, the US role as anchor of the global legal order was already looking unreliable before Trump’s election. Washington has faced growing resistance at home to its global responsibilities. This, together with the idiosyncratic rise of countries such as China, has made the US an increasingly unreliable and narrowly transactional leader.
  • More recently, hard-to-regulate issues such as foreign direct investment, technology transfer and data flows, often with national security implications, are increasingly undermining the ideal of multilateral global governance. Institutions such as the World Trade Organization, focused on cross-border trade in goods and services, are becoming less relevant.
  • Recent US actions against the Chinese technology firm Huawei show the Trump administration’s willingness to decouple the US market from China and try to drag other economies with it. As far as possible, other governments should resist taking sides. A complete separation of the global economy into rival spheres is probably unfeasible, and certainly highly undesirable.
  • Although future US administrations may be less wantonly destructive, it is not realistic to expect them to resume America’s former role. Nor can the US simply be replaced with another power. Instead, coalitions of governments with interests in international rules-based orders will need to form. These coalitions will need to show due deference to issues like investment and national security, especially where attempts to bind governments by multilateral rules are likely to provoke a severe backlash from domestic constituencies.




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Could Brexit Open Up a New Market for Latin American Agriculture?

8 October 2019

Dr Christopher Sabatini

Senior Research Fellow for Latin America, US and the Americas Programme

Anar Bata

Coordinator, US and the Americas Programme
The demand will be there, but a range of barriers are likely to limit growth in agricultural trade links between the UK and Latin America.

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An area of forest-pasture integration prepared to receive dairy cattle for feeding in Ipameri, Brazil. Photo: Getty Images.

Currently 73% of all UK agricultural imports come from the EU. That heavy dependence sparked a report by the British parliament expressing concern about the UK’s food security in the immediate aftermath of Brexit.

Meanwhile, Latin America’s agricultural powerhouses Brazil and Argentina only accounted for a total of 1.6% of the UK’s agricultural market across eight sectors in 2018. A growing relationship would seem to be an obvious fit post-Brexit – but a number of structural issues stand in the way.

There is certainly scope for increasing Latin American agricultural exports to the UK given current trade patterns. Two of the main agricultural imports that the UK buys from the EU are meat products, representing 82% of UK imports in that category, and dairy products and eggs; 98% of UK’s dairy- and egg-related external supply came from the EU. In both these areas, Brazil and Argentina could have comparative advantages, including lower prices.

But any improvement in agricultural trade links will depend on two factors: 1) how the UK leaves the EU: whether it crashes out, negotiates an easy exit or leaves at all; and 2) whether Latin American agricultural producers can improve their environmental practices and can meet the production standards established by the EU and likely maintained by a post-Brexit Britain.

Some of the key issues that will affect this are:

Tariff structures

On the UK side, there is pressure by domestic agricultural producers to raise UK tariffs to allow them to expand their local market share. Yet, despite the pressures from local farmers, the UK has laid out two scenarios.

In one case, the UK government has stated that in the event of a no-deal Brexit, tariffs will be lowered to 0%, but there is no firm commitment and this would likely be temporary. It is also unlikely that those would apply to all agricultural products. In the case of beef imports (of which Argentina and Brazil are major exporters), the UK has proposed that ‘no deal’ would bring a reduction on tariffs on a range of beef products of roughly half.

Meanwhile, tariffs on EU imports could go up. Even if the UK establishes 0% tariffs on EU products, it’s possible that the EU will not reciprocate, instead choosing to revert to the World Trade Organization’s most-favoured-nation tariffs. To take one example of what that would mean, under existing most-favoured-nation tariffs on beef, the tariffs range from €6.80 per 100 kilograms of full bovine carcasses or half carcasses all the way up to €161.10 for 160 kilograms of prepared or preserved meat, including sausages.

Free trade agreements between the EU and Latin American countries

The EU has free trade agreements with the Central American bloc of Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama; Mexico; Chile; and the Andean countries of Colombia, Ecuador, and Peru. In all those cases, the UK has expressed its desire to maintain its liberal trade framework with those countries.

Even if the UK leaves without a deal and tariffs do increase on EU agricultural exports, though, these Western Hemisphere economies are unlikely to see a large boost in their food exports to the UK. Chile and other large fruit producers are already locked into the Chinese market. And the real agricultural powerhouses, Argentina and Brazil, are now part of the EU trade agreement with Mercosur.

Since that agreement is not yet in force, the UK and Mercosur would need to negotiate a separate agreement. Such an agreement may be easier to ratify than the EU agreement since there is only one partner (the UK) for such a deal, but the likely change in government in Argentina after the 27 October elections may make it difficult to secure a deal on the Mercosur side.

Some EU trade agreements also include arrangements for tariff rate quotas. An EU quota with Argentina, for example, allows more than 280,000 tonnes of lamb to be imported to the EU duty free from Argentina, among other countries. It is unclear whether these quotas will be maintained or even expanded by the UK post-Brexit.  

Phytosanitary standards and rules governing the treatment of animals

Non-tariff barriers concerning production practices could play a key role. The large UK consumer organization Which? raised the concern before parliament that in the scramble to replace EU food imports, the UK could diverge from EU standards on animal cloning, the use of growth hormones and hygiene in poultry production. Pressure to maintain those standards would likely exclude many products from South America.

Beyond the regulatory barriers, there is also the possibility that UK consumers may reject agricultural products produced in less sustainable and humane conditions, or in countries (such as Brazil) that are seen by the public as abusing the environment.

In short, an increase in Latin American agricultural exports to the UK market may not happen as easily or as quickly as some hope after Brexit. In fact, it may not happen at all. But if Latin American countries – Argentina and Brazil in particular – want to capture this potential new market, the first step both should be to improve their environmental profile and standards at both the government and producer level.




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The African Continental Free Trade Area Could Boost African Agency in International Trade

10 December 2019

Tighisti Amare

Assistant Director, Africa Programme

Treasure Thembisile Maphanga

Director, Trade and Industry, African Union Commission (2012–19)
The agreement, which entered into force in May, could be a major step for Africa’s role in international trade, if the continent can overcome barriers to implementation.

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Delegates arrive at the closing ceremony of the African Union summit in Niger in July. Photo: Getty Images.

The entry into force of the African Continental Free Trade Area (AfCFTA) on 30 May, after only three years of negotiations, is an economic, political and diplomatic milestone for the African Union (AU) and its member states, crucial for economic growth, job creation, and making Africa a meaningful player in international trade. But the continent will have to work together to ensure that the potential benefits are fully realized.

A necessary innovation

With its advances in maintaining peace and security, abundant natural resources, high growth rates, improved linkages to global supply chains and a youthful population, Africa is emerging as a new global centre of economic growth, increasingly sought after as a partner by the world’s biggest economies. Governments from across Africa have been taking a more assertive role in international markets, including through proactive diversification of trading partners, and the continent remains a strong advocate for the multilateral trading system.

However, this is not yet reflected in outcomes. The African Union does not have observer status at the World Trade Organization, despite diplomatic efforts in the past decade. Africa has less than a three per cent share of global trade, and the growing trend towards protectionism across the global economy may only increase the vulnerability of a disunited Africa. Its fractured internal market means that trade within Africa is lower than for any other region on the globe, with intra-African trade just 18 per cent of overall exports, as compared to 70 per cent in Europe.

The AfCFTA is the continent’s tool to address the disparity between Africa’s growing economic significance and its peripheral place in the global trade system, to build a bridge between present fragmentation and future prosperity. It is an ambitious, comprehensive agreement covering trade in goods, services, investment, intellectual property rights and competition policy. It has been signed by all of Africa’s states with the exception of Eritrea.

It is the AU's Agenda 2063 flagship project, brought about by the decisions taken at the January 2012 African Union Summit to boost intra-African trade and to fast track the establishment of the Continental Free Trade Area. It builds upon ambitions enshrined in successive agreements including the Lagos Plan of Action and the Abuja Treaty. Access to new regional markets and reduced non-tariff barriers are intended to help companies scale up, driving job creation and poverty reduction, as well as attracting inward investment to even Africa’s smaller economies.

The signing in 2018 of the instruments governing the Single Air Transport Market and the Protocol on Free Movement of Persons, Right of Residence and Right of Establishment provided another step towards the gradual elimination of barriers to the movement of goods, services and people within the continent.

Tests to come

However, while progress is being made towards the ratification of the AfCFTA, much remains to be done before African countries can fully trade under its terms. The framework for implementation is still under development, and the creation of enabling infrastructure that is critical for connectivity will take time to develop and requires extensive investment.

Africa’s Future in a Changing Global Order: Africa’s Economic Diplomacy

Treasure Thembisile Maphanga talks about the international implications of the African Continental Free Trade Agreement (AfCFTA).

So, the first test for the AfCFTA will be the level to which Africa’s leaders make it a domestic priority, and whether a consensus can be maintained across the AU’s member states as the costs of implementation become clear.

There is no guarantee that the gains of free trade will be evenly distributed. They will mainly depend on the extent to which countries embrace industrialization, liberalization of their markets and opening of their borders for free movement of goods and people – policies that some incumbent leaders may be reluctant to implement. Political will to maintain a unified negotiating position with diverse stakeholders, including the private sector, will come under increasing stress.  

A second challenge is how the AfCFTA relates to already existing trade arrangements, notably with the EU.  The AU has long preferred to pursue a continent-to-continent trading arrangement instead of the bilateral Economic Partnership Agreements being sought by the EU under the African, Caribbean and Pacific (ACP) framework to which, with the exception of Algeria, Egypt, Libya, Morocco, Tunisia and South Africa, all African states belong. The signing of the AfCFTA is one important step towards making this possible.

But there are currently negotiations under the ACP to replace the Cotonou Accord (the framework governing trade between ACP members and the EU, including Economic Partnership Agreements [EPAs], that is due to expire in 2020). Negotiations on the African pillar of the accord are due to take place after the AfCFTA has entered into force. So African states and the AU will face the challenge of balancing their commitment to the ACP bloc with pursuing their own interests.

And though the AfCFTA should supersede any other agreements, the EPAs or their successors, will continue to govern day-to-day trading, in parallel to the new pan-African market. It is not yet clear how these contradictions will be reconciled.

A new role for the AU?

The AU will need to play an active role as the main interlocutor with Africa´s international trading partners, with the AfCFTA secretariat being the arbiter of internal tensions and trade disputes. The AU´s engagement at continental level has to date revolved mainly around headline political diplomacy, security and peacekeeping. With the continental free market becoming a reality, an effective pivot to economic diplomacy will be critical for growth and development.

With the AfCFTA, the AU has endeavoured to address Africa’s unsustainable position in global trade, to stimulate growth, economic diversification and jobs for its growing population. Much will depend on the commitment of African leaders to maintaining a unified negotiating position to implement the agreement and the AU’s capacity to effectively move from political to economic diplomacy.




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The EU Cannot Build a Foreign Policy on Regulatory Power Alone

11 February 2020

Alan Beattie

Associate Fellow, Global Economy and Finance Programme and Europe Programme
Brussels will find its much-vaunted heft in setting standards cannot help it advance its geopolitical interests.

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EU Commission President Ursula von der Leyen speaks at the European Parliament in Strasbourg in February. Photo: Getty Images.

There are two well-established ideas in trade. Individually, they are correct. Combined, they can lead to a conclusion that is unfortunately wrong.

The first idea is that, across a range of economic sectors, the EU and the US have been engaged in a battle to have their model of regulation accepted as the global one, and that the EU is generally winning.

The second is that governments can use their regulatory power to extend strategic and foreign policy influence.

The conclusion would seem to be that the EU, which has for decades tried to develop a foreign policy, should be able to use its superpower status in regulation and trade to project its interests and its values abroad.

That’s the theory. It’s a proposition much welcomed by EU policymakers, who know they are highly unlikely any time soon to acquire any of the tools usually required to run an effective foreign policy.

The EU doesn’t have an army it can send into a shooting war, enough military or political aid to prop up or dispense of governments abroad, or a centralized intelligence service. Commission President Ursula von der Leyen has declared her outfit to be a ‘geopolitical commission’, and is casting about for any means of making that real.

Through the ‘Brussels effect’ whereby European rules and standards are exported via both companies and governments, the EU has indeed won many regulatory battles with the US.

Its cars, chemicals and product safety regulations are more widely adopted round the world than their American counterparts. In the absence of any coherent US offering, bar some varied state-level systems, the General Data Protection Regulation (GDPR) is the closest thing the world has to a single model for data privacy, and variants of it are being adopted by dozens of countries.

The problem is this. Those parts of global economic governance where the US is dominant – particularly the dollar payments system – are highly conducive to projecting US power abroad. The extraterritorial reach of secondary sanctions, plus the widespread reliance of banks and companies worldwide on dollar funding – and hence the American financial system – means that the US can precisely target its influence.

The EU can enforce trade sanctions, but not in such a powerful and discriminatory way, and it will always be outgunned by the US. Donald Trump could in effect force European companies to join in his sanctions on Iran when he pulled out of the nuclear deal, despite EU legislation designed to prevent their businesses being bullied. He can go after the chief financial officer of Huawei for allegedly breaching those sanctions.

By contrast, the widespread adoption of GDPR or data protection regimes inspired by it may give the EU a warm glow of satisfaction, but it cannot be turned into a geopolitical tool in the same way.

Nor, necessarily, does it particularly benefit the EU economy. Europe’s undersized tech sector seems unlikely to unduly benefit from the fact that data protection rules were written in the EU. Indeed, one common criticism of the regulations is that they entrench the power of incumbent tech giants like Google.

There is a similar pattern at work in the adoption of new technologies such as artificial intelligence and the Internet of Things. In that field, the EU and its member states are also facing determined competition from China, which has been pushing its technologies and standards through forums such as the International Telecommunication Union.

The EU has been attempting to write international rules for the use of AI which it hopes to be widely adopted. But again, these are a constraint on the use of new technologies largely developed by others, not the control of innovation.

By contrast, China has created a vast domestic market in technologies like facial recognition and unleashed its own companies on it. The resulting surveillance kit can then be marketed to emerging market governments as part of China’s enduring foreign policy campaign to build up supporters in the developing world.

If it genuinely wants to turn its economic power into geopolitical influence – and it’s not entirely clear what it would do with it if it did – the EU needs to recognize that not all forms of regulatory and trading dominance are the same.

Providing public goods to the world economy is all very well. But unless they are so particular in nature that they project uniquely European values and interests, that makes the EU a supplier of useful plumbing but not a global architect of power.

On the other hand, it could content itself with its position for the moment. It could recognize that not until enough hard power – guns, intelligence, money – is transferred from the member states to the centre, or until the member states start acting collectively, will the EU genuinely become a geopolitical force. Speaking loudly and carrying a stick of foam rubber is rarely a way to gain credibility in international relations.

This article is part of a series of publications and roundtable discussions in the Chatham House Global Trade Policy Forum.




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Can the UK Strike a Balance Between Openness and Control?

2 March 2020

Hans Kundnani

Senior Research Fellow, Europe Programme
Rather than fetishizing free trade, Britain should aim to be a model for a wider recalibration of sustainable globalization.

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Boris Johnson speaks at the Old Naval College in Greenwich on 3 February. Photo: Getty Images.

This week the UK will start negotiating its future relationship with the European Union. The government is trying to convince the EU that it is serious about its red lines and is prepared to walk away from negotiations if the UK’s ‘regulatory freedom’ is not accepted – a no-deal scenario that would result in tariffs between the EU and the UK. Yet at the same time the story it is telling the world is that Britain is ‘re-emerging after decades of hibernation as a campaigner for global free trade’, as Boris Johnson put it in his speech in Greenwich a few weeks ago.

The EU is understandably confused. It’s a bit odd to claim to be campaigning for free trade at the exact moment you are creating new barriers to trade. If Britain were so committed to frictionless trade, it wouldn’t have left the EU in the first place – and having decided to leave, it would have sought to maintain a close economic relationship with the EU, like that of Norway, rather than seek a basic trade deal like Canada’s. 

As well as creating confusion, the narrative also absurdly idealizes free trade. Johnson invoked Richard Cobden and the idea that free trade is ‘God’s diplomacy – the only certain way of uniting people in the bonds of peace since the more freely goods cross borders the less likely it is that troops will ever cross borders’. But the idea that free trade prevents war was shattered by the outbreak of the First World War, which brought to an end the first era of globalization.

We also know that the domestic effects of free trade are more complex and problematic than Johnson suggested. Economic liberalization increases efficiency by removing friction but also creates disruption and has huge distributional consequences – that is, it creates winners and losers. In a democracy, these consequences need to be mitigated.

In any case, the world today is not the same as the one in which Cobden lived. Tariffs are at a historically low level – and many non-tariff barriers have also been removed. In other words, most of the possible gains from trade liberalization have already been realized. Johnson talked about the dangers of a new wave of protectionism. But as the economist Dani Rodrik has argued, the big problem in the global economy is no longer a lack of openness, it is a lack of democratic legitimacy.

The UK should therefore abandon this confusing and misleading narrative and own the way it is actually creating new barriers to trade – and do a better job of explaining the legitimate reasons for doing so. Instead of simplistically talking up free trade, we should be talking about the need to balance openness and economic efficiency with democracy and a sense of control, which is ultimately what Brexit was all about. Instead of claiming to be a ‘catalyst for free trade’, as Johnson put it, the UK should be talking about how it is trying to recalibrate globalization and, in doing so, make it sustainable.

In the three decades after the end of the Cold War, globalization got out of control as barriers to the movement of capital and goods were progressively removed – what Rodrik called ‘hyper-globalization’ to distinguish it from the earlier, more moderate phase of globalization. This kind of deep integration necessitated the development of a system of rules, which have constrained the ability of states to pursue the kind of economic policy, particularly industrial policy, they want, and therefore undermined democracy.

Hyper-globalization created a sense that ‘the nation state has fundamentally lost control of its destiny, surrendering to anonymous global forces’, as the economist Barry Eichengreen put it. Throughout the West, countries are all struggling with the same dilemma – how to reconcile openness and deep integration on the one hand, and democracy, sovereignty and a sense of control on the other.

Within the EU, however, economic integration and the abolition of barriers to the movement of capital and goods went further than in the rest of the world – and the evolution of the principle of freedom of movement after the Maastricht Treaty meant that barriers to the internal movement of people were also eliminated as the EU was enlarged. What happened within the EU might be thought of as ‘hyper-regionalization’ – an extreme example, in a regional context, of a global trend.

EU member states have lost control to an even greater extent than other nation states – albeit to anonymous regional rather than global forces – and this loss of control was felt intensely within the EU. It is therefore logical that this led to an increase in Euroscepticism. Whereas the left wants to restore some barriers to the movement of capital and goods, the right wants to restore barriers to the movement of people.

However, having left the EU, the UK is uniquely well placed to find a new equilibrium. The UK has an ideological commitment to free trade that goes back to the movement to abolish the Corn Laws in the 1840s – which Johnson’s speech expressed. It is difficult to imagine the UK becoming protectionist in any meaningful sense. But at the same time, it has a well-developed sense of national and popular sovereignty, and the sense that the two go together – which is why it was so sensitive to the erosion of them through the EU. This means that Britain is unlikely to go to one extreme or the other.

In other words, the UK may be the ideal country to find a new balance between openness and integration on the one hand, and a sense of control on the other. If it can find this balance – if it can make Brexit work – the UK could be a model for a wider recalibration of sustainable globalization. That, rather than fetishizing free trade, is the real contribution the UK can make.

A version of this article was originally published in the Observer.




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How images frame China's role in African development

7 May 2020 , Volume 96, Number 3

George Karavas

Political leaders, policy-makers and academics routinely refer to development as an objective process of social change through the use of technical, value-free terms. Images of poverty and inequality are regularly presented as evidence of a world that exists ‘out there’ where development unfolds. This way of seeing reflects the value of scientific forms of knowledge but also sits in tension with the normative foundations of development that take European modernization and industrialization as the benchmark for comparison. The role images play in this process is often overlooked. This article argues that a dominant mode of visuality based on a Cartesian separation between subject and object, underpinning the ascendance of European hegemony and colonialism, aligns with the core premises of orthodox development discourse. An example of how visual representations of development matter is presented through images of Africa–China relations in western media sources. Using widely circulated images depicting China's impact on African development in western news media sources as an example of why visual politics matters for policy-making, the article examines how images play a role in legitimizing development planning by rendering associated forms of epistemological and structural violence ‘invisible to the viewer’.




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Phosphatidylinositol Metabolism, Phospholipases, Lipidomics, and Cancer:In Memoriam of Michael J. O. Wakelam (1955-2020)

Edward A Dennis
Apr 28, 2020; 0:jlr.T120000868v1-jlr.T120000868
Tribute




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Episode 63 - The Internet of the French (IotF) New Surface Pro and Netflix vs Cannes

This week we dive into the new Surface Pro with Digital Arts' Neil Bennett. Who is it for and is it that different to the last one? And are 2 in 1 devices really the future of computing? Then Techworld's Scott Carey, fresh back from Cannes, discusses why the French film industry booed at a Netflix film - why was it there in the first place? Is the film industry being that affected by tech giants like Amazon? Tech Advisor's Dom Preston chimes in to let us know. Finally, we all quickly nerded out about Alien: Covenant. Mild spoiler alert!  


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Episode 105 - The Internet of Good & Bad (IoG&B) Google Rubin scandal and iPhone XR hands-on

It's episode 105, and David Price takes on hosting duties as the team dissect the best and absolute worst of the week's tech developments.


Scott Carey talks us through the troubling and wide-ranging allegations of sexual misconduct at Google, and discusses how this relates to the tech industry's culture of protected privilege, and to the #metoo movement.


Then Henry Burrell, fresh from a briefing at Apple HQ, reports his distinctly positive first impressions of the iPhone XR, which he would gladly recommend to tech newbie grandmas, and also to Scott.

 

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Phosphatidylinositol Metabolism, Phospholipases, Lipidomics, and Cancer:In Memoriam of Michael J. O. Wakelam (1955-2020) [Tribute]




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Can Ukraine’s Appeal to the International Courts Work?

3 April 2020

Kateryna Busol

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme
First in a two-part series analysing why Ukraine’s attempts at international justice are worth taking - and outlining how the impact goes far beyond just the Russia-Ukraine conflict. Part one examines the response of the International Court of Justice (ICJ) to the possibility of holding Russia accountable as a state.

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Rally in support of keeping Crimea as part of Ukraine. Photo by Spencer Platt/Getty Images.

Russia’s ongoing occupation of Ukraine’s Crimean peninsula and support of separatist hostilities in the eastern provinces of Donbas have resulted in 1.5 million internally displaced persons, 3,000 civilians killed, and a growing list of alleged violations of international law and socio-economic hardship.

But Ukraine is struggling in its efforts to hold Russia accountable – either as a state or through individual criminal responsibility - as it cannot unilaterally ask any international court to give an overall judgment on the conflict.

So it focuses on narrower issues, referring them to authorised adjudication and arbitration platforms such as the International Court of Justice (ICJ), European Court of Human Rights, UNCLOS arbitration, and the International Criminal Court (ICC). These options are limited, but still worth taking - and their relevance is proving to be far wider than the Russia-Ukraine conflict.

Policy of cultural eradication

In 2017, Ukraine initiated proceedings against Russia at the ICJ on the basis of two international treaties: the International Convention on the Elimination of All Forms of Racial Discrimination (CERD), with regard to Crimea; and the International Convention for the Suppression of the Financing of Terrorism (ICSFT), with regard to Donbas.

Under the CERD, Ukraine alleges Russia has carried out a policy of cultural eradication of ethnic Ukrainians and Crimean Tatars in Crimea, including enforced disappearances, no education in the Ukrainian and Crimean Tatar languages, and the ban of the Mejlis, the main representative body of the Crimean Tatars.

Under the ICSFT, Ukraine alleges Russia has supported terrorism by providing funds, weapons and training to illegal armed groups in eastern Ukraine. In particular Ukraine alleges Russian state responsibility - through its proxies - for downing the infamous MH17 flight.

Both these treaties are binding upon Ukraine and Russia and entitle an individual state party to refer a dispute concerning them to the ICJ, but certain procedural pre-conditions must first be exhausted. These include a failed attempt to settle a dispute either through negotiations or the CERD Committee (for the CERD) or unsuccessful negotiations and arbitration (for the ICSFT).

Russia challenged Ukraine’s compliance with the pre-conditions, but the ICJ disagreed with Russia’s submission that Ukraine had to resort both to negotiations and to the CERD Committee. For the first time, the court clarified these procedures under the CERD were two means to reach the same aim, and therefore alternative and not cumulative.

Requiring states to avail of both procedures before going to the ICJ would undermine the very purpose of the CERD to eliminate racial discrimination promptly, and ensure the availability of effective domestic protection and remedies.

The relevance of this clarification transcends the Ukraine-Russia dispute. With the rise of discriminatory practices, from populist hate-filled rhetoric endangering vulnerable communities to large-scale persecution such as that of the Rohingyas, the UN’s principal judicial body is sending a clear larger message to the world: such practices are unacceptable and must be dealt with expeditiously and efficiently. If states fail to do so, there are now fewer procedural impediments to do it internationally.

The ICJ also confirmed Ukraine had complied with both procedural preconditions under the ICSFT and that it would give judgement on the alleged failure of Russia to take measures to prevent the financing of terrorism. The outcome of this will be of great importance to the international community, given the general lack of international jurisprudence on issues of terrorism.

The court’s interpretation of knowledge and intent in terrorism financing, as well as clarification of the term ‘funds’, is particularly relevant both for the Ukraine-Russia case and for international law.

As the final judgement may take several years, the ICJ granted some provisional measures requested by Ukraine in April 2017. The court obliged Russia to ensure the availability of education in Ukrainian and enable the functioning of the Crimean Tatar representative institutions, including the Mejlis.

When Russia contested Ukraine’s references to the alleged Stalin-ordered deportation of the Crimean Tatars and the rule of law in the Soviet Union being hypocritical, by arguing that history did not matter, the court disagreed.

In fact, Judge James Crawford emphasised the relevance of the ‘historical persecution’ of Crimean Tatars and the role of Mejlis in advancing and protecting their rights in Crimea ‘at the time of disruption and change’.

These conclusions are important reminders that the historical inheritance of injustices inflicted on vulnerable groups should be taken into account when nations address their imperial legacies.

The court’s provisional measures and Judge Crawford’s position are particularly relevant in light of Russia’s policy of the total - territorial, historical, cultural – ‘russification’ of Crimea, as they highlight the role of the historical background for assessing the alleged discriminatory and prosecutorial policy of Russia’s occupying authorities against the Crimean Tatars.

The ICJ’s judgement on the merits of this as well as other human rights, and terrorism issues of Crimea and Donbas will be an important consideration for the international community in its view of the Russia-Ukraine armed conflict and the sanctions policy against Russia.

The development of this case also has a mutually catalysing impact on Ukraine’s efforts to establish those individually criminally responsible for atrocities in Crimea and Donbas, through domestic proceedings and through the International Criminal Court.

Ukraine’s attempts to seek individual criminal responsibility for gross abuses in Donbas and Crimea at the International Criminal Court (ICC) are assessed in part two of this series, coming soon.




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Can Morocco Effectively Handle the COVID-19 Crisis?

6 April 2020

Dr Mohammed Masbah

Associate Fellow, Middle East and North Africa Programme

Anna Jacobs

Senior Research Assistant, Brookings Doha Center
The Moroccan government is capitalizing on a burst of unity, social solidarity and public support in the face of a crisis. However, if it fails to effectively mitigate the public health and economic impacts of the COVID-19 pandemic, this spirit of solidarity and cooperation will not last long.

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A general view of empty stores during curfew as a precaution against the new type of coronavirus (COVID-19) in Rabat, Morocco on 1 April 2020. Photo by Jalal Morchidi/Anadolu Agency via Getty Images.

In Morocco, the COVID-19 pandemic has increased public trust in government, but people still have doubts about the effectiveness of the healthcare system. According to a recent study conducted by the Moroccan Institute for Policy Analysis (MIPA), the majority of Moroccans surveyed are generally satisfied with the measures taken by the government to battle the coronavirus. However, the same survey also shows that Moroccans do not have confidence in the healthcare sector’s ability to respond to this pandemic.

The positive perceptions of the government’s response can be explained by the swift and strict measures enacted. King Mohammed VI held a high-level meeting with the prime minister, the minister of health, and top security officials on 17 March and a few days later, on 20 March, the Moroccan government declared a state of health emergency and began to implement aggressive measures to contain the virus.

This has included closing airports, schools, mosques, cafés and shops – with the exception of food markets – preventing large gatherings, as well as strict guidelines to ensure social distancing. As of 2 April, nearly 5000 people have been arrested for violating the state of health emergency.

In order to address urgent medical needs and to mitigate the economic impact of the pandemic, the King ordered the creation of an emergency fund, raising more than 32.7 billion Moroccan Dirhams ($3.2 billion). The Ministry of Finance will begin to make cash transfers to vulnerable citizens, and especially those who have lost their jobs. However, the stipulations surrounding these cash transfers will be decided in the coming weeks.

Updates about the virus are communicated daily by the Ministry of Health, despite growing criticism of its communication strategy. As of 4 April, Moroccan authorities have confirmed 883 cases and 58 deaths.

Call for national unity

In times like these, there is a call for unity in the face of a national and global crisis, and opposition groups such as Adl wal Ihssan and Rif activists have expressed their support for government measures and have encouraged people to follow the new guidelines and restrictions. However, despite calls to release political prisoners, Moroccan authorities have not indicated that they will do so. This is a missed opportunity vis-à-vis the opposition because it could have served as a way to further strengthen national unity during the crisis.

These are all promising signs and point to what is likely to be a short-term burst in unity and institutional trust. However, the institutional weaknesses in governance and the healthcare system have not disappeared, which is why this increase in institutional trust should be taken with a grain of salt.

Public trust issues

This pandemic poses tremendous challenges for governments across the globe, and this holds especially true for states in the Middle East and North Africa region, where citizens do not approve of government performance and do not trust key state institutions. The 2019 Arab Barometer survey found that Moroccans do not trust most of the country’s political institutions (notably the parliament and the Council of Ministers) and the level of satisfaction with the government’s performance remains extremely low.

On the public health front, as shown in two of MIPA’s recent surveys, trust in the healthcare system is also very low. Around three-quarters of those surveyed do not trust Moroccan hospitals, highlighting the acute structural problems in the healthcare system. In fact, there is a stark divide between private and public healthcare, as well as a huge gap in access to healthcare facilities between urban and rural areas. Most of the country’s hospitals and doctors are located in major urban areas and the only three laboratories with capabilities for COVID-19 testing are located in Rabat and Casablanca, but even there, testing capacity is very limited.

Similar to other countries, there could be a major shortage of doctors and medical equipment throughout Morocco. So far, the Ministry of Finance has said that 2 billion dirhams of the emergency fund will go towards purchasing medical equipment such as beds, ventilators, tests, prevention kits and radiology equipment, but the timeline remains unclear.

A vulnerable economy

There is significant concern about the medium- and long-term economic impact of the virus. Two of the country’s key economic sectors have already been hit hard: agriculture and tourism. The agricultural sector was already struggling due to the impact of drought, while the coronavirus pandemic is likely to impact Morocco’s tourism industry not just this year, but well into 2021. In terms of government response, the emergency fund is a strong start, but questions surrounding the management of these funds have already been raised.

The most vulnerable parts of the population have been affected by the economic crisis because of the country’s bulging informal sector – in which most people work - and a very weak private sector. In fact, two-thirds of the workforce are not covered by a pension plan, almost half of the working population does not currently benefit from medical coverage and there is no social care system for vulnerable parts of the population. As of 1 April, more than 700,000 workers have lost their jobs.

Moving forward?

Even if public perceptions of the government’s response are positive at the moment, this is most likely a short-term surge that should not be taken for granted. Despite the efforts made by the government, Morocco’s health system is not equipped to handle this crisis. Even with the new measures that have been implemented, if the spread of the virus gets out of control, more funds, more doctors, and more equipment will be needed. Given the structural weaknesses of the healthcare system, this will be an uphill battle.

Moreover, even if the government manages to mitigate the public health impact, the economic consequences will be dire—especially in the tourism industry—and will severely hurt those workers in the informal sector who are living without a safety net. In Morocco, this category represents most of the working population.

This crisis highlights that the Moroccan government must urgently tackle its large portfolio of unfinished reforms, notably in healthcare, the economy, and labour rights. So far, the government is capitalizing on the spirit of unity, social solidarity and public support. The future trajectory of the pandemic and the effectiveness of governance will determine if this spirit of solidarity will last. If the government fails to effectively mitigate the public health and economic impacts of this pandemic, this solidarity and cooperation will not last long.




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In Search of the American State

6 April 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The urgent need for US leadership to drive forward a coordinated international response to coronavirus is developing rapidly alongside snowballing demands for Washington to step up its efforts at home.

2020-04-06-US-covid-washington

Exercising in front of a deserted Lincoln Memorial in Washington, DC. Photo by Win McNamee/Getty Images.

As the US surgeon general warns Americans to brace for ‘our Pearl Harbor moment’, the US faces a week in which it may see the worst of the global pandemic. The absence of US leadership at the global level has enabled the Security Council’s inaction. And at the G7, President Trump actively obstructed efforts to agree a joint statement.

US efforts to increase its support of international aid to the tune of $274million are minimal, not least in light of a 50% reduction in its support for the World Health Organization (WHO) and radically diminished support for other global health programmes as well. International coordination is essential to mitigate unregulated competition for critical medical supplies, manage border closures, and guarantee international economic stability.

True, it won’t be possible to control the epidemic at home if the global effort to defeat the pandemic fails. But the absence of leadership from Washington at home is palpable. And what happens at home sets a natural limit on America’s internationalism.

Both solution and problem

In response to the coronavirus crisis, the US state is proving to be a solution - and a problem. The dramatic response to the economic crisis is evident with the $2.3trillion stimulus package signed into law by President Trump boldly supported by both Democrats and Republicans in the most significant piece of bipartisan legislation passed in decades.

America’s political economy is unrecognisable, moving left and looking increasingly more European each week as Congress and the executive branch agree a series of stimulus packages designed to protect citizens and businesses. Some elements of this legislation were more familiar to Americans, notably $200bn in corporate tax breaks.

But Congress also agreed unemployment insurance, and cheques - one in April, one in May – to be sent directly to those Americans most directly hit by the economic impact of COVID-19. In effect, this is adopting a temporary universal basic income.

The stimulus plan also dedicated $367bn to keep small businesses afloat for as long as the economy is shuttered. Already the government is negotiating a fourth stimulus package, but the paradox is that without rigorous steps to halt the health crisis, no level of state intervention designed to solve the economic response will be sufficient.

The scale of the state’s economic intervention is unprecedented, but it stands in stark contrast to Washington’s failure to coordinate a national response to America’s health crisis. An unregulated market for personal protective equipment and ventilators is driving up competition between cities, states, and even the federal government.

In some cases, cities and states are reaching out directly beyond national borders to international organisations, foreign firms and even America’s geopolitical competitors as they search for suppliers. In late March, the city of New York secured a commitment from the United Nations to donate 250,000 protective face masks.

Now Governor Cuomo has announced New York has secured a shipment of 140 ventilators from the state of Oregon, and 1,000 ventilators from China. The Patriots even sent their team plane to China to pick up medical supplies for the state of Massachusetts. And following a phone call between President Putin and President Trump, Russia sent a plane with masks and medical equipment to JFK airport in New York.

Networks of Chinese-Americans in the United States are rapidly mobilising their networks to access supplies and send them to doctors and nurses in need. And innovative and decisive action by governors, corporates, universities and mayors drove America’s early response to coronavirus.

This was critical to slowing the spread of COVID-19 by implementing policies that rapidly drove social distancing. But the limits of decentralized and uncoordinated action are now coming into sharp focus. President Trump has so far refused to require stay-at-home orders across all states, leaving this authority to individual governors. Unregulated competition has driven up prices with the consequence that critical supplies are going to the highest bidder, not those most in need.

Governor Cuomo’s call for a nationwide buying consortium has so far gone unheeded and, although the Federal Emergency Management Agency has attempted to deliver supplies to states most in need, the Strategic National Stockpile is depleting fast. Without critical action, the federal government risks hindering the ability of cities and states to get the supplies they need.

But President Trump is reluctant to fully deploy his powers under the Defense Production Act (DPA). In March, he did invoke the DPA to require certain domestic manufacturers to produce ventilators. But calls for it to be used to require manufacturers to produce PPE (personal protective equipment), control costs, and manage allocations has so far gone unheeded by a president generally opposed to state interventions for managing the economy.

It is true that federalism and a deep belief in competition are critical to the fabric of US history and politics, and innovations made possible by market values of entrepreneurism and competition cannot be underestimated. In the search for a vaccine, this could still prove to be key.

But with current estimates that more Americans will die from coronavirus than were killed in the Korean and Vietnam wars combined, it is clear now is the time to reimagine and reinvent the role of the American state.

In the absence of a coordinated effort driven by the White House, governors are working together to identify the areas of greatest need. Whether this will lead to a recasting of the American state and greater demand for a deeper and more permanent social safety net is a key question in the months ahead.

In the short-term the need for coordinated state action at the national level is self-evident. US leadership globally, to manage the health crisis and its economic impacts, is also vital. But this is unlikely to be forthcoming until America gets its own house in order.